SummaryBackgroundMore than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia.MethodsFrom 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples.Findings6022 pSBI episodes were identified among 63 114 babies (95·4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13·2 (95% credible interval [CrI] 11·2–15·6) per 1000 livebirths and of viral infections was 10·1 (9·4–11·6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5·4, 95% CrI 4·8–6·3 episodes per 1000 livebirths), followed by Ureaplasma spp (2·4, 1·6–3·2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs.InterpretationNon-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal.FundingBill & Melinda Gates Foundation

Our results suggest that the two alternative antibiotic regimens for outpatient treatment of clinical signs of severe infection in young infants whose parents refused hospital admission are as efficacious as the standard regimen. This finding could increase treatment options in resource-poor settings when referral care is not available or acceptable.

BackgroundNeonatal mortality is declining slowly compared to under-five mortality in many developing countries including Afghanistan. About three-fourths of these deaths occur in the early neonatal period (i.e., the first week of life). Although a number of studies investigated determinants of early neonatal mortality in other countries, there is a lack of evidence regarding this in Afghanistan. This study investigated determinants of early neonatal mortality in Afghanistan.MethodsData from the Afghanistan Demographic and Health Survey 2015 (AfDHS 2015) were analyzed. After reporting the weighted frequency distributions of selected factors, a multilevel logistic regression model revealed adjusted associations of factors with early neonatal mortality.ResultsA total of 19,801 weighted live-births were included in our analysis; 266 (1.4%) of the newborns died in this period. Multivariable analysis found that multiple gestations (adjusted odds ratio (AOR): 9.3; 95% confidence interval (CI): 5.7–15.0), larger (AOR: 2.9; 95% CI: 2.2–3.8) and smaller (AOR: 1.8; 95% CI: 1.2–2.6) than average birth size, maternal age ≤ 18 years (AOR: 1.8; 95% CI: 1.1–3.2) and ≥ 35 years (AOR: 1.7; 95% CI: 1.3–2.3), and birth interval of < 2 years (AOR: 2.6; 95% CI: 1.4–4.9) had higher odds of early neonatal mortality. On the other hand, antenatal care by a skilled provider (AOR: 0.7; 95% CI: 0.5–0.9), facility delivery (AOR: 0.7; 955 CI: 0.5–0.9), paternal higher education level (AOR: 0.7; 95% CI: 0.5–1.0), living in north-western (AOR: 0.3; 95% CI: 0.1–0.6), central-western regions (AOR: 0.5; 95% CI: 0.3–0.9) and in a community with higher maternal education level (AOR: 0.4; 95% CI: 0.2–0.9) had negative association.ConclusionsSeveral individual, maternal and community level factors influence early neonatal deaths in Afghanistan; significance of the elements of multiple levels indicates that neonatal survival programs should follow a multifaceted approach to incorporate these associated factors. Programs should focus on birth interval prolongation with the promotion of family planning services, utilization of antenatal care and institutional delivery services along with management of preterm and sick infants to prevent this large number of deaths in this period.

BackgroundUrinary tract infection (UTI) in pregnancy, including asymptomatic bacteriuria, is associated with maternal morbidity and adverse pregnancy outcomes, including preterm birth and low birthweight. In low-middle income countries (LMICs), the capacity for screening and treatment of UTIs is limited. The objective of this study was to describe the population-based prevalence, risk factors, etiology and antimicrobial resistance patterns of UTIs in pregnancy in Bangladesh.MethodsIn a community-based cohort in Sylhet district, Bangladesh, urine specimens were collected at the household level in 4242 pregnant women (< 20 weeks gestation) for culture and antibiotic susceptibility testing. Basic descriptive analysis was performed, as well as logistic regression to calculate adjusted odds ratios (aOR) for UTI risk factors.ResultsThe prevalence of UTI was 8.9% (4.4% symptomatic UTI, 4.5% asymptomatic bacteriuria). Risk factors for UTI in this population included maternal undernutrition (mid-upper arm circumference <23 cm: aOR= 1.29, 95% CI: 1.03–1.61), primiparity (aOR= 1.45, 95% CI: 1.15–1.84), and low paternal education (no education: aOR= 1.56, 95% CI: 1.09–2.22). The predominant uro-pathogens were E. coli (38% of isolates), Klebsiella (12%), and staphyloccocal species (23%). Group B streptococcus accounted for 5.3% of uro-pathogens. Rates of antibiotic resistance were high, with only two-thirds of E. coli susceptible to 3rd generation cephalosporins.ConclusionsIn Sylhet, Bangladesh, one in 11 women had a UTI in pregnancy, and approximately half of cases were asymptomatic. There is a need for low-cost and accurate methods for UTI screening in pregnancy and efforts to address increasing rates of antibiotic resistance in LMIC.

This diagnostic/prognostic study describes the use of cell-free transcriptomics, urine metabolomics, and plasma proteomics for identifying the biological measurements associated with preterm birth.

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh’s national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia .  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

IntroductionReducing neonatal mortality rate (NMR) is a challenge in many low- and middle-income countries including Bangladesh. In 2014, the estimated NMR in this country was 28 per 1,000 live births. This rate is higher in rural regions compared to the national average. Currently, Sylhet Division has the highest NMR in Bangladesh. Investigating rates and determinants of neonatal mortality in rural regions of this high-risk division is particularly important to implement evidence-based programs. This study examined rates and determinants of neonatal deaths in a large rural cohort in Sylhet Division.MethodsWe analyzed data from a multi-country cohort study, Aetiology of Neonatal Infections in South Asia. From November 2011 to December 2013, this study was conducted in two rural sub-districts in Sylhet Division. Community health workers followed 28,960 pregnant women and their newborns up to two months postpartum and collected data on pregnancy outcomes and newborns’ survival status. The NMR was obtained by dividing total number of neonatal deaths with all studied newborns. Logistic regression was employed to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with neonatal mortality. Stata 14.0 was used for data analysis.ResultsThis study analyzed data of 21,227 newborns. The NMR was 43.4 (95% CI: 39.3–48.0) per 1,000 live births (N = 922). Multivariable analysis showed that the odds of neonatal mortality were significantly higher among male newborns (AOR: 1.5, 95% CI: 1.2–1.8), babies born before 34 weeks of gestation (AOR: 5.0, 95% CI: 4.1–6.1), those who were twins or triplets (AOR: 6.2, 95% CI: 3.6–10.9), and first-born child (AOR: 2.9, 95% CI: 1.6–5.3). Additionally, maternal age 30–35 years (AOR: 1.4, 95% CI: 1.-1.8), history of child death (AOR: 1.6, 95% CI: 1.2–2.2), and delivery complications (AOR: 2.1, 95% CI: 1.6–2.6) had positive associations with neonatal deaths.ConclusionPublic health programs in Bangladesh need to adopt a comprehensive strategy to address the individual, maternal, and intrapartum factors associated with neonatal mortality in rural regions. Interventions should aim to prioritize managing pre-term deliveries, first-born child, and delivery complications among pregnant women.

BackgroundReducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.MethodsWe conducted a matched case-control (1:3) study of 98 young infants aged 0–59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n = 18); the secondary outcome was bacteremia (n = 10).ResultsAng-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p = 0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p = 0.016) and in infants with bacteremia (aOR 5.72, p = 0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p = 0.013).ConclusionsThis study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1087-x) contains supplementary material, which is available to authorized users.