Shifts in geographic distribution and antimicrobial resistance during a prolonged typhoid fever outbreak--Bundibugyo and Kasese Districts, Uganda, 2009-2011

Abstract

Background: Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo.

Methodology/principal findings: A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009-December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1-December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates.

Conclusions/significance: Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future.

Figure 1. Map of Uganda showing affected districts.

Figure 2. Typhoid fever cases by month of illness onset and intestinal perforation status.

(A) Kasese District, August 1, 2009–December 31, 2011, n = 695 with known or estimated onset date and known intestinal perforation status (B) Bundibugyo District, January 1–December 31, 2011, n = 293 with known or estimated onset date and known intestinal perforation status.

Figure 3. Cases of typhoid fever in Bundibugyo, by age, gender, and intestinal perforation status.

January 1–December 31, 2011, n = 244 with known age, sex, and intestinal perforation status, *P = 0.03 and **P = 0.0006.

Figure 4. Diversity of PFGE patterns among Salmonella Typhi isolated from Kasese and Bundibugyo patients.

Each XbaI/BlnI PFGE pattern combination is represented by a different shading; pattern combinations designated by letter are shared across districts and/or years. Salmonella Typhi isolated from October 18–December 31, 2011 were from 13 Bundibugyo and 5 Kasese patients; among these, we observed 6 and 4 pattern combinations, respectively. Investigations in Kasese from March 4–April 17, 2009 yielded 33 Salmonella Typhi isolates, among these 13 pattern combinations were identified .