Showing papers by "International Centre for Diarrhoeal Disease Research, Bangladesh published in 2014"
University of Washington1, Sapienza University of Rome2, Mekelle University3, University of Texas at San Antonio4, King Saud bin Abdulaziz University for Health Sciences5, Debre markos University6, Emory University7, University of Oxford8, University of Cartagena9, United Nations Population Fund10, University of Birmingham11, Stanford University12, Aga Khan University13, University of Melbourne14, National Taiwan University15, University of Cambridge16, University of California, San Diego17, Public Health Foundation of India18, Public Health England19, University of Peradeniya20, Harvard University21, National Institutes of Health22, Tehran University of Medical Sciences23, Auckland University of Technology24, University of Sheffield25, University of Western Australia26, Karolinska Institutet27, Birzeit University28, Brandeis University29, American Cancer Society30, Ochsner Medical Center31, Yonsei University32, University of Bristol33, Heidelberg University34, Vanderbilt University35, South African Medical Research Council36, Jordan University of Science and Technology37, New Generation University College38, Northeastern University39, Simmons College40, Norwegian Institute of Public Health41, Boston University42, Chinese Center for Disease Control and Prevention43, University of Bari44, University of São Paulo45, University of Otago46, University of Crete47, International Centre for Diarrhoeal Disease Research, Bangladesh48, Fred Hutchinson Cancer Research Center49, Teikyo University50, Bhabha Atomic Research Centre51, University of Tokyo52, Finnish Institute of Occupational Health53, Heriot-Watt University54, University of Alabama at Birmingham55, Griffith University56, National Center for Disease Control and Public Health57, University of California, Irvine58, Johns Hopkins University59, New York University60, University of Queensland61, Universidade Federal de Minas Gerais62, National Research University – Higher School of Economics63, University of Bergen64, Columbia University65, Shandong University66, University of North Carolina at Chapel Hill67, Fujita Health University68, Korea University69, Chongqing Medical University70, Zhejiang University71
TL;DR: The global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013 is estimated using a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
9,180 citations
Nicholas J Kassebaum1, Amelia Bertozzi-Villa1, Megan Coggeshall1, Katya Anne Shackelford1 +349 more•Institutions (179)
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.
1,383 citations
Christopher J L Murray1, Katrina F Ortblad1, Caterina Guinovart1, Stephen S Lim1 +367 more•Institutions (179)
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
875 citations
University of Nottingham1, King Saud Medical City2, International Centre for Diarrhoeal Disease Research, Bangladesh3, Government Medical College, Thiruvananthapuram4, Centers for Disease Control and Prevention5, Ljubljana University Medical Centre6, Kantonsspital St. Gallen7, Institut de veille sanitaire8, Children's Hospital at Westmead9, Mexican Social Security Institute10, Medical University of Vienna11, Capital Medical University12, University of Barcelona13, University of Colorado Denver14, State University of West Paraná15, Sheba Medical Center16, University of Manitoba17, Peking University18, National Institutes of Health19, Hospital General Universitario Gregorio Marañón20, Statens Serum Institut21, Imperial College London22, Boston Children's Hospital23, Peking Union Medical College Hospital24, Dhaka Medical College and Hospital25, Universidade Federal de Ciências da Saúde de Porto Alegre26, Gold Coast Hospital27, Tehran University of Medical Sciences28, University of Oxford29, University of Zagreb30, Pamela Youde Nethersole Eastern Hospital31, Stellenbosch University32, Shiraz University of Medical Sciences33, Tan Tock Seng Hospital34, University of Helsinki35, China Medical University (PRC)36, King Hussein Cancer Center37, University of Toronto38, Alfaisal University39, Erciyes University40, Lithuanian University of Health Sciences41, Military Medical Academy42, University of Bergen43, Haukeland University Hospital44, Johns Hopkins University School of Medicine45, Shahid Beheshti University of Medical Sciences and Health Services46, University of Birmingham47, Rambam Health Care Campus48, Vanderbilt University49, Charité50, University of Bristol51, Yüzüncü Yıl University52, Oswaldo Cruz Foundation53, Rzeszów University54, University Hospital of Basel55, Medical University of Warsaw56, University of Alberta Hospital57, University of Alberta58, University of Hong Kong59, National Center for Immunization and Respiratory Diseases60, VU University Medical Center61
TL;DR: There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset, and early treatment versus no treatment was also associated with a reduction in mortality risk.
527 citations
University of Maryland, College Park1, Wellcome Trust Sanger Institute2, University of Maryland, Baltimore3, Medical Research Council4, International Centre for Diarrhoeal Disease Research, Bangladesh5, Centers for Disease Control and Prevention6, University of Florida7, Emory University8, University of Virginia9
TL;DR: Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.
Abstract: Background: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease. Results: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age. Conclusions: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.
314 citations
TL;DR: Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses.
Abstract: OBJECTIVE: Oral vaccine efficacy is low in less-developed countries, perhaps due to intestinal dysbiosis. This study determined if stool microbiota composition predicted infant oral and parenteral vaccine responses.
METHODS: The stool microbiota of 48 Bangladeshi infants was characterized at 6, 11, and 15 weeks of age by amplification and sequencing of the 16S ribosomal RNA gene V4 region and by Bifidobacterium -specific, quantitative polymerase chain reaction. Responses to oral polio virus (OPV), bacille Calmette-Guerin (BCG), tetanus toxoid (TT), and hepatitis B virus vaccines were measured at 15 weeks by using vaccine-specific T-cell proliferation for all vaccines, the delayed-type hypersensitivity skin-test response for BCG, and immunoglobulin G responses using the antibody in lymphocyte supernatant method for OPV, TT, and hepatitis B virus. Thymic index (TI) was measured by ultrasound.
RESULTS: Actinobacteria (predominantly Bifidobacterium longum subspecies infantis ) dominated the stool microbiota, with Proteobacteria and Bacteroidetes increasing by 15 weeks. Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales , Pseudomonadales , and Clostridiales were associated with neutrophilia and lower vaccine responses.
CONCLUSIONS: Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses. Vaccine responsiveness may be improved by promoting intestinal bifidobacteria and minimizing dysbiosis early in infancy.
303 citations
TL;DR: A quadrivalent vaccine that includes O antigens from S. sonnei, S. flexneri, and S.flexneri 6 should provide broad protection in Shigella case isolates.
Abstract: Background Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged Methods Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Results Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. Conclusions A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens.
268 citations
TL;DR: Molecular diagnostic tests can detect pathogens with high sensitivity and ascribe diarrhoeal associations based on quantification, including in mixed infections, providing rich and unprecedented measurements of infectious causes.
Abstract: Summary Background Childhood diarrhoea can be caused by many pathogens that are difficult to assay in the laboratory. Molecular diagnostic techniques provide a uniform method to detect and quantify candidate enteropathogens. We aimed to develop and assess molecular tests for identification of enteropathogens and their association with disease. Methods We developed and assessed molecular diagnostic tests for 15 enteropathogens across three platforms—PCR-Luminex, multiplex real-time PCR, and TaqMan array card—at five laboratories worldwide. We judged the analytical and clinical performance of these molecular techniques against comparator methods (bacterial culture, ELISA, and PCR) using 867 diarrhoeal and 619 non-diarrhoeal stool specimens. We also measured molecular quantities of pathogens to predict the association with diarrhoea, by univariate logistic regression analysis. Findings The molecular tests showed very good analytical and clinical performance at all five laboratories. Comparator methods had limited sensitivity compared with the molecular techniques (20–85% depending on the target) but good specificity (median 97·3%, IQR 96·5–98·9; mean 95·2%, SD 9·1). Positive samples by comparator methods usually had higher molecular quantities of pathogens than did negative samples, across almost all platforms and for most pathogens (p Campylobacter jejuni and Campylobacter coli, Cryptosporidium spp, enteropathogenic Escherichia coli , heat-stable enterotoxigenic E coli , rotavirus, Shigella spp and enteroinvasive E coli , and Vibrio cholerae —the strength of association with diarrhoea increased at higher pathogen loads. For example, Shigella spp at a Cq range of 15–20 had an odds ratio of 8·0 (p Interpretation Molecular diagnostic tests can be implemented successfully and with fidelity across laboratories around the world. In the case of diarrhoea, these techniques can detect pathogens with high sensitivity and ascribe diarrhoeal associations based on quantification, including in mixed infections, providing rich and unprecedented measurements of infectious causes. Funding Bill & Melinda Gates Foundation Next Generation Molecular Diagnostics Project.
252 citations
TL;DR: The review confirmed the major conclusion of earlier reviews based on the pre-2000 literature - that households in LMICs bear a high but variable burden of OOP health expenditure and policymakers need to include non-health system interventions in addition to support formal insurance programs to ameliorate the economic impacts of health shocks.
Abstract: Poor health is a source of impoverishment among households in low -and middle- income countries (LMICs) and a subject of voluminous literature in recent years. This paper reviews recent empirical literature on measuring the economic impacts of health shocks on households. Key inclusion criteria were studies that explored household level economic outcomes (burden of out-of-pocket (OOP) health spending, labour supply responses and non-medical consumption) of health shocks and sought to correct for the likely endogeneity of health shocks, in addition to studies that measured catastrophic and impoverishment effects of ill health. The review only considered literature in the English language and excluded studies published before 2000 since these have been included in previous reviews. We identified 105 relevant articles, reports, and books. Our review confirmed the major conclusion of earlier reviews based on the pre-2000 literature - that households in LMICs bear a high but variable burden of OOP health expenditure. Households use a range of sources such as income, savings, borrowing, using loans or mortgages, and selling assets and livestock to meet OOP health spending. Health shocks also cause significant reductions in labour supply among households in LMICs, and households (particularly low-income ones) are unable to fully smooth income losses from moderate and severe health shocks. Available evidence rejects the hypothesis of full consumption insurance in the face of major health shocks. Our review suggests additional research on measuring and harmonizing indicators of health shocks and economic outcomes, measuring economic implications of non-communicable diseases for households and analyses based on longitudinal data. Policymakers need to include non-health system interventions, including access to credit and disability insurance in addition to support formal insurance programs to ameliorate the economic impacts of health shocks.
169 citations
Centers for Disease Control and Prevention1, National Institute of Virology2, International Centre for Diarrhoeal Disease Research, Bangladesh3, Thailand Ministry of Public Health4, Ministry of Health (Cambodia)5, Pasteur Institute6, World Health Organization7, Singapore Ministry of Health8, Ministry of Health (Malaysia)9, Research Institute for Tropical Medicine10
TL;DR: Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equators without a distinct peak in influenza activity can base vaccination timing on local factors.
Abstract: Objective To characterize influenza seasonality and identify the best time of the year for vaccination against influenza in tropical and subtropical countries of southern and south-eastern Asia that lie north of the equator. Methods Weekly influenza surveillance data for 2006 to 2011 were obtained from Bangladesh, Cambodia, India, Indonesia, the Lao People's Democratic Republic, Malaysia, the Philippines, Singapore, Thailand and Viet Nam. Weekly rates of influenza activity were based on the percentage of all nasopharyngeal samples collected during the year that tested positive for influenza virus or viral nucleic acid on any given week. Monthly positivity rates were then calculated to define annual peaks of influenza activity in each country and across countries. Findings Influenza activity peaked between June/July and October in seven countries, three of which showed a second peak in December to February. Countries closer to the equator had year-round circulation without discrete peaks. Viral types and subtypes varied from year to year but not across countries in a given year. The cumulative proportion of specimens that tested positive from June to November was > 60% in Bangladesh, Cambodia, India, the Lao People's Democratic Republic, the Philippines, Thailand and Viet Nam. Thus, these tropical and subtropical countries exhibited earlier influenza activity peaks than temperate climate countries north of the equator. Conclusion Most southern and south-eastern Asian countries lying north of the equator should consider vaccinating against influenza from April to June; countries near the equator without a distinct peak in influenza activity can base vaccination timing on local factors.
154 citations
TL;DR: The decrease in MMR in Bangladesh seems to have been the result of factors both within and outside the health sector, and holds important lessons for other countries as the world discusses and decides on the post-MDG goals and strategies.
TL;DR: The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation, as well as the many different approaches to programmatic MTB/RIF implementation.
Abstract: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.
TL;DR: The burden of mental disorders is high in Bangladesh, yet a largely unrecognized and under-researched area, and further well-designed epidemiological and clinical research are needed to improve the mental health services in Bangladesh.
Abstract: Mental disorders constitute a major public health problem globally with higher burden in low and middle-income countries. In Bangladesh, systematically-collected data on mental disorders are scarce and this leaves the extent of the problem not so well defined. We reviewed the literature on mental health disorders in Bangladesh to summarize the available data and identify evidence gaps. We identified relevant literature on mental disorders within Bangladesh published between 1975 and October, 2013 through a systematic and comprehensive search. Relevant information from the selected articles was extracted and presented in tables. We identified 32 articles which met our pre-defined eligibility criteria. The reported prevalence of mental disorders varied from 6.5 to 31.0% among adults and from 13.4 to 22.9% among children. Some awareness regarding mental health disorders exists at community level. There is a negative attitude towards treatment of those affected and treatment is not a priority in health care delivery. Mental health services are concentrated around tertiary care hospitals in big cities and absent in primary care. The burden of mental disorders is high in Bangladesh, yet a largely unrecognized and under-researched area. To improve the mental health services in Bangladesh, further well-designed epidemiological and clinical research are needed.
