Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study

Katherine L. O'Brien, Henry C. Baggett, W. Abdullah Brooks, Daniel R. Feikin, Laura L. Hammitt, Melissa M. Higdon, Stephen R.C. Howie, Maria Deloria Knoll, Karen L. Kotloff, Orin S. Levine, Shabir A. Madhi, David R. Murdoch, Christine Prosperi, J. Anthony G. Scott, Qiyuan Shi, Donald M. Thea, Zhenke Wu, Scott L. Zeger, Peter V. Adrian, Pasakorn AkarasewiTrevor P. Anderson, Martin Antonio, Juliet O. Awori, Vicky L. Baillie, Charatdao Bunthi, James Chipeta, Mohammod Jobayer Chisti, Jane Crawley, Andrea N. DeLuca, Amanda J. Driscoll, Bernard E. Ebruke, Hubert P. Endtz, Nicholas Fancourt, Wei Fu, Doli Goswami, Michelle J. Groome, Meredith Haddix, Lokman Hossain, Yasmin Jahan, E. Wangeci Kagucia, Alice Kamau, Ruth A. Karron, Sidi Kazungu, Nana Kourouma, Locadiah Kuwanda, Geoffrey Kwenda, Mengying Li, Eunice M. Machuka, Grant Mackenzie, Nasreen Mahomed, Susan A. Maloney, Jessica L. McLellan, Joanne L. Mitchell, David P. Moore, Susan C. Morpeth, Azwifarwi Mudau, Lawrence Mwananyanda, James Mwansa, Micah Silaba Ominde, Uma Onwuchekwa, Daniel E. Park, Julia Rhodes, Pongpun Sawatwong, Phil Seidenberg, Arifin Shamsul, Eric A.F. Simões, Seydou Sissoko, Somwe Wa Somwe, Samba O. Sow, Mamadou Sylla, Boubou Tamboura, Milagritos D. Tapia, Somsak Thamthitiwat, Aliou Toure, Nora L. Watson, Khalequ Zaman, Syed M.A. Zaman

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Bill & Melinda Gates Foundation.

Original languageEnglish (US)
Pages (from-to)757-779
Number of pages23
JournalThe Lancet
Volume394
Issue number10200
DOIs
StatePublished - Aug 31 2019

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HIV Infections
Case-Control Studies
Pneumonia
Paramyxoviridae Infections
Respiratory Syncytial Viruses
Metapneumovirus
Human Influenza
Viruses
Rhinovirus
Bacteria
Thorax
X-Rays
Gambia
Staphylococcal Pneumonia
Mali
Zambia
Pneumocystis carinii
Haemophilus influenzae type b
Bordetella pertussis
Bangladesh

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia : the PERCH multi-country case-control study. / O'Brien, Katherine L.; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Higdon, Melissa M.; Howie, Stephen R.C.; Deloria Knoll, Maria; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; Prosperi, Christine; Scott, J. Anthony G.; Shi, Qiyuan; Thea, Donald M.; Wu, Zhenke; Zeger, Scott L.; Adrian, Peter V.; Akarasewi, Pasakorn; Anderson, Trevor P.; Antonio, Martin; Awori, Juliet O.; Baillie, Vicky L.; Bunthi, Charatdao; Chipeta, James; Chisti, Mohammod Jobayer; Crawley, Jane; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Endtz, Hubert P.; Fancourt, Nicholas; Fu, Wei; Goswami, Doli; Groome, Michelle J.; Haddix, Meredith; Hossain, Lokman; Jahan, Yasmin; Kagucia, E. Wangeci; Kamau, Alice; Karron, Ruth A.; Kazungu, Sidi; Kourouma, Nana; Kuwanda, Locadiah; Kwenda, Geoffrey; Li, Mengying; Machuka, Eunice M.; Mackenzie, Grant; Mahomed, Nasreen; Maloney, Susan A.; McLellan, Jessica L.; Mitchell, Joanne L.; Moore, David P.; Morpeth, Susan C.; Mudau, Azwifarwi; Mwananyanda, Lawrence; Mwansa, James; Silaba Ominde, Micah; Onwuchekwa, Uma; Park, Daniel E.; Rhodes, Julia; Sawatwong, Pongpun; Seidenberg, Phil; Shamsul, Arifin; Simões, Eric A.F.; Sissoko, Seydou; Wa Somwe, Somwe; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Tapia, Milagritos D.; Thamthitiwat, Somsak; Toure, Aliou; Watson, Nora L.; Zaman, Khalequ; Zaman, Syed M.A.

In: The Lancet, Vol. 394, No. 10200, 31.08.2019, p. 757-779.

