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Find video protocols related to scientific articles indexed in Pubmed.
Malaria and HIV Infection in Mozambican Pregnant Women Are Associated With Reduced Transfer of Antimalarial Antibodies to Their Newborns.
J. Infect. Dis.
PUBLISHED: 09-30-2014
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?Malaria and human immunodeficiency virus (HIV) infection during pregnancy affect the transplacental transfer of antibodies against several pathogens from mother to fetus, although the effect of malaria and HIV infection on the transfer of antimalarial antibodies remains unclear.
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Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.
PLoS Med.
PUBLISHED: 09-01-2014
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Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).
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Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial.
PLoS Med.
PUBLISHED: 09-01-2014
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Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ) is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.
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Pregnancy and malaria exposure are associated with changes in the B cell pool and in plasma eotaxin levels.
J. Immunol.
PUBLISHED: 08-18-2014
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Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD(-)) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone-like MBC, and their levels correlated with both Plasmodium vivax- and Plasmodium falciparum-specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development.
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Estimated risk of placental infection and low birthweight attributable to Plasmodium falciparum malaria in Africa in 2010: a modelling study.
Lancet Glob Health
PUBLISHED: 07-23-2014
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Plasmodium falciparum infection during pregnancy leads to adverse outcomes including low birthweight; however, contemporary estimates of the potential burden of malaria in pregnancy in Africa (in the absence of interventions) are poor. We aimed to estimate the need to protect pregnant women from malaria across Africa.
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A quality control program within a clinical trial Consortium for PCR protocols to detect Plasmodium species.
J. Clin. Microbiol.
PUBLISHED: 04-16-2014
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Malaria parasite infections that are only detectable by molecular methods are highly prevalent and represent a potential transmission reservoir. The methods used to detect these infections are not standardized, and their operating characteristics are often unknown. We designed a proficiency panel of Plasmodium spp. in order to compare the accuracy of parasite detection of molecular protocols used by labs in a clinical trial consortium. Ten dried blood spots (DBSs) were assembled that contained P. falciparum, P. vivax, P. malariae, and P. ovale; DBSs contained either a single species or a species mixed with P. falciparum. DBS panels were tested in 9 participating laboratories in a masked fashion. Of 90 tests, 68 (75.6%) were correct; there were 20 false-negative results and 2 false positives. The detection rate was 77.8% (49/63) for P. falciparum, 91.7% (11/12) for P. vivax, 83.3% (10/12) for P. malariae, and 70% (7/10) for P. ovale. Most false-negative P. falciparum results were from samples with an estimated ? 5 parasites per ?l of blood. Between labs, accuracy ranged from 100% to 50%. In one lab, the inability to detect species in mixed-species infections prompted a redesign and improvement of the assay. Most PCR-based protocols were able to detect P. falciparum and P. vivax at higher densities, but these assays may not reliably detect parasites in samples with low P. falciparum densities. Accordingly, formal quality assurance for PCR should be employed whenever this method is used for diagnosis or surveillance. Such efforts will be important if PCR is to be widely employed to assist malaria elimination efforts.
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Mefloquine safety and tolerability in pregnancy: a systematic literature review.
Malar. J.
PUBLISHED: 02-24-2014
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Control of malaria in pregnant women is still a major challenge as it constitutes an important cause of maternal and neonatal mortality. Mefloquine (MQ) has been used for malaria chemoprophylaxis in non-immune travellers for several decades and it constitutes a potential candidate for intermittent preventive treatment in pregnant women (IPTp).
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Impact of HIV exposure on health outcomes in HIV-negative infants born to HIV-positive mothers in Sub-Saharan Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-21-2014
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Up to 30% of infants may be HIV-exposed noninfected (ENI) in countries with high HIV prevalence, but the impact of maternal HIV on the child's health remains unclear.
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Severity of anaemia is associated with bone marrow haemozoin in children exposed to Plasmodium falciparum.
Br. J. Haematol.
PUBLISHED: 01-06-2014
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There are no large-scale ex vivo studies addressing the contribution of Plasmodium falciparum in the bone marrow to anaemia. The presence of malaria parasites and haemozoin were studied in bone marrows from 290 anaemic children attending a rural hospital in Mozambique. Peripheral blood infections were determined by microscopy and polymerase chain reactions. Bone marrow parasitaemia, haemozoin and dyserythropoiesis were microscopically assessed. Forty-two percent (123/290) of children had parasites in the bone marrow and 49% (111/226) had haemozoin, overlapping with parasitaemia in 83% (92/111) of cases. Sexual and mature asexual parasites were highly prevalent (62% gametocytes, 71% trophozoites, 23% schizonts) suggesting their sequestration in this tissue. Sixteen percent (19/120) of children without peripheral infection had haemozoin in the bone marrow. Haemozoin in the bone marrow was independently associated with decreased Hb concentration (P = 0·005) and was more common in dyserythropoietic bone marrows (P = 0·010). The results of this ex vivo study suggest that haemozoin in the bone marrow has a role in the pathogenesis of malarial-anaemia through ineffective erythropoiesis. This finding may have clinical implications for the development of drugs targeted to prevent and treat malarial-anaemia.
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Perceptions of malaria in pregnancy and acceptability of preventive interventions among Mozambican pregnant women: implications for effectiveness of malaria control in pregnancy.
PLoS ONE
PUBLISHED: 01-01-2014
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Intermittent Preventive Treatment (IPTp) and insecticide treated nets (ITNs) are recommended malaria in pregnancy preventive interventions in sub-Saharan Africa. Despite their cost-effectiveness and seemingly straight-forward delivery mechanism, their uptake remains low. We aimed at describing perceptions of pregnant women regarding malaria and the recommended prevention interventions to understand barriers to uptake and help to improve their effectiveness.
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Molecular evidence for the localization of Plasmodium falciparum immature gametocytes in the bone marrow.
Blood
PUBLISHED: 12-13-2013
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Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as the bone marrow have never been assessed by molecular techniques with increased sensitivities than optical microscopy. We quantified P. falciparum sexual stages in bone marrow (n=174) and peripheral blood (n=70) of Mozambican anemic children by quantitative polymerase chain reaction (qPCR) targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45) and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P. falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n=136) and peripheral blood (n=25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% versus 20%, p<0.001; and intermediate: 80% versus 16%; p<0.001), as were transcript levels (p<0.001 for both stages). In contrast, mature gametocytes were more prevalent (100% versus 51%, p<0.001) and abundant (p<0.001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95%CI[1.49-8.53]) and dyserythropoiesis (6.21, 95%CI[2.24-17.25]) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as a relationship between hematological disturbances and gametocyte development in this tissue.
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Profile: Manhiça Health Research Centre (Manhiça HDSS).
Int J Epidemiol
PUBLISHED: 10-26-2013
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The Manhiça Health Research Centre, established in 1996 in a rural area of southern Mozambique, currently follows around 92 000 individuals living in approximately 20 000 enumerated and geo-positioned households. Its main strength is the possibility of linking demographic data and clinical data to promote and conduct biomedical research in priority health areas. Socio-demographic data are updated twice a year and clinical data are collected on a daily basis. The data collected in Manhiça HDSS comprises household and individual characteristics, household socio-economic assets, vital data, migration, individual health history and cause of death, among others. Studies conducted in this HDSS contributed to guide the health authorities and decision-making bodies to define or adjust health policies such as the introduction of Mozambiques expanded programme of immunization with different vaccines (Haemophilus influenzae type b, Pneumococcus) or the development of the concept of Intermittent Preventive Treatment for Infants (IPTi) that led to the World Health Organization recommendation of this method as best practice for the control of malaria among infants. Manhiças data can be accessed through a formal request to Diana Quelhas (diana.quelhas@manhica.net) accompanied by a proposal that will be analysed by the Manhiça HDSS internal scientific and ethics committees.
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Severe malnutrition among children under the age of 5 years admitted to a rural district hospital in southern Mozambique.
Public Health Nutr
PUBLISHED: 05-02-2013
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To describe the burden, clinical characteristics and prognostic factors of severe malnutrition in children under the age of 5 years.
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Rosetting in Plasmodium vivax: a cytoadhesion phenotype associated with anaemia.
PLoS Negl Trop Dis
PUBLISHED: 04-01-2013
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Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates.
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Improved pregnancy outcomes in women exposed to malaria with high antibody levels against Plasmodium falciparum.
J. Infect. Dis.
PUBLISHED: 02-28-2013
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Antibodies against VAR2CSA, the Plasmodium falciparum variant surface antigen that binds placental chondroitin sulfate A, have been suggested to mediate protection against malaria in pregnancy but also to be markers of infection. Here, we aimed to identify clinically relevant antibody responses, taking into consideration variations in parasite exposure and human immunodeficiency virus type 1 (HIV) infection status.
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Breast Milk and Gut Microbiota in African Mothers and Infants from an Area of High HIV Prevalence.
PLoS ONE
PUBLISHED: 01-01-2013
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Human milk and infant gut microbiota are essential for the immune system maturation and protection against infections. There is scarce information on the microbiological composition of breast milk in general, and none from developing countries. The objective of the study was to characterize the breast milk and gut microbiota from mothers and infants from southern Mozambique, where infections and breastfeeding are prevalent.
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VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.
PLoS ONE
PUBLISHED: 01-01-2013
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Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.
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Age-dependent IgG subclass responses to Plasmodium falciparum EBA-175 are differentially associated with incidence of malaria in Mozambican children.
Clin. Vaccine Immunol.
PUBLISHED: 12-14-2011
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Plasmodium falciparum blood-stage antigens such as merozoite surface protein 1 (MSP-1), apical membrane antigen 1 (AMA-1), and the 175-kDa erythrocyte binding antigen (EBA-175) are considered important targets of naturally acquired immunity to malaria. However, it is not clear whether antibodies to these antigens are effectors in protection against clinical disease or mere markers of exposure. In the context of a randomized, placebo-controlled trial of intermittent preventive treatment in infants conducted between 2002 and 2004, antibody responses to Plasmodium falciparum blood-stage antigens in a cohort of 302 Mozambican children were evaluated by immunofluorescence antibody test and enzyme-linked immunosorbent assay at 5, 9, 12, and 24 months of age. We found that IgG subclass responses to EBA-175 were differentially associated with the incidence of malaria in the follow-up period. A double amount of cytophilic IgG1 or IgG3 was associated with a significant decrease in the incidence of malaria (incidence rate ratio [IRR] = 0.49, 95% confidence interval [CI] = 0.25 to 0.97, and P = 0.026 and IRR = 0.44, CI = 0.19 to 0.98, and P = 0.037, respectively), while a double amount of noncytophilic IgG4 was significantly correlated with an increased incidence of malaria (IRR = 3.07, CI = 1.08 to 8.78, P = 0.020). No significant associations between antibodies to the 19-kDa fragment of MSP-1 (MSP-1(19)) or AMA-1 and incidence of malaria were found. Age, previous episodes of malaria, present infection, and neighborhood of residence were the main factors influencing levels of antibodies to all merozoite antigens. Deeper understanding of the acquisition of antibodies against vaccine target antigens in early infancy is crucial for the rational development and deployment of malaria control tools in this vulnerable population.
