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Clin Infect Dis. 2017 Jun 15;64(suppl_3):S317-S327. doi: 10.1093/cid/cix100.

Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.

Author information

1
Global Disease Detection Center, Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
2
Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
3
The Emmes Corporation, Rockville.
4
International Vaccine Access Center, and.
5
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
6
International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka and Matlab.
7
Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
8
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
9
Medical Research Council Unit, Basse, The Gambia.
10
Department of Paediatrics University of Auckland, and.
11
Centre for International Health, University of Otago, Dunedin, New Zealand.
12
Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development, Institute of Global Health, University of Maryland School of Medicine, Baltimore.
13
Bill & Melinda Gates Foundation, Seattle, Washington.
14
Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, and.
15
Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Unit, University of the Witwatersrand, Johannesburg, South Africa.
16
Department of Pathology, University of Otago, and.
17
Microbiology Unit, Canterbury Health Laboratories, Christchurch, New Zealand.
18
Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, United Kingdom.
19
Center for Global Health and Development, Boston University School of Public Health, Massachusetts.
20
Microbiology and Infection Unit, Warwick Medical School, University of Warwick, Coventry, and.
21
Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, United Kingdom.
22
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
23
University Teaching Hospital, Lusaka, Zambia.
24
Department of International Health, Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
25
Department of Paediatrics & Child Health, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, South Africa.
26
Microbiology Laboratory, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
27
Milken Institute School of Public Health, Department of Epidemiology and Biostatistics, George Washington University, District Columbia.
28
National Institute of Health, Ministry of Public Health, Nonthaburi, and.
29
Nakhon Phanom Provincial Health Office, Nakhon Phanom, Thailand.
30
Centre pour le Développement des Vaccins (CVD-Mali), Bamako, Mali; and.
31
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Abstract

Background.:

Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association.

Methods.:

PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens.

Results.:

Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001).

Conclusions.:

Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

KEYWORDS:

children; colonization; etiology; pneumococcus; pneumonia

PMID:
28575365
PMCID:
PMC5850437
DOI:
10.1093/cid/cix100
[Indexed for MEDLINE]
Free PMC Article

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