In JoVE (1)

Other Publications (199)

Articles by Robert H Gilman in JoVE

Other articles by Robert H Gilman on PubMed

Epilepsy and Neurocysticercosis in Atahualpa: a Door-to-door Survey in Rural Coastal Ecuador

Epilepsia. Apr, 2005  |  Pubmed ID: 15816956

To determine the prevalence of epilepsy and the role of neurocysticercosis in the occurrence of epilepsy in Atahualpa.

The Epidemiology of Intestinal Microsporidiosis in Patients with HIV/AIDS in Lima, Peru

The Journal of Infectious Diseases. May, 2005  |  Pubmed ID: 15838792

We studied microsporidiosis in human immunodeficiency virus-positive patients in 2 Lima hospitals. Of 2652 patients, 66% were male, 6% received antiretroviral therapy (ART), and the median CD4 lymphocyte count was 131 cells/microL. Sixty-seven patients (3%) had microsporidiosis; stool specimens from 56 were identified as having Enterocytozoon bieneusi of 10 different genotypes. The 2 most common genotypes, Peru-1 and Peru-2, were not associated with significant increases in chronic diarrhea; other genotypes were associated with a 4-fold increased risk. Risk factors for E. bieneusi infection segregated by genotype: contact with duck or chicken droppings and lack of running water, flush toilet, or garbage collection with genotype Peru-1 and watermelon consumption with other genotypes. Shortened survival was associated with low CD4 lymphocyte count (P<.0001), no ART (P<.0001), and cryptosporidiosis (P=.004) but not with microsporidiosis (P=.48). Our data suggest the possibility of zoonotic E. bieneusi transmission and an association with poor sanitary conditions.

Screening for Cystic Echinococcosis in an Endemic Region of Peru Using Portable Ultrasonography and the Enzyme-linked Immunoelectrotransfer Blot (EITB) Assay

Parasitology Research. Jun, 2005  |  Pubmed ID: 15875215

Cystic echinococcosis (CE) caused by the larval form of Echinococcus granulosus is a major public health problem in sheep-raising regions of the World. This study compared portable ultrasound with the enzyme-linked immunoelectrotransfer blot (EITB) assay as screening methods to estimate the prevalence of human CE in a remote village in the Peruvian Andes. Three hundred eighty-nine villagers were examined by portable ultrasound and blood samples were drawn by venipuncture. Sera were collected and tested for antibodies against CE using an EITB assay. Cystic lesions were classified based on their ultrasound morphologic characteristics. The prevalence of human CE using portable ultrasound and the EITB assay were 4.9% and 2.6%, respectively. Fifty-three percent of subjects with CE were EITB positive. Portable ultrasound was well received by the community, augmented CE detection and allowed a faster estimate of human infection than the EITB assay.

Risk Factors for Canine Echinococcosis in an Endemic Area of Peru

Veterinary Parasitology. Jun, 2005  |  Pubmed ID: 15893076

An epidemiological study was conducted in a highland rural community in Peru to determine risk factors for canine echinococcosis caused by Echinococcus granulosus. Dogs were diagnosed using a coproantigen enzyme-linked immunosorbent assay (ELISA). Dog owners were interviewed prior to stool collection and asked for attitudes, practices and beliefs likely to be associated with local patterns of E. granulosus transmission. Univariate and multivariate analysis were used to determine odds ratios (OR) and their 95% confidence intervals (CI). The main risk factors found to be significantly associated with canine echinococcosis by univariate analysis were dog age (3-25 months) (OR, 5.14; CI, 1.7-15.7), female sex (OR, 4.3; CI, 1.4-13.3) and having been fed hydatid infected offal (OR, 2.9; 95% CI, 1.0-8.6). There was complete lack of knowledge about echinococcosis transmission. In addition to periodic dog treatment, control programs need to emphasize education of the human population to increase knowledge of parasite transmission and to change human practices associated with high rates of infection.

Vaccination of Pigs to Control Human Neurocysticercosis

The American Journal of Tropical Medicine and Hygiene. Jun, 2005  |  Pubmed ID: 15964973

Taenia solium taeniasis/cysticercosis is a zoonotic disease complex in which the pig is an obligate intermediate host. The infection is widespread, particularly in the developing world, and neurocysticercosis is a major cause of human neurologic disease where the parasite is endemic. Despite easy availability, effective anti-parasitic drugs have not been deployed effectively to control disease transmission. We have investigated a vaccine strategy to prevent parasite infection of the pig intermediate host. Such a strategy would interrupt the parasite's life cycle and eliminate the source of infection for humans. Two recombinant antigens selected from the parasite oncosphere life cycle stage were tested in vaccination trials in pigs that were challenged orally with Taenia solium eggs. Both antigens were highly effective in protecting the pigs against infection with the parasite (98.6% and 99.9% protection, respectively). No viable cysts were found in eight pigs vaccinated with one of the antigens. A recombinant subunit vaccine based on oncosphere antigens has the potential to improve the available control measures for T. solium and thereby reduce or eliminate neurocysticercosis.

Failure to Complete the TB Diagnostic Algorithm in Urban Perú: a Study of Contributing Factors

Tropical Doctor. Apr, 2005  |  Pubmed ID: 15970047

Detection of Muscle Calcifications by Thigh CT Scan in Neurocysticercosis Patients

Transactions of the Royal Society of Tropical Medicine and Hygiene. Oct, 2005  |  Pubmed ID: 16099008

Twenty-five patients with calcified neurocysticercosis (two to four intraparenchymal brain calcifications) were asked to have a non-contrasted computed tomography (CT) scan of the thighs to determine the frequency of muscle calcifications detected by this technique. Thirteen (52%) showed one or more muscle calcifications. The numbers of calcifications in the thighs and the brain were not correlated. Patients with a positive CT scan for muscle calcifications were also examined by X-rays to compare both methods. Only 6 of 13 had visible calcifications on X-ray. Thigh CT scans can demonstrate muscle calcifications in a significant proportion of patients with calcified neurocysticercosis.

Monocyte-astrocyte Networks and the Regulation of Chemokine Secretion in Neurocysticercosis

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2005  |  Pubmed ID: 16116219

Neurocysticercosis, caused by infection with larval Taenia solium, is a major cause of epilepsy worldwide. Larval degeneration, which is symptomatic, results in inflammatory cell influx. Astrocytes, the most abundant cell type and major cytokine-producing cell within the CNS, may be important in orchestrating inflammatory responses after larval degeneration. We investigated the effects of direct stimulation and of conditioned medium from T. solium larval Ag (TsAg)-stimulated monocytes (CoMTsAg) on neutrophil and astrocyte chemokine release. CoMTsAg, but not control conditioned medium, stimulated astrocyte CCL2/MCP-1 (161.5 +/- 16 ng/ml), CXCL8/IL-8 (416 +/- 6.2 ng/ml), and CXCL10/IFN-gamma-inducible protein (9.07 +/- 0.6 ng/ml) secretion after 24 h, whereas direct astrocyte or neutrophil stimulation with TsAg had no effect. There was rapid accumulation of CCL2 and CXCL8 mRNA within 1 h, with somewhat delayed expression of CXCL10 mRNA initially detected 8 h poststimulation. Neutralizing anti-TNF-alpha inhibited CoMTsAg-induced CCL2 mRNA accumulation by up to 99%, causing total abolition of CXCL10 and up to 77% reduction in CXCL8 mRNA. CoMTsAg induced maximal nuclear binding of NF-kappaB p65 and p50 by 1 h, with IkappaBalpha and IkappaBbeta decay within 15 min. In addition, CoMTsAg induced transient nuclear binding of AP-1, which peaked 4 h poststimulation. In NF-kappaB blocking experiments using pyrrolidine dithiocarbamate, CoMTsAg-induced CCL2 secretion was reduced by up to 80% (p = 0.0006), whereas CXCL8 was inhibited by up to 75% (p = 0.0003). In summary, the data show that astrocytes are an important source of chemokines following larval Ag stimulation. Such chemokine secretion is NF-kappaB dependent, likely to involve AP-1, and is regulated in a paracrine loop by monocyte-derived TNF-alpha.

Taeniasis and Cysticercosis in Housemaids Working in Affluent Neighborhoods in Lima, Peru

The American Journal of Tropical Medicine and Hygiene. Sep, 2005  |  Pubmed ID: 16172470

Taenia solium taeniasis/cysticercosis is endemic in most developing countries, where it is an important cause of epileptic seizures and other neurologic symptoms. In industrialized countries, cysticercosis results from travel or immigration of tapeworm carriers from endemic areas. In both endemic and nonendemic countries, housemaids commonly immigrate from cysticercosis-endemic areas and can transmit the infection if they carry the adult tapeworm. Between July 2001 and July 2002, 1,178 housemaids (961 of them work in the top five most affluent districts of Lima, a metropolis of 8 million inhabitants considered nonendemic for cysticercosis) were evaluated for serum antibodies to Taenia solium and stool microscopy for taeniasis and cysticercosis. The serosurvey revealed a prevalence of cysticercosis-specific antibodies of 14.6% (95% CI: 12.6-16.6%), and stool microscopy detected 12 T. solium tapeworm carriers, for a prevalence of taeniasis of 1.2% (95% CI: 0.6-1.8%). A nonrandom sample of 26 seropositive housemaids was examined by brain CT and 50% of them had brain lesions compatible with neurocysticercosis, mainly calcifications. From the families who used a tapeworm-carrier housemaid, cysticercosis antibodies were detected in 6 (23%) of 26 persons who agreed to participate. One seropositive member of the employer families was symptomatic for seizures and had brain calcifications. The prevalence of tapeworm infections in this housemaid group is similar to levels in endemic areas, constituting a source of neurocysticercosis infection.

Short Report: Secondary Transmission in Porcine Cysticercosis: Description and Their Potential Implications for Control Sustainability

The American Journal of Tropical Medicine and Hygiene. Sep, 2005  |  Pubmed ID: 16172471

Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. The pig is the natural intermediate host, harboring the larvae or cysticerci. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier (developing taeniasis) and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-fecal transmission. Here we show evidence of an alternative pig-to-pig route of transmission, previously not suspected to exist. In a series of four experiments, naive sentinel pigs were exposed to pigs that had been infected orally with tapeworm segments (containing infective eggs) and moved to a clean environment. Consistently in all four experiments, at least one of the sentinel pigs became seropositive or infected with parasite cysts with much lower cyst burdens than did primarily infected animals. Second-hand transmission of Taenia solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harboring heavy parasite burdens and many more harboring small numbers of parasites. This route of transmission opens new avenues for consideration with respect to control strategies.

Does Traditional Medicine Use Hamper Efforts at Tuberculosis Control in Urban Peru?

The American Journal of Tropical Medicine and Hygiene. Sep, 2005  |  Pubmed ID: 16172483

Decades of social and political unrest have contributed to the urbanization of the population of Peru with large-scale migration from rural Andean and Amazonian communities to overcrowded shantytowns around Lima. We administered a face-to-face survey questionnaire to 116 patients with suspected and proven tuberculosis (TB) in northern Lima to determine the extent to which the use of traditional therapies from indigenous regions persists and the impact of any such use on TB control. Sixty-three percent of participants reported some form of self-treatment prior to presentation to the National Tuberculosis Program; 52% of them used traditional remedies. Symptom duration was longer among self-remedy users than non-users (median = 25 versus 15 days; P = 0.07) and among those exclusively using western remedies rather than traditional remedies (median = 30 versus 15 days; P = 0.01). We thus found no evidence that use of traditional remedies has an appreciable effect on diagnostic delay in Lima.

Changes in Serum Immunoglobulin G Levels As a Marker for Cryptosporidium Sp. Infection in Peruvian Children

Journal of Clinical Microbiology. Oct, 2005  |  Pubmed ID: 16208002

In a retrospective analysis, we assessed the usefulness of two serologic enzyme-linked immunosorbent assays as epidemiologic tools for the detection of cryptosporidiosis episodes in children from a Peruvian community. The incidence rate determined by the serologic assay was higher than the rate determined by stool microscopy (0.77 versus 0.41 infection/child-year of surveillance).

Serodiagnosis of Neurocysticercosis Using Synthetic 8-kD Proteins: Comparison of Assay Formats

The American Journal of Tropical Medicine and Hygiene. Oct, 2005  |  Pubmed ID: 16222024

The assay of choice for serological detection of cysticercosis in humans and pigs is the enzyme-linked immunoelectrotransfer blot (EITB), a Western blot assay that relies on the use of seven lentil-lectin-purified glycoproteins (LLGPs) derived from Taenia solium metacestodes. The EITB is has a sensitivity of 98% and a specificity of 100% in detecting cysticercosis, yet scarcity of native source material and the labor-intensive process of metacestode purification hinder its practicality. These limitations have necessitated the reproduction of the EITB antigens in synthetic forms. Four chemically synthesized LLGP antigens, TS14, TS18var1, TSRS1, and TSRS2var1, were assayed individually by enzyme-linked immunosorbent assay (ELISA) and Western blot for immunoreactivity against a large cohort of sera from clinically defined neurocysticercosis patients. The sensitivity and specificity of all four of these antigens using the ELISA format were well below the standards set by the LLGP EITB, whereas results of the Western blot format closely mirrored those of the LLGP EITB.

Diversity of Bat-associated Leptospira in the Peruvian Amazon Inferred by Bayesian Phylogenetic Analysis of 16S Ribosomal DNA Sequences

The American Journal of Tropical Medicine and Hygiene. Nov, 2005  |  Pubmed ID: 16282313

The role of bats as potential sources of transmission to humans or as maintenance hosts of leptospires is poorly understood. We quantified the prevalence of leptospiral colonization in bats in the Peruvian Amazon in the vicinity of Iquitos, an area of high biologic diversity. Of 589 analyzed bats, culture (3 of 589) and molecular evidence (20 of 589) of leptospiral colonization was found in the kidneys, yielding an overall colonization rate of 3.4%. Infection rates differed with habitat and location, and among different bat species. Bayesian analysis was used to infer phylogenic relationships of leptospiral 16S ribosomal DNA sequences. Tree topologies were consistent with groupings based on DNA-DNA hybridization studies. A diverse group of leptospires was found in peri-Iquitos bat populations including Leptospira interrogans (5 clones), L. kirschneri (1), L. borgpetersenii (4), L. fainei (1), and two previously undescribed leptospiral species (8). Although L. kirschenri and L. interrogans have been previously isolated from bats, this report is the first to describe L. borgpetersenii and L. fainei infection of bats. A wild animal reservoir of L. fainei has not been previously described. The detection in bats of the L. interrogans serovar Icterohemorrhagiae, a leptospire typically maintained by peridomestic rats, suggests a rodent-bat infection cycle. Bats in Iquitos maintain a genetically diverse group of leptospires. These results provide a solid basis for pursuing molecular epidemiologic studies of bat-associated Leptospira, a potentially new epidemiologic reservoir of transmission of leptospirosis to humans.

[Comparison of the Prevalence of Helicobacter Pylori Stomach Infection in Peruvian and Japanese Population]

Acta Gastroenterologica Latinoamericana. 2005  |  Pubmed ID: 16496853

To compare the prevalence of Helicobacter pylori infection in native Peruvians and Japaneses residing in Peru.

Transmission Dynamics of Taenia Solium and Potential for Pig-to-pig Transmission

Parasitology International. 2006  |  Pubmed ID: 16352459

Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier, and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-faecal transmission. Here we review transmission dynamics of porcine cysticercosis including an alternative pig-to-pig route of transmission, previously not suspected to exist. Second-hand transmission of T. solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harbouring heavy parasite burdens and many more harbouring small numbers of parasites.

Helicobacter Pylori-associated Chronic Atrophic Gastritis Involving the Gastric Body and Severe Disease by Vibrio Cholerae

Transactions of the Royal Society of Tropical Medicine and Hygiene. Jun, 2006  |  Pubmed ID: 16376396

Evidence has associated chronic infection by Helicobacter pylori with chronic gastritis, low gastric acid production and an increased risk of life-threatening cholera. However, the relationship of specific patterns of histological damage in the gastric mucosa associated with H. pylori infection and the occurrence of cholera has not been described. The purpose of this study was to compare the gastric pH and histopathological findings in gastric biopsies taken from patients with severe diarrhoeal disease due to Vibrio cholerae with those taken from a control (cholera-negative) population. Thirty-five H. pylori-positive patients who had severe dehydration from culture-confirmed cholera (cases) and 40 patients with H. pylori but with no history of cholera (controls) were recruited. Gastric pH was measured and multiple biopsies were taken from the gastric antrum and body for histopathological examination. The results revealed that patients with severe cholera had a significantly higher prevalence of hypochlorhydria at endoscopy compared with controls. Furthermore, cases had significantly more chronic atrophic gastritis (45.7% vs. 12.5%; P=0.002) and intestinal metaplasia (37.1% vs. 2.5%; P<0.01) in the gastric body than controls. Our findings suggest that the nature and location of these gastric lesions may predispose a subset of H. pylori-infected individuals to severe disease by V. cholerae.

The Effect of Deforestation on the Human-biting Rate of Anopheles Darlingi, the Primary Vector of Falciparum Malaria in the Peruvian Amazon

The American Journal of Tropical Medicine and Hygiene. Jan, 2006  |  Pubmed ID: 16407338

To examine the impact of tropical rain-forest destruction on malaria, we conducted a year-long study of the rates at which the primary malaria vector in the Amazon, Anopheles darlingi, fed on humans in areas with varying degrees of ecological alteration in the Peruvian Amazon. Mosquitoes were collected by human biting catches along the Iquitos-Nauta road at sites selected for type of vegetation and controlled for human presence. Deforested sites had an A. darlingi biting rate that was more than 278 times higher than the rate determined for areas that were predominantly forested. Our results indicate that A. darlingi displays significantly increased human-biting activity in areas that have undergone deforestation and development associated with road development.

Seroepidemiology of Strongyloidiasis in the Peruvian Amazon

The American Journal of Tropical Medicine and Hygiene. Jan, 2006  |  Pubmed ID: 16407351

A stool and serosurvey for Strongyloides stercoralis was conducted in a community in the Peruvian Amazon region. Strongyloidiasis stercoralis was identified in the stool of 69 (8.7%) of 792 participants. Six hundred nine sera were tested using by an enzyme-linked immunosorbent assay (ELISA), which had a sensitivity of 92% and a specificity of 94%; 442 (72%) were positive. In multivariable logistic regression models, having S. stercoralis in stool was associated with hookworm in the same specimen (odds ratio [OR] = 4.44, 95% confidence interval [CI] = 2.02-9.79), occasionally or never wearing shoes (OR = 1.89, 95% CI = 1.10-3.27), and increasing age (OR = 1.012 for each one-year increase, 95% CI = 1.00-1.03). Similarly, occasionally or never wearing shoes (OR = 1.54, 95% CI = 1.01-2.37) and increasing age (OR = 1.04 for each one-year increase, 95% CI = 1.02-1.06) were associated with an increased risk of a positive S. stercoralis ELISA result. The ELISA had a negative predictive value of 98% and is an excellent screening test for strongyloidiasis.

Efficacy of a 3-day Course of Albendazole Treatment in Patients with a Single Neurocysticercosis Cyst

Clinical Neurology and Neurosurgery. Feb, 2006  |  Pubmed ID: 16412842

Longitudinal Analysis of Cryptosporidium Species-specific Immunoglobulin G Antibody Responses in Peruvian Children

Clinical and Vaccine Immunology : CVI. Jan, 2006  |  Pubmed ID: 16426009

Cryptosporidium species are ubiquitous in the environment and are frequently detected in the stools of children who live where sanitation conditions are poor. To better characterize the immune response to these parasites, we monitored immunoglobulin G (IgG) antibody levels in a cohort of children from Lima, Peru. Two new enzyme-linked immunosorbent assays based on the C. parvum (bovine, subtype IIa) Iowa strain 17-kDa and 27-kDa antigens were used to measure IgG antibody levels in longitudinal serum samples. Antibody responses were detected during infections with C. parvum, C. felis, and C. meleagridis and with four different subtypes of C. hominis. We also noted that the magnitude of the antibody response was related to the number of previous infections and that older children generally had higher levels of antibodies to the two C. parvum antigens. Antibody responses were not associated with infections with either Cyclospora sp. or Giardia sp. We believe the antibody assays will be important tools for monitoring the success of future public health interventions.

Taenia Solium and Taenia Ovis: Stage-specific Expression of the Vaccine Antigen Genes, TSOL18, TSOL16, and Homologues, in Oncospheres

Experimental Parasitology. Aug, 2006  |  Pubmed ID: 16510142

Recombinant antigens that have been cloned from Taenia solium and Taenia ovis have been shown to be highly effective when used as vaccines against cysticercosis in the intermediate hosts. This study investigated the presence of mRNA encoding the TSOL18 and TSOL16 antigens in different life-cycle stages of T. solium, and their related homologues in T. ovis. Reverse transcription-PCR and Southern blotting demonstrated that the antigens are stage-specifically expressed in the oncosphere. The apparent absence of expression of TSOL18 in the metacestode life-cycle stage suggests that the vaccine based on this antigen targets exclusively the early stages in the development of the parasite.

