A preliminary study of pneumonia etiology among hospitalized children in Kenya.
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ABSTRACT: Background
Pneumonia is the leading cause of childhood death in the developing world. Higher-quality etiological data are required to reduce this mortality burden.Methods
We conducted a case-control study of pneumonia etiology among children aged 1-59 months in rural Kenya. Case patients were hospitalized with World Health Organization-defined severe pneumonia (SP) or very severe pneumonia (VSP); controls were outpatient children without pneumonia. We collected blood for culture, induced sputum for culture and multiplex polymerase chain reaction (PCR), and obtained oropharyngeal swab specimens for multiplex PCR from case patients, and serum for serology and nasopharyngeal swab specimens for multiplex PCR from case patients and controls.Results
Of 984 eligible case patients, 810 (84%) were enrolled in the study; 232 (29%) had VSP. Blood cultures were positive in 52 of 749 case patients (7%). A predominant potential pathogen was identified in sputum culture in 70 of 417 case patients (17%). A respiratory virus was detected by PCR from nasopharyngeal swab specimens in 486 of 805 case patients (60%) and 172 of 369 controls (47%). Only respiratory syncytial virus (RSV) showed a statistically significant association between virus detection in the nasopharynx and pneumonia hospitalization (odds ratio, 12.5; 95% confidence interval, 3.1-51.5). Among 257 case patients in whom all specimens (excluding serum specimens) were collected, bacteria were identified in 24 (9%), viruses in 137 (53%), mixed viral and bacterial infection in 39 (15%), and no pathogen in 57 (22%); bacterial causes outnumbered viral causes when the results of the case-control analysis were considered.Conclusions
A potential etiology was detected in >75% of children admitted with SP or VSP. Except for RSV, the case-control analysis did not detect an association between viral detection in the nasopharynx and hospitalization for pneumonia.
SUBMITTER: Hammitt LL
PROVIDER: S-EPMC3297554 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundIn the 1980s, Streptococcus pneumoniae and Haemophilus influenzae were identified as the principal causes of severe pneumonia in children. We investigated the etiology of severe childhood pneumonia in Kenya after introduction of conjugate vaccines against H. influenzae type b, in 2001, and S. pneumoniae, in 2011.MethodsWe conducted a case-control study between August 2011 and November 2013 among residents of the Kilifi Health and Demographic Surveillance System 28 days to 59 months of age. Cases were hospitalized at Kilifi County Hospital with severe or very severe pneumonia according to the 2005 World Health Organization definition. Controls were randomly selected from the community and frequency matched to cases on age and season. We tested nasal and oropharyngeal samples, sputum, pleural fluid, and blood specimens and used the Pneumonia Etiology Research for Child Health Integrated Analysis, combining latent class analysis and Bayesian methods, to attribute etiology.ResultsWe enrolled 630 and 863 HIV-uninfected cases and controls, respectively. Among the cases, 282 (44%) had abnormal chest radiographs (CXR positive), 33 (5%) died in hospital, and 177 (28%) had diagnoses other than pneumonia at discharge. Among CXR-positive pneumonia cases, viruses and bacteria accounted for 77% (95% CrI: 67%-85%) and 16% (95% CrI: 10%-26%) of pneumonia attribution, respectively. Respiratory syncytial virus, S. pneumoniae and H. influenza, accounted for 37% (95% CrI: 31%-44%), 5% (95% CrI: 3%-9%), and 6% (95% CrI: 2%-11%), respectively.ConclusionsRespiratory syncytial virus was the main cause of CXR-positive pneumonia. The small contribution of H. influenzae type b and pneumococcus to pneumonia may reflect the impact of vaccine introductions in this population.
| S-EPMC8448399 | biostudies-literature
Project description:BackgroundRecognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance.MethodsWe analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics.ResultsA total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings.ConclusionsCoinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.
