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

Patricia B. Pavlinac, James A. Platts-Mills, Kirkby D. Tickell, Jie Liu, Jane Juma, Furqan Kabir, Joseph Nkeze, Catherine Okoi, Darwin J. Operario, Jashim Uddin, Shahnawaz Ahmed, Pedro L. Alonso, Martin Antonio, Stephen M. Becker, Robert F. Breiman, Abu S.G. Faruque, Barry Fields, Jean Gratz, Rashidul Haque, Anowar HossainM. Jahangir Hossain, Sheikh Jarju, Farah Qamar, Najeeha Talat Iqbal, Brenda Kwambana, Inacio Mandomando, Timothy L. McMurry, Caroline Ochieng, John B. Ochieng, Melvin Ochieng, Clayton Onyango, Sandra Panchalingam, Adil Kalam, Fatima Aziz, Shahida Qureshi, Thandavarayan Ramamurthy, James H. Roberts, Debasish Saha, Samba O. Sow, Suzanne E. Stroup, Dipika Sur, Boubou Tamboura, Mami Taniuchi, Sharon M. Tennant, Anna Roose, Deanna Toema, Yukun Wu, Anita Zaidi, James P. Nataro, Myron M. Levine, Eric R. Houpt, Karen L. Kotloff

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9 Citations (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)E569-E579
JournalClinical Infectious Diseases
Volume73
Issue number3
DOIs
Publication statusPublished - 1 Aug 2021

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