TL;DR: Early prenatal arsenic exposure appears to decrease DNA methylation in boys, with more pronounced effects in boys than in girls, whereas much weaker associations were observed with arsenic exposure in late compared with early gestation.
Abstract: Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value -0.62), but in girls only 207 (41%) showed inverse correlation (r S -values>-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.
TL;DR: E effects of poverty on children’s cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in thefirst 5 years of life.
Abstract: OBJECTIVE: We aimed to determine the timing and size of the cognitive deficit associated with poverty in the first 5 years of life and to examine the role of parental characteristics, pre- and postnatal growth, and stimulation in the home in Bangladeshi children. We hypothesized that the effect of poverty on cognition begins in infancy and is mainly mediated by these factors. METHODS: We enrolled 2853 singletons, a subsample from a pregnancy supplementation trial in a poor rural area. We assessed mental development at 7, 18, and 64 months; anthropometry at birth, 12, 24, and 64 months; home stimulation at 18 and 64 months; and family’s socioeconomic background. In multiple regression analyses, we examined the effect of poverty at birth on IQ at 64 months and the extent that other factors mediated the effect. RESULTS: A mean cognitive deficit of 0.2 (95% confidence interval –0.4 to –0.02) z scores between the first and fifth wealth quintiles was apparent at 7 months and increased to 1.2 (95% confidence interval –1.3 to –1.0) z scores of IQ by 64 months. Parental education, pre- and postnatal growth in length, and home stimulation mediated 86% of the effects of poverty on IQ and had independent effects. Growth in the first 2 years had larger effects than later growth. Home stimulation had effects throughout the period. CONCLUSIONS: Effects of poverty on children’s cognition are mostly mediated through parental education, birth size, growth in the first 24 months, and home stimulation in the first 5 years.
TL;DR: Elevated childhood arsenic exposure appeared to reduce cell-mediated immunity, possibly linked to reduced concentrations of Th1 cytokines, in children with recent infections.
TL;DR: The prevalence of EBF in Mirzapur (36%) is lower than the national figure (64%).
Abstract: Exclusive breastfeeding (EBF) means that the infant receives only breast milk for the first six months of life after birth. In Bangladesh, the prevalence of EBF remained largely unchanged for nearly two decades and was 43% in 2007. However, in 2011, a prevalence of 64% was reported, an increase by 21 percentage points. The reasons for this large change remain speculative at this point. Thus to investigate the issue further, this study was conducted. The objective was to assess the prevalence of EBF and associated factors among mothers having children aged 0–6 months in rural Bangladesh. A cross-sectional study was conducted in Mirzapur Upazilla (sub district) among 121 mothers of infants aged 0–6 months. Eligible mothers were identified and randomly selected using the demographic surveillance system’s computerized database that is updated weekly. A semi-structured questionnaire was used for interviews that inquired information on socio-demographic characteristics, obstetric, health service, breastfeeding related factors (initiation of breastfeeding, prelacteal feeding and colostrum feeding) and economic factors. EBF prevalence was calculated using 24 hour recall method. In multivariate analysis, a logistic regression model was developed using stepwise modeling to analyze the factors associated with EBF. The prevalence of EBF in the last 24 hours preceding the survey was 36%. Bivariate and multivariate analysis revealed no significant association between EBF and its possible predictors at 0.05 level of alpha. However, there was some evidence of an association between EBF and having a caesarean delivery (OR = 0.47, 95% CI: 0.21, 1.06). In multivariate analysis, type of delivery: caesarean (AOR = 0.45, 95% CI: 0.19, 1.03) and wealth quintile: richer (AOR = 2.40, 95% CI: 0.94, 6.16) also showed some evidence of an association with EBF. The prevalence of EBF in Mirzapur (36%) is lower than the national figure (64%). Prelacteal feeding was not uncommon. These findings suggest that there is a need for breastfeeding support provided by health services. Hence, promotion of EBF during the first six months of life needs to be addressed and future breastfeeding promotion programmes should give special attention to those women who are not practicing EBF.
TL;DR: The rationale for the microbiologic assays chosen and methodologies used to accomplish the MAL-ED goals are described, including harmonized protocols to test for a diverse range of enteropathogens and maximum laboratory throughput and minimum cost.
