Showing papers by "International Centre for Diarrhoeal Disease Research, Bangladesh published in 2017"

A Review on Antibiotic Resistance: Alarm Bells are Ringing

Abstract: Antibiotics are the 'wonder drugs' to combat microbes. For decades, multiple varieties of antibiotics have not only been used for therapeutic purposes but practiced prophylactically across other industries such as agriculture and animal husbandry. Uncertainty has arisen, as microbes have become resistant to common antibiotics while the host remains unaware that antibiotic resistance has emerged. The aim of this review is to explore the origin, development, and the current state of antibiotic resistance, regulation, and challenges by examining available literature. We found that antibiotic resistance is increasing at an alarming rate. A growing list of infections i.e., pneumonia, tuberculosis, and gonorrhea are becoming harder and at times impossible to treat while antibiotics are becoming less effective. Antibiotic-resistant infections correlate with the level of antibiotic consumption. Non-judicial use of antibiotics is mostly responsible for making the microbes resistant. The antibiotic treatment repertoire for existing or emerging hard-to-treat multidrug-resistant bacterial infections is limited, resulting in high morbidity and mortality report. This review article reiterates the optimal use of antimicrobial medicines in human and animal health to reduce antibiotic resistance. Evidence from the literature suggests that the knowledge regarding antibiotic resistance in the population is still scarce. Therefore, the need of educating patients and the public is essential to fight against the antimicrobial resistance battle.

Exome-wide association study of plasma lipids in > 300,000 individuals

Abstract: We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

Potential predatory and legitimate biomedical journals: can you tell the difference? A cross-sectional comparison.

Abstract: The Internet has transformed scholarly publishing, most notably, by the introduction of open access publishing. Recently, there has been a rise of online journals characterized as ‘predatory’, which actively solicit manuscripts and charge publications fees without providing robust peer review and editorial services. We carried out a cross-sectional comparison of characteristics of potential predatory, legitimate open access, and legitimate subscription-based biomedical journals. On July 10, 2014, scholarly journals from each of the following groups were identified – potential predatory journals (source: Beall’s List), presumed legitimate, fully open access journals (source: PubMed Central), and presumed legitimate subscription-based (including hybrid) journals (source: Abridged Index Medicus). MEDLINE journal inclusion criteria were used to screen and identify biomedical journals from within the potential predatory journals group. One hundred journals from each group were randomly selected. Journal characteristics (e.g., website integrity, look and feel, editors and staff, editorial/peer review process, instructions to authors, publication model, copyright and licensing, journal location, and contact) were collected by one assessor and verified by a second. Summary statistics were calculated. Ninety-three predatory journals, 99 open access, and 100 subscription-based journals were analyzed; exclusions were due to website unavailability. Many more predatory journals’ homepages contained spelling errors (61/93, 66%) and distorted or potentially unauthorized images (59/93, 63%) compared to open access journals (6/99, 6% and 5/99, 5%, respectively) and subscription-based journals (3/100, 3% and 1/100, 1%, respectively). Thirty-one (33%) predatory journals promoted a bogus impact metric – the Index Copernicus Value – versus three (3%) open access journals and no subscription-based journals. Nearly three quarters (n = 66, 73%) of predatory journals had editors or editorial board members whose affiliation with the journal was unverified versus two (2%) open access journals and one (1%) subscription-based journal in which this was the case. Predatory journals charge a considerably smaller publication fee (median $100 USD, IQR $63–$150) than open access journals ($1865 USD, IQR $800–$2205) and subscription-based hybrid journals ($3000 USD, IQR $2500–$3000). We identified 13 evidence-based characteristics by which predatory journals may potentially be distinguished from presumed legitimate journals. These may be useful for authors who are assessing journals for possible submission or for others, such as universities evaluating candidates’ publications as part of the hiring process.

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

Abstract: Danish Saleheen, Benjamin Voight and colleagues perform genome-wide analysis of multi-ancestry cohorts to identify genetic associations with type 2 diabetes (T2D) and coronary heart disease (CHD). They find novel loci and show that 24% of T2D loci are also associated with CHD and that greater genetic risk of T2D increases risk of CHD. To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.

Impact of clinical registries on quality of patient care and clinical outcomes: A systematic review.

