Showing papers by "International Centre for Diarrhoeal Disease Research, Bangladesh published in 2016"

Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

Abstract: Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant).

A Worldwide Map of Plasmodium Falciparum K13-Propeller Polymorphisms

Abstract: BACKGROUND: Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. METHODS: We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. RESULTS: We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. CONCLUSIONS: No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

Abstract: Background The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies.

Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics.

Abstract: Childhood undernutrition is a major global health challenge. Although current therapeutic approaches have reduced mortality in individuals with severe disease, they have had limited efficacy in ameliorating long-term sequelae, notably stunting, immune dysfunction, and neurocognitive deficits. Recent work is providing insights about the role of impaired development of the human gut microbiota in disease pathogenesis, leading to new concepts for treatment and prevention. These findings raise intriguing basic questions about the mechanisms that direct normal gut microbial community assembly and functional maturation. Designing and implementing new microbiota-directed therapeutics for undernutrition highlights the need to simultaneously consider a variety of features of human biology as well as broader societal issues.

Reasons for Preference of Home Delivery with Traditional Birth Attendants (TBAs) in Rural Bangladesh: A Qualitative Exploration

Abstract: Background and Objectives Although Bangladesh has made significant progress in reducing maternal and child mortality in the last decade, childbirth assisted by skilled attendants has not increased as much as expected. An objective of the Bangladesh National Strategy for Maternal Health 2014–2024 is to reduce maternal mortality to 50/100,000 live births. It also aims to increase deliveries with skilled birth attendants to more than 80% which remains a great challenge, especially in rural areas. This study explores the underlying factors for the major reliance on home delivery with Traditional Birth Attendants (TBA) in rural areas of Bangladesh. Methods This was a qualitative cross-sectional study. Data were collected between December 2012 and February 2013 in Sunamganj district of Sylhet division and data collection methods included key informant interviews (KII) with stakeholders; formal and informal health service providers and health managers; and in-depth interviews (IDI) with community women to capture a range of information. Key questions were asked of all the study participants to explore the question of why women and their families prefer home delivery by TBA and to identify the factors associated with this practice in the local community. Results The study shows that home delivery by TBAs remain the first preference for pregnant women. Poverty is the most frequently cited reason for preferring home delivery with a TBA. Other major reasons include; traditional views, religious fallacy, poor road conditions, limited access of women to decision making in the family, lack of transportation to reach the nearest health facility. Apart from these, community people also prefer home delivery due to lack of knowledge and awareness about service delivery points, fear of increased chance of having a caesarean delivery at hospital, and lack of female doctors in the health care facilities. Conclusions The study findings provide us a better understanding of the reasons for preference for home delivery with TBA among this population. These identified factors can inform policy makers and program implementers to adopt socially and culturally appropriate interventions that can improve deliveries with skilled attendants and thus contribute to the reduction of maternal and neonatal mortality and morbidity in rural Bangladesh.

Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource Settings: Results From the MAL-ED Study.

Abstract: Background. Enteropathogen infections have been associated with enteric dysfunction and impaired growth in children in low-resource settings. In a multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of Campylobacter infection in the first 2 years of life. Methods. Children were actively followed up until 24 months of age. Diarrheal and nondiarrheal stool samples were collected and tested by enzyme immunoassay for Campylobacter. Stool and blood samples were assayed for markers of intestinal permeability and inflammation. Results. A total of 1892 children had 7601 diarrheal and 26 267 nondiarrheal stool samples tested for Campylobacter. We describe a high prevalence of infection, with most children (n = 1606; 84.9%) having a Campylobacter-positive stool sample by 1 year of age. Factors associated with a reduced risk of Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95% confidence interval, .47–.67), treatment of drinking water (0.76; 0.70–0.83), access to an improved latrine (0.89; 0.82–0.97), and recent macrolide antibiotic use (0.68; 0.63–0.74). A high Campylobacter burden was associated with a lower length-for-age Z score at 24 months (−1.82; 95% confidence interval, −1.94 to −1.70) compared with a low burden (−1.49; −1.60 to −1.38). This association was robust to confounders and consistent across sites. Campylobacter infection was also associated with increased intestinal permeability and intestinal and systemic inflammation. Conclusions. Campylobacter was prevalent across diverse settings and associated with growth shortfalls. Promotion of exclusive breastfeeding, drinking water treatment, improved latrines, and targeted antibiotic treatment may reduce the burden of Campylobacter infection and improve growth in children in these settings.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.

Abstract: BackgroundA single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic. MethodsNonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline. ResultsA total...

Optimization of Quantitative PCR Methods for Enteropathogen Detection.

