Omicron infection increases IgG binding to spike protein of predecessor variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in India in 2020-2022 was driven predominantly by Wild (Wuhan-Hu-1 and D614G), Delta, and Omicron variants. The aim of this study was to examine the effect of infections on the humoral immune response and cross-reactivity to spike proteins of Wuhan-Hu-1, Delta, C.1.2., and Omicron. Residual archival sera (N = 81) received between January 2020 and March 2022 were included. Infection status was inferred by a positive SARS-CoV-2 RT-PCR and/or serology (anti-N and anti-S antibodies) and sequencing of contemporaneous samples (N = 18) to infer lineage. We estimated the levels and cross-reactivity of infection-induced sera including Wild, Delta, Omicron as well as vaccine breakthrough infections (Delta and Omicron). We found an approximately two-fold increase in spike-specific IgG antibody binding in post-Omicron infection compared with the pre-Omicron period, whilst the change in pre- and post-Delta infections were similar. Further investigation of Omicron-specific humoral responses revealed primary Omicron infection as an inducer of cross-reactive antibodies against predecessor variants, in spite of the weaker degree of humoral response compared to Wuhan-Hu-1 and Delta infection. Intriguingly, Omicron vaccine-breakthrough infections when compared with primary infections, exhibited increased humoral responses against RBD (7.7-fold) and Trimeric S (Trimeric form of spike protein) (34.6-fold) in addition to increased binding of IgGs towards previously circulating variants (4.2 - 6.5-fold). Despite Delta breakthrough infections showing a higher level of humoral response against RBD (2.9-fold) and Trimeric S (5.7-fold) compared to primary Delta sera, a demonstrably reduced binding (36%-49%) was observed to Omicron spike protein. Omicron vaccine breakthrough infection results in increased intensity of humoral response and wider breadth of IgG binding to spike proteins of antigenically-distinct, predecessor variants.

Soil-transmitted helminth infections after mass drug administration for lymphatic filariasis in rural southern India.

OBJECTIVES: Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. METHODS: Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. RESULTS: Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. CONCLUSION: Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.

Body iron and lead status in early childhood and its effects on development and cognition: a longitudinal study from urban Vellore.

OBJECTIVE: Early childhood factors can have persisting effects on development and cognition in children. We propose to explore the trends of Fe deficiency and Pb toxicity in early childhood and their association with child development at 2 years of age and cognition at 5 years. DESIGN: Longitudinal birth cohort study. SETTING: Urban slum, Vellore, India. PARTICIPANTS: Children enrolled at birth were followed up regularly in the first 2 years with developmental and cognitive assessments at 2 and 5 years of age, respectively. RESULTS: The birth cohort enrolled 251 children with 228 children followed up at 2 years and 212 at 5 years of age. Fe deficiency (ID) was highest at 15 months of age and improved subsequently at 24 months. Blood Pb levels (BLL) remained high at all age groups with an increasing trend with age; 97 % at 36 months having high BLL. Persistent high mean BLL at 15 and 24 months had negative association with both cognition and expressive language raw scores of 24 months, while high mean BLL at 15, 24 and 36 months had no significant association with any of the domains of cognition at 5 years of age. Early childhood cumulative body Fe status at 7, 15 and 24 months did not show any association with child development at 2 years, but was associated with verbal, performance and processing speed components of cognition at 5 years. CONCLUSIONS: Optimising body Fe status and limiting Pb exposure in early childhood can augment child development and school entry cognition.

Risk factors for acquisition of scrub typhus in children admitted to a tertiary centre and its surrounding districts in South India: a case control study.

