Modifiable risk factors for typhoid intestinal perforations during a large outbreak of typhoid fever, Kampala Uganda, 2015

Background: Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. Methods: We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st - 23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. Results: Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (ORadj = 2.2, 95% CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment >= 10 days after onset (ORadj = 11, 95% CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (ORadj = 9.0, 95% CI = 1.1-78). Conclusion: Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment.