Baggett Henry C, Watson Nora L, Deloria Knoll Maria, Brooks W Abdullah, Feikin Daniel R, Hammitt Laura L, Howie Stephen R C, Kotloff Karen L, Levine Orin S, Madhi Shabir A, Murdoch David R, Scott J Anthony G, Thea Donald M, Antonio Martin, Awori Juliet O, Baillie Vicky L, DeLuca Andrea N, Driscoll Amanda J, Duncan Julie, Ebruke Bernard E, Goswami Doli, Higdon Melissa M, Karron Ruth A, Moore David P, Morpeth Susan C, Mulindwa Justin M, Park Daniel E, Paveenkittiporn Wantana, Piralam Barameht, Prosperi Christine, Sow Samba O, Tapia Milagritos D, Zaman Khalequ, Zeger Scott L, O'Brien Katherine L
Global Disease Detection Center, Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi.
Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Clin Infect Dis. 2017 Jun 15;64(suppl_3):S317-S327. doi: 10.1093/cid/cix100.
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.
以往研究提示上呼吸道肺炎球菌定植密度与肺炎球菌肺炎之间存在关联，但儿童相关数据有限。我们利用儿童健康肺炎病因研究（PERCH）的数据评估了这种潜在关联。
PERCH是一项在7个国家开展的病例对照研究，这7个国家分别为孟加拉国、冈比亚、肯尼亚、马里、南非、泰国和赞比亚。病例为1至59个月大因世界卫生组织定义的重度或极重度肺炎住院的儿童。对照从社区中随机选取。微生物学确诊的肺炎球菌肺炎（MCPP）通过在相关正常无菌体液中检测到肺炎球菌来确诊。通过对鼻咽/口咽标本进行定量聚合酶链反应分析计算定植密度。
56例MCPP病例（MCPP病例组）的定植密度中位数（17.28×10⁶拷贝/毫升）超过无MCPP病例（非MCPP病例组）（0.75×10⁶拷贝/毫升）和对照组（0.60×10⁶拷贝/毫升）（P均<0.001）。使用约登指数区分MCPP病例与对照组的最佳密度>6.9 log₁₀拷贝/毫升；总体而言，敏感性为64%，特异性为92%，不同地点表现有所差异。当将MCPP病例与标本采集前接受过抗生素治疗的对照组区分开时，阈值较低（≥4.4 log₁₀拷贝/毫升）。在4035例非MCPP病例中，500例（12%）的肺炎球菌定植密度>6.9 log₁₀拷贝/毫升；高于此临界值与胸部X线片显示的肺泡实变、极重度肺炎、血氧饱和度<92%、C反应蛋白≥40毫克/升以及未接受抗生素预处理相关（P均<0.001）。
肺炎球菌定植密度>6.9 log₁₀拷贝/毫升与MCPP密切相关，可用于改善儿童肺炎研究中肺炎球菌肺炎患病率的估计。我们的研究结果不支持在临床环境中将其用于个体诊断。