Abstract: A central hypothesis of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study is that enteropathogens contribute to growth faltering. To examine this question, the MAL-ED network of investigators set out to achieve 3 goals: (1) develop harmonized protocols to test for a diverse range of enteropathogens, (2) provide quality-assured and comparable results from 8 global sites, and (3) achieve maximum laboratory throughput and minimum cost. This paper describes the rationale for the microbiologic assays chosen and methodologies used to accomplish the 3 goals.
TL;DR: There is no single best-performing coding method for verbal autopsies across various studies and metrics and there is little current justification for CCVA to replace PCVA, particularly as physician diagnosis remains the worldwide standard for clinical diagnosis on live patients.
Abstract: Computer-coded verbal autopsy (CCVA) methods to assign causes of death (CODs) for medically unattended deaths have been proposed as an alternative to physician-certified verbal autopsy (PCVA). We conducted a systematic review of 19 published comparison studies (from 684 evaluated), most of which used hospital-based deaths as the reference standard. We assessed the performance of PCVA and five CCVA methods: Random Forest, Tariff, InterVA, King-Lu, and Simplified Symptom Pattern. The reviewed studies assessed methods’ performance through various metrics: sensitivity, specificity, and chance-corrected concordance for coding individual deaths, and cause-specific mortality fraction (CSMF) error and CSMF accuracy at the population level. These results were summarized into means, medians, and ranges. The 19 studies ranged from 200 to 50,000 deaths per study (total over 116,000 deaths). Sensitivity of PCVA versus hospital-assigned COD varied widely by cause, but showed consistently high specificity. PCVA and CCVA methods had an overall chance-corrected concordance of about 50% or lower, across all ages and CODs. At the population level, the relative CSMF error between PCVA and hospital-based deaths indicated good performance for most CODs. Random Forest had the best CSMF accuracy performance, followed closely by PCVA and the other CCVA methods, but with lower values for InterVA-3. There is no single best-performing coding method for verbal autopsies across various studies and metrics. There is little current justification for CCVA to replace PCVA, particularly as physician diagnosis remains the worldwide standard for clinical diagnosis on live patients. Further assessments and large accessible datasets on which to train and test combinations of methods are required, particularly for rural deaths without medical attention.
TL;DR: In the acute phase of cholera, MAIT cells are activated, depleted from the periphery, and as part of the innate response against V. cholerae infection, are possibly involved in mechanisms underlying class switching of antibody responses to T cell-independent antigens.
Abstract: Background: Mucosal Associated Invariant T (MAIT) cells are innate-like T cells found in abundance in the intestinal mucosa, and are thought to play a role in bridging the innate-adaptive interface. Methods: We measured MAIT cell frequencies and antibody responses in blood from patients presenting with cultureconfirmed severe cholera to a hospital in Dhaka, Bangladesh at days 2, 7, 30, and 90 of illness. Results: We found that MAIT (CD3 + CD4 2 CD161 hi Va7.2 + ) cells were maximally activated at day 7 after onset of cholera. In adult patients, MAIT frequencies did not change over time, whereas in child patients, MAITs were significantly decreased at day 7, and this decrease persisted to day 90. Fold changes in MAIT frequency correlated with increases in LPS IgA and IgG, but not LPS IgM nor antibody responses to cholera toxin B subunit. Conclusions: In the acute phase of cholera, MAIT cells are activated, depleted from the periphery, and as part of the innate response against V. cholerae infection, are possibly involved in mechanisms underlying class switching of antibody responses to T cell-independent antigens.
TL;DR: In infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity, and the use of PCR is proposed because it retains high sensitivity, can ascertain burden, and can distinguish between Campyloblacter infections at the species level.
Abstract: Campylobacter is a common bacterial enteropathogen that can be detected in stool by culture, enzyme immunoassay (EIA), or PCR. We compared culture for C. jejuni/C. coli, EIA (ProSpecT), and duplex PCR to distinguish Campylobacter jejuni/C. coli and non-jejuni/coli Campylobacter on 432 diarrheal and matched control stool samples from infants in a multisite longitudinal study of enteric infections in Tanzania, Bangladesh, and Peru. The sensitivity and specificity of culture were 8.5% and 97.6%, respectively, compared with the results of EIA and 8.7% and 98.0%, respectively, compared with the results of PCR for C. jejuni/C. coli. Most (71.6%) EIA-positive samples were positive by PCR for C. jejuni/C. coli, but 27.6% were positive for non-jejuni/coli Campylobacter species. Sequencing of 16S rRNA from 53 of these non-jejuni/coli Campylobacter samples showed that it most closely matched the 16S rRNA of C. hyointestinalis subsp. lawsonii (56%), C. troglodytis (33%), C. upsaliensis (7.7%), and C. jejuni/C. coli (2.6%). Campylobacter-negative stool spiked with each of the above-mentioned Campylobacter species revealed reactivity with EIA. PCR detection of Campylobacter species was strongly associated with diarrhea in Peru (odds ratio [OR] = 3.66, P < 0.001) but not in Tanzania (OR = 1.56, P = 0.24) or Bangladesh (OR = 1.13, P = 0.75). According to PCR, Campylobacter jejuni/C. coli infections represented less than half of all infections with Campylobacter species. In sum, in infants in developing country settings, the ProSpecT EIA and PCR for Campylobacter reveal extremely high rates of positivity. We propose the use of PCR because it retains high sensitivity, can ascertain burden, and can distinguish between Campylobacter infections at the species level.