BACKGROUND: Scrub typhus is a mite borne zoonosis common in the tropics with no good preventive strategy. Children are also affected leading to considerable morbidity and mortality. We conducted a case control study and a vector survey to determine the risk factors for acquisition of scrub typhus. METHODS: A case control study with a 1:2 case control ratio was conducted over a 2 year period at a tertiary care centre and its surrounding districts in South India. Cases were children < 15 years with confirmed scrub typhus. Controls were age and locality matched community controls without fever. Demographic, environmental and behavioural risk factors were obtained in cases and controls by an interview and an environmental survey. A vector survey was also undertaken in the immediate vicinity of the cases. RESULTS: Case Control study: 101 cases and 167 controls were analysed. On multivariate analysis, significant association was observed with environmental factors such as the presence of a water body within 100 m of the house (OR 3.56(1.36,9.75); p 0.011), cooking outside the house (OR 5.61 (1.51,23.01); p 0.011), owning pets (OR 3.33(1.16,9.09); p 0.031), and the presence of bushes within 5 m of the house (OR 2.78 (1.11,7.69); p 0.033). Of the behavioural factors, the child going to school by a vehicle (OR 3.12 (2.29,8.37); p 0.006) was associated with an increased risk. Drying clothes on a clothesline showed a trend towards protection from acquiring scrub typhus (OR 0.31 (0.08, 1.08); p 0.077). Vector survey:26 rodents were trapped in as many houses. Trombiculid mites were isolated in 24 houses with 9(34.6%) being able to transmit scrub typhus. 254 trombiculid mites belonging to four species and two genera were collected. Leptotrombidium deliense, (33.5%). Schoengastiella ligula, (11.0%) of the total mite specimens collected. S. ligula always co-existed with L. deliense. The estimated Chigger index for Leptotrombidium deliense and Schoengastiella ligula was 3.27and 1.08 per animal respectively. CONCLUSIONS: Our study highlights risk factors for scrub typhus, some of which may be modifiable. A clean peri-domestic environment free of vegetation, drying clothes on a clothesline and cooking indoors may decrease the risk of scrub typhus.

Natural History of Cryptosporidiosis in a Birth Cohort in Southern India.

BACKGROUND: Cryptosporidium is a leading cause of moderate to severe childhood diarrhea in resource-poor settings. Understanding the natural history of cryptosporidiosis and the correlates of protection are essential to develop effective and sustainable approaches to disease control and prevention. METHODS: Children (N = 497) were recruited at birth in semiurban slums in Vellore, India, and followed for 3 years with twice-weekly home visits. Stool samples were collected every 2 weeks and during diarrheal episodes were tested for Cryptosporidium species by polymerase chain reaction (PCR). Serum samples obtained every 6 months were evaluated for seroconversion, defined as a 4-fold increase in immunoglobulin G directed against Cryptosporidium gp15 and/or Cp23 antigens between consecutive sera. RESULTS: Of 410 children completing follow-up, 397 (97%) acquired cryptosporidiosis by 3 years of age. PCR identified 1053 episodes of cryptosporidiosis, with an overall incidence of 0.86 infections per child-year by stool and serology. The median age for the first infection was 9 (interquartile range, 4-17) months, indicating early exposure. Although infections were mainly asymptomatic (693 [66%]), Cryptosporidium was identified in 9.4% of diarrheal episodes. The proportion of reinfected children was high (81%) and there was clustering of asymptomatic and symptomatic infections (P < .0001 for both). Protection against infection increased with the order of infection but was only 69% after 4 infections. Cryptosporidium hominis (73.3%) was the predominant Cryptosporidium species, and there was no species-specific protection. CONCLUSIONS: There is a high burden of endemic cryptosporidiosis in southern India. Clustering of infection is suggestive of host susceptibility. Multiple reinfections conferred some protection against subsequent infection.

Epidemiology & risk factors of scrub typhus in south India.