Abstract: Detection and quantification of enteropathogens in stool specimens is useful for diagnosing the cause of diarrhea but is technically challenging. Here we evaluate several important determinants of quantification: specimen collection, nucleic acid extraction, and extraction and amplification efficiency. First, we evaluate the molecular detection and quantification of pathogens in rectal swabs versus stool, using paired flocked rectal swabs and whole stool collected from 129 children hospitalized with diarrhea in Tanzania. Swabs generally yielded a higher quantification cycle (Cq) (average 29.7, standard deviation 3.5 vs. 25.3 ± 2.9 from stool, P<0.001) but were still able to detect 80% of pathogens with a Cq < 30 in stool. Second, a simplified total nucleic acid (TNA) extraction procedure was compared to separate DNA and RNA extractions and showed 92% (318/344) sensitivity and 98% (951/968) specificity, with no difference in Cq value for the positive results (ΔCq(DNA+RNA-TNA) = -0.01 ± 1.17, P = 0.972, N = 318). Third, we devised a quantification scheme that adjusts pathogen quantity to the specimen’s extraction and amplification efficiency, and show that this better estimates the quantity of spiked specimens than the raw target Cq. In sum, these methods for enteropathogen quantification, stool sample collection, and nucleic acid extraction will be useful for laboratories studying enteric disease.

Soil salinity, household wealth and food insecurity in tropical deltas: evidence from south-west coast of Bangladesh.

Abstract: As a creeping process, salinisation represents a significant long-term environmental risk in coastal and deltaic environments. Excess soil salinity may exacerbate existing risks of food insecurity in densely populated tropical deltas, which is likely to have a negative effect on human and ecological sustainability of these regions and beyond. This study focuses on the coastal regions of the Ganges–Brahmaputra delta in Bangladesh, and uses data from the 2010 Household Income and Expenditure Survey and the Soil Resource Development Institute to investigate the effect of soil salinity and wealth on household food security. The outcome variables are two widely used measures of food security: calorie availability and household expenditure on food items. The main explanatory variables tested include indicators of soil salinity and household-level socio-economic characteristics. The results of logistic regression show that in unadjusted models, soil salinisation has a significant negative effect on household food security. However, this impact becomes statistically insignificant when households’ wealth is taken into account. The results further suggest that education and remittance flows, but not gender or working status of the household head, are significant predictors of food insecurity in the study area. The findings indicate the need to focus scholarly and policy attention on reducing wealth inequalities in tropical deltas in the context of the global sustainable deltas initiative and the proposed Sustainable Development Goals.

Willingness-to-Pay for Community-Based Health Insurance among Informal Workers in Urban Bangladesh

Abstract: INTRODUCTION Reliance on out-of-pocket payment for healthcare may lead poor households to undertake catastrophic health expenditure, and risk-pooling mechanisms have been recommended to mitigate such burdens for households in Bangladesh. About 88% of the population of Bangladesh depends on work in the informal sector. We aimed to estimate willingness-to-pay (WTP) for CBHI and identify its determinants among three categories of urban informal workers rickshaw-pullers, shopkeepers and restaurant workers. METHODS The bidding game version of contingent valuation method was used to estimate weekly WTP. In three urban locations 557 workers were interviewed using a structured questionnaire during 2010 and 2011. Multiple-regression analysis was used to predict WTP by demographic and household characteristics, occupation, education level and past illness. RESULTS WTP for a CBHI scheme was expressed by 86.7% of informal workers. Weekly average WTP was 22.8 BDT [Bangladeshi Taka; 95% confidence interval (CI) 20.9-24.8] or 0.32 USD and varied significantly across occupational groups (p = 0.000) and locations (p = 0.003). WTP was highest among rickshaw-pullers (28.2 BDT or 0.40 USD; 95% CI: 24.7-31.7), followed by restaurant workers (20.4 BDT 0.29 USD; 95% CI: 17.0-23.8) and shopkeepers (19.2 BDT or 0.27 USD; 95% CI: 16.1-22.4). Multiple regression analysis identified monthly income, occupation, geographical location and educational level as the key determinants of WTP. WTP increased 0.196% with each 1% increase in monthly income, and was 26.9% lower among workers with up to a primary level of education versus those with higher than primary, but less than one year of education. CONCLUSION Informal workers in urban areas thus are willing to pay for CBHI and socioeconomic differences explain the magnitude of WTP. The policy maker might think introducing community-based model including public-community partnership model for healthcare financing of informal workers. Decision making regarding the implementation of such schemes should consider worker location and occupation.

How social structures, space, and behaviors shape the spread of infectious diseases using chikungunya as a case study.

