Showing papers by "International Centre for Diarrhoeal Disease Research, Bangladesh published in 2012"

Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study

Abstract: Summary Background 18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. Methods We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0–17 years, 18–64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. Findings We estimate that globally there were 201 200 respiratory deaths (range 105 700–395 600) with an additional 83 300 cardiovascular deaths (46 000–179 900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Interpretation Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. Funding None.

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

Abstract: There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

The Global Enteric Multicenter Study (GEMS) of Diarrheal Disease in Infants and Young Children in Developing Countries: Epidemiologic and Clinical Methods of the Case/Control Study

Abstract: Background. Diarrhea is a leading cause of illness and death among children aged <5 years in developing countries. This paper describes the clinical and epidemiological methods used to conduct the Global Enteric Multicenter Study (GEMS), a 3-year, prospective, age-stratified, case/control study to estimate the population-based burden, microbiologic etiology, and adverse clinical consequences of acute moderate-to-severe diarrhea (MSD) among a censused population of children aged 0–59 months seeking care at health centers in sub-Saharan Africa and South Asia. Methods. GEMS was conducted at 7 field sites, each serving a population whose demography and healthcare utilization practices for childhood diarrhea were documented. We aimed to enroll 220 MSD cases per year from selected health centers serving each site in each of 3 age strata (0–11, 12–23, and 24–59 months), along with 1–3 matched community controls. Cases and controls supplied clinical, epidemiologic, and anthropometric data at enrollment and again approximately 60 days later, and provided enrollment stool specimens for identification and characterization of potential diarrheal pathogens. Verbal autopsy was performed if a child died. Analytic strategies will calculate the fraction of MSD attributable to each pathogen and the incidence, financial costs, nutritional consequences, and case fatality overall and by pathogen. Conclusions. When completed, GEMS will provide estimates of the incidence, etiology, and outcomes of MSD among infants and young children in sub-Saharan Africa and South Asia. This information can guide development and implementation of public health interventions to diminish morbidity and mortality from diarrheal diseases.

Contribution of Enteric Infection, Altered Intestinal Barrier Function, and Maternal Malnutrition to Infant Malnutrition in Bangladesh

Abstract: Background. Malnourished children are at increased risk for death due to diarrhea. Our goal was to determine the contribution of specific enteric infections to malnutrition-associated diarrhea and to determine the role of enteric infections in the development of malnutrition. Methods. Children from an urban slum in Bangladesh were followed for the first year of life by every-other-day home visits. Enteropathogens were identified in diarrheal and monthly surveillance stools; intestinal barrier function was measured by serum endocab antibodies; and nutritional status was measured by anthropometry. Results. Diarrhea occurred 4.69 ± 0.19 times per child per year, with the most common infections caused by enteric protozoa (amebiasis, cryptosporidiosis, and giardiasis), rotavirus, astrovirus, and enterotoxigenic Escherichia coli (ETEC). Malnutrition was present in 16.3% of children at birth and 42.4% at 12 months of age. Children malnourished at birth had increased Entamoeba histolytica, Cryptosporidium, and ETEC infections and more severe diarrhea. Children who became malnourished by 12 months of age were more likely to have prolonged diarrhea, intestinal barrier dysfunction, a mother without education, and low family expenditure. Conclusions. Prospective observation of infants in an urban slum demonstrated that diarrheal diseases were associated with the development of malnutrition that was in turn linked to intestinal barrier disruption and that diarrhea was more severe in already malnourished children. The enteric protozoa were unexpectedly important causes of diarrhea in this setting. This study demonstrates the complex interrelationship of malnutrition and diarrhea in infants in low-income settings and points to the potential for infectious disease interventions in the prevention and treatment of malnutrition.

Global burden of maternal and child undernutrition and micronutrient deficiencies.

