Effects of household concrete floors on maternal and child health - the CRADLE trial: a randomised controlled trial protocol.

Introduction: Early life soil-transmitted helminth infection and diarrhea are associated with growth faltering, anemia, impaired child development, and mortality. Exposure to fecally contaminated soil inside the home may be a key contributor to enteric infections, and a large fraction of rural homes in low-income countries have soil floors. The objective of this study is to measure the effect of installing concrete floors in homes with soil floors on child soil-transmitted helminth infection and other maternal and child health outcomes in rural Bangladesh. Methods and analysis: The Cement-based flooRs AnD chiLd hEalth (CRADLE) trial is an individually randomised trial in Sirajganj and Tangail districts, Bangladesh. Households with a pregnant woman, a soil floor, walls that are not made of mud will be eligible, and no plan to relocate for 3 years. We will randomise 800 households to intervention or control (1:1) within geographic blocks of 10 households to account for strong geographic clustering of enteric infection. Laboratory staff and data analysts will be blinded; participants will be unblinded. We will install concrete floors when the birth cohort is in utero and measure outcomes at child ages 3, 6, 12, 18, and 24 months. The primary outcome is prevalence of any soil-transmitted helminth infection (Ascaris lumbricoides, Necator americanus, or Trichuris trichiura) detected by qPCR at 6, 12, 18, or 24 months follow-up in the birth cohort. Secondary outcomes include household floor and child hand contamination with E. coli, extended-spectrum beta-lactamase producing E. coli, and soil-transmitted helminth DNA; child diarrhea, growth, and cognitive development; and maternal stress and depression. Ethics and dissemination: Study protocols have been approved by institutional review boards at Stanford University and the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). We will report findings on ClinicalTrials.gov, in peer-reviewed publications, and in stakeholder workshops in Bangladesh. Trial registration number: NCT05372068, pre-results.

Intrapartum and postpartum antibiotic use in seven low- and middle-income countries: Findings from the A-PLUS trial.

OBJECTIVE: To describe the intrapartum and postpartum use of non-study antibiotics in low- and middle-income countries (LMICs) during the double-blinded NICHD Global Network Azithromycin in Labor (A-PLUS) trial. DESIGN: The antibiotic use sub-study was a planned prospective, observational sub-study of the A-PLUS trial. SETTINGS: The study was carried out in hospitals or health centres affiliated with eight sites of the Global Network for Women's and Children's Health Research (Global Network) in seven countries: Bangladesh, Pakistan, India (two sites), Kenya, Zambia, The Democratic Republic of the Congo (DRC) and Guatemala. POPULATION: Totally, 29 278 pregnant women enrolled in the A-PLUS trial. METHODS: We collected data on 29 278 pregnant women admitted to a facility for delivery related to non-study antibiotic use overall and during three time periods: (1) in the facility prior to delivery, (2) after delivery until facility discharge and (3) after discharge to 42 days post-partum. MAIN OUTCOME MEASURES: Non-study antibiotic use overall and for treatment or prophylaxis by the site during the three time periods. RESULTS: Of the 29 278 women in the study, 5020 (17.1%; 95% CI 16.7%-17.6%) received non-study antibiotics in the facility prior to delivery, 11 956 (40.8%; 95% CI 40.3%-41.4%) received non-study antibiotics in the facility after delivery, and 13 390 (47.6%; 95% CI 47.0%-48.2%) women received non-study antibiotics after delivery and after facility discharge. Antibiotics were prescribed more often among women in the Asian and Guatemalan sites than in the African sites. In the three time-periods, among those receiving antibiotics, prophylaxis was the indication in 82.3%, 97.7% and 90.7% of the cases, respectively. The type of antibiotics used varied substantially by time-period and site, but generally, penicillin-type drugs, cephalosporin-type drugs and metronidazole were used more frequently than other types. CONCLUSIONS: Across the eight sites of the Global Network, in the facility before delivery, and in the post-partum periods before and after facility discharge, antibiotics were used frequently, but use was highly variable by site and time-period.

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh, 2011-2014.

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = -0.59 log copies per gram of stool; 95% confidence interval [CI], -.99 to -.19). Duration of illness was on average 0.47 days (95% CI, -.23 to 1.17 days) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of rotavirus gastroenteritis. Clinical Trials Registration . NCT01375647.

Malnutrition: From Mother to Child.

Malnutrition in children, defined as a child who is more than 2 standard deviations below the norm for height- or weight-for-age, is a pervasive, population-wide problem in low- and middle-income countries. Malnutrition is associated with increased infant mortality and delayed neurocognitive development. A recent pooled analysis of more than 30 longitudinal cohort studies demonstrated that the conditions mothers lived in during pregnancy, and their access to adequate nutrition, was a major factor in the subsequent growth and health of their children. We review here this analysis and the hypothesis that interventions to address childhood malnutrition need to start before birth and continue throughout the critical first 1,000 days of life.

Influence of hydrometeorological risk factors on child diarrhea and enteropathogens in rural Bangladesh.

BACKGROUND: A number of studies have detected relationships between weather and diarrhea. Few have investigated associations with specific enteric pathogens. Understanding pathogen-specific relationships with weather is crucial to inform public health in low-resource settings that are especially vulnerable to climate change. OBJECTIVES: Our objectives were to identify weather and environmental risk factors associated with diarrhea and enteropathogen prevalence in young children in rural Bangladesh, a population with high diarrheal disease burden and vulnerability to weather shifts under climate change. METHODS: We matched temperature, precipitation, surface water, and humidity data to observational longitudinal data from a cluster-randomized trial that measured diarrhea and enteropathogen prevalence in children 6 months-5.5 years from 2012-2016. We fit generalized additive mixed models with cubic regression splines and restricted maximum likelihood estimation for smoothing parameters. RESULTS: Comparing weeks with 30°C versus 15°C average temperature, prevalence was 3.5% higher for diarrhea, 7.3% higher for Shiga toxin-producing Escherichia coli (STEC), 17.3% higher for enterotoxigenic E. coli (ETEC), and 8.0% higher for Cryptosporidium. Above-median weekly precipitation (median: 13mm; range: 0-396mm) was associated with 29% higher diarrhea (adjusted prevalence ratio 1.29, 95% CI 1.07, 1.55); higher Cryptosporidium, ETEC, STEC, Shigella, Campylobacter, Aeromonas, and adenovirus 40/41; and lower Giardia, sapovirus, and norovirus prevalence. Other associations were weak or null. DISCUSSION: Higher temperatures and precipitation were associated with higher prevalence of diarrhea and multiple enteropathogens; higher precipitation was associated with lower prevalence of some enteric viruses. Our findings emphasize the heterogeneity of the relationships between hydrometeorological variables and specific enteropathogens, which can be masked when looking at composite measures like all-cause diarrhea. Our results suggest that preventive interventions targeted to reduce enteropathogens just before and during the rainy season may more effectively reduce child diarrhea and enteric pathogen carriage in rural Bangladesh and in settings with similar meteorological characteristics, infrastructure, and enteropathogen transmission.

The infant gut microbiome and cognitive development in malnutrition.

Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.

Genetic Susceptibility to Astrovirus Diarrhea in Bangladeshi Infants.

Background: Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development. Methods: To address our hypothesis that host genetic risk factors are associated with astrovirus disease susceptibility, we performed a genome-wide association study of astrovirus infection in the first year of life from children enrolled in 2 Bangladeshi birth cohorts. Results: We identified a novel region on chromosome 1 near the loricrin gene (LOR) associated with astrovirus diarrheal infection (rs75437404; meta-analysis P = 8.82 × 10-9; A allele odds ratio, 2.71) and on chromosome 10 near the prolactin releasing hormone receptor gene (PRLHR) (rs75935441; meta-analysis P = 1.33 × 10-8; C allele odds ratio, 4.17). The prolactin-releasing peptide has been shown to influence feeding patterns and energy balance in mice. In addition, several single-nucleotide polymorphisms in the chromosome 1 locus have previously been associated with expression of innate immune system genes PGLYRP4, S100A9, and S100A12. Conclusions: This study identified 2 significant host genetic regions that may influence astrovirus diarrhea susceptibility and should be considered in further studies.

Multidimensional evaluation of the early emergence of executive function and development in Bangladeshi children using nutritional and psychosocial intervention: A randomized controlled trial protocol.

INTRODUCTION: Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regulation of these children. METHODS: The primary outcome of this prospective, randomized controlled trial is to study the development of executive functions (EFs) and emotion regulation (ER) in this cohort. Moderate acute malnourished (MAM; WLZ/WHZ <-2 and ≥-3 z-score, and/or 11.5 cm ≤ MUAC < 12.5cm; n = 140)children aged around one year (11m-13m) in Mirpur, Dhaka, Bangladesh will be randomized (1:1) to receive either locally produced Ready to Use Supplementary Food (RUSF) or Enhanced Ready to Use Supplementary Food (E-RUSF) until anthropometric recovery (WLZ/WHZ > -1SD), or for 3 months after enrollment (whichever is earlier). The randomized MAMs groups will be given either Small Quantity Lipid Based Nutrient Supplement (SQLNS) or Enhanced Small Quantity Lipid Based Nutrient Supplement (E-SQLNS), respectively until the end of the 2-year follow up period. Standard psychosocial stimulation will be provided to the MAMs intervention groups. Biological samples will be collected, anthropometric and neurocognitive assessments will be performed at 2 (22m-26m) and 3 (34m-38m) years of age. Two control groups will be recruited: 1), non-malnourished one-year (11m-13m) old children (WLZ/WHZ score>-1SD; n = 70); and 2) three-year (34m-38m) old children (n = 70) with untreated MAM (WHZ <-2 and ≥-3 z-score, and/or 11.5≤MUAC<12.5 cm). The 3-year-old MAM reference group will be assessed once and provided with 2 months of nutritional rehabilitation support (RUSF Nutriset's Plumpy'Sup™).

Infant Non-Secretor Histoblood Group Antigen Phenotype Reduces Susceptibility to Both Symptomatic and Asymptomatic Rotavirus Infection.

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case-control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

Systemic inflammation, enteropathogenic E. Coli, and micronutrient insufficiencies in the first trimester as possible predictors of preterm birth in rural Bangladesh: a prospective study.

BACKGROUND: An incomplete understanding of preterm birth is especially concerning for low-middle income countries, where preterm birth has poorer prognoses. While systemic proinflammatory processes are a reportedly normal component of gestation, excessive inflammation has been demonstrated as a risk factor for preterm birth. There is minimal research on the impact of excessive maternal inflammation in the first trimester on the risk of preterm birth in low-middle income countries specifically. METHODS: Pregnant women were enrolled at the rural Bangladesh site of the National Institute of Child Health Global Network Maternal Newborn Health Registry. Serum samples were collected to measure concentrations of the inflammatory markers C-reactive protein (CRP) and Alpha-1-acid glycoprotein (AGP), and stool samples were collected and analyzed for enteropathogens. We examined associations of maternal markers in the first-trimester with preterm birth using logistic regression models. CRP and AGP were primarily modeled with a composite inflammation predictor. RESULTS: Out of 376 singleton births analyzed, 12.5% were preterm. First trimester inflammation was observed in 58.8% of all births, and was significantly associated with increased odds of preterm birth (adjusted odds ratio [aOR] = 2.23; 95% confidence interval [CI]: 1.03, 5.16), independent of anemia. Maternal vitamin B12 insufficiency (aOR = 3.33; 95% CI: 1.29, 8.21) and maternal anemia (aOR = 2.56; 95% CI: 1.26, 5.17) were also associated with higher odds of preterm birth. Atypical enteropathogenic E. coli detection showed a significant association with elevated AGP levels and was significantly associated with preterm birth (odds ratio [OR] = 2.36; 95% CI: 1.21, 4.57), but not associated with CRP. CONCLUSIONS: Inflammation, anemia, and vitamin B12 insufficiency in the first trimester were significantly associated with preterm birth in our cohort from rural Bangladesh. Inflammation and anemia were independent predictors of premature birth in this low-middle income setting where inflammation during gestation was widespread. Further research is needed to identify if infections such as enteropathogenic E. coli are a cause of inflammation in the first trimester, and if intervention for infection would decrease preterm birth.

Safety and durable immunogenicity of the TV005 tetravalent dengue vaccine, across serotypes and age groups, in dengue-endemic Bangladesh: a randomised, controlled trial.

