Enhanced responses with various approaches to Active Case Detection: Active case detection and treatment

Background

The goal of malaria elimination in low transmission settings requires a shift from early diagnosis and treatment of symptomatic individuals to a strategy of enhanced surveillance in which there is Active Case Detection (ACD). A particular variant of this approach is that of Re-Active Case Detection (RACD) which involves following up on index cases. Follow up includes enhanced testing of individuals in the same household, neighbourhood, or peers of the index case. This intensified but focal approach is justified by the known heterogeneity of transmission in low transmission settings; so called “hot spots”.

Although ACD is a recommended intervention in low transmission settings, evidence for its effectiveness is sparse. There are also different ACD strategies that can be used to guide a range of responses. The approaches of interest in this project involve either: 1) a process of diagnostic screening and then treating positives (i.e. either mass screen and treat or focal screen and treat) or 2) targeted mass drug administration without prior screening. There is a need to determine the efficacy and operational feasibility of these approaches in different epidemiological settings.

Potential limitations of these different ACD approaches to impact transmission is likely to be determined by the operational challenges of achieving high coverage for these approaches, the continued importation of parasites, and the ability of current field diagnostics to detect very low density infections by using a nucleic acid amplification method called loop-mediated isothermal amplification or LAMP).

Overall goal:

To develop interventional tools and approaches to actively screen households that have an index malaria case and to implement treatment to eliminate the asymptomatic reservoir of parasites.

Project methodology:

Confirmed index cases of malaria will be identified and mapped using our GIS mapping system. Due to the expected low/sub-microscopic parasitemic levels in these provinces, we propose that individuals living in households of a confirmed index case will be followed up and invited to enroll in a randomised study of either hMDA or FSAT.

One hundred index cases will be identified and for each case, up to 20 individuals living in the same household or peers of the index case will be invited to participate (i.e. total n=2000). Each individual will be randomised to hMDA or FSAT. All participants will have a brief clinical history taken, temperature recorded and finger prick samples obtained for thick/ thin smear, filter paper collection and microtainer lithium heparin blood sample collected (up to 300ul). These samples will be used for LAMP, microscopy, malaria serology and real-time PCR (at Burnet Institute). Those randomised to hMDA will receive a treatment course of ACT according to National Guidelines without the test results being available. Those randomised to FSAT will only be offered treatment if found to be parasite positive by LAMP or microscopy. LAMP testing will be performed on the hMDA group also but the results will not determine treatment.

Any symptomatic individual will be assessed by RDT or microscopy and will receive routine care for malaria according to National treatment guidelines if appropriate. Permission will be sought to also collect the blood samples outlined above.

Screening and collection of samples will be conducted by both VHMs and commune health personnel. Questionnaires will be filled in to capture data that may explain how foci of asymptomatic parasitaemia changes according to risk factors such as proximity to forest, age, or occupational activities of the household members. Identified cases will be geo-referenced to assess the potential spatio-temporal relationship of asymptomatic cases following the detection of an index symptomatic case. Any parasite positive samples will be included in the genetic epidemiology sub-study.

The following parameters will be determined:

• Proportion of infected (by LAMP and PCR) in households where a malaria case has been reported.
• Proportion of infected individuals with malaria parasites in index households according to distance to forest, location and occupation of the head of household
• Cost, resources/personnel needed and time spent for hMDA vs. FSAT
• Cost per case investigation conducted, cost per additional positive case identified. An attempt will be made to determine the cost-effectiveness FSAT in different scenarios, e.g. number of households screened (5 vs. 10), time to screening (from time of index case diagnosis), etc.

Asymptomatic Reservoir
Drug-based Strategies
Financing & Economics
Surveillance

Oct 2015 — Dec 2016

Vietnam

Malaria Control and Outreach for Mobile and Migrant Populations along the Vietnam-Cambodia Border

Reactive strategies