Validation of String Test for Diagnosis of Helicobacter Pylori Infections

Journal of Clinical Microbiology. Mar, 2006  |  Pubmed ID: 16517886

The method of recovering Helicobacter pylori DNA or viable cells absorbed on a string that a person has swallowed and that is retrieved an hour later (string test) should be a useful alternative to traditional analysis of cells or DNA obtained by endoscopy, which is invasive, uncomfortable, relatively costly, and ill-suited for community-based and pediatric studies. Here we assayed the sensitivity and validity of the string test versus conventional endoscopic biopsy for detecting and analyzing H. pylori infection. Forty-four people with gastric complaints were studied using both H. pylori culture and urease gene (ureB) PCR. H. pylori organisms cultured from strings and biopsy specimens from the same patients were fingerprinted by the randomly amplified polymorphic DNA (RAPD) method. Biopsy sections were also hematoxylin and eosin and silver stained for H. pylori detection. H. pylori was cultured from 80% of strings and detected by PCR from 91% of strings from participants whose biopsies had been H. pylori positive by culture, PCR, and/or histology. Strains recovered from strings and biopsy specimens yielded identical or closely related RAPD profiles in each of the 24 cases tested. We conclude that the string test is a useful method for H. pylori recovery and analysis when relatively noninvasive procedures are needed.

Characterization and Cloning of T24, a Taenia Solium Antigen Diagnostic for Cysticercosis

Molecular and Biochemical Parasitology. May, 2006  |  Pubmed ID: 16540186

The third and final diagnostic antigen of the lentil lectin purified glycoproteins (LLGP) extracted from the larval stage of Taenia solium has been characterized, cloned, and expressed. T24 is an integral membrane protein that belongs to the tetraspanin superfamily. It migrates at a position corresponding to 24-kDa and as a homodimer at 42-kDa. Antibodies from cysticercosis patients recognize secondary structure epitopes that are dependent upon correctly formed disulfide bonds. A portion of T24, the large, extracellular loop domain, was expressed in an immunologically reactive form in insect cells. When tested in a Western blot assay with a large battery of serum samples, this protein, T24H, has a sensitivity of 94% (101/107), for detecting cases of cysticercosis with two or more viable cysts, and a specificity of 98% (284/290). The identification and expression of T24H sets the stage for the development of an ELISA suitable for testing single samples and for large-scale serosurveys that is not dependent upon the isolation and purification of antigens from parasite materials.

Clinical Correlates of Tuberculosis Co-infection in HIV-infected Children Hospitalized in Peru

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. Jul, 2006  |  Pubmed ID: 16540360

In developing countries, tuberculosis (TB) is responsible for almost 250,000 deaths among children yearly. Active TB in children with human immunodeficiency virus (HIV) infection is difficult to diagnose and progresses rapidly to death. The aim of this preliminary study was to investigate the prevalence and clinical correlates of TB-related illness among HIV-infected children admitted to an infectious diseases ward in Peru, a country where TB is highly endemic.

La Cuerda Dulce--a Tolerability and Acceptability Study of a Novel Approach to Specimen Collection for Diagnosis of Paediatric Pulmonary Tuberculosis

BMC Infectious Diseases. 2006  |  Pubmed ID: 16595008

Recent data demonstrate the utility of the string test for the diagnosis of sputum-scarce HIV-associated TB in adults. We hypothesized that, if well-tolerated by children, this simple tool might offer a breakthrough in paediatric TB diagnosis. Thus the objective of this study, undertaken in the paediatric service of the Hospital Nacional Dos de Mayo, Lima, Perú, was to determine the tolerability and acceptability of the string test to paediatric TB suspects, their parents and nursing staff.

Polymerase Chain Reaction and Molecular Genotyping to Monitor Parasitological Response to Anti-malarial Chemotherapy in the Peruvian Amazon

The American Journal of Tropical Medicine and Hygiene. Apr, 2006  |  Pubmed ID: 16606982

Over the past decade, anti-malarial drug resistance has rapidly become a major public health problem in the Peruvian Amazon. This study compared polymerase chain reaction (PCR) to light microscopy for diagnosing and monitoring the parasitological response of malaria patients to anti-malarial chemotherapy in the Peruvian Amazon region of Iquitos. Typing of P. falciparum using MSP1, MSP2, and glutamine-rich protein distinguished among infecting parasites. Most (73%) P. falciparum patients were parasitologically resistant to sulfadoxine-pyrimethamine (RI = 10, RII = 1). Sensitivity of microscopy was lower than PCR (69% for P. vivax and 78% for P. falciparum), but parasite clearance times were comparable between microscopy and PCR. PCR sensitively and specifically detected mixed infections and low-level parasitemia indicative of drug resistance, making this approach of practical use for the control of malaria at the public health level. Genotyping malaria parasites will be useful to distinguish drug failure from new infections in clinical trials of anti-malarial drugs in the Peruvian Amazon region.

Understandings of Reproductive Tract Infections in a Peri-urban Pueblo Joven in Lima, Peru

BMC Women's Health. 2006  |  Pubmed ID: 16670025

Control programs for Reproductive Tract Infections (RTIs) typically focus on increasing awareness of risks associated with different forms of sexual contact, and pay little attention to how or why people may link RTIs to other features of their physical or social environments. This paper describes how women in a peri-urban pueblo joven located in the coastal desert surrounding Lima, Peru conceptualize the links between RTIs, sexual behaviour, personal hygiene, and the adverse environment in which they live.

Infrequent MODS TB Culture Cross-contamination in a High-burden Resource-poor Setting

Diagnostic Microbiology and Infectious Disease. Sep, 2006  |  Pubmed ID: 16678991

One obstacle to wider use of rapid liquid culture-based tuberculosis diagnostics such as the microscopic observation drug susceptibility (MODS) assay is concern about cross-contamination. We investigated the rate of laboratory cross-contamination in MODS, automated MBBacT, and Lowenstein-Jensen (LJ) cultures performed in parallel, through triangulation of microbiologic (reculturing stored samples), molecular (spoligotype/RFLP), and clinical epidemiologic data. At least 1 culture was positive for Mycobacterium tuberculosis for 362 (11%) of 3416 samples; 53 were regarded as potential cross-contamination suspects. Cross-contamination accounted for 17 false-positive cultures from 14 samples representing 0.41% (14/3416) and 0.17% (17/10248) of samples and cultures, respectively. Positive predictive values for MODS, MBBacT (bioMérieux, Durham, NC), and LJ were 99.1%, 98.7%, and 99.7%, and specificity was 99.9% for all 3. Low rates of cross-contamination are achievable in mycobacterial laboratories in resource-poor settings even when a large proportion of samples are infectious and highly sensitive liquid culture-based diagnostics such as MODS are used.

Mixed Cryptosporidium Infections and HIV

Emerging Infectious Diseases. Jun, 2006  |  Pubmed ID: 16707069

Mixed Cryptosporidium infections were detected in 7 of 21 patients with a diagnosis of rare Cryptosporidium canis or C. felis infections; 6 patients were infected with 2 Cryptosporidium spp. and 1 patient with 3 species. Mixed infections may occur more frequently than previously believed and should be considered when assessing cryptosporidiosis.

Development of a Normal Human Immunoglobulin G Standard Curve for Enzyme-linked Immunosorbent Assay: Use for Comparison of Antigen Efficacy

Journal of Immunoassay & Immunochemistry. 2006  |  Pubmed ID: 16711254

Internal standard reference curves are used in enzyme-linked immunosorbent assay (ELISA) plates to control for inter- and intra-assay variance. To compare the diagnostic potential of multiple T. solium antigens on an unbiased, universal scale, we have created a standard curve using normal, human immunoglobulin G (hIgG). The hIgG curve is inexpensive and simple to prepare, and remains stable at 5 degrees C for at least one year, with a coefficient of variance of less than 10%. The hIgG standard curve has proven a critical tool for the comparison of several diagnostic antigens slated for assay development.

Aegicerin, the First Oleanane Triterpene with Wide-ranging Antimycobacterial Activity, Isolated from Clavija Procera

Journal of Natural Products. May, 2006  |  Pubmed ID: 16724857

An ethanol extract of the Peruvian plant Clavija procera, a member of the rare Theophrastaceae family, was fractionated using a colorimetric bioassay-guided protocol against Mycobacterium tuberculosis (MTB), yielding the oleanane triterpenoid aegicerin (1) as the active constituent. Its MIC values ranged between 1.6 and 3.12 microg/mL against 37 different sensitive and resistant MTB strains (1 H37Rv, 21 susceptible clinical isolates, 2 INH-resistant clinical isolates, and 13 MDR clinical isolates).

Improved Recovery of Mycobacterium Tuberculosis from Children Using the Microscopic Observation Drug Susceptibility Method

Pediatrics. Jul, 2006  |  Pubmed ID: 16751616

The diagnosis of pulmonary tuberculosis presents challenges in children, because symptoms are nonspecific, sputa are not accessible, and Mycobacterium tuberculosis cultures and smears often are negative. The Microscopic Observation Drug Susceptibility technique is a simple, inexpensive method for Mycobacterium tuberculosis isolation with superior speed and sensitivity over Lowenstein-Jensen culture in studies of adults with pulmonary tuberculosis. The objective of this study was to determine whether Microscopic Observation Drug Susceptibility culture can improve the sensitivity and the speed of Mycobacterium tuberculosis recovery among Peruvian children with symptoms suggestive of pulmonary tuberculosis.

An Intervention-control Study of Corralling of Free-ranging Chickens to Control Campylobacter Infections Among Children in a Peruvian Periurban Shantytown

The American Journal of Tropical Medicine and Hygiene. Jun, 2006  |  Pubmed ID: 16760519

Campylobacter jejuni is a major cause of diarrhea among children in developing countries. Since free-ranging chickens are a major source of Campylobacter infections, we hypothesized that corralling of these chickens would result in decreased rates of Campylobacter infections and Campylobacter-related diarrhea. We tested this hypothesis in Peruvian families in a periruban shantytown with free-ranging chickens and randomized by household using a (corralling) intervention versus control study design. Samples from participants and chickens were cultured for Campylobacter at the start of surveillance, and samples from children less than six years of age with diarrhea episodes and two sentinel chickens were cultured for Campylobacter monthly. Overall, 4,257 human stool specimens and 3,950 avian stool specimens were cultured over a 17-month period. Rates of Campylobacter-related diarrhea in children were significantly higher in the corral group, which demonstrated twice the incidence of Campylobacter diarrhea compared with controls overall, and seven times the rate of Campylobacter diarrhea versus controls in the subset with more than 20 household chickens. Rates of asymptomatic infection with Campylobacter were similar. Although corralling may be useful if corrals are distant from living quarters, it is not advisable as a control measure for Campylobacter in communities such as this.

Neurocysticercal Antigens Stimulate Chemokine Secretion from Human Monocytes Via an NF-kappaB-dependent Pathway

Microbes and Infection / Institut Pasteur. Jun, 2006  |  Pubmed ID: 16815071

Neurocysticercosis, infection with larval Taenia solium, is a common, serious neuroparasitic infection. Larval degeneration results in inflammatory cell influx and granuloma formation which leads to clinical symptomatology. The role of chemokines in such cell influx is unknown. We demonstrate that monocyte stimulation by T. solium larval antigen (TsAg) results in a differential profile of CXCL8/IL-8 (146.5+/-8.5ng/ml after 24h), CCL2/MCP-1 (267+/-4 ng/ml after 48 h) and CCL3/MIP-1alpha (1.72+/-0.43 ng/ml after 8 h) secretion. There was coordinate mRNA accumulation reaching maximum at 1h for CCL3 and 2 h for CXCL8 and CCL2. TsAg induced maximal nuclear binding of p65, p50 and c-rel subunits of the transcriptional regulator NF-kappaB by 2 h. IkappaBalpha but not IkappaBbeta was degraded within 10 min before resynthesis by 2 h. Pre-treatment with the broad-spectrum NF-kappaB inhibitor pyrrolidine dithiocarbamate caused complete abrogation of TsAg-induced CCL2 secretion (p=0.005) and 91% reduction of CXCL8 secretion (p=0.0003). TsAg was unable to induce CXCL8 promoter activity in Toll-like receptor (TLR)-2 or TLR-4/MD-2 transfected HeLa cells in the absence of lectins or other adaptor molecules. In summary, our data demonstrate that TsAg induces chemokine secretion via specific pathways dependent on NF-kappaB but not TLR-4/TLR-2, and indicate a potential mechanism whereby larval degeneration results in brain inflammation.

Effectiveness of Enterobacterial Repetitive Intergenic Consensus PCR and Random Amplified Polymorphic DNA Fingerprinting for Helicobacter Pylori Strain Differentiation

Applied and Environmental Microbiology. Jul, 2006  |  Pubmed ID: 16820463

We compared the robustness and discriminatory power of the enterobacterial repetitive intergenic consensus (ERIC) and random amplified polymorphic DNA (RAPD) fingerprinting methods for detecting cases of mixed Helicobacter pylori infection in Peruvian shantytown residents. H. pylori isolates from 63 participants were cultured, and five single colonies and a pool of additional colonies from each participant were analyzed by ERIC-PCR and by RAPD tests with four 10-nucleotide primers (one primer per reaction). There was 94% agreement between the ERIC and RAPD profiles in classifying sets of isolates as uniform versus closely related but not identical versus probably unrelated, indicating a high kappa statistic of 0.8942. Subtle differences in related ERIC or RAPD patterns likely reflect gene transfer between strains, recombination, and/or mutation, whereas markedly different patterns reflect infection by unrelated strains. At least half of infected shantytown residents seemed to carry more than one H. pylori strain, although in 19 of 31 persons, the strains were closely related. Three RAPD tests, each with a different primer, were needed to achieve the sensitivity of one ERIC test. ERIC-PCR constitutes a resource- and time-efficient method for H. pylori strain differentiation.

Comparison of Altitude Effect on Mycobacterium Tuberculosis Infection Between Rural and Urban Communities in Peru

The American Journal of Tropical Medicine and Hygiene. Jul, 2006  |  Pubmed ID: 16837708

The mechanism of high altitude effect on tuberculosis (TB) infection has not been fully established. We previously reported a lower positive tuberculin skin test (TST) prevalence in high altitude villages compared with sea level communities in Peru. In this study, four additional communities were tested to assess whether decreased TB transmission was also in urban environments at high altitude. TST results from 3,629 individuals in nine communities were analyzed using generalized estimating equations to account for community clustering. Positive TST prevalence was not significantly different between the urban highland and the urban non-highland communities after adjusting for age, household contacts with a TST-positive person or a TB case, and presence of a Bacillus Calmette-Guérin vaccination scar. The effect of population concentration and increased contact with active TB overwhelmed the protective effect of altitude in urban highlands. Highland cities require the same preventive efforts against TB as non-highland communities.

Limited Diversity of Anopheles Darlingi in the Peruvian Amazon Region of Iquitos

The American Journal of Tropical Medicine and Hygiene. Aug, 2006  |  Pubmed ID: 16896125

Anopheles darlingi is the most important malaria vector in the Amazon basin of South America, and is capable of transmitting both Plasmodium falciparum and P. vivax. To understand the genetic structure of this vector in the Amazonian region of Peru, a simple polymerase chain reaction (PCR)-based test to identify this species of mosquito was used. A random amplified polymorphic DNA-PCR was used to study genetic variation at the micro-geographic level in nine geographically separate populations of An. darlingi collected in areas with different degrees of deforestation surrounding the city of Iquitos. Within-population genetic diversity in nine populations, as quantified by the expected heterozygosity (H(E)), ranged from 0.27 to 0.32. Average genetic distance (F(ST)) among these populations was 0.017. These results show that the nine studied populations are highly homogeneous, suggesting that strategies can be developed to combat this malaria vector as a single epidemiologic unit.

Determining Risk for Severe Leptospirosis by Molecular Analysis of Environmental Surface Waters for Pathogenic Leptospira

PLoS Medicine. Aug, 2006  |  Pubmed ID: 16933963

Although previous data indicate that the overall incidence of human leptospirosis in the Peruvian Amazon is similar in urban and rural sites, severe leptospirosis has been observed only in the urban context. As a potential explanation for this epidemiological observation, we tested the hypothesis that concentrations of more virulent Leptospira would be higher in urban than in rural environmental surface waters.

Outbreak of Cyclosporiasis at a Naval Base in Lima, Peru

The American Journal of Tropical Medicine and Hygiene. Sep, 2006  |  Pubmed ID: 16968939

Cyclospora cayetanensis is emerging as an important cause of food-borne diarrheal outbreaks, especially in developed regions like the United States and Europe. We describe an outbreak of cyclosporiasis in Peruvian naval recruits that we believe to be the first among a local population in a developing region.

Postmortem Findings and Opportunistic Infections in HIV-positive Patients from a Public Hospital in Peru

Pathology, Research and Practice. 2006  |  Pubmed ID: 16979302

There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed.

Microscopic-observation Drug-susceptibility Assay for the Diagnosis of TB

The New England Journal of Medicine. Oct, 2006  |  Pubmed ID: 17035648

New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug-resistant tuberculosis in sputum has been demonstrated in proof-of-principle studies of the microscopic-observation drug-susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth.

Periurban Trypanosoma Cruzi-infected Triatoma Infestans, Arequipa, Peru

Emerging Infectious Diseases. Sep, 2006  |  Pubmed ID: 17073082

In Arequipa, Peru, vectorborne transmission of Chagas disease by Triatoma infestans has become an urban problem. We conducted an entomologic survey in a periurban community of Arequipa to identify risk factors for triatomine infestation and determinants of vector population densities. Of 374 households surveyed, triatomines were collected from 194 (52%), and Trypanosoma cruzi-carrying triatomines were collected from 72 (19.3%). Guinea pig pens were more likely than other animal enclosures to be infested and harbored 2.38x as many triatomines. Stacked brick and adobe enclosures were more likely to have triatomines, while wire mesh enclosures were protected against infestation. In human dwellings, only fully stuccoed rooms were protected against infestation. Spatially, households with triatomines were scattered, while households with T. cruzi-infected triatomines were clustered. Keeping small animals in wire mesh cages could facilitate control of T. infestans in this densely populated urban environment.

Development of a Multilocus Sequence Typing Tool for Cryptosporidium Hominis

The Journal of Eukaryotic Microbiology. 2006  |  Pubmed ID: 17169064

Tuberculosis Mortality, Drug Resistance, and Infectiousness in Patients with and Without HIV Infection in Peru

The American Journal of Tropical Medicine and Hygiene. Dec, 2006  |  Pubmed ID: 17172361

The effects of HIV co-infection and multi-drug resistant tuberculosis (MDRTB) on tuberculosis prognosis are poorly defined. Therefore, we studied infectiousness and mortality of 287 tuberculosis patients treated with standard, directly observed, short-course therapy in the Peruvian community. During 6-17 months of treatment, 49 (18%) of patients died, of whom 48 (98%) had AIDS and 28 (57%) had MDRTB; 17/31 (55%) of MDRTB-patients with AIDS died within 2 months of diagnosis, before traditional susceptibility testing would have identified their MDRTB. Most non-MDRTB became smear- and culture-negative within 6 weeks of therapy, whereas most MDRTB remained sputum-culture-positive until death or treatment completion. HIV-negative patients with non-MDRTB had good outcomes. However, MDRTB was associated with prolonged infectiousness and HIV co-infection with early mortality, indicating a need for greater access to anti-retroviral therapy. Furthermore, early and rapid tuberculosis drug-susceptibility testing and infection control are required so that MDRTB can be appropriately treated early enough to reduce mortality and transmission.

Decrease in Prevalence of Peptic Ulcer and Gastric Adenocarcinoma at the Policlínico Peruano Japones, Lima, Peru, Between the Years 1985 and 2002. Analysis of 31,446 Patients

Acta Gastroenterologica Latinoamericana. Sep, 2006  |  Pubmed ID: 17407990

To determine the prevalence of peptic ulcer and gastric adenocarcinoma in a population of middle and high socio-economic status in Lima, Peru, between 1985 and 2002.

Prevalence of Sexually Transmitted Infections and High-risk Sexual Behaviors in Heterosexual Couples Attending Sexually Transmitted Disease Clinics in Peru

Sexually Transmitted Diseases. Jun, 2007  |  Pubmed ID: 17075438

The objectives of this study were to determine the prevalence of sexually transmitted infection (STIs) in heterosexual couples and the sexual behaviors associated with their acquisition.

A Simple Method for Collecting Measured Whole Blood with Quantitative Recovery of Antibody Activities for Serological Surveys

Journal of Immunological Methods. Mar, 2007  |  Pubmed ID: 17270207

Compliance and acceptance for the finger-prick method of blood collection is generally better than for venipuncture. A finger-prick method of blood collection with quantitative antibody recovery is even more important for seroepidemiological surveys. Finger-prick blood collected and dried onto filter paper has been used; but, unfortunately, this method has several disadvantages, including loss of antibody activity, possible contact contamination from blood spots on adjacent filter papers, and difficulties in extracting antibodies, justifying the search for other methods of collecting and transporting blood samples. We report on a simple method of collecting a measured amount of finger-prick blood onto a sample pad, which is immediately transferred to storage/extraction buffer. The diluted blood sample is never dried, and because of the storage buffer, can be transported and stored without refrigeration. Furthermore, the diluted blood samples can then be tested directly without further preparation. We systematically compared several storage/extraction buffers and commercially available filter papers. We showed that antibody recovery was not significantly affected by the type of filter papers used but was significantly affected by the storage/extraction buffer used. The best such buffer is StabilZyme Select.

