L. Hobbs1, L. Sukri1, S. Datta1, S. Kyung2, J. Lee2, K. Neuzil1, R. Zellweger2, F. Marks2 2International Vaccine Institute (IVI), Gwanak-gu, SEOUL, South Korea 1University Of Maryland, Center For Vaccine Development And Global Health, Baltimore, MD, USA
Introduction: Despite being a vaccine-preventable disease, typhoid fever remains a leading cause of morbidity and mortality in resource-limited areas and particularly in the pediatric population. A complication of typhoid fever, typhoid intestinal perforation (TIP), is a major cause of emergency abdominal surgery in many African countries. Since many endemic countries have incomplete typhoid burden data due to limited blood culture capabilities, identification of TIP in the operating room is an important indicator of disease burden. This study aims to quantify TIP burden in children from six African countries to inform prevention strategies, including the use of typhoid conjugate vaccines (TCV).
Methods: As part of the Severe Typhoid Fever Surveillance in Africa (SETA) program, patients with clinical suspicion of non-traumatic intestinal perforation were recruited from six African countries: Burkina Faso, Democratic Republic of Congo, Ethiopia, Ghana, Madagascar, and Nigeria. Included subjects were <18 years, had fever or history of fever, and clinical suspicion of non-traumatic intestinal perforation. Participants were followed until hospital discharge. A sub-group analysis of participants who underwent laparotomy to determine cause of abdominal pain was completed and operative findings and sterile site cultures were described.
Results: Of the 27,866 participants enrolled in SETA between 2016 and 2021, 233 were pediatric participants who underwent laparotomy and met inclusion criteria. Of these, 75% (175/233) had surgically confirmed TIP, characterized as at least one oval perforation along the anti-mesenteric border of the small intestine. For these 175 participants with a documented laparotomy consistent with TIP, 12% (21/175) also had blood culture data, that was positive for S. Typhi. The overall case fatality rate (CFR) was 7.7% (18/233), increasing to 19% (4/21) in patients with both surgical and culture-confirmed typhoid. Among those children presenting with peritonitis but without operative evidence of typhoid, appendicitis was diagnosed in 16 and gastric perforation in four. Additionally, a positive correlation between seasonality of all culture-confirmed typhoid cases and seasonality of non-traumatic intestinal perforations and surgically confirmed TIP was established.
Conclusion: Preventing typhoid fever requires several approaches including improved sanitation systems, access to clean water, improved access to healthcare systems, and the introduction of TCV. Including TIP as a surrogate marker for typhoid burden will be essential in the most resource-burdened regions and should be used to promote wider TCV introduction. Although TIP currently remains a major cause of pediatric peritonitis in sub-Saharan Africa, with the assistance of surgeons, typhoid fever and its severe complications can become a disease of the past.