Deloria Knoll Maria, Morpeth Susan C, Scott J Anthony G, Watson Nora L, Park Daniel E, Baggett Henry C, Brooks W Abdullah, Feikin Daniel R, Hammitt Laura L, Howie Stephen R C, Kotloff Karen L, Levine Orin S, O'Brien Katherine L, Thea Donald M, Ahmed Dilruba, Antonio Martin, Awori Juliet O, Baillie Vicky L, Chipeta James, Deluca Andrea N, Dione Michel, Driscoll Amanda J, Higdon Melissa M, Jatapai Anchalee, Karron Ruth A, Mazumder Razib, Moore David P, Mwansa James, Nyongesa Sammy, Prosperi Christine, Seidenberg Phil, Siludjai Duangkamon, Sow Samba O, Tamboura Boubou, Zeger Scott L, Murdoch David R, Madhi Shabir A
Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi.
Clin Infect Dis. 2017 Jun 15;64(suppl_3):S357-S367. doi: 10.1093/cid/cix149.
BACKGROUND.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia.
METHODS.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls.
RESULTS.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls.
CONCLUSIONS.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.
在9个非洲和亚洲地区，通过lytA聚合酶链反应（PCR）检测血液中的肺炎球菌，对诊断儿童肺炎球菌肺炎的诊断准确性较差。我们评估了血液lytA定量在诊断肺炎球菌肺炎中的价值。
儿童健康肺炎病因研究（PERCH）病例对照研究对1至59个月龄因肺炎体征住院的儿童以及年龄频率匹配的社区对照进行了全血PCR检测肺炎球菌。比较了微生物学确诊的肺炎球菌肺炎（MCPP）病例、非肺炎球菌病原体确诊病例、未确诊病例和对照中PCR阳性参与者的负荷分布。受试者操作特征分析确定了区分MCPP病例与对照的“最佳阈值”。
在血液中检测到肺炎球菌PCR的291例病例中的290例和273例对照中的273例有负荷数据。MCPP病例的负荷高于对照（中位数分别为4.0×10³和0.19×10³拷贝/毫升），但有很大重叠（范围分别为0.16 - 989.9×10³拷贝/毫升和0.01 - 551.9×10³拷贝/毫升）。高负荷（≥2.2 log10拷贝/毫升）的比例在MCPP病例中为62.5%，在未确诊病例中为4.3%，在非肺炎球菌病原体确诊病例中为9.3%，在对照中为3.1%。对照中血液中的肺炎球菌负荷与呼吸道疾病无关（P = 0.32）。高血液肺炎球菌负荷与未确诊病例胸部X光片上的肺泡实变有关，与未确诊病例（而非对照）中高（>6.9 log10拷贝/毫升）的鼻咽/口咽负荷和C反应蛋白≥40毫克/升有关（两者P < 0.01）。
血液中肺炎球菌定量PCR在识别个体儿童肺炎球菌肺炎方面的诊断效用有限，但在流行病学研究中可能具有参考价值。