Swine Cysticercosis Hotspots Surrounding Taenia Solium Tapeworm Carriers

The American Journal of Tropical Medicine and Hygiene. Feb, 2007  |  Pubmed ID: 17297051

We estimated the Taenia solium swine cysticercosis risk gradient surrounding tapeworm carriers in seven rural communities in Peru. At baseline, the prevalences of taeniasis by microscopy and swine cysticercosis by serology were 1.2% (11 of 898) and 30.8% (280 of 908), respectively. The four-month cumulative seroincidence was 9.8% (30 of 307). The unadjusted swine seroprevalence and seroincidence rates increased exponentially by 12.0% (95% confidence [CI] = 9.7-14.3%) and 32.8% (95% CI = 25.0-41.0%), respectively when distance to carriers decreased by half. Swine seroprevalence was 18.4% at > 500 meters from a carrier, 36.5% between 51 and 500 meters, and 68.9% within 50 meters (P < 0.001). Swine seroincidence also displayed a strong gradient near tapeworm carriers (3.8%, 12.2%, and 44.0%; P < 0.001). Within 50 meters, swine seroprevalence appeared unaffected if the owners harbored tapeworms, although pigs owned by a tapeworm carrier had a four times higher seroincidence compared with other pigs (P = 0.005). In rural areas, swine cysticercosis occurs in high-risk hotspots around carriers where control interventions could be delivered.

Natural Ventilation for the Prevention of Airborne Contagion

PLoS Medicine. Feb, 2007  |  Pubmed ID: 17326709

Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings.

Evaluation of Brucellosis by PCR and Persistence After Treatment in Patients Returning to the Hospital for Follow-up

The American Journal of Tropical Medicine and Hygiene. Apr, 2007  |  Pubmed ID: 17426173

Polymerase chain reaction (PCR) was applied to confirm the diagnosis of brucellosis and to study its clearance in response to the standard treatment regimen with doxycycline and rifampin at hospitals in Callao and Lima, Peru. The PCR confirmed the diagnosis in 23 (91.7%) patients with brucellosis including 12 culture-confirmed cases. For patients treated at the hospital in Callao, PCR was positive for all samples collected during and at the conclusion of treatment and for 76.9% of follow-up samples collected on average 15.9 weeks after completion of treatment. For patients treated at the hospital in Lima, PCR tests were positive for 81.8% of samples collected during treatment, for 33.3% of samples collected at the conclusion of treatment, and for > or = 50% of samples collected at first, second, and third post-treatment follow-up. Thus, Brucella DNA may persist in the serum weeks to months after completion of the standard treatment regimen.

Possible Transmission of Cryptosporidium Canis Among Children and a Dog in a Household

Journal of Clinical Microbiology. Jun, 2007  |  Pubmed ID: 17442794

In a longitudinal cohort diarrhea study, a girl living in Lima, Peru, and her brother and dog were diagnosed with Cryptosporidium canis infections during the same period. Both children had transient diarrhea, but the dog was asymptomatic. This is the first report of possible transmission of cryptosporidiosis between humans and dogs.

The Detection of Airborne Transmission of Tuberculosis from HIV-infected Patients, Using an in Vivo Air Sampling Model

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. May, 2007  |  Pubmed ID: 17443474

Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures.

Economic Burden of Neurocysticercosis: Results from Peru

Transactions of the Royal Society of Tropical Medicine and Hygiene. Aug, 2007  |  Pubmed ID: 17507067

Neurocysticercosis (NCC) is a major cause of neurological morbidity in the developing world. This study aimed to assess the treatment costs and productivity losses associated with NCC in Peru. NCC patients were identified through retrospective chart analysis. Patients meeting inclusion criteria were interviewed in order to obtain data on symptom history, treatment costs, productivity losses and health service utilisation patterns. These data were modelled to determine average treatment costs and productivity losses over 2 years. Our findings show that treatment costs and productivity losses consume 54% of an annual minimum wage salary during the first year of treatment and 16% during the second year. Diagnosis (36%) and drug therapy (27%) represent the most expensive healthcare-related costs. These costs are prohibitive for some-8% of our study sample had no diagnostic tests during their first 6 months of disease, and two-thirds of those who delayed treatment reportedly did so due to their inability to pay. Two-thirds of wage-earners lost their jobs owing to NCC and only 61% were able to re-engage in wage-earning activities. This study highlights the need to expand financial coverage to ensure the poor have access to health services and do not become further impoverished.

Prevention and Control of Cystic Echinococcosis

The Lancet Infectious Diseases. Jun, 2007  |  Pubmed ID: 17521591

Human cystic echinococcosis (hydatid disease) continues to be a substantial cause of morbidity and mortality in many parts of the world. Elimination is difficult to obtain and it is estimated that, using current control options, achieving such a goal will take around 20 years of sustained efforts. Since the introduction of current (and past) hydatid control campaigns, there have been clear technological improvements made in the diagnosis and treatment of human and animal cystic echinococcosis, the diagnosis of canine echinococcosis, and the genetic characterisation of strains and vaccination against Echinococcus granulosus in animals. Incorporation of these new measures could increase the efficiency of hydatid control programmes, potentially reducing the time required to achieve effective prevention of disease transmission to as little as 5-10 years.

Development of an Enzyme-linked Immunoelectrotransfer Blot (EITB) Assay Using Two Baculovirus Expressed Recombinant Antigens for Diagnosis of Taenia Solium Taeniasis

The Journal of Parasitology. Apr, 2007  |  Pubmed ID: 17539427

Taeniasis diagnosis is an important step in the control and elimination of both cysticercosis and taeniasis. We report the development of 2 serological taeniasis diagnostic tests using recombinant antigens rES33 and rES38 expressed by baculovirus in insect cells in an EITB format. In laboratory testing with defined sera from nonendemic areas, rES33 has a sensitivity of 98% (n = 167) and a specificity of 99% (n = 310) (J index: 0.97); rES38 has a sensitivity of 99% (n = 146) and a specificity of 97% (n = 275) (J index: 0.96). Independent field testing in Peru showed 97% (n = 203) of the taeniasis sera were positive with rES33, and 100% of the nontaeniasis sera (n = 272) were negative with rES33; 98% (n = 198) of taeniasis sera were positive with rES38, and 91% (n = 274) of the nontaeniasis sera were negative with rES38. Among the Peruvian sera tested, 17 of 26 Peruvian Taenia saginata sera were false positive with rES38 test. Both tests were also examined with cysticercosis sera, with a positive rate ranging from 21% to 46%. rES33 and rES38 tests offer sensitive and specific diagnosis of taeniasis and easy sample collection through finger sticks that can be used in large-scale studies. They are currently being used in cysticercosis elimination programs in Peru.

Differences in Clinical Manifestations Among Cryptosporidium Species and Subtypes in HIV-infected Persons

The Journal of Infectious Diseases. Sep, 2007  |  Pubmed ID: 17674309

We performed a cross-sectional study to determine the epidemiology of Cryptosporidium in human immunodeficiency virus (HIV)-infected persons at 3 diagnostic levels: microscopy, genotypes of Cryptosporidium, and subtype families of C. hominis and C. parvum. The study enrolled 2,490 HIV-infected persons in Lima, Peru, and 230 were microscopy positive for Cryptosporidium infection. Specimens from 193 participants were available for genotyping. They had C. hominis (141 persons), C. parvum (22 persons), C. meleagridis (17 persons), C. canis (6 persons), C. felis (6 persons), and C. suis (1 person) infection. Although microscopy results showed that Cryptosporidium infections were associated with diarrhea, only infections with C. canis, C. felis, and subtype family Id of C. hominis were associated with diarrhea, and infection with C. parvum was associated with chronic diarrhea and vomiting. These results demonstrate that different Cryptosporidium genotypes and subtype families are linked to different clinical manifestations.

Strategies for the Elimination of Taeniasis/cysticercosis

Journal of the Neurological Sciences. Nov, 2007  |  Pubmed ID: 17681546

Advances in the field of neurocysticercosis continue to shape our understanding of the disease and our efforts to control it. Several attempts have been made to eradicate the disease with active interventions such as changing domestic pig-raising practices, mass chemotherapy of porcine cysticercosis and taeniasis, selective detection and treatment of taeniasis, and community health education. Moreover, ongoing progress in the diagnosis of taeniasis and the development of a porcine vaccine against cysticercosis in Australia, Mexico and Peru has yielded at least one effective vaccine that is currently available. Thus far, however, attempted interventions have only been successful in temporarily disrupting transmission of the disease. Controlled data on the efficacy and acceptability of the different interventions is urgently needed to provide a base-line schematic for intervention which could later be tailored to each particular endemic scenario.

Taenia Solium Oncosphere Adhesion to Intestinal Epithelial and Chinese Hamster Ovary Cells in Vitro

Infection and Immunity. Nov, 2007  |  Pubmed ID: 17698575

The specific mechanisms underlying Taenia solium oncosphere adherence and penetration in the host have not been studied previously. We developed an in vitro adhesion model assay to evaluate the mechanisms of T. solium oncosphere adherence to the host cells. The following substrates were used: porcine intestinal mucosal scrapings (PIMS), porcine small intestinal mucosal explants (PSIME), Chinese hamster ovary cells (CHO cells), epithelial cells from ileocecal colorectal adenocarcinoma (HCT-8 cells), and epithelial cells from colorectal adenocarcinoma (Caco-2 cells). CHO cells were used to compare oncosphere adherence to fixed and viable cells, to determine the optimum time of oncosphere incubation, to determine the role of sera and monolayer cell maturation, and to determine the effect of temperature on oncosphere adherence. Light microscopy, scanning microscopy, and transmission microscopy were used to observe morphological characteristics of adhered oncospheres. This study showed in vitro adherence of activated T. solium oncospheres to PIMS, PSIME, monolayer CHO cells, Caco-2 cells, and HCT-8 cells. The reproducibility of T. solium oncosphere adherence was most easily measured with CHO cells. Adherence was enhanced by serum-binding medium with >5% fetal bovine serum, which resulted in a significantly greater number of oncospheres adhering than the number adhering when serum at a concentration less than 2.5% was used (P < 0.05). Oncosphere adherence decreased with incubation of cells at 4 degrees C compared with the adherence at 37 degrees C. Our studies also demonstrated that T. solium oncospheres attach to cells with elongated microvillus processes and that the oncospheres expel external secretory vesicles that have the same oncosphere processes.

Multinucleate Giant Cells Release Functionally Unopposed Matrix Metalloproteinase-9 in Vitro and in Vivo

The Journal of Infectious Diseases. Oct, 2007  |  Pubmed ID: 17763331

Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix metalloproteinase (MMP)-9, the major monocyte-derived matrix metalloproteinase, is key in inflammatory tissue damage. At 72 h, MGCs secrete 153 +/- 2.5 ng/mL MMP-9, compared with 115 +/- 3.8 ng/mL during macrophage differentiation (P<.05). In contrast, the level of MGC secretion-specific tissue inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, is lower (P<.05). Mature MGCs secrete constitutively greater concentrations of MMP-9 than do monocytes or macrophages (P<.05). MGCs in tuberculous lymph-node biopsy samples express high MMP-9 levels adjacent to areas of necrosis, whereas TIMP-1 is not detected. Thus, MGCs are potentially important sources of MMP-9 secretion and may contribute to inflammatory tissue damage in human tuberculosis.

Polymerase Chain Reaction Detection of Plasmodium Vivax and Plasmodium Falciparum DNA from Stored Serum Samples: Implications for Retrospective Diagnosis of Malaria

The American Journal of Tropical Medicine and Hygiene. Sep, 2007  |  Pubmed ID: 17827357

Polymerase chain reaction (PCR) detection of Plasmodium DNA is highly sensitive in diagnosing malaria. The specimen of choice for this assay has been whole blood samples from malaria patients. To retrospectively determine malaria infection rates in populations or cohorts for whom stored serum samples are available, we determined the ability of a nested PCR assay to detect Plasmodium DNA in stored serum samples. The PCR result was positive in 20 of 23 serum samples from patients with microscopy-confirmed malaria and negative in 8 of 8 healthy controls, resulting in a sensitivity of 87% and specificity of 100%. In all positive samples, species were correctly identified by PCR except for one case where a mixed infection was detected. The PCR is able to detect Plasmodium DNA in serum samples frozen up to 2.5 years and has the potential for the retrospective identification of malaria parasitemia in patient cohorts to determine potential interactions of malaria and other diseases such as human immunodeficiency virus/acquired immunodeficiency syndrome.

Characterization of a Novel Taenia Solium Oncosphere Antigen

Molecular and Biochemical Parasitology. Dec, 2007  |  Pubmed ID: 17850901

Infections due to Taenia solium in humans (taeniasis/cysticercosis) remain a complex health problem, particularly in developing countries. We identified two oncosphere proteins that might protect the porcine intermediate host against cysticercosis and therefore help prevent disease in humans. One of these proteins was further identified by two-dimensional gel electrophoresis and micro-sequencing. The gene encoding this protective protein was also identified, cloned and characterized. The native 31.5 kDa protein Tso31 has four variants at the cDNA level. The longest sequence from which the others seem to derive, encodes a 253 amino acid peptide. The predicted protein has a molecular weight of 25.1 kDa, one putative N-glycosylation site, two fibronectin type III domains, and one C terminal transmembrane domain. The gene structure of the protein consists of four exons and three introns. The finding of one gene and four different cDNAs for Tso31 suggests the existence of a possible mechanism of differential splicing in this parasite. The Tso31 protein is exclusive to T. solium oncospheres with a putative protein structure of an extra-cellular receptor-like protein. The Tso31 protein was expressed as a recombinant protein fused to GST and tested in a vaccine to determine its effectiveness in protecting pigs against cysticercosis. Only two pigs out of eight vaccinated were protected and although the total median number of cyst decreased in vaccinated pigs compared to controls this decrease was not statistically significant (P = 0.09).

Comparison of the Peptidase Activity in the Oncosphere Excretory/secretory Products of Taenia Solium and Taenia Saginata

The Journal of Parasitology. Aug, 2007  |  Pubmed ID: 17918349

We compared the peptidase activities of the excretory/secretory (E/S) antigens of oncospheres of Taenia solium and related, but nonpathogenic, Taenia saginata. Taenia solium and T. saginata oncospheres were cultured, and the spent media of 24-, 48-, 72-, and 96-hr fractions were analyzed. Activities for serine peptidases (chymotrypsin-, trypsin-, and elastase-like), cysteine peptidases (cathepsin B-, cathepsin L-, and calpaine-like), and aminopeptidase (B-like peptidases) were tested fluorometrically with peptides coupled to 7-amino-4-methylcoumarin. In both species, the E/S antigens showed cysteine, serine, and aminopeptidase activities. Although no particular peptidase had high activity in T. solium, and was absent in T. saginata, or vice versa, different patterns of activity were found. A chymotrypsin-like peptidase showed the highest activity in both parasites, and it had 10 times higher activity in T. solium than in T. saginata. Trypsin-like and cathepsin B-like activities were significantly higher in T. solium. Minimal levels of cathepsin B were present in both species, and higher levels of elastase-like and cathepsin L-like activity were observed in T. saginata. Taenia solium and T. saginata have different levels and temporal activities of proteolytic enzymes that could play a modulator role in the host specificity for larval invasion through penetration of the intestinal mucosa.

Fecal Contamination of Drinking Water Within Peri-urban Households, Lima, Peru

The American Journal of Tropical Medicine and Hygiene. Oct, 2007  |  Pubmed ID: 17978074

We assessed fecal contamination of drinking water in households in 2 peri-urban communities of Lima, Peru. We measured Escherichia coli counts in municipal source water and, within households, water from principal storage containers, stored boiled drinking water, and water in a serving cup. Source water was microbiologically clean, but 26 (28%) of 93 samples of water stored for cooking had fecal contamination. Twenty-seven (30%) of 91 stored boiled drinking water samples grew E. coli. Boiled water was more frequently contaminated when served in a drinking cup than when stored (P < 0.01). Post-source contamination increased successively through the steps of usage from source water to the point of consumption. Boiling failed to ensure safe drinking water at the point of consumption because of easily contaminated containers and poor domestic hygiene. Hygiene education, better point-of-use treatment and storage options, and in-house water connections are urgently needed.

Evaluation and Treatment of Chagas Disease in the United States: a Systematic Review

JAMA : the Journal of the American Medical Association. Nov, 2007  |  Pubmed ID: 18000201

Because of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease).

Human Brucellosis

The Lancet Infectious Diseases. Dec, 2007  |  Pubmed ID: 18045560

Human brucellosis still presents scientists and clinicians with several challenges, such as the understanding of pathogenic mechanisms of Brucella spp, the identification of markers for disease severity, progression, and treatment response, and the development of improved treatment regimens. Molecular studies have shed new light on the pathogenesis of Brucella spp, and new technologies have permitted the development of diagnostic tools that will be useful in developing countries, where brucellosis is still a very common but often neglected disease. However, further studies are needed to establish optimum treatment regimens and local and international control programmes. This Review summarises current knowledge of the pathogenic mechanisms, new diagnostic advances, therapeutic options, and the situation of developing countries in regard to human brucellosis.

Targeted Screening Strategies to Detect Trypanosoma Cruzi Infection in Children

PLoS Neglected Tropical Diseases. 2007  |  Pubmed ID: 18160979

Millions of people are infected with Trypanosoma cruzi, the causative agent of Chagas disease in Latin America. Anti-trypanosomal drug therapy can cure infected individuals, but treatment efficacy is highest early in infection. Vector control campaigns disrupt transmission of T. cruzi, but without timely diagnosis, children infected prior to vector control often miss the window of opportunity for effective chemotherapy.

Zinc Cream and Reliability of Tuberculosis Skin Testing

Emerging Infectious Diseases. Jul, 2007  |  Pubmed ID: 18214192

In 50 healthy Peruvian shantytown residents, zinc cream applied to tuberculosis skin-test sites caused a 32% increase in induration compared with placebo cream. Persons with lower plasma zinc had smaller skin-test reactions and greater augmentation with zinc cream. Zinc deficiency caused false-negative skin-test results, and topical zinc supplementation augmented antimycobacterial immune responses enough to improve diagnosis.

Nested PCR for Specific Diagnosis of Taenia Solium Taeniasis

Journal of Clinical Microbiology. Jan, 2008  |  Pubmed ID: 17989190

Taeniasis due to Taenia solium is a disease with important public health consequences, since the larval stage is not exclusive to the animal intermediate, the pig, but also infects humans, causing neurocysticercosis. Early diagnosis and treatment of T. solium tapeworm carriers is important to prevent human cysticercosis. Current diagnosis based on microscopic observation of eggs lacks both sensitivity and specificity. In the present study, a nested-PCR assay targeting the Tso31 gene was developed for the specific diagnosis of taeniasis due to T. solium. Initial specificity and sensitivity testing was performed using stored known T. solium-positive and -negative samples. The assay was further analyzed under field conditions by conducting a case-control study of pretreatment stool samples collected from a population in an area of endemicity. Using the archived samples, the assay showed 97% (31/32) sensitivity and 100% (123/123) specificity. Under field conditions, the assay had 100% sensitivity and specificity using microscopy/enzyme-linked immunosorbent assay coproantigen testing as the gold standards. The Tso31 nested PCR described here might be a useful tool for the early diagnosis and prevention of taeniasis/cysticercosis.

Isolation of Cytotoxic Metabolites from Targeted Peruvian Amazonian Medicinal Plants

Journal of Natural Products. Jan, 2008  |  Pubmed ID: 18163590

The antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2',4'-dihydroxy-6'-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13-acetate (7), respectively. Eight human tumor cell lines and two nontumorigenic cell lines were used in this investigation. Their in vitro activity against Mycobacterium tuberculosis is also reported.

Diagnosis of Cystic Echinococcosis, Central Peruvian Highlands

Emerging Infectious Diseases. Feb, 2008  |  Pubmed ID: 18258119

We evaluated prevalence of cystic echinococcosis (CE) in a central Peruvian Highland district by using 4 diagnostic methods: ultrasonography for 949 persons, radiography for 829, and 2 serologic tests for 929 (2 immunoblot formats using bovine hydatid cyst fluid [IBCF] and recombinant EpC1 glutathione S-transferase [rEpC1-GST] antigens). For the IBCF and rEpC1-GST testing, prevalence of liver and pulmonary CE was 4.7% and 1.1% and seropositivity was 8.9% and 19.7%, respectively. Frequency of seropositive results for IBCF and rEpC1-GST testing was 35.7% and 16.7% (all hepatic cysts), 47.1% and 29.4% (hepatic calcifications excluded), and 22.2% and 33.3% (lung cysts), respectively. Weak immune response against lung cysts, calcified cysts, small cysts, and cysts in sites other than lung and liver might explain the poor performance of the serodiagnostic tests. We confirm that CE is highly endemic to Peru and emphasize the limited performance of available serologic assays in the field.

Improved Diagnosis of Pleural Tuberculosis Using the Microscopic- Observation Drug-susceptibility Technique

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Mar, 2008  |  Pubmed ID: 18300380

Tests for pleural tuberculosis are insensitive and expensive. We compared nonproprietary microscopic-observation drug-susceptibility (MODS) culture with Löwenstein-Jensen culture for evaluation of pleural specimens. MODS culture was associated with greatly increased diagnostic sensitivity and shorter time to diagnosis, compared with Löwenstein-Jensen culture (sensitivity of culture of biopsy specimens, 81% vs.51%; time to diagnosis, 11 days vs. 24 days; P < .001). The MODS technique is inexpensive, allows drug-susceptibility testing, and is a considerably improved diagnostic method for pleural tuberculosis.

The Peruvian Contribution to the Knowledge of the Role of Helicobacter Pylori Infection in the Genesis of Gastric Premalignant Lesions That Predispose to Gastric Cancer

Gastroenterology. Mar, 2008  |  Pubmed ID: 18325406

Improved Molecular Technique for the Differentiation of Neotropical Anopheline Species

The American Journal of Tropical Medicine and Hygiene. Mar, 2008  |  Pubmed ID: 18337348

We evaluated a PCR-RFLP of the ribosomal internal transcribed spacer 2 region (ITS2) to distinguish species of Anopheles commonly reported in the Amazon and validated this method using reared F1 offspring. The following species of Anopheles were used for molecular analysis: An. (Nys.) benarrochi, An. (Nys.) darlingi, An. (Nys.) nuneztovari, An. (Nys.) konderi, An. (Nys.) rangeli, and An. (Nys.) triannulatus sensu lato (s.l.). In addition, three species of the subgenus Anopheles, An. (Ano.) forattini, An. (Ano.) mattogrossensis, and An. (Ano.) peryassui were included for testing. Each of the nine species tested yielded diagnostic banding patterns. The PCR-RFLP method was successful in identifying all life stages including exuviae with small fractions of the sample. The assay is rapid and can be applied as an unbiased confirmatory method for identification of morphologic variants, disputed samples, imperfectly preserved specimens, and life stages from which taxonomic keys do not allow for definitive species determination.

Human Leptospirosis Caused by a New, Antigenically Unique Leptospira Associated with a Rattus Species Reservoir in the Peruvian Amazon

PLoS Neglected Tropical Diseases. 2008  |  Pubmed ID: 18382606

As part of a prospective study of leptospirosis and biodiversity of Leptospira in the Peruvian Amazon, a new Leptospira species was isolated from humans with acute febrile illness. Field trapping identified this leptospire in peridomestic rats (Rattus norvegicus, six isolates; R. rattus, two isolates) obtained in urban, peri-urban, and rural areas of the Iquitos region. Novelty of this species was proven by serological typing, 16S ribosomal RNA gene sequencing, pulsed-field gel electrophoresis, and DNA-DNA hybridization analysis. We have named this species "Leptospira licerasiae" serovar Varillal, and have determined that it is phylogenetically related to, but genetically distinct from, other intermediate Leptospira such as L. fainei and L. inadai. The type strain is serovar Varillal strain VAR 010(T), which has been deposited into internationally accessible culture collections. By microscopic agglutination test, "Leptospira licerasiae" serovar Varillal was antigenically distinct from all known serogroups of Leptospira except for low level cross-reaction with rabbit anti-L. fainei serovar Hurstbridge at a titer of 1:100. LipL32, although not detectable by PCR, was detectable in "Leptospira licerasiae" serovar Varillal by both Southern blot hybridization and Western immunoblot, although on immunoblot, the predicted protein was significantly smaller (27 kDa) than that of L. interrogans and L. kirschneri (32 kDa). Isolation was rare from humans (2/45 Leptospira isolates from 881 febrile patients sampled), but high titers of MAT antibodies against "Leptospira licerasiae" serovar Varillal were common (30%) among patients fulfilling serological criteria for acute leptospirosis in the Iquitos region, and uncommon (7%) elsewhere in Peru. This new leptospiral species reflects Amazonian biodiversity and has evolved to become an important cause of leptospirosis in the Peruvian Amazon.

Brucellosis in Household Members of Brucella Patients Residing in a Large Urban Setting in Peru

The American Journal of Tropical Medicine and Hygiene. Apr, 2008  |  Pubmed ID: 18385354

During home visits and using a point-of-care test for brucellosis, we screened the household members of adult patients found to have brucellosis by investigation at the Hospital Nacional Daniel Alcides Carrión in Callao, Peru. A total of 206 household members of 43 patients were screened, and 15 (7.3%) household members in 10 (23.3%) households tested seropositive. Brucellosis was diagnosed in 14 of them, all but 4 presenting with acute or subacute uncomplicated disease. Regardless of attempts to control brucellosis in Peru, the disease continues to be reasonably common among household members of brucellosis patients. Household members presumably remain the single most important identifiable risk group in an urban setting, and screening them provides an effective means for their early diagnosis. Although contact with livestock was rare, the consumption of unpasteurized dairy products was reported by almost all patients with brucellosis, their household members, and hospitalized non-brucellosis patients.

Use of PCR to Improve Diagnostic Yield in an Outbreak of Cyclosporiasis in Lima, Peru

Transactions of the Royal Society of Tropical Medicine and Hygiene. Jul, 2008  |  Pubmed ID: 18433812

Protozoal diseases are increasingly recognized as the cause of diarrhoeal outbreaks in both developed and developing countries. Cyclospora cayetanensis has been responsible for several epidemics in the last decade. In March 2005, an outbreak of diarrhoea was identified in recruits at the Ancon Naval Base in Lima, Peru. A case-control study was carried out. The overall diarrhoea attack rate was 53% (45/85). Complete data from 52 recruits were available for the analysis; 37 met the criteria for case and 15 for control. The epidemic curve indicated a point source transmission, with cases occurring over 9 days with a peak on the fifth day. Cyclospora cayetanensis was found in 7/37(18.9%) cases and 1/15 (6.7%) controls via standard microscopic techniques. PCR for C. cayetanensis detected 20/35 (57.1%) cases and 3/15 (20%) controls, demonstrating the improved diagnostic yield of this technique. This is the second report to characterize an outbreak of diarrhoea due to C. cayetanensis in Peru among a local population. The epidemiology and clinical course were similar to other reported outbreaks in developed regions. PCR greatly increased the number of C. cayetanensis cases detected during this outbreak, allowing the correct identification of its aetiology.

Links Between Sex-related Expectations About Alcohol, Heavy Episodic Drinking and Sexual Risk Among Young Men in a Shantytown in Lima, Peru

International Family Planning Perspectives. Mar, 2008  |  Pubmed ID: 18440913

Alcohol use is frequently identified as a contributor to risky sexual behaviors; however, research results are mixed. Given the conflicting evidence, researchers have focused on other factors, such as expectations about alcohol's effects that might help explain the relationship of alcohol use and risky sexual behaviors.

Tuberculosis Diagnosis and Multidrug Resistance Testing by Direct Sputum Culture in Selective Broth Without Decontamination or Centrifugation

Journal of Clinical Microbiology. Jul, 2008  |  Pubmed ID: 18448689

Tuberculosis culture usually requires sputum decontamination and centrifugation to prevent cultures from being overgrown by contaminating bacteria and fungi. However, decontamination destroys many tuberculous bacilli, and centrifugation often is not possible in resource-poor settings. We therefore assessed the performance of Mycobacterium tuberculosis culture with unprocessed samples plated directly by using tuberculosis-selective media and compared this procedure to conventional culture using centrifuge decontamination. Quadruplicate aliquots of strain H37RV were cultured in 7H9 broth with and without selective antimicrobials and after centrifuge decontamination. The subsequent comparison was made with 715 sputum samples. Split paired sputum samples were cultured conventionally with centrifuge decontamination and by direct culture in tuberculosis-selective media containing antibiotics. Centrifuge decontamination reduced tuberculosis H37RV colonies by 78% (P < 0.001), whereas direct culture in tuberculosis-selective media had no inhibitory effect. Similarly, in sputum cultures that were not overgrown by contaminants, conventional culture yielded fewer tuberculosis colonies than direct culture (P < 0.001). However, the sensitivity of conventional culture was greater than that of direct culture, because samples were less affected by contamination. Thus, of the 340 sputum samples that were tuberculosis culture positive, conventional culture detected 97%, whereas direct culture detected 81% (P < 0.001). Conventional and direct cultures both took a median of 8.0 days to diagnose tuberculosis (P = 0.8). In those direct cultures that detected drug resistance or susceptibility, there was a 97% agreement with the results of conventional culture (Kappa agreement statistic, 0.84; P < 0.001). Direct culture is a simple, low-technology, and rapid technique for diagnosing tuberculosis and determining drug susceptibility. Compared to that of conventional culture, direct culture has reduced sensitivity because of bacterial overgrowth, but in basic laboratories this deficit may be outweighed by the ease of use.

Variation in the Prevalence of Gastric Cancer in Perú

International Journal of Cancer. Journal International Du Cancer. Jul, 2008  |  Pubmed ID: 18449884

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.

Chagas Disease Transmission in Periurban Communities of Arequipa, Peru

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Jun, 2008  |  Pubmed ID: 18462104

Chagas disease, caused by Trypanosoma cruzi infection, is an urban problem in Arequipa, Peru, and the epidemiology of Chagas disease is likely to be quite different in this area, compared with in rural zones.

Anti-infective and Cytotoxic Compounds Present in Blepharodon Nitidum

Planta Medica. Mar, 2008  |  Pubmed ID: 18484532

A pharmacological screening of the ethanol extract and fractions of Blepharodon nitidum led to the isolation of fourteen compounds, two of which, 24-hydroperoxycycloart-25-en-3beta-ol and 25-hydroperoxycycloart-23-en-3beta-ol, exhibited in vitro anti- Mycobacterium tuberculosis and antileishmanial activities, as well as significant cytotoxic activity against a panel of human tumor cell lines.

Performance of Oscillometric Blood Pressure Devices in Children in Resource-poor Settings

European Journal of Cardiovascular Prevention and Rehabilitation : Official Journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. Jun, 2008  |  Pubmed ID: 18525395

To compare oscillometric blood pressure devices with mercury sphygmomanometry in children.

Multi-country Analysis of the Effects of Diarrhoea on Childhood Stunting

International Journal of Epidemiology. Aug, 2008  |  Pubmed ID: 18567626

Diarrhoea is an important cause of death and illness among children in developing countries; however, it remains controversial as to whether diarrhoea leads to stunting. We conducted a pooled analysis of nine studies that collected daily diarrhoea morbidity and longitudinal anthropometry to determine the effects of the longitudinal history of diarrhoea prior to 24 months on stunting at age 24 months. Data covered a 20-year period and five countries. We used logistic regression to model the effect of diarrhoea on stunting. The prevalence of stunting at age 24 months varied by study (range 21-90%), as did the longitudinal history of diarrhoea prior to 24 months (incidence range 3.6-13.4 episodes per child-year, prevalence range 2.4-16.3%). The effect of diarrhoea on stunting, however, was similar across studies. The odds of stunting at age 24 months increased multiplicatively with each diarrhoeal episode and with each day of diarrhoea before 24 months (all P < 0.001). The adjusted odds of stunting increased by 1.13 for every five episodes (95% CI 1.07-1.19), and by 1.16 for every 5% unit increase in longitudinal prevalence (95% CI 1.07-1.25). In this assembled sample of 24-month-old children, the proportion of stunting attributed to >or=5 diarrhoeal episodes before 24 months was 25% (95% CI 8-38%) and that attributed to being ill with diarrhoea for >or=2% of the time before 24 months was 18% (95% CI 1-31%). These observations are consistent with the hypothesis that a higher cumulative burden of diarrhoea increases the risk of stunting.

Peptide YY: a Gut Hormone Associated with Anorexia During Infectious Diarrhea in Children

The Journal of Pediatrics. Nov, 2008  |  Pubmed ID: 18571670

To evaluate the effects of diarrhea on appetite among Peruvian children age 12 to 71 months and to assess whether elevated plasma levels of peptide YY, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta contribute to anorexia in this population.

Absence of Brain Involvement and Factors Related to Positive Serology in a Prospective Series of 61 Cases with Pulmonary Hydatid Disease

The American Journal of Tropical Medicine and Hygiene. Jul, 2008  |  Pubmed ID: 18606768

A prospective series of 65 patients with surgically confirmed lung cystic hydatid disease was evaluated in terms of their radiologic characteristics, serologic response, and presence of cysts in other organs. Cysts were mostly single and located in lower lung lobes. Liver compromise was found in 34% of the patients. Despite a systematic search, no patient showed brain cysts in this series. Twelve patients had previous hydatid disease: six in the liver and eight in the lung (two had involvement of both organs in the past). Serology using bovine cyst fluid in an immunoblot assay was 85% sensitive. Serologic response was not associated with number or cyst or compromise of other organs but was clearly associated to the presence of at least one complicated cyst. Cyst status in terms of complications should be described to allow appropriate assessment of serologic evaluations.

Human Hydatid Disease in Peru is Basically Restricted to Echinococcus Granulosus Genotype G1

The American Journal of Tropical Medicine and Hygiene. Jul, 2008  |  Pubmed ID: 18606769

A molecular PCR study using DNA from 21 hydatid cysts was performed to determine which strain type is responsible for human infection in Peru. The mitochondrial cytochrome c oxidase subunit 1 (CO1) gene was amplified in 20 out of 21 samples, revealing that all but 1 sample (19/20, 95%) belonged to the common sheep strain (G1). The remaining samples belonged to the camel strain (G6). The G1 genotype was most frequently found in human cases of cystic hydatid disease (CHD) in Peru. Local control measures should focus primarily on decreasing dog and sheep infection rather than intermediate reservoirs.

Lack of an Adverse Effect of Giardia Intestinalis Infection on the Health of Peruvian Children

American Journal of Epidemiology. Sep, 2008  |  Pubmed ID: 18669932

Giardia intestinalis is a common gastrointestinal protozoan worldwide, but its effects on childhood growth in developing countries are not clearly understood. The authors aimed to describe its effects on child growth. They followed 220 Peruvian children daily for diarrhea, weekly for stool samples, and monthly for anthropometry. The authors modeled the effect of nutritional status on the risk of Giardia infection and the risk of diarrhea attributable to Giardia using negative binomial regression. They modeled the effects of Giardia infection on growth using linear regression, with 85% of children becoming infected with Giardia and 87% of these becoming reinfected. In multivariable analysis, the risk of Giardia infection did not vary with weight for age (relative risk = 1.00, 95% confidence interval: 0.89, 1.12) or height for age (relative risk = 0.92, 95% confidence interval: 0.82, 1.04). Giardiasis did not affect growth at 1 or 2 months following the first infection at any age interval. The longitudinal prevalence of Giardia between 6 and 24 months of age was not associated with height gain in that interval (p = 0.981). Giardia was not associated with an increased risk of diarrhea at any age interval. Study results question the importance of Giardia as a childhood pathogen in developing countries where giardiasis is hyperendemic.

Surveillance for Early Silicosis in High Altitude Miners Using Pulse Oximetry

International Journal of Occupational and Environmental Health. Jul-Sep, 2008  |  Pubmed ID: 18686718

Two cross-sectional studies in a high altitude region of Perú evaluated the role of pulse oximetry for detection of silicosis in high-altitude miners. In study one, exercise pulse oximetry and chest radiographs were used to evaluate 343 silica-exposed miners and 141 unexposed subjects for evidence of silicosis. Study 2 investigated the association between exercise oxygen saturation and silicosis in 32 non-silicotic and 65 silicotic miners. In study one, age (Odds Ratio [OR] 1.10, 95% Cofidence Interval (CI) 1.07-1.12) and resting oxygen saturation (OR 0.95, 95%CI 0.90-0.99) were associated with silicosis. In study two, years of mining employment (OR 1.14, 95%CI 1.05-1.23) and exercise oxygen saturation at 30% maximum heart rate (OR 0.86, 95%CI 0.75-0.99) were associated with silicosis. Hypoxemia at rest and with exercise is associated with silicosis in high altitude miners. Pulse oximetry should be further investigated as a screening tool for silicosis at high altitudes.

Inter- and Intra-assay Reproducibility of Microplate Alamar Blue Assay Results for Isoniazid, Rifampicin, Ethambutol, Streptomycin, Ciprofloxacin, and Capreomycin Drug Susceptibility Testing of Mycobacterium Tuberculosis

Journal of Clinical Microbiology. Oct, 2008  |  Pubmed ID: 18701659

The intersample and intrasample variability of the results obtained with the microplate Alamar blue assay for the indirect drug susceptibility testing of Mycobacterium tuberculosis was investigated. Between 1.2 and 8.5% of paired MICs differed by more than one twofold dilution, resulting in discordant susceptible-resistant designations at frequencies between 0.6% (rifampin) and 18.9% (ethambutol).

Hypertension Among Adults in a Deprived Urban Area of Peru - Undiagnosed and Uncontrolled?

BMC Research Notes. 2008  |  Pubmed ID: 18710540

In Peru, cardiovascular disease was the second most common cause of death in those aged 65 years or more in 2000. Hypertension is a major modifiable risk factor for cardiovascular disease, and if treated can significantly reduce cardiovascular disease risk. The objectives of this study were to investigate the prevalence of hypertension and levels of awareness, treatment and control in a deprived urban area of Peru.

Epidemiology of Highly Endemic Multiply Antibiotic-resistant Shigellosis in Children in the Peruvian Amazon

Pediatrics. Sep, 2008  |  Pubmed ID: 18710884

Our goal was to estimate the impact of a Shigella vaccine in an area where shigellosis is endemic by characterizing the disease burden and antibiotic-resistance profiles of isolates and by determining the prevalence of Shigella flexneri serotypes.

Pedestrian Road Traffic Injuries in Urban Peruvian Children and Adolescents: Case Control Analyses of Personal and Environmental Risk Factors

PloS One. 2008  |  Pubmed ID: 18781206

Child pedestrian road traffic injuries (RTIs) are an important cause of death and disability in poorer nations, however RTI prevention strategies in those countries largely draw upon studies conducted in wealthier countries. This research investigated personal and environmental risk factors for child pedestrian RTIs relevant to an urban, developing world setting.

Synthesis, Cytotoxicity, and Anti-Trypanosoma Cruzi Activity of New Chalcones

Journal of Medicinal Chemistry. Oct, 2008  |  Pubmed ID: 18798609

Synthesis of a cytotoxic dihydrochalcone, first isolated from a traditional Amazonian medicinal plant Iryanthera juruensis Warb (Myristicaceae), followed by a comprehensive SAR analysis of saturated and unsaturated chalcone synthetic intermediates, led to the identification of analogues with selective and significant in vitro anti- Trypanosoma cruzi activity. Further SAR studies were undertaken with the synthesis of 21 new chalcones containing two allyloxy moieties that resulted in the discovery of 2',4'-diallyloxy-6'-methoxy chalcones with improved selectivity against this parasite at concentrations below 25 microM, four of which exhibited a selectivity index greater than 12.

The Infectiousness of Tuberculosis Patients Coinfected with HIV

PLoS Medicine. Sep, 2008  |  Pubmed ID: 18798687

The current understanding of airborne tuberculosis (TB) transmission is based on classic 1950s studies in which guinea pigs were exposed to air from a tuberculosis ward. Recently we recreated this model in Lima, Perú, and in this paper we report the use of molecular fingerprinting to investigate patient infectiousness in the current era of HIV infection and multidrug-resistant (MDR) TB.

Cryptosporidium Species and Subtypes and Clinical Manifestations in Children, Peru

Emerging Infectious Diseases. Oct, 2008  |  Pubmed ID: 18826821

To determine whether clinical manifestations are associated with genotypes or subtypes of Cryptosporidium spp., we studied a 4-year longitudinal birth cohort of 533 children in Peru. A total of 156 infection episodes were found in 109 children. Data from first infections showed that C. hominis was associated with diarrhea, nausea, vomiting, general malaise, and increased oocyst shedding intensity and duration. In contrast, C. parvum, C. meleagridis, C. canis, and C. felis were associated with diarrhea only. C. hominis subtype families were identified (Ia, Ib, Id, and Ie); all were associated with diarrhea. Ib was also associated with nausea, vomiting, and general malaise. All C. parvum specimens belonged to subtype family IIc. Analysis of risk factors did not show associations with specific Cryptosporidium spp. genotypes or subtypes. These findings strongly suggest that Cryptosporidium spp. and subtypes are linked to different clinical manifestations in children.

Impregnated Netting Slows Infestation by Triatoma Infestans

The American Journal of Tropical Medicine and Hygiene. Oct, 2008  |  Pubmed ID: 18840739

We used sentinel animal enclosures to measure the rate of infestation by the Chagas disease vector, Triatoma infestans, in an urban community of Arequipa, Peru, and to evaluate the effect of deltamethrin-impregnated netting on that rate. Impregnated netting decreased the rate of infestation of sentinel enclosures (rate ratio, 0.23; 95% confidence interval, 0.13-0.38; P < 0.001), controlling for the density of surrounding vector populations and the distance of these to the sentinel enclosures. Most migrant insects were early-stage nymphs, which are less likely to carry the parasitic agent of Chagas disease, Trypanosoma cruzi. Spread of the vector in the city therefore likely precedes spread of the parasite. Netting was particularly effective against adult insects and late-stage nymphs; taking into account population structure, netting decreased the reproductive value of migrant populations from 443.6 to 40.5. Impregnated netting can slow the spread of T. infestans and is a potentially valuable tool in the control of Chagas disease.

