As the interactions of phage with mammalian innate and adaptive immune systems are better delineated and with our ability to recognize and eliminate toxins and other potentially harmful phage gene products, the potential of phage therapies is now being realized. Early efforts to use phage therapeutically were hampered by inadequate phage purification and limited knowledge of phage-bacterial and phage-human relations. However, although use of phage as an antibacterial therapy in countries that require controlled clinical studies has been hampered by the high costs of patient trials, their use as vaccines and the use of phage components such as lysolytic enzymes or lysozymes has progressed to the point of commercial applications. Recent studies concerning the intimate associations between mammalian hosts and bacterial and phage microbiomes should hasten this progress.
Cayler cardiofacial syndrome is characterised by congenital unilateral hypoplasia of the depressor anguli oris muscle (DAOM) in association with congenital cardiac defects. Hypoplasia of this muscle causes inability to move one corner of the mouth downward and outward while crying or grimacing, giving rise to an 'asymmetric crying face' appearance. A variety of congenital cardiac defects have been described. Occasionally, other organ system anomalies may be additionally present. We present an instance of right-sided hypoplasia of the DAOM in a male newborn, which additionally had dextrocardia as a component of situs inversus totalis. To our knowledge, situs inversus totalis has not been previously documented as a part of this syndrome. Additionally, we reiterate that paediatricians need to be aware that this minor facial anomaly may be associated with severe internal organ system anomalies, with cardiac being most common.
In order to better characterize the Bacillus anthracis typing phage AP50c, we designed a genetic screen to identify its bacterial receptor. Mariner transposon insertions or targeted deletions of the structural gene for the S-layer protein Sap and the sporulation genes spo0A, spo0B, and spo0F in B. anthracis Sterne resulted in phage resistance with concomitant defects in phage adsorption and infectivity. Electron microscopy of bacteria incubated with AP50c revealed phage particles associated with the surface of bacilli of the Sterne strain but not with the surfaces of ?sap, ?spo0A, ?spo0B, or ?spo0F mutants. The amount of Sap in the S-layer of each of the spo0 mutant strains was substantially reduced compared to the parent strain, and incubation of AP50c with purified recombinant Sap led to substantial reduction in phage activity. Phylogenetic analysis based on whole genome sequences of B. cereus sensu lato strains revealed several closely-related B. cereus and B. thuringiensis strains that carry sap genes with very high similarities to that of B. anthracis. Complementation of the ?sap mutant in trans with the wild-type B. anthracis sap or the sap gene from either of two different B. cereus strains that are sensitive to AP50c infection restored phage sensitivity, and electron microscopy confirmed attachment of phage particles to the surface of each of the complemented strains. Based on these data, we postulate that Sap is involved in AP50c infectivity, most likely acting as the phage receptor, and that the spo0 genes may regulate synthesis of Sap and/or formation of the S-layer.
Vibrio cholerae O139 Bengal is the only serogroup other than O1 implicated in cholera epidemics. We describe the isolation and characterization of an O139 serogroup-specific phage, vB_VchP_VchO139-I (?VchO139-I) that has similar host range and virion morphology as phage vB_VchP_JA1 (?JA1) described previously. We aimed at a complete molecular characterization of both phages and elucidation of their genetic and structural differences and assessment of their genetic relatedness to the N4-like phage group.
We report a newborn with methicillin-resistant Staphylococcus aureus mediated necrotizing fasciitis after Bacilli-Calmette-Guerin vaccination. Radical debridement of the affected area coupled with twice daily surgical honey dressing and intravenous vancomycin and clindamycin resulted in satisfactory healing.