Abstract: Background Clinical quality registries (CQRs) are playing an increasingly important role in improving health outcomes and reducing health care costs. CQRs are established with the purpose of monitoring quality of care, providing feedback, benchmarking performance, describing pattern of treatment, reducing variation and as a tool for conducting research. Objectives To synthesise the impact of clinical quality registries (CQRs) as an 'intervention' on (I) mortality/survival; (II) measures of outcome that reflect a process or outcome of health care; (III) health care utilisation; and (IV) healthcare-related costs. Methods The following electronic databases were searched: MEDLINE, EMBASE, CENTRAL, CINAHL and Google Scholar. In addition, a review of the grey literature and a reference check of citations and reference lists within articles was undertaken to identify relevant studies in English covering the period January 1980 to December 2016. The PRISMA-P methodology, checklist and standard search strategy using pre-defined inclusion and exclusion criteria and structured data extraction tools were used. Data on study design and methods, participant characteristics attributes of included registries and impact of the registry on outcome measures and/or processes of care were extracted. Results We identified 30102 abstracts from which 75 full text articles were assessed and finally 17 articles were selected for synthesis. Out of 17 studies, six focused on diabetes care, two on cardiac diseases, two on lung diseases and others on organ transplantations, rheumatoid arthritis, ulcer healing, surgical complications and kidney disease. The majority of studies were "before after" design (#11) followed by cohort design (#2), randomised controlled trial (#2), experimental non randomised study and one cross sectional comparison. The measures of impact of registries were multifarious and included change in processes of care, quality of care, treatment outcomes, adherence to guidelines and survival. Sixteen of 17 studies demonstrated positive findings in their outcomes after implementation of the registry. Conclusions Despite the large number of published articles using data derived from CQRs, few have rigorously evaluated the impact of the registry as an intervention on improving health outcomes. Those that have evaluated this impact have mostly found a positive impact on healthcare processes and outcomes. Trial registration PROSPERO CRD42015017319.

Animal Feces Contribute to Domestic Fecal Contamination: Evidence from E. coli Measured in Water, Hands, Food, Flies, and Soil in Bangladesh.

Abstract: Fecal-oral pathogens are transmitted through complex, environmentally mediated pathways. Sanitation interventions that isolate human feces from the environment may reduce transmission but have shown limited impact on environmental contamination. We conducted a study in rural Bangladesh to (1) quantify domestic fecal contamination in settings with high on-site sanitation coverage; (2) determine how domestic animals affect fecal contamination; and (3) assess how each environmental pathway affects others. We collected water, hand rinse, food, soil, and fly samples from 608 households. We analyzed samples with IDEXX Quantitray for the most probable number (MPN) of E. coli. We detected E. coli in source water (25%), stored water (77%), child hands (43%), food (58%), flies (50%), ponds (97%), and soil (95%). Soil had >120 000 mean MPN E. coli per gram. In compounds with vs without animals, E. coli was higher by 0.54 log10 in soil, 0.40 log10 in stored water and 0.61 log10 in food (p < 0.05). E. coli in stored w...

Distribution and Determinants of Low Birth Weight in Developing Countries.

Abstract: Objectives: Low birth weight (LBW) is a major public health concern, especially in developing countries, and is frequently related to child morbidity and mortality. This study aimed to identify key determinants that influence the prevalence of LBW in selected developing countries. Methods: Secondary data analysis was conducted using 10 recent Demography and Health Surveys from developing countries based on the availability of the required information for the years 2010 to 2013. Associations of demographic, socioeconomic, community-based, and individual factors of the mother with LBW in infants were evaluated using multivariate logistic regression analysis. Results: The overall prevalence of LBW in the study countries was 15.9% (range, 9.0 to 35.1%). The following factors were shown to have a significant association with the risk of having an LBW infant in developing countries: maternal age of 35 to 49 years (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.2 to 3.1; p<0.01), inadequate antenatal care (ANC) (aOR, 1.7; 95% CI, 1.1 to 2.8; p<0.01), illiteracy (aOR, 1.5; 95% CI, 1.1 to 2.7; p<0.001), delayed conception (aOR, 1.8; 95% CI, 1.4 to 2.5; p<0.001), low body mass index (aOR, 1.6; 95% CI, 1.2 to 2.1; p<0.001) and being in the poorest socioeconomic stratum (aOR, 1.4; 95% CI, 1.1 to 1.8; p<0.001). Conclusions: This study demonstrated that delayed conception, advanced maternal age, and inadequate ANC visits had independent effects on the prevalence of LBW. Strategies should be implemented based on these findings with the goal of developing policy options for improving the overall maternal health status in developing countries.