DNA-level Diversity and Relatedness of Helicobacter Pylori Strains in Shantytown Families in Peru and Transmission in a Developing-country Setting

Journal of Clinical Microbiology. Dec, 2008  |  Pubmed ID: 18842944

The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti-H. pylori measures to be applied communitywide.

Polymerase Chain Reaction for Chronic Trypanosoma Cruzi Infection Yields Higher Sensitivity in Blood Clot Than Buffy Coat or Whole Blood Specimens

The American Journal of Tropical Medicine and Hygiene. Nov, 2008  |  Pubmed ID: 18981520

Trypanosoma cruzi polymerase chain reaction (PCR) is widely used, but sensitivity varies widely. We compared PCR using 121/122 primers targeting kinetoplast minicircle DNA in whole blood, buffy coat, and clot from Bolivian women. Sensitivity was significantly higher in clot (60.1%) than buffy coat (46.5%) or whole blood (40%). The use of clot could simplify specimen collection while improving sensitivity.

Perilesional Brain Oedema and Seizure Activity in Patients with Calcified Neurocysticercosis: a Prospective Cohort and Nested Case-control Study

Lancet Neurology. Dec, 2008  |  Pubmed ID: 18986841

Cysticercosis due to Taenia solium is a cause of adult-acquired seizures and epilepsy even in patients with only calcified larval cysts. Transient perilesional brain oedema is seen around the calcified foci but its importance, association with seizures, incidence, and pathophysiology are unknown.

Diagnosis of Pediatric Pulmonary Tuberculosis by Stool PCR

The American Journal of Tropical Medicine and Hygiene. Dec, 2008  |  Pubmed ID: 19052299

Pediatric pulmonary tuberculosis diagnosis is difficult because young children are unable to expectorate sputum samples. Testing stool for tuberculosis DNA from swallowed sputum may diagnose pulmonary tuberculosis. Hospitalized children with suspected tuberculosis had stool, nasopharyngeal, and gastric aspirates cultured that confirmed pulmonary tuberculosis in 16/236 patients. Twenty-eight stored stools from these 16 children were used to evaluate stool polymerase chain reaction (PCR) for tuberculosis diagnosis compared with 28 stool samples from 23 healthy control children. Two DNA extraction techniques were used: fast-DNA mechanical homogenization and Chelex-resin chemical extraction. DNA was tested for tuberculosis DNA with a hemi-nested IS6110 PCR. PCR after Fast-DNA processing was positive for 6/16 culture-proven tuberculosis patients versus 5/16 after Chelex extraction (sensitivity 38% and 31%, respectively). All controls were negative (specificity 100%). If sensitivity can be increased, stool PCR would be a rapid, non-invasive, and relatively bio-secure initial test for children with suspected pulmonary tuberculosis.

Direct Observation of Hygiene in a Peruvian Shantytown: Not Enough Handwashing and Too Little Water

Tropical Medicine & International Health : TM & IH. Nov, 2008  |  Pubmed ID: 19055623

To document frequency of hygiene practices of mothers and children in a shantytown in Lima, Peru.

MLVA Genotyping of Human Brucella Isolates from Peru

Transactions of the Royal Society of Tropical Medicine and Hygiene. Apr, 2009  |  Pubmed ID: 19027131

Recent human Brucella melitensis isolates from Peru were genotyped by multiple locus variable number repeat analysis. All 24 isolates originated from hospitalized patients living in the central part of Peru and consisted of six genomic groups comprising two to four isolates and nine unique genotypes. The isolates were most closely related to the two previously genotyped isolates from Mexico, with a maximum distance of 2 to 4. The Peruvian strains were clearly distinct from the East and West Mediterranean groups of B. melitensis genotypes, suggesting that they may constitute a unique Latin American cluster.

Can the Power of Mobile Phones Be Used to Improve Tuberculosis Diagnosis in Developing Countries?

Transactions of the Royal Society of Tropical Medicine and Hygiene. Jun, 2009  |  Pubmed ID: 19036392

The low-cost Microscopic Observation Drug Susceptibility (MODS) assay is a non-proprietary test that delivers rapid and accurate diagnosis of tuberculosis (TB) and multidrug-resistant TB. Although methodologically straightforward, implementation is challenging in isolated settings where personnel trained in plate reading are lacking. One affordable strategy to address this shortfall is the use of mobile phones, first to transmit images captured by an inverted microscope to a remote site where pattern recognition is performed by trained personnel, and second to receive the resulting output of this analysis. Such a system could be used for training of laboratory personnel through distance learning, resolution of equivocal appearances and quality assurance.

A Novel Taenia Solium Protein That Resembles Troponin T Proteins

The Journal of Parasitology. Jun, 2009  |  Pubmed ID: 19090648

Taenia solium Linnaeus, 1758 is responsible for taeniasis and cysticercosis, which are 2 serious health problems, particularly in developing countries. The attempt to identify a 22.5kD possible protective oncospheral antigen by 2-dimensional gel-electrophoresis, micro-sequencing, and cDNA library screening produced a protein of 42kD that possesses a conserved domain similar to that of troponin T. Five variants that showed differences at the 5' end were observed at the cDNA level. Hyper-immune rabbit sera developed against recombinant GST fused protein identified the protein exclusively on activated oncospheres. The 42kD protein was tested in an enzyme-linked immunoassay (ELISA) alone and then together with the Tso31 protein for the diagnosis of human cysticercosis. When both antigens were combined, the test was found to be 85% sensitive and 65% specific. The 42kD is a novel T. solium protein that is present exclusively on activated oncospheres of this parasite, with poor diagnostic activity against taeniasis or human cysticercosis.

Sexual Behavior and Drug Consumption Among Young Adults in a Shantytown in Lima, Peru

BMC Public Health. 2009  |  Pubmed ID: 19152702

Risky sexual behaviors of young adults have received increasing attention during the last decades. However, few studies have focused on the sexual behavior of young adults in shantytowns of Latin America. Specifically, studies on the association between sexual behaviors and other risk factors for sexually transmitted infections (STI) and HIV/AIDS transmission, such as the consumption of illicit drugs or alcohol are scarce in this specific context.

Helicobacter Pylori CagA Phosphorylation-independent Function in Epithelial Proliferation and Inflammation

Cell Host & Microbe. Jan, 2009  |  Pubmed ID: 19154985

CagA, a major virulence factor of Helicobacter pylori (Hp), is delivered into gastric epithelial cells and exists in phosphorylated and nonphosphorylated forms. The biological activity of the phosphorylated form is well established; however, function(s) of the nonphosphorylated form remain elusive. Here, we report that a conserved motif in the C-terminal region of CagA, which is distinct from the EPIYA motifs used for phosphorylation and which we designate CRPIA (conserved repeat responsible for phosphorylation-independent activity), plays pivotal roles in Hp pathogenesis. The CRPIA motif in nonphosphorylated CagA was involved in interacting with activated Met, the hepatocyte growth factor receptor, leading to the sustained activation of phosphatidylinositol 3-kinase/Akt signaling in response to Hp infection. This in turn led to the activation of beta-catenin and NF-kappaB signaling, which promote proliferation and inflammation, respectively. Thus, nonphosphorylated CagA activity contributes to the epithelial proliferative and proinflammatory responses associated with development of chronic gastritis and gastric cancer.

Frequency of Diarrhoea As a Predictor of Elevated Blood Pressure in Children

Journal of Hypertension. Feb, 2009  |  Pubmed ID: 19155783

Diarrhoeal illness is a major public health problem for children worldwide, particularly among developing countries, and is a proxy condition for severe dehydration. It has been hypothesized that severe dehydration in the first 6 months of life could be associated with increased blood pressure later in life. This study aimed to explore whether frequency of diarrhoea is associated with elevated blood pressure in children in a setting with a high incidence of diarrhoeal disease.

Taenia Solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

PLoS Neglected Tropical Diseases. 2009  |  Pubmed ID: 19172178

Neurocysticercosis accounts for 30%-50% of all late-onset epilepsy in endemic countries. We assessed the clustering patterns of Taenia solium human cysticercosis seropositivity and seizures around tapeworm carriers in seven rural communities in Peru.

Short Report: Serologic Evidence of Human Ehrlichiosis in Peru

The American Journal of Tropical Medicine and Hygiene. Feb, 2009  |  Pubmed ID: 19190221

A serosurvey for human ehrlichiosis caused by Ehrlichia chaffeensis and Anaplasma phagocytophilum was performed in different regions of Peru by using indirect immunofluorescence assays (IFAs). Regions included an urban community in a shantytown in Lima (Pampas) and three rural communities located on the northern coast of Peru (Cura Mori), in the southern Peruvian Andes (Cochapata), and in the Peruvian jungle region (Santo Tomas). An overall E. chaffeensis seroprevalence of 13% (21 of 160) was found by IFA. Seroprevalences in females and males was 15% (16 of 106) and 9% (5 of 53), respectively. Seroprevalences in Cura Mori, Cochapata, Pampas, and Santo Tomas were 25% (10 of 40), 23% (9 of 40), 3% (1 of 40), and 3% (1 of 40), respectively. Seroprevalences in Cura Mori and Cochapata were significantly higher than in Santo Tomas or Pampas (P < 0.01). No sera were reactive to A. phagocytophilum. These findings suggest that human infection with E. chaffeensis occurs in Peru. Further studies are needed to characterize Ehrlichia species in Peru, their vectors and their clinical significance.

A Multipronged Approach to the Study of Peruvian Ethnomedicinal Plants: a Legacy of the ICBG-Peru Project

Journal of Natural Products. Mar, 2009  |  Pubmed ID: 19199646

A multidisciplinary and international team of scientists was assembled in the early 1990s to conduct an ethnobotanical study of plants used by the Aguaruna people of the Peruvian Amazon forest. The initial ethnobotanical project, carried out under the auspices of an International Cooperative Biodiversity Grant (ICBG), led to the collection of approximately 4000 plant species. Some members of the original team of scientists have continued this collaboration by focusing on potential sources of new anticancer, anti-infective, and wound-healing agents. This effort has uncovered several secondary metabolites representing a wide variety of chemical diversity. In this short review we describe some bioactive compounds of interest as part of our continuing collaboration.

Effect of Pyrazinamidase Activity on Pyrazinamide Resistance in Mycobacterium Tuberculosis

Tuberculosis (Edinburgh, Scotland). Mar, 2009  |  Pubmed ID: 19249243

Resistance of Mycobacterium tuberculosis to pyrazinamide is associated with mutations in the pncA gene, which codes for pyrazinamidase. The association between the enzymatic activity of mutated pyrazinamidases and the level of pyrazinamide resistance remains poorly understood. Twelve M. tuberculosis clinical isolates resistant to pyrazinamide were selected based on Wayne activity and localization of pyrazinamidase mutation. Recombinant pyrazinamidases were expressed and tested for their kinetic parameters (activity, k(cat), K(m), and efficiency). Pyrazinamide resistance level was measured by Bactec-460TB and 7H9 culture. The linear correlation between the resistance level and the kinetic parameters of the corresponding mutated pyrazinamidase was calculated. The enzymatic activity and efficiency of the mutated pyrazinamidases varied with the site of mutation and ranged widely from low to high levels close to the corresponding of the wild type enzyme. The level of resistance was significantly associated with pyrazinamidase activity and efficiency, but only 27.3% of its statistical variability was explained. Although pyrazinamidase mutations are indeed associated with resistance, the loss of pyrazinamidase activity and efficiency as assessed in the recombinant mutated enzymes is not sufficient to explain a high variability of the level of pyrazinamide resistance, suggesting that complementary mechanisms for pyrazinamide resistance in M. tuberculosis with mutations in pncA are more important than currently thought.

Evaluation of Nitazoxanide and Oxfendazole Efficacy Against Cystic Echinococcosis in Naturally Infected Sheep

The American Journal of Tropical Medicine and Hygiene. Mar, 2009  |  Pubmed ID: 19270283

Cystic echinococosis (CE) is a public health problem caused by Echinococcus granulosus. We aimed to determine the efficacy of nitazoxanide (NTZ) and oxfendazole (OXF) against CE in naturally infected sheep. A total of 151 ewes were assigned to the following groups: 15 mg/kg of NTZ weekly for five weeks (NTZ5); two rounds of 15 mg/ kg of NTZ a day for five days (NTZ5x2) two weeks apart; 30 mg/kg of OXF a week for 11 weeks (OXF11); 30 mg/kg of OXF plus 15 mg/kg of NTZ a week for 11 weeks (OXF/NTZ); and the control group. OXF11 and OXF/NTZ decreased the number of fertile cysts, increased the number of degenerated cysts, and were more efficacious (49.6-61.2%) against lung cysts and liver cysts (91.8-100%) than any other treatment group. OXF might be an additional strategy for control programs and an optional treatment of human CE after it is licensed.

Urine Antigen Detection for the Diagnosis of Human Neurocysticercosis

The American Journal of Tropical Medicine and Hygiene. Mar, 2009  |  Pubmed ID: 19270285

Neurocysticercosis (NCC) is a major cause of seizures and epilepsy. Diagnosis is based on brain imaging, supported by immunodiagnosis in serum or cerebrospinal fluid (CSF). Lumbar puncture is invasive and painful. Blood sampling is slightly painful and poorly accepted. Urine antigen detection has been used for other parasites and tried in NCC with suboptimal performance. We used a monoclonal antibody-based ELISA to detect Taenia solium antigens in urine from 87 Peruvian neurocysticercosis patients (viable cysts, N = 34; subarachnoid cysticercosis, N = 10; degenerating parasites, N = 7; calcified lesions, N = 36) and 32 volunteers from a non-endemic area of Peru. Overall sensitivity of urine antigen detection for viable parasites was 92%, which decreased to 62.5% in patients with a single cyst. Most patients (30/36, 83%) with only calcified cysticercosis were urine antigen negative. Antigen levels in paired serum/urine samples (evaluated in 19 patients) were strongly correlated. Non-invasive urine testing for T. solium antigens provides a useful alternative for NCC diagnosis.

Geographic Variation in the Sensitivity of Recombinant Antigen-based Rapid Tests for Chronic Trypanosoma Cruzi Infection

The American Journal of Tropical Medicine and Hygiene. Mar, 2009  |  Pubmed ID: 19270291

Chagas disease affects 8-11 million people throughout the Americas. Early detection is crucial for timely treatment and to prevent non-vectorial transmission. Recombinant antigen-based rapid tests had high sensitivity and specificity in laboratory evaluations, but no Peruvian specimens were included in previous studies. We evaluated Stat-Pak and Trypanosoma Detect rapid tests in specimens from Bolivia and Peru. Specimens positive by three conventional assays were confirmed positives; specimens negative by two or more assays were confirmed negatives. In Bolivian specimens, Stat-Pak and Trypanosoma Detect tests were 87.5% and 90.7% sensitive, respectively; both showed 100% specificity. Sensitivity in Peruvian specimens was much lower: 26.6-33.0% (Stat-Pak) and 54.3-55.2% (Trypanosoma Detect); both had specificities > 98%. Even in Bolivian specimens, these sensitivities are inadequate for stand-alone screening. The low sensitivity in Peru may be related to parasite strain differences. Chagas disease rapid tests should be field tested in each geographic site before widespread implementation for screening.

Spatial Patterns in Discordant Diagnostic Test Results for Chagas Disease: Links to Transmission Hotspots

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Apr, 2009  |  Pubmed ID: 19278335

Diagnosis of Chagas disease is hindered by discordance between screening and confirmatory test results for Trypanosoma cruzi infection. In periurban Arequipa, Peru, spatial analysis revealed that individuals with discordant test results are spatially clustered in hotspots of T. cruzi transmission, suggesting that discordant results likely represent true infections in this setting.

Upper-room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

PLoS Medicine. Mar, 2009  |  Pubmed ID: 19296717

Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air.

Epilepsy and Neurocysticercosis: an Incidence Study in a Peruvian Rural Population

Neuroepidemiology. 2009  |  Pubmed ID: 19325247

Epilepsy is a serious neurological disorder and neurocysticercosis (NCC), the central nervous system infection by the larvae of Taenia solium, is the main cause of acquired epilepsy in developing countries. NCC is becoming more frequent in industrialized countries due to immigration from endemic areas. Previously reported epilepsy incidences range from 30 to 50/100,000 people in industrialized countries and 90 to 122/100,000 people in developing countries.

Comparison of Culture Techniques at Different Stages of Brucellosis

The American Journal of Tropical Medicine and Hygiene. Apr, 2009  |  Pubmed ID: 19346389

The lysis centrifugation technique is preferred for culturing Brucella spp. at all stages of brucellosis because it yields 25% more positive results and on average provides results 10 days earlier than the Ruiz-Castaneda method. This lysis method is inexpensive and easier to use and may be used in laboratories with limited expertise or equipment if all safety precautions are taken.

Detection of Taenia Solium Antigens and Anti-T. Solium Antibodies in Paired Serum and Cerebrospinal Fluid Samples from Patients with Intraparenchymal or Extraparenchymal Neurocysticercosis

The Journal of Infectious Diseases. May, 2009  |  Pubmed ID: 19358669

Neurocysticercosis (NCC) is a frequent cause of epilepsy worldwide. Compared with the more common parenchymal brain cysts, extraparenchymal infections are difficult to manage and have a poor prognosis. Serological assays are used to detect circulating Taenia solium antigens or anti-T. solium antibodies in serum or cerebrospinal fluid (CSF) samples. There are no guidelines on whether to use serum or CSF specimens for a particular assay.

Utility of a Protein Fraction with Cathepsin L-Like Activity Purified from Cysticercus Fluid of Taenia Solium in the Diagnosis of Human Cysticercosis

The American Journal of Tropical Medicine and Hygiene. Jun, 2009  |  Pubmed ID: 19478259

Neurocysticercosis, an endemic parasitic disease in most developing countries, is caused by Taenia solium and compromises the human central nervous system. Cathepsin L-like proteases are secreted by several parasites including T. solium and constitute important antigens for immunodiagnostics. A protein fraction with cathepsin L-like activity was purified from the cysticercus fluid by size exclusion and ion exchange chromatography. Cathepsin L-like activity was measured fluorometrically by detecting the hydrolysis of the fluorogenic substrate Z-Phe-Arg-AMC. The purified protein fraction included antigens of 53 and 25 kD that were tested in a Western immunoblot and in an enzyme-linked immunosorbent assay (ELISA) for detection of human cysticercosis. The sensitivity of the Western immunoblot was 96% for patients infected with multiple cysts and 78% for patients with a single cyst. Specificity was 98%. The sensitivity of the ELISA was 98% in patients with multiple cysts and 84% in patients with a single cyst. Specificity was 92.7%.

The Effect on Cardiovascular Risk Factors of Migration from Rural to Urban Areas in Peru: PERU MIGRANT Study

BMC Cardiovascular Disorders. 2009  |  Pubmed ID: 19505331

Mass-migration observed in Peru from the 1970s occurred because of the need to escape from politically motivated violence and work related reasons. The majority of the migrant population, mostly Andean peasants from the mountainous areas, tends to settle in clusters in certain parts of the capital and their rural environment could not be more different than the urban one. Because the key driver for migration was not the usual economic and work-related reasons, the selection effects whereby migrants differ from non-migrants are likely to be less prominent in Peru. Thus the Peruvian context offers a unique opportunity to test the effects of migration.

Sputum PCR-single-strand Conformational Polymorphism Test for Same-day Detection of Pyrazinamide Resistance in Tuberculosis Patients

Journal of Clinical Microbiology. Sep, 2009  |  Pubmed ID: 19535526

Pyrazinamide is a first-line drug for treating tuberculosis, but pyrazinamide resistance testing is usually too slow to guide initial therapy, so some patients receive inappropriate therapy. We therefore aimed to optimize and evaluate a rapid molecular test for tuberculosis drug resistance to pyrazinamide. Tuberculosis PCR-single-strand conformational polymorphism (PCR-SSCP) was optimized to test for mutations causing pyrazinamide resistance directly from sputum samples and Mycobacterium tuberculosis isolates. The reliability of PCR-SSCP tests for sputum samples (n = 65) and Mycobacterium tuberculosis isolates (n = 185) from 147 patients was compared with four tests for pyrazinamide resistance: Bactec-460 automated culture, the Wayne biochemical test, DNA sequencing for pncA mutations, and traditional microbiological broth culture. PCR-SSCP provided interpretable results for 96% (46/48) of microscopy-positive sputum samples, 76% (13/17) of microscopy-negative sputum samples, and 100% of Mycobacterium tuberculosis isolates. There was 100% agreement between PCR-SSCP results from sputum samples and Mycobacterium tuberculosis isolates and 100% concordance between 50 blinded PCR-SSCP rereadings by three observers. PCR-SSCP agreement with the four other tests for pyrazinamide resistance varied from 89 to 97%. This was similar to how frequently the four other tests for pyrazinamide resistance agreed with each other: 90 to 94% for Bactec-460, 90 to 95% for Wayne, 92 to 95% for sequencing, and 91 to 95% for broth culture. PCR-SSCP took less than 24 hours and cost approximately $3 to $6, in contrast with the other assays, which took 3 to 14 weeks and cost $7 to $47. In conclusion, PCR-SSCP is a relatively reliable, rapid, and inexpensive test for pyrazinamide resistance that indicates which patients should receive pyrazinamide from the start of therapy, potentially preventing months of inappropriate treatment.