Abstract: Maternal and child undernutrition and micronutrient deficiencies affect approximately half of the world’s population. These conditions include intrauterine growth restriction (IUGR), low birth weight, protein-energy malnutrition, chronic energy deficit of women, and micronutrient deficiencies. Although the rates of stunting or chronic protein-energy malnutrition are increasing in Africa, the absolute numbers of stunted children are much higher in Asia. The four common micronutrient deficiencies include those of iron, iodine, vitamin A, and zinc. All these conditions are responsible directly or indirectly for more than 50% of all under-5 deaths globally. According to more recent estimates, IUGR, stunting and severe wasting are responsible for one third of under-5 mortality. About 12% of deaths among under-5 children are attributed to the deficiency of the four common micronutrients. Despite tremendous progress in different disciplines and unprecedented improvement with many health indicators, persistently high undernutrition rates are a shame to the society. Human development is not possible without taking care to control undernutrition and micronutrient deficiencies. Poverty, food insecurity, ignorance, lack of appropriate infant and young child feeding practices, heavy burden of infectious illnesses, and poor hygiene and sanitation are factors responsible for the high levels of maternal and child undernutrition in developing countries. These factors can be controlled or removed by scaling up direct nutrition interventions and eliminating the root conditions including female illiteracy, lack of livelihoods, lack of women’s empowerment, and poor hygiene and sanitation.

Seasonality, timing, and climate drivers of influenza activity worldwide

Abstract: Background. Although influenza is a vaccine-preventable disease that annually causes substantial disease burden, data on virus activity in tropical countries are limited. We analyzed publicly available influenza data to better understand the global circulation of influenza viruses. Method. We reviewed open-source, laboratory-confirmed influenza surveillance data. For each country, we abstracted data on the percentage of samples testing positive for influenza each epidemiologic week from the annual number of samples testing positive for influenza. The start of influenza season was defined as the first week when the proportion of samples that tested positive remained above the annual mean. We assessed the relationship between percentage of samples testing positive and mean monthly temperature with use of regression models. Findings. We identified data on laboratory-confirmed influenza virus infection from 85 countries. More than one influenza epidemic period per year was more common in tropical countries (41%) than in temperate coun- tries (15%). Year-round activity (ie, influenza virus identified each week having ≥10 specimens submitted) oc- curred in 3 (7%) of 43 temperate, 1 (17%) of 6 subtropical, and 11 (37%) of 30 tropical countries with available data (P= .006). Percentage positivity was associated with low temperature (P= .001). Interpretation. Annual influenza epidemics occur in consistent temporal patterns depending on climate.

How to do a good systematic review of effects in international development: a tool kit

Abstract: We provide a ‘how to’ guide to undertake systematic reviews of effects in international development, by which we mean, synthesis of literature relating to the effectiveness of particular development interventions. Our remit includes determining the review's questions and scope, literature search, critical appraisal, methods of synthesis including meta-analysis, and assessing the extent to which generalisable conclusions can be drawn using a theory-based approach. Our work draws on the experiences of the International Initiative for Impact Evaluation's (3ie's) systematic reviews programme.

Maternal cadmium exposure during pregnancy and size at birth: a prospective cohort study.

Abstract: Background: Cadmium (Cd) is an embryotoxic and teratogenic metal in a variety of animal species, but data from humans are limited. Objectives: The aim of the present study was to assess the effects of maternal Cd exposure in pregnancy on size at birth. Methods: This prospective cohort study was nested in a population-based nutritional supplementation trial in pregnancy conducted in rural Bangladesh. We selected women recruited from February 2002 through January 2003 who had a singleton birth with measurements of size at birth and had donated a urine sample in early pregnancy for Cd analyses (n = 1,616). Urinary Cd was measured with inductively coupled plasma mass spectrometry and adjusted for specific gravity. Results: Multiple linear regression analyses adjusted for sex and other potential confounders showed that maternal urinary Cd (median, 0.63 μg/L) was significantly negatively associated with birth weight [unstandardized regression coefficient B = –31.0; 95% confidence interval (CI): –59, –2.8] and head circumference (B = –0.15; 95% CI: –0.27, –0.026). However, associations appeared to be limited to girls, with little evidence of effects in boys. A 1-μg/L increase in Cd in maternal urine was associated with a 0.26-cm (95% CI: –0.43, –0.088 cm) and 0.24-cm (95% CI: –0.44, –0.030 cm) decrease in girls’ head and chest circumferences, respectively, and a 45-g (95% CI: –82.5, 7.3 g) decrease in birth weight. Quantile regression analyses indicated that associations with maternal Cd were similar for girls of smaller (25th percentile) and larger (50th and 75th percentiles) sizes at birth. Conclusion: We found evidence of a sex difference in the association between maternal Cd exposure and birth size, which was apparent only in girls. Results add support for the need to reduce Cd pollution to improve public health.

