Early detection of cholera epidemics to support control in fragile states: estimation of delays and potential epidemic sizes.

Abstract

Cholera epidemics continue to challenge disease control, particularly in fragile and conflict-affected states. Rapid detection and response to small cholera clusters is key for efficient control before an epidemic propagates. To understand the capacity for early response in fragile states, we investigated delays in outbreak detection, investigation, response, and laboratory confirmation, and we estimated epidemic sizes. We assessed predictors of delays, and annual changes in response time. We compiled a list of cholera outbreaks in fragile and conflict-affected states from 2008 to 2019. We searched for peer-reviewed articles and epidemiological reports. We evaluated delays from the dates of symptom onset of the primary case, and the earliest dates of outbreak detection, investigation, response, and confirmation. Information on how the outbreak was alerted was summarized. A branching process model was used to estimate epidemic size at each delay. Regression models were used to investigate the association between predictors and delays to response. Seventy-six outbreaks from 34 countries were included. Median delays spanned 1-2 weeks: from symptom onset of the primary case to presentation at the health facility (5 days, IQR 5-5), detection (5 days, IQR 5-6), investigation (7 days, IQR 5.8-13.3), response (10 days, IQR 7-18), and confirmation (11 days, IQR 7-16). In the model simulation, the median delay to response (10 days) with 3 seed cases led to a median epidemic size of 12 cases (upper range, 47) and 8% of outbreaks ≥ 20 cases (increasing to 32% with a 30-day delay to response). Increased outbreak size at detection (10 seed cases) and a 10-day median delay to response resulted in an epidemic size of 34 cases (upper range 67 cases) and < 1% of outbreaks < 20 cases. We estimated an annual global decrease in delay to response of 5.2% (95% CI 0.5-9.6, p = 0.03). Outbreaks signaled by immediate alerts were associated with a reduction in delay to response of 39.3% (95% CI 5.7-61.0, p = 0.03). From 2008 to 2019, median delays from symptom onset of the primary case to case presentation and to response were 5 days and 10 days, respectively. Our model simulations suggest that depending on the outbreak size (3 versus 10 seed cases), in 8 to 99% of scenarios, a 10-day delay to response would result in large clusters that would be difficult to contain. Improving the delay to response involves rethinking the integration at local levels of event-based detection, rapid diagnostic testing for cluster validation, and integrated alert, investigation, and response.