Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries

OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1–6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7–13 and 14–27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period

COVID-19 vaccination coverage is extremely low among older population in Bangladesh : findings from a cross-sectional study

This cross-sectional study was conducted in September 2021 among 1,045 Bangladeshi older adults aged 60 years or above to explore the COVID-19 vaccination coverage and its associated factors. We used a semi-structured questionnaire to collect data on participants’ sociodemographic and lifestyle characteristics, and COVID-19 related information (selected based on an extensive literature review). A multinomial logistic regression model was used to identify the factors independently associated with vaccine receipt. Nearly, two-thirds of the participants (64.5%) were unvaccinated and 12.5% received a single dose. Among the unvaccinated, approximately 94% reported that there was a problem in accessing the vaccine. We found that participants with formal schooling had 42% lower risk of being unvaccinated (RRR (Relative Risk Ratio) = 0.58, 95% CI 0.42–0.80) or 39% lower risk of receiving a single dose (RRR = 0.61, 95% CI 0.39–0.96) than the participants having no formal schooling. The middle family monthly income groups had 65% higher risk (RRR = 1.65, 95% CI 1.17–2.32) and rural participants had 84% higher risk (RRR = 1.84, 95% CI 1.26–2.70) of not receiving vaccines compared to their counterparts. Also, the participants with non-communicable chronic conditions had a significantly lower risk of being unvaccinated (RRR = 0.49, 95% CI 0.35–0.68) or receiving a single dose (RRR = 0.49, 95% CI 0.31–0.77) compared to their counterparts. This finding may help strengthen the existing efforts to maximize vaccine coverage among older populations in Bangladesh and reach herd immunity to break the transmission chain and gain greater overall population protection more rapidly

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries.

Objective: To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries. Methods: We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality. Findings: Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality. Conclusion: Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings

Incidence and risk factors of neonatal infections in a rural Bangladeshi population: a community-based prospective study

Background: Infections cause about one fifth of the estimated 2.7 million annual neonatal deaths worldwide. Population-based data on burden and risk factors of neonatal infections are lacking in developing countries, which are required for the appropriate design of effective preventive and therapeutic interventions in resource-poor settings. Methods: We used data from a community-based cluster-randomized trial conducted to evaluate the impact of two umbilical cord cleansing regimens with chlorhexidine solution on neonatal mortality and morbidity in a rural area of Sylhet District in Bangladesh. Newborns were assessed four times in the first 9 days of life by trained community health workers (CHWs) using a WHO IMCI-like clinical algorithm. Cumulative incidence of the first episode of infections in the first 9 days of life was estimated using survival analysis technique accounting for survival bias and competing risk of death before the occurrence of infection. A multivariable generalized estimating equation log-binomial regression model was used to identify factors independently associated with infections. Results: Between 2007 and 2009, 30,267 newborns who received at least one postnatal assessment visit by a CHW within the first 9 days of life were included in this study. Cumulative incidence of infections in the first 9 days of life was 14.5% (95% CI 14.1\u201314.9%). Significant risk factors included previous child death in the family [RR 1.10 (95% CI 1.02\u20131.19)]; overcrowding [RR 1.14 (95% CI 1.04\u20131.25)]; home delivery [RR 1.86 (95% CI 1.58\u20132.19)]; unclean cord care [RR 1.15 (95% CI 1.03\u20131.28)]; multiple births [RR 1.34 (95% CI 1.15\u20131.56)]; low birth weight [reference: 65 2500 g, RR (95% CI) for < 1500, 1500\u20131999, and 2000\u20132499 g were 4.69 (4.01\u20135.48), 2.15 (1.92\u20132.42), and 1.15 (1.07\u20131.25) respectively]; and birth asphyxia [RR 1.65 (1.51\u20131.81)]. Higher pregnancy order lowered the risk of infections in the study population [compared to first pregnancy, RR (95% CI) for second, third, and 65 fourth pregnancy babies were 0.93 (0.85\u20131.02), 0.88 (0.79\u20130.97), and 0.79 (0.71\u20130.87), respectively]. Conclusion: Neonatal infections and associated deaths can be reduced by identifying and following up high-risk mothers and newborns and promoting facility delivery and clean cord care in resource-poor countries like Bangladesh where the burden of clinically ascertained neonatal infections is high. Further research is needed to measure the burden of infections in the entire neonatal period, particularly in the second fortnight and its association with essential newborn care. Trial registration: NCT00434408. Registered February 9, 2007

