Anna Roca

Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.

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

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.

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 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.

Community-acquired bacteremia among children admitted to a rural hospital in Mozambique.

Background: Although community-acquired bacteremia is an important cause of childhood mortality in Africa, recognition of disease burden and potential impact of bacterial vaccines is limited. Methods: Blood cultures for bacterial pathogens were conducted systematically among children <15 years of age admitted to Manhiça District Hospital, from 2001 to 2006. Results: Blood-stream infections were identified in 8% (1550/19,896) of pediatric hospital admissions. Nontyphoidal Salmonella (NTS) and Pneumococcus were the most prevalent pathogens isolated (26% and 25% of 1550 cases, respectively). Until 28 days of life, Staphylococcus aureus (39%) and group B Streptococcus (20%) predominated. Incidence of community-acquired bacteremia per 100,000 child-years was 1730/105 in children <1 year old, 782/105 in 1–4 year oldd, and 49/105 in children 5 years and older. Case-fatality of bacteremia was 12%. Community-acquired bacteremia associated mortality accounted for 21% (162/788) of hospital deaths. Resistance to antibiotics commonly used in Mozambique was high among invasive isolates of Haemophilus influenzae, Escherichia coli, and NTS. Conclusions: Community-acquired bacteremia is an important cause of pediatric hospital admission and death in rural African hospitals. The high burden of disease, mortality, and pattern of antibiotic resistance associated with bacteremia underscore the need for prevention in Sub-Saharan Africa.

Respiratory syncytial virus infection: denominator-based studies in Indonesia, Mozambique, Nigeria and South Africa

OBJECTIVE To assess the burden of respiratory syncytial virus (RSV)-associated lower respiratory infections (LRI) in children in four developing countries. METHODS A WHO protocol for prospective population-based surveillance of acute respiratory infections in children aged less than 5 years was used at sites in Indonesia, Mozambique, Nigeria and South Africa. RSV antigen was identified by enzyme-linked immunosorbent assay performed on nasopharyngeal specimens from children meeting clinical case definitions. FINDINGS Among children aged < 5 years, the incidence of RSV-associated LRI per 1000 child-years was 34 in Indonesia and 94 in Nigeria. The incidence of RSV-associated severe LRI per 1000 child-years was 5 in Mozambique, 10 in Indonesia, and 9 in South Africa. At all study sites, the majority of RSV cases occurred in infants. CONCLUSION These studies demonstrate that RSV contributes to a substantial but quite variable burden of LRI in children aged < 5 years in four developing countries. The possible explanations for this variation include social factors, such as family size and patterns of seeking health care; the proportion of children infected by human immunodeficiency syndrome (HIV); and differences in clinical definitions used for obtaining samples. The age distribution of cases indicates the need for an RSV vaccine that can protect children early in life.

Severe malaria and concomitant bacteraemia in children admitted to a rural Mozambican hospital

Objectives  To describe the prevalence, aetiology and prognostic implications of coexisting invasive bacterial disease in children admitted with severe malaria in a rural Mozambican Hospital.

Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique

Background. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in infants throughout most of the world, but little is known about RSV infection in Africa where LRTI are among the leading causes of infant and childhood death. Methods. The study took place in a rural district hospital in southern Mozambique between October, 1998, and May, 2000. From all children (n = 5635) <1 year of age presenting to an outpatient department with cough or nasal secretion and all children (n = 1307) <5 years of age admitted to hospital with a LRTI, a nasopharyngeal aspirate was collected and tested for RSV by enzyme-linked immunosorbent assay (Abbott). Results. RSV infection was found in 8.6% of study infants in the outpatient department and 10.6% of admitted children with LRTI. Cases presented in predictable yearly outbreaks during the warm and rainy season. Lower respiratory tract involvement was frequent (59.7%). Cough, chest indrawing and increased respiratory rate were all independently related to RSV infection. Wheezing was infrequent. Bacterial coinfection (4.6%) and the case-fatality rate (3.4%) were low. Conclusions. There is a substantial burden of disease attributable to RSV infection in this rural African setting, with the highest incidence and severity occurring in young infants.

Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial

In a cluster-randomized trial conducted in Gambian villages, Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults.

Genetic variability among group A and B respiratory syncytial viruses in Mozambique: identification of a new cluster of group B isolates.

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory tract infection in children and vulnerable adults, but little is known regarding RSV infection in Africa. In this report, a recent RSV outbreak in Mozambique was studied and results showed that 275 of 3192 (8.6%) nasopharyngeal aspirates tested were RSV-positive by ELISA. RSV presents two antigenic groups (A and B) with a high genetic and antigenic variability between and within them. Analysis by a new RFLP assay of RT-PCR amplified N protein gene products showed a higher prevalence of group B RSV than that of group A (85% versus 15%). However, genetic variability of the G protein gene was higher among group A RSV strains. The frequency and pattern of glycosylation sites were also quite different between both groups. In addition, two different phylogenetic clusters of Mozambican viruses were found within each group, but only sequences from cluster B-I were relatively distinct from previously described isolates. The implications of such differences in the antigenic and immunogenic characteristics of each group are discussed.

Invasive pneumococcal disease in children <5 years of age in rural Mozambique

Objectives  To estimate the incidence and epidemiological characteristics of invasive pneumococcal disease (IPD) in children <5 years of age living in a rural area of southern Mozambique.