BACKGROUND: Morbidity and mortality from dengue virus (DENV) is rapidly growing in the large populations of south Asia. Few formal evaluations of candidate dengue vaccine candidates have been undertaken in India, Pakistan, or Bangladesh. Tetravalent vaccines must be tested for safety and immunogenicity in all age groups and in those previously exposed and naive to DENV infections. TV005 is a live, attenuated tetravalent dengue vaccine. We evaluated the safety and immunogenicity of a single dose of TV005 across age groups in dengue-endemic Bangladesh. METHODS: We performed a randomised, placebo-controlled age de-escalating clinical trial of TV005 at a single clinical site in dengue-endemic Dhaka, Bangladesh, following a technology transfer from the USA. Healthy (as determined by history, clinical examination, and safety laboratory test results) volunteers aged 1-50 years were randomly assigned 3:1 (stratified by four age groups) to receive a single dose of TV005 vaccine or placebo. Participants were followed up for 3 years. The study was double blind and was unmasked at day 180; outcome assessors, clinic staff, and volunteers remained blind throughout. Primary outcomes were safety, evaluated per-protocol as proportion of volunteers with solicited related adverse events of any severity through 28 days post dosing, and post-vaccination seropositivity by day 180 using serotype-specific neutralising antibodies (PRNT50 ≥10). Secondary outcomes included viremia, impact of past dengue exposure, and durability of antibody responses. This study is registered with Clinicaltrials.gov, NCT02678455, and is complete. FINDINGS: Between March 13, 2016, and Feb 14, 2017, 192 volunteers were enrolled into four age groups (adults [18-50 years; 20 male and 28 female], adolescents [11-17 years; 27 male and 21 female], children [5-10 years; 15 male and 33 female], and young children [1-4 years; 29 male and 19 female]) with 48 participant per group. All participants were Bangladeshi. Vaccination was well tolerated and most adverse events were mild. Rash was the most common vaccine-associated solicited adverse event, in 37 (26%) of 144 vaccine recipients versus six (12%) of 48 placebo recipients; followed by fever in seven (5% of 144) and arthralgias in seven (6% of 108), which were only observed in vaccine recipients. Post-vaccine, volunteers of all ages (n=142) were seropositive to most serotypes with 118 (83%) seropositive to DENV 1, 141 (99%) to DENV 2, 137 (96%) to DENV 3, and 124 (87%) to DENV 4, overall by day 180. Post-vaccination, viraemia was not consistently found and antibody titres were higher (10-15-fold for DENV 1-3 and 1·6-fold for DENV 4) in individuals with past dengue exposure compared with the dengue-naive participants (DENV 1 mean 480 [SD 4·0] vs 32 [2·4], DENV 2 1042 [3·2] vs 105 [3·1], DENV 3 1406 [2·8] vs 129 [4·7], and DENV 4 105 [3·3] vs 65 [3·1], respectively). Antibody titres to all serotypes remained stable in most adults (63-86%) after 3 years of follow-up. However, as expected for individuals without past exposure to dengue, titres for DENV 1, 3, and 4 waned by 3 years in the youngest (1-4 year old) cohort (69% seropositive for DENV 2 and 22-28% seropositive for DENV 1, 3, and 4). INTERPRETATION: With 3 years of follow-up, the single-dose tetravalent dengue vaccine, TV005, was well tolerated and immunogenic for all four serotypes in young children to adults, including individuals with no previous dengue exposure. FUNDING: National Institutes of Health-National Institute of Allergy and Infectious Diseases Intramural Research Program and Johns Hopkins University. TRANSLATION: For the Bangla translation of the abstract see Supplementary Materials section.

Detection and absolute quantification of Lactiplantibacillus plantarum ATCC 202195 by quantitative real-time PCR.

IMPORTANCE: When administered for seven consecutive days shortly after birth, the probiotic bacterium Lactiplantibacillus plantarum ATCC 202195 plus fructooligosaccharide (FOS) was reported to reduce sepsis and lower respiratory tract infection events during early infancy in a randomized trial in India. Since probiotic effects are often strain specific, strain-level detection and quantification by routine molecular methods enables the monitoring of safety outcomes, such as probiotic-associated bacteremia, and allows for the quality of probiotic interventions to be assessed and monitored (i.e., verify strain identity and enumerate). Despite the potential clinical applications of L. plantarum ATCC 202195, an assay to detect and quantify this strain has not previously been described. Herein, we report the design of primer and probe sequences to detect L. plantarum ATCC 202195 and the development and optimization of a real-time PCR assay to detect and quantify the strain with high specificity and high sensitivity.

Adherence to Anti-Malarial Treatment in Malaria Endemic Areas of Bangladesh.

Ensuring adherence to antimalarial treatment is crucial for achieving a radical cure and elimination of malaria, especially in hard-to-reach areas. We conducted this study to assess the current scenario of drug adherence in four endemic sub-districts of Bangladesh. Among 110 enrolled participants, 70% were mono-infected with Plasmodium falciparum and the remaining 30% with P. vivax. The overall treatment adherence frequency was 92.7% (95% CI: 83.0-96.3%). A total of eight participants were found to be nonadherent to treatment and all of them were from Bandarban. Level of nonadherence was equally observed in two age groups: 11-17 and 18+ years. However, male participants (n = 6) were found to be more nonadherent than females (n = 2). Among 7.3% with nonadherence to treatment, a single participant with P. falciparum mono-infection refused to take medication and became nonadherent. Remaining participants stated that they were feeling well and going to work, thus leaving treatment course uncompleted. Although overall compliance with malaria medication seems good, a gradual increase in noncompliance to P. vivax malaria treatment suggests that the National Malaria Elimination Program must be enhanced and monitored to fulfil the projected malaria elimination goal before 2030 from Bangladesh.

Maternal and perinatal outcomes of women with vaginal birth after cesarean section compared to repeat cesarean birth in select South Asian and Latin American settings of the global network for women's and children's health research.