Use of antibiotics in children younger than two years in eight countries: a prospective cohort study

Abstract: Objective To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics. Methods Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers' reports at twice-weekly visits over the children's first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class. Findings Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites. Conclusion Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest.

Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis

Abstract: Summary Background Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature. Methods For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232. Findings Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, I 2 =58%) and effectiveness of 76% (62–85, I 2 =0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], I 2 =0%) was lower than in those 5 years or older (64% [58–70], I 2 =0%; p I 2 =45%) in the first year and 59% (49–67, I 2 =0) in the second year. The efficacy reduced to 39% (13 to 57, I 2 =48%) in the third year, and 26% (−46 to 63, I 2 =74%) in the fourth year. Interpretation Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control. Funding The Bill & Melinda Gates Foundation.

The prevalence of underweight, overweight and obesity in Bangladeshi adults: Data from a national survey

Abstract: This article was published in the PLoS ONE [© 2017 Biswas et al ] and the definitive version is available at: https://doiorg/101371/journalpone0177395 The Journal's website is at: http://journalsplosorg/plosone/article?id=101371/journalpone0177395

Determinants and Impact of Giardia Infection in the First 2 Years of Life in the MAL-ED Birth Cohort.

Abstract: Background. Giardia are among the most common enteropathogens detected in children in low-resource settings. We describe here the epidemiology of infection with Giardia in the first 2 years of life in the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED), a multisite birth-cohort study. Methods. From 2089 children, 34916 stool samples collected during monthly surveillance and episodes of diarrhea were tested for Giardia using an enzyme immunoassay. We quantified the risk of Giardia detection, identified risk factors, and assessed the associations with micronutrients, markers of gut inflammation and permeability, diarrhea, and growth using multivariable linear regression. Results. The incidence of at least 1 Giardia detection varied according to site (range, 37.7%-96.4%) and was higher in the second year of life. Exclusive breastfeeding (HR for first Giardia detection in a monthly surveillance stool sample, 0.46 [95% confidence interval (CI), 0.28-0.75]), higher socioeconomic status (HR, 0.74 [95% CI, 0.56-0.97]), and recent metronidazole treatment (risk ratio for any surveillance stool detection, 0.69 [95% CI, 0.56-0.84]) were protective. Persistence of Giardia (consecutive detections) in the first 6 months of life was associated with reduced subsequent diarrheal rates in Naushahro Feroze, Pakistan but not at any other site. Giardia detection was also associated with an increased lactulose/mannitol ratio. Persistence of Giardia before 6 months of age was associated with a -0.29 (95% CI, -0.53 to -0.05) deficit in weight-for-age z score and -0.29 (95% CI, -0.64 to 0.07) deficit in length-for-age z score at 2 years. Conclusions. Infection with Giardia occurred across epidemiological contexts, and repeated detections in 40% of the children suggest that persistent infections were common. Early persistent infection with Giardia, independent of diarrhea, might contribute to intestinal permeability and stunted growth.

Catastrophic healthcare expenditure and poverty related to out-of-pocket payments for healthcare in Bangladesh-an estimation of financial risk protection of universal health coverage.

Abstract: The Sustainable Development Goals target to achieve Universal Health Coverage (UHC), including financial risk protection (FRP) among other dimensions. There are four indicators of FRP, namely incidence of catastrophic health expenditure (CHE), mean positive catastrophic overshoot, incidence of impoverishment and increase in the depth of poverty occur for high out-of-pocket (OOP) healthcare spending. OOP spending is the major payment strategy for healthcare in most low-and-middle-income countries, such as Bangladesh. Large and unpredictable health payments can expose households to substantial financial risk and, at their most extreme, can result in poverty. The aim of this study was to estimate the impact of OOP spending on CHE and poverty, i.e. status of FRP for UHC in Bangladesh. A nationally representative Household Income and Expenditure Survey 2010 was used to determine household consumption expenditure and health-related spending in the last 30 days. Mean CHE headcount and its concentration indices (CI) were calculated. The propensity of facing CHE for households was predicted by demographic and socioeconomic characteristics. The poverty headcount was estimated using 'total household consumption expenditure' and such expenditure without OOP payments for health in comparison with the poverty-line measured by cost of basic need. In absolute values, a pro-rich distribution of OOP payment for healthcare was found in urban and rural Bangladesh. At the 10%-threshold level, in total 14.2% of households faced CHE with 1.9% overshoot. 16.5% of the poorest and 9.2% of the richest households faced CHE. An overall pro-poor distribution was found for CHE (CI = -0.064) in both urban and rural households, while the former had higher CHE incidences. The poverty headcount increased by 3.5% (5.1 million individuals) due to OOP payments. Reliance on OOP payments for healthcare in Bangladesh should be reduced for poverty alleviation in urban and rural Bangladesh in order to secure FRP for UHC.