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Alterations in T cell subsets in human immunodeficiency virus-infected adults with co-infections in southern Mozambique.
Am. J. Trop. Med. Hyg.
PUBLISHED: 10-07-2011
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T cell activation and depletion of naive T cells are hallmarks of human immunodeficiency virus (HIV) pathogenesis. This study explored the relationships between certain co-infections (including syphilis, hepatitis B and C, human T cell lymphotrophic viruses I and II [HTLV-I/II], Kaposi sarcoma-associated herpesvirus [KSHV], Plasmodium falciparum malaria, and tuberculosis), and levels of activated CD8 and CD4 T cell subsets as well as naive and memory CD4 T cells in HIV-infected adults in a rural area of southern Mozambique. We found that syphilis infection and to a lesser extent HTLV-I/II seropositivity were independently associated with higher CD8 T cell activation (CD8+ CD38+ HLA-DR+) whereas only syphilis was associated with higher CD4 T cell activation. Furthermore, KSHV and HTLV-I/II seropositivities were independently associated with a lower percentage of naive CD4 T cells (CD4+ CD45RA+ CD62L+). These results highlight the importance of screening and prompt treatment of syphilis, and raise questions as to whether HIV-positive persons with certain chronic viral co-infections should initiate combined antiretroviral therapy at higher CD4 cell counts.
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Development of vaccines to prevent malaria in pregnant women: WHO MALVAC meeting report.
Expert Rev Vaccines
PUBLISHED: 09-17-2011
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The major public health consequences of malaria in pregnancy have long been acknowledged. However, further information is still required for development and implementation of a malaria vaccine specifically directed to prevent malaria in pregnant women and improve maternal, fetal and infant outcomes. The WHO Malaria Vaccine Advisory Committee (MALVAC) provides guidance to the WHO on strategic priorities and research needs for development of vaccines to prevent malaria. Here we summarize the discussions and conclusions of a MALVAC scientific forum meeting on considerations in the development of vaccines to prevent malaria in pregnant women. This report includes brief summaries of what is known, and major knowledge gaps in disease burden estimation, pathogenesis and immunity, and the challenges with current preventive strategies for malaria in pregnancy. We conclude with the formulation of a conceptual framework for research and development for vaccines to prevent malaria in pregnant women.
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Cost-effectiveness of intermittent preventive treatment of malaria in infants (IPTi) for averting anaemia in Gabon: a comparison between intention to treat and according to protocol analyses.
Malar. J.
PUBLISHED: 09-02-2011
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In Gabon, the impact of intermittent preventive treatment of malaria in infants (IPTi) was not statistically significant on malaria reduction, but the impact on moderate anaemia was, with some differences between the intention to treat (ITT) and the according to protocol (ATP) trial analyses. Specifically, ATP was statistically significant, while ITT analysis was borderline. The main reason for the difference between ITT and ATP populations was migration.
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Costs associated with low birth weight in a rural area of Southern Mozambique.
PLoS ONE
PUBLISHED: 07-26-2011
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Low Birth Weight (LBW) is prevalent in low-income countries. Even though the economic evaluation of interventions to reduce this burden is essential to guide health policies, data on costs associated with LBW are scarce. This study aims to estimate the costs to the health system and to the household and the Disability Adjusted Life Years (DALYs) arising from infant deaths associated with LBW in Southern Mozambique.
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Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges.
Malar. J.
PUBLISHED: 07-08-2011
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Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.
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A targeted association study of immunity genes and networks suggests novel associations with placental malaria infection.
PLoS ONE
PUBLISHED: 06-29-2011
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A large proportion of the death toll associated with malaria is a consequence of malaria infection during pregnancy, causing up to 200,000 infant deaths annually. We previously published the first extensive genetic association study of placental malaria infection, and here we extend this analysis considerably, investigating genetic variation in over 9,000 SNPs in more than 1,000 genes involved in immunity and inflammation for their involvement in susceptibility to placental malaria infection. We applied a new approach incorporating results from both single gene analysis as well as gene-gene interactions on a protein-protein interaction network. We found suggestive associations of variants in the gene KLRK1 in the single gene analysis, as well as evidence for associations of multiple members of the IL-7/IL-7R signalling cascade in the combined analysis. To our knowledge, this is the first large-scale genetic study on placental malaria infection to date, opening the door for follow-up studies trying to elucidate the genetic basis of this neglected form of malaria.
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Erythropoietin levels are not independently associated with malaria-attributable severe disease in Mozambican children.
PLoS ONE
PUBLISHED: 06-02-2011
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Severe malaria is difficult to differentiate from other forms of malaria or other infections with similar symptoms. Any parameter associated to malaria-attributable severe disease could help to improve severe malaria diagnosis.
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Transcription of var genes other than var2csa in Plasmodium falciparum parasites infecting Mozambican pregnant women.
J. Infect. Dis.
PUBLISHED: 06-02-2011
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Increased susceptibility to Plasmodium falciparum infection during pregnancy has been attributed to the accumulation of infected erythrocytes in the placenta. This phenomenon is mediated by a var gene coding for VAR2CSA, which adheres to chondroitin sulphate A. However, the contribution of parasites transcribing other var genes to maternal infections has not been well characterized.
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Pyrethroid use-malaria control and individual applications by households for other pests and home garden use.
