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
Document Type
Article
Department
Paediatrics and Child Health
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.
Publication (Name of Journal)
Clinical Infectious Diseases
Recommended Citation
Pavlinac, P. B.,
Platts-Mills, J. A.,
Tickell, K. D.,
Kabir, F.,
Qamar, F.,
Iqbal, N.,
Kalam, A.,
Aziz, F.,
Qureshi, S.,
Zaidi, A.
(2021). 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. Clinical Infectious Diseases, 73(3), e569-e579.
Available at:
https://ecommons.aku.edu/pakistan_fhs_mc_women_childhealth_paediatr/932