Young Infant Mortality Associated with Preterm and Small-for-Gestational-Age Births in Rural Bangladesh: A Prospective Cohort Study.

OBJECTIVE: To assess the relative risk of mortality in infants born preterm and small for gestational age (SGA) during the first and second months of life in rural Bangladesh. STUDY DESIGN: We analyzed data from a cohort of pregnant women and their babies in Sylhet, Bangladesh, assembled between 2011 and 2014. Community health workers visited enrolled babies up to 10 times from birth to age 59 days. Survival status was recorded at each visit. Gestational age was estimated from mother's reported last menstrual period. Birth weights were measured within 72 hours of delivery. SGA was defined using the INTERGROWTH-21st standard. We estimated unadjusted and adjusted hazard ratios (HRs) and corresponding 95% CIs for babies born preterm and SGA separately for the first and second month of life using bivariate and multivariable weighted Cox regression models. RESULTS: The analysis included 17 643 singleton live birth babies. Compared with infants born at term-appropriate for gestational age, in both unadjusted and adjusted analyses, infants born preterm-SGA had the greatest risk of death in the first (HR 13.25, 95% CI 8.65-20.31; adjusted HR 12.05, 95% CI 7.82-18.57) and second month of life (HR 4.65, 95% CI 1.93-11.23; adjusted HR 4.1, 95% CI 1.66-10.15), followed by infants born preterm-appropriate for gestational age and term-SGA. CONCLUSIONS: The risk of mortality in infants born preterm and/or SGA is increased and extends through the second month of life. Appropriate interventions to prevent and manage complications caused by prematurity and SGA could improve survival during and beyond the neonatal period.

Analysis of isolates from Bangladesh highlights multiple ways to carry resistance genes in Salmonella Typhi.

BACKGROUND: Typhoid fever, caused by Salmonella Typhi, follows a fecal-oral transmission route and is a major global public health concern, especially in developing countries like Bangladesh. Increasing emergence of antimicrobial resistance (AMR) is a serious issue; the list of treatments for typhoid fever is ever-decreasing. In addition to IncHI1-type plasmids, Salmonella genomic island (SGI) 11 has been reported to carry AMR genes. Although reports suggest a recent reduction in multidrug resistance (MDR) in the Indian subcontinent, the corresponding genomic changes in the background are unknown. RESULTS: Here, we assembled and annotated complete closed chromosomes and plasmids for 73 S. Typhi isolates using short-length Illumina reads. S. Typhi had an open pan-genome, and the core genome was smaller than previously reported. Considering AMR genes, we identified five variants of SGI11, including the previously reported reference sequence. Five plasmids were identified, including the new plasmids pK91 and pK43; pK43and pHCM2 were not related to AMR. The pHCM1, pPRJEB21992 and pK91 plasmids carried AMR genes and, along with the SGI11 variants, were responsible for resistance phenotypes. pK91 also contained qnr genes, conferred high ciprofloxacin resistance and was related to the H58-sublineage Bdq, which shows the same phenotype. The presence of plasmids (pHCM1 and pK91) and SGI11 were linked to two H58-lineages, Ia and Bd. Loss of plasmids and integration of resistance genes in genomic islands could contribute to the fitness advantage of lineage Ia isolates. CONCLUSIONS: Such events may explain why lineage Ia is globally widespread, while the Bd lineage is locally restricted. Further studies are required to understand how these S. Typhi AMR elements spread and generate new variants. Preventive measures such as vaccination programs should also be considered in endemic countries; such initiatives could potentially reduce the spread of AMR.

Follow-up of cases of Haemophilus influenzae type b meningitis to determine its long-term sequelae.