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Project description:BackgroundChildhood pneumonia in developing countries is the foremost cause of morbidity and death. Fresh information on etiology is needed, considering the changing epidemiology of pneumonia in the setting of greater availability of effective vaccines, changing antibiotic use and improved access to care. We report here the Zambia site results of the Pneumonia Etiology Research for Child Health study on the etiology of pneumonia among HIV-uninfected children in Lusaka, Zambia.MethodsWe conducted a case-control study of HIV-uninfected children age 1-59 months admitted with World Health Organization-defined severe or very severe pneumonia to a large tertiary care hospital in Lusaka. History, physical examination, chest radiographs (CXRs), blood cultures and nasopharyngeal/oropharyngeal swabs were obtained and tested by polymerase chain reaction and routine microbiology for the presence of 30 bacteria and viruses. From age and seasonally matched controls, we tested blood and nasopharyngeal/oropharyngeal samples. We used the Pneumonia Etiology Research for Child Health integrated analysis to determine the individual and population etiologic fraction for individual pathogens as the cause of pneumonia.ResultsAmong the 514 HIV-uninfected case children, 208 (40.5%) had abnormal CXRs (61 of 514 children were missing CXR), 8 (3.8%) of which had positive blood cultures. The overall mortality was 16.0% (82 deaths). The etiologic fraction was highest for respiratory syncytial virus [26.1%, 95% credible interval (CrI): 17.0-37.7], Mycobacterium tuberculosis (12.8%, 95% CrI: 4.3-25.3) and human metapneumovirus (12.8%, CrI: 6.1-21.8).ConclusionsChildhood pneumonia in Zambia among HIV-uninfected children is most frequently caused by respiratory syncytial virus, M. tuberculosis and human metapneumovirus, and the mortality remains high.
| S-EPMC8448410 | biostudies-literature
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.
| S-EPMC8448411 | biostudies-literature
Project description:BackgroundCommunity-acquired pneumonia (CAP) 2007 guidelines from the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) recommend a respiratory fluoroquinolone or beta-lactam plus macrolide as first-line antibiotics for adults hospitalized with CAP. Few studies have assessed guideline-concordant antibiotic use for patients hospitalized with CAP after the 2007 IDSA/ATS guidelines. We examine antibiotics prescribed and associated factors in adults hospitalized with CAP.MethodsFrom January 2010 to June 2012, adults hospitalized with clinical and radiographic CAP were enrolled in a prospective Etiology of Pneumonia in the Community study across 5 US hospitals. Patients were interviewed using a standardized questionnaire, and medical charts were reviewed. Antibiotics prescribed were classified according to defined nonrecommended CAP antibiotics. We assessed factors associated with nonrecommended CAP antibiotics using logistic regression.ResultsAmong enrollees, 1843 of 1874 (98%) ward and 440 of 446 (99%) ICU patients received ≥1 antibiotic ≤24 hours after admission. Ward patients were prescribed a respiratory fluoroquinolone alone (n = 613; 33%), or beta-lactam plus macrolide (n = 365; 19%), beta-lactam alone (n = 240; 13%), among other antibiotics, including vancomycin (n = 235; 13%) or piperacillin/tazobactam (n = 157; 8%) ≤24 hours after admission. Ward patients with known risk for healthcare-associated pneumonia (HCAP), recent outpatient antibiotic use, and in-hospital antibiotic use <6 hours after admission were significantly more likely to receive nonrecommended CAP antibiotics.ConclusionsAlthough more than half of ward patients received antibiotics concordant with IDSA/ATS guidelines, a number received nonrecommended CAP antibiotics, including vancomycin and piperacillin/tazobactam; risk factors for HCAP, recent outpatient antibiotic, and rapid inpatient antibiotic use contributed to this. This hypothesis-generating descriptive epidemiology analysis could help inform antibiotic stewardship efforts, reinforces the need to harmonize guidelines for CAP and HCAP, and highlights the need for improved diagnostics to better equip clinicians.
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Project description:BackgroundIn Latin America, community-acquired pneumonia remains a major cause of morbidity and mortality among children. Few studies have examined the etiology of pneumonia in Ecuador.MethodsThis observational study was part of a randomized, double blind, placebo-controlled clinical trial conducted among children aged 2-59 months with severe pneumonia in Quito, Ecuador. Nasopharyngeal and blood samples were tested for bacterial and viral etiology by polymerase chain reaction. Risk factors for specific respiratory pathogens were also evaluated.ResultsAmong 406 children tested, 159 (39.2%) had respiratory syncytial virus (RSV), 71 (17.5%) had human metapneumovirus (hMPV), and 62 (15.3%) had adenovirus. Streptococcus pneumoniae was identified in 37 (9.2%) samples and Mycoplasma pneumoniae in three (0.74%) samples. The yearly circulation pattern of RSV (P = 0.0003) overlapped with S. pneumoniae, (P = 0.03) with most cases occurring in the rainy season. In multivariable analysis, risk factors for RSV included younger age (adjusted odds ratio [aOR] = 1.9, P = 0.01) and being underweight (aOR = 1.8, P = 0.04). Maternal education (aOR = 0.82, P = 0.003), pulse oximetry (aOR = 0.93, P = 0.005), and rales (aOR = 0.25, P = 0.007) were associated with influenza A. Younger age (aOR = 3.5, P = 0.007) and elevated baseline respiratory rate were associated with HPIV-3 infection (aOR = 0.94, P = 0.03).ConclusionThese results indicate the importance of RSV and influenza, and potentially modifiable risk factors including undernutrition and future use of a RSV vaccine, when an effective vaccine becomes available.Trial registrationClinicalTrials.gov NCT 00513929.
| S-EPMC5300242 | biostudies-literature
Project description:BackgroundPneumonia is the major contributor to under 5 childhood mortality globally. We evaluated the etiology of pneumonia amongst HIV-uninfected South African children enrolled into the Pneumonia Etiology Research for Child Health case-control study.MethodsCases, 1-59 months of age hospitalized with World Health Organization clinically defined severe/very severe pneumonia, were frequency-matched by age and season to community controls. Nasopharyngeal-oropharyngeal swabs were analyzed using polymerase chain reaction for 33 respiratory pathogens, and whole blood was tested for pneumococcal autolysin. Cases were also tested for Mycobacterium tuberculosis. Population etiologic fractions (EF) of pneumonia with radiologic evidence of consolidation/infiltrate were derived for each pathogen through Bayesian analysis.ResultsOf the 805 HIV-uninfected cases enrolled based on clinical criteria, radiologically confirmed pneumonia was evident in 165 HIV-exposed, -uninfected, and 246 HIV-unexposed children. In HIV-exposed and HIV-unexposed children, respiratory syncytial virus was the most important pathogen with EFs of 31.6% [95% credible interval (CrI), 24.8%-38.8%] and 36.4% (95% CrI, 30.5%-43.1%), respectively. M. tuberculosis contributed EFs of 11.6% (95% CrI, 6.1%-18.8%) in HIV-exposed and 8.3% (95% CrI, 4.5%-13.8%) in HIV-unexposed children, including an EF of 16.3% (95% CrI, 6.1%-33.3%) in HIV-exposed children ≥12 months of age. Bacteremia (3.0% vs. 1.6%) and case fatality risk (3.6% vs. 3.7%) were similar in HIV-exposed and HIV-unexposed children.ConclusionsVaccination strategies targeting respiratory syncytial virus should be prioritized for prevention of pneumonia in children. Furthermore, interventions are required to address the high burden of tuberculosis in the pathogenesis of acute community-acquired pneumonia in settings such as ours.
| S-EPMC8448398 | biostudies-literature
Project description:It is unclear whether the infectious etiology of severe bronchiolitis affects short-term outcomes, such as posthospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse.We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007-2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent bronchiolitis visit or scheduled visit at which additions to the bronchiolitis medications were made) during the 2 weeks after hospital discharge.Among 1836 enrolled children with 2-week, follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV coinfection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (odds ratio: 0.99; 95% confidence interval: 0.52-1.90; P = 0.98), whereas those with RSV/RV coinfection were more likely to have relapse (odds ratio: 1.54; 95% confidence interval: 1.03-2.30; P = 0.03).In this prospective, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that RSV/RV coinfection was independently associated with a higher likelihood of bronchiolitis relapse. Present data support the concept that the infectious etiology of severe bronchiolitis affects short-term outcomes.