TL;DR: TheMAL-ED study site in Bangladesh is representative of a typical urban slum of Dhaka city in terms of demographics, socioeconomic status, and general health indicators.
Abstract: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study site in Bangladesh is located in the capital city of Dhaka in an urban slum that has one of the highest population densities in the world. The site is in the Bauniabadh area of Mirpur, Dhaka. A typical squatter settlement, the average family size of households in Mirpur Bauniabadh is 4.5, with 48% females. About 20% of households have a monthly income of only US$62. About 30% of mothers never attended school, and only 3% obtained secondary school education. The majority of the people are day laborers, garment workers, and transport workers. About 72% of caregivers always wash their hands after helping the child defecate and 6.6% never wash their hands. The diarrheal attack rate for Mirpur is 4.69 episodes per child per year. The study site is representative of a typical urban slum of Dhaka city in terms of demographics, socioeconomic status, and general health indicators.
TL;DR: In resource poor settings with high burden of preterm birth, alike Bangladesh, pre term birth risk could be reduced by close monitoring and/or frequent follow-up of women with history of child death and antenatal complications, by encouraging women to seek antenatal care from qualified providers, to adopt birth preparedness planning and to maintain good nutritional status.
Abstract: Globally, about 15 million neonates are born preterm and about 85% of global preterm birth occurs in Asia and Africa regions. We aimed to estimate the incidence and risk factors for preterm birth in a rural Bangladeshi cohort. Between June 2007 and September 2009, community health workers prospectively collected data from 32,126 mother-live-born baby pairs on household socio-demographic status, pregnancy history, antenatal care seeking and newborn gestational age determined by recall of date of last menstrual period. Among all live births, 22.3% were delivered prior to 37 weeks of gestation (i.e. preterm); of which 12.3% were born at 35–36 weeks of gestation (late preterm), 7.1% were born at 32–34 weeks (moderate preterm), and 2.9% were born at 28–31 weeks of gestation (very preterm). Overall, the majority of preterm births (55.1%) were late preterm. Risk of preterm birth was lower among women with primary or higher level of education (RR: 0.92; 95% CI: 0.88, 0.97), women who sought antenatal care at least once during the index pregnancy (RR: 0.86; 95% CI: 0.83, 0.90), and women who had completed all birth preparedness steps (RR: 0.32; 95% CI: 0.30, 0.34). In contrast, risk of preterm birth was higher among women with a history of child death (RR: 1.05; 95% CI: 1.01, 1.10), who had mid-upper arm circumference (MUAC) ≤250 mm, indicative of under nutrition (for women having MUAC <214 mm the risk was higher; RR: 1.26; 95% CI: 1.17, 1.35), who reported an antenatal complication (RR: 1.32; 95% CI: 1.14, 1.53), and who received iron-folic acid supplementation for 2–6 months during the index pregnancy (RR: 1.33; 95% CI: 1.24, 1.44). In resource poor settings with high burden of preterm birth, alike Bangladesh, preterm birth risk could be reduced by close monitoring and/or frequent follow-up of women with history of child death and antenatal complications, by encouraging women to seek antenatal care from qualified providers, to adopt birth preparedness planning and to maintain good nutritional status. Additional research is needed to further explore the associations of antenatal iron supplementation and maternal nutritional status on preterm birth.
TL;DR: The results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types.