BACKGROUND & OBJECTIVES: Scrub typhus is a major public health threat in South and Southeastern Asian countries including India. Understanding local patterns of disease and factors that place individuals at risk is pivotal to future preventive measures against scrub typhus. The primary aim of this study was to identify specific epidemiological and geographical factors associated with an increased risk of developing scrub typhus in this region. METHODS: We mapped 709 patients from Tamil Nadu, Andhra Pradesh and Telangana who were admitted to the Christian Medical College (CMC) Hospital, Vellore, Tamil Nadu, India, for the period 2006-2011, assessed seasonality using monthly counts of scrub typhus cases, and conducted a case-control study among a subset of patients residing in Vellore. RESULTS: The geographic distribution of cases at CMC Hospital clusters around the Tamil Nadu-Andhra Pradesh border. However, distinct hotspots clearly exist distal to this area, near Madurai and the coast in Tamil Nadu, and in the Northeast of Andhra Pradesh. Seasonally, the highest numbers of cases were observed in the cooler months of the year, i.e. September to January. In the case-control analysis, cases were more likely to be agricultural laborers (OR 1.79, 95% CI 1.01 - 3.15), not wear a shirt at home (OR 4.23, 95% CI 1.12 - 16.3), live in houses adjacent to bushes or shrubs (OR 1.95, 95% CI 1.08 - 3.53), and live in a single room home (OR 1.75, 95% CI 1.02 - 3.01). On binary logistic regression, the first three of these variables were statistically significant. INTERPRETATION & CONCLUSIONS: With the growing number of cases detected in India, scrub typhus is fast emerging as a public health threat and further research to protect the population from this deadly infection is essential. Health education campaigns focusing on the agricultural workers of Southern India, especially during the cooler months of the year, can serve as an important public health measure to control infection.

Comparative evaluation of validity and cost-benefit analysis of rapid diagnostic test (RDT) kits in diagnosis of dengue infection using composite reference criteria: A cross-sectional study from south India.

BACKGROUND & OBJECTIVES: Rapid diagnostic test (RDT) kits are widely used in India for the diagnosis of dengue infection. It is important to evaluate the validity and reliability of these RDTs. The study was aimed to determine the sensitivity, specificity and predictive value of four commercially available RDTs [Panbio Dengue Duo cassette, Standard Diagnostics (SD) Bioline Dengue Duo, J. Mitra Dengue Day-1 test and Reckon Dengue IgG/IgM] against composite reference criteria (CRC), and compare the cost of the tests. METHODS: In this prospective observational study for diagnostic accuracy, we tested stored blood samples from 132 cases of dengue and 149 controls of other infections as classified based on CRC, with all the four RDTs. The CRC was based on the epidemiological considerations, common clinical features and laboratory abnormalities. The non-dengue controls were the cases of proven alternative diagnosis. The diagnostic performances of the tests were compared in terms of sensitivity, specificity and predictive value along with the cost involved per test. RESULTS: The sensitivity of the Panbio and SD RDT kits was found to be 97.7 and 64.3% respectively, and the specificities were 87.8 and 96.6% respectively. The sensitivity of the NS1 antigen capture by SD Duo, Reckon, J. Mitra RDTs was 20.9, 18.6 and 27.1% respectively. The prevalence of dengue specific IgG antibody with Panbio RDT kits was 49.3%. The cost per test for Panbio, SD, Reckon and J. Mitra is US$ 6.90, 4.27, 3.29 and 3.61 respectively. CONCLUSION: It was concluded that in dengue outbreak, Panbio IgM capture RDT alone is reliable and easily available test which can be used in acute phase of dengue infection in any resource limited set up. NS1 capture rates by any of the other three RDTs might not be reliable for the diagnosis of acute dengue infection.

Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial.

BACKGROUND: Intestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV. METHODS: We did an open-label, randomised controlled trial in children aged 1-4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1:1) to receive 0·5 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005. FINDINGS: Between Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vaccine group (risk ratio 0·62, 95% CI 0·40-0·97, p=0·0375; 0·30, 0·18-0·49, p<0·0001). No adverse events were related to the study interventions. INTERPRETATION: The substantial boost in intestinal immunity conferred by a supplementary dose of IPV given to children younger than 5 years who had previously received OPV shows a potential role for this vaccine in immunisation activities to accelerate eradication and prevent outbreaks of poliomyelitis. FUNDING: Bill & Melinda Gates Foundation.

Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. METHODS: We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). FINDINGS: 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product. INTERPRETATION: Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. FUNDING: Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

Comparison of fieldworker interview and a pictorial diary method for recording morbidity of infants in semi-urban slums.