Neonatal outcomes after influenza immunization during pregnancy: a randomized controlled trial

Abstract: Background: There are limited data about the effect of maternal influenza infection on fetuses and newborns. We performed a secondary analysis of data from the Mother’s Gift project, a randomized study designed to test the effectiveness of inactivated influenza and pneumococcal vaccines during pregnancy. Methods: In the Mother’s Gift project, 340 pregnant women in Bangladesh received either inactivated influenza vaccine or 23-valent pneumococcal polysaccharide vaccine (control). This study was performed from August 2004 through December 2005. We performed a secondary analysis of outcomes following maternal influenza immunization during two periods: when influenza virus was not circulating (September 2004 through January 2005) and when influenza virus was circulating (February through October 2005). We assessed gestational age, mean birth weight and the proportion of infants who were small for gestational age. Results: During the period with no circulating influenza virus, there were no differences in the incidence of respiratory illness with fever per 100 person-months among mothers and infants in the two groups (influenza vaccine: 3.9; control: 4.0; p > 0.9). The proportion of infants who were small for gestational age and the mean birth weight were similar between groups (small for gestational age: influenza vaccine 29.1%, control 34.3%; mean birth weight: influenza vaccine 3083 g, control 3053 g). During the period with circulating influenza virus, there was a substantial reduction in the incidence per 100 person-months of respiratory illness with fever among the mothers and infants who had received the influenza vaccine (influenza vaccine: 3.7; control: 7.2; p = 0.0003). During this period, the proportion of infants who were small for gestational age was lower in the influenza vaccine group than in the control group (25.9% v. 44.8%; p = 0.03). The mean birth weight was higher among infants whose mothers received the influenza vaccine than among those who received the control vaccine during this period (3178 g v. 2978 g; p = 0.02). Interpretation: During the period with circulating influenza virus, maternal immunization during pregnancy was associated with a lower proportion of infants who were small for gestational age and an increase in mean birth weight. These data need confirmation but suggest that prevention of influenza infection in pregnancy can influence intrauterine growth. Trial Registration: ClinicalTrials.gov: NCT 00142389

The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study

Abstract: The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.

Genomic diversity of 2010 Haitian cholera outbreak strains

Abstract: The millions of deaths from cholera during the past 200 y, coupled with the morbidity and mortality of cholera in Haiti since October 2010, are grim reminders that Vibrio cholerae, the etiologic agent of cholera, remains a scourge. We report the isolation of both V. cholerae O1 and non-O1/O139 early in the Haiti cholera epidemic from samples collected from victims in 18 towns across eight Arrondissements of Haiti. The results showed two distinct populations of V. cholerae coexisted in Haiti early in the epidemic. As non-O1/O139 V. cholerae was the sole pathogen isolated from 21% of the clinical specimens, its role in this epidemic, either alone or in concert with V. cholerae O1, cannot be dismissed. A genomic approach was used to examine similarities and differences among the Haitian V. cholerae O1 and V. cholerae non-O1/O139 strains. A total of 47 V. cholerae O1 and 29 V. cholerae non-O1/O139 isolates from patients and the environment were sequenced. Comparative genome analyses of the 76 genomes and eight reference strains of V. cholerae isolated in concurrent epidemics outside Haiti and 27 V. cholerae genomes available in the public database demonstrated substantial diversity of V. cholerae and ongoing flux within its genome.

Determinants of inappropriate complementary feeding practices in infant and young children in Bangladesh: secondary data analysis of Demographic Health Survey 2007