Cardiovascular diseases, mostly a lifestyle related disease is going to be an epidemic in near future. Eighty per cent deaths due to cardiovascular diseases occur in low and middle-income group of people. A cross-sectional observational study was undertaken among 208 care-providers of different departments of the Institute of Postgraduate Medical Education and Research, Kolkata to assess the prevalence of general, physical activity related and dietary risk factors. The study subjects were classified into medical (doctors), auxiliary (nurses, technical staffs) and supportive (peons, sweepers) categories according to their job responsibilities. With the help of risk factor scoring system developed by the investigators the prevalence of different category of risk factors were compared among different categories of care-providers in association with some related biological characteristics. The general risk factors found significantly increased (p < 0.001) with increase in age. The physical activity related risk scores were more in females than males. But the difference was not statistically significant. The supportive staffs had significantly higher general risk factors than doctors and auxiliary staffs. Regarding physical activity related risk factors it was significantly lower in supportive staffs than the other two categories. The picture was different in case of dietary risk factors that were found to be significantly lowest among auxiliary staffs.
Burn injuries constitute a major public health problem. A hospital-based descriptive observational study was conducted among 83 burn patients admitted in the Institute of Post Graduate Medical Education and Research, Kolkata in 2008 to assess the demographic and clinical profile of burn patients and to study the medicolegal and social causes. Majority of patients were females (61.5%), literates (78.4%), hindus (79.5%) and in the age group of 20-39 years (56.6%). Occupation-wise housewives were 36.1% followed by students (16.8%).Majority of the cases (61.4%) were accidental whereas suicidal and homicidal cases were 18.1% and 20.5% respectively. According to the size 25.3% patients had 20% -39% of body surface burns and 21.7% had 80% or more burns. 53% of the cases were given blood transfusion and 23.5% died in the study period.
Falciparum malaria is occasionally associated with multiple organ system complications. However, acute pancreatitis rarely occurs as a part of the spectrum. A 13-year-old boy presented with falciparum malaria complicated predominantly by acute pancreatitis. He recovered satisfactorily with supportive measures. To our knowledge, there are less than 10 such documented instances in the literature and they are mostly adults. Acute abdomen in Plasmodium falciparum infection may reveal pancreatitis which should be detected at the earliest.
Communicable diseases continue to be a major problem in India, a large number of which can be prevented by health education, targeting specially the deficiencies and for which a baseline assessment is essential.
Seckel syndrome (Online Mendelian Inheritance in Man database Number 210600) is the classic prototype of primordial bird-headed dwarfism. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities of the cardiovascular, hematopoietic, endocrine, and central nervous systems are described. The full phenotypic spectrum of this clinically and genetically heterogeneous syndrome is yet to be delineated. Presented herein is a boy 2 years and 5 months old, with Seckel syndrome, born to second-degree consanguineous Muslim parents. In addition to the classic phenotype of the disorder, this patient had both, an open and a closed lip schizencephaly detected on cranial computed tomography (CT) scan. To our knowledge, the association of schizencephaly and Seckel syndrome is not described previously in the English language literature. In addition, presented briefly is a review of the anatomical cerebral cortical malformations associated with this syndrome.
Thrombocytopenia of varying magnitude, usually without hemorrhagic manifestations, is commonly observed in Plasmodium falciparum and Plasmodium vivax malaria. However, severe thrombocytopenia associated with bleeding manifestations in malarial infection is distinctly unusual. The pathogenesis of this condition remains speculative till date, although several hypotheses have been put forward. We report a case of 4-year-old boy with P. vivax malaria, who developed severe thrombocytopenia during the course of his infection manifested by bleeding from skin and mucosal surfaces. He improved with antimalarial and intravenous immunoglobulin therapy. Clinicians caring for children should be aware of potential bleeding manifestations that may be the result of apparently innocuous infection like vivax malaria.
Transient affliction of the cranial nerves may at times be either the presenting feature or complication of otherwise uncomplicated Kawasaki disease (KD) in infants and children. The present report describes a 6 year 9 month old boy with classical KD who developed right-sided oculomotor nerve palsy (manifested by ipsilateral ptosis and medial rectus palsy) resulting in symptoms like severe nausea, intense frontal headache and double vision. The palsy resolved within 5 days of intravenous immunoglobulin therapy, with no residual ophthalmological abnormality at 6 weeks. Besides increased intracranial pressure, which commonly occurs during the course of KD in children, secondary to aseptic meningitis, intense headache in such children may have cranial nerve paresis as accentuating factors.
