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Lancet. 2019 Jun 27. pii: S0140-6736(19)30721-4. doi: 10.1016/S0140-6736(19)30721-4. [Epub ahead of print]
[h=1]Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study.[/h] Pneumonia Etiology Research for Child Health (PERCH) Study Group.
[h=3]Collaborators (77)[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings.
[h=4]METHODS:[/h] We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data.
[h=4]FINDINGS:[/h] Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41?8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99?7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31?7%) of 1752 cases (range by site 10?6-97?3%). 30-day case-fatality ratio was 6?4% (114 of 1769 cases). Blood cultures were positive in 56 (3?2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33?9%] of 56). Almost all cases (98?9%) and controls (98?0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61?4% (95% credible interval [CrI] 57?3-65?6) of causes, whereas bacteria accounted for 27?3% (23?3-31?6) and Mycobacterium tuberculosis for 5?9% (3?9-8?3). Viruses were less common (54?5%, 95% CrI 47?4-61?5 vs 68?0%, 62?7-72?7) and bacteria more common (33?7%, 27?2-40?8 vs 22?8%, 18?3-27?6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31?1%, 95% CrI 28?4-34?2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction.
[h=4]INTERPRETATION:[/h] In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes.
[h=4]FUNDING:[/h] Bill & Melinda Gates Foundation.
Copyright ? 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID: 31257127 DOI: 10.1016/S0140-6736(19)30721-4
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[h=1]Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study.[/h] Pneumonia Etiology Research for Child Health (PERCH) Study Group.
[h=3]Collaborators (77)[/h]
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings.
[h=4]METHODS:[/h] We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data.
[h=4]FINDINGS:[/h] Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41?8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99?7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31?7%) of 1752 cases (range by site 10?6-97?3%). 30-day case-fatality ratio was 6?4% (114 of 1769 cases). Blood cultures were positive in 56 (3?2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33?9%] of 56). Almost all cases (98?9%) and controls (98?0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61?4% (95% credible interval [CrI] 57?3-65?6) of causes, whereas bacteria accounted for 27?3% (23?3-31?6) and Mycobacterium tuberculosis for 5?9% (3?9-8?3). Viruses were less common (54?5%, 95% CrI 47?4-61?5 vs 68?0%, 62?7-72?7) and bacteria more common (33?7%, 27?2-40?8 vs 22?8%, 18?3-27?6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31?1%, 95% CrI 28?4-34?2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction.
[h=4]INTERPRETATION:[/h] In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes.
[h=4]FUNDING:[/h] Bill & Melinda Gates Foundation.
Copyright ? 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID: 31257127 DOI: 10.1016/S0140-6736(19)30721-4
Free full text