Linking Deforestation to Malaria in the Amazon: Characterization of the Breeding Habitat of the Principal Malaria Vector, Anopheles Darlingi

The American Journal of Tropical Medicine and Hygiene. Jul, 2009  |  Pubmed ID: 19556558

This study examined the larval breeding habitat of a major South American malaria vector, Anopheles darlingi, in areas with varying degrees of ecologic alteration in the Peruvian Amazon. Water bodies were repeatedly sampled across 112 km of transects along the Iquitos-Nauta road in ecologically varied areas. Field data and satellite imagery were used to determine the landscape composition surrounding each site. Seventeen species of Anopheles larvae were collected. Anopheles darlingi larvae were present in 87 of 844 sites (10.3%). Sites with A. darlingi larvae had an average of 24.1% forest cover, compared with 41.0% for sites without A. darlingi (P < 0.0001). Multivariate analysis identified seasonality, algae, water body size, presence of human populations, and the amount of forest and secondary growth as significant determinants of A. darlingi presence. We conclude that deforestation and associated ecologic alterations are conducive to A. darlingi larval presence, and thereby increase malaria risk.

Global Health Training is Not Only a Developed-country Duty

Journal of Public Health Policy. Jul, 2009  |  Pubmed ID: 19597458

Norovirus Highly Prevalent Cause of Endemic Acute Diarrhea in Children in the Peruvian Amazon

The Pediatric Infectious Disease Journal. Sep, 2009  |  Pubmed ID: 19636281

To determine the burden of norovirus infections in children stools from a longitudinal community cohort were evaluated using reverse transcription polymerase chain reaction. Norovirus was detected in 21.3% of diarrheal and 8.0% of nondiarrheal stools (P < 0.01). Norovirus diarrhea was highly associated with age and the odds ratio for norovirus diarrhea fell by 2.8% per month (OR = 0.97, 95% CI: 0.95-0.99). Norovirus seems to be an important etiology of community acquired diarrhea in this study population.

Molecular Epidemiology of Brucella Genotypes in Patients at a Major Hospital in Central Peru

Journal of Clinical Microbiology. Oct, 2009  |  Pubmed ID: 19656979

The multiple-locus variable-number repeat analysis of 90 human Brucella melitensis isolates from a large urban area in central Peru revealed variations at 4 (Bruce07, Bruce09, Bruce18, and Bruce42) out of 16 loci investigated, of which 1 (Bruce42) also is used for species identification. Ten genotypes were identified, separated by the number of Bruce42 repeats into two groups that may have distinct phenotypic characteristics. Whereas genotypes with five or six Bruce42 repeats were cultured mainly from adult patients, genotypes with three Bruce42 repeats were isolated from children and young adolescents as well as from adults. In addition, the isolates with three Bruce42 repeats were obtained more often from patients with splenomegaly (P = 0.02) or hepatomegaly (P = 0.006). An annual variation in the diversity of genotypes was observed, possibly reflecting changes in sources of fresh dairy products, supply routes to city shops and markets, and the movement of infected dairy goat herds.

Gender Differences in Sex-related Alcohol Expectancies in Young Adults from a Peri-urban Area in Lima, Peru

Revista Panamericana De Salud Pública = Pan American Journal of Public Health. Jun, 2009  |  Pubmed ID: 19695144

To estimate the effect of sex-related alcohol expectancies (SRAE) on hazardous drinking prevalence and examine gender differences in reporting SRAE.

Helicobacter Pylori's Plasticity Zones Are Novel Transposable Elements

PloS One. 2009  |  Pubmed ID: 19727398

Genes present in only certain strains of a bacterial species can strongly affect cellular phenotypes and evolutionary potentials. One segment that seemed particularly rich in strain-specific genes was found by comparing the first two sequenced Helicobacter pylori genomes (strains 26695 and J99) and was named a "plasticity zone".

Interleukin-1 Beta Single-nucleotide Polymorphism's C Allele is Associated with Elevated Risk of Gastric Cancer in Helicobacter Pylori-infected Peruvians

The American Journal of Tropical Medicine and Hygiene. Nov, 2009  |  Pubmed ID: 19861615

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.

Congenital Trypanosoma Cruzi Transmission in Santa Cruz, Bolivia

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Dec, 2009  |  Pubmed ID: 19877966

We conducted a study of congenital Trypanosoma cruzi infection in Santa Cruz, Bolivia. Our objective was to apply new tools to identify weak points in current screening algorithms, and find ways to improve them.

Preliminary Population-based Epidemiological and Clinical Data on 2009 Pandemic H1N1 Influenza A (pH1N1) from Lima, Peru

Influenza and Other Respiratory Viruses. Nov, 2009  |  Pubmed ID: 19903205

Factors Associated with Delayed Tuberculosis Test-seeking Behavior in the Peruvian Amazon

The American Journal of Tropical Medicine and Hygiene. Dec, 2009  |  Pubmed ID: 19996443

This study aimed to determine the psychosocial factors associated with delayed test-seeking among tuberculosis patients. The duration of symptoms before seeking medical care was assessed by interview for 108 newly diagnosed pulmonary tuberculosis patients in the city of Iquitos in the Peruvian Amazon, which has high tuberculosis incidence. Beliefs associated with test-seeking behavior and delay was assessed in these patients. The median delay from symptom onset to seeking diagnostic testing was 61 days (inter-quartile range 30-91 days). The belief that tuberculosis is curable was associated with a 100% longer test-seeking delay; the perception that tuberculosis was common was associated with a 57% longer delay; male gender was associated with a 48% longer delay; and education less than complete secondary schooling was associated with a 44% longer delay. In conclusion, current health promotion activities that emphasize tuberculosis curability and high prevalence may paradoxically increase test-seeking delay and therefore require prospective evaluation.

Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

PLoS Neglected Tropical Diseases. 2009  |  Pubmed ID: 20016830

Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission.

Multiantigen Print Immunoassay for Comparison of Diagnostic Antigens for Taenia Solium Cysticercosis and Taeniasis

Clinical and Vaccine Immunology : CVI. Jan, 2010  |  Pubmed ID: 19906893

One of the best-characterized tests for the diagnosis of neurocysticercosis is the enzyme-linked immunoelectrotransfer blot assay, developed at the CDC, which uses lentil lectin-purified glycoproteins (LLGPs) extracted from Taenia solium cysticerci. The purification of the LLGP antigens has been difficult to standardize, and the polyacrylamide gel system used for the immunoblot assay is not easily transferable to other laboratories. In this study, we developed a multiantigen printing immunoassay (MAPIA) to compare the performance of multiple recombinant Taenia solium proteins with the potential for the detection of cysticercosis and taeniasis. We prepared MAPIA strips using six cysticercosis and two taeniasis diagnostic proteins and compared the performance of the proteins with sera collected from defined cysticercosis and taeniasis cases. Of the six cysticercosis antigens, rT24H performed well in detecting cases with two or more viable cysts in the brain (sensitivity and specificity, 97% and 99.4%, respectively); the use of a combination of cysticercosis antigens did not improve the sensitivity of the test and decreased the specificity. None of the antigens could differentiate the different clinical presentations of cysticercosis. Both of the taeniasis antigens (rES33 and rES38) had the same sensitivity of 99.4% and specificities of 93.9% and 94.5%, respectively. Some cross-reactivity against rES33 and rES38 was found, especially with sera from cases infected with Schistosoma mansoni. We conclude that MAPIA is a simple and effective tool that may be used to compare antibody responses to different cysticercosis and taeniasis antigens and, in this case, may be useful for the rapid detection of T. solium cases.

STAT3, P38 MAPK, and NF-kappaB Drive Unopposed Monocyte-dependent Fibroblast MMP-1 Secretion in Tuberculosis

American Journal of Respiratory Cell and Molecular Biology. Oct, 2010  |  Pubmed ID: 19915152

Tissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells. We investigated mechanisms regulating Mtb-induced collagenolytic activity in fibroblasts in vitro and in patients. Lung fibroblasts were stimulated with conditioned media from Mtb-infected monocytes (CoMTb). CoMTb induced sustained increased MMP-1 (74 versus 16 ng/ml) and decreased tissue inhibitor of metalloproteinase (TIMP)-1 (8.6 versus 22.3 ng/ml) protein secretion. CoMTb induced a 2.7-fold increase in MMP-1 promoter activation and a 2.5-fold reduction in TIMP-1 promoter activation at 24 hours (P = 0.01). Consistent with this, TIMP-1 did not co-localize with fibroblasts in patient granulomas. MMP-1 up-regulation and TIMP-1 down-regulation were p38 (but not extracellular signal-regulated kinase or c-Jun N-terminal kinase) mitogen-activated protein kinase-dependent. STAT3 phosphorylation was detected in fibroblasts in vitro and in tuberculous granulomas. STAT3 inhibition reduced fibroblast MMP-1 secretion by 60% (P = 0.046). Deletion of the MMP-1 promoter NF-κB-binding site abrogated promoter induction in response to CoMTb. TNF-α, IL-1β, or Oncostatin M inhibition in CoMTb decreased MMP-1 secretion by 65, 63, and 25%, respectively. This cytokine cocktail activated the same signaling pathways in fibroblasts and induced MMP-1 secretion similar to that induced by CoMTb. This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-κB, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients.

Cytotoxic and Anti-infective Sesquiterpenes Present in Plagiochila Disticha (Plagiochilaceae) and Ambrosia Peruviana (Asteraceae)

Planta Medica. May, 2010  |  Pubmed ID: 19960415

A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, Plagiochila disticha and Ambrosia peruviana, led to the isolation and characterization of three ENT-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A ( 1), I ( 2), and R ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their in vitro antileishmanial, trypanocidal, and antituberculosis activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes, as well as against MDR and sensitive strains of Mycobacterium tuberculosis, respectively.

Peruvian and Globally Reported Amino Acid Substitutions on the Mycobacterium Tuberculosis Pyrazinamidase Suggest a Conserved Pattern of Mutations Associated to Pyrazinamide Resistance

Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases. Mar, 2010  |  Pubmed ID: 19963078

Resistance to pyrazinamide in Mycobacterium tuberculosis is usually associated with a reduction of pyrazinamidase activity caused by mutations in pncA, the pyrazinamidase coding gene. Pyrazinamidase is a hydrolase that converts pyrazinamide, the antituberculous drug against the latent stage, to the active compound, pyrazinoic acid. To better understand the relationship between pncA mutations and pyrazinamide resistance, it is necessary to analyze the distribution of pncA mutations from pyrazinamide resistant strains. We determined the distribution of Peruvian and globally reported pncA missense mutations from M. tuberculosis clinical isolates resistant to pyrazinamide. The distributions of the single amino acid substitutions were compared at the secondary structure domains level. The distribution of the Peruvian mutations followed a similar pattern as the mutations reported globally. A consensus clustering of mutations was observed in hot-spot regions located in the metal coordination site and to a lesser extent in the active site of the enzyme. The data was not able to reject the null hypothesis that both distributions are similar, suggesting that pncA mutations associated to pyrazinamide resistance in M. tuberculosis, follow a conserved pattern responsible to impair the pyrazinamidase activity.

Comparison of Two Types of Epidemiological Surveys Aimed at Collecting Daily Clinical Symptoms in Community-based Longitudinal Studies

Annals of Epidemiology. Feb, 2010  |  Pubmed ID: 20123166

Investigators use prospective community-based studies to collect longitudinal information on childhood diarrhea. The interval in which data are collected may affect the accuracy and interpretation of results. Our objective was to compare data of reported daily clinical symptoms from surveys conducted daily versus twice-weekly surveys.

Development and Evaluation of a Magnetic Immunochromatographic Test to Detect Taenia Solium, Which Causes Taeniasis and Neurocysticercosis in Humans

Clinical and Vaccine Immunology : CVI. Apr, 2010  |  Pubmed ID: 20181766

Taeniasis/cysticercosis caused by Taenia solium is a frequent parasitic infection of the human brain in most of the world. Rapid and simple screening tools to identify taeniasis and cysticercosis cases are needed for control programs, mostly to identify tapeworm carriers which are the source of infection and need to be treated, or as tools for point-of-care case detection or confirmation. These screening assays should be affordable, reliable, rapid, and easy to perform. Immunochromatographic tests meet these criteria. To demonstrate proof of principle, we developed and evaluated two magnetic immunochromatographic tests (MICTs) for detection of human Taenia solium taeniasis antibodies (ES33-MICT) and neurocysticercosis antibodies (T24-MICT). These assays detected stage-specific antibodies by using two recombinant proteins, rES33 for detection of taeniasis antibodies and rT24H for detection of cysticercosis antibodies. The sensitivity and specificity of the ES33-MICT to detect taeniasis infections were 94.5% and 96%, respectively, and those of the T24-MICT to detect cases of human cysticercosis with two or more viable brain cysts were 93.9% and 98.9%, respectively. These data provide proof of principle that the ES33- and T24-MICTs provide rapid and suitable methods to identify individuals with taeniasis and cysticercosis.

Evaluation of Oxfendazole, Praziquantel and Albendazole Against Cystic Echinococcosis: a Randomized Clinical Trial in Naturally Infected Sheep

PLoS Neglected Tropical Diseases. 2010  |  Pubmed ID: 20186332

Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus. We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep.

Microscopic Observation Drug Susceptibility Assay for Tuberculosis Screening Before Isoniazid Preventive Therapy in HIV-infected Persons

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Apr, 2010  |  Pubmed ID: 20192727

Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons.

Evaluation of Molecular Tools for Detection and Drug Susceptibility Testing of Mycobacterium Tuberculosis in Stool Specimens from Patients with Pulmonary Tuberculosis

Journal of Clinical Microbiology. May, 2010  |  Pubmed ID: 20200293

Pulmonary tuberculosis diagnosis is difficult when patients cannot produce sputum. Most sputum is swallowed, and tuberculosis DNA can survive intestinal transit. We therefore evaluated molecular testing of stool specimens for detecting tuberculosis originating from the lungs. Paired stool and sputum samples (n=159) were collected from 89 patients with pulmonary tuberculosis. Control stool samples (n=47) were collected from patients without tuberculosis symptoms. Two techniques for DNA extraction from stool samples were compared, and the diagnostic accuracy of the PCR in stool was compared with the accuracy of sputum testing by PCR, microscopy, and culture. A heminested IS6110-PCR was used for tuberculosis detection, and IS6110-PCR-positive stool samples then underwent rifampin sensitivity testing by universal heteroduplex generator PCR (heteroduplex-PCR) assay. For newly diagnosed pulmonary tuberculosis patients, stool IS6110-PCR had 86% sensitivity and 100% specificity compared with results obtained by sputum culture, and stool PCR had similar sensitivities for HIV-positive and HIV-negative patients (P=0.3). DNA extraction with commercially available spin columns yielded greater stool PCR sensitivity than DNA extraction with the in-house Chelex technique (P=0.007). Stool heteroduplex-PCR had 98% agreement with the sputum culture determinations of rifampin resistance and multidrug resistance. Tuberculosis detection and drug susceptibility testing by stool PCR took 1 to 2 days compared with an average of 9 weeks to obain those results by traditional culture-based testing. Stool PCR was more sensitive than sputum microscopy and remained positive for most patients for more than 1 week of treatment. In conclusion, stool PCR is a sensitive, specific, and rapid technique for the diagnosis and drug susceptibility testing of pulmonary tuberculosis and should be considered when sputum samples are unavailable.

What is Adolescence?: Adolescents Narrate Their Lives in Lima, Peru

Journal of Adolescence. Aug, 2010  |  Pubmed ID: 20207410

This study explores the lives of Peruvian adolescents in a low-income human settlement outside of Lima. Twenty 12-17 year olds were asked to narrate their own life stories using the life history narrative research method. Holistic content analysis was coupled with a grounded-theory approach to explore these data. Intergenerational responsibility, family tensions, economic pressures, racism and violence emerged without prompting and dominated the narrators' life stories, underscoring the degree to which these adolescents lack access to the supportive individuals and structures that are key to positive adolescent development. The challenges faced by these and the other 5.8 million 10-19 year olds in Peru require increased attention to the role of families, peers and communities in ensuring that adolescents are able to maintain their well-being and achieve their future expectations.

Development of Low-cost Inverted Microscope to Detect Early Growth of Mycobacterium Tuberculosis in MODS Culture

PloS One. 2010  |  Pubmed ID: 20351778

The microscopic observation drug susceptibility (MODS) assay for rapid, low-cost detection of tuberculosis and multidrug resistant tuberculosis depends upon visualization of the characteristic cording colonies of Mycobacterium tuberculosis in liquid media. This has conventionally required an inverted light microscope in order to inspect the MODS culture plates from below. Few tuberculosis laboratories have this item and the capital cost of $5,000 for a high-end microscope could be a significant obstacle to MODS roll-out.

Trypanoside, Anti-tuberculosis, Leishmanicidal, and Cytotoxic Activities of Tetrahydrobenzothienopyrimidines

Bioorganic & Medicinal Chemistry. Apr, 2010  |  Pubmed ID: 20356752

The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug-optimization and drug-development efforts for use as therapeutic agents in developing countries.

Adolescents Can Know Best: Using Concept Mapping to Identify Factors and Pathways Driving Adolescent Sexuality in Lima, Peru

Social Science & Medicine (1982). Jun, 2010  |  Pubmed ID: 20382462

The primary objective of this study was to identify and describe individual- and environmental-level factors that Peruvian adolescents perceive to be related to adolescent sexuality. A series of concept mapping sessions were carried out from January-March 2006 with 63 15-17 year olds from a low-income community near Lima in order for adolescents to: (1) brainstorm items that they thought were related to sexuality, (2) sort, group and rate items to score their importance for sexuality-related outcomes, and (3) create pathways from the groups of items to engaging in sex. Brainstorming resulted in 61 items, which participants grouped into 11 clusters. The highest rated clusters were personal values, respect and confidence in partner relationships, future achievements and parent-child communication. The pathway of decision-making about having sex primarily contained items rated as only moderately important. This study identified important understudied factors, new perspectives on previously-recognized factors, and possible pathways to sexual behavior. These interesting and provocative findings underscore the importance of directly integrating adolescent voices into future sexual and reproductive health research, policies and programs that target this population.

Development and Evaluation of Porcine Cysticercosis QuickELISA in Triturus EIA Analyzer

Journal of Immunoassay & Immunochemistry. Jan, 2010  |  Pubmed ID: 20391018

We evaluated three diagnostic antigens (recombinant GP50, recombinant T24H, and synthetic Ts18var1) for cysticercosis and found that all three performed well in detecting cysticercosis in humans and pigs in several assay formats. These antigens were adapted to a new antibody detection format (QuickELISA). With one single incubation step which involves all reactants except the enzyme substrate, the QuickELISA is particularly suited for automation. We formatted the QuickELISA for the Triturus EIA analyzer for testing large numbers of samples. We found that in QuickELISA formats rGP50 and rT24H have better sensitivity and specificity than sTs18var1 for detecting porcine cysticercosis.

Migration Surrogates and Their Association with Obesity Among Within-country Migrants

Obesity (Silver Spring, Md.). Nov, 2010  |  Pubmed ID: 20395946

Limited studies have evaluated the link between acculturation and health outcomes of within-country migrants. The objective of this study was to evaluate whether well-known acculturation surrogates were associated with obesity among Peruvian rural-to-urban migrants. We performed a cross-sectional survey, the PERU MIGRANT study, using single-stage random sampling. Evaluation included weight, height, and waist circumference (WC) as well as acculturation surrogates. Obesity was assessed using BMI and WC. Length of residence, age at migration, language proficiency, and language preferences (Spanish or Quechua) were assessed in logistic regression models to calculate odd ratios and 95% confidence intervals adjusting for potential confounders. A total of 589 rural-to-urban migrants were enrolled. The mean age was 47.8 (s.d.: 11.7, range: 30-92), and 280 (47.5%) were men. Obesity prevalence assessed using BMI was 30.4% among women and 10.7% among men (P < 0.001), whereas abdominal obesity assessed using WC was 29.1% among women and 19.1% among men (P < 0.01). Obesity was associated with older age at first migration, language speaking proficiency, and language preferences. The association between obesity and acculturation surrogates is variable in this population. Thus, acculturation per se can explore positive channels associated with better health outcomes. The patterns shown in this report suggest a more complex association for these factors.

Antimycobacterial Metabolites from Plectranthus: Royleanone Derivatives Against Mycobacterium Tuberculosis Strains

Chemistry & Biodiversity. Apr, 2010  |  Pubmed ID: 20397225

The antimycobacterial activities of eight diterpenes, 1-8, isolated previously from Plectranthus and eleven esters, 9-19, of 7alpha-acetoxy-6beta,12-dihydroxyabieta-8,12-diene-11,14-dione (5) were evaluated against the MTB strains H(37)Rv and MDR. Only diterpenoids with a quinone framework revealed anti-MTB activity. Abietane 5 and its 6,12-dibenzoyl, 12-methoxybenzoyl, 12-chlorobenzoyl, and 12-nitrobenzoyl esters, 9, 11, 12, and 13, respectively, showed potent activities against the MDR strain with MIC values between 3.12 and 0.39 microg/ml. Cytotoxic activities towards 3T3 and Vero cells were also evaluated. Compound 11, with the best selectivity index, may be a suitable lead for further chemical modifications. The complete structural elucidation of the new esters, 9-14, 16, 18, and 19, as well as the NMR data of known derivatives 15 and 17 are reported.

