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

被引:93
作者
Baggett, Henry C. [1 ,2 ]
Watson, Nora L. [3 ]
Knoll, Maria Deloria [4 ]
Brooks, W. Abdullah [5 ,6 ,7 ]
Feikin, Daniel R. [4 ,8 ]
Hammitt, Laura L. [4 ,7 ,9 ]
Howie, Stephen R. C. [10 ,11 ,12 ]
Kotloff, Karen L. [13 ]
Levine, Orin S. [4 ,14 ]
Madhi, Shabir A. [15 ,16 ]
Murdoch, David R. [17 ,18 ]
Scott, J. Anthony G. [9 ,19 ]
Thea, Donald M. [20 ]
Antonio, Martin [10 ,21 ,22 ]
Awori, Juliet O. [9 ]
Baillie, Vicky L. [15 ,16 ]
DeLuca, Andrea N. [4 ,23 ]
Driscoll, Amanda J. [4 ]
Duncan, Julie [24 ]
Ebruke, Bernard E. [10 ]
Goswami, Doli [7 ]
Higdon, Melissa M. [4 ]
Karron, Ruth A. [25 ]
Moore, David P. [15 ,16 ,26 ,27 ]
Morpeth, Susan C. [19 ,28 ]
Mulindwa, Justin M. [24 ]
Park, Daniel E. [4 ,29 ]
Paveenkittiporn, Wantana [30 ]
Piralam, Barameht [31 ]
Prosperi, Christine [4 ]
Sow, Samba O. [32 ]
Tapia, Milagritos D. [13 ]
Zaman, Khalequ [7 ]
Zeger, Scott L. [33 ]
O'Brien, Katherine L. [4 ]
机构
[1] Thailand Minist Publ Health, US Centers Dis Control & Prevent Collaborat, Global Dis Detect Ctr, Nonthaburi, Thailand
[2] Ctr Global Hlth, Ctr Dis Control & Prevent, Div Global Hlth Protect, Atlanta, GA USA
[3] Emmes Corp, Rockville, MD USA
[4] Hopkins Bloomberg Sch Publ Hlth, Int Vaccine Access Ctr, Baltimore, MD USA
[5] Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA
[6] Int Ctr Diarrhoeal Dis Res Icddr B, Dhaka, Bangladesh
[7] Natl Ctr Immunizat & Resp Dis, Centers Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA
[8] Natl Ctr Immunizat & Resp Dis, Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA
[9] Kenya Govt Med Res Ctr, Wellcome Trust Res Programme, Kilifi, Kenya
[10] MRC Unit, Basse, Gambia
[11] Univ Auckland, Dept Pediat, Dunedin, New Zealand
[12] Univ Otago, Ctr Int Hlth, Dunedin, New Zealand
[13] Univ Maryland, Sch Med, Inst Global Hlth, Ctr Vaccine Dev,Dept Pediat,Div Infect Dis & Trop, Baltimore, MD USA
[14] Bill & Melinda Gates Fdn, Seattle, WA USA
[15] Univ Witwatersrand, Resp & Meningeal Pathogens Res Unit, Med Res Council, Johannesburg, South Africa
[16] Univ Witwatersrand, Natl Res Fdn, Vaccine Preventable Dis Unit, Dept Sci & Technol, Johannesburg, South Africa
[17] Univ Otago, Dept Pathol, Christchurch, New Zealand
[18] Canterbury Hlth Labs, Microbiol Lab, Christchurch, New Zealand
[19] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England
[20] Boston Univ, Sch Publ Hlth, Ctr Global Hlth & Dev, Boston, MA USA
[21] Univ Warwick, Warwick Med Sch, Microbiol & Infect Unit, Coventry, W Midlands, England
[22] London Sch Hyg Trop Med, Dept Pathogen Mol Biol, London, England
[23] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA
[24] Univ Teaching Hosp, Lusaka, Zambia
[25] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD USA
[26] Chris Hani Baragwanath Acad Hosp, Dept Paediat & Child Hlth, Soweto, South Africa
[27] Univ Witwatersrand, Johannesburg, South Africa
[28] Middlemore Hosp, Counties Manukau Dist Hlth Board, Microbiol Lab, Auckland, New Zealand
[29] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Epidemiol & Biostat, Washington, DC USA
[30] Minist Publ Hlth, Natl Inst Hlth, Nonthaburi, Thailand
[31] Nakhon Phanom Prov Hlth Off, Nakhon Phanom, Thailand
[32] Ctr Dev Vaccins CVD Mali, Bamako, Mali
[33] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA
基金
比尔及梅琳达.盖茨基金会; 英国惠康基金;
关键词
pneumococcus; colonization; pneumonia; children; etiology; POLYMERASE-CHAIN-REACTION; CONJUGATE VACCINE; STANDARDIZED INTERPRETATION; CHEST RADIOGRAPHS; ETIOLOGY RESEARCH; INFLUENZA-VIRUS; YOUNG-CHILDREN; DISEASE; BLOOD; LOAD;
D O I
10.1093/cid/cix100
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 x 10(6) copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 x 10(6)) and controls (0.60 x 10(6)) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log(10) copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (>= 4.4 log(10) 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 log(10) 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 log(10) 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.
引用
收藏
页码:S317 / S327
页数:11
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