Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate ...the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.
Summary Background 18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be ...only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. Methods We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0–17 years, 18–64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. Findings We estimate that globally there were 201 200 respiratory deaths (range 105 700–395 600) with an additional 83 300 cardiovascular deaths (46 000–179 900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Interpretation Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. Funding None.
Dengue viruses are responsible for over 100 million infections a year worldwide and are a public health concern in Bangladesh. Although risk of transmission is high, data on vector population ...characteristics are scanty in Bangladesh; therefore, a comprehensive prediction of the patterns of local virus transmission is not possible. Recognizing these gaps, multi-year entomological surveys were carried out in Dhaka, where the disease is most frequently reported. The specific objectives of the present study are threefold: i) to determine the risk factors for the presence of Aedes mosquitoes; ii) to identify the types of most productive and key containers; and iii) to estimate the effects of climatic factors on Aedes abundance in the city of Dhaka, Bangladesh. Entomological surveys were conducted in 12 out of 90 wards in Dhaka. These wards were selected using a probability proportional sampling procedure during the monsoon seasons in 2011, 2012 and 2013 and in the dry season in 2012. All containers inside and around sampled households were inspected for mosquito larvae and pupae, and containers were classified according to their relative size, use pattern, and materials of construction. During the study period (2011-2013), 12,680 larvae and pupae were collected. About 82% of the identified immature mosquitoes were Aedes aegypti, while the remainder were Ae. albopictus and other mosquito species. The largest number of immature mosquitoes was collected from tires and refrigerator trays during 2011 and 2012 monsoon seasons. Conversely, plastic drums were the most productive during the 2012 dry and 2013 monsoon season. Vehicle parts and discarded construction materials were the most efficient producers of Aedes mosquitoes in all surveys. The presence of Aedes mosquitoes was significantly (p < 0.05) higher in low socio-economic zones of Dhaka. Container location, presence of vegetation, and availability of shade for containers were also significantly associated with finding immature Aedes mosquitoes, based on multivariable analysis after confounder adjustment. Rainfall, temperature, and relative humidity also significantly affected the mean abundance of mosquitoes. Proper use, disposal, and recycling of the containers that effectively produce large numbers of Aedes vector mosquitoes may decrease the risk of arboviral transmission.
Oseltamivir has been used to treat children with influenza for nearly 2 decades, with treatment currently approved for infants aged ≥2 weeks. However, efficacy and safety remain controversial. Newer ...randomized, placebo-controlled trials (RCTs), not included in previous meta-analyses, can add to the evidence base.
We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a 2-stage, random-effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RMST) by treatment group. We also examined complications and safety.
We identified 5 trials that included 2561 patients in the intention-to-treat (ITT) and 1598 in the intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference, -17.6 hours; 95% confidence interval CI, -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours; 95% CI, -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group.
Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.
Summary Background The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory ...infections associated with influenza in children younger than 5 years. Methods We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality. Findings We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49–162 million) new cases of influenza (data from nine studies), 20 million (13–32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1–2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28 000–111 500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting. Interpretation Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available. Funding WHO; Bill & Melinda Gates Foundation.
