Epidemiology and etiology of childhood pneumonia

Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years. The incidence in this age group is estimated to be 0.29 episodes per child-year in developing and 0.05 episodes per child-year in developed countries. This translates into about 156 million new episodes each year worldwide, of which 151 million episodes are in the developing world. Most cases occur in India (43 million), China (21 million) and Pakistan (10 million), with additional high numbers in Bangladesh, Indonesia and Nigeria (6 million each). Of all community cases, 7-13% are severe enough to be life-threatening and require hospitalization. Substantial evidence revealed that the leading risk factors contributing to pneumonia incidence are lack of exclusive breastfeeding, undernutrition, indoor air pollution, low birth weight, crowding and lack of measles immunization. Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and south-east Asia. Although based on limited available evidence, recent studies have identified Streptococcus pneumoniae, Haemophilus influenzae and respiratory syncytial virus as the main pathogens associated with childhood pneumonia.     

Global illness and deaths caused by rotavirus disease in children

To estimate the global illness and deaths caused by rotavirus disease, we reviewed studies published from 1986 to 2000 on deaths caused by diarrhea and on rotavirus infections in children. We assessed rotavirus-associated illness in three clinical settings (mild cases requiring home care alone, moderate cases requiring a clinic visit, and severe cases requiring hospitalization) and death rates in countries in different World Bank income groups. Each year, rotavirus causes approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000-592,000 deaths (median, 440,000 deaths) in children <5 years of age. By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 65 will be hospitalized, and approximately 1 in 293 will die. Children in the poorest countries account for 82% of rotavirus deaths. The tremendous incidence of rotavirus disease underscores the urgent need for interventions, such as vaccines, particularly to prevent childhood deaths in developing nations.     

Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.     

Better newborn vitamin D status lowers RSV-associated bronchiolitis in infants

Each year 1.5 million children under the age of 5 years die from pneumonia. In the United States, respiratory syncytial virus (RSV) is the number one cause of bronchiolitis and pneumonia in children under 1 year of age. Low serum 25(OH)D is associated with an increased risk of lower respiratory tract infections (LRTI). Two recent studies have provided important information concerning the association between cord blood 25(OH)D and subsequent risk of developing respiratory infection in very young children. These findings support the need in future studies to determine the extent to which an intervention to change the vitamin D status of mothers during pregnancy can reduce the risk of RSV-associated LRTI in their offspring. An answer to this question would have significant worldwide public health importance given the high prevalence of low vitamin D status worldwide and the high mortality burden accompanying infectious lung diseases in young children.     

Community-based estimates of incidence and risk factors for childhood pneumonia in Western Sydney

The aim was to estimate the community incidence and risk factors for all-cause pneumonia in children in Western Sydney, Australia. A cross-sectional randomized computer-assisted telephone interview was conducted in July 2000, in Western Sydney. Parents of 2020 children aged between 5 and 14 years were interviewed about their child's respiratory health since birth. No verification of reported diagnosis was available. Logistic regression analysis was used to determine risk factors for pneumonia. A lifetime diagnosis of pneumonia was reported in 137/2020 (68%) children, giving an estimated incidence in the study sample of 7.6/1000 person-years. Radiological confirmation was reported in 85% (117/137). Hospitalization was reported in 41% (56/137) and antibiotic therapy in 93% (127/137) of cases. Using logistic regression modelling, statistically significant associations with pneumonia were a reported history of either asthma, bronchitis or other lung problems and health problems affecting other systems. In most cases, the diagnosis of asthma preceded the diagnosis of pneumonia. The community incidence of all causes of pneumonia is not well enumerated, either in adults or in children. This study provides community-based incidence data. The incidence of hospitalization for pneumonia in this study is comparable to estimates from studies in comparable populations, suggesting that retrospective parental report for memorable events is likely to be valid. We found a relationship between pneumonia and childhood respiratory diseases such as asthma, which has implications for targeted vaccination strategies.     

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.     

