Infectious Diseases and Vaccine Sciences: Strategic Directions

Despite substantial progress, infectious diseases remain important causes of ill-health and premature deaths in Bangladesh. Bangladesh has experienced a >90% reduction in the incidence of deaths due to childhood diarrhoea over the last 25 years. Further reductions can be achieved through the introduction of effective vaccines against rotavirus and improvements in home hygiene, quality of drinking-water, and clinical case management, including appropriate use of oral rehydration solution and zinc. Pneumonia is now the leading cause of childhood deaths in Bangladesh, and the pneumonia-specific child mortality is largely unchanged over the last 25 years. Reductions in mortality due to pneumonia can be achieved through the introduction of protein conjugate vaccines against Haemophilus influenza type b and Streptococcus pneumoniae, improvements in case management, including efforts to prevent delays in providing appropriate treatment, and the wider use of zinc. Tuberculosis is responsible for an estimated 70,000 deaths each year in Bangladesh. Although services for directly-observed therapy have expanded markedly, improved case finding and involvement of private practitioners will be important to reduce the burden of disease

Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.

Background. There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods. In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. Results. Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)–positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (\u3c3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. Conclusions. There is evidence for an association between H. influenzaecolonization density and H. influenzae–confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings

Human Metapneumovirus Infection among Children, Bangladesh

We confirmed circulation of human metapneumovirus (HMPV) among children with febrile and respiratory illness in an urban slum in Dhaka, Bangladesh, during active surveillance in 2001. HMPV was the most common single virus identified among febrile children and appears to contribute to the high rates of illness in this population

Infectious Diseases and Vaccine Sciences: Strategic Directions

Despite substantial progress, infectious diseases remain important causes of ill-health and premature deaths in Bangladesh. Bangladesh has experienced a >90% reduction in the incidence of deaths due to childhood diarrhoea over the last 25 years. Further reductions can be achieved through the introduction of effective vaccines against rotavirus and improvements in home hygiene, quality of drinking-water, and clinical case management, including appropriate use of oral rehydration solution and zinc. Pneumonia is now the leading cause of childhood deaths in Bangladesh, and the pneumonia-specific child mortality is largely unchanged over the last 25 years. Reductions in mortality due to pneumonia can be achieved through the introduction of protein conjugate vaccines against Haemophilus influenza type b and Streptococcus pneumoniae , improvements in case management, including efforts to prevent delays in providing appropriate treatment, and the wider use of zinc. Tuberculosis is responsible for an estimated 70,000 deaths each year in Bangladesh. Although services for directly-observed therapy have expanded markedly, improved case finding and involvement of private practitioners will be important to reduce the burden of disease

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: A systematic review and modelling study

Background: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.Methods: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.Findings: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.Interpretation: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.Funding: Bill & Melinda Gates Foundation

Causes of Early Childhood Deaths in Urban Dhaka, Bangladesh

Data on causes of early childhood death from low-income urban areas are limited. The nationally representative Bangladesh Demographic and Health Survey 2007 estimates 65 children died per 1,000 live births. We investigated rates and causes of under-five deaths in an urban community near two large pediatric hospitals in Dhaka, Bangladesh and evaluated the impact of different recall periods. We conducted a survey in 2006 for 6971 households and a follow up survey in 2007 among eligible remaining households or replacement households. The initial survey collected information for all children under five years old who died in the previous year; the follow up survey on child deaths in the preceding five years. We compared mortality rates based on 1-year recall to the 4 years preceding the most recent 1 year. The initial survey identified 58 deaths among children <5 years in the preceding year. The follow up survey identified a mean 53 deaths per year in the preceding five years (SD±7.3). Under-five mortality rate was 34 and neonatal mortality was 15 per thousand live births during 2006–2007. The leading cause of under-five death was respiratory infections (22%). The mortality rates among children under 4 years old for the two time periods (most recent 1-year recall and the 4 years preceding the most recent 1 year) were similar (36 versus 32). The child mortality in urban Dhaka was substantially lower than the national rate. Mortality rates were not affected by recall periods between 1 and 5 years

Tropical influenza and weather variability among children in an urban low-income population in Bangladesh

Background: Influenza seasonality in the tropics is poorly understood and not as well documented as in temperate regions. In addition, low-income populations are considered highly vulnerable to such acute respiratory disease, owing to limited resources and overcrowding. Nonetheless, little is known about their actual disease burden for lack of data. We therefore investigated associations between tropical influenza incidence and weather variability among children under five in a poor urban area of Dhaka, Bangladesh.Design: Acute respiratory illness data were obtained from a population-based respiratory and febrile illness surveillance dataset of Kamalapur, a low-income urban area in southeast Dhaka. Analyzed data were from January 2005 through December 2008. Nasopharyngeal wash specimens were collected from every fifth eligible surveillance participant during clinic visits to identify influenza virus infection with viral culture and reverse transcriptase?polymerase chain reaction. Time series analysis was conducted to determine associations between the number of influenza cases per week and weather factors. Zero-inflated Poisson and generalized linear Poisson models were used in the analysis for influenza A and B, respectively.Results: Influenza A had associations with minimum temperature, relative humidity (RH), sunlight duration, and rainfall, whereas only RH was associated with influenza B. Although associations of the other weather factors varied between the two subtypes, RH shared a similar positive association when humidity was approximately 50?70%.Conclusions: Our findings of a positive RH association is consistent with prior studies, and may suggest the viral response in the tropics. The characteristics of settlement areas, population demographics, and typical overcrowding of urban poverty may also contribute to different impacts of rainfall from higher economic population. Further investigations of associations between tropical influenza and weather variability for urban low-income populations are required for better understanding