Abstract: Purpose: We utilized whole-genome mapping of promoters that are activated by DNA hypomethylation in hepatocellular carcinoma (HCC) clinical samples to shortlist novel targets for anticancer therapeutics. We provide a proof of principle of this approach by testing six genes short-listed in our screen for their essential role in cancer growth and invasiveness. Experimental Design: We used siRNA- or shRNA-mediated depletion to determine whether inhibition of these genes would reduce human tumor xenograft growth in mice as well as cell viability, anchorage-independent growth, invasive capacities, and state of activity of nodal signaling pathways in liver, breast, and bladder cancer cell lines. Results: Depletion of EXOSC4 , RNMT , SENP6 , WBSCR22 , RASAL2 , and NENF effectively and specifically inhibits cancer cell growth and cell invasive capacities in different types of cancer, but, remarkably, there is no effect on normal cell growth, suggesting a ubiquitous causal role for these genes in driving cancer growth and metastasis. Depletion of RASAL2 and NENF in vitro reduces their growth as explants in vivo in mice. RASAL2 and NENF depletion interferes with AKT, WNT, and MAPK signaling pathways as well as regulation of epigenetic proteins that were previously demonstrated to drive cancer growth and metastasis. Conclusion: Our results prove that genes that are hypomethylated and induced in tumors are candidate targets for anticancer therapeutics in multiple cancer cell types. Because these genes are particularly activated in cancer, they constitute a group of targets for specific pharmacologic inhibitors of cancer and cancer metastasis. Clin Cancer Res; 20(12); 3118–32. ©2014 AACR .
TL;DR: Investigation of ever-married women's exposure to IPV and their children's nutritional status in Bangladesh contributes to growing body of evidence showing that IPV can also compromise children's growth, supporting the need to incorporate efforts to address IPV in child health and nutrition programmes and policies.
Abstract: Domestic violence, in particular intimate partner violence (IPV), has been recognized as a leading cause of mortality and morbidity among women of reproductive age. The effects of IPV against women on their children's health, especially their nutritional status has received less attention but needs to be evaluated to understand the comprehensive public health implications of IPV. The aim of current study was to investigate the association between women's exposure to IPV and their children's nutritional status, using data from the 2007 Bangladesh Demographic and Health Survey (BDHS). Logistic regression models were used to estimate association between ever-married women's lifetime exposure to physical and sexual violence by their spouses and nutritional status of their children under 5 years. Of 2042 women in the BDHS survey with at least one child under 5 years of age, 49.4% reported lifetime experience of physical partner violence while 18.4% reported experience of sexual partner violence. The prevalence of stunting, wasting and underweight in their children under 5 years was 44.3%, 18.4% and 42.0%, respectively. Women were more likely to have a stunted child if they had lifetime experience of physical IPV [odds ratio n = 2027 (OR)adj, 1.48; 95% confidence interval (CI), 1.23-1.79] or had been exposed to sexual IPV (n = 2027 OR(adj), 1.28; 95% CI, 1.02-1.61). The present findings contribute to growing body of evidence showing that IPV can also compromise children's growth, supporting the need to incorporate efforts to address IPV in child health and nutrition programmes and policies.
International Centre for Diarrhoeal Disease Research, Bangladesh1, University of Ouagadougou2, College of Health Sciences, Bahrain3, All India Institute of Medical Sciences4, Gadjah Mada University5, Imperial College London6, Kenya Medical Research Institute7, University of London8, Institut de recherche pour le développement9, Umeå Centre for Global Health Research10, University of KwaZulu-Natal11, Hanoi Medical University12, University of the Witwatersrand13, Swiss Tropical and Public Health Institute14
TL;DR: This dataset documents individual deaths across Africa and Asia in a standardised way, and on an unprecedented scale, and supports the need for continued work towards much wider implementation of universal civil registration of deaths by cause on a worldwide basis.
