Epidemiology and risk factors for pneumonia severity and mortality in Bangladeshi children <5 years of age before 10-valent pneumococcal conjugate vaccine introduction.

BACKGROUND: Pneumonia is the leading infectious cause of morbidity and mortality in young children in Bangladesh. We present the epidemiology of pneumonia in Bangladeshi children <5 years before 10-valent pneumococcal conjugate vaccine introduction and investigate factors associated with disease severity and mortality. METHODS: Children aged 2-59 months admitted to three Bangladeshi hospitals with pneumonia (i.e., cough or difficulty breathing and age-specific tachypnea without danger signs) or severe pneumonia (i.e., cough or difficulty breathing and ≥1 danger signs) were included. Demographic, clinical, laboratory, and vaccine history data were collected. We assessed associations between characteristics and pneumonia severity and mortality using multivariable logistic regression. RESULTS: Among 3639 Bangladeshi children with pneumonia, 61% had severe disease, and 2% died. Factors independently associated with severe pneumonia included ages 2-5 months (adjusted odds ratio [aOR] 1.60 [95% CI: 1.26-2.01]) and 6-11 months (aOR 1.31 [1.10-1.56]) relative to 12-59 months, low weight for age (aOR 1.22 [1.04-1.42]), unsafe drinking water source (aOR 2.00 [1.50-2.69]), higher paternal education (aOR 1.34 [1.15-1.57]), higher maternal education (aOR 0.74 [0.64-0.87]), and being fully vaccinated for age with pentavalent vaccination (aOR 0.64 [0.51-0.82]). Increased risk of pneumonia mortality was associated with age <12 months, low weight for age, unsafe drinking water source, lower paternal education, disease severity, and having ≥1 co-morbid condition. CONCLUSIONS: Modifiable factors for severe pneumonia and mortality included low weight for age and access to safe drinking water. Improving vaccination status could decrease disease severity.

Provider performance and facility readiness for managing infections in young infants in primary care facilities in rural Bangladesh.

BACKGROUND: Neonatal infections remain a leading cause of newborn deaths globally. In 2015, WHO issued guidelines for managing possible serious bacterial infection (PSBI) in young infants (0-59 days) using simplified antibiotic regimens when compliance with hospital referral is not feasible. Bangladesh was one of the first countries to adopt WHO's guidelines for implementation. We report results of an implementation research study that assessed facility readiness and provider performance in three rural sub-districts of Bangladesh during August 2015-August 2016. METHODS: This study took place in 19 primary health centers. Facility readiness was assessed using checklists completed by study staff at three time points. To assess provider performance, we extracted data for all infection cases from facility registers and compared providers' diagnosis and treatment against the guidelines. We plotted classification and dosage errors across the study period and superimposed a locally weighted smoothed (LOWESS) curve to analyze changes in performance over time. Focus group discussions (N = 2) and in-depth interviews (N = 28) with providers were conducted to identify barriers and facilitators for facility readiness and provider performance. RESULTS: At baseline, none of the facilities had adequate supply of antibiotics. During the 10-month period, 606 sick infants with signs of infection presented at the study facilities. Classification errors were identified in 14.9% (N = 90/606) of records. For infants receiving the first dose(s) of antibiotic treatment (N = 551), dosage errors were identified in 22.9% (N = 126/551) of the records. Distribution of errors varied by facility (35.7% [IQR: 24.7-57.4%]) and infection severity. Errors were highest at the beginning of the study period and decreased over time. Qualitative data suggest errors in early implementation were due to changes in providers' assessment and treatment practices, including confusion about classifying an infant with multiple signs of infection, and some providers' concerns about the efficacy of simplified antibiotic regimens. CONCLUSIONS: Strategies to monitor early performance and targeted supports are important for enhancing implementation fidelity when introducing complex guidelines in new settings. Future research should examine providers' assessment of effectiveness of simplified treatment and address misconceptions about superiority of broader spectrum antibiotics for treating community-acquired neonatal infections in this context.

Caregiver acceptability of the guidelines for managing young infants with possible serious bacterial infections (PSBI) in primary care facilities in rural Bangladesh.

