Research Projects : Export

Objective

Evaluate the effectiveness of the Case Area Targeted Intervention (CATI) approach in reducing the incidence of new cases during cholera outbreaks.  And in so doing, to determine factors that support optimal delivery and interventions for CATIs towards cholera reduction in humanitarian settings and fragile states.

Aim

The primary aim is to characterize the relationship between CATI activation time (time between case presentation at a cholera treatment facility and the start of the CATI intervention) and cholera incidence in the area covered by CATI interventions. Secondary aims include:

• Document procedures of implementing CATIs and develop recommendations to maximize their impact in future cholera outbreaks.
• Describe the integration of water, sanitation, and hygiene (WASH) and health activities delivered via CATI.
• Characterize the relationship between CATI completeness (in terms of coverage within the specified geographic area and activities implemented within households) and incidence of new cholera cases.
• Estimate CATI effectiveness using secondary parameters (e.g. reported diarrheal incidence, free chlorine residual (FCR) in the drinking water sample, and knowledge and practices to prevent cholera transmission).
• Document coordination mechanisms between Ministries, United Nations (UN) agencies, Clusters, and non-governmental organizations (NGOs) and develop recommendations for coordination in future responses.

Study Design

The proposed research will be conducted in future cholera outbreaks that take place in recognized humanitarian contexts in at least two different countries; locations will be selected based on where cholera outbreaks occur and the presence of a CATI implementing partner.  Organizations that frequently implement CATI interventions during cholera response that have agreed to partner with JHSPH include Action Against Hunger, Solidarités International, and Medair. Countries with humanitarian emergencies that are at high risk of cholera outbreaks include Democratic Republic of the Congo, Nigeria, Ethiopia, Mozambique and Yemen, though it is possible that other humanitarian contexts may serve as a research location if a cholera outbreak occurs and one of the aforementioned implementing partners responds with a CATI intervention.

The JHSPH IRB approval has classified this study as Non-Human Subjects Research.   Government or IRB approval will be attained prior to conducting the research.

The research team will be present at the site as soon as possible after the first cholera case has been documented and begin data collection as soon as feasible. If travel to the study location is not feasible for security reasons, the JHSPH research team will conduct the study remotely through the partner organization that is providing on-the-ground CATI response to the cholera outbreak.

Because the aim of the research is to evaluate CATIs as delivered by NGOs in response to a cholera outbreak, a randomized design is not possible. Thus, we will rely on comparison groups that will occur naturally, according to the outbreak size and capacity of the response organization. This will necessitate a flexible sampling approach.

We anticipate the primary comparison will be rapid vs. delayed CATI implementation (e.g. end stage of outbreak); however, it is also possible that areas with no CATI implementation could be used as a comparison group [in outbreaks where there is insufficient capacity to respond to all cases].  Additional points of comparison may include the delay between case presentation and CATI implementation:  e.g. CATI implemented within 24h, in 2 days, in 3 days, in 4 days, etc.

The proposed research is an observational study of cholera interventions implemented by NGOs in response to cholera outbreaks (i.e. no intervention is proposed).  The study will include the following components:

• Observation of CATI delivery
• Key informant interviews: 1) NGO staff members delivering the CATI intervention to characterize perceived strengths and weakness of the intervention, household selection, logistical processes and implementation challenges; 2) Humanitarian response managers from the partner NGO, UN agencies, national governments and other organizations engaged in the cholera response to ascertain perceptions of the response, coordination and CATI delivery and implementation
• Cholera treatment facility line lists: Information from cholera line lists is used to plan CATI interventions, where each individual on the line list (i.e. a cholera case) receives a household visit from a CATI team. The JHSPH study team will request line lists from health facilities [which may be augmented by the study team] to evaluate coverage of CATI interventions.
• Follow up survey: The household follow up survey will be conducted approximately 14 days after the presentation of the suspected cholera case at a cholera treatment facility. The exact sampling approach will depend on the density of housing in the community and the CATI implementation strategy. Household surveys will enquire about receipt of the CATI intervention, household composition, incidence of diarrhea and diarrhea care seeking among household members in the period since CATI implementation (or case presentation if there was no CATI), knowledge and practices of hygiene behaviors and observation of free chlorine level (FCR) in stored drinking water.