Prevalence of enterotoxigenic Escherichia coli-associated diarrhoea and carrier state in the developing world

This study assesses the importance of enterotoxigenic Escherichia coli (ETEC) as a diarrhoeal agent in developing countries. Odds ratios were calculated for incurring ETEC-associated diarrhoea based on data reported between 1970 and 1999. Carriage of ETEC was associated with diarrhoea in children aged less than five years, except for hospitalized infants aged 0-11 month(s) and children aged 1-4 year(s) at outpatient clinics. Two hundred and eighty million episodes of diarrhoea due to ETEC were seen yearly among those aged less than five years, and close to 50 million children of this age group were asymptomatic carriers of ETEC. Every 7th diarrhoeal episode in children aged less than one year and close to 25% of diarrhoeal cases in children aged 1-4 year(s) were due to ETEC. A child born in a developing country is likely to experience 0.5 diarrhoeal episodes per year caused by ETEC until the age of five years, after which the yearly incidence drops to 0.1. To conclude, ETEC remains an important diarrhoeal pathogen among children in the developing world.     

The preventable burden of pneumococcal disease in the developing world

The efficacy of pneumococcal conjugate vaccines (PCV) and their remarkable success in operational use in North America challenge us to define the burden of pneumococcal disease and the likely benefits of PCV use in developing countries. Community-based incidence studies of invasive pneumococcal disease (IPD) and vaccine probe analyses of efficacy trials suggest there are approximately 814,000 pneumococcal deaths in children aged <5 years in developing countries each year and 1-4 million episodes of pneumococcal pneumonia in Africa alone. PCV will be effective where there is a demonstrable burden of IPD attributable to vaccine serotypes but herd protection and serotype replacement effects are unpredictable given existing knowledge of pneumococcal epidemiology in developing countries. Operational use of PCV in well-monitored settings is required to estimate these effects.     

Methodological and quality issues in epidemiological studies of acute lower respiratory infections in children in developing countries

Acute respiratory infections are the most important single cause of global burden of disease in young children globally and a major cause of child mortality. A recent review of studies reporting the incidence of acute lower respiratory infections (ALRI) in young children in the developing world was carried out by the WHO Child Health Epidemiology Reference Group in order to inform global burden of disease estimates. The review highlighted the low number of community-based longitudinal studies of ALRI incidence in young children which met minimum quality criteria. It underscored the need to give attention to issues of study design and the reporting of a basic minimum dataset which describes circumstances under which the studies were being conducted and the key design features of the study which may influence the ALRI estimate. This paper aims to provide methodological guidelines for the design, conduct, and reporting of epidemiological studies of ALRI in under-5s in developing countries. It discusses determinants of study quality related to both study design and statistical analysis and also issues requiring further research. It is hoped that these guidelines will stimulate further work in this field and encourage the publication of reports which contain sufficient data to permit a meaningful meta-analysis of the data, thus forming the basis of more reliable future estimates of global burden of ALRI.     

Evaluation of vaccines for the prevention of pneumonia in children in developing countries.

This paper evaluates vaccines designed to prevent pneumonia among children in developing countries. Additionally, the article discusses the measurement of vaccine efficacy, as well as the potential of vaccine trials to provide information on the etiology of pneumonia and the need for an antibiotic treatment for various categories of acute respiratory infections (ARI). The three approaches to pneumococcal vaccine development include: 1) polysaccharide vaccines; 2) protein-polysaccharide conjugate vaccines; and 3) vaccines based on common protein antigens. The trial design was performed by individual randomization and randomization in clusters. Vaccines were evaluated in terms of the protection they provide against diseases with an unknown pathogen. The clinical and radiologic evaluation of pneumococcal vaccine trials served three related functions: 1) defining the ability of the vaccines to prevent severe pneumonia; 2) measuring the impact of the vaccine on the total burden of pneumonia that is defined by the World Health Organization; and 3) subdividing documented ARI episodes along clinical and radiological lines. Pneumococcal vaccine trials are essential in understanding the nature of pneumococcal disease among children in developing countries, as well as the public health utility of vaccines for its prevention.     

