The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.
The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.
复制标题
DOI：
10.1093/cid/ciaa1545
复制
发表时间：
2021-08-02
期刊：
影响因子：
--
通讯作者：
Kotloff KL
中科院分区：
文献类型：
--
作者：
Pavlinac PB;Platts-Mills JA;Tickell KD;Liu J;Juma J;Kabir F;Nkeze J;Okoi C;Operario DJ;Uddin J;Ahmed S;Alonso PL;Antonio M;Becker SM;Breiman RF;Faruque ASG;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;Roose A;Toema D;Wu Y;Zaidi A;Nataro JP;Levine MM;Houpt ER;Kotloff KL
志贺氏菌是儿童腹泻的主要原因，也是疫苗开发的目标。儿科现场疫苗效力试验需要微生物学和临床病例定义。在全球肠道多中心研究(GEMS)中，我们比较了培养阳性志贺氏菌和培养阴性、定量聚合酶链式反应(QPCR)可归因于志贺氏菌(由IPAH基因周期阈值定义为27.9)的儿童中重度腹泻(MSD)病例的特征。在志贺氏菌MSD病例中，我们确定了死亡的危险因素，并得出了临床严重程度评分。与培养阳性志贺氏菌病病例(n = 745)相比，培养阴性/qPCR型志贺氏菌病例(n = 852)更有可能在12个月以下、发育迟缓、腹泻持续时间更长，并且不太可能有高粪便频率或发烧。在脱水、住院或严重分级方面，与改良的Vesikari评分没有差异。22例(1.8%)志贺氏菌MSD病例在出现在卫生机构后14天内死亡，其中59.1%的死亡病例为培养阴性病例。年龄 <；12个月、出现前腹泻持续时间、呕吐、发育迟缓、消瘦和住院与死亡率相关。模型得出的评分为脱水、住院和较长的腹泻持续时间分配了分数，但在预测14天死亡率方面并不比修正的Vesikari评分明显更好。在疫苗试验中，与严重疾病或痢疾相一致的综合严重程度评分可能是严重志贺氏菌病的实用临床终点。依靠培养进行微生物确认可能会漏掉相当数量的志贺氏菌病例，但目前需要测量血清型特异性免疫。在较小和发育迟缓的儿童中，分子方法比微生物培养更常见地鉴定志贺氏菌。包含脱水、住院和腹泻持续时间的简化临床评分可以用于根据疫苗试验终点预测死亡的能力按严重程度对终点进行分层。
Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity. Molecular methods identified Shigella more commonly than microbiologic culture in younger and stunted children. A simplified clinical score containing dehydration, hospitalization, and diarrhea duration could be used to stratify vaccine trial endpoints by severity based on its ability to predict death.
登录
查看更多内容
影响因子：
5.1
作者：
HUSKINS, WC;GRIFFITHS, JK;BENNISH, ML
通讯作者：
BENNISH, ML
影响因子：
4.5
作者：
Lamberti LM;Fischer Walker CL;Black RE
通讯作者：
Black RE
DOI：
10.4269/ajtmh.14-0727
发表时间：
2015-08
期刊：
The American journal of tropical medicine and hygiene
影响因子：
--
作者：
Lamberti LM;Fischer Walker CL;Taneja S;Mazumder S;Black RE
通讯作者：
Black RE
影响因子：
168.9
作者：
Kotloff, Karen L.;Nataro, James P.;Levine, Myron M.
通讯作者：
Levine, Myron M.
影响因子：
3.8
作者：
Anderson, John D.;Bagamian, Karoun H.;Rheingans, Richard
通讯作者：
Rheingans, Richard