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The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

ABSTRACT: Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations.

SUBMITTER: Feikin DR

PROVIDER: S-EPMC5447852 | biostudies-other | 2017 Jun

REPOSITORIES: biostudies-other

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The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

Feikin Daniel R DR Hammitt Laura L LL Murdoch David R DR O'Brien Katherine L KL Scott J Anthony G JAG

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20170601 suppl_3

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology stud ...[more]

PMID: 28575369

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Project description:BackgroundDespite recent declines in new pediatric HIV infections and childhood HIV-related deaths, pneumonia remains the leading cause of death in HIV-infected children under 5. We describe the patient population, etiology and outcomes of childhood pneumonia in Zambian HIV-infected children.MethodsAs one of the 9 sites for the Pneumonia Etiology Research for Child Health study, we enrolled children 1-59 months of age presenting to University Teaching Hospital in Lusaka, Zambia, with World Health Organization-defined severe and very severe pneumonia. Controls frequency-matched on age group and HIV infection status were enrolled from the Lusaka Pediatric HIV Clinics as well as from the surrounding communities. Clinical assessments, chest radiographs (CXR; cases) and microbiologic samples (nasopharyngeal/oropharyngeal swabs, blood, urine, induced sputum) were obtained under highly standardized procedures. Etiology was estimated using Bayesian methods and accounted for imperfect sensitivity and specificity of measurements.ResultsOf the 617 cases and 686 controls enrolled in Zambia over a 24-month period, 103 cases (16.7%) and 85 controls (12.4%) were HIV infected and included in this analysis. Among the HIV-infected cases, 75% were <1 year of age, 35% received prophylactic trimethoprim-sulfamethoxazole, 13.6% received antiretroviral therapy and 36.9% of caregivers reported knowing their children's HIV status at time of enrollment. A total of 35% of cases had very severe pneumonia and 56.3% had infiltrates on CXR. Bacterial pathogens [50.6%, credible interval (CrI): 32.8-67.2], Pneumocystis jirovecii (24.9%, CrI: 15.5-36.2) and Mycobacterium tuberculosis (4.5%, CrI: 1.7-12.1) accounted for over 75% of the etiologic fraction among CXR-positive cases. Streptococcus pneumoniae (19.8%, CrI: 8.6-36.2) was the most common bacterial pathogen, followed by Staphylococcus aureus (12.7%, CrI: 0.0-25.9). Outcomes were poor, with 41 cases (39.8%) dying in hospital.ConclusionsHIV-infected children in Zambia with severe and very severe pneumonia have poor outcomes, with continued limited access to care, and the predominant etiologies are bacterial pathogens, P. jirovecii and M. tuberculosis.

Project description:BackgroundPneumonia remains the leading cause of death among children <5 years of age beyond the neonatal period in Thailand. Using data from the Pneumonia Etiology Research for Child Health (PERCH) Study, we provide a detailed description of pneumonia cases and etiology in Thailand to inform local treatment and prevention strategies in this age group.MethodsPERCH, a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children 1-59 months of age. The Thailand site enrolled children for 24 consecutive months during January 2012-February 2014 with staggered start dates in 2 provinces. Cases were children hospitalized with pre-2013 WHO-defined severe or very severe pneumonia. Community controls were randomly selected from health services registries in each province. Analyses were restricted to HIV-negative cases and controls. We calculated adjusted odds ratios (ORs) and 95% CIs comparing organism prevalence detected by nasopharyngeal/oropharyngeal (NP/OP) polymerase chain reaction between cases and controls. The PERCH Integrated Analysis (PIA) used Bayesian latent variable analysis to estimate pathogen-specific etiologic fractions and 95% credible intervals.ResultsOver 96% of both cases (n = 223) and controls (n = 659) had at least 1 organism detected; multiple organisms were detected in 86% of cases and 88% of controls. Among 98 chest Radiograph positive (CXR+) cases, respiratory syncytial virus (RSV) had the highest NP/OP prevalence (22.9%) and the strongest association with case status (OR 20.5; 95% CI: 10.2, 41.3) and accounted for 34.6% of the total etiologic fraction. Tuberculosis (TB) accounted for 10% (95% CrI: 1.6-26%) of the etiologic fraction among CXR+ cases.DiscussionMore than one-third of hospitalized cases of severe and very severe CXR+ pneumonia among children 1-59 months of age in Thailand were attributable to RSV. TB accounted for 10% of cases, supporting evaluation for TB among children hospitalized with pneumonia in high-burden settings. Similarities in pneumonia etiology in Thailand and other PERCH sites suggest that global control strategies based on PERCH study findings are relevant to Thailand and similar settings.

Project description:Soon after its identification, norovirus (NoV) has been indicated as one of the most common causes of outbreaks of acute gastroenteritis (AGE) and sporadic acute diarrhea episodes in subjects of any age. In 2016 the World Health Organization stated that the development of a NoV vaccine should be considered an absolute priority. Unfortunately, the development of an effective NoV vaccine has proven extremely difficult, and only in recent years, some preparations have been tested in humans in advanced clinical trials. In this paper, reasons that justify efforts to develop a NoV vaccine, difficulties encountered during NoV vaccine development, and NoV vaccine candidates will be discussed. In recent years, identification of some NoV antigens that alone or in combination with other viral antigens can induce a potentially protective immune response has led to the development of a large series of preparations that seem capable of coping with the problems related to NoV infection. Epidemiological and immunological studies have shown that multivalent vaccines, including both GI and GII NoV, are the only solution to induce sufficiently broad protection. However, even if the road to formulation of an effective and safe NoV vaccine seems to be definitively traced, many problems still need to be solved before the total burden of NoV infections can be adequately controlled. Whether currently available vaccines are able to protect against all the heterologous NoV strains and the variants of the most common serotypes that frequently emerge and cause outbreaks must be defined. Moreover, as performed clinical trials have mainly enrolled adults, it is mandatory to know whether vaccines are effective in all age groups, including younger children. Finally, we must know the immune response of immunocompromised patients and the duration of protection induced by NoV vaccines. Only when all these problems have been solved will it be possible to establish an effective immunization schedule against NoV infection and calculate whether systematic vaccination can be cost effective.

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The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

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The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

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