Evidence-based approaches to childhood stunting in low and middle income countries: a systematic review

Abstract: Objective We systematically evaluated health and nutrition programmes to identify context-specific interventional packages that might help to prioritise the implementation of programmes for reducing stunting in low and middle income countries (LMICs). Methods Electronic databases were used to systematically review the literature published between 1980 and 2015. Additional articles were identified from the reference lists and grey literature. Programmes were identified in which nutrition-specific and nutrition-sensitive interventions had been implemented for children under 5 years of age in LMICs. The primary outcome was a change in stunting prevalence, estimated as the average annual rate of reduction (AARR). A realist approach was applied to identify mechanisms underpinning programme success in particular contexts and settings. Findings Fourteen programmes, which demonstrated reductions in stunting, were identified from 19 LMICs. The AARR varied from 0.6 to 8.4. The interventions most commonly implemented were nutrition education and counselling, growth monitoring and promotion, immunisation, water, sanitation and hygiene, and social safety nets. A programme was considered to have effectively reduced stunting when AARR≥3%. Successful interventions were characterised by a combination of political commitment, multi-sectoral collaboration, community engagement, community-based service delivery platform, and wider programme coverage and compliance. Even for similar interventions the outcome could be compromised if the context differed. Interpretation For all settings, a combination of interventions was associated with success when they included health and nutrition outcomes and social safety nets. An effective programme for stunting reduction embraced country-level commitment together with community engagement and programme context, reflecting the complex nature of exposures of relevance. PROSPERO registration number CRD42016043772.

Women's and men's reports of past-year prevalence of intimate partner violence and rape and women's risk factors for intimate partner violence: A multicountry cross-sectional study in Asia and the Pacific

Abstract: Background Understanding the past-year prevalence of male-perpetrated intimate partner violence (IPV) and risk factors is essential for building evidence-based prevention and monitoring progress to Sustainable Development Goal (SDG) 5.2, but so far, population-based research on this remains very limited. The objective of this study is to compare the population prevalence rates of past-year male-perpetrated IPV and nonpartner rape from women’s and men’s reports across 4 countries in Asia and the Pacific. A further objective is to describe the risk factors associated with women’s experience of past-year physical or sexual IPV from women’s reports and factors driving women’s past-year experience of partner violence. Methods and findings This paper presents findings from the United Nations Multi-country Study on Men and Violence in Asia and the Pacific. In the course of this study, in population-based cross-sectional surveys, 5,206 men and 3,106 women aged 18–49 years were interviewed from 4 countries: Cambodia, China, Papua New Guinea (PNG), and Sri Lanka. To measure risk factors, we use logistic regression and structural equation modelling to show pathways and mediators. The analysis was not based on a written plan, and following a reviewer’s comments, some material was moved to supplementary files and the regression was performed without variable elimination. Men reported more lifetime perpetration of IPV (physical or sexual IPV range 32.5%–80%) than women did experience (physical or sexual IPV range 27.5%–67.4%), but women’s reports of past-year experience (physical or sexual IPV range 8.2%–32.1%) were not very clearly different from men’s (physical or sexual IPV range 10.1%–34.0%). Women reported much more emotional/economic abuse (past-year ranges 1.4%–5.7% for men and 4.1%–27.7% for women). Reports of nonpartner rape were similar for men (range 0.8%–1.9% in the past year) and women (range 0.4%–2.3% in past year), except in Bougainville, where they were higher for men (11.7% versus 5.7%). The risk factor modelling shows 4 groups of variables to be important in experience of past-year sexual and/or physical IPV: (1) poverty, (2) all childhood trauma, (3) quarrelling and women’s limited control in relationships, and (4) partner factors (substance abuse, unemployment, and infidelity). The population attributable fraction (PAF) was largest for quarrelling often, but the second greatest PAF was for the group related to exposure to violence in childhood. The relationship control variable group had the third highest PAF, followed by other partner factors. Currently married women were also more at risk. In the structural model, a resilience pathway showed less poverty, higher education, and more gender-equitable ideas were connected and conveyed protection from IPV. These are all amenable risk factors. This research was cross-sectional, so we cannot be sure of the temporal sequence of exposure, but the outcome being a past-year measure to some extent mitigates this problem. Conclusions Past-year IPV indicators based on women’s reported experience that were developed to track SDG 5 are probably reasonably reliable but will not always give the same prevalence as may be reported by men. Report validity requires further research. Interviews with men to track past-year nonpartner rape perpetration are feasible and important. The findings suggest a range of factors are associated with past-year physical and/or sexual IPV exposure; of particular interest is the resilience pathway suggested by the structural model, which is highly amenable to intervention and explains why combining economic empowerment of women and gender empowerment/relationship skills training has been successful. This study provides additional rationale for scaling up violence prevention interventions that combine economic and gender empowerment/relationship skills building of women, as well as the value of investing in girls’ education with a view to long-term violence reduction.

