Intestinal Perforations Associated With a High Mortality and Frequent Complications During an Epidemic of Multidrug-resistant Typhoid Fever in Blantyre, Malawi

Abstract

Background Typhoid fever remains a major source of morbidity and mortality in low-income settings. Its most feared complication is intestinal perforation. However, due to the paucity of diagnostic facilities in typhoid-endemic settings, including microbiology, histopathology, and radiology, the etiology of intestinal perforation is frequently assumed but rarely confirmed. This poses a challenge for accurately estimating burden of disease. Methods We recruited a prospective cohort of patients with confirmed intestinal perforation in 2016 and performed enhanced microbiological investigations (blood and tissue culture, plus tissue polymerase chain reaction [PCR] for Salmonella Typhi). In addition, we used a Poisson generalized linear model to estimate excess perforations attributed to the typhoid epidemic, using temporal trends in S. Typhi bloodstream infection and perforated abdominal viscus at Queen Elizabeth Central Hospital from 2008–2017. Results We recruited 23 patients with intraoperative findings consistent with intestinal perforation. 50% (11/22) of patients recruited were culture or PCR positive for S. Typhi. Case fatality rate from typhoid-associated intestinal perforation was substantial at 18% (2/11). Our statistical model estimates that culture-confirmed cases of typhoid fever lead to an excess of 0.046 perforations per clinical typhoid fever case (95% CI, .03–.06). We therefore estimate that typhoid fever accounts for 43% of all bowel perforation during the period of enhanced surveillance. Conclusions The morbidity and mortality associated with typhoid abdominal perforations are high. By placing clinical outcome data from a cohort in the context of longitudinal surgical registers and bacteremia data, we describe a valuable approach to adjusting estimates of the burden of typhoid fever.

Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children

“…6 , 7 , 8 In Malawi and other countries in East and Southern Africa, MDR H58 S. typhi emerged in 2010 following its introduction from Asia, 9 , 7 becoming the predominant blood-stream infection among adults and children, with 2% case fatality and 5% rate of small bowel perforation. 10 , 11 , 12 Emerging antimicrobial resistance to fluoroquinolones has been documented in East Africa, 7 , 13 Nigeria, 6 and Democratic Republic of Congo. 14 Extensively drug-resistant (XDR) typhoid, resistant to fluoroquinolones and 3 rd generation cephalosporins, is established in Pakistan.…”

Estimating the effect of vaccination on antimicrobial-resistant typhoid fever in 73 countries supported by Gavi: a mathematical modelling study

“…Patients infected with antimicrobial-resistant strains of typhoid fever are likely to have poorer outcomes, including prolonged illness and higher risk of relapse, complications, and possibly death. 21 , 22 However, there is also greater uncertainty in the number of deaths and DALYs that can potentially be averted through TCV introduction. More research is needed to better understand the risk of hospitalisation and death from typhoid fever and how it varies for antimicrobial-resistant versus antimicrobial-sensitive strains.…”

Estimating the economic burden of typhoid in children and adults in Blantyre, Malawi: A costing cohort study

“…This may be due to higher pay and greater staff-to-patient ratios in those contexts compared to Malawi. The highest costs were incurred for inpatients with severe disease, an outcome not uncommon in Malawi’s context [ 27 ]. Although few such outlying cases may occur, they contribute to the overall cost burden and should be planned for in facility budgeting.…”