Summary Background Influenza causes substantial morbidity and mortality worldwide. Few data exist for the efficacy of neuraminidase inhibitors, which are the only readily available influenza ...treatment options, especially in low-income settings. We assessed the efficacy of treatment with the neuraminidase inhibitor oseltamivir to reduce patient illness and viral shedding in people with influenza, in whom treatment was started within 5 days of symptom onset, in an urban setting in Bangladesh. Methods We undertook a double-blind, randomised, controlled trial between May, 2008, and December, 2010. Patients with a positive rapid influenza test identified by surveillance of households in Kamalapur, Bangladesh were randomly allocated on a 1:1 basis to receive oseltamivir or placebo twice daily for 5 days. Randomisation lists for individuals enrolled less than 48 h and 48 h or longer since illness onset were generated with permuted blocks of variable length between two and eight. Participants and study staff were masked to treatment group. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days later, and were visited daily to record symptoms. All specimens were tested for influenza with reverse-transcriptase PCR, and if the result was positive, we isolated the virus. The primary endpoints were duration of clinical illness and viral shedding in patients treated less than and more than 48 h since illness onset and the frequency of oseltamivir resistance during treatment. Analyses were intention to treat unless otherwise specified. This trial is registered with ClinicalTrials.gov , number NCT00707941. Findings Overall, 1190 people with a median age of 5 years (IQR 2–9) were enrolled: 794 (67%) less than 48 h since symptom onset and 396 (33%) 48 h or longer since symptom onset. 592 participants were assigned to placebo and 598 to oseltamivir. The median duration of symptoms was shorter in the oseltamivir group (3 days, IQR 1–5) than in the placebo group (4 days, 1–6; p=0·01). When stratified by timing of treatment initiation, in participants enrolled 48 h or longer since illness onset, the median duration of symptoms was similar in both groups (oseltamivir 3 days IQR 2–5, placebo 3 days 1–5; p=0·04). The median duration of symptoms was reduced by 1 day in the group given oseltamivir who were enrolled less than 48 h since symptom onset compared with those given placebo, but this difference was not significant. In those with all swab specimens (n=1134), oseltamivir significantly reduced virus isolation on days 2 (placebo 374 66% vs oseltamivir 321 56%; difference 15·2%, 95% CI 9·5–20·8, p=0·0004), 4 (241 43% vs 174 30%; difference 30·2%, 95% CI 24·6–35·8, p<0·0001), and 7 (68 12% vs 36 6%; difference 47·5%, 95% CI 44·2–50·8, p=0·0009). In participants enrolled 48 h or longer since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2 and 4, but not day 7. In participants enrolled less than 48 h since illness onset, oseltamivir treatment significantly reduced virus isolation on days 2, 4, and 7. The emergency of resistance to oseltamivir during treatment was rare overall (<1%) and in influenza A H1N1pdm09 viruses (3·9%). Interpretation Oseltamivir treatment resulted in a modest reduction in the duration of symptoms and virus shedding in people with uncomplicated influenza infections, even when treatment was started 48 h or longer after illness onset. Funding Centers for Disease Control and Prevention (in agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh).
Better understanding the etiology-specific incidence of severe acute respiratory infections (SARIs) in resource-poor, rural settings will help further develop and prioritize prevention strategies. To ...address this gap in knowledge, we conducted a longitudinal study to estimate the incidence of SARIs among children in rural Bangladesh.
During June through October 2010, we followed children aged <5 years in 67 villages to identify those with cough, difficulty breathing, age-specific tachypnea and/or danger signs in the community or admitted to the local hospital. A study physician collected clinical information and obtained nasopharyngeal swabs from all SARI cases and blood for bacterial culture from those hospitalized. We tested swabs for respiratory syncytial virus (RSV), influenza viruses, human metapneumoviruses, adenoviruses and human parainfluenza viruses 1-3 (HPIV) by real-time reverse transcription polymerase chain reaction. We calculated virus-specific SARI incidence by dividing the number of new illnesses by the person-time each child contributed to the study.
We followed 12,850 children for 279,029 person-weeks (pw) and identified 141 SARI cases; 76 (54%) at their homes and 65 (46%) at the hospital. RSV was associated with 7.9 SARI hospitalizations per 100,000 pw, HPIV3 2.2 hospitalizations/100,000 pw, and influenza 1.1 hospitalizations/100,000 pw. Among non-hospitalized SARI cases, RSV was associated with 10.8 illnesses/100,000 pw, HPIV3 1.8/100,000 pw, influenza 1.4/100,000 pw, and adenoviruses 0.4/100,000 pw.
Respiratory viruses, particularly RSV, were commonly associated with SARI among children. It may be useful to explore the value of investing in prevention strategies, such as handwashing and respiratory hygiene, to reduce respiratory infections among young children in such settings.
Pneumonia is the leading cause of child mortality worldwide. The role of influenza in childhood pneumonia in tropical developing countries is poorly understood. We undertook population-based ...surveillance among low-income urban preschool children to determine its role in childhood pneumonia.
Longitudinal prospective active surveillance was conducted among randomly selected households in a poor urban area of Dhaka. Nasopharyngeal washes were collected from 1 in 5 children for influenza culture isolation. Clinical data were collected at clinical presentation and through the illness course.
