Shigella in Africa: New Insights From the Vaccine Impact on Diarrhea in Africa (VIDA) Study

Irene N Kasumba, Henry Badji, Helen Powell, M Jahangir Hossain, Richard Omore, Samba O Sow, Jennifer R Verani, James A Platts-Mills, Marc-Alain Widdowson, Syed M A Zaman, Jennifer Jones, Sunil Sen, Jasnehta Permala-Booth, Shamima Nasrin, Anna Roose, Dilruba Nasrin, John Benjamin Ochieng, Jane Juma, Sanogo Doh, Joquina Chiquita M Jones, Martin Antonio, Alex O Awuor, Ciara E Sugerman, Nora Watson, Christopher Focht, Jie Liu, Eric Houpt, Karen L Kotloff, Sharon M Tennant, Irene N Kasumba, Henry Badji, Helen Powell, M Jahangir Hossain, Richard Omore, Samba O Sow, Jennifer R Verani, James A Platts-Mills, Marc-Alain Widdowson, Syed M A Zaman, Jennifer Jones, Sunil Sen, Jasnehta Permala-Booth, Shamima Nasrin, Anna Roose, Dilruba Nasrin, John Benjamin Ochieng, Jane Juma, Sanogo Doh, Joquina Chiquita M Jones, Martin Antonio, Alex O Awuor, Ciara E Sugerman, Nora Watson, Christopher Focht, Jie Liu, Eric Houpt, Karen L Kotloff, Sharon M Tennant

Abstract

Background: We evaluated the burden of Shigella spp from children aged 0-59 months with medically attended moderate-to-severe diarrhea and matched controls at sites in Mali, The Gambia, and Kenya participating in the Vaccine Impact on Diarrhea in Africa (VIDA) study from 2015 to 2018.

Methods: Shigella spp were identified using coprocultures and serotyping in addition to quantitative polymerase chain reaction (qPCR). Episode-specific attributable fractions (AFe) for Shigella were calculated using Shigella DNA quantity; cases with AFe ≥0.5 were considered to have shigellosis.

Results: The prevalence of Shigella was determined to be 359 of 4840 (7.4%) cases and 83 of 6213 (1.3%) controls by culture, and 1641 of 4836 (33.9%) cases and 1084 of 4846 (22.4%) controls by qPCR (cycle threshold <35); shigellosis was higher in The Gambia (30.8%) than in Mali (9.3%) and Kenya (18.7%). Bloody diarrhea attributed to Shigella was more common in 24- to 59-month-old children (50.1%) than 0- to 11-month-old infants (39.5%). The Shigella flexneri serogroup predominated among cases (67.6% of isolates), followed by Shigella sonnei (18.2%), Shigella boydii (11.8%), and Shigella dysenteriae (2.3%). The most frequent S. flexneri serotypes were 2a (40.6%), 1b (18.8%), 6 (17.5%), 3a (9.0%), and 4a (5.1%). Drug-specific resistance among 353 (98.3%) Shigella cases with AMR data was as follows: trimethoprim-sulfamethoxazole (94.9%), ampicillin (48.4%), nalidixic acid (1.7%), ceftriaxone (0.3%), azithromycin (0.3%), and ciprofloxacin (0.0%).

Conclusions: A high prevalence of shigellosis continues in sub-Saharan Africa. Strains are highly resistant to commonly used antibiotics while remaining susceptible to ciprofloxacin, ceftriaxone, and azithromycin.

Keywords: Africa; Shigella; children; diarrhea; dysentery.

Conflict of interest statement

Potential conflicts of interest. K. L. K. reports consultation fees and travel support from PATH and the University of Washington related to diarrheal diseases and grant support to her institution from the National Institutes of Health, Institut Pasteur, and the Bill & Melinda Gates Foundation. M.-A. W. reports receiving funding from the CDC and the Institute of Tropical Medicine. S. M. T. reports multiple grants (paid to institution) from the National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome Trust, Affinivax, Lumen Biosciences, PATH, and Medical Research Council; payments as royalties related to intellectual property for Salmonella vaccines and Klebsiella/Pseudomonas vaccines; consulting fees and travel support from the University of Washington for a grant proposal; multiple planned, issued, and pending patents on Salmonella, Klebsiella, and Pseudomonas vaccines; and multiple unpaid committee roles with the American Society of Tropical Medicine and Hygiene. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
The age distribution among children with moderate-to-severe diarrhea (MSD) attributable to Shigella/enteroinvasive Escherichia coli by quantitative polymerase chain reaction at each site.
Figure 2.
Figure 2.
Clinical syndromes among shigellosis cases. Proportions of attributable Shigella/enteroinvasive Escherichia coli cases with bloody, acute watery, and persistent watery diarrhea are shown by age group and Vaccine Impact on Diarrhea in Africa (VIDA) study sites.
Figure 3.
Figure 3.
Seasonality of attributable and nonattributable Shigella moderate-to-severe diarrhea (MSD) cases in The Gambia, Mali, and Kenya during the Vaccine Impact on Diarrhea in Africa (VIDA) study. Data are shown as the number of attributable (episode-specific attributable fraction [AFe] ≥0.5, dark gray bar) and nonattributable cases (cycle threshold <35 and AFe <0.5, light gray bar) per month weighted by the number of children with MSD who could have been enrolled by site (as opposed to the capped enrollment number). Dotted line represents maximum monthly temperature and shaded box represent months with rainfall above the study period average. Abbreviations: Ct, cycle threshold; MSD, moderate-to-severe diarrhea; qPCR, quantitative polymerase chain reaction.
Figure 4.
Figure 4.
Proportion of Shigella serogroups from stools of cases of moderate-to-severe diarrhea at the 3 Vaccine Impact on Diarrhea in Africa (VIDA) study sites. The frequency of Shigella-positive cases during 3 study periods (Global Enteric Multicenter Study [GEMS], GEMS-1A, and VIDA) is shown for each of the 3 study sites in sub-Saharan Africa.
Figure 5.
Figure 5.
Proportion of strains in each Shigella serogroup that exhibited antimicrobial resistance, by site. Abbreviation: SXT, trimethoprim-sulfamethoxazole.
Figure 6.
Figure 6.
Annual proportions of isolates that displayed antimicrobial resistance, by site. Abbreviations: GEMS, Global Enteric Multicenter Study; SXT, trimethoprim-sulfamethoxazole; VIDA, Vaccine Impact on Diarrhea in Africa.

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Source: PubMed

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