PLoS Medicine, 2018, Vol.15(2)
Background Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, “ring” size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa. Methods and findings We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N’Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in the number of people needed to target to avert a single case of cholera, compared to mass campaigns in high-cholera-risk neighborhoods. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for OCV and POUWT. Adding POUWT or antibiotics to OCV provided only marginal impact and efficiency improvements. Starting CATIs early in an epidemic with OCV and POUWT targeting those within 100 m of an incident case household reduced epidemic durations by 70% (IQR 65% to 75%) and the number of cases by 82% (IQR 71% to 88%) compared to uncontrolled epidemics. CATIs used late in epidemics, even after the peak, were estimated to avert relatively few cases but substantially reduced the number of epidemic days (e.g., by 28% [IQR 15% to 45%] for OCV in a 100-m radius). While this study is based on a rigorous, data-driven approach, the relatively high uncertainty about the ways in which POUWT and antibiotic interventions reduce cholera risk, as well as the heterogeneity in outbreak dynamics from place to place, limits the precision and generalizability of our quantitative estimates. Conclusions In this study, we found that CATIs using OCV, antibiotics, and water treatment interventions at an appropriate radius around cases could be an effective and efficient way to fight cholera epidemics. They can provide a complementary and efficient approach to mass intervention campaigns and may prove particularly useful during the initial phase of an outbreak, when there are few cases and few available resources, or in order to shorten the often protracted tails of cholera epidemics. In a modeling study, Andrew Azman and colleagues investigate the potential value of targeted interventions for control of cholera outbreaks. Author summary Why was this study done? The risk of cholera around households of cholera cases is higher than in the general population in the days after cholera symptoms start. Rapid targeting of cholera interventions to neighbors of cholera cases may provide an effective and resource-efficient way to avert cholera cases and deaths and reduce the duration of epidemics. Interventions targeted to neighbors of cases using combinations of antibiotics, oral cholera vaccine, and/or water, sanitation, and hygiene measures have been used in Africa and the Americas to fight cholera, yet limited evidence exists on the potential impact of this approach, the optimal mix of interventions, and the extent of the target population. What did the researchers do and find? Using computational models, we simulated cholera epidemics similar to a large urban cholera outbreak in Chad and evaluated the potential impact of targeted interventions administered to people living within a fixed radius (e.g., 100 m) around reported cholera cases. Targeted interventions with oral cholera vaccine were predicted to have the largest impact on reducing cases and shortening epidemics, followed by water treatment interventions and by prophylactic antibiotics, regardless of when interventions started during epidemics. The combined use of oral cholera vaccine and water treatment within 100 m around cases starting early in epidemics were estimated to lead to 70% (interquartile range [IQR] 65% to 75%) fewer epidemic days and 82% (IQR 71% to 88%) fewer cases than uncontrolled epidemics. Compared to traditional mass intervention campaigns, targeted interventions can have a similar or larger impact on epidemics and use less resources. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for oral cholera vaccine and point-of-use water treatment. What do these findings mean? Interventions targeted to neighbors of cholera cases can be an effective and resource-efficient strategy to fight cholera epidemics; they may be particularly useful during the early phase of an outbreak, when the number of cases is still low, and to truncate the tails of outbreaks, after a mass intervention campaign. While field studies and/or clinical trials are needed to measure the effectiveness of targeted interventions, these results provide a rationale to focus efforts on interventions with oral cholera vaccine and water treatment interventions in a roughly 100-m radius around case households.
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