Indications and determinants of caesarean section delivery: Evidence from a population-based study in Matlab, Bangladesh

Abstract: Background and methods Caesarean section (C-section) is a major obstetric intervention for saving lives of women and their newborns from pregnancy and childbirth related complications. Un-necessary C-sections may have adverse impact upon maternal and neonatal outcomes. In Bangladesh there is paucity of data on clinical indication of C-section at population level. We conducted a retrospective study in icddr,b Health and Demographic Surveillance System (HDSS) area of Matlab to look into the indications and determinants of C-sections. All resident women in HDSS service area who gave birth in 2013 with a known birth outcome, were included in the study. Women who underwent C-section were identified from birth and pregnancy files of HDSS and their indication for C-section were collected reviewing health facility records where the procedure took place, supplemented by face-to-face interview of mothers where data were missing. Indications of C-section were presented as frequency distribution and further divided into different groups following 3 distinct classification systems. Socio-demographic predictors were explored following statistical method of binary logistic regression. Findings During 2013, facility delivery rate was 84% and population based C-section rate was 35% of all deliveries in icddr,b service area. Of all C-sections, only 1.4% was conducted for Absolute Maternal Indications (AMIs). Major indications of C-sections included: repeat C-section (24%), foetal distress (21%), prolonged labour (16%), oligohydramnios (14%) and post-maturity (13%). More than 80% C-sections were performed in for-profit private facilities. Probability of C-section delivery increased with improved socio-economic status, higher education, lower birth order, higher age, and with more number of Antenatal Care use and presence of bad obstetric history. Eight maternal deaths occurred, of which five were delivered by C-section. Conclusions C-section rate in this area was much higher than national average as well as global recommendations. Very few of C-sections were undertaken for AMIs. Routine monitoring of clinical indication of C-section in public and private facilities is needed to ensure rational use of the procedure.

Coping strategies related to food insecurity at the household level in Bangladesh.

Abstract: This article was published in the PLoS ONE [© 2017 Farzana et al.] and the definitive version is available at: https://doi.org/10.1371/journal.pone.0171411 The Journal's website is at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171411