BACKGROUND: Cohort studies conducted in low-income countries generally use trained fieldworkers for collecting data on home visits. In industrialised countries, researchers use less resource intensive methods, such as self-administered structured questionnaires or symptom diaries. This study compared and assessed the reliability of the data on diarrhoea, fever and cough/cold in children as obtained by a pictorial diary maintained by the mother and collected separately by a fieldworker. METHODS: A sample of 205 children was randomly selected from an ongoing birth cohort study. Pictorial diaries were distributed weekly to mothers of study children who were asked to maintain a record of morbidity for four weeks. We compared the reliability and completeness of the data on diarrhoea, fever and cough/cold obtained by the two methods. RESULTS: Of 205 participants, 186 (91%) ever made a record in the diary and 62 (30%) mothers maintained the diary for all 28 days. The prevalence-adjusted bias-adjusted kappa statistics for diarrhoea, fever, cough/cold and for a healthy child were 92%, 79%, 35% and 35% respectively. CONCLUSION: Diary recording was incomplete in the majority of households. When recorded, the morbidity data by the pictorial diary method for acute illnesses were reliable. Strategies are needed to address behavioural factors affecting maternal recording such that field studies can obtain accurate morbidity measurements with limited resources.

Protective effect of natural rotavirus infection in an Indian birth cohort.

BACKGROUND: More than 500,000 deaths are attributed to rotavirus gastroenteritis annually worldwide, with the highest mortality in India. Two successive, naturally occurring rotavirus infections have been shown to confer complete protection against moderate or severe gastroenteritis during subsequent infections in a birth cohort in Mexico. We studied the protective effect of rotavirus infection on subsequent infection and disease in a birth cohort in India (where the efficacy of oral vaccines in general has been lower than expected). METHODS: We recruited children at birth in urban slums in Vellore; they were followed for 3 years after birth, with home visits twice weekly. Stool samples were collected every 2 weeks, as well as on alternate days during diarrheal episodes, and were tested by means of enzyme-linked immunosorbent assay and polymerase-chain-reaction assay. Serum samples were obtained every 6 months and evaluated for seroconversion, defined as an increase in the IgG antibody level by a factor of 4 or in the IgA antibody level by a factor of 3. RESULTS: Of 452 recruited children, 373 completed 3 years of follow-up. Rotavirus infection generally occurred early in life, with 56% of children infected by 6 months of age. Levels of reinfection were high, with only approximately 30% of all infections identified being primary. Protection against moderate or severe disease increased with the order of infection but was only 79% after three infections. With G1P[8], the most common viral strain, there was no evidence of homotypic protection. CONCLUSIONS: Early infection and frequent reinfection in a locale with high viral diversity resulted in lower protection than has been reported elsewhere, providing a possible explanation why rotavirus vaccines have had lower-than-expected efficacy in Asia and Africa. (Funded by the Wellcome Trust.).

Genetic characterization of Spinocerebellar ataxia 1 in a South Indian cohort.

BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is a late onset autosomal dominant cerebellar ataxia, caused by CAG triplet repeat expansion in the ATXN1 gene. The frequency of SCA1 occurrence is more in Southern India than in other regions as observed from hospital-based studies. However there are no reports on variability of CAG repeat expansion, phenotype-genotype association and founder mutations in a homogenous population from India. METHODS: Genomic DNA isolated from buccal mouthwash of the individuals in the cohort was used for PCR-based diagnosis of SCA1. Subsequently SNP's found within the ATXN1 loci were identified by Taqman allelic discrimination assays. Significance testing of the genotype-phenotype associations was calculated by Kruskal-Wallis ANOVA test with post-hoc Dunnett's test and Pearson's correlation coefficient. RESULTS: By genetic analysis of an affected population in Southern India we identified 21 pre-symptomatic individuals including four that were well past the average age of disease onset of 44 years, 16 symptomatic and 63 normal individuals. All pre-symptomatic cases harbor "pure" expansions of greater than 40 CAGs. Genotyping to test for the presence of two previously identified SNPs showed a founder effect of the same repeat carrying allele as in the general Indian population. We show that SCA1 disease onset is significantly delayed when transmission of the disease is maternal. CONCLUSIONS: Our finding of early disease onset in individuals with a paternally inherited allele could serve as valuable information for clinicians towards early detection of SCA1 in patients with affected fathers. Identification of older pre-symptomatic individuals (n = 4) in our cohort among individuals with a shared genetic and environmental background, suggests that second site genetic or epigenetic modifiers might significantly affect SCA1 disease progression. Moreover, such undetected SCA1 cases could underscore the true prevalence of SCA1 in India.

