Reactive household-based self-administered treatment against residual malaria transmission: a cluster randomised trial

Thanks to preventive interventions such as long-lasting insecticidal bed nets and indoor residual spraying, and prompt and efficacious treatments, the malaria burden has decreased substantially over the last decade in several countries, including some in sub-Saharan Africa. Nevertheless, current interventions are unable to interrupt transmission which is maintained by a (probably) large and hidden human reservoir of infection, meaning a proportion of individuals carrying a malaria infection without any symptom. The latter are not sick but they can still infect mosquito vectors that, once infectious, infect other individuals. Several approaches have been proposed to deal with the human reservoir of infection and include the administration of an efficacious treatment to the whole population (mass drug administration), general or targeted screening and treatment of infected individuals. They all require major efforts by the health system, exclude the active participation of the local communities, and, for the screening and treatment approaches the field-based diagnostic tests are not sufficiently sensitive to detect all infected individuals. We propose a novel approach in which clinical malaria cases diagnosed in health facilities are considered index cases around which malaria-infected individuals are probably clustered. Therefore, the intervention will consist in providing to malaria patients (or the parent/guardian in case of children) sufficient doses of dihydroartemisinin-piperaquine, the second line treatment in The Gambia, to systematically treat all members of the household, i .e. reactive household-based self-administered treatment (RHOST). Health staff will follow the treatment by liaising via telephone with the resident village health worker, who will check a few days after completion of the treatment course whether this has been taken at the correct dosage by all household members. The village health worker will also assess for and document any adverse events.
The intervention will be optimized by carrying out, during the first year of its implementation, formative research that will provide sufficient information to adapt RHOST to the local context and, at the same time, actively engage local communities. Formative research will (i) provide baseline data relevant to RHOST; (ii) develop and test health Information, Education and Communication (IEC) messages and strategies for RHOST through a community-based and participatory approach; (iii) monitor and evaluate IEC messages and strategies for the continuous adaptation of RHOST to the local context. This phase will be followed by the implementation of a locally adapted RHOST and the evaluation of its impact on the human reservoir of malaria infection. The primary outcome will be the prevalence of malaria infection determined by molecular methods in all age groups at the end of the second transmission season following the intervention. The impact on the local health system, e.g. stock and flow of antimalarial medication, impact on the activities of the health workforce, will be assessed. The economic evaluation will estimate the incremental cost and cost-effectiveness of the intervention using the trial outcome measures.
The trial will be carried out in The Gambia, in the North Bank West Region, stretching from the coast up to the town of Farafenni, as the coverage of preventive intervention is high and malaria prevalence low. In intervention villages, RHOST will be implemented while in the control villages there will be no additional intervention besides the standard control measures implemented by the National Malaria Control Program and routine clinical care provided by health facilities. The trial will be implemented in 32 moderate sized (400- 800 persons) villages, 16 in the intervention and 16 in the control arm, which will provide sufficient power to detect a significant difference between the 2 study arms.

We propose to evaluate a novel approach to decrease and possibly stop residual malaria transmission; it combines targeted treatment of potential malaria carriers with a strong community involvement (both households of malaria patients and other organizations/structures in the communities). More specifically, the intervention consists in providing malaria patients (or the parent/guardian in case of children) diagnosed at health facilities with sufficient doses of dihydroartemisinin-piperaquine, the second line treatment in The Gambia, to systematically treat all members of their household., i.e. reactive household-based self-administered treatment (RHOST). RHOST will be tested through a community-based, cluster-randomized trial and will be preceded by a phase of formative research in which health Information, Education and Communication messages and strategies for RHOST through a community-based and participatory approach will be developed and continuously monitored to adapt RHOST to the local context and maximize its impact. The primary outcome will be malaria infection prevalence at the end of the second transmission season as determined by molecular methods. Secondary outcomes will include incidence of clinical malaria; prevalence of antimalarial drug resistance molecular markers; impact on the local health system; treatment coverage; and comprehension and acceptability of the intervention. The study will be carried out in The Gambia, in the North Bank West Region, stretching from the coast up to the town of Farafenni, as the coverage of preventive intervention is high and malaria prevalence low; it will include 32 medium sized (400-800) villages, 16 per arm. The sample size is estimated assuming RHOST will decrease malaria prevalence in the intervention villages by 60% or more (from 5% to 2% or less), with 80% power and at 5% significance level.

We are proposing to evaluate a new approach to deal with the human reservoir of malaria transmission, which would be applicable to many countries with residual malaria transmission. The intervention is based on the strong participation of the communities involved. National Malaria Control Programs as well as international agencies and donors interested in malaria elimination will benefit of the results of this trial as they will be provided with a new way of dealing with residual transmission. In addition, we will provide also information on the intervention's impact on the health local services and on its cost. The intervention is based on the strong participation of the local communities that will increase their ownership on the results obtained. In case of positive results, communities living in malaria endemic areas will benefit of the substantial reduction or interruption of malaria transmission, which will result in a reduction of the malaria burden.