Isolated cranial nerve paresis in childhood hepatitis A virus infection is rare. The authors report an instance of concomitant right-hand side palatal and abducens palsy, developing in the course of an otherwise uncomplicated hepatitis A virus infection in a 5-year-old girl. The neurological complications were transient, and she recovered completely with supportive therapy.
Men who have Sex with Men (MSM) are a vulnerable population and need special attention in the fight against the global pandemic of HIV/AIDS. A study was conducted in an MSM clinic to find out to their varied socio-demographic characteristics, their knowledge and attitude towards HIV/AIDS, and its association with their different sexual practices.
India remains endemic for both vivax malaria and tuberculosis. In spite of the high burden of tuberculosis in the country, reports on congenital tuberculosis in the literature are limited. We report herein an unusual instance of co-occurrence of perinatal falciparum malaria and tuberculosis in a 34-day-old female newborn, who presented with symptoms of sepsis. The diagnosis was based on the demonstration of Plasmodium falciparum on peripheral blood smear and tubercle bacilli in gastric aspirate samples. The maternal history for falciparum malaria was positive during her eighth month of pregnancy and the father was an open case of sputum smear-positive pulmonary tuberculosis. She responded dramatically to combined antimalarial and antitubercular chemotherapy. A search for combined etiologies in presumed sepsis in the newborn, guided by history, physical examination, and laboratory investigations, is warranted.
Mefloquine, a commonly used oral antimalarial is occasionally associated with severe, neuropsychiatric adverse effects, especially in adults. Such events are extremely rare in children. The authors report on an 11-year-old, otherwise healthy girl from Eastern India, a malaria-endemic region, who developed mania and psychosis following intake of a therapeutic dose of mefloquine for Plasmodium falciparum malaria. She recovered satisfactorily with risperidone therapy. To our knowledge, there is only one documented instance of mefloquine-induced psychosis in the pediatric literature to date. Those caring for children need to realize that severe neuropsychiatric manifestations may be seen in the pediatric age group. A positive history of intake of the offending drug with careful exclusion of other etiologies usually clinches the diagnosis.
Wilson disease is a relatively rare inherited disorder of copper accumulation and toxicity, caused by a defect in an enzyme that is part of the pathway of biliary excretion of excess copper. A 17-year-old boy presented with numerous episodes of hypokalemic weakness of the lower limbs of undetermined etiology since 12 years of age. Clinically, lower-motor neuron type of weakness of the limbs with preserved reflexes and paucity of sensory abnormalities were prominent. The investigations revealed distal renal tubular acidosis, hepatitis, and bilateral Kayser-Fleischer ring. The diagnosis of Wilson disease was confirmed by the demonstration of low serum ceruloplasmin, high serum copper, and high urinary copper excretion per se and after penicillamine challenge. He responded satisfactorily to penicillamine and zinc. Careful search of an underlying etiology in children presenting with hypokalemic weakness of the limbs in the face of metabolic acidosis and unexplained hepatitis may reveal Wilson disease.
The association of viral hepatitis and acute pancreatitis is well described in the literature. Most of the cases occur in conjunction with fulminant hepatitis A and hepatitis B virus infections. The recent literature reports increasing number of cases of this complication secondary to hepatitis E virus (HEV) infection, mostly in young adults in regions endemic for the virus. Till date, to the authors knowledge, there are 14 well-documented cases of HEV-associated acute pancreatitis in the literature. This study reports on a 7-year-old boy from India deficient in glucose 6 phosphate dehydrogenase (G6PD) with moderately severe pancreatitis, manifesting during the course of nonfulminant acute HEV infection. He developed extremely high serum bilirubin levels, probably attributed to the concomitant viral infection and his G6PD status. He recovered completely with conservative therapy. The present child is the youngest ever reported case till date with this complication secondary to HEV infection.