Research output: Contribution to journalArticle

O'Brien, KL, Baggett, HC, Brooks, WA, Feikin, DR, Hammitt, LL, Higdon, MM, Howie, SRC, Deloria Knoll, M, Kotloff, KL, Levine, OS, Madhi, SA, Murdoch, DR, Prosperi, C, Scott, JAG, Shi, Q, Thea, DM, Wu, Z, Zeger, SL, Adrian, PV, Akarasewi, P, Anderson, TP, Antonio, M, Awori, JO, Baillie, VL, Bunthi, C, Chipeta, J, Chisti, MJ, Crawley, J, DeLuca, AN, Driscoll, AJ, Ebruke, BE, Endtz, HP, Fancourt, N, Fu, W, Goswami, D, Groome, MJ, Haddix, M, Hossain, L, Jahan, Y, Kagucia, EW, Kamau, A, Karron, RA, Kazungu, S, Kourouma, N, Kuwanda, L, Kwenda, G, Li, M, Machuka, EM, Mackenzie, G, Mahomed, N, Maloney, SA, McLellan, JL, Mitchell, JL, Moore, DP, Morpeth, SC, Mudau, A, Mwananyanda, L, Mwansa, J, Silaba Ominde, M, Onwuchekwa, U, Park, DE, Rhodes, J, Sawatwong, P, Seidenberg, P, Shamsul, A, Simões, EAF, Sissoko, S, Wa Somwe, S, Sow, SO, Sylla, M, Tamboura, B, Tapia, MD, Thamthitiwat, S, Toure, A, Watson, NL, Zaman, K & Zaman, SMA 2019, 'Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study', The Lancet, vol. 394, no. 10200, pp. 757-779. https://doi.org/10.1016/S0140-6736(19)30721-4
O'Brien, Katherine L. ; Baggett, Henry C. ; Brooks, W. Abdullah ; Feikin, Daniel R. ; Hammitt, Laura L. ; Higdon, Melissa M. ; Howie, Stephen R.C. ; Deloria Knoll, Maria ; Kotloff, Karen L. ; Levine, Orin S. ; Madhi, Shabir A. ; Murdoch, David R. ; Prosperi, Christine ; Scott, J. Anthony G. ; Shi, Qiyuan ; Thea, Donald M. ; Wu, Zhenke ; Zeger, Scott L. ; Adrian, Peter V. ; Akarasewi, Pasakorn ; Anderson, Trevor P. ; Antonio, Martin ; Awori, Juliet O. ; Baillie, Vicky L. ; Bunthi, Charatdao ; Chipeta, James ; Chisti, Mohammod Jobayer ; Crawley, Jane ; DeLuca, Andrea N. ; Driscoll, Amanda J. ; Ebruke, Bernard E. ; Endtz, Hubert P. ; Fancourt, Nicholas ; Fu, Wei ; Goswami, Doli ; Groome, Michelle J. ; Haddix, Meredith ; Hossain, Lokman ; Jahan, Yasmin ; Kagucia, E. Wangeci ; Kamau, Alice ; Karron, Ruth A. ; Kazungu, Sidi ; Kourouma, Nana ; Kuwanda, Locadiah ; Kwenda, Geoffrey ; Li, Mengying ; Machuka, Eunice M. ; Mackenzie, Grant ; Mahomed, Nasreen ; Maloney, Susan A. ; McLellan, Jessica L. ; Mitchell, Joanne L. ; Moore, David P. ; Morpeth, Susan C. ; Mudau, Azwifarwi ; Mwananyanda, Lawrence ; Mwansa, James ; Silaba Ominde, Micah ; Onwuchekwa, Uma ; Park, Daniel E. ; Rhodes, Julia ; Sawatwong, Pongpun ; Seidenberg, Phil ; Shamsul, Arifin ; Simões, Eric A.F. ; Sissoko, Seydou ; Wa Somwe, Somwe ; Sow, Samba O. ; Sylla, Mamadou ; Tamboura, Boubou ; Tapia, Milagritos D. ; Thamthitiwat, Somsak ; Toure, Aliou ; Watson, Nora L. ; Zaman, Khalequ ; Zaman, Syed M.A. / Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia : the PERCH multi-country case-control study. In: The Lancet. 2019 ; Vol. 394, No. 10200. pp. 757-779.
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title = "Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study",
abstract = "Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Bill & Melinda Gates Foundation.",
author = "O'Brien, {Katherine L.} and Baggett, {Henry C.} and Brooks, {W. Abdullah} and Feikin, {Daniel R.} and Hammitt, {Laura L.} and Higdon, {Melissa M.} and Howie, {Stephen R.C.} and {Deloria Knoll}, Maria and Kotloff, {Karen L.} and Levine, {Orin S.} and Madhi, {Shabir A.} and Murdoch, {David R.} and Christine Prosperi and Scott, {J. Anthony G.} and Qiyuan Shi and Thea, {Donald M.} and Zhenke Wu and Zeger, {Scott L.} and Adrian, {Peter V.} and Pasakorn Akarasewi and Anderson, {Trevor P.} and Martin Antonio and Awori, {Juliet O.} and Baillie, {Vicky L.} and Charatdao Bunthi and James Chipeta and Chisti, {Mohammod Jobayer} and Jane Crawley and DeLuca, {Andrea N.} and Driscoll, {Amanda J.} and Ebruke, {Bernard E.} and Endtz, {Hubert P.} and Nicholas Fancourt and Wei Fu and Doli Goswami and Groome, {Michelle J.} and Meredith Haddix and Lokman Hossain and Yasmin Jahan and Kagucia, {E. Wangeci} and Alice Kamau and Karron, {Ruth A.} and Sidi Kazungu and Nana Kourouma and Locadiah Kuwanda and Geoffrey Kwenda and Mengying Li and Machuka, {Eunice M.} and Grant Mackenzie and Nasreen Mahomed and Maloney, {Susan A.} and McLellan, {Jessica L.} and Mitchell, {Joanne L.} and Moore, {David P.} and Morpeth, {Susan C.} and Azwifarwi Mudau and Lawrence Mwananyanda and James Mwansa and {Silaba Ominde}, Micah and Uma Onwuchekwa and Park, {Daniel E.} and Julia Rhodes and Pongpun Sawatwong and Phil Seidenberg and Arifin Shamsul and Sim{\~o}es, {Eric A.F.} and Seydou Sissoko and {Wa Somwe}, Somwe and Sow, {Samba O.} and Mamadou Sylla and Boubou Tamboura and Tapia, {Milagritos D.} and Somsak Thamthitiwat and Aliou Toure and Watson, {Nora L.} and Khalequ Zaman and Zaman, {Syed M.A.}",
year = "2019",
month = "8",
day = "31",
doi = "10.1016/S0140-6736(19)30721-4",
language = "English (US)",
volume = "394",
pages = "757--779",
journal = "The Lancet",
issn = "0140-6736",
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TY - JOUR

