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Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study

2024; Oxford University Press; Volume: 11; Issue: Supplement_1 Linguagem: Inglês

10.1093/ofid/ofad650

2328-8957

Prisca Benedicto-Matambo, Lindsay Avolio, Henry Badji, Rabab Batool, Farhana Khanam, Stephen Munga, Milagritos D. Tapia, Pablo Peñataro Yori, Alex O Awuor, Bubacarr Ceesay, Jennifer Cornick, Nigel A. Cunliffe, Paul F. Garcia Bardales, Christopher D. Heaney, Aneeta Hotwani, Mahzabeen Ireen, Md Taufiqul Islam, Ousman Jallow, Robert W. Kaminski, Wagner V Shapiama Lopez, Victor Maiden, Usman N. Ikumapayi, Ruth Nyirenda, John B. Ochieng, Richard Omore, Maribel Paredes Olórtegui, Patricia B. Pavlinac, Nora Pisanic, Firdausi Qadri, Sonia Qureshi, Nazia Rahman, Elizabeth T. Rogawski McQuade, Francesca Schiaffino, Ousman Secka, Catherine Sonye, Shazia Sultana, Drissa Timite, Awa Traoré, Mohammad Tahir Yousafzai, Md Taufiqur Rahman Bhuiyan, M Jahangir Hossain, Khuzwayo C. Jere, Margaret Kosek, Karen L. Kotloff, Farah Naz Qamar, Samba O. Sow, James A Platts-Mills,

Escherichia coli research studies

Abstract Background Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)–based microbiologic end points for vaccine trials. Methods We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella-positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated. Conclusions The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella, describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates.