SummaryBackgroundThe 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.MethodsWe 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region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies.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.FindingsWe 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.InterpretationSevere 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.FundingWHO.

These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

A study sample of 7,010 episodes of invasive Streptococcus pneumoniae disease was obtained by combining 13 existing datasets. Disease episodes due to each of 12 pneumococcal serogroups (1, 3-9, 14, 18, 19, and 23) were then compared with episodes in a constant internal control group to describe serogroup-specific variations in disease frequency by age, sex, and geographic origin. The results are presented as odds ratios (with 95% confidence intervals) derived by logistic regression, with adjustment for the major confounders, including dataset of origin. Variation in the male:female ratios between serogroups is small, suggesting that capsular characteristics are an unlikely explanation for the male preference of S. pneumoniae. Serogroups associated with higher nasopharyngeal prevalence (e.g., 19 and 24) are relatively more common in Europe and North American, while the invasive serotypes 1 and 5 are much more common in South America. The custom of reporting serogroup frequencies in two age groups, children and adults, conceals much of the variation in the age distributions across the whole span of life. The reduction of risk associated with serogroups 6, 14, 18, 19, and 23 beyond childhood follows different gradients, being most abrupt in serogroups 14 and most gradual in serogroup 18. The relative risk of disease with serotype 1 declines steadily throughout life, while with serotypes 3 and 8 it increases over middle age. Serogroups 7 and 23 are found unusually frequently in the third decade of life. Because of the wide differences in the epidemiology of individual serogroups of S. pneumoniae, it is questionable whether pneumococcal infection should continue to be classified as a single disease entity.

A collection of 165 adenovirus strains isolated from nasopharyngeal aspirates of children hospitalized for acute lower respiratory infection in Argentina, Chile, and Uruguay between 1991 and 1994 was studied by restriction enzyme analysis (work performed in the Department of Virology, University of Umeå). Of the isolates, 71% (n = 117) were identified as members of subgenus B. Of these, 101 (61.2%) corresponded to genome type 7h, four (2.4%) to genome type 3p2, four (2.4%) to genome type 11a, one (0.6%) to genome type 7b, and one (0.6%) to genome type 7c. Two isolates that were neutralized as serotype 3 and four isolates that were neutralized as serotype 7 exhibited novel BamHI cleavage profiles corresponding to three new genome types denominated 3x, 7i, and 7j. Subgenus C members represented 28.5% of all typed isolates. Five different genome types of Ad1, seven genome types of Ad2, and three genome types of Ad5 were identified of, which two, two, and one, respectively, were found to correspond to new DNA variants. Only one isolate (0.6%) corresponded to Ad4 of subgenus E. Ad7h was isolated from 17 of the 18 fatal cases recorded among the patients included in the study.

The genetic and antigenic variability of the G glycoproteins from 76 human respiratory syncytial (RS) viruses (subgroup A) isolated during six consecutive epidemics in either Montevideo, Uruguay, or Madrid, Spain, have been analyzed. Genetic diversity was evaluated for all viruses by the RNase A mismatch cleavage method and for selected strains by dideoxy sequencing. The sequences reported here were added to those published for six isolates from Birmingham, United Kingdom, and for two reference strains (A2 and Long), to derive a phylogenetic tree of subgroup A viruses that contained two main branches and several subbranches. During the same epidemic, viruses from different branches were isolated. In addition, closely related viruses were isolated in distant places and in different years. These results illustrate the capacity of the virus to spread worldwide, influencing its mode of evolution. The antigenic analysis of all isolates was carried out with a panel of anti-G monoclonal antibodies that recognized strain-specific (or variable) epitopes. A close correlation between genetic relatedness and antigenic relatedness in the G protein was observed. These results, together with an accumulation of amino acid changes in a major antigenic area of the G glycoprotein, suggest that immune selection may be a factor influencing the generation of RS virus diversity. The pattern of RS virus evolution is thus similar to that described for influenza type B viruses, expect that the level of genetic divergence among the G glycoproteins of RS virus isolates is the highest reported for an RNA virus gene product.

In this study, previous use of penicillin or ampicillin and private medical coverage were associated with having DRSP. Children with nonmeningeal invasive disease responded equally well to penicillin regardless of the penicillin susceptibility of their pneumococcal isolate.

Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae promise to be an effective public health intervention for children, especially in an era of increasing antimicrobial resistance. To characterize the distribution of capsular types in Latin America, surveillance for invasive pneumococcal infection in children < or = 5 years of age was done in six countries between February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were from children with pneumonia, and 52% were isolated from blood. The 15 most common of the capsular types prevalent throughout the region accounted for 87.7% of all isolates. Overall, 24.9% of isolates had diminished susceptibility to penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance. Three customized vaccine formulas containing 7, 12, and 15 capsular types were found to have regional coverages of 72%, 85%, and 88%, respectively. This study emphasizes the need for local surveillance for invasive pneumococcal disease prior to the development and evaluation of protein-polysaccharide conjugate vaccines for children.

Four hundred ninety-nine methicillin-resistant