OBJECTIVE: To measure physical and neurologic impact of Haemophilus influenzae type b (Hib) meningitis on surviving children through short- and long-term follow-up. STUDY DESIGN: Cases of Hib meningitis, diagnosed at a tertiary level pediatric hospital, were subjected to short- and long-term follow-up and compared with age, sex, and area of residence matched healthy controls. Follow-up assessments included thorough physical and neurodevelopmental assessments using a standardized protocol by a multidisciplinary team. RESULTS: Assessments of short-term follow-up cohort (n = 64) revealed hearing, vision, mental, and psychomotor deficits in 7.8%, 3%, 20%, and 25% of the cases, respectively. Deficits were 10%, 1.4%, 21%, and 25% in long-term follow-up cohort (n = 71), in that order. Mental and psychomotor deficits were found in 2% of the controls, none of whom had vision or hearing deficits. CONCLUSIONS: In addition to risk of death, Hib meningitis in children causes severe disabilities in survivors. These data facilitated a comprehensive understanding of the burden of Hib meningitis, specifically in developing countries where disabled children remain incapacitated because of lack of resources and facilities. The evidence generated from this study is expected to provide a compelling argument in favor of introduction and continuation of Hib conjugate vaccine in the national immunization program for children.

Impact of introduction of the Haemophilus influenzae type b conjugate vaccine into childhood immunization on meningitis in Bangladeshi infants.

OBJECTIVES: Some Asian countries have been reluctant to adopt Haemophilus influenzae type b (Hib) conjugate vaccination because of uncertainty over disease burden. We assessed the impact of introduction of Hib conjugate vaccine into the Expanded Program on Immunization in Bangladesh on purulent and laboratory-confirmed H influenzae meningitis. STUDY DESIGN: Within a well-defined catchment area around 2 surveillance hospitals in Dhaka, Bangladesh, we compared the incidence of Hib meningitis confirmed by culture, latex agglutination, and polymerase chain reaction assay among infants 1 year before and 1 year after introduction of Hib conjugate vaccine. We adjusted the incidence rate for the proportion of children who sought care at the surveillance hospitals. RESULTS: Among infants, the incidence of confirmed Hib meningitis decreased from 92-16 cases per 100,000 within 1 year of vaccine introduction (vaccine preventable incidence = 76; 95% CI 18, 135 per 100,000). The incidence of purulent meningitis decreased from 1659-1159 per 100,000 (vaccine preventable incidence = 500; 95% CI: 203, 799 per 100,000). During the same time period, there was no significant difference in the incidence of meningitis due to Streptococcus pneumoniae. CONCLUSIONS: Introduction of conjugate Hib conjugate vaccine into Bangladesh Expanded Program on Immunization markedly reduced the burden of Hib and purulent meningitis.

Simplified age-weight mortality risk classification for very low birth weight infants in low-resource settings.

OBJECTIVE: To identify a valid neonatal mortality risk prediction score feasible for use in developing countries. STUDY DESIGN: Retrospective study of 467 neonates, < or =1500 g, enrolled in trials during 1998 to 2005 at tertiary care children's hospitals in Dhaka, Bangladesh, and Cairo, Egypt, and a community field site in Sarlahi District, Nepal. We derived simplified mortality risk scores and compared their predictive accuracy with the modified Clinical Risk Index for Babies (CRIB) II. Outcome was death during hospital stay (Dhaka and Cairo) or end of the neonatal period (Nepal). RESULTS: The area under the curve receiver operating characteristic was 0.62, 0.71, 0.68, and 0.69 on the basis of the (a) CRIB II applied to the Dhaka-Cairo dataset; (b) an 18-category, simplified age, weight, sex score; (c) a binary-risk simplified age-weight (SAW) classification derived from the Dhaka-Cairo dataset; and (d) external validation of the binary-risk SAW classification in the Nepal dataset, respectively. Mortality risk prediction with the SAW classification on the basis of gestational age (< or =29 weeks) or weight (<1000 g) was improved (P = .048) compared with CRIB II. CONCLUSIONS: The SAW classification is a markedly simplified mortality risk prediction score for use in identifying high-risk, very low birth weight neonates in developing country settings for whom urgent referral is indicated.

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics.

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.