Cloning and Characterization of the Acidic Ribosomal Protein P2 of Cryptosporidium Parvum, a New 17-kilodalton Antigen

Clinical and Vaccine Immunology : CVI. Jun, 2010  |  Pubmed ID: 20410328

Cryptosporidium infection is commonly observed among children and immunocompromised individuals in developing countries, but large-scale outbreaks of disease among adults have not been reported. In contrast, outbreaks of cryptosporidiosis in the United States and Canada are increasingly common among patients of all ages. Thus, it seems likely that residents of regions where Cryptosporidium is highly endemic acquire some level of immunity, while residents of the developed world do not. A new immunodominant Cryptosporidium parvum antigen in the 15- to 17-kDa size range was identified as the Cryptosporidium parvum 60S acidic ribosomal protein P2 (CpP2). We developed a recombinant protein-based enzyme-linked immunosorbent assay for serologic population surveillance for antibodies that was 89% sensitive and 92% specific relative to the results of the large-format Western blot assay. The human IgG response is directed almost exclusively toward the highly conserved, carboxy-terminal 15 amino acids of the protein. Although IgG antibody cross-reactivity was documented with sera from patients with acute babesiosis, the development of an anti-CpP2 antibody response in our Peru study population correlated better with Cryptosporidium infection than with infection by any other parasitic protozoan. In Haiti, the prevalence of antibodies to CpP2 plateaus at 11 to 20 years of age. Because anti-CpP2 IgG antibodies were found only among residents of countries in the developing world where Cryptosporidium infection occurs early and often, we propose that this response may be a proxy for the intensity of infection and for acquired immunity.

Risk Factors for Antibiotic-resistant Escherichia Coli Carriage in Young Children in Peru: Community-based Cross-sectional Prevalence Study

The American Journal of Tropical Medicine and Hygiene. May, 2010  |  Pubmed ID: 20439971

Few studies have examined the influence of individual-, household-, and community-scale risk factors on carriage of resistant commensal bacteria. We determined children's medical, agricultural, and environmental exposures by household, pharmacy, and health facility surveys and Escherichia coli cultures of children, mothers' hands, household animals, and market chickens in Peru. Among 522 children with a positive stool culture, by log-binomial regression, using "any antibiotic" and 1-14 (versus 0) sulfa doses in the past 3 months increased children's risk, respectively, for ampicillin- and sulfamethoxazole-resistant E. coli carriage (P = 0.01-0.02). Each household member taking "any antibiotic" increased children's risk for sulfamethoxazole- and multidrug-resistant E. coli carriage (P < 0.0001). Residence in a zone where a larger proportion of households served home-raised chicken (as contrasted with intensively antibiotic-raised market chicken) protected against carrying E. coli resistant to all drugs (P = 0.0004-0.04). Environmental contamination with drug-resistant bacteria appeared to significantly contribute to children's carriage of antibiotic-resistant E. coli.

Large Scale Immune Profiling of Infected Humans and Goats Reveals Differential Recognition of Brucella Melitensis Antigens

PLoS Neglected Tropical Diseases. 2010  |  Pubmed ID: 20454614

Brucellosis is a widespread zoonotic disease that is also a potential agent of bioterrorism. Current serological assays to diagnose human brucellosis in clinical settings are based on detection of agglutinating anti-LPS antibodies. To better understand the universe of antibody responses that develop after B. melitensis infection, a protein microarray was fabricated containing 1,406 predicted B. melitensis proteins. The array was probed with sera from experimentally infected goats and naturally infected humans from an endemic region in Peru. The assay identified 18 antigens differentially recognized by infected and non-infected goats, and 13 serodiagnostic antigens that differentiate human patients proven to have acute brucellosis from syndromically similar patients. There were 31 cross-reactive antigens in healthy goats and 20 cross-reactive antigens in healthy humans. Only two of the serodiagnostic antigens and eight of the cross-reactive antigens overlap between humans and goats. Based on these results, a nitrocellulose line blot containing the human serodiagnostic antigens was fabricated and applied in a simple assay that validated the accuracy of the protein microarray results in the diagnosis of humans. These data demonstrate that an experimentally infected natural reservoir host produces a fundamentally different immune response than a naturally infected accidental human host.

Chagas Cardiomyopathy in the Context of the Chronic Disease Transition

PLoS Neglected Tropical Diseases. 2010  |  Pubmed ID: 20502520

Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common.

Prolonged Infectiousness of Tuberculosis Patients in a Directly Observed Therapy Short-course Program with Standardized Therapy

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Aug, 2010  |  Pubmed ID: 20624064

Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program.

Diagnostic Approaches for Paediatric Tuberculosis by Use of Different Specimen Types, Culture Methods, and PCR: a Prospective Case-control Study

The Lancet Infectious Diseases. Sep, 2010  |  Pubmed ID: 20656559

The diagnosis of pulmonary tuberculosis presents challenges in children because symptoms are non-specific, specimens are difficult to obtain, and cultures and smears of Mycobacterium tuberculosis are often negative. We assessed new diagnostic approaches for tuberculosis in children in a resource-poor country.

Mechanisms Regulating Monocyte CXCL8 Secretion in Neurocysticercosis and the Effect of Antiparasitic Therapy

Journal of Immunology (Baltimore, Md. : 1950). Oct, 2010  |  Pubmed ID: 20826750

Neurocysticercosis (NCC) due to infection with Taenia solium is a major cause of epilepsy worldwide. Larval degeneration, which may follow antiparasitic treatment, results in clinical symptoms due to inflammatory cell influx. Mechanisms regulating this are not well understood, but chemokines have a key role. Stimulation of human monocytes by cyst Ags from NCC-infected pigs showed that scolex and membrane Ags drive CXCL8 and CCL2 secretion. Antiparasitic treatment of pigs increased CXCL8 in response to brain, but not muscle, cyst Ags. Cyst-fluid Ags did not elicit monocyte chemokine secretion, inhibited LPS-induced CXCL8 by up to 89%, but did not alter CCL2 secretion. This effect was inhibited by anti-IL-10 Abs. Plasma CXCL8, TNF-α, IL-10, eotaxin, IL-1, IL-1ra, soluble IL-1R-II, and soluble TNFR-I and -II levels were evaluated in 167 NCC patients. Patients had lower plasma CXCL8 and TNF-α concentrations than control subjects. In summary, larval Ags from brain and muscle cysts differentially regulate chemokine secretion. Cyst-fluid inhibits CXCL8, and this is blocked by anti-IL-10 Abs. CXCL8 concentrations are decreased in patient plasma. Following anti-parasitic therapy, scolex and membrane Ags are exposed, and cyst fluid is decreased, leading to inflammatory cell influx. Taken together, the cellular, porcine, and human data may explain, in part, why NCC is usually asymptomatic but may cause proinflammatory symptoms, particularly following treatment.

Physical Activity and Cardiovascular Risk Factors Among Rural and Urban Groups and Rural-to-urban Migrants in Peru: a Cross-sectional Study

Revista Panamericana De Salud Pública = Pan American Journal of Public Health. Jul, 2010  |  Pubmed ID: 20857014

To compare physical activity and sedentary behavior patterns of rural-to-urban migrants in Peru versus lifetime rural and urban residents and to determine any associations between low physical activity and four cardiovascular risk factors: obesity (body mass index > 30 kg/m²), systolic and diastolic blood pressure, hypertension, and metabolic syndrome.

Optimizing Tuberculosis Testing for Basic Laboratories

The American Journal of Tropical Medicine and Hygiene. Oct, 2010  |  Pubmed ID: 20889887

Optimal tuberculosis testing usually involves sputum centrifugation followed by broth culture. However, centrifuges are biohazardous and scarce in the resource-limited settings where most tuberculosis occurs. To optimize tuberculosis testing for these settings, centrifugation of 111 decontaminated sputum samples was compared with syringe-aspiration through polycarbonate membrane-filters that were then cultured in broth. To reduce the workload of repeated microscopic screening of broth cultures for tuberculosis growth, the colorimetric redox indicator 2,3-diphenyl-5-(2-thienyl) tetrazolium chloride was added to the broth, which enabled naked-eye detection of culture positivity. This combination of filtration and colorimetric growth-detection gave similar results to sputum centrifugation followed by culture microscopy regarding mean colony counts (43 versus 48; P = 0.6), contamination rates (0.9% versus 1.8%; P = 0.3), and sensitivity (94% versus 95%; P = 0.7), suggesting equivalency of the two methods. By obviating centrifugation and repeated microscopic screening of cultures, this approach may constitute a more appropriate technology for rapid and sensitive tuberculosis diagnosis in basic laboratories.

The Prevalence of Angina Symptoms and Association with Cardiovascular Risk Factors, Among Rural, Urban and Rural to Urban Migrant Populations in Peru

BMC Cardiovascular Disorders. 2010  |  Pubmed ID: 20932298

Rural-to-urban migration in low- and middle-income countries causes an increase in individual cardiovascular risk. Cost-effective interventions at early stages of the natural history of coronary disease such as angina may stem an epidemic of premature coronary deaths in these countries. However, there are few data on the prevalence of angina in developing countries, whilst the understanding the aetiology of angina is complicated by the difficulty in measuring it across differing populations.

Molecular Analysis of Household Transmission of Giardia Lamblia in a Region of High Endemicity in Peru

The Journal of Infectious Diseases. Dec, 2010  |  Pubmed ID: 20977340

Giardia lamblia is ubiquitous in multiple communities of nonindustrialized nations. Genotypes A1, A2, and B (Nash groups 1, 2, and 3, respectively) are found in humans, whereas genotypes C and D are typically found in dogs. However, genotypes A and B have occasionally been identified in dogs.

Helicobacter Pylori from Peruvian Amerindians: Traces of Human Migrations in Strains from Remote Amazon, and Genome Sequence of an Amerind Strain

PloS One. 2010  |  Pubmed ID: 21124785

The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes.

[Epidemiology and Control of Cysticercosis in Peru]

Revista Peruana De Medicina Experimental Y Salud Pública. Oct-Dec, 2010  |  Pubmed ID: 21308201

Neurocysticercosis, the infection of the human central nervous system by the larval stage of the cestode Taenia solium, is an important cause of epilepsy and other neurological manifestations in Peru and most developing countries. Since 1987, the Cysticercosis Working Group in Peru has performed a series of epidemiological studies which led to estimate the impact and to better understand the transmission of Taenia solium. This information was later applied to the design and execution of a control program in Tumbes, in the Northern Coast of Peru. This paper reviews the main epidemiological findings, as well as the conceptual framework of the elimination program and the tools used. Advances in the control of taeniasis/cysticercosis in our country open the road towards its elimination and potential eradication.

Wealth and Its Associations with Enteric Parasitic Infections in a Low-income Community in Peru: Use of Principal Component Analysis

The American Journal of Tropical Medicine and Hygiene. Jan, 2011  |  Pubmed ID: 21212198

The association of wealth and infections with Giardia, Cryptosporidium, Cyclospora, and microsporidia were examined in a longitudinal cohort conducted in Peru from 2001 to 2006. Data from 492 participants were daily clinical manifestations, weekly copro-parasitological diagnosis, and housing characteristics and assets owned (48 variables), and these data were used to construct a global wealth index using principal component analysis. Data were analyzed using continuous and categorical (wealth tertiles) models. Participant's mean age was 3.43 years (range = 0-12 years), with average follow-up of 993 days. Univariate and multivariate analyses identified significant associations between wealth and infections with Giardia and microsporidia. Participants with greater wealth indexes were associated with protection against Giardia (P < 0.001) and persistent Giardia infections (> 14 days). For microsporidia, greater wealth was protective (P = 0.066 continuous and P = 0.042 by tertiles). Contrarily, infections with Cryptosporidium and Cyclospora were independent of wealth. Thus, subtle differences in wealth may affect the frequency of specific parasitic infections within low-income communities.

Autonomic Dysfunction and Risk Factors Associated with Trypanosoma Cruzi Infection Among Children in Arequipa, Peru

The American Journal of Tropical Medicine and Hygiene. Jan, 2011  |  Pubmed ID: 21212207

Chagas disease affects an estimated 8 million people in Latin America. Infected individuals have 20-30% lifetime risk of developing cardiomyopathy, but more subtle changes in autonomic responses may be more frequent. We conducted a matched case-control study of children in Arequipa, Peru, where triatomine infestation and Trypanosoma cruzi infection are emerging problems. We collected data on home environment, history, physical examination, electrocardiogram, and autonomic testing. Signs of triatomine infestation and/or animals sleeping in the child's room and household members with Chagas disease were associated with increased infection risk. Electrocardiogram findings did not differ between cases and controls. However, compared with control children, infected children had blunted autonomic responses by three different measures, the Valsalva maneuver, the cold pressor test, and the orthostatic test. T. cruzi-infected children show autonomic dysfunction, although the prognostic value of this finding is not clear. Sustained vector control programs are essential to decreasing future T. cruzi infections.

Effects of Distance from a Heavily Transited Avenue on Asthma and Atopy in a Periurban Shantytown in Lima, Peru

The Journal of Allergy and Clinical Immunology. Apr, 2011  |  Pubmed ID: 21237505

Proximity to roadways increases the risk of asthma in developed countries; however, relatively little is known about this relationship in developing countries, where rapid and uncontrolled growth of cities has resulted in urban sprawl and heavy traffic volumes.

Pharmacokinetics of Combined Treatment with Praziquantel and Albendazole in Neurocysticercosis

British Journal of Clinical Pharmacology. Jul, 2011  |  Pubmed ID: 21332573

Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis.

A History of Chagas Disease Transmission, Control, and Re-emergence in Peri-rural La Joya, Peru

PLoS Neglected Tropical Diseases. 2011  |  Pubmed ID: 21364970

The history of Chagas disease control in Peru and many other nations is marked by scattered and poorly documented vector control campaigns. The complexities of human migration and sporadic control campaigns complicate evaluation of the burden of Chagas disease and dynamics of Trypanosoma cruzi transmission.

A Worldwide Analysis of Beta-defensin Copy Number Variation Suggests Recent Selection of a High-expressing DEFB103 Gene Copy in East Asia

Human Mutation. Jul, 2011  |  Pubmed ID: 21387465

Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region.

Dihydro-β-agarofuran Sesquiterpenes Isolated from Celastrus Vulcanicola As Potential Anti-Mycobacterium Tuberculosis Multidrug-resistant Agents

Bioorganic & Medicinal Chemistry. Apr, 2011  |  Pubmed ID: 21419633

In the present study, we report four new dihydro-β-agarofuran sesquiterpenes (1-4), which were isolated from the leaves of Celastrus vulcanicola, in addition to five derivatives (5-9). Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, X-ray studies, chemical correlations and biogenetic means. Compounds 1-9 and the previously reported sesquiterpenes 10-25 have been tested as potential antimycobacterial agents against sensitive and resistant Mycobacterium tuberculosis strains. 1α-Acetoxy-6β,9β-dibenzoyloxy-dihydro-β-agarofuran (20) exhibited antituberculosis activity against the MDR TB strain with a MIC value of 6.2 μg/mL, comparable to or better than isoniazid or rifampin, two of the best first-line drugs commonly used in the treatment of TB. The structure-activity relationship is discussed.

Anti-triatomine Saliva Immunoassays for the Evaluation of Impregnated Netting Trials Against Chagas Disease Transmission

International Journal for Parasitology. May, 2011  |  Pubmed ID: 21426907

Insecticide-impregnated nets can kill triatomine bugs, but it remains unclear whether they can protect against Chagas disease transmission. In a field trial in Quequeña, Peru, sentinel guinea pigs placed in intervention enclosures covered by deltamethrin-treated nets showed significantly lower antibody responses to saliva of Triatoma infestans compared with animals placed in pre-existing control enclosures. Our results strongly suggest that insecticide-treated nets prevent triatomine bites and can thereby protect against infection with Trypanosoma cruzi. Anti-salivary immunoassays are powerful new tools to evaluate intervention strategies against Chagas disease.

Serologic Diagnosis of Human Taenia Solium Cysticercosis by Using Recombinant and Synthetic Antigens in QuickELISAâ„¢

The American Journal of Tropical Medicine and Hygiene. Apr, 2011  |  Pubmed ID: 21460015

Diagnosis of Taenia solium cysticercosis is an important component in the control and elimination of cysticercosis and taeniasis. New detection assays using recombinant and synthetic antigens originating from the lentil lectin-purified glycoproteins (LLGPs) of T. solium cysticerci were developed in a QuickELISAâ„¢ format. We analyzed a panel of 474 serum samples composed of 108 serum samples from donors with two or more viable cysts, 252 serum samples from persons with other parasitic infections, and 114 serum samples from persons with no documented illnesses. The sensitivities and specificities of T24H QuickELISAâ„¢, GP50 QuickELISAâ„¢, and Ts18var1 QuickELISAâ„¢ were 96.3% and 99.2%, 93.5% and 98.6%, and 89.8% and 96.4%, respectively, for detecting cases with multiple, viable cysts. T24H QuickELISAâ„¢ performs best among the three assays, and has sensitivity and specificity values comparable to those of the LLGP enzyme-linked immunosorbent blot. The QuickELISAâ„¢ are simple, rapid quantitative methods for detecting antibodies specific for T. solium cysticerci antigens.

A1C As a Diagnostic Criteria for Diabetes in Low- and Middle-income Settings: Evidence from Peru

PloS One. 2011  |  Pubmed ID: 21464957

To determine the prevalence of type 2 diabetes mellitus, in three groups of Peruvian adults, using fasting glucose and glycosylated hemoglobin (A1C).

Cytotoxic and Anti-infective Phenolic Compounds Isolated from Mikania Decora and Cremastosperma Microcarpum

Planta Medica. Sep, 2011  |  Pubmed ID: 21472652

An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes.

Differences in Cardiovascular Risk Factors in Rural, Urban and Rural-to-urban Migrants in Peru

Heart (British Cardiac Society). May, 2011  |  Pubmed ID: 21478383

To assess differences in cardiovascular risk profiles among rural-to-urban migrants and non-migrant groups.

Autosome STRs in Native South America-Testing Models of Association with Geography and Language

American Journal of Physical Anthropology. Jul, 2011  |  Pubmed ID: 21520008

Information on one Ecuadorian and three Peruvian Amerindian populations for 11 autosomal short tandem repeat (STR) loci is presented and incorporated in analyses that includes 26 other Native groups spread all over South America. Although in comparison with other studies we used a reduced number of markers, the number of populations included in our analyses is currently unmatched by any genome-wide dataset. The genetic polymorphisms indicate a clear division of the populations into three broad geographical areas: Andes, Amazonia, and the Southeast, which includes the Chaco and southern Brazil. The data also show good agreement with proposed hypotheses of splitting and dispersion of major language groups over the last 3,000 years. Therefore, relevant aspects of Native American history can be traced using as few as 11 STR autosomal markers coupled with a broad geographic distribution of sampled populations.

[Health-related Quality of Life Among Urban and Rural to Urban Migrant Populations in Lima, Peru]

Revista Peruana De Medicina Experimental Y Salud Pública. Mar, 2011  |  Pubmed ID: 21537767

To explore if there is a difference in the perception and self reported quality of life between rural-to-urban migrants and urban groups.

The Effect of Rural-to-urban Migration on Social Capital and Common Mental Disorders: PERU MIGRANT Study

Social Psychiatry and Psychiatric Epidemiology. Jun, 2011  |  Pubmed ID: 21667301

OBJECTIVE: This study aims to investigate whether there are differences in the prevalence of common mental disorders and social capital between migrant and non-migrant groups in Peru. METHODOLOGY: The PERU MIGRANT study is a cross-sectional study comprising three groups: an urban group from a shanty town in Lima; a rural group from a community in Ayacucho-Peru; and a migrant group originally from Ayacucho currently living in the same urban shanty town. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12), and social capital was assessed using the Short Social Capital Assessment Tool (SASCAT). Poisson regression with robust standard errors was used to estimate prevalence ratios. RESULTS: The overall prevalence of common mental disorders was 39.4%; the highest prevalence was observed in the rural group. Similar patterns were observed for cognitive social capital and structural social capital. However after adjustment for sex, age, family income and education, all but one of the significant relationships was attenuated, suggesting that in this population migration per se does not impact on common mental health disorders or social capital. CONCLUSIONS: In the PERU MIGRANT study, we did not observe a difference in the prevalence of common mental disorders, cognitive and structural social capital between migrant and urban groups. This pattern of associations was also similar in rural and urban groups, except that a higher prevalence ratio of structural social capital was observed in the rural group.

Cavia Porcellus As a Model for Experimental Infection by Trypanosoma Cruzi

The American Journal of Pathology. Jul, 2011  |  Pubmed ID: 21703410

The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 10(4) trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were sacrificed 5, 15, 20, 25, 40, 55, 115, 165, and 365 days after inoculation. During the acute phase (15 to 55 days), we observed parasitemia (with a peak on day 20) and positive IgM and IgG Western blots with anti-shed acute-phase antigen bands. The cardiac tissue showed vasculitis, necrosis (on days 40 to 55), moderate to severe inflammation, and abundant amastigote nests. Smaller numbers of amastigote nests were also present in kidney, brain, and other organs. In the early chronic phase (115 to 165 days), parasitemia disappeared and anti-T. cruzi IgG antibodies were still detectable. In cardiac tissue, the number of amastigote nests and the grade of inflammation decreased. In the chronic phase (365 days), the cardiac tissue showed vasculitis and fibrosis; detectable parasite DNA was associated with higher grades of inflammation. The experimental T. cruzi infection model in guinea pigs shows kinetics and pathologic changes similar to those of the human disease.