From April 1, 2004 through December 31, 2007, 12,062 children presented in clinic with eligible febrile and respiratory illnesses, from whom 321 influenza isolates were obtained from 2370 nasopharyngeal washes (13.5%), representing 16,043 child-years of observation (adjusted influenza incidence 102 episodes/1000 child-years). There were 8198 pneumonia episodes during the period (pneumonia incidence 511 episodes/1000 child-years). Ninety influenza-positive children (28%) developed pneumonia during their illness. Among influenza culture-positive children, those with pneumonia were younger than those without (23.4 vs. 29.7 months, ANOVA: P < 0.001). Pneumonia was more commonly associated with Influenza A (H3N2) than either A (H1N1) or B infections (age-adjusted relative odds (RO) 2.98, 95% CI: 1.56, 5.71 and 2.75, 95% CI: 1.52, 4.98, respectively). Influenza was associated with 10% all childhood pneumonia.
Influenza is a major contributor to childhood pneumonia both through high influenza infection incidence and high pneumonia prevalence among infected children. Its contribution to early childhood pneumonia appears under-appreciated in high pneumonia-endemic tropical settings. Influenza vaccine trials against childhood pneumonia are warranted.
Pneumonia is an illness, usually caused by infection, in which the lungs become inflamed and congested, reducing oxygen exchange and leading to cough and breathlessness. It affects individuals of all ...ages but occurs most frequently in children and the elderly. Among children, pneumonia is the most common cause of death worldwide. Historically, in developed countries, deaths from pneumonia have been reduced by improvements in living conditions, air quality, and nutrition. In the developing world today, many deaths from pneumonia are also preventable by immunization or access to simple, effective treatments. However, as we highlight here, there are critical gaps in our understanding of the epidemiology, etiology, and pathophysiology of pneumonia that, if filled, could accelerate the control of pneumonia and reduce early childhood mortality.
Dengue virus (DENV) activity has been reported in Dhaka, Bangladesh since the early 1960s with the greatest burden of dengue fever and dengue hemorrhagic fever cases observed in 2000. Since this ...time, the intensity of dengue activity has varied from year to year, and its determining factors remained relatively unknown. In light of such gaps in knowledge, the main objectives of this study were to determine the magnitude of seroprevalence and seroconversion among the surveyed population, and establish the individual/household level risk factors for the presence of DENV antibodies among all age groups of target populations in the city of Dhaka.
Considering the lack of fine scale investigations on the factors driving dengue activity in Bangladesh, a prospective cohort study involving serological surveys was undertaken with participant interviews and blood donation across the city of Dhaka in 2012. Study participants were recruited from 12 of 90 wards and blood samples were collected during both the pre-monsoon (n = 1125) and post-monsoon (n = 600) seasons of 2012. The findings revealed that the seroprevalence in all pre-monsoon samples was 80.0% (900/1125) while the seropositivity in the pre-monsoon samples that had paired post-monsoon samples was 83.3% (503/600). Of the 97 paired samples that were negative at the pre-monsoon time point, 56 were positive at the post-monsoon time point. This resulted in a seroprevalence of 93.2% (559/600) among individuals tested during the post-monsoon period. Seroprevalence trended higher with age with children exhibiting a lower seropositivity as compared to adults. Results from this study also indicated that DENV strains were the only flaviviruses circulating in Dhaka in 2012. A multivariate analysis revealed that age, possession of indoor potted plants, and types of mosquito control measures were significant factors associated with DENV seroprevalence; while attendance in public/mass gatherings, and use of mosquito control measures were significantly associated with DENV seroconversion after adjusting for all other variables.
Our study suggests that there is a high level of endemic dengue virus circulation in the city of Dhaka which has resulted in significant DENV seroprevalence among its residents. Seropositivity increased with age, however, a substantial proportion of children are at risk for DENV infections. Our serological analysis also documents considerable DENV seroconversion among study participants which indicates that a large proportion of the population in the city of Dhaka were newly exposed to DENV during the study period (pre-and post-monsoon 2012). High levels of seroconversion suggest that there was an intense circulation of DENV in 2012 and this may have resulted in a significant risk for viral associated illness. Findings of our study further indicated that home-based interventions, such as removing indoor potted plants and increased bed net use, in addition to vector control measures in public parks, would reduce exposure to DENV and further decrease risk of viral associated disease.
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