Md. Yunus

Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

Surveillance of rotavirus in a rural diarrhoea treatment centre in Bangladesh, 2000-2006

Rotavirus was detected in 33% of 4519 children less than 5 years of age admitted with diarrhoea to treatment centres at Matlab in rural Bangladesh from 2000 to 2006. Highest rotavirus detection rates were in children aged 6-11 months with 56% being less than 1 year old. The peak seasonal detection was in July-September and December-February. The population-based incidence rates of rotavirus ranged from 10.8 to 19.6/1000 children less than 5 years of age. G1 serotype predominated between June 2002-May 2005 and June 2005-May 2006 the predominant type was G2 (41%) followed by G1 (22%) and G9 (22%). Rotavirus is an important cause of childhood diarrhoea in rural Bangladesh and this burden may be reduced with a rotavirus vaccination programme.

Intussusception Surveillance in a Rural Demographic Surveillance Area in Bangladesh

BACKGROUND Rotavirus is the leading cause of diarrhea-related morbidity and mortality in developing countries, including Bangladesh. The licensed vaccine Rotashield was withdrawn from the market because of an increased risk of intussusception. This study was undertaken to estimate the background incidence rates of intussusception among children aged <2 years, using retrospective and prospective studies in a rural demographic surveillance area in Bangladesh. METHODS All hospital charts of children aged <2 years who presented to the Matlab Hospital and 2 other treatment centers of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), during January 2001-August 2004 were reviewed retrospectively. A prospective surveillance was performed from August 2004 through December 2006 at the 3 treatment centers of ICDDR,B serving Matlab, 4 district and subdistrict government hospitals, and 3 district-based private clinics, to determine population-based rates of intussusception with use of Brighton Collaboration case definitions. All suspected cases of intussusception were referred to the Matlab Hospital by community health research workers for further assessment by a trained medical officer, including performance of an ultrasound examination. RESULTS In total, 2856 charts of children aged <2 years were reviewed retrospectively, and 4 probable cases and 19 possible cases of intussusception were identified. In the prospective surveillance, of 1508 potential cases, including 41 referred by community health research workers, only 2 cases met the case definition of probable intussusception, and 1 case met the definition of possible intussusception. A total of 123 patients had ultrasound examinations performed. The population-based rates of probable and possible cases of intussusception among children aged <2 years were 0-17.8 and 17.7-81.7 cases per 100,000 children per year, respectively. In the retrospective and prospective surveillance, the rates were 0-18.7 and 0-97 cases per 100,000 children per year, respectively. CONCLUSIONS The incidence of intussusception was low among children in Bangladesh. A surveillance system for intussusception has been fully established in the Matlab surveillance area to diagnose, treat, and refer potential cases. This study provides useful information for detection of intussusception during future studies of new-generation rotavirus vaccines and also provides background incidence rates for comparison when rotavirus vaccines are introduced.

Screening for gene–environment (G×E) interaction using omics data from exposed individuals: an application to gene-arsenic interaction

Identifying gene–environment interactions is a central challenge in the quest to understand susceptibility to complex, multi-factorial diseases. Developing an understanding of how inter-individual variability in inherited genetic variation alters the effects of environmental exposures will enhance our knowledge of disease mechanisms and improve our ability to predict disease and target interventions to high-risk sub-populations. Limited progress has been made identifying gene–environment interactions in the epidemiological setting using existing statistical approaches for genome-wide searches for interaction. In this paper, we describe a novel two-step approach using omics data to conduct genome-wide searches for gene–environment interactions. Using existing genome-wide SNP data from a large Bangladeshi cohort study specifically designed to assess the effect of arsenic exposure on health, we evaluated gene-arsenic interactions by first conducting genome-wide searches for SNPs that modify the effect of arsenic on molecular phenotypes (gene expression and DNA methylation features). Using this set of SNPs showing evidence of interaction with arsenic in relation to molecular phenotypes, we then tested SNP–arsenic interactions in relation to skin lesions, a hallmark characteristic of arsenic toxicity. With the emergence of additional omics data in the epidemiologic setting, our approach may have the potential to boost power for genome-wide interaction research, enabling the identification of interactions that will enhance our understanding of disease etiology and our ability to develop interventions targeted at susceptible sub-populations.

Co-occurring eQTLs and mQTLs: detecting shared causal variants and shared biological mechanisms

Inherited genetic variation impacts local gene expression and DNA methylation in humans. Expression and methylation quantitative trait loci (cis-eQTLs and cis-mQTLs) often occur at the same genomic location, suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, we use “co-localization” methods to identify 3,695 eQTL-mQTL pairs that are likely to share a causal variant. Using partial correlation analysis and mediation analysis, we identify >500 pairs with evidence of a causal relationships between expression and methylation (i.e., shared mechanism) with many additional pairs that we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite effects on expression and methylation, although a many affect multiple CpGs in opposite directions. Evidence of shared SNP-age interaction also supports shared mechanisms for two eQTL-mQTL pairs. This work demonstrates the pervasiveness of co-regulated expression and methylation traits in the human genome. This approach can be applied to other types of molecular QTLs to enhance our understanding of regulatory mechanisms.