Effect of Urbanisation on Asthma, Allergy and Airways Inflammation in a Developing Country Setting

Thorax. Dec, 2011  |  Pubmed ID: 21730351

Asthma is a growing public health problem in developing countries. However, few studies have studied the role of urbanisation in this phenomenon. It was hypothesised that children living in a peri-urban setting in Peru have higher rates of asthma and allergy than rural counterparts.

Attenuated CagA Oncoprotein in Helicobacter Pylori from Amerindians in Peruvian Amazon

The Journal of Biological Chemistry. Aug, 2011  |  Pubmed ID: 21757722

Population genetic analyses of bacterial genes whose products interact with host tissues can give new understanding of infection and disease processes. Here we show that strains of the genetically diverse gastric pathogen Helicobacter pylori from Amerindians from the remote Peruvian Amazon contain novel alleles of cagA, a major virulence gene, and reveal distinctive properties of their encoded CagA proteins. CagA is injected into the gastric epithelium where it hijacks pleiotropic signaling pathways, helps Hp exploit its special gastric mucosal niche, and affects the risk that infection will result in overt gastroduodenal diseases including gastric cancer. The Amerindian CagA proteins contain unusual but functional tyrosine phosphorylation motifs and attenuated CRPIA motifs, which affect gastric epithelial proliferation, inflammation, and bacterial pathogenesis. Amerindian CagA proteins induced less production of IL-8 and cancer-associated Mucin 2 than did those of prototype Western or East Asian strains and behaved as dominant negative inhibitors of action of prototype CagA during mixed infection of Mongolian gerbils. We suggest that Amerindian cagA is of relatively low virulence, that this may have been selected in ancestral strains during infection of the people who migrated from Asia into the Americas many thousands of years ago, and that such attenuated CagA proteins could be useful therapeutically.

Cysticercosis of the Central Nervous System: How Should It Be Managed?

Current Opinion in Infectious Diseases. Oct, 2011  |  Pubmed ID: 21788891

Taenia solium neurocysticercosis (NCC) has been long recognized as an important cause of neurological morbidity in most of the world. Unwarranted generalization of diagnostic and treatment recommendations made it difficult to assess individual prognosis and responses for each type of NCC. Understanding of the main clinical presentations (dependent on number, location, size, and stage of parasites, as well as on the immune response of the host) allows a better view of treatment options and expected outcomes.

Acute and Congenital Chagas Disease

Advances in Parasitology. 2011  |  Pubmed ID: 21820550

The acute phase of Chagas disease lasts 4-8 weeks and is characterized by microscopically detectable parasitaemia. Symptoms are usually mild with severe acute disease occurring in less than 1% of patients. Orally transmitted Trypanosoma cruzi outbreaks can have more severe acute morbidity and higher mortality than vector-borne infection. Congenital T. cruzi infection occurs in 1-10% of infants of infected mothers. Most congenital infections are asymptomatic or cause non-specific signs, requiring laboratory screening for detection. A small proportion of congenital infections cause severe morbidity with hepatosplenomegaly, anaemia, meningoencephalitis and/or respiratory insufficiency, with an associated high mortality. Infected infants are presumed to carry the same 20-30% lifetime risk of cardiac or gastrointestinal disease as other infected individuals. Most control programs in Latin America employ prenatal serological screening followed by microscopic examination of cord blood from infants of seropositive mothers. Recent data confirm that polymerase chain reaction (PCR) is more sensitive and detects congenital infections earlier than conventional techniques. For infants not diagnosed at birth, conventional serology is recommended at at 6 to 9 months of age. In programs that have been evaluated, less than 20% of at risk infants completed all steps of the screening algorithm. A sensitive, specific and practical screening test for newborns is needed to enable Chagas disease to be added to newborn screening programs.

Systems Biology Approach Predicts Antibody Signature Associated with Brucella Melitensis Infection in Humans

Journal of Proteome Research. Oct, 2011  |  Pubmed ID: 21863892

A complete understanding of the factors that determine selection of antigens recognized by the humoral immune response following infectious agent challenge is lacking. Here we illustrate a systems biology approach to identify the antibody signature associated with Brucella melitensis (Bm) infection in humans and predict proteomic features of serodiagnostic antigens. By taking advantage of a full proteome microarray expressing previously cloned 1406 and newly cloned 1640 Bm genes, we were able to identify 122 immunodominant antigens and 33 serodiagnostic antigens. The reactive antigens were then classified according to annotated functional features (COGs), computationally predicted features (e.g., subcellular localization, physical properties), and protein expression estimated by mass spectrometry (MS). Enrichment analyses indicated that membrane association and secretion were significant enriching features of the reactive antigens, as were proteins predicted to have a signal peptide, a single transmembrane domain, and outer membrane or periplasmic location. These features accounted for 67% of the serodiagnostic antigens. An overlay of the seroreactive antigen set with proteomic data sets generated by MS identified an additional 24%, suggesting that protein expression in bacteria is an additional determinant in the induction of Brucella-specific antibodies. This analysis indicates that one-third of the proteome contains enriching features that account for 91% of the antigens recognized, and after B. melitensis infection the immune system develops significant antibody titers against 10% of the proteins with these enriching features. This systems biology approach provides an empirical basis for understanding the breadth and specificity of the immune response to B. melitensis and a new framework for comparing the humoral responses against other microorganisms.

Sustainability of Solar Disinfection to Provide Safe Drinking Water in Rural Peru

Public Health Reports (Washington, D.C. : 1974). Sep-Oct, 2011  |  Pubmed ID: 21886341

TsAg5, a Taenia Solium Cysticercus Protein with a Marginal Trypsin-like Activity in the Diagnosis of Human Neurocysticercosis

Molecular and Biochemical Parasitology. Dec, 2011  |  Pubmed ID: 21893105

Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva. Although the mechanism of infection is not completely understood, it is likely driven by proteolytic activity that degrades the intestinal wall to facilitate oncosphere penetration and further infection. We analyzed the publicly available T. solium EST/DNA library and identified two contigs comprising a full-length cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium cDNA sequence included a proteolytic trypsin-like-domain in the C-terminal region, and a thrombospondin type-1 adherence-domain in the N-terminal region. Both the trypsin-like and adherence domains were expressed independently as recombinant proteins in bacterial systems. TsAg5 showed marginal trypsin-like activity and high sequence similarity to Ag5. The purified antigens were tested in a Western immunoblot assay to diagnose human neurocysticercosis. The sensitivity of the trypsin-like-domain was 96.36% in patients infected with extraparenchymal cysts, 75.44% in patients infected with multiple cysts, and 39.62% in patients with a single cyst. Specificity was 76.70%. The thrombospondin type-1 adherence-domain was not specific for neurocysticercosis.

Retracing Micro-epidemics of Chagas Disease Using Epicenter Regression

PLoS Computational Biology. Sep, 2011  |  Pubmed ID: 21935346

Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.

Evaluation of Bleach-sedimentation for Sterilising and Concentrating Mycobacterium Tuberculosis in Sputum Specimens

BMC Infectious Diseases. 2011  |  Pubmed ID: 21985457

Bleach-sedimentation may improve microscopy for diagnosing tuberculosis by sterilising sputum and concentrating Mycobacterium tuberculosis. We studied gravity bleach-sedimentation effects on safety, sensitivity, speed and reliability of smear-microscopy.

Socio-demographics and the Development of Malaria Elimination Strategies in the Low Transmission Setting

Acta Tropica. Nov, 2011  |  Pubmed ID: 22100446

This analysis presents a comprehensive description of malaria burden and risk factors in Peruvian Amazon villages where malaria transmission is hypoendemic. More than 9000 subjects were studied in contrasting village settings within the Department of Loreto, Peru, where most malaria occurs in the country. Plasmodium vivax is responsible for more than 75% of malaria cases; severe disease from any form of malaria is uncommon and death rare. The association between lifetime malaria episodes and individual and household covariates was studied using polychotomous logistic regression analysis, assessing effects on odds of some vs. no lifetime malaria episodes. Malaria morbidity during lifetime was strongly associated with age, logging, farming, travel history, and living with a logger or agriculturist. Select groups of adults, particularly loggers and agriculturists acquire multiple malaria infections in transmission settings outside of the main domicile, and may be mobile human reservoirs by which malaria parasites move within and between micro-regions within malaria endemic settings. For example, such individuals might well be reservoirs of transmission by introducing or reintroducing malaria into their home villages and their own households, depending on vector ecology and the local village setting. Therefore, socio-demographic studies can identify people with the epidemiological characteristic of transmission risk, and these individuals would be prime targets against which to deploy transmission blocking strategies along with insecticide treated bednets and chemoprophylaxis.

Presence of Methicillin-resistant Staphylococcus Aureus in Pigs in Peru

PloS One. 2011  |  Pubmed ID: 22174831

We report the first detection of methicillin-resistant Staphylococcus aureus isolates in pigs in Peru. The isolates belong to a livestock-associated lineage previously reported in North America and Europe, CC398, and a highly virulent USA300-like ST8-IV variant, which is the predominant community-associated lineage in Latin America.

Cough Detection Algorithm for Monitoring Patient Recovery from Pulmonary Tuberculosis

Conference Proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference. Aug, 2011  |  Pubmed ID: 22255711

In regions of the world where tuberculosis (TB) poses the greatest disease burden, the lack of access to skilled laboratories is a significant problem. A lab-free method for assessing patient recovery during treatment would be of great benefit, particularly for identifying patients who may have drug-resistant tuberculosis. We hypothesize that cough analysis may provide such a test. In this paper we describe algorithm development in support of a pilot study of TB patient coughing. We describe several approaches to event detection and classification, and show preliminary data which suggest that cough count decreases after the start of treatment in drug-responsive patients. Our eventual goal is development of a low-cost ambulatory cough analysis system that will help identify patients with drug-resistant tuberculosis.

Pyrazinoic Acid Efflux Rate in Mycobacterium Tuberculosis is a Better Proxy of Pyrazinamide Resistance

Tuberculosis (Edinburgh, Scotland). Jan, 2012  |  Pubmed ID: 22004792

Pyrazinamide is one of the most important drugs in the treatment of latent Mycobacterium tuberculosis infection. The emergence of strains resistant to pyrazinamide represents an important public health problem, as both first- and second-line treatment regimens include pyrazinamide. The accepted mechanism of action states that after the conversion of pyrazinamide into pyrazinoic acid by the bacterial pyrazinamidase enzyme, the drug is expelled from the bacteria by an efflux pump. The pyrazinoic acid is protonated in the extracellular environment and then re-enters the mycobacterium, releasing the proton and causing a lethal disruption of the membrane. Although it has been shown that mutations causing significant loss of pyrazinamidase activity significantly contribute to pyrazinamide resistance, the mechanism of resistance is not completely understood. The pyrazinoic acid efflux rate may depend on multiple factors, including pyrazinamidase activity, intracellular pyrazinamidase concentration, and the efficiency of the efflux pump. Whilst the importance of the pyrazinoic acid efflux rate to the susceptibility to pyrazinamide is recognized, its quantitative effect remains unknown. Thirty-four M. tuberculosis clinical isolates and a Mycobacterium smegmatis strain (naturally resistant to PZA) were selected based on their susceptibility to pyrazinamide, as measured by Bactec 460TB and the Wayne method. For each isolate, the initial velocity at which pyrazinoic acid is released from the bacteria and the initial velocity at which pyrazinamide enters the bacteria were estimated. The data indicated that pyrazinoic acid efflux rates for pyrazinamide-susceptible M. tuberculosis strains fell within a specific range, and M. tuberculosis strains with a pyrazinoic acid efflux rate below this range appeared to be resistant. This finding contrasts with the high pyrazinoic acid efflux rate for M. smegmatis, which is innately resistant to pyrazinamide: its pyrazinoic acid efflux rate was found to be 900 fold higher than the average efflux rate for M. tuberculosis strains. No significant variability was observed in the pyrazinamide flux rate. The pyrazinoic acid efflux rate explained 61% of the variability in Bactec pyrazinamide susceptibility, 24% of Wayne activity, and 51% of the Bactec 460TB growth index. In contrast, pyrazinamidase activity accounted for only 27% of the Bactec pyrazinamide susceptibility. This finding suggests that mechanisms other than pncA mutations (reduction of pyrazinamidase activity) are also implicated in pyrazinamide resistance, and that pyrazinoic acid efflux rate acts as a better proxy for pyrazinamide resistance than the presence of pncA mutations. This is relevant to the design of molecular diagnostics for pyrazinamide susceptibility, which currently rely on pncA gene mutation detection.

The Highly Antigenic 53/25kDa Taenia Solium Protein Fraction with Cathepsin-L Like Activity is Present in the Oncosphere/cysticercus and Induces Non-protective IgG Antibodies in Pigs

Veterinary Immunology and Immunopathology. Jan, 2012  |  Pubmed ID: 22119017

Cathepsin L-like proteases are secreted by several parasites including Taenia solium. The mechanism used by T. solium oncospheres to degrade and penetrate the intestine and infect the host is incompletely understood. It is assumed that intestinal degradation is driven by the proteolytic activity of enzymes secreted by the oncosphere. Blocking the proteolytic activity by an antibody response would prevent the oncosphere penetration and further infection. Serine and cysteine proteases including chymotrypsin, trypsin, elastase, and cathepsin L, are secreted by T. solium and Taenia saginata oncospheres when cultured in vitro, being potential vaccine candidates. However, the purification of a sufficient quantity of proteases secreted by oncospheres to conduct a vaccine trial is costly and lengthy. A 53/25kDa cathepsin L-like fraction partially purified from T. solium cyst fluid was described previously as an important antigen for immunodiagnostics. In this study we found that this antigen is present in the T. solium oncosphere and is also secreted by the cysticercus. This protein fraction was tested for its ability to protect pigs against an oral challenge with T. solium oncospheres in a vaccine trial. IgG antibodies against the 53/25kDa cathepsin L-like protein fraction were elicited in the vaccinated animals but did not confer protection.

Standardization of a Fluorescent-based Quantitative Adhesion Assay to Study Attachment of Taenia Solium Oncosphere to Epithelial Cells in Vitro

Journal of Immunological Methods. Feb, 2012  |  Pubmed ID: 22178422

To fully understand the preliminary stages of Taenia solium oncosphere attachment in the gut, adequate tools and assays are necessary to observe and quantify this event that leads to infection. A fluorescent-based quantitative adhesion assay, using biotinylated activated-oncospheres and monolayers of Chinese hamster ovary cells (CHO-K1) or human intestinal monolayer cells (INT-407, HCT-8 or HT-29), was developed to study initial events during the infection of target cells and to rapidly quantify the in vitro adhesion of T. solium oncospheres. Fluorescein streptavidin was used to identify biotinylated activated-oncospheres adhered to cells. This adherence was quantified using an automated fluorescence plate reader, and the results were expressed as fluorescence intensity values. A series of three assays were performed. The first was to identify the optimum number of biotinylated activated-oncospheres to be used in the adhesion assay. The goal of the second assay was to validate this novel method with the established oncosphere-binding system using the immunofluorescent-antibody assay (IFA) method to quantify oncosphere adhesion. A total of 10,000 biotinylated activated-oncospheres were utilized to assess the role of sera and laminin (LM) in oncosphere adherence to a CHO-K1 cell monolayer. The findings that sera and LM increase the adhesion of oncospheres to monolayer cells were similar to results that were previously obtained using the IFA method. The third assay compared the adherence of biotinylated activated-oncospheres to different types of human intestinal monolayer cells. In this case, the fluorescence intensity was greatest when using the INT-407 cell monolayer. We believe this new method of quantification offers the potential for rapid, large-scale screening to study and elucidate specific molecules and mechanisms involved in oncosphere-host cell attachment.

Addressing Geographical Variation in the Progression of Non-communicable Diseases in Peru: the CRONICAS Cohort Study Protocol

BMJ Open. 2012  |  Pubmed ID: 22240652

Background The rise in non-communicable diseases in developing countries has gained increased attention. Given that around 80% of deaths related to non-communicable diseases occur in low- and middle-income countries, there is a need for local knowledge to address such problems. Longitudinal studies can provide valuable information about disease burden of non-communicable diseases in Latin America to inform both public health and clinical settings. Methods The CRONICAS cohort is a longitudinal study performed in three Peruvian settings that differ by degree of urbanisation, level of outdoor and indoor pollution and altitude. The author sought to enrol an age- and sex-stratified random sample of 1000 participants at each site. Study procedures include questionnaires on socio-demographics and well-known risk factors for cardiopulmonary disease, blood draw, anthropometry and body composition, blood pressure and spirometry before and after bronchodilators. All participants will be visited at baseline, at 20 and 40 months. A random sample of 100 households at each site will be assessed for 24 h particulate matter concentration. Primary outcomes include prevalence of risk factors for cardiopulmonary diseases, changes in blood pressure and blood glucose over time and decline in lung function. Discussion There is an urgent need to characterise the prevalence and burden of non-communicable diseases in low- and middle-income countries. Peru is a middle-income country currently undergoing a rapid epidemiological transition. This longitudinal study will provide valuable information on cardiopulmonary outcomes in three different settings and will provide a platform to address potential interventions that are locally relevant or applicable to other similar settings in Latin America.

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

PLoS Neglected Tropical Diseases. Jan, 2012  |  Pubmed ID: 22253939

Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment.

Comparative Effects of Vivax Malaria, Fever and Diarrhoea on Child Growth

International Journal of Epidemiology. Jan, 2012  |  Pubmed ID: 22258823

BACKGROUND: The adverse impact of Plasmodium vivax on child health beyond acute febrile illness is poorly studied. The effect of vivax malaria on child growth was evaluated and compared with diarrhoeal disease and non-specific fever. METHODS: Using data from a 43-month longitudinal cohort of children 0-72 months of age (n = 442) in the Peruvian Amazon, ponderal and linear growth velocities over 2-, 4- and 6-month periods were examined using longitudinal models and related to the incidence of disease during the same period. RESULTS: An episode of vivax malaria led to 138.6 g (95% confidence interval (CI) 81.9-195.4), 108.6 g (62.8-153.2) and 61 g (20.9-101.1) less weight gain over 2-, 4- and 6-month intervals, respectively. These deficits were larger than both diarrhoea (21.9, 17.2 and 13.8 g less weight gain, respectively) and fever (39.0, 30.3 and 25.6 g less weight gain, respectively). An incident episode of vivax also led to 0.070 cm (0.004-0.137) and 0.083 cm (0.015-0.151) less linear growth over 4 and 6 months, respectively, which were also larger than deficits from diarrhoea (0.029 and 0.028 cm, respectively) and fever (not associated with linear growth deficits). Despite the larger effect of P. vivax incident episodes on growth of a particular child, diarrhoeal disease had a larger cumulative impact on growth deficits as diarrhoeal incidence rates in this community are >10-fold higher than vivax malaria. CONCLUSIONS: Disease control measures for vivax malaria and diarrhoeal disease have the potential to improve the growth of children in endemic areas.

Computerised Lung Sound Analysis to Improve the Specificity of Paediatric Pneumonia Diagnosis in Resource-poor Settings: Protocol and Methods for an Observational Study

BMJ Open. 2012  |  Pubmed ID: 22307098

WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries.

T. Solium Taeniasis Coproantigen Detection is an Early Indicator of Treatment Failure for Taeniasis

Clinical and Vaccine Immunology : CVI. Feb, 2012  |  Pubmed ID: 22336287

Taenia solium causes taeniasis and cysticercosis, a zoonotic complex associated with a significant burden of epilepsy in most countries. Reliable diagnosis and efficacious treatment of taeniasis are needed for disease control. Currently, cure can only be confirmed after a period of at least one month, by negative stool microscopy. This study assessed the performance of coproantigen ELISA (CoAg-ELISA) detection for the early evaluation of the efficacy of antiparasitic treatment in human T. solium taeniasis. We followed 69 tapeworm carriers who received niclosamide as standard treatment. Stool samples were collected on days 1, 3, 7, 15, 30, and 90 after treatment and processed by microscopy and CoAg-ELISA. The efficacy of niclosamide was 77.9% (53/68). Thirteen patients received a second course of treatment and completed the follow up. CoAg-ELISA was therefore evaluated in a total of 81 cases (68 treatments, 13 re-treatments). In successful treatments (n=64), the proportion of patients who became negative CoAg-ELISA was 62.5% after 3 days, 89.1% after 7 days, 96.9% after 15 days, and 100% after 30 days. In treatment failures (n=17), the CoAg-ELISA was positive in 70.6% of patients after three days, 94.1% after 7 days, and in 100% after 15 and 30 days. Only 2 of 17 treatment failures became positive for microscopy by day 30. The presence of one scolex but not multiple scolices in post-treatment stools was strongly associated with cure (OR 52.5% p<0.001). CoAg-ELISA is useful to assess treatment failure in taeniasis. Early assessment at day 15 would detect treatment failure before patients become infective.

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