Prevalence & risk factors for soil transmitted helminth infection among school children in south India.

BACKGROUND & OBJECTIVES: Soil-transmitted helminths (STH) are a major public health problem in tropical and sub-tropical countries, affecting the physical growth and cognitive development in school-age children. This study was aimed to assess the prevalence and risk factors of STH infection among school children aged 6 -14 yr in Vellore and Thiruvanamalai districts in south India. METHODS: Children aged 6-14 yr, going to government and government aided schools (n=33, randomly selected) in Vellore and Thiruvanamalai districts were screened to estimate the prevalence of STH, and a case control study was done on a subset to assess the risk factors for the infection. RESULTS: The prevalence of STH was 7.8 per cent, varying widely in schools from 0 to 20.4 per cent, in 3706 screened children. Hookworm (8.4%) rates were high in rural areas, while Ascaris (3.3%) and Trichuris (2.2%) were more prevalent among urban children. Consumption of deworming tablets (OR=0.25, P < 0.01) offered protection, while residing in a field hut (OR=6.73, P=0.02) and unhygienic practices like open air defaecation (OR=5.37, P < 0.01), keeping untrimmed nails (OR=2.53, P=0.01) or eating food fallen on the ground (OR=2.52, P=0.01) were important risk factors for STH infection. INTERPRETATION & CONCLUSIONS: Our study indicated that school children with specific risk factors in the studied area were vulnerable subpopulation with elevated risk of STH infection. Identifying risk factors and dynamics of transmission in vulnerable groups can help to plan for effective prevention strategies.

Cryptosporidiosis among children in an endemic semiurban community in southern India: does a protected drinking water source decrease infection?

BACKGROUND: A quasi-experimental study was conducted to determine whether or not a protected water supply (bottled drinking water) could prevent or delay cryptosporidial infections among children residing in an endemic community. METHODS: A total of 176 children residing in a semiurban slum area in southern India were enrolled preweaning and received either bottled (n = 90) or municipal (n = 86) drinking water based on residence in specific streets. Weekly surveillance visits were conducted until children reached their second birthday. Stool samples were collected every month and during diarrheal episodes, and were tested for the presence of Cryptosporidium species by polymerase chain reaction. Differences in the incidence of cryptosporidiosis between bottled and municipal water groups were compared using Poisson survival models, and a propensity score model was developed to adjust for the effect of potential confounders. RESULTS: A total of 186 episodes of cryptosporidiosis, mostly asymptomatic, were observed in 118 (67%) children during the follow-up period at a rate of 0.59 episodes per child-year. Diarrhea associated with Cryptosporidium species tended to be longer in duration and more severe. Stunting at 6 months was associated with a higher risk of cryptosporidiosis (rate ratio [RR] = 1.40; 95% confidence interval [CI], 1.03-1.91). A higher gastrointestinal disease burden was also seen in children with cryptosporidiosis. Drinking bottled water was not associated with a reduced risk of cryptosporidiosis (adjusted RR = 0.86; 95% CI, .60-1.23). CONCLUSIONS: This study documented a high burden of cryptosporidiosis among children in an endemic Indian slum community. The lack of association between drinking bottled water and cryptosporidiosis suggests possible spread from asymptomatically infected individuals involving multiple transmission pathways.

Prevalence and clustering of soil-transmitted helminth infections in a tribal area in southern India.