The conventional and most accepted method of measuring the lytic activity of a phage against its bacterial host is the plaque assay. This method is laborious, time consuming and expensive, especially in high throughput analyses where multiple phage-bacterial interactions are required to be monitored simultaneously. It can also vary considerably with the experimenter and by the growth and plating conditions. Alternatively, the lytic activity can be measured indirectly by following the decrease in optical density of the bacterial cultures owing to lysis. Here we describe an automated, high throughput, indirect liquid lysis assay to evaluate phage growth using the OmniLog(TM) system. The OmniLog(TM) system uses redox chemistry, employing cell respiration as a universal reporter. During active growth of bacteria, cellular respiration reduces a tetrazolium dye and produces a color change that is measured in an automated fashion. On the other hand, successful phage infection and subsequent growth of the phage in its host bacterium results in reduced bacterial growth and respiration and a concomitant reduction in color. Here we show that microtiter plate wells inoculated with Bacillus anthracis and phage show decreased or no growth, compared with the wells containing bacteria only or phage resistant bacteria plus phage. Also, we show differences in the kinetics of bacterial growth and the timing of appearance of phage resistant bacteria in the presence of individual phages or a cocktail of B. anthracis specific phages. The results of these experiments indicate that the OmniLog(TM) system could be used reliably for indirectly measuring phage growth in high throughput host range and phage and antibiotics combination studies.
In May of 2011, an enteroaggregative Escherichia coli O104:H4 strain that had acquired a Shiga toxin 2-converting phage caused a large outbreak of bloody diarrhea in Europe which was notable for its high prevalence of hemolytic uremic syndrome cases. Several studies have described the genomic inventory and phylogenies of strains associated with the outbreak and a collection of historical E. coli O104:H4 isolates using draft genome assemblies. We present the complete, closed genome sequences of an isolate from the 2011 outbreak (2011C-3493) and two isolates from cases of bloody diarrhea that occurred in the Republic of Georgia in 2009 (2009EL-2050 and 2009EL-2071). Comparative genome analysis indicates that, while the Georgian strains are the nearest neighbors to the 2011 outbreak isolates sequenced to date, structural and nucleotide-level differences are evident in the Stx2 phage genomes, the mer/tet antibiotic resistance island, and in the prophage and plasmid profiles of the strains, including a previously undescribed plasmid with homology to the pMT virulence plasmid of Yersinia pestis. In addition, multiphenotype analysis showed that 2009EL-2071 possessed higher resistance to polymyxin and membrane-disrupting agents. Finally, we show evidence by electron microscopy of the presence of a common phage morphotype among the European and Georgian strains and a second phage morphotype among the Georgian strains. The presence of at least two stx2 phage genotypes in host genetic backgrounds that may derive from a recent common ancestor of the 2011 outbreak isolates indicates that the emergence of stx2 phage-containing E. coli O104:H4 strains probably occurred more than once, or that the current outbreak isolates may be the result of a recent transfer of a new stx2 phage element into a pre-existing stx2-positive genetic background.
About 400 million individuals worldwide have been affected by the inherited disorder of glucose-6-phosphate dehydrogenase (G6PD) deficiency that predisposes individuals to neonatal jaundice or hemolytic crisis due to drugs or infections. A descriptive observational study with longitudinal design was undertaken among 109 live newborns, delivered in labor room of IPGME and R, Kolkata during the period from June to August 2009. An objective of the study was to estimate the occurrence of G6PD deficiency among newborns and its association with different socio-demographic, clinical and gestational characteristics. 14.68% newborns were found G6PD deficient. This occurrence was not significantly related to gender, religion and ethnicity, consanguineous marriage of the parents, gestational age and birth weight of the baby. Development of severe jaundice (total serum bilirubin >15 mg/dl) was found 23.8% among G6PD deficient babies and 12.5% among non-G6PD deficient. This difference was statistically not significant.
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