Shigella isolates from the global enteric multicenter study inform vaccine development

Sofie Livio, Nancy A. Strockbine, Sandra Panchalingam, Sharon M. Tennant, Eileen M. Barry, Mark E. Marohn, Martin Antonio, Anowar Hossain, Inacio Mandomando, John B. Ochieng, Joseph O. Oundo, Shahida Qureshi, Thandavarayan Ramamurthy, Boubou Tamboura, Richard A. Adegbola, Mohammed Jahangir Hossain, Debasish Saha, Sunil Sen, Abu Syed Golam Faruque, Pedro L. AlonsoRobert F. Breiman, Anita K.M. Zaidi, Dipika Sur, Samba O. Sow, Lynette Y. Berkeley, Ciara E. O'Reilly, Eric D. Mintz, Kousick Biswas, Dani Cohen, Tamer H. Farag, Dilruba Nasrin, Yukun Wu, William C. Blackwelder, Karen L. Kotloff, James P. Nataro, Myron M. Levine*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

275 Scopus citations

Abstract

Background. Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged <60 months and matched controls without diarrhea during 3 years at 4 sites in Africa and 3 in Asia. Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. Methods. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Results. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. Conclusions. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens.

Original languageEnglish
Pages (from-to)933-941
Number of pages9
JournalClinical Infectious Diseases
Volume59
Issue number7
DOIs
StatePublished - 1 Oct 2014

Keywords

  • Serotyping
  • Shigella
  • Shigellosis
  • Vaccines

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