Abstract: Suboptimal and inappropriate complementary feeding practices are one of the major causes of child undernutrition in the first 2 years of life in South Asian countries including Bangladesh. The aim of this study was to use the newly developed World Health Organization infant feeding indicators to identify the potential risk factors associated with inappropriate complementary feeding practices. We used data for 1728 children aged 6-23 months obtained from nationally representative data from the 2007 Bangladesh Demographic and Health Survey to assess the association between complementary feeding and other characteristics using multivariate models. Only 71% of infants were consuming soft, semi-solid and solid food by 6-8 months of age. In the multivariate analysis, mothers who had no education had a higher risk for not introducing timely complementary feeds [adjusted odds ratio (AOR)=2.14; 95% confidence interval (CI): 1.08-4.23, P=0.03], not meeting the minimum dietary diversity (AOR=1.69; 95% CI: 1.14-2.54, P=0.01), minimum acceptable diet (AOR=1.70, 95% CI: 1.09-2.67, P=0.02) and minimum meal frequency (AOR=1.73; 95% CI: 1.20-2.49, P=0.003) than the mothers who had secondary or higher education. Infants born in Sylhet, Chittagong and Barisal division had higher risks for not meeting minimum dietary diversity, meal frequency and acceptable diet (P<0.001). The poorest two quintiles had poor levels of minimum meal frequency but dietary quality improved with age. In Bangladesh addressing the fourth Millennium Development Goal (MDG) target will require substantial improvement in complementary feeding practices. Appropriate Infant and Young Child feeding massages should to be development and delivered through existing health system.

Date palm sap linked to nipah virus outbreak in bangladesh, 2008

Abstract: Introduction: We investigated a cluster of patients with encephalitis in the Manikgonj and Rajbari Districts of Bangladesh in February 2008 to determine the etiology and risk factors for disease. Methods: We classified persons as confirmed Nipah cases by the presence of immunoglobulin M antibodies against Nipah virus (NiV), or by the presence of NiV RNA or by isolation of NiV from cerebrospinal fluid or throat swabs who had onset of symptoms between February 6 and March 10, 2008. We classified persons as probable cases if they reported fever with convulsions or altered mental status, who resided in the outbreak areas during that period, and who died before serum samples were collected. For the case–control study, we compared both confirmed and probable Nipah case-patients to controls, who were free from illness during the reference period. We used motion-sensor-infrared cameras to observe bat's contact of date palm sap. Results: We identified four confirmed and six probable case-patients, nine (9...

Nutrition of Children and Women in Bangladesh: Trends and Directions for the Future

Abstract: Although child and maternal malnutrition has been reduced in Bangladesh, the prevalence of underweight (weight-for-age z-score <-2) among children aged less than five years is still high (41%). Nearly one-third of women are undernourished with body mass index of <18.5 kg/m 2 . The prevalence of anaemia among young infants, adolescent girls, and pregnant women is still at unacceptable levels. Despite the successes in specific programmes, such as the Expanded Programme on Immunization and vitamin A supplementation, programmes for nutrition interventions are yet to be implemented at scale for reaching the entire population. Given the low annual rate of reduction in child undernutrition of 1.27 percentage points per year, it is unlikely that Bangladesh would be able to achieve the United Nations’ Millennium Development Goal to address undernutrition. This warrants that the policy-makers and programme managers think urgently about the ways to accelerate the progress. The Government, development partners, non-government organizations, and the academia have to work in concert to improve the coverage of basic and effective nutrition interventions, including exclusive breastfeeding, appropriate complementary feeding, supplementation of micronutrients to children, adolescent girls, pregnant and lactating women, management of severe acute malnutrition and deworming, and hygiene interventions, coupled with those that address more structural causes and indirectly improve nutrition. The entire health system needs to be revitalized to overcome the constraints that exist at the levels of policy, governance, and service-delivery, and also for the creation of demand for the services at the household level. In addition, management of nutrition in the aftermath of natural disasters and stabilization of prices of foods should also be prioritized.

Comparisons of complementary feeding indicators and associated factors in children aged 6–23 months across five South Asian countries

Abstract: Improving infant and young child feeding practices will help South Asian countries achieve the Millennium Development Goal of reducing child mortality. This paper aims to compare key indicators of complementary feeding and their determinants in children aged 6-23 months across five South Asian countries - Bangladesh, India, Nepal, Pakistan and Sri Lanka. The latest Demographic and Health Survey and National Family Health Survey India data were used. The analyses were confined to last-born children aged 6-23 months - 1728 in Bangladesh, 15,028 in India, 1428 in Nepal, 2106 in Sri Lanka and 443 infants aged 6-8 months in Pakistan. Introduction of solid, semi-solid or soft foods, minimum dietary diversity, minimum meal frequency and minimum acceptable diet, and their significant determinants were compared across the countries. Minimum dietary diversity among children aged 6-23 months ranged from 15% in India to 71% in Sri Lanka, with Nepal (34%) and Bangladesh (42%) in between. Minimum acceptable diet among breastfed children was 9% in India, 32% in Nepal, 40% in Bangladesh and 68% in Sri Lanka. The most consistent determinants of inappropriate complementary feeding practices across all countries were the lack of maternal education and lower household wealth. Limited exposure to media, inadequate antenatal care and lack of post-natal contacts by health workers were among predictors of inappropriate feeding. Overall, complementary feeding practices among children aged 6-23 months need improvement in all South Asian countries. More intensive interventions are necessary targeting the groups with sup-optimal practices, while programmes that cover entire populations are being continued.