T1 - Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia

T2 - the PERCH multi-country case-control study

AU - O'Brien, Katherine L.

AU - Baggett, Henry C.

AU - Brooks, W. Abdullah

AU - Feikin, Daniel R.

AU - Hammitt, Laura L.

AU - Higdon, Melissa M.

AU - Howie, Stephen R.C.

AU - Deloria Knoll, Maria

AU - Kotloff, Karen L.

AU - Levine, Orin S.

AU - Madhi, Shabir A.

AU - Murdoch, David R.

AU - Prosperi, Christine

AU - Scott, J. Anthony G.

AU - Shi, Qiyuan

AU - Thea, Donald M.

AU - Wu, Zhenke

AU - Zeger, Scott L.

AU - Adrian, Peter V.

AU - Akarasewi, Pasakorn

AU - Anderson, Trevor P.

AU - Antonio, Martin

AU - Awori, Juliet O.

AU - Baillie, Vicky L.

AU - Bunthi, Charatdao

AU - Chipeta, James

AU - Chisti, Mohammod Jobayer

AU - Crawley, Jane

AU - DeLuca, Andrea N.

AU - Driscoll, Amanda J.

AU - Ebruke, Bernard E.

AU - Endtz, Hubert P.

AU - Fancourt, Nicholas

AU - Fu, Wei

AU - Goswami, Doli

AU - Groome, Michelle J.

AU - Haddix, Meredith

AU - Hossain, Lokman

AU - Jahan, Yasmin

AU - Kagucia, E. Wangeci

AU - Kamau, Alice

AU - Karron, Ruth A.

AU - Kazungu, Sidi

AU - Kourouma, Nana

AU - Kuwanda, Locadiah

AU - Kwenda, Geoffrey

AU - Li, Mengying

AU - Machuka, Eunice M.

AU - Mackenzie, Grant

AU - Mahomed, Nasreen

AU - Maloney, Susan A.

AU - McLellan, Jessica L.

AU - Mitchell, Joanne L.

AU - Moore, David P.

AU - Morpeth, Susan C.

AU - Mudau, Azwifarwi

AU - Mwananyanda, Lawrence

AU - Mwansa, James

AU - Silaba Ominde, Micah

AU - Onwuchekwa, Uma

AU - Park, Daniel E.

AU - Rhodes, Julia

AU - Sawatwong, Pongpun

AU - Seidenberg, Phil

AU - Shamsul, Arifin

AU - Simões, Eric A.F.

AU - Sissoko, Seydou

AU - Wa Somwe, Somwe

AU - Sow, Samba O.

AU - Sylla, Mamadou

AU - Tamboura, Boubou

AU - Tapia, Milagritos D.

AU - Thamthitiwat, Somsak

AU - Toure, Aliou

AU - Watson, Nora L.

AU - Zaman, Khalequ

AU - Zaman, Syed M.A.

PY - 2019/8/31

Y1 - 2019/8/31

N2 - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Bill & Melinda Gates Foundation.

AB - Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: Bill & Melinda Gates Foundation.

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UR - http://www.scopus.com/inward/citedby.url?scp=85069522084&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(19)30721-4

DO - 10.1016/S0140-6736(19)30721-4

M3 - Article

C2 - 31257127

AN - SCOPUS:85069522084

VL - 394

SP - 757

EP - 779

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 10200

ER -