Safety and effi cacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial

Background Severe infections remain one of the main causes of neonatal deaths worldwide. Possible severe infection is diagnosed in young infants (aged 0–59 days) according to the presence of one or more clinical signs. The recommended treatment is hospital admission with 7–10 days of injectable antibiotic therapy. In low-income and middle-income countries, barriers to hospital care lead to delayed, inadequate, or no treatment for many young infants. We aimed to identify eff ective alternative antibiotic regimens to expand treatment options for situations where hospital admission is not possible. Methods We did this randomised, open-label, equivalence trial in four urban hospitals and one rural fi eld site in Bangladesh to determine whether two alternative antibiotic regimens with reduced numbers of injectable antibiotics combined with oral antibiotics had similar effi cacy and safety to the standard regimen, which was also used as outpatient treatment. We randomly assigned infants who showed at least one clinical sign of severe, but not critical, infection (except fast breathing alone), whose parents refused hospital admission, to one of the three treatment regimens. We stratifi ed randomisation by study site and age (<7 days or 7–59 days) using computer-generated randomisation sequences. The standard treatment was intramuscular procaine benzylpenicillin and gentamicin once per day for 7 days (group A). The alternative regimens were intramuscular gentamicin once per day and oral amoxicillin twice per day for 7 days (group B) or intramuscular procaine benzylpenicillin and gentamicin once per day for 2 days, then oral amoxicillin twice per day for 5 days (group C). The primary outcome was treatment failure within 7 days after enrolment. Assessors of treatment failure were masked to treatment allocation. Primary analysis was per protocol. We used a prespecifi ed similarity margin of 5% to assess equivalence between regimens. This study is registered with ClinicalTrials.gov, number NCT00844337. Findings Between July 1, 2009, and June 30, 2013, we recruited 2490 young infants into the trial. We assigned 830 infants to group A, 831 infants to group B, and 829 infants to group C. 2367 (95%) infants fulfi lled per-protocol criteria. 78 (10%) of 795 per-protocol infants had treatment failure in group A compared with 65 (8%) of 782 infants in group B (risk diff erence –1·5%, 95% CI –4·3 to 1·3) and 64 (8%) of 790 infants in group C (–1·7%, –4·5 to 1·1). In group A, 14 (2%) infants died before day 15, compared with 12 (2%) infants in group B and 12 (2%) infants in group C. Non-fatal relapse rates were similar in all three groups (12 [2%] infants in group A vs 13 [2%] infants in group B and 10 [1%] infants in group C). Interpretation 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 effi cacious as the standard regimen. This fi nding could increase treatment options in resource-poor settings when referral care is not available or acceptable

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries.

OBJECTIVE: To estimate neonatal mortality, particularly within 24 hours of birth, in six low- and lower-middle-income countries. METHODS: We analysed epidemiological data on a total of 149 570 live births collected between 2007 and 2013 in six prospective randomized trials and a cohort study from predominantly rural areas of Bangladesh, Ghana, India, Pakistan, the United Republic of Tanzania and Zambia. The neonatal mortality rate and mortality within 24 hours of birth were estimated for all countries and mortality within 6 hours was estimated for four countries with available data. The findings were compared with published model-based estimates of neonatal mortality. FINDINGS: Overall, the neonatal mortality rate observed at study sites in the six countries was 30.5 per 1000 live births (range: 13.6 in Zambia to 47.4 in Pakistan). Mortality within 24 hours was 14.1 per 1000 live births overall (range: 5.1 in Zambia to 20.1 in India) and 46.3% of all neonatal deaths occurred within 24 hours (range: 36.2% in Pakistan to 65.5% in the United Republic of Tanzania). Mortality in the first 6 hours was 8.3 per 1000 live births, i.e. 31.9% of neonatal mortality. CONCLUSION: Neonatal mortality within 24 hours of birth in predominantly rural areas of six low- and lower-middle-income countries was higher than model-based estimates for these countries. A little under half of all neonatal deaths occurred within 24 hours of birth and around one third occurred within 6 hours. Implementation of high-quality, effective obstetric and early newborn care should be a priority in these settings

Validation of community health worker identification of maternal puerperal sepsis using a clinical diagnostic algorithm in Bangladesh and Pakistan.

BACKGROUND: Puerperal sepsis (PP sepsis) is a leading cause of maternal mortality globally. The majority of maternal sepsis cases and deaths occur at home and remain undiagnosed and under-reported. In this paper, we present findings from a nested case-control study in Bangladesh and Pakistan which sought to assess the validity of community health worker (CHW) identification of PP sepsis using a clinical diagnostic algorithm with physician assessment and classification used as the gold standard. METHODS: Up to 300 postpartum women were enrolled in each of the 3 sites 1) Sylhet, Bangladesh (n = 278), 2) Karachi, Pakistan (n = 278) and 3) Matiari, Pakistan (n = 300). Index cases were women with suspected PP Sepsis as diagnosed by CHWs clinical assessment of one or more of the following signs and symptoms: temperature (recorded fever ≥38.1°C, reported history of fever, lower abdominal or pelvic pain, and abnormal or foul-smelling discharge. Each case was matched with 3 control women who were diagnosed by CHWs to have no infection. Cases and controls were assessed by trained physicians using the same algorithm implemented by the CHWs. Using physician assessment as the gold standard, Kappa statistics for reliability and diagnostic validity (sensitivity and specificity) are presented with 95% CI. Sensitivity and specificity were adjusted for verification bias. RESULTS: The adjusted sensitivity and specificity of CHW identification of PP sepsis across all sites was 82% (Karachi: 78%, Matiari: 78%, Sylhet: 95%) and 90% (Karachi: 95%, Matiari: 85%, Sylhet: 90%) respectively. CHW-Physician agreement was highest for moderate and high fever (range across sites: K = 0.84-0.97) and lowest for lower abdominal pain (K = 0.30-0.34). The clinical signs and symptoms for other conditions were reported infrequently, however, the CHW-physician agreement was high for all symptoms except severe headache/ blurred vision (K = 0.13-0.38) and reported "lower abdominal pain without fever" (K = 0.39-0.57). CONCLUSION: In all sites, CHWs with limited training were able to identify signs and symptoms and to classify cases of PP sepsis with high validity. Integrating postpartum infection screening into existing community-based platforms and post-natal visits is a promising strategy to monitor women for PP sepsis - improving delivery of cohesive maternal and child health care in low resource settings

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh [version 1; referees: 1 approved, 2 approved with reservations]

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

An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis Thaliana is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications

Infectious aetiologies of neonatal illness in south Asia classified using WHO definitions: a primary analysis of the ANISA study.

BACKGROUND: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. METHODS: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. FINDINGS: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. INTERPRETATION: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. FUNDING: The Bill and Melinda Gates Foundation