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.
Pavlinac, Patricia B;
Platts-Mills, James A;
Tickell, Kirkby D;
Liu, Jie;
Juma, Jane;
Kabir, Furqan;
Nkeze, Joseph;
Okoi, Catherine;
Operario, Darwin J;
Uddin, Jashim;
+42 more...Ahmed, Shahnawaz;
Alonso, Pedro L;
Antonio, Martin;
Becker, Stephen M;
Breiman, Robert F;
Faruque, Abu SG;
Fields, Barry;
Gratz, Jean;
Haque, Rashidul;
Hossain, Anowar;
Hossain, M Jahangir;
Jarju, Sheikh;
Qamar, Farah;
Iqbal, Najeeha Talat;
Kwambana, Brenda;
Mandomando, Inacio;
McMurry, Timothy L;
Ochieng, Caroline;
Ochieng, John B;
Ochieng, Melvin;
Onyango, Clayton;
Panchalingam, Sandra;
Kalam, Adil;
Aziz, Fatima;
Qureshi, Shahida;
Ramamurthy, Thandavarayan;
Roberts, James H;
Saha, Debasish;
Sow, Samba O;
Stroup, Suzanne E;
Sur, Dipika;
Tamboura, Boubou;
Taniuchi, Mami;
Tennant, Sharon M;
Roose, Anna;
Toema, Deanna;
Wu, Yukun;
Zaidi, Anita;
Nataro, James P;
Levine, Myron M;
Houpt, Eric R;
Kotloff, Karen L;
(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.
ISSN 1058-4838
DOI: https://doi.org/10.1093/cid/ciaa1545
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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.