Mycobacterial Dormancy Systems and Host Responses in Tuberculosis

Abstract: Tuberculosis caused by the intracellular pathogen, Mycobacterium tuberculosis (Mtb) claims more than 1.5 million lives worldwide, annually. Despite promulgation of multipronged strategies to prevent and control tuberculosis, there is no significant downfall occurring in the number of new cases; and adding to this is the relapse of the disease due to the emergence of antibiotic resistance and the ability of Mtb to remain dormant after primary infection. The pathology of Mtb is complex and largely attributed to immune evading strategies that this pathogen adopts to establish primary infection, its persistence in the host and reactivation of pathogenicity under favorable conditions. In this review, we present various bio-chemical, immunological and genetic strategies unleashed by Mtb inside the host for its survival. The bacterium enables itself to establish a niche by evading immune recognition via resorting to masking, establishment of dormancy by manipulating immune receptor responses, altering innate immune cell fate, enhancing granuloma formation and developing antibiotic tolerance. Besides these, the regulatory entities such as DosR and its regulon, encompassing a variety of effector proteins play a key role in maintaining the dormant nature of this pathogen. Further, reactivation of Mtb allows relapse of the disease and is favored by the genes of the Rtf family and the conditions that suppress the immune system of the host. Identification of target genes and characterizing the function of their respective antigens involved in primary infection, dormancy and reactivation would likely provide vital clues to design novel drugs and / or vaccines to contain this disease at multiple levels.

Disruption, not displacement: Environmental variability and temporary migration in Bangladesh.

Abstract: Mass migration is one of the most concerning potential outcomes of global climate change. Recent research into environmentally induced migration suggests that relationship is much more complicated than originally posited by the 'environmental refugee' hypothesis. Climate change is likely to increase migration in some cases and reduce it in others, and these movements will more often be temporary and short term than permanent and long term. However, few large-sample studies have examined the evolution of temporary migration under changing environmental conditions. To address this gap, we measure the extent to which temperature, precipitation, and flooding can predict temporary migration in Matlab, Bangladesh. Our analysis incorporates high-frequency demographic surveillance data, a discrete time event history approach, and a range of sociodemographic and contextual controls. This approach reveals that migration declines immediately after flooding but quickly returns to normal. In contrast, optimal precipitation and high temperatures have sustained positive effects on temporary migration that persist over one to two year periods. Building on previous studies of long-term migration, these results challenge the common assumption that flooding, precipitation extremes and high temperatures will consistently increase temporary migration. Instead, our results are consistent with a livelihoods interpretation of environmental migration in which households draw on a range of strategies to cope with environmental variability.

Autism Spectrum disorders (ASD) in South Asia: a systematic review

Abstract: Autism spectrum disorders (ASD) are a group of complex neurodevelopmental disorders. The prevalence of ASD in many South Asian countries is still unknown. The aim of this study was to systematically review available epidemiological studies of ASD in this region to identify gaps in our current knowledge. We searched, collected and evaluated articles published between January 1962 and July 2016 which reported the prevalence of ASD in eight South Asian countries. The search was conducted in line with the PRISMA guidelines. We identified six articles from Bangladesh, India, and Sri Lanka which met our predefined inclusion criteria. The reported prevalence of ASD in South Asia ranged from 0.09% in India to 1.07% in Sri Lanka that indicates up to one in 93 children have ASD in this region. Alarmingly high prevalence (3%) was reported in Dhaka city. Study sample sizes ranged from 374 in Sri Lanka to 18,480 in India. The age range varied between 1 and 30 years. No studies were found which reported the prevalence of ASD in Pakistan, Nepal, Bhutan, Maldives and Afghanistan. This review identifies methodological differences in case definition, screening instruments and diagnostic criteria among reported three countries which make it very difficult to compare the studies. Our study is an attempt at understanding the scale of the problem and scarcity of information regarding ASD in the South Asia. This study will contribute to the evidence base needed to design further research and make policy decisions on addressing this issue in this region. Knowing the prevalence of ASD in South Asia is vital to ensure the effective allocation of resources and services.

Manganese in Drinking Water and Cognitive Abilities and Behavior at 10 Years of Age: A Prospective Cohort Study.

Abstract: Background: Cross-sectional studies have indicated impaired neurodevelopment with elevated drinking water manganese concentrations (W-Mn), but potential susceptible exposure windows are unknown. Ob...

Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh

Abstract: A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes.

Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990–2013: findings from the Global Burden of Disease Study 2013

Abstract: Objectives We used findings from the Global Burden of Disease Study 2013 to report the burden of musculoskeletal disorders in the Eastern Mediterranean Region (EMR). Methods The burden of musculoskeletal disorders was calculated for the EMR's 22 countries between 1990 and 2013. A systematic analysis was performed on mortality and morbidity data to estimate prevalence, death, years of live lost, years lived with disability and disability-adjusted life years (DALYs). Results For musculoskeletal disorders, the crude DALYs rate per 100 000 increased from 1297.1 (95% uncertainty interval (UI) 924.3-1703.4) in 1990 to 1606.0 (95% UI 1141.2-2130.4) in 2013. During 1990-2013, the total DALYs of musculoskeletal disorders increased by 105.2% in the EMR compared with a 58.0% increase in the rest of the world. The burden of musculoskeletal disorders as a proportion of total DALYs increased from 2.4% (95% UI 1.7-3.0) in 1990 to 4.7% (95% UI 3.6-5.8) in 2013. The range of point prevalence (per 1000) among the EMR countries was 28.2-136.0 for low back pain, 27.3-49.7 for neck pain, 9.7-37.3 for osteoarthritis (OA), 0.6-2.2 for rheumatoid arthritis and 0.1-0.8 for gout. Low back pain and neck pain had the highest burden in EMR countries. Conclusions This study shows a high burden of musculoskeletal disorders, with a faster increase in EMR compared with the rest of the world. The reasons for this faster increase need to be explored. Our findings call for incorporating prevention and control programmes that should include improving health data, addressing risk factors, providing evidence-based care and community programmes to increase awareness.

Comparative Genomic Analysis of Globally Dominant ST131 Clone with Other Epidemiologically Successful Extraintestinal Pathogenic Escherichia coli (ExPEC) Lineages.

Abstract: Escherichia coli sequence type 131 (ST131), a pandemic clone responsible for the high incidence of extraintestinal pathogenic E. coli (ExPEC) infections, has been known widely for its contribution to the worldwide dissemination of multidrug resistance. Although other ExPEC-associated and extended-spectrum-β-lactamase (ESBL)-producing E. coli clones, such as ST38, ST405, and ST648 have been studied widely, no comparative genomic data with respect to other genotypes exist for ST131. In this study, comparative genomic analysis was performed for 99 ST131 E. coli strains with 40 genomes from three other STs, including ST38 (n = 12), ST405 (n = 10), and ST648 (n = 18), and functional studies were performed on five in-house strains corresponding to the four STs. Phylogenomic analysis results from this study corroborated with the sequence type-specific clonality. Results from the genome-wide resistance profiling confirmed that all strains were inherently multidrug resistant. ST131 genomes showed unique virulence profiles, and analysis of mobile genetic elements and their associated methyltransferases (MTases) has revealed that several of them were missing from the majority of the non-ST131 strains. Despite the fact that non-ST131 strains lacked few essential genes belonging to the serum resistome, the in-house strains representing all four STs demonstrated similar resistance levels to serum antibactericidal activity. Core genome analysis data revealed that non-ST131 strains usually lacked several ST131-defined genomic coordinates, and a significant number of genes were missing from the core of the ST131 genomes. Data from this study reinforce adaptive diversification of E. coli strains belonging to the ST131 lineage and provide new insights into the molecular mechanisms underlying clonal diversification of the ST131 lineage. IMPORTANCEE. coli, particularly the ST131 extraintestinal pathogenic E. coli (ExPEC) lineage, is an important cause of community- and hospital-acquired infections, such as urinary tract infections, surgical site infections, bloodstream infections, and sepsis. The treatment of infections caused by ExPEC has become very challenging due to the emergence of resistance to the first-line as well as the last-resort antibiotics. This study analyzes E. coli ST131 against three other important and globally distributed ExPEC lineages (ST38, ST405, and ST648) that also produced extended-spectrum β-lactamase (ESBL). This is perhaps the first study that employs the high-throughput whole-genome sequence-based approach to compare and study the genomic features of these four ExPEC lineages in relation to their functional properties. Findings from this study highlight the differences in the genomic coordinates of ST131 with respect to the other STs considered here. Results from this comparative genomics study can help in advancing the understanding of ST131 evolution and also offer a framework towards future developments in pathogen identification and targeted therapeutics to prevent diseases caused by this pandemic E. coli ST131 clone.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study

Abstract: Background Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association Methods PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia Controls were randomly selected from the community Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens Results Median colonization density among 56 cases with MCPP (MCPP cases; 1728 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 075 × 106) and controls (060 × 106) (each P 69 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site The threshold was lower (≥44 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >69 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation Conclusions Pneumococcal colonization density >69 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies Our findings do not support its use for individual diagnosis in a clinical setting