| S-EPMC4145057 | biostudies-literature
Project description:BackgroundChildhood community acquired pneumonia (CAP) is a significant problem in developing countries, and confirmation of microbial etiology is important for individual, as well as public health. However, there is paucity of data from a large cohort, examining multiple biological specimens for diverse pathogens (bacteria and viruses). The Community Acquired Pneumonia Etiology Study (CAPES) was designed to address this knowledge gap.MethodsWe enrolled children with CAP (based on WHO IMCI criteria of tachypnea with cough or breathing difficulty) over 24 consecutive months, and recorded presenting symptoms, risk factors, clinical signs, and chest radiography. We performed blood and nasopharyngeal aspirate (NPA) bacterial cultures, and serology (Mycoplasma pneumoniae, Chlamydophila pneumoniae). We also performed multiplex PCR for 25 bacterial/viral species in a subgroup representing 20% of the cohort. Children requiring endotracheal intubation underwent culture and PCR of bronchoalveolar lavage (BAL) specimens.FindingsWe enrolled 2345 children. NPA and blood cultures yielded bacteria in only 322 (13.7%) and 49 (2.1%) children respectively. In NPA, Streptococcus pneumoniae (79.1%) predominated, followed by Haemophilus influenzae (9.6%) and Staphylococcus aureus (6.8%). In blood, S. aureus (30.6%) dominated, followed by S. pneumoniae (20.4%) and Klebsiella pneumoniae (12.2%). M. pneumoniae and C. pneumoniae serology were positive in 4.3% and 1.1% respectively. Multiplex PCR in 428 NPA specimens identified organisms in 422 (98.6%); of these 352 (82.2%) had multiple organisms and only 70 (16.4%) had a single organism viz. S. pneumoniae: 35 (50%), Cytomegalovirus (CMV): 13 (18.6%), Respiratory Syncytial Virus (RSV): 9 (12.9%), other viruses: 6 (8.7%), S. aureus: 5 (7.1%), and H. influenzae: 2 (2.9%). BAL PCR (n?=?30) identified single pathogens in 10 (S. pneumoniae-3, CMV-3, S. aureus-2, H. influenzae-2) and multiple pathogens in 18 children. There were 108 (4.6%) deaths. The pattern of pathogens identified did not correlate with pneumonia severity or mortality.ConclusionsThe majority of children with CAP have multiple pathogens (bacteria and viruses). S. pneumoniae and S. aureus predominate in NPA and blood respectively. CMV and RSV were the dominant respiratory viruses in NPA and BAL. The presence of multiple pathogens, especially organisms associated with nasopharyngeal carriage, precludes confirmation of a causal relationship in most cases.
| S-EPMC4623579 | biostudies-literature
Project description:Background and objectivesPneumonia is a leading cause of hospitalization and readmission in children. Understanding the patient characteristics associated with pneumonia readmissions is necessary to inform interventions to reduce avoidable hospitalizations and related costs. The objective of this study was to characterize readmission rates, and identify factors and costs associated with readmission among children previously hospitalized with pneumonia.MethodsRetrospective cohort study of children hospitalized with pneumonia at the 43 hospitals included in the Pediatric Health Information System between January 1, 2008, and December 31, 2011. The primary outcome was all-cause readmission within 30 days after hospital discharge, and the secondary outcome was pneumonia-specific readmission. We used multivariable regression models to identify patient and hospital characteristics and costs associated with readmission.ResultsA total of 82?566 children were hospitalized with pneumonia (median age, 3 years; interquartile range 1-7). Thirty-day all-cause and pneumonia-specific readmission rates were 7.7% and 3.1%, respectively. Readmission rates were higher among children <1 year of age, as well as in patients with previous hospitalizations, longer index hospitalizations, and complicated pneumonia. Children with chronic medical conditions were more likely to experience all-cause (odds ratio 3.0; 95% confidence interval 2.8-3.2) and pneumonia-specific readmission (odds ratio 1.8; 95% confidence interval 1.7-2.0) compared with children without chronic medical conditions. The median cost of a readmission ($11?344) was higher than that of an index admission ($4495; P = .01). Readmissions occurred in 8% of pneumonia hospitalizations but accounted for 16.3% of total costs for all pneumonia hospitalizations.ConclusionsReadmissions are common after hospitalization for pneumonia, especially among young children and those with chronic medical conditions, and are associated with substantial costs.
| S-EPMC4531280 | biostudies-literature