OBJECTIVES: To estimate the prevalence, spatial patterns and clustering in the distribution of soil-transmitted helminth (STH) infections, and factors associated with hookworm infections in a tribal population in Tamil Nadu, India. METHODS: Cross-sectional study with one-stage cluster sampling of 22 clusters. Demographic and risk factor data and stool samples for microscopic ova/cysts examination were collected from 1237 participants. Geographical information systems mapping assessed spatial patterns of infection. RESULTS: The overall prevalence of STH was 39% (95% CI 36%­42%), with hookworm 38% (95% CI 35­41%) and Ascaris lumbricoides 1.5% (95% CI 0.8­2.2%). No Trichuris trichiura infection was detected. People involved in farming had higher odds of hookworm infection (1.68, 95% CI 1.31­2.17, P < 0.001). In the multiple logistic regression, adults (2.31, 95% CI 1.80­2.96, P < 0.001), people with pet cats (1.55, 95% CI 1.10­2.18, P = 0.011) and people who did not wash their hands with soap after defecation (1.84, 95% CI 1.27­2.67, P = 0.001) had higher odds of hookworm infection, but gender and poor usage of foot wear did not significantly increase risk. Cluster analysis, based on design effect calculation, did not show any clustering of cases among the study population; however, spatial scan statistic detected a significant cluster for hookworm infections in one village. CONCLUSION: Multiple approaches including health education, improving the existing sanitary practices and regular preventive chemotherapy are needed to control the burden of STH in similar endemic areas.

Use of serum vitamin B12 level as a marker to differentiate idiopathic noncirrhotic intrahepatic portal hypertension from cryptogenic cirrhosis.

BACKGROUND AND AIMS: Idiopathic non-cirrhotic intrahepatic portal hypertension (NCIPH) is often mis-diagnosed as cryptogenic cirrhosis. Serum vitamin B12 levels can be raised in cirrhosis, probably because of excess release or reduced clearance. Because NCIPH is characterised by long periods of preserved liver function, we examined whether serum B12 level could be used as a marker to differentiate NCIPH from cryptogenic cirrhosis. METHODS: We analysed serum B12 levels in 45 NCIPH and 43 cryptogenic cirrhosis patients from January 2009 to September 2011. RESULTS: Serum B12 levels were significantly lower in NCIPH patients than in cryptogenic cirrhosis patients (p < 0.001) and were useful in differentiating the two disorders (area under ROC: 0.84; 95% C.I: 0.76-0.93). Low serum B12 level (≤250 pg/ml) was noted in 25/72 (35%) healthy controls, 14/42 (33%) NCIPH patients, and 1/38 (3 %) cryptogenic cirrhosis patients. In patients with intrahepatic portal hypertension of unknown cause, serum B12 level ≤ 250 pg/ml was useful for diagnosing NCIPH (positive predictive value: 93 %, positive likelihood ratio 12.7), and serum B12 level >1,000 pg/ml was useful in ruling out NCIPH (negative predictive value: 86 %, negative likelihood ratio: 6.67). Low serum B12 levels (≤250 pg/ml) correlated with diagnosis of NCIPH after adjusting for possible confounders (O.R: 13.6; 95% C.I:1.5-126.2). Among patients in Child's class A, serum B12 level was ≤250 pg/ml in 14/35 NCIPH patients compared with 1/21 cryptogenic cirrhosis patients (O.R: 13.3; 95% C.I: 1.6-111). CONCLUSION: Serum vitamin B12 level seems to be a useful non-invasive marker for differentiation of NCIPH from cryptogenic cirrhosis.

Evaluation of a programme for prevention of vertical transmission of hepatitis B in a rural block in southern India.

BACKGROUND & OBJECTIVES: This study was undertaken to evaluate a community based programme of antenatal screening for hepatitis B surface antigen (HBsAg) and selective immunization of children commencing at birth, at a secondary care hospital in south India. The primary objective was to assess immunization coverage among children born to HBsAg positive women; secondary objectives were to study the prevalence of HBsAg among antenatal women, prevalence of HBsAg among immunized children (to estimate vaccine efficacy), seroconversion rate and relationship of maternal hepatitis B e antigen (HBeAg) to hepatitis infection. METHODS: The prevalence of hepatitis B antigen among antenatal women and immunization coverage achieved with hepatitis B vaccine in a rural block in Vellore, Tamil Nadu were assessed through examination of records. Children born between May 2002 and December 2007 to hepatitis B positive women were followed up for a serological evaluation, based on which vaccine efficacy and the effect of maternal hepatitis B e antigen (HBeAg) on breakthrough infection was estimated. RESULTS: The prevalence of hepatitis B surface antigen among antenatal women was 1.58 % (95% CI: 1.35-1.81%). Vaccine coverage for three doses as per a recommended schedule (including a birth dose) was 70 per cent, while 82.4 per cent eventually received three doses (including a birth dose). Estimated vaccine efficacy was 68 per cent and seroconversion 92.4 per cent in children aged 6-24 months. Maternal HBeAg was significantly associated with either anti-HBc or HBsAg in immunized children, RR=5.89 (95% CI: 1.21-28.52%). INTERPRETATION & CONCLUSIONS: The prevalence of hepatitis B among antenatal women in this region was low and a programme of selective immunization was found to be feasible, achieving a high coverage for three doses of the vaccine including a birth dose.

Burden of childhood diseases and malnutrition in a semi-urban slum in southern India.

BACKGROUND: India has seen rapid unorganized urbanization in the past few decades. However, the burden of childhood diseases and malnutrition in such populations is difficult to quantify. The morbidity experience of children living in semi-urban slums of a southern Indian city is described. METHODS: A total of 176 children were recruited pre-weaning from four geographically adjacent, semi-urban slums located in the western outskirts of Vellore, Tamil Nadu for a study on water safety and enteric infections and received either bottled or municipal drinking water based on their area of residence. Children were visited weekly at home and had anthropometry measured monthly until their second birthday. RESULTS: A total of 3932 episodes of illness were recorded during the follow-up period, resulting in an incidence of 12.5 illnesses/child-year, with more illness during infancy than in the second year of life. Respiratory, mostly upper respiratory infections, and gastrointestinal illnesses were most common. Approximately one-third of children were stunted at two years of age, and two-thirds had at least one episode of growth failure during the two years of follow up. No differences in morbidity were seen between children who received bottled and municipal water. CONCLUSIONS: Our study found a high burden of childhood diseases and malnutrition among urban slum dwellers in southern India. Frequent illnesses may adversely impact children's health and development, besides placing an additional burden on families who need to seek healthcare and find resources to manage illness.

Molecular characteristics of meningiomas in a cohort of Indian patients: loss of heterozygosity analysis of chromosomes 22, 17, 14 and 10.

BACKGROUND: Though, loss of heterozygosity (LOH) at chromosome 22q is considered to be the most likely initiating event in the formation of meningiomas, LOH at other chromosomes (1, 3, 6, 9, 10, 11, 14.17, and 18) have been implicated in its progression. The aim of this study was to analyze microsatellite markers on a select set of chromosomes including, 22q, 10q, 14q, and 17p for LOH in patients with meningiomas. MATERIALS AND METHODS: Tumor tissue and its corresponding blood sample were collected from 27 patients with meningioma. Four polymorphic microsatellite markers (D10S520, D17S1289, D14S555, and D22S417) were characterized for LOH analysis. RESULTS: There were 14 World Health Organization (WHO) grade I, 12 WHO grade II and 1 WHO grade III meningiomas. LOH was seen most often at D22S417 with an equal distribution between the grades (33% of informative samples in each grade). Though, LOH at D14S555 was seen in 50% of informative WHO grade II tumors, compared to 11.1% of informative WHO grade I tumors it did not reach statistical significance. However, allelic imbalance (AI) at D14S555 was significantly associated with atypia (P = 0.05). LOH at D17S1289 was seen only in one tumor sample, and none of the informative samples displayed LOH at D10S520. CONCLUSION: The frequency and equal distribution of LOH at chromosome 22 supports the hypothesis that it is an early event in the tumorigenesis of meningiomas. The association of AI at D14S555 in WHO grade II meningiomas needs to be investigated on a larger set of samples.