Environ Int
PUBLISHED: 04-06-2011
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Presence of pyrethroid insecticides in human breast milk and in thatch wall material of dwellings from Southern Africa subtropical area (Manhiça, Mozambique) was investigated to assess potential pyrethroid route of human exposure. Human breast milk samples were collected during 2002 when pyrethroids were widely used as insecticides for mosquito bed nets in Mozambique for malaria control. The median concentration value of total pyrethroids ranged between 87 and 1200ng/glw, with ?-cyhalothrin being the most predominant pyrethroid in human breast milk contributing for 35% of the total amount. Moreover, and for the first time, an isomer-specific enrichment was found in human breast milk, showing a selective isomeric accumulation or metabolism in the human body. Based on the calculated pyrethroid concentrations in human breast milk, the daily ingestion rate of pyrethroid was estimated. The nursing infant dietary intake ranged from 0.67 to 9.0?g(kg of body weight)(-1)day(-1). In addition, thatch materials collected after the reintegration of dichlorodiphenyltrichloroethene (DDT) as insecticide residual spraying (IRS) in Mozambique, showed the presence of pyrethroids with concentration values ranging between 6.9 and 700ng/gdw. In thatch material as well as in human breast milk, pyrethroid contamination was mainly attributed to the agriculture usage of this insecticide knowing that agriculture represent the 80% of the economy in Mozambique. However, a possible usage of this insecticide as IRS in Mozambique cannot be excluded despite their low efficiency for malaria control. The continued use of these compounds (both for agriculture and malaria prevention) and the ingestion rates calculated from the breast milk concentrations indicate that these insecticides cannot be overlooked for the assessment of the lactation risks of breastfeeding infants from the Manhiça region.
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Association of severe malaria outcomes with platelet-mediated clumping and adhesion to a novel host receptor.
PLoS ONE
PUBLISHED: 04-02-2011
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Severe malaria has been attributed partly to the sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the microvasculature of vital host organs. Identification of P. falciparum cytoadherence phenotypes that are associated with severe malaria may lead to the development of novel strategies against life-threatening malaria.
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HIV and placental infection modulate the appearance of drug-resistant Plasmodium falciparum in pregnant women who receive intermittent preventive treatment.
Clin. Infect. Dis.
PUBLISHED: 03-29-2011
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Factors involved in the development of resistance to sulphadoxine-pyrimethamine (SP) by Plasmodium falciparum, particularly in the context of intermittent preventive treatment during pregnancy (IPTp), are not well known. We aimed to determine the impact of IPTp and human immunodeficiency virus (HIV) infection on molecular markers of SP resistance and the clinical relevance of resistant infections.
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Assessment of exposure to DDT and metabolites after indoor residual spraying through the analysis of thatch material from rural African dwellings.
Environ Sci Pollut Res Int
PUBLISHED: 03-21-2011
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We report on the analysis of 4,4-dichlorodiphenyltrichloroethane (4,4-DDT) and its metabolites in thatch and branch samples constituting the wall materials of dwellings from South African subtropical areas. This approach was used to assess the exposure to DDT in the residents of the dwellings after indoor residual spraying (IRS) following recommended sanitation practices against malaria vectors.
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Concentration of DDT compounds in breast milk from African women (Manhiça, Mozambique) at the early stages of domestic indoor spraying with this insecticide.
Chemosphere
PUBLISHED: 03-19-2011
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Breast milk concentrations of 4,4-DDT and its related compounds were studied in samples collected in 2002 and 2006 from two populations of mothers in Manhiça, Mozambique. The 2006 samples were obtained several months after implementation of indoor residual spraying (IRS) with DDT for malaria vector control in dwellings and those from 2002 were taken as reference prior to DDT use. A significant increase in 4,4-DDT and its main metabolite, 4,4-DDE, was observed between the 2002 (median values 2.4 and 0.9 ng/ml, respectively) and the 2006 samples (7.3 and 2.6 ng/ml, respectively, p<0.001 and 0.019, respectively). This observation identifies higher body burden intakes of these compounds in pregnant women already in these initial stages of the IRS program. The increase in both 4,4-DDT and 4,4-DDE suggest a rapid transformation of DDT into DDE after incorporation of the insecticide residues. The median baseline concentrations in breast milk in 2002 were low, and the median concentrations in 2006 (280 ng/g lipid) were still lower than in other world populations. However, the observed increases were not uniform and in some individuals high values (5100 ng/g lipid) were determined. Significant differences were found between the concentrations of DDT and related compounds in breast milk according to parity, with higher concentrations in primiparae than multiparae women. These differences overcome the age effect in DDT accumulation between the two groups and evidence that women transfer a significant proportion of their body burden of DDT and its metabolites to their infants.
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Prospects for malaria elimination in non-Amazonian regions of Latin America.
Acta Trop.
PUBLISHED: 02-22-2011
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Latin America contributes 1-1.2 million clinical malaria cases to the global malaria burden of about 300 million per year. In 21 malaria endemic countries, the population at risk in this region represents less than 10% of the total population exposed worldwide. Factors such as rapid deforestation, inadequate agricultural practices, climate change, political instability, and both increasing parasite drug resistance and vector resistance to insecticides contribute to malaria transmission. Recently, several malaria endemic countries have experienced a significant reduction in numbers of malaria cases. This is most likely due to actions taken by National Malaria Control Programs (NMCP) with the support from international funding agencies. We describe here the research strategies and activities to be undertaken by the Centro Latino Americano de Investigación en Malaria (CLAIM), a new research center established for the non-Amazonian region of Latin America by the National Institute of Allergy and Infectious Diseases (NIAID). Throughout a network of countries in the region, initially including Colombia, Guatemala, Panama, and Peru, CLAIM will address major gaps in our understanding of changing malaria epidemiology, vector biology and control, and clinical malaria mainly due to Plasmodium vivax. In close partnership with NMCPs, CLAIM seeks to conduct research on how and why malaria is decreasing in many countries of the region as a basis for developing and implementing new strategies that will accelerate malaria elimination.
