Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.
Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.
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DOI：
10.1016/s0140-6736(16)31529-x
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发表时间：
2016-09-24
期刊：
影响因子：
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通讯作者：
Houpt ER
中科院分区：
文献类型：
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作者：
Liu J;Platts-Mills JA;Juma J;Kabir F;Nkeze J;Okoi C;Operario DJ;Uddin J;Ahmed S;Alonso PL;Antonio M;Becker SM;Blackwelder WC;Breiman RF;Faruque AS;Fields B;Gratz J;Haque R;Hossain A;Hossain MJ;Jarju S;Qamar F;Iqbal NT;Kwambana B;Mandomando I;McMurry TL;Ochieng C;Ochieng JB;Ochieng M;Onyango C;Panchalingam S;Kalam A;Aziz F;Qureshi S;Ramamurthy T;Roberts JH;Saha D;Sow SO;Stroup SE;Sur D;Tamboura B;Taniuchi M;Tennant SM;Toema D;Wu Y;Zaidi A;Nataro JP;Kotloff KL;Levine MM;Houpt ER
腹泻是世界范围内儿童死亡的第二大原因，但不同的诊断方法和不同的测试特征可能会使确定原因变得复杂。我们在全球肠道多中心研究（GEMS）中使用定量分子诊断方法重新评估腹泻的原因。GEMS是一项针对非洲和亚洲5岁以下儿童中度至重度腹泻的研究。我们使用定量实时PCR（qPCR）检测来自GEMS的病例和匹配的无症状对照的粪便样本中的32种肠道病原体，并将病原体特异性归因发病率与原始GEMS微生物学方法（包括培养、EIA和逆转录酶PCR）所发现的发病率进行比较。我们计算了修订后的病原体特异性疾病负担，并评估了个别儿童的病因。我们分析了5304个样本对。对于大多数病原体，qPCR的发生率高于原始方法，特别是对于腺病毒40/41（约5倍）、志贺氏菌属或肠侵袭性大肠埃希菌（EIEC）和空肠弯曲菌或大肠埃希菌（约2倍）以及热稳定肠毒素产生大肠埃希菌（[ST-ETEC]约1.5倍）。6种最易归因的病原体依次为志贺氏菌属、轮状病毒、腺病毒40/41、ST-ETEC、隐孢子虫属和弯曲杆菌属。在人群水平上，病原体可归因的肠道负担为89.3%（95%CI 83.2 - 96.0），而在原始GEMS分析中为51.5%（48.0 - 55.0）。前6位致病菌占腹泻总致病菌数的77.8%（74.6 ~ 80.9）。使用模型衍生的定量截断值评估单个腹泻病例，5304例病例中有2254例（42.5%）检出一种腹泻相关病原体，2063例（38.9%）检出两种或两种以上病原体，志贺氏菌属和轮状病毒是与混合感染儿童腹泻最密切相关的病原体。定量分子诊断方法改善了腹泻病因的人群水平和病例水平特征，并表明与六种病原体相关的疾病负担很高，应优先考虑靶向治疗。比尔和梅林达·盖茨基金会。
Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni or C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2–96·0) at the population level, compared with 51·5% (48·0–55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6–80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. Bill & Melinda Gates Foundation.