INTRODUCTION: Many infants with possible serious bacterial infections (PSBI) do not receive inpatient treatment because hospital care may not be affordable, accessible, or acceptable for families. In 2015, WHO issued guidelines for managing PSBI in young infants (0-59 days) with simpler antibiotic regimens when hospital care is not feasible. Bangladesh adopted WHO's guidelines for implementation in outpatient primary health centers. We report results of an implementation research study that assessed caregiver acceptability of the guidelines in three rural sub-districts of Bangladesh during early implementation (October 2015-August 2016). METHODS: We included 19 outpatient primary health centers involved in the initial rollout of the infection management guidelines. We extracted data for all PSBI cases (N = 192) from facility registers to identify gaps in referral feasibility, simplified antibiotic treatment, and follow-up. Focus group discussions (FGD) and in-depth interviews (IDI) were conducted with both caregivers (6 FGDs; 23 IDIs) and providers (2 FGDs; 28 IDIs) to assess caregiver acceptability of the guidelines. RESULTS: Referral to the hospital was not feasible for many families (83.3%; N = 160/192) and acceptance varied by infection severity. Barriers to referral feasibility included economic and household factors, and previous experiences with poor quality of care at the sub-district hospital. Conversely, providers and caregivers indicated high acceptability of simplified antibiotic treatment. 80% (N = 96/120) of infants with clinical severe infection for whom referral was not feasible returned to the facility for the second antibiotic injection. Some providers reported developing local solutions-including engaging informal providers in treatment of the infant-to address organizational barriers and promote treatment compliance. Follow-up of young infants receiving simplified treatment is critical, but only 67.4% (N = 87/129) of infants received fourth day follow-up. Some providers' reported deviations from the guidelines that shifted responsibility of follow-up to the caregiver, which may have contributed to lapses. CONCLUSION: Caregivers' perception of trust and communication with providers were influential in caregiver acceptability of care. Few caregivers accepted referral to the sub-district hospital, suggesting low acceptability of this option. When referral was not feasible, many caregivers reported satisfaction with simplified antibiotic treatment. Local solutions described by providers require further examination in this context to assess the safety and potential value of these strategies in outpatient treatment. Our findings suggest strengthening providers' interpersonal skills could improve caregiver acceptability of the guidelines.

The Direct and Indirect Impact of SARS-CoV-2 Infections on Neonates: A Series of 26 Cases in Bangladesh.

BACKGROUND: The impact of SARS-CoV-2 on neonates remains largely unknown in low- and middle-income countries (LMICs). We provide an epidemiologic and clinical report of SARS-CoV-2 infections in neonates hospitalized in Bangladesh. METHODS: Outborn neonates admitted to Dhaka Shishu Hospital, a tertiary-care referral hospital, between 29 March and 1 July were screened for SARS-CoV-2. We reviewed clinical data, including chest radiograph and laboratory reports, and conducted SARS-CoV-2 genome sequencing. Patients were followed-up for 27-75 days. A subset of caregivers was also tested. RESULTS: Of 83 neonates tested, 26 were positive (median age 8 days). Most neonates were admitted with diagnosis unrelated to SARS-CoV-2: 11 presented with serious non-communicable diseases, 7 with early-onset sepsis, 5 with late-onset sepsis and 2 with pneumonia. In 3 of 5 chest radiograph, infiltrates and ground-glass or patchy opacities were noted. Two neonates developed metabolic acidosis, one developed disseminated intravascular coagulation. Most SARS-CoV-2 positive neonates were referred to government-designated COVID-19 hospitals, leading to gaps in treatment. Twenty-three neonates could be followed-up: 12 were healthy, 8 died and 3 were still seeking medical care. Of 9 caregivers tested, 8 were positive. CONCLUSIONS: SARS-CoV-2 may have serious adverse effects on children born in LMICs. The virus likely contributed directly to two deaths, but the remaining 6 neonates who died had serious comorbidities. Positive SARS-CoV-2 test results led to gaps in immediate clinical care for other morbidities, which likely contributed to adverse outcomes. This case series emphasizes the need to understand COVID-19 in neonates in LMICs and its indirect impacts.

Rotavirus Surveillance at a WHO-Coordinated Invasive Bacterial Disease Surveillance Site in Bangladesh: A Feasibility Study to Integrate Two Surveillance Systems.

The World Health Organization (WHO) currently coordinates rotavirus diarrhea and invasive bacterial disease (IBD) surveillance at 178 sentinel sites in 60 countries. However, only 78 sites participate in both surveillance systems using a common sentinel site. Here, we explored the feasibility of extending a WHO-IBD surveillance platform to generate data on the burden of rotaviral diarrhea and its epidemiological characteristics to prepare the countries to measure the impact of rotaviral vaccine. A six-month (July to December, 2012) surveillance, managed by IBD team, collected stool samples and clinical data from under-five children with acute watery diarrhea at an IBD sentinel site. Samples were tested for rotavirus antigen by ELISA and genotyped by PCR at the regional reference laboratory (RRL). Specimens were collected from 79% (n=297) of eligible cases (n=375); 100% of which were tested for rotavirus by ELISA and 54% (159/297) of them were positive. At RRL, all the cases were confirmed by PCR and genotyped (99%; 158/159). The typing results revealed the predominance of G12 (40%; 64/159) genotype, followed by G1 (31%; 50/159) and G9 (19%; 31/159). All in all, this exploratory surveillance collected the desired demographic and epidemiological data and achieved almost all the benchmark indicators of WHO, starting from enrollment number to quality assurance through a number of case detection, collection, and testing of specimens and genotyping of strains at RRL. The success of this WHO-IBD site in achieving these benchmark indicators of WHO can be used by WHO as a proof-of-concept for considering integration of rotavirus surveillance with WHO-IBD platforms, specifically in countries with well performing IBD site and no ongoing rotavirus surveillance.