The Monitoring and Evaluation of a Multicountry Surveillance Study, the Severe Typhoid Fever in Africa Program.

BACKGROUND: There is limited information on the best practices for monitoring multicountry epidemiological studies. Here, we describe the monitoring and evaluation procedures created for the multicountry Severe Typhoid Fever in Africa (SETA) study. METHODS: Elements from the US Food and Drug Administration (FDA) and European Centre for Disease Prevention and Control (ECDC) recommendations on monitoring clinical trials and data quality, respectively were applied in the development of the SETA monitoring plan. The SETA core activities as well as the key data and activities required for the delivery of SETA outcomes were identified. With this information, a list of key monitorable indicators was developed using on-site and centralized monitoring methods, and a dedicated monitoring team was formed. The core activities were monitored on-site in each country at least twice per year and the SETA databases were monitored centrally as a collaborative effort between the International Vaccine Institute and study sites. Monthly reports were generated for key indicators and used to guide risk-based monitoring specific for each country. RESULTS: Preliminary results show that monitoring activities have increased compliance with protocol and standard operating procedures. A reduction in blood culture contamination following monitoring field visits in two of the SETA countries are preliminary results of the impact of monitoring activities. CONCLUSIONS: Current monitoring recommendations applicable to clinical trials and routine surveillance systems can be adapted for monitoring epidemiological studies. Continued monitoring efforts ensure that the procedures are harmonized across sites. Flexibility, ongoing feedback, and team participation yield sustainable solutions.

Characterization of Typhoid Intestinal Perforation in Africa: Results From the Severe Typhoid Fever Surveillance in Africa Program.

Background: Typhoid intestinal perforation (TIP) remains the most serious complication of typhoid fever. In many countries, the diagnosis of TIP relies on intraoperative identification, as blood culture and pathology capacity remain limited. As a result, many cases of TIP may not be reported as typhoid. This study demonstrates the burden of TIP in sites in Burkina Faso, Democratic Republic of Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria. Methods: Patients with clinical suspicion of nontraumatic intestinal perforation were enrolled and demographic details, clinical findings, surgical records, blood cultures, tissue biopsies, and peritoneal fluid were collected. Participants were then classified as having confirmed TIP, probable TIP, possible TIP, or clinical intestinal perforation based on surgical descriptions and cultures. Results: A total of 608 participants were investigated for nontraumatic intestinal perforation; 214 (35%) participants had surgically-confirmed TIP and 33 participants (5%) had culture-confirmed typhoid. The overall proportion of blood or surgical site Salmonella enterica subspecies enterica serovar Typhi positivity in surgically verified TIP cases was 10.3%. TIP was high in children aged 5-14 years in DRC, Ghana, and Nigeria. We provide evidence for correlation between monthly case counts of S. Typhi and the occurrence of intestinal perforation. Conclusions: Low S. Typhi culture positivity rates, as well as a lack of blood and tissue culture capability in many regions where typhoid remains endemic, significantly underestimate the true burden of typhoid fever. The occurrence of TIP may indicate underlying typhoid burden, particularly in countries with limited culture capability.