Abstract: Whether an individual becomes infected in an infectious disease outbreak depends on many interconnected risk factors, which may relate to characteristics of the individual (e.g., age, sex), his or her close relatives (e.g., household members), or the wider community. Studies monitoring individuals in households or schools have helped elucidate the determinants of transmission in small social structures due to advances in statistical modeling; but such an approach has so far largely failed to consider individuals in the wider context they live in. Here, we used an outbreak of chikungunya in a rural community in Bangladesh as a case study to obtain a more comprehensive characterization of risk factors in disease spread. We developed Bayesian data augmentation approaches to account for uncertainty in the source of infection, recall uncertainty, and unobserved infection dates. We found that the probability of chikungunya transmission was 12% [95% credible interval (CI): 8–17%] between household members but dropped to 0.3% for those living 50 m away (95% CI: 0.2–0.5%). Overall, the mean transmission distance was 95 m (95% CI: 77–113 m). Females were 1.5 times more likely to become infected than males (95% CI: 1.2–1.8), which was virtually identical to the relative risk of being at home estimated from an independent human movement study in the country. Reported daily use of antimosquito coils had no detectable impact on transmission. This study shows how the complex interplay between the characteristics of an individual and his or her close and wider environment contributes to the shaping of infectious disease epidemics.

Role of the Gut Microbiota of Children in Diarrhea Due to the Protozoan Parasite Entamoeba histolytica

Abstract: Children in developing countries are continually exposed to enteric pathogens [1–4]. This results in high rates of morbidity and mortality, especially in infants [5]. The outcome of an Entamoeba histolytica exposure can be diarrhea, dysentery, or amebic liver abscess, with the latter occurring mainly in men [6]. Disease, however, occurs in a minority of E. histolytica infections (approximately 20%) [6]. While both host and parasite factors contribute to outcome, they do not entirely explain susceptibility [7–9]. A prospective longitudinal study of enteric pathogens in a slum community in Dhaka, Bangladesh, has provided a rich data set to identify parameters important for protection and disease. It has been previously shown that children in this study cohort who are malnourished at birth are more susceptible to amebiasis and in general experience more-severe diarrhea [2]. There is evidence in support of both passive and active acquired immunity. Infants with mothers with high levels of breast milk anti-galactose/N-acetylgalactosamine (Gal/GalNAc) lectin immunoglobulin A (IgA) had fewer E. histolytica infections, and children with fecal IgA anti-Gal/GalNAc lectin IgA also had a lower incidence of new infection [10, 11]. Weaning and the introduction of supplementary food into the diet is known to trigger changes in the bacterial composition of the microbiome that include increases in Prevotellaceae and Bacteroides species [12, 13]. The first 2 years of life in general is a period of rapid immune and microbiome maturation, which, in this population, may be disrupted by malnutrition and environmental insult [13–15]. Here we describe the natural history of amebiasis in the first 2 years of life in infants from an urban slum in Dhaka. The cumulative incidence of amebic infection and diarrhea, the association of protection with anti-Gal/GalNAc lectin IgA, the impact of parasite burden on symptoms, and potential role of Prevotella copri in E. histolytica diarrhea are described.

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Abstract: Background Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhica, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved.

Nipah Virus Transmission from Bats to Humans Associated with Drinking Traditional Liquor Made from Date Palm Sap, Bangladesh, 2011-2014.

Abstract: Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From December 2010 through March 2014, hospital-based encephalitis surveillance in Bangladesh identified 18 clusters of NiV infection. The source of infection for case-patients in 3 clusters in 2 districts was unknown. A team of epidemiologists and anthropologists investigated these 3 clusters comprising 14 case-patients, 8 of whom died. Among the 14 case-patients, 8 drank fermented date palm sap (tari) regularly before their illness, and 6 provided care to a person infected with NiV. The process of preparing date palm trees for tari production was similar to the process of collecting date palm sap for fresh consumption. Bat excreta was reportedly found inside pots used to make tari. These findings suggest that drinking tari is a potential pathway of NiV transmission. Interventions that prevent bat access to date palm sap might prevent tari-associated NiV infection.

Mobile suitcase laboratory for rapid detection of Leishmania donovani using recombinase polymerase amplification assay.

Abstract: Leishmania donovani (LD) is a protozoan parasite transmitted to humans from sand flies, which causes Visceral Leishmaniasis (VL). Currently, the diagnosis is based on presence of the anti-LD antibodies and clinical symptoms. Molecular diagnosis would require real-time PCR, which is not easy to implement at field settings. In this study, we report on the development and testing of a recombinase polymerase amplification (RPA) assay for the detection of LD. A genomic DNA sample was applied to determine the assay analytical sensitivity. The cross-reactivity of the assay was tested by DNA of Leishmania spp. and of pathogens considered for differential diagnosis. The clinical performance of the assay was evaluated on LD positive and negative samples. All results were compared with real-time PCR. To allow the use of the assay at field settings, a mobile suitcase laboratory (56 × 45.5 × 26.5 cm) was developed and operated at the local hospital in Mymensingh, Bangladesh. The LD RPA assay detected equivalent to one LD genomic DNA. The assay was performed at constant temperature (42 °C) in 15 min. The RPA assay also detected other Leishmania species (L. major, L. aethiopica and L. infantum), but did not identify nucleic acid of other pathogens. Forty-eight samples from VL, asymptomatic and post-kala-azar dermal leishmaniasis subjects were detected positive and 48 LD-negative samples were negative by both LD RPA and real-time PCR assays, which indicates 100 % agreement. The suitcase laboratory was successfully operated at the local hospital by using a solar-powered battery. DNA extraction was performed by a novel magnetic bead based method (SpeedXtract), in which a simple fast lysis protocol was applied. Moreover, All reagents were cold-chain independent. The mobile suitcase laboratory using RPA is ideal for rapid sensitive and specific detection of LD especially at low resource settings and could contribute to VL control and elimination programmes.

Prevalence and Health Care-Seeking Behavior for Childhood Diarrheal Disease in Bangladesh.

Abstract: In Bangladesh, the burden of diarrheal diseases is significant among children <5 years old. The objective of this study is to capture the prevalence of and health care-seeking behavior for childhood diarrheal diseases (CDDs) and to identify the factors associated with CDDs at a population level in Bangladesh. We use a logistic regression approach to model careseeking based on individual characteristics. The overall diarrhea prevalence among children <5 years old was found to be 5.71%. Some factors found to significantly influence the health care-seeking pattern were age and sex of the children, nutritional score, age and education of mothers, wealth index, and access to electronic media. The health care service could be improved through working in partnership with public facilities, private health care practitioners, and community-based organizations, so that all strata of the population get equitable access in cases of childhood diarrhoea.

Norovirus Infection and Acquired Immunity in 8 Countries: Results From the MAL-ED Study

Abstract: Background. Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life. Methods. A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity. Results. Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was comparable to other enteropathogens, with the exception of rotavirus. Incidence of genogroup II (GII) infection was higher than genogroup I and peaked at 6–11 months across sites. Undernutrition was a risk factor for symptomatic norovirus infection, with an increase in 1 standard deviation of length-for-age z score associated with a 17% reduction (odds ratio, 0.83 [95% confidence interval, .72–.97]; P = .011) in the odds of experiencing diarrhea when norovirus was present, after accounting for genogroup, rotavirus vaccine, and age. Evidence of acquired immunity was observed among GII infections only: Children with prior GII infection were found to have a 27% reduction in the hazard of subsequent infection (hazard ratio, 0.727; P = .010). Conclusions. The high prevalence of norovirus across 8 sites in highly variable epidemiologic settings and demonstration of protective immunity for GII infections provide support for investment in vaccine development.

Natural History of Cryptosporidiosis in a Longitudinal Study of Slum-Dwelling Bangladeshi Children: Association with Severe Malnutrition.

Abstract: BACKGROUND: Cryptosporidiosis is a common cause of infectious diarrhea in young children worldwide and is a significant contributor to under-five mortality. Current treatment options are limited in young children. In this study we describe the natural history of Cryptosporidium spp. infection in a birth cohort of children in Bangladesh and evaluate for association with malnutrition. METHODOLOGY/PRINCIPAL FINDINGS: This is a longitudinal birth cohort study of 392 slum-dwelling Bangladeshi children followed over the first two years of life from 2008 to 2014. Children were monitored for diarrheal disease and stool was tested for intestinal protozoa. Anthropometric measurements were taken at 3-month intervals. A subset of Cryptosporidium positive stools were genotyped for species and revealed that C. hominis was isolated from over 90% of samples. In the first two years of life 77% of children experienced at least one infection with Cryptosporidium spp. Non-diarrheal infection (67%) was more common than diarrheal infection (6.3%) although 27% of children had both types of infection. Extreme poverty was associated with higher rates of infection (chi-square 49.7% vs 33.3% p = 0.006). Malnutrition was common in this cohort 56% of children had stunted growth by age two. Children with Cryptosporidium spp. infection had a greater than 2-fold increased risk of severe stunting at age two compared to uninfected children (odds ratio 2.69 95% CI 1.17 6.15 p = 0.019) independent of sex income maternal body-mass index maternal education and weight for age adjusted z (WAZ) score at birth. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium infection is common (77%) in this cohort of slum-dwelling Bangladeshi children and both non-diarrheal and diarrheal infections are significantly associated with a childs growth at 2 years of age.

Socio-Economic Inequality of Chronic Non-Communicable Diseases in Bangladesh.

Abstract: This article was published in the PLoS ONE [© 2016 Biswas et al.] and the definitive version is available at: http://doi.org/10.1371/journal.pone.0167140 The Journal's website is at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167140