Cardiovascular diseases and type 2 diabetes in Bangladesh: a systematic review and meta-analysis of studies between 1995 and 2010.

Abstract: Belief is that chronic disease prevalence is rising in Bangladesh since death from them has increased. We reviewed published cardiovascular (CVD) and Type 2 Diabetes Mellitus (T2DM) studies between 1995 and 2010 and conducted a meta-analysis of disease prevalence. A systematic search of CVD and T2DM studies yielded 29 eligible studies (outcome: CVD only = 12, T2DM only = 9, both = 8). Hypertension (HTN) was the primary outcome of CVD studies. HTN and T2DM were defined with objective measures and standard cut-off values. We assessed the study quality based on sampling frame, sample size, and disease evaluation. Random effects models calculated pooled disease prevalence (95% confidence interval) in studies with general population samples (n = 22). The pooled HTN and T2DM prevalence were 13.7% (12.1%–15.3%) and 6.7% (4.9%–8.6%), respectively. Both diseases exhibited a secular trend by 5-year intervals between 1995 and 2010 (HTN = 11.0%, 12.8%, 15.3%, T2DM = 3.8%, 5.3%, 9.0%). HTN was higher in females (M vs. F: 12.8% vs.16.1%) but T2DM was higher in males (M vs. F: 7.0% vs. 6.2%) (non-significant). Both HTN and T2DM were higher in urban areas (urban vs. rural: 22.2% vs. 14.3% and 10.2% vs. 5.1% respectively) (non-significant). HTN was higher among elderly and among working professionals. Both HTN and T2DM were higher in ‘high- quality’ studies. There is evidence of a rising secular trend of HTN and T2DM prevalence in Bangladesh. Future research should focus on the evolving root causes, incidence, and prognosis of HTN and T2DM.

Influence of Prenatal Arsenic Exposure and Newborn Sex on Global Methylation of Cord Blood DNA

Abstract: Background An emerging body of evidence indicates that early-life arsenic (As) exposure may influence the trajectory of health outcomes later in life. However, the mechanisms underlying these observations are unknown.

Genome-Wide Association Study Identifies Chromosome 10q24.32 Variants Associated with Arsenic Metabolism and Toxicity Phenotypes in Bangladesh

Abstract: Arsenic contamination of drinking water is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer. There is inter-individual variation in arsenic metabolism efficiency and susceptibility to arsenic toxicity; however, the basis of this variation is not well understood. Here, we have performed the first genome-wide association study (GWAS) of arsenic-related metabolism and toxicity phenotypes to improve our understanding of the mechanisms by which arsenic affects health. Using data on urinary arsenic metabolite concentrations and approximately 300,000 genome-wide single nucleotide polymorphisms (SNPs) for 1,313 arsenic-exposed Bangladeshi individuals, we identified genome-wide significant association signals (P<5×10−8) for percentages of both monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) near the AS3MT gene (arsenite methyltransferase; 10q24.32), with five genetic variants showing independent associations. In a follow-up analysis of 1,085 individuals with arsenic-induced premalignant skin lesions (the classical sign of arsenic toxicity) and 1,794 controls, we show that one of these five variants (rs9527) is also associated with skin lesion risk (P = 0.0005). Using a subset of individuals with prospectively measured arsenic (n = 769), we show that rs9527 interacts with arsenic to influence incident skin lesion risk (P = 0.01). Expression quantitative trait locus (eQTL) analyses of genome-wide expression data from 950 individual's lymphocyte RNA suggest that several of our lead SNPs represent cis-eQTLs for AS3MT (P = 10−12) and neighboring gene C10orf32 (P = 10−44), which are involved in C10orf32-AS3MT read-through transcription. This is the largest and most comprehensive genomic investigation of arsenic metabolism and toxicity to date, the only GWAS of any arsenic-related trait, and the first study to implicate 10q24.32 variants in both arsenic metabolism and arsenical skin lesion risk. The observed patterns of associations suggest that MMA% and DMA% have distinct genetic determinants and support the hypothesis that DMA is the less toxic of these two methylated arsenic species. These results have potential translational implications for the prevention and treatment of arsenic-associated toxicities worldwide.