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Parity and placental infection affect antibody responses against Plasmodium falciparum during pregnancy.
Infect. Immun.
PUBLISHED: 02-07-2011
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Women are at higher risk of Plasmodium falciparum infection when pregnant. The decreasing risk of malaria with subsequent pregnancies is attributed to parity-dependent acquisition of antibodies against placental parasites expressing variant surface antigens, VAR2CSA, that mediate placental sequestration through adhesion to chondroitin sulfate A (CSA). However, modulation of immunity during pregnancy may also contribute to increase the risk of malaria. We compared antibody responses among 30 Mozambican primigravidae and 60 multigravidae at delivery, 40 men, and 40 children. IgG levels were measured against the surface antigens of erythrocytes infected with P. falciparum isolated from 12 pregnant women (4 placental and 8 peripheral blood isolates) and 26 nonpregnant hosts. We also measured IgG levels against merozoite recombinant antigens and total IgG. Placental P. falciparum infection was associated with increased levels of total IgG as well as IgG levels against merozoite antigens and parasite isolates from pregnant and nonpregnant hosts. We therefore stratified comparisons of antibody levels by placental infection. Compared to multigravidae, uninfected primigravidae had lower total IgG as well as lower levels of IgGs against peripheral blood isolates from both pregnant and nonpregnant hosts. These differences were not explained by use of bed nets, season at delivery, neighborhood of residence, or age. Compared to men, infected primigravidae had higher levels of IgGs against isolates from pregnant women and CSA-binding lines but not against other isolates, supporting the concept of a pregnancy-specific development of immunity to these parasite variants. Results of this study show that parity and placental infection can modulate immune responses during pregnancy against malaria parasites.
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Rapid suppression of HIV-RNA is associated with improved control of immune activation in Mozambican adults initiating antiretroviral therapy with low CD4 counts.
AIDS Res. Hum. Retroviruses
PUBLISHED: 01-24-2011
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The rapidity of HIV-RNA suppression after initiation of combined antiretroviral therapy (cART) may impact immune reconstitution in developing countries, where patients initiate cART at low CD4 T cell counts. One hundred and thirty-five HIV-1 Mozambican adults initiating cART were prospectively followed over 16 months within a larger observational study. Plasma HIV-RNA, CD4 counts, and CD8 T cell activation were monitored at the pre-cART visit and at 4, 10, and 16 months during cART. Of the 89 patients with available HIV-RNA data at pre-cART and 4 and 10 months post-cART, 68% (60/89) suppressed HIV-RNA at 4 months and were defined as "early virological controllers"(EC). Twenty of the 29 remaining patients who did not control HIV-RNA at 4 months did so at 10 months and were classified as "late virological controllers"(LC). Nine (10%) patients did not control HIV-RNA at either time point. Both initiating an EFV-containing cART regimen and having pre-cART tuberculosis were significantly associated with early HIV-RNA suppression if locked into a multivariate model [EFV OR: 13.6 (95% CI 1.7; 108.1) p = 0.014) tuberculosis OR: 11.0 (95% CI 1.4; 87.9) p = 0.024]. EC demonstrated significantly lower median activated CD8 T cells at 4, 10, and 16 months post-cART than did LC. Approximately 63% (12/19) of LC experienced reappearance of detectable HIV-RNA at 6 months postcontrol as compared to 15% (2/60) of EC (p = 0.001). This study suggests that rapid suppression of HIV-RNA may lead to a lower rate of reappearance of HIV-RNA, which could impact CD8 T cell activation levels in patients initiating cART at low CD4 counts.
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Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique.
PLoS ONE
PUBLISHED: 01-18-2011
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There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique.
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Impact of malaria at the end of pregnancy on infant mortality and morbidity.
J. Infect. Dis.
PUBLISHED: 01-03-2011
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There is some consensus that malaria in pregnancy may negatively affect infants mortality and malaria morbidity, but there is less evidence concerning the factors involved.
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IgG against Plasmodium falciparum variant surface antigens and growth inhibitory antibodies in Mozambican children receiving intermittent preventive treatment with sulfadoxine-pyrimethamine.
Immunobiology
PUBLISHED: 11-23-2010
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This study aimed to evaluate whether intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) had an effect on the acquisition of IgG against Plasmodium falciparum variant surface antigens (VSA) and growth-inhibitory antibodies in Manhiça, Mozambique. In addition, we assessed factors affecting the magnitude of these responses and the association between antibody levels and protection against malaria. IgG to VSA expressed by MOZ2, R29 and E8B parasite isolates were measured in plasma samples collected at 5, 9, 12 and 24 months of age by flow cytometry. Growth-inhibitory antibodies in dialyzed plasmas using GFP-D10 parasites were measured by flow cytometry at 12 and 24 months. IPTi-SP did not significantly modify the levels of IgG against VSA nor the growth-inhibitory capacity of antibodies up to 2 years of age. Age but not previous episodes of malaria influenced the magnitude of these responses. In addition, anti-VSA IgG levels were 7% higher in children with current P. falciparum infection and were associated with neighborhood of residence. Children aged 24 months had 10% less parasite growth than those aged 12 months (95% CI 0.88-0.93, P<0.0001). Growth-inhibitory antibodies correlated with levels of IgG against AMA-1, when evaluating the 10% (R(2)=0.444, P=0.049) and 20% (R(2)=0.230, P=0.037) highest inhibitory samples. None of the responses were associated with subsequent risk of malaria. In conclusion, IPTi-SP does not negatively affect the development of antibody responses thought to be major contributors to the acquisition of immunity to malaria in infancy.
