W. Abdullah Brooks

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

BACKGROUNDnThe 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.nnnMETHODSnWe 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by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies.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.nnnFINDINGSnWe 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.nnnINTERPRETATIONnInfluenza 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.nnnFUNDINGnWHO; Bill & Melinda Gates Foundation.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis.

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 265u2008000 (95% CI 160u2008000–450u2008000) 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.

Bacteremic Typhoid Fever in Children in an Urban Slum, Bangladesh

We confirmed a bacteremic typhoid fever incidence of 3.9 episodes/1,000 person-years during fever surveillance in a Dhaka urban slum. The relative risk for preschool children compared with older persons was 8.9. Our regression model showed that these children were clinically ill, which suggests a role for preschool immunization.

Pneumonia research to reduce childhood mortality in the developing world

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.

Influenza is a major contributor to childhood pneumonia in a tropical developing country

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Leptospirosis during Dengue Outbreak, Bangladesh

We collected acute-phase serum samples from febrile patients at 2 major hospitals in Dhaka, Bangladesh, during an outbreak of dengue fever in 2001. A total of 18% of dengue-negative patients tested positive for leptospirosis. The case-fatality rate among leptospirosis patients (5%) was higher than among dengue fever patients (1.2%).

Identification of In Vivo-Induced Bacterial Protein Antigens during Human Infection with Salmonella enterica Serovar Typhi

ABSTRACT We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses.

Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

Burden of typhoid and paratyphoid fever in a densely populated urban community, Dhaka, Bangladesh

BACKGROUNDnWe conducted blood culture surveillance to estimate the incidence of typhoid and paratyphoid fever among urban slum residents in Dhaka, Bangladesh.nnnMETHODSnBetween January 7, 2003 and January 6, 2004, participants were visited weekly to detect febrile illnesses. Blood cultures were obtained at the clinic from patients with fever (≥38°C). Salmonella isolates were assayed for antimicrobial susceptibility.nnnRESULTSnForty Salmonella Typhi and eight Salmonella Paratyphi A were isolated from 961 blood cultures. The incidence of typhoid fever was 2.0 episodes/1000 person-years, with a higher incidence in children aged<5 years (10.5/1000 person-years) than in older persons (0.9/1000 person-years) (relative risk=12, 95% confidence interval (CI) 6.3-22.6). The incidence of paratyphoid fever was 0.4/1000 person-years without variation by age group. Sixteen S. Typhi isolates were multidrug-resistant (MDR). All S. Paratyphi isolates were pan-susceptible. The duration of fever among patients with an MDR S. Typhi infection was longer than among patients with non-MDR S. Typhi (16±8 vs. 11±4 days, p=0.02) and S. Paratyphi (10±2 days, p=0.04) infections.nnnCONCLUSIONSnTyphoid fever is more common than paratyphoid fever in the urban Bangladeshi slum; children<5 years old have the highest incidence. Multidrug resistance is common in S. Typhi isolates and is associated with prolonged illness. Strategies for typhoid fever prevention in children aged<5 years in Bangladesh, including immunization, are needed.

Multihospital Surveillance of Pneumonia Burden among Children Aged <5 Years Hospitalized for Pneumonia in Bangladesh

BACKGROUNDnPneumonia contributes substantially to childhood mortality in Bangladesh. We conducted a study to characterize the disease severity and risk factors for mortality among children hospitalized for pneumonia in Bangladesh.nnnMETHODSnWe analyzed data on hospitalization, patient characteristics, and mortality collected by a multicenter hospital-based surveillance of pneumonia in Bangladesh.nnnRESULTSnFrom May 2004 through April 2007, 4155 children aged 2-59 months who met a pneumonia case definition adopted by GAVIs Pneumococcal Vaccines Accelerated Development and Introduction Plan-sponsored surveillance networks were enrolled after blood culture specimens were obtained. The mean duration (+/-SD) from illness onset to hospital admission was 6+/- days; 1842 children (44%) received antimicrobial treatment before hospitalization, and an additional 924 (22%) received antimicrobial treatment after admission to the hospital. Bacteria were isolated from 161 (4%) of the 4155 specimens, including 10 (6%) Streptococcus pneumoniae isolates and 5 (3%) Haemophilus influenzae type b isolates. The case-fatality rate for pneumonia in the hospital was 4% (150 deaths), and the children who died did so after a median of 2 days of hospitalization (range, 0-24 days). Infancy was highly associated with death due to pneumonia (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-3.2), as were very severe pneumonia (OR, 7.9; 95% CI, 5.6-11.2), a blood culture positive for bacteria (OR, 3.4; 95% CI, 2.0-5.8), severe malnutrition (OR, 4.6; 95% CI, 2.9-7.4), and delayed admission (mean [+/-SD] duration from illness onset to admission, 6+/-6 days, compared with 5+/-4 days for survivors; P< .04).nnnCONCLUSIONSnThe prevalence of pneumonia among children aged <5 years in hospitals in Bangladesh is high. However, the isolation rate of bacteria is low, possibly because of the high (68%) background use of antibiotics. Multiple risk factors associated with pneumonia case fatality suggest multiple strategies, including vaccines, to reduce pneumonia-related and overall child mortality in Bangladesh.