Cholera continues to pose a major global public health threat and is a marker of inequality and poverty as it reflects the lack of access to basic water and sanitation infrastructures. The risk of the spread of cholera is particularly high in humanitarian settings and fragile contexts.

Cholera transmission risk is higher for cholera case household members and nearby households. Mass interventions to contain cholera outbreaks are not resource efficient.  Preventive interventions targeting cholera case-households and neighbors have been found effective in past outbreaks. These interventions are often referred to as case area targeted interventions (CATIs). CATIs predominantly include water, sanitation, and hygiene (WASH) activities but can also include epidemiological surveillance, and health (clinical) services, primarily oral vaccination and antibiotic chemoprophylaxis.

There are limited studies on the best practices and effectiveness of CATIs in humanitarian settings.   This study aims to identify those factors that support optimal delivery and interventions of these CATIs for cholera reduction in humanitarian settings and fragile states.  The study design centers around observing the CATI activities of partner organizations as they respond to a cholera outbreaks in known humanitarian or fragile settings.

There is limited evidence studying the mechanisms, composition, interventions, timing, effectiveness of CATIs in humanitarian settings. This proposed research for CATI in humanitarian settings will focus on variations in CATI implementation and timing, monitoring and evaluation, and coordination and integration with the aim of expanding available evidence that can be used to inform the development of operational guidance for CATI interventions in cholera response.

Burden

Cholera, caused by V. cholerae, is a killer disease. In Bangladesh, cholera occurs endemically at defined seasons resulting significant morbidity and mortality each year. V. cholerae is a native flora of the estuarine aquatic environment. The bacterium existing in the environment is found mostly in a dormant, non-cultivable state; and can regain active state and flourish to initiate the seasonal epidemics of cholera. Although seasonal cholera is driven by natural climate factors, the disease takes the turn of epidemic through rapid transmission of infectious V. cholerae via fecal-oral mode as marginal people relies on contaminated surface water for drinking and other domestic purposes.

Knowledge gap

We want to understand V. cholerae growth response, particularly what triggers the bacterium to be active from dormant non-culturable state, and if locally available no-cost items such as ashes could kill the infectious bacterium shed in stool to decontaminate the environment; the aim is to develop a sustainable method to prevent cholera transmission.

Relevance

This study will generate knowledge on V. cholerae growth responses, and no-cost method of stool decontamination, and the aim is prevent cholera transmission.

Hypothesis

• Climatic and human factors contribute to active growth of V. cholerae responsible for seasonal cholera to prevent cholera transmission
• Wood ashes might provide a sustainable method of stool decontamination to prevent V. cholerae transmission

Objectives

• Study the environmental and human factors activating naturally occurring non-cuturable V. cholerae that initiates seasonal cholera
• Test efficacy of wood ashes in decontaminating V. cholerae shed in stools to reduce cholera transmission

Methods

Water samples will be collected from four Mathbaria sites, and temperature, turbidity, pH, salinity, total dissolved solids and conductivity of water monitored bi-weekly during March-May and September-November and monthly for the rest of the year. Toxigenic V. cholerae will be isolated (Alam et al. 2006a) and characterized in terms of virulence adaptive polymorphisms (VAPs) and molecular fingerprinting. Also, laboratory microcosms will be constructed with two toxigenic V. cholerae to test growth response of the bacterium, and the role of cyanobacteria (Islam et al., 1990a; Islam et al., 1990b) and bile will be monitored at different temperatures, pH, salinity, and conductivity. In this study, efficacy of decontamination of discarded diarrheal stools carrying V. cholerae would be monitored and compared with commercially available disinfectant such as bleaching powder.

Outcome measures/variables

Growth response of V. cholerae to different climate factors, and the role of cyanobacteria and bile in microcosms would be an outcome to measure. V. cholerae burden in cholera stool at different concentrations and time of treatment with wood-ashes would also be an outcome measure.

Vibrio cholerae often escapes culturing methods while in a dormant and non-culturable state in the aquatic environment, although they can become actively growing to cause seasonal epidemicsof cholera. We designed this study to unveil the climate and/or natural no-cost substaces that could drive the growth responses of the bacterium to be able to aid diseases prevention in endemic settings.

