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
AuthorPavlinac, Patricia B
Platts-Mills, James A
Tickell, Kirkby D
Operario, Darwin J
Alonso, Pedro L
Becker, Stephen M
Breiman, Robert F
Faruque, Abu S G
Hossain, M Jahangir
Iqbal, Najeeha Talat
McMurry, Timothy L
Ochieng, John B
Roberts, James H
Sow, Samba O
Stroup, Suzanne E
Tennant, Sharon M
Nataro, James P
Levine, Myron M
Houpt, Eric R
Kotloff, Karen L
JournalClinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
PublisherOxford University Press
MetadataShow full item record
AbstractBACKGROUND: 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. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Rights/Terms© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
Keywordpolymerase chain reaction
vaccine clinical trial
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16650
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