Phage-bacterial interactions in the evolution of toxigenic Vibrio cholerae.

Abstract: Understanding the genetic and ecological factors which support the emergence of new clones of pathogenic bacteria is vital to develop preventive measures. Vibrio cholerae the causative agent of cholera epidemics represents a paradigm for this process in that this organism evolved from environmental non-pathogenic strains by acquisition of virulence genes. The major virulence factors of V. cholerae, cholera toxin (CT) and toxin coregulated pilus (TCP) are encoded by a lysogenic bacteriophage (CTXw) and a pathogenicity island, respectively. Additional phages which cooperate with the CTXw in horizontal transfer of genes in V. cholerae have been characterized, and the potential exists for discovering yet new phages or genetic elements which support the transfer of genes for environmental fitness and virulence leading to the emergence of new epidemic strains. Phages have also been shown to play a crucial role in modulating seasonal cholera epidemics. Thus, the complex array of natural phenomena driving the evolution of pathogenic V. cholerae includes among other factors, phages that either participate in horizontal gene transfer or in a bactericidal selection process favoring the emergence of new clones of V. cholerae.

A Global Comparative Evaluation of Commercial Immunochromatographic Rapid Diagnostic Tests for Visceral Leishmaniasis

Abstract: Visceral leishmaniasis (VL) is a parasitic disease transmitted through the bite of an infected phlebotomine sandfly [1]. The clinical syndrome is characterized by fever, weight loss, splenomegaly, and pancytopenia and is nearly always fatal if left untreated. Though visceral leishmaniasis is endemic in >60 countries, 90% of the 200 000–400 000 annual cases occur in just 6 countries: Bangladesh, Brazil, Ethiopia, India, Nepal, and Sudan [2]. Parasitological confirmation remains the reference standard for diagnosis but is not very sensitive unless a spleen puncture is performed. The invasiveness and potentially fatal complications associated with splenic aspiration has motivated the development of noninvasive serological tests such as direct agglutination test (DAT) [3] and lateral flow immunochromatographic tests (ICT), commonly referred to as rapid diagnostic tests (RDTs). To be useful, VL RDTs must have adequate (1) sensitivity to detect a high proportion of clinical cases, (2) specificity to accurately discriminate VL from other relevant disease conditions, (3) thermal stability for accuracy to be maintained after transport and storage in ambient conditions, and (4) ease of use to allow the correct interpretation of results. A meta-analysis [4] and a multicenter evaluation [5] corroborated earlier findings of high diagnostic accuracy of the rK39 ICT and led to its adoption as a diagnostic test in the Indian subcontinent VL Elimination Initiative. The enthusiasm and rapid uptake of RDTs for VL in the Asian region has prompted a surge of commercial tests targeting serum antibodies to rK39 and other antigens (eg, rKE16) [6]. However, in other endemic regions such as East Africa, reports of lower test sensitivity [7–9] have left the role of RDTs less clear. Moreover, there are few, if any, reports of diagnostic accuracy in the peer-reviewed literature for tests other than the Kalazar Detect (Inbios International) and DiaMed-IT LEISH (Bio-Rad Laboratories) and equally few head-to-head comparisons. Essential characteristics as heat stability are rarely assessed. As independent data on how well these assays meet criteria are lacking in countries without regulation by national testing authorities, the UNICEF/World Bank/United Nations Development Programme/World Health Organization (WHO) Special Programme for Research and Training in Tropical Diseases (TDR) coordinated a multiregional head-to-head laboratory-based evaluation of 4 commercially available RDTs in 3 global regions of VL endemicity using well-characterized panels of human sera; a fifth RDT was included in the Indian subcontinent.