Abstract: Background : Because most deaths in Africa and Asia are not well documented, estimates of mortality are often made using scanty data. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering all deaths over time and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. Objective : To build a large standardised mortality database from African and Asian sites, detailing the relevant methods, and use it to describe cause-specific mortality patterns. Design : Individual demographic and verbal autopsy (VA) data from 22 INDEPTH sites were collated into a standardised database. The INDEPTH 2013 population was used for standardisation. The WHO 2012 VA standard and the InterVA-4 model were used for assigning cause of death. Results : A total of 111,910 deaths occurring over 12,204,043 person-years (accumulated between 1992 and 2012) were registered across the 22 sites, and for 98,429 of these deaths (88.0%) verbal autopsies were successfully completed. There was considerable variation in all-cause mortality between sites, with most of the differences being accounted for by variations in infectious causes as a proportion of all deaths. Conclusions : This dataset documents individual deaths across Africa and Asia in a standardised way, and on an unprecedented scale. While INDEPTH sites are not constructed to constitute a representative sample, and VA may not be the ideal method of determining cause of death, nevertheless these findings represent detailed mortality patterns for parts of the world that are severely under-served in terms of measuring mortality. Further papers explore details of mortality patterns among children and specifically for NCDs, external causes, pregnancy-related mortality, malaria, and HIV/AIDS. Comparisons will also be made where possible with other findings on mortality in the same regions. Findings presented here and in accompanying papers support the need for continued work towards much wider implementation of universal civil registration of deaths by cause on a worldwide basis. Keywords : mortality; cause of death; Africa; Asia; verbal autopsy; INDEPTH Network (Published: 29 October 2014) Citation : Glob Health Action 2014, 7 : 25362 - http://dx.doi.org/10.3402/gha.v7.25362 SPECIAL ISSUE : This paper is part of the Special Issue: INDEPTH Network Cause-Specific Mortality . More papers from this issue can be found at http://www.globalhealthaction.net
Johns Hopkins University1, Christian Medical College & Hospital2, University of Bergen3, Tribhuvan University4, RMIT University5, State University of Ceará6, Aga Khan University7, University of Illinois at Chicago8, International Centre for Diarrhoeal Disease Research, Bangladesh9, National Institutes of Health10
TL;DR: The focus of the current article is on the collection of data to describe the nature and adequacy of infant feeding, energy and nutrient intakes, and the chosen indicators to capture micronutrient status in children over time.
Abstract: The overall goal of The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study is to evaluate the roles of repeated enteric infection and poor dietary intakes on the development of malnutrition, poor cognitive development, and diminished immune response. The use of 8 distinct sites for data collection from Latin America, sub-Saharan Africa, and South Asia allow for an examination of these relationships across different environmental contexts. Key to testing study hypotheses is the collection of appropriate data to characterize the dietary intakes and nutritional status of study children from birth through 24 months of age. The focus of the current article is on the collection of data to describe the nature and adequacy of infant feeding, energy and nutrient intakes, and the chosen indicators to capture micronutrient status in children over time.
TL;DR: Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia, and the underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.
Abstract: Background: Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death.Methods: Young children (< 5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr, b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died.Results: Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9-35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66-7.97) and age,12 months (OR 2.54, 95% CI 1.1-8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p, 0.001) compared to those who survived.Conclusion and Significance: Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.
TL;DR: The first randomized controlled phase I trial of an anti-inflammatory drug for EE was found to be safe in short-term treatment of a small number of severely malnourished children, although efficacy was not established.
Abstract: Environmental enteropathy (EE) is a poorly defined state of intestinal inflammation without overt diarrhea that occurs in individuals exposed over time to poor sanitation and hygiene. It is implicated as a cause of stunting and malnutrition, oral vaccine failure and impaired development in children from low-income countries. The burden on child health of malnutrition alone, which affects 25% of all children and is estimated to result in more than a million deaths annually due to heightened susceptibility to infection, makes urgent a solution to EE. Efforts are thus underway to treat EE even while work continues to identify it through the use of non-invasive biomarkers, and delineate its pathogenesis. A recent study published in BMC Medicine reports the first randomized controlled phase I trial of an anti-inflammatory drug for EE. The aminosalicylate mesalazine was found to be safe in short-term treatment of a small number of severely malnourished children, although efficacy was not established. Whether such treatment trials are premature, or instead a way both to understand and intervene in EE, is the focus of this article. Please see related article: http://www.biomedcentral.com/1741-7015/12/133.
TL;DR: It is suggested that, in addition to human population density, composition and structure of the landscape shared by P. giganteus and humans may influence the geographic distribution of Nipah virus spillovers.
Abstract: Nipah virus has caused recurring outbreaks in central and northwest Bangladesh (the “Nipah Belt”). Little is known about roosting behavior of the fruit bat reservoir, Pteropus giganteus, or factors driving spillover. We compared human population density and ecological characteristics of case villages and control villages (no reported outbreaks) to understand their role in P. giganteus roosting ecology and Nipah virus spillover risk. Nipah Belt villages have a higher human population density (P < 0.0001), and forests that are more fragmented than elsewhere in Bangladesh (0.50 versus 0.32 patches/km2, P < 0.0001). The number of roosts in a village correlates with forest fragmentation (r = 0.22, P = 0.03). Villages with a roost containing Polyalthia longifolia or Bombax ceiba trees were more likely case villages (odds ratio [OR] = 10.8, 95% confidence interval [CI] = 1.3–90.6). This study suggests that, in addition to human population density, composition and structure of the landscape shared by P. giganteus and humans may influence the geographic distribution of Nipah virus spillovers.