OBJECTIVE: Our objective was to analyze a prospective population-based registry including five sites in four low- and middle-income countries to observe characteristics associated with vaginal birth after cesarean versus repeat cesarean birth, as well as maternal and newborn outcomes associated with the mode of birth among women with a history of prior cesarean. HYPOTHESIS: Maternal and perinatal outcomes among vaginal birth after cesarean section will be similar to those among recurrent cesarean birth. METHODS: A prospective population-based study, including home and facility births among women enrolled from 2017 to 2020, was performed in communities in Guatemala, India (Belagavi and Nagpur), Pakistan, and Bangladesh. Women were enrolled during pregnancy, and delivery outcome data were collected within 42 days after birth. RESULTS: We analyzed 8267 women with a history of prior cesarean birth; 1389 (16.8%) experienced vaginal birth after cesarean, and 6878 (83.2%) delivered by a repeat cesarean birth. Having a repeat cesarean birth was negatively associated with a need for curettage (ARR 0.12 [0.06, 0.25]) but was positively associated with having a blood transfusion (ARR 3.74 [2.48, 5.63]). Having a repeat cesarean birth was negatively associated with stillbirth (ARR 0.24 [0.15, 0.49]) and, breast-feeding within an hour of birth (ARR 0.39 [0.30, 0.50]), but positively associated with use of antibiotics (ARR 1.51 [1.20, 1.91]). CONCLUSIONS: In select South Asian and Latin American low- and middle-income sites, women with a history of prior cesarean birth were 5 times more likely to deliver by cesarean birth in the hospital setting. Those who delivered vaginally had less complicated pregnancy and labor courses compared to those who delivered by repeat cesarean birth, but they had an increased risk of stillbirth. More large scale studies are needed in Low Income Country settings to give stronger recommendations. TRIAL REGISTRATION: NCT01073475, Registered February 21, 2010, https://clinicaltrials.gov/ct2/show/record/NCT01073475 .

Differences in Rotavirus Shedding and Duration by Infant Oral Rotavirus Vaccination Status in Dhaka, Bangladesh 2011 - 2014.

To evaluate how breakthrough rotavirus disease contributes to transmission, we examined the impact of rotavirus vaccination on fecal shedding and duration of illness. We used multivariable linear regression to analyze rotavirus quantity by RT-qPCR and duration among 184 episodes of rotavirus diarrhea positive by ELISA in the PROVIDE study. Vaccinated children had less fecal viral shedding compared to unvaccinated children (mean difference = -0.59 log copies per gram of stool, 95% CI: -0.99, -0.19). Duration of illness was on average 0.47 days (95% CI: -0.23, 1.17) shorter among vaccinated children. Rotarix vaccination reduces shedding burden among breakthrough cases of RVGE.

We estimated the effect of rotavirus vaccination on duration and quantity of rotavirus shed during rotavirus gastroenteritis in Bangladesh. Virus quantity was lower in symptomatic vaccinated children compared to symptomatic unvaccinated children, but differences in episode duration were small.

Dried Blood Spots (DBS): A suitable alternative to using whole blood samples for diagnostic testing of visceral leishmaniasis in the post-elimination era.

BACKGROUND: Serum or whole blood collection, processing, transport and storage still present significant challenges in low resource settings where mass surveillance is required to sustain disease elimination. Therefore, in this study, we explored the diagnostic efficacy of dried blood spots (DBS) as a minimally invasive and potentially cost-effective alternative sampling technique to whole blood sampling procedures for subsequent detection of Leishmania donovani antibodies or DNA. METHODOLOGY AND PRINCIPAL FINDINGS: Archived serum, DNA samples from whole blood of visceral leishmaniasis (VL) cases and healthy controls, and DBS from corresponding cases and controls, were used. Both molecular and serological assays were optimized to detect L. donovani antibodies or DNA in DBS elute and results were compared against those obtained with whole blood. Serological assays (both rK28 ELISA and rK39 ELISA) of DBS samples showed sensitivity and specificity of 100% and had excellent agreement with results from whole blood samples (kappa value ranged from 0.98-1). Bland-Altman analysis of OD values from rK28-ELISA with DBS elute and patients' serum showed an excellent agreement (ICC = 0.9) whereas a good agreement (ICC = 0.8) was observed in the case of rK39-ELISA. However, qPCR and RPA of DBS samples had a diminished sensitivity of 76% and 68%, respectively, and poor agreement was observed with the whole blood samples. CONCLUSION: Our results demonstrate that DBS offer excellent diagnostic efficiency for serological assays and represent a viable alternative to whole blood sampling procedures.