Maternal Morbidity and Disability and Their Consequences: Neglected Agenda in Maternal Health

Abstract: Not available DOI: http://dxdoiorg/103329/jhpnv30i211294 J HEALTH POPUL NUTR 2012 Jun;30(2):124-130

Phase variable O antigen biosynthetic genes control expression of the major protective antigen and bacteriophage receptor in Vibrio cholerae O1.

Abstract: The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system and is of critical importance for vaccine design. We used an O1-specific lytic bacteriophage as a tool to probe the capacity of V. cholerae to alter its O1 antigen and identified a novel mechanism by which this organism can modulate O antigen expression and exhibit intra-strain heterogeneity. We identified two phase variable genes required for O1 antigen biosynthesis, manA and wbeL. manA resides outside of the previously recognized O1 antigen biosynthetic locus, and encodes for a phosphomannose isomerase critical for the initial step in O1 antigen biosynthesis. We determined that manA and wbeL phase variants are attenuated for virulence, providing functional evidence to further support the critical role of the O1 antigen for infectivity. We provide the first report of phase variation modulating O1 antigen expression in V. cholerae, and show that the maintenance of these phase variable loci is an important means by which this facultative pathogen can generate the diverse subpopulations of cells needed for infecting the host intestinal tract and for escaping predation by an O1-specific phage.

Association of antenatal care with facility delivery and perinatal survival – a population-based study in Bangladesh

Abstract: Antenatal Care (ANC) during pregnancy can play an important role in the uptake of evidence-based services vital to the health of women and their infants Studies report positive effects of ANC on use of facility-based delivery and perinatal mortality However, most existing studies are limited to cross-sectional surveys with long recall periods, and generally do not include population-based samples This study was conducted within the Health and Demographic Surveillance System (HDSS) of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) in Matlab, Bangladesh The HDSS area is divided into an icddr,b service area (SA) where women and children receive care from icddr,b health facilities, and a government SA where people receive care from government facilities In 2007, a new Maternal, Neonatal, and Child Health (MNCH) program was initiated in the icddr,b SA that strengthened the ongoing maternal and child health services including ANC We estimated the association of ANC with facility delivery and perinatal mortality using prospectively collected data from 2005 to 2009 Using a before-after study design, we also determined the role of ANC services on reduction of perinatal mortality between the periods before (2005 – 2006) and after (2008–2009) implementation of the MNCH program Antenatal care visits were associated with increased facility-based delivery in the icddr,b and government SAs In the icddr,b SA, the adjusted odds of perinatal mortality was about 2-times higher (odds ratio (OR) 191; 95% confidence intervals (CI): 150, 242) among women who received ≤1 ANC compared to women who received ≥3 ANC visits No such association was observed in the government SA Controlling for ANC visits substantially reduced the observed effect of the intervention on perinatal mortality (OR 064; 95% CI: 052, 078) to non-significance (OR 081; 95% CI: 065, 101), when comparing cohorts before and after the MNCH program initiation (Sobel test of mediation P < 0001) ANC visits are associated with increased uptake of facility-based delivery and improved perinatal survival in the icddr,b SA Further testing of the icddr,b approach to simultaneously improving quality of ANC and facility delivery care is needed in the existing health system in Bangladesh and in other low-income countries to maximize health benefits to mothers and newborns

Characterization of Nipah Virus from Outbreaks in Bangladesh, 2008–2010

Abstract: Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. The initial outbreak of NiV infection occurred in Malaysia and Singapore in 1998–1999; relatively small, sporadic outbreaks among humans have occurred in Bangladesh since 2001. We characterized the complete genomic sequences of identical NiV isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from Bangladesh. All sequences from patients in Bangladesh comprised a distinct genetic group. However, the detection of 3 genetically distinct sequences from patients in the districts of Faridpur and Gopalganj indicated multiple co-circulating lineages in a localized region over a short time (January–March 2010). Sequence comparisons between the open reading frames of all available NiV genes led us to propose a standardized protocol for genotyping NiV; this protcol provides a simple and accurate way to classify current and future NiV sequences.

Effects of a community-based approach of food and psychosocial stimulation on growth and development of severely malnourished children in Bangladesh: a randomised trial.

Abstract: Effects of a community-based approach of food and psychosocial stimulation on growth and development of severely malnourished children in Bangladesh: a randomised trial