Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

Surgical management of typhoid intestinal perforations at Mbarara Regional Referral Hospital; a pilot, prospective cohort study

Johanna Riesel, MD

Summary

BACKGROUND: Typhoid Fever is a life-threatening illness endemic to many low-and middle-income countries (LMICs) due to poor sanitation and hygiene. If left untreated, it progresses to perforations of the intestines, commonly referred to “Typhoid Intestinal Perforations” (TIP). There are an estimated 12-20 million cases of Salmonella Typhi infections per year, and In one study from Western Uganda, nearly half of all Typhoid cases progressed to TIP and the majority of patients affected were 19 years or younger. GAP: TIP are a common source of morbidity and mortality in pediatric populations in Low-and Middle-Income Countries (LMICs), yet no evidence-based approach to surgical management or improving surgical outcomes of this condition exists. HYPOTHESIS: A Planned Second Look (PSL) procedure will improve post-operative mortality and morbidity for patients with TIP. METHODS: This was a pilot, prospective cohort study in which patients are stratified by illness severity using the Mannheim Peritonitis Index (MPI). Patients who presented to the Emergency Ward at Mbarara Regional Referral Hospital in Uganda with an acute abdomen were eligible for enrollment in the study. Pregnant women, children under 1 year of age, prisoners, patients with TIP initially managed at another hospital, and patients who die prior to or during their operative procedure, and patients with acute abdomens not caused by Typhoid infections were excluded. Patients in the first cohort would receive routine surgical care at Mbarara Regional Referral Hospital in Uganda. Patients in the second cohort with MPI scores>26 would be eligible for the PSL procedure. If it was not safe to proceed with the PSL, the standard of care was maintained. RESULTS: In an 11-month collection period, 75 patients were enrolled in the study. Of those, 36 patients had confirmed Typhoid infections that led to typhoid intestinal perforations (TIP). Surgical resources and operative time were too sparse to guarantee a standardized PSL for patients who qualified for the intervention, and thus it was not conducted, and the standard of care was maintained. Patients of all ages presented with Typhoid perforations, however, the median age of patients with Typhoid perforations was 19 yr (IQR 23). The disease equally affected men and women (M= 53%). There was no statistically significant difference in presenting symptoms for patients with TIP versus patients with other causes of acute abdomens. Patients with Typhoid perforations were significant healthier (fewer comorbidities) than those with an acute abdomen that was not caused by Typhoid perforations (p= 0.002). However, patients who presented with a typhoid perforation were significantly more ill than those with an acute abdomen not caused by Typhoid infection (p<0.0001) as reflected in MPI scores. For patients with Typhoid perforations, the median MPI was: 26 (IQR 11), indicating severe illness severity. Median length of hospital stay for patients with TIP was 16 days (IQR 13) as opposed to those without TIP (7 days (IQR 2)) (p=0.049). 96% of patients with TIP required intensive monitoring after their initial surgical procedure. 53% percent of patients with confirmed TIP required an unplanned secondary procedure, the most common of which was a secondary washout for ongoing intraabdominal infection (84%). Patients with TIP with MPI scores of 26 or greater were not statistically more likely to experience a higher rate of morbidity or mortality than those with an MPI of 25 or less. 19.4% of patients required an ileostomy. There were 7 deaths in patients with TPI (19%). All deceased patients had a presenting MPI of 20 or greater, and most had an MPI >30, indicating severe illness at the time of presentation to the hospital. IMPACT: This study demonstrates that TIP, previously referred to as a “scourge” of pediatric populations in low-income settings, remains a challenging surgical condition that is difficult to manage in settings were diagnoses are delayed and surgical resources are scarce. This study demonstrates that severe Typhoid infections largely affect the young and healthy and cause severe systemic illness that has a high incidence of morbidity and mortality. This supports the need for further study and dedicated resources to improve surgical management and outcomes in this critically ill population. Overall, the incidence of TIP in this region has decreased since 2012, which is a promising nod towards prevention. However, nearly 50% of patients requiring emergent abdominal surgery at a busy tertiary teaching hospital in southwestern Uganda were those with TIP. While the community measures to prevent Typhoid infections are well documented, barriers to preventing and treating Typhoid infections are significant in the limited-resource setting. Until we can ensure clean drinking water, sanitation, and an ideal health care delivery system for all, TIP will continue to cause death and disabilit

Supervising Institution:
Massachusetts General Hospital

Mentors
John Meara

Project Location:
Uganda, United States

Award Amount:
$26,742