The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review

BackgroundLower respiratory tract infections (LRTI) are a major cause of morbidity and mortality worldwide, particularly in young children and older adults. Influenza is known to cause severe disease but the risk of developing LRTI following influenza virus infection in various populations has not been systematically reviewed. Such data are important for estimating the impact specific influenza vaccine programs would have on LRTI outcomes in a community. We sought to review the published literature to determine the risk of developing LRTI following an influenza virus infection in individuals of any age.Methods and findingsWe conducted a systematic review to identify prospective studies that estimated the incidence of LRTI following laboratory-confirmed influenza virus infection. We searched PubMed, Medline, and Embase databases for relevant literature. We supplemented this search with a narrative review of influenza and LRTI. The systematic review identified two prospective studies that both followed children less than 5 years. We also identified one additional pediatric study from our narrative review meeting the study inclusion criteria. Finally, we summarized recent case-control studies on the etiology of pneumonia in both adults and children.ConclusionsThere is a dearth of prospective studies evaluating the risk of developing LRTI following influenza virus infection. Determining the burden of severe LRTI that is attributable to influenza is necessary to estimate the benefits of influenza vaccine on this important public health outcome. Vaccine probe studies are an efficient way to evaluate these questions and should be encouraged going forward.     

Population-based study of acute respiratory infections in children,Greenland

Acute respiratory infections (ARI) are frequent in Inuit children, in terms of incidence and severity. A cohort of 294 children <2 years of age was formed in Sisimiut, a community on the west coast of Greenland, and followed from 1996 to 1998. Data on ARI were collected during weekly visits at home and child-care centers; visits to the community health center were also recorded. The cohort had respiratory symptoms on 41.6% and fever on 4.9% of surveyed days. The incidence of upper and lower respiratory tract infections was 1.6 episodes and 0.9 episodes per 100 days at risk, respectively. Up to 65% of the episodes of ARI caused activity restriction; 40% led to contact with the health center. Compared with studies from other parts of the world, the incidence of ARI appears to be high in Inuit children.     

Acute respiratory infections in children: a community based longitudinal study in south India

A community based longitudinal study was conducted in Malpe, a coastal village of Udupi district, Karnataka state, to investigate acute respiratory infections (ARI) in children. A cohort of 91 children under 3 years of age were followed up for 1 year, leading to 2047 fortnightly observation. On an average every child had 11.3 months of follow up. The overall incidence of ARI was 6.42 episodes per child per year. On an average each episode lasted for 5.06 days. Mean duration of ARI during one year was 32.5 days per child. Most of the ARI episodes in children (91.3%) were of simple Cough & Cold (no pneumonia). However, 8.2% developed pneumonia and only 0.51% had severe pneumonia. Incidence of ARI was almost same in male and female children. There was no significant difference in incidence among various age groups. But the incidence of pneumonia was significantly higher among infants (p<0.00002). Children of poor housing with smoke producing conditions suffered more frequently (p,002).     

The burden of disease from indoor air pollution in developing countries: comparison of estimates

Four different methods have been applied to estimate the burden of disease due to indoor air pollution from household solid fuel use in developing countries (LDCs). The largest number of estimates involves applying exposure-response information from urban ambient air pollution studies to estimate indoor exposure concentrations of particulate air pollution. Another approach is to construct child survival curves using the results of large-scale household surveys, as has been done for India. A third approach involves cross-national analyses of child survival and household fuel use. The fourth method, referred to as the 'fuel-based' approach, which is explored in more depth here, involves applying relative risk estimates from epidemiological studies that use exposure surrogates, such as fuel type, to estimates of household solid fuel use to determine population attributable fractions by disease and age group. With this method and conservative assumptions about relative risks, 4-5 percent of the global LDC totals for both deaths and DALYs (disability adjusted life years) from acute respiratory infections, chronic obstructive pulmonary disease, tuberculosis, asthma, lung cancer, ischaemic heart disease, and blindness can be attributed to solid fuel use in developing countries. Acute respiratory infections in children under five years of age are the largest single category of deaths (64%) and DALYs (81%) from indoor air pollution, apparently being responsible globally for about 1.2 million premature deaths annually in the early 1990s.     

Estimates of incidence and costs of intestinal infectious diseases in the United States

The incidence of acute episodes of intestinal infectious diseases in the United States was estimated through analysis of community-based studies and national interview surveys. Their differing results were reconciled by adjusting the study population age distributions in the community-based studies, by excluding those cases that also showed respiratory symptoms, and by accounting for structural differences in the surveys. The reconciliation process provided an estimate of 99 million acute cases of either vomiting or diarrhea, or both, each year in this country, half of which involved more than a full day of restricted activity. The analysis was limited to cases of acute gastrointestinal diseases with vomiting or diarrhea but without respiratory symptoms. Physicians were consulted for 8.2 million illnesses; 250,000 of these required hospitalization. In 1985, hospitalizations incurred $560 million in medical costs and $200 million in lost productivity. Nonhospitalized cases (7.9 million) for which physicians were consulted incurred $690 million in medical costs and $2.06 billion in lost productivity. More than 90 million cases for which no physician was consulted cost an estimated $19.5 billion in lost productivity. The estimates excluded such costs as death, pain and suffering, lost leisure time, financial losses to food establishments, and legal expenses. According to these estimates, medical costs and lost productivity from acute intestinal infectious diseases amount to a minimum of about $23 billion a year in the United States.     

Estimating the vaccine-preventable burden of hospitalized pneumonia among young Mozambican children

Polysaccharide-protein conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have proven efficacy against radiologically confirmed pneumonia. Measurement of pneumonia incidence provides a platform to estimate of the vaccine-preventable burden. Over 24 months, we conducted surveillance for radiologically confirmed severe pneumonia episodes among children <2 years of age admitted to a rural hospital in Manhiça, southern Mozambique. Study children were tested for HIV during the second year of surveillance. Severe pneumonia accounted for 15% of 5132 hospital admissions and 32% of in-hospital mortality among children <2 years of age. Also, 43% of chest radiographs were interpreted as radiologically confirmed pneumonia. HIV-infection was associated with 81% of fatal pneumonia episodes among children tested for HIV. The minimum incidence rate of radiologically confirmed pneumonia requiring hospitalization was 19 episodes/1000 child-years. Incidence rates among HIV-infected children were 9.3–19.0-fold higher than HIV-uninfected. Introduction of Hib and pneumococcal conjugate vaccines would have a substantial impact on pneumonia hospitalizations among African children if vaccine effects are similar to those observed in clinical trials.     

Association of diarrhoea and upper respiratory infections with weight and height gains in Bangladeshi children aged 5 to 11 years

INTRODUCTION: The association between infection and growth delay is not well documented in school-age children in developing countries. We conducted a prospective cohort study to examine the association between infectious disease and weight and height gains among Bangladeshi children. METHODS: A one-year follow-up study was performed to elucidate the determinants and consequences of physical growth of children under five years of age. The study included 135 households randomly selected from four villages in the Matlab area. RESULTS: The most frequent infections were upper respiratory infections (mean = 4 episodes or 27 days per year) followed by non-dysenteric diarrhoea (mean = 2.3 episodes or 15 days per year) and dysentery (mean = 0.2 episodes or 2 days per year). The number of episodes and their duration decreased significantly with age. Over a 12-month period the mean weight gain was 1.3 kg and the mean increase in height was 2.9 cm. The total number of days when diarrhoea occurred was negatively associated with annual weight gain (regression coefficient beta = -7 g per day, P = 0.02), with adjustment for age, sex, energy and protein intake, and household land ownership. The incidence of diarrhoeal disease was significantly associated with weight gain in intermediate models but only marginally associated with it in the final multivariate model (P = 0.08). Neither the incidence nor the duration of upper respiratory infections was associated with weight gain. Height gain was not significantly associated with the duration or incidence of either category of illness. Diarrhoea was a significant correlate of retarded weight gain among children above preschool age, whereas upper respiratory infections were not. DISCUSSION: Diarrhoeal morbidity slowed growth in children well beyond the weaning age, suggesting that increased attention should be given to the study of the continuous impact of diarrhoea in children aged over 5 years. An understanding of the determinants of growth in school-age children in developing countries would maximize the health and developmental outcomes that are the target of international child survival strategies at younger ages.     

Estimating the Haemophilus influenzae type b (Hib) disease burden and the impact of Hib vaccine in Fiji

AIMS: To estimate Haemophilus influenzae type b (Hib) disease burden in Fiji in children under the age of 5 years (under-5s) prior to vaccine introduction. To compare estimates from WHO's Hib rapid assessment tool (RAT), with that from decline in disease after vaccine introduction. METHODS: Laboratory data (meningitis), hospitalization and mortality data (pneumonia and meningitis) before and after Hib vaccine introduction were collected. The RAT protocol provides two independent estimates of pre-vaccine disease burden (one based on meningitis incidence laboratory data and the other based on mortality statistics). A third estimate uses the decline in disease following vaccine introduction. RESULTS: The decline in meningitis hospitalizations implies a pre-vaccine Hib meningitis incidence of 66 per 100,000 in under-5s. This compares with a pre-vaccine RAT estimate of Hib meningitis incidence of 84 per 100,000 (for 1992-1993). The RAT estimated the total annual pre-vaccine Hib burden (meningitis plus pneumonia) at 476 cases and 36 deaths per year ("meningitis incidence method") and 70 cases and 5 deaths ("child mortality method"). Hib vaccine led to declines of 32% (95% confidence interval (CI)=11-48%), and 78% (95% CI=22-94%) for all under-5s meningitis hospitalizations and deaths, respectively. There was no similar consistent decline in pneumonia hospitalizations or deaths after vaccine introduction, except for a statistically significant reduction in pneumonia mortality in children aged under 1 year. CONCLUSIONS: Hib disease constitutes an important burden on the health of Pacific children that can be rapidly reduced with Hib vaccine. In this setting, routine morbidity statistics (comparing pre-and post-vaccine) provided an estimate of Hib meningitis burden which is broadly similar to that of the Hib RAT, suggesting that both might be valid ways to estimate Hib meningitis incidence. However, Hib pneumonia burden could not be estimated from routine statistics.     

The magnitude of the global problem of diarrhoeal disease: a ten-year update.

In order to update global estimates of diarrhoeal morbidity and mortality in developing countries, we carried out a review of articles published from 1980 to the present and calculated median estimates for the incidence of diarrhoea and diarrhoeal mortality among under-5-year-olds. The incidence of diarrhoea obtained (2.6 episodes per child per year) was virtually the same as that estimated by Snyder & Merson in 1982, while the global mortality estimate was lower (3.3 million deaths per year; range, 1.5-5.1 million). The mortality estimate is based on a small number of active surveillance and prospective studies, and thus associated with a large degree of uncertainty, reflecting the weakness of the global database. However, many surveys reporting reductions in mortality in several locations are consistent with a decreased estimate for mortality. More accurate execution of WHO survey methods, including population-based sampling in representative locations, and repeat surveys every 5 years, are needed to monitor the progress of diarrhoeal disease control programmes and trends in diarrhoeal morbidity and mortality over time.     

2008年长春地区小儿急性呼吸道感染状况与疾病负担的研究

目的:了解2008年长春地区小儿急性呼吸道感染发病情况与疾病负担,为控制小儿急性呼吸道感染提供依据。方法:以2008年长春市儿童医院住院的急性呼吸道感染患儿为研究对象,用荧光定量PCR方法进行肺炎支原体检测,对患儿临床资料进行流行病学分析。结果:2008年长春地区小儿急性呼吸道感染发病率为33.67%(4 923/14 620),其中临床诊断急性上呼吸道感染(包括鼻炎、咽炎、扁桃体炎、喉炎)为14.08%(693/4 923)、急性支气管炎为4.12%(203/4 923)、急性毛细支气管炎为1.95%(96/4 923)、支气管肺炎为76.88%(3 785/4 923)、大叶性肺炎1.14%(56/4 923)、肺炎支原体肺炎1.83%(90/4 923);患儿年龄均值为(28.59±20.32)月龄;发病人数1月份最多,5月份开始下降,10月份再次增多;平均住院天数为7天,平均每个患儿住院医疗费用3 275.15元,总耗资约1 912万元,1例因急性呼吸道感染死亡。结论:长春地区小儿急性呼吸道感染住院人数多、耗资大,控制小儿急性呼吸道感染是对社会和家庭的挑战也是儿科医务工作者的当务之急。