Vibrio cholerae is an aquatic bacterium which passes the interepidemic period in a dormant and non-culturable state. The well-defined climate or natural factors driving the growth responses of the bacterium could aid in diseases prevention in endemic settings.

For over ten years, we have sought how best to develop decision-support tools for clinicians treating diarrhoeal disease. This is important because of a need to rapidly train large numbers of providers during cholera outbreaks, rapidly re-educate when guidelines change, address inappropriate antibiotic use, and allow for differences in epidemiology by season and place. We have built tools in both paper and digital formats, and evaluated their impact in clinical trials. Now, we are collaboratively building digital tools that depend on models developed through machine learning. In a large international collaboration, we have built and evaluated improved algorithms to assess dehydration for children and adults (project led by A. Levine at Brown University) and provide a probability that a patient has only a viral disease based on real-time weather, clinical and epidemiologic data (project led by D. Leung at Utah University). In addition to helping to improve cholera response, these tools represent a significant shift in how clinical decision-support might be in 10 years.

The impact of this research is to first improve rehydration and antibiotic guideline adherence. Secondly, the impact is to make possible dynamic decision-support that is responsive to where and when the patient is being treated.

Background

Globally, the risk of small-scale cholera outbreaks propagating rapidly and enlarging extensively remains substantial. As opposed to relying on mass, community-wide approaches, cholera control strategies could focus on proactively containing the first clusters. Case-area targeted interventions (CATI) are based on the premise that early cluster detection can trigger a rapid, localised response in the high-risk radius around one or several households to reduce transmission sufficiently to extinguish the outbreak or reduce its spread. Current evidence supports a high-risk spatiotemporal zone of 100 to 250 meters around case-households for 7 days.

We hypothesize that the prompt application of CATI will reduce household transmission and transmission in the wider ring. This will result in reduced incidence in the ring and reduced clustering of cases. The local focus of CATI will enable active case-finding and sustained uptake of interventions. This will result in prompt access to care for detected cases, and reduced mortality and community transmission.

Methods

We propose to evaluate the effectiveness of a CATI strategy using an observational study design during an acute cholera epidemic, with clearly-defined measures of the effectiveness of the CATI package. In addition, we intend to evaluate the feasibility, costs, and process of implementing this approach. The CATI package delivered by Médecins Sans Frontières’ (MSF) will incorporate key transmission-reducing interventions (including household-level water, sanitation, and hygiene measures, active case-finding, antibiotic chemoprophylaxis, and, single-dose oral cholera vaccination (OCV)) which aim to rapidly reduce the risk of infection in the household and in the ring around the primary case household. MSF will decide on the contents of the CATI package used, the radius of intervention and the prioritization strategy used if the caseload is higher than the operational capacity, based on national policies, the local context, and operational considerations. In scenarios where preventative vaccination has been recently conducted or is planned, CATI and its evaluation will focus on implementation before and during the mass campaign, or in areas where vaccination coverage was sub-optimal.

The study design is based on comparing the effects of CATIs that rapidly provide protection in averting later generations of cases when compared with progressively-delayed CATIs. A regression analysis will be used to model the observed incidence of enriched RDT-positive cholera as a function of the delay to intervention (in days). The delay will reflect the inverse strength of rapid response. Groups, as a function of their delays to intervention, will serve as internal controls.

Case-area targeted interventions (CATI) are based on the premise that early cluster detection can trigger a rapid, localised response in the high-risk radius around one or several households to reduce transmission sufficiently to extinguish the outbreak or reduce its spread.

We propose to evaluate the effectiveness of a CATI strategy using an observational study design during an acute cholera epidemic, with clearly-defined measures of the effectiveness of the CATI package. In addition, we intend to evaluate the feasibility, costs, and process of implementing this approach. The CATI package delivered by Médecins Sans Frontières’ (MSF) will incorporate key transmission-reducing interventions (including household-level water, sanitation, and hygiene measures, active case-finding, antibiotic chemoprophylaxis, and, single-dose oral cholera vaccination (OCV) ) which aim to rapidly reduce the risk of infection in the household and in the ring around the primary case household.

CATI has been highlighted as a major component of the GTFCC’s global research agenda. Therefore, conducting a rigorous prospective evaluation of the effectiveness of CATI, which includes OCV and explains the pathway to impact, is an important and timely question for outbreak control.