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Persistence of Plasmodium falciparum parasites in infected pregnant Mozambican women after delivery.
Infect. Immun.
PUBLISHED: 11-01-2010
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Pregnant women are susceptible to Plasmodium falciparum parasites that sequester in the placenta. The massive accumulation of infected erythrocytes in the placenta has been suggested to trigger the deleterious effects of malaria in pregnant women and their offspring. The risk of malaria is also high during the postpartum period, although mechanisms underlying this susceptibility are not known. Here, we aimed to identify host factors contributing to the risk of postpartum infections and to determine the origin of postpartum parasites by comparing their genotypes with those present at the time of delivery. To address this, blood samples were collected at delivery (n = 402) and postpartum (n = 354) from Mozambican women enrolled in a trial of intermittent preventive treatment in pregnancy (IPTp). P. falciparum was detected by real-time quantitative PCR (qPCR), and the parasite merozoite surface protein 1 (msp-1) and msp-2 genes were genotyped. Fifty-seven out of 354 (16%) women were infected postpartum as assessed by qPCR, whereas prevalence by optical microscopy was only 4%. Risk of postpartum infection was lower in older women (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.15 to 0.81) and higher in women with a placental infection at delivery (OR = 4.20, 95% CI = 2.19 to 8.08). Among 24 women with matched infections, 12 (50%) were infected postpartum with at least one parasite strain that was also present in their placentas. These results suggest that parasites infecting pregnant women persist after delivery and increase the risk of malaria during the postpartum period. Interventions that reduce malaria during pregnancy may translate into a lower risk of postpartum infection.
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Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.
Lancet Oncol.
PUBLISHED: 10-15-2010
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Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer.
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Antimicrobial drug resistance trends of bacteremia isolates in a rural hospital in southern Mozambique.
Am. J. Trop. Med. Hyg.
PUBLISHED: 07-03-2010
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Antibiotic resistance in Africa is increasing but insufficiently recognized as a public health problem. However, there are scarce data for antimicrobial resistance trends among bloodstream isolates in sub-Saharan Africa. Antimicrobial drug resistance trends among bacteria isolated from blood of children < 15 years of age admitted to the Manhiça District Hospital in Mozambique during May 2001-April 2006 were monitored by disk diffusion. We documented a linear trend of increasing resistance throughout the study period to chloramphenicol among isolates of Non-typhi Salmonella (P < 0.001), Escherichia coli (P = 0.002), Staphylococcus aureus (P < 0.001), and Haemophilus influenzae (P < 0.001). Increasing resistance to ampicillin was also observed for H. influenzae isolates (P < 0.001). We report trends of increasing resistance among the most frequent etiologies of bacteremia to the most commonly used antibiotics for empirical therapy in this community. Quinolones and third-generation cephalosporines may be needed in the short term to manage community-acquired infections.
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Cost-effectiveness of intermittent preventive treatment of malaria in pregnancy in southern Mozambique.
PLoS ONE
PUBLISHED: 05-26-2010
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Malaria in pregnancy is a public health problem for endemic countries. Economic evaluations of malaria preventive strategies in pregnancy are needed to guide health policies.
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Prevalence and risk factors of sexually transmitted infections and cervical neoplasia in women from a rural area of southern Mozambique.
Infect Dis Obstet Gynecol
PUBLISHED: 05-12-2010
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There is limited information on the prevalence of sexually transmitted infections and the prevalence of cervical neoplasia in rural sub-Saharan Africa. This study describes the prevalence and the etiology of STIs and the prevalence of cervical neoplasia among women in southern Mozambique. An age-stratified cross-sectional study was performed where 262 women aged 14 to 61 years were recruited at the antenatal clinic (59%), the family-planning clinic (7%), and from the community (34%). At least one active STI was diagnosed in 79% of women. Trichomonas vaginalis was present in 31% of all study participants. The prevalence of Neisseria gonorrhea and Chlamydia trachomatis were 14% and 8%, respectively, and Syphilis was diagnosed in 12% of women. HPV DNA was detected in 40% of women and cervical neoplasia was diagnosed in 12% of all women. Risk factors associated with the presence of some of the STIs were being divorced or widowed, having more than one sexual partner and having the partner living in another area. A higher prevalence was observed in the reproductive age group and some of the STIs were more frequently diagnosed in pregnant women. STI control programs are a priority to reduce the STIs burden, including HIV and cervical neoplasia.
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Current knowledge and challenges of antimalarial drugs for treatment and prevention in pregnancy.
Expert Opin Pharmacother
PUBLISHED: 04-23-2010
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Malaria infection during pregnancy is a major public health problem worldwide, with 50 million pregnancies exposed to the infection every year. Approximately 25,000 maternal deaths and between 75,000 and 200,000 infant deaths could be prevented each year by effective malaria control in pregnancy. Antimalarial drug treatment and prevention has been hampered by the appearance of drug resistance, which has been a particular problem in pregnancy due to the inherent safety issues.
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The cost-effectiveness of intermittent preventive treatment for malaria in infants in Sub-Saharan Africa.
PLoS ONE
PUBLISHED: 02-18-2010
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Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials.
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Malaria prevention with IPTp during pregnancy reduces neonatal mortality.
PLoS ONE
PUBLISHED: 01-28-2010
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In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.
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Long-term safety and efficacy of the RTS,S/AS02A malaria vaccine in Mozambican children.
J. Infect. Dis.
PUBLISHED: 07-03-2009
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We previously reported that the RTS,S/AS02A vaccine had an acceptable safety profile, was immunogenic, and demonstrated efficacy against Plasmodium falciparum malaria disease for 21 months.
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Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital.
Trop. Med. Int. Health
PUBLISHED: 06-22-2009
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To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital.
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Determinants of household demand for bed nets in a rural area of southern Mozambique.
Malar. J.
PUBLISHED: 06-15-2009
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A key to making insecticide-treated nets (ITNs) a long-term, sustainable solution to the spread of malaria is understanding what drives their purchase and use. Few studies have analysed the determinants of demand for bed nets for malaria prevention at the household level, and in particular, how demand for nets compares with demand for other mosquito prevention methods.
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A variant in the gene FUT9 is associated with susceptibility to placental malaria infection.
Hum. Mol. Genet.
PUBLISHED: 05-21-2009
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Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200 000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A single nucleotide polymorphism (SNP) located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (odds ratio = 2.31, permutation P-value=0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.
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Impact of maternal human immunodeficiency virus infection on birth outcomes and infant survival in rural Mozambique.
Am. J. Trop. Med. Hyg.
PUBLISHED: 05-02-2009
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We assessed the effect of maternal human immunodeficiency virus (HIV) infection on birth outcomes and infant survival in rural Mozambique. Pregnant women attending the antenatal clinic were recruited. These women and their infants were followed-up for one year. Birth outcomes were assessed at delivery and infant HIV status was determined at 1 and 12 months of age. Women positive for HIV were more likely to have anemia at delivery than women negative for HIV (51.3% versus 35.4%; P < 0.001). Infants born to HIV-positive mothers had a significantly higher post-neonatal mortality rate than infants born to HIV-negative mothers (7.8% versus 1.9%; P < 0.001). The rate of transmission of HIV by breastfeeding during the first year of life was 15.1% (95% confidence interval = CI 7.6-22.4). Assessment of the impact of HIV infection on birth outcomes in rural Africa is essential for tailoring public health measures to reduce mother-to-child transmission of HIV and excess infant mortality.
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Severe pneumonia in Mozambican young children: clinical and radiological characteristics and risk factors.
J. Trop. Pediatr.
PUBLISHED: 04-28-2009
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Pneumonia is a leading cause of hospitalization and death among children in Africa. We describe the clinical presentation of severe pneumonia among hospitalized children in a malaria endemic area with a high prevalence of HIV infection.
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Dihydroartemisinin-piperaquine and artemether-lumefantrine for treating uncomplicated malaria in African children: a randomised, non-inferiority trial.
PLoS ONE
PUBLISHED: 03-12-2009
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Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children.
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Cost-effectiveness of malaria intermittent preventive treatment in infants (IPTi) in Mozambique and the United Republic of Tanzania.
Bull. World Health Organ.
PUBLISHED: 03-11-2009
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To estimate the cost-effectiveness of malaria intermittent preventive treatment in infants (IPTi) using sulfadoxine-pyrimethamine (SP).
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Clinico-pathological discrepancies in the diagnosis of causes of maternal death in sub-Saharan Africa: retrospective analysis.
PLoS Med.
PUBLISHED: 01-10-2009
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Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death.
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Community-acquired bacteremia among children admitted to a rural hospital in Mozambique.
Pediatr. Infect. Dis. J.
PUBLISHED: 01-10-2009
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Although community-acquired bacteremia is an important cause of childhood mortality in Africa, recognition of disease burden and potential impact of bacterial vaccines is limited.
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Sub-microscopic infections and long-term recrudescence of Plasmodium falciparum in Mozambican pregnant women.
Malar. J.
PUBLISHED: 01-09-2009
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Control of malaria in pregnancy remains a public health challenge. Improvements in its correct diagnosis and the adequacy of protocols to evaluate anti-malarial drug efficacy in pregnancy, are essential to achieve this goal.
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Plasmodium vivax congenital malaria in an area of very low endemicity in Guatemala: implications for clinical and epidemiological surveillance in a malaria elimination context.
Malar. J.
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This is a report of the first Plasmodium vivax congenital malaria case in Guatemala and the first case in Latin America with genotypical, histological and clinical characterization. The findings show that maternal P. vivax infection still occurs in areas that are in the pathway towards malaria elimination, and can be associated with detrimental health effects for the neonate. It also highlights the need in very low transmission areas of not only maintaining, but increasing awareness of the problem and developing surveillance strategies, based on population risk, to detect the infection especially in this vulnerable group of the population.
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Challenges in the diagnosis of iron deficiency in children exposed to high prevalence of infections.
PLoS ONE
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While WHO guidelines recommend iron supplements to only iron-deficient children in high infection pressure areas, these are rarely implemented. One of the reasons for this is the commonly held view that iron supplementation increases the susceptibility to some infectious diseases including malaria. Secondly, currently used markers to diagnose iron deficiency are also modified by infections. With the objective of improving iron deficiency diagnosis and thus, its management, we evaluated the performance of iron markers in children exposed to high infection pressure.
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Population characteristics of young African women influencing prenatal exposure to DDT (Manhiça, Mozambique).
Environ Sci Pollut Res Int
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The concentrations of dichlorodiphenyltrichloroethane (DDT) compounds in cord blood of 214 children born between 2003 and 2006 in Manhiça (Mozambique) have been determined. In this time interval, corresponding to the period before DDT reintroduction for indoor residual spraying, the observed values averaged 0.8 and 0.4 ng/ml for 4,4-dichlorodiphenyldichloroethylene (4,4-DDE) and 4,4-DDT, respectively, and were similar to those found in western countries. However, the 4,4-DDT/4,4-DDE ratio was high indicating that the inputs of these compounds arriving to children in utero originated from recent uses of the insecticide. The strongest factor affecting DDT concentration was parity. A well-defined decreasing concentration trend was observed for the cord blood concentrations in the period of study. The trend was also observed for multiparae and primiparae mothers independently. Children from multiparae women showed much lower concentrations than primiparae women. Children from mothers with secondary school level exhibited lower concentrations of these pesticides than mothers with lower degree of education.
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Efficacy of mefloquine intermittent preventive treatment in pregnancy against Schistosoma haematobium infection in Gabon: a nested randomized controlled assessor-blinded clinical trial.
Clin. Infect. Dis.
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Urogenital schistosomiasis is a major public health problem in sub-Saharan Africa, and routine programs for screening and treatment of pregnant women are not established. Mefloquine-currently evaluated as a potential alternative to sulfadoxine-pyrimethamine as intermittent preventive treatment against malaria in pregnancy (IPTp)-is known to exhibit activity against Schistosoma haematobium. In this study we evaluated the efficacy of mefloquine IPTp against S. haematobium infection in pregnant women.
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Placental infection with Plasmodium vivax: a histopathological and molecular study.
J. Infect. Dis.
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Evidence of the presence of Plasmodium vivax in the placenta is scarce and inconclusive. This information is relevant to understanding whether P. vivax affects placental function and how it may contribute to poor pregnancy outcomes.
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Comparison of placental blood microscopy and the ICT HRP2 rapid diagnostic test to detect placental malaria.
Trans. R. Soc. Trop. Med. Hyg.
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Monitoring interventions to prevent malaria in pregnancy requires sensitive detection of placental infection. Rapid diagnostic tests (RDTs) are good candidates, but little information is available on their sensitivity on placental blood. We have evaluated the agreement (kappa coefficient) between microscopy and a Plasmodium falciparum histidine-rich protein 2 (HRP2)-based immuno-chromatographic test (ICT) on placental blood from 1151 women at delivery. Prevalences of placental infection by microscopy and RDT were 5.1% and 5.0%, respectively, showing 82.9% agreement (p<0.0001). Discordances were found at low parasitemias (<500 parasites/?L) or negative microscopy. The results suggest that the HRP2-RDTs from ICT diagnostics is a good alternative to microscopy for diagnosing placental malaria at delivery.
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Intermittent preventive treatment of malaria in pregnant women and infants: making best use of the available evidence.
Expert Opin Pharmacother
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Malaria continues to represent a huge global health burden on the most vulnerable populations. The Intermittent Preventive Treatment (IPT) strategy has been shown to be an efficacious intervention in preventing most of the deleterious effects of malaria in pregnant women and infants. Yet, the effectiveness of the IPT strategy may be impaired by the increasing resistance to sulfadoxine-pyrimethamine (SP), and the scarcity of alternative antimalarial drugs.
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Low antibodies against Plasmodium falciparum and imbalanced pro-inflammatory cytokines are associated with severe malaria in Mozambican children: a case-control study.
Malar. J.
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The factors involved in the progression from Plasmodium falciparum infection to severe malaria (SM) are still incompletely understood. Altered antibody and cellular immunity against P. falciparum might contribute to increase the risk of developing SM.
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Immunoglobulins against the surface of Plasmodium falciparum-infected erythrocytes increase one month after delivery.
Malar. J.
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The risk of Plasmodium falciparum malaria increases during pregnancy and at early postpartum. Immunological and physiological alterations associated with pregnancy that persist after delivery may contribute to the susceptibility to P. falciparum during early postpartum period.
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How hidden can malaria be in pregnant women? Diagnosis by microscopy, placental histology, polymerase chain reaction and detection of histidine-rich protein 2 in plasma.
Clin. Infect. Dis.
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Accurate diagnosis of malaria infection during pregnancy remains challenging because of low parasite densities and placental sequestration of Plasmodium falciparum. The performance of different methods to detect P. falciparum in pregnancy and the clinical relevance of undetected infections were evaluated.
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Inadequate efficacy of a new formulation of fosmidomycin-clindamycin combination in Mozambican children less than three years old with uncomplicated Plasmodium falciparum malaria.
Antimicrob. Agents Chemother.
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The combination of fosmidomycin and clindamycin (F/C) is effective in adults and older children for the treatment of malaria and could be an important alternative to existing artemisinin-based combinations (ACTs) if proven to work in younger children. We conducted an open-label clinical trial to assess the efficacy, safety, and tolerability of F/C for the treatment of uncomplicated P. falciparum malaria in Mozambican children <3 years of age. Aqueous solutions of the drugs were given for 3 days, and the children were followed up for 28 days. The primary outcome was the PCR-corrected adequate clinical and parasitological response at day 28. Secondary outcomes included day 7 and 28 uncorrected cure rates and fever (FCT) and parasite (PCT) clearance times. Fifty-two children were recruited, but only 37 patients were evaluable for the primary outcome. Day 7 cure rates were high (94.6%; 35/37), but the day 28 PCR-corrected cure rate was 45.9% (17/37). The FCT was short (median, 12 h), but the PCT was longer (median, 72 h) than in previous studies. Tolerability was good, and most common adverse events were related to the recurrence of malaria. The poor efficacy observed for the F/C combination may be a consequence of the new formulations used, differential bioavailability in younger children, naturally occurring variations in parasite sensitivity to the drugs, or an insufficient enhancement of their effects by naturally acquired immunity in young children. Additional studies should be conducted to respond to the many uncertainties arising from this trial, which should not discourage further evaluation of this promising combination.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.