Evaluation of Reactive Focal Mass Drug Administration (rfMDA) +/- Reactive Focal Vector Control (RAVC) in Namibia

Malaria Clinical Trial

Official title: Targeted Parasite Elimination in the Human and Mosquito to Reduce Malaria Transmission: A Cluster Randomised Controlled Factorial Design Trial of Reactive Focal Drug Administration (rfMDA) Versus Reactive Case Detection (RACD), With and Without Reactive Vector Control (RAVC), From the Low Endemic Setting of Namibia

Status Completed

Clinical Trial Summary

This is a cluster randomised controlled trial with factorial study design comparing the impact of reactive community-based malaria interventions: 1) presumptive treatment (or rfMDA, reactive focal mass drug administration) versus reactive case detection (RACD), and 2) reactive IRS (indoor residual spraying) versus control on the incidence of malaria in Namibia.

Clinical Trial Description

In recent years, many countries, including Namibia, have experienced reductions in malaria transmission in association with the scale-up of effective interventions and are now moving towards malaria elimination. In malaria control, the goal is to reduce the clinical burden of malaria. In malaria elimination, the aim is to interrupt transmission, and it becomes necessary to address not only symptomatic malaria, but also asymptomatic infections that contribute to transmission. Since malaria transmission is highly geographically heterogeneous, elimination activities should target hot spots, or areas where the risk of future infection is highest. Hence, in the transition from control to elimination, enhanced surveillance and response is necessary to target hot spots with interventions to interrupt transmission.

Reactive case detection (RACD), active surveillance in communities around passively detected cases, is a recommended elimination strategy to identify secondary cases and hot spots. However, RACD can be labour-, time-, and cost- intensive, and misses people who are absent during screening or refuse to have their blood drawn. Furthermore, both microscopy and rapid diagnostic tests (RDTs) utilized in RACD have shortcomings, for instance, the suboptimal sensitivity of RDTs for low parasite density and non-falciparum infections. Polymerase chain reaction (PCR) offers markedly improved sensitivity over RDTs but requires hours of processing time, sophisticated technical skills, and expensive equipment. Given these limitations, presumptive treatment may be a more feasible and effective strategy to reduce and interrupt transmission.

Reactive focal mass drug administration (rfMDA), a form of presumptive treatment, has been used successfully in China to overcome some of the weaknesses of RACD. rfMDA targets remaining reservoirs of infection in low endemic settings by treating everyone at high risk (subjects residing around an index case), rather than rely on RDT results, which have been shown to miss infections. In a low transmission setting such as Namibia, only a small proportion of the populations is at high risk of infection, therefore, only a small number of people need to be targeted (perhaps 20-50 people). Additional indoor residual spraying (IRS) targeted to homes in high risk locations can also be implemented.

rfMDA is a promising strategy, but evidence does not yet exist to prove its efficacy in Africa. Questions remain about where to target rfMDA, what drugs to use, and whether drugs should be used alone or in combination with additional vector control. For rfMDA to be most successful, it is necessary to kill parasites in the human as well as the vector population of the target area. However, one challenge of pre-transmission season IRS is that it is difficult to predict where future infections will occur. A reactive approach, in conjunction with the pre-transmission approach, will ensure coverage of effective vector control in the highest risk areas. Further, if there is unknown resistance to the insecticide used during pre-transmission season, the subsequent reactive use of a different, and presumably effective insecticide, will provide better protection.

In this study the investigators will utilise a cluster randomized controlled study design to evaluate rfMDA in response to a passively identified index case and compare it to RACD. The investigators will study each intervention (rfMDA, RACD) both with and without additional focal insecticide spraying.

56 enumeration areas (EAs) within catchment areas of 11 study health facilities will be randomized to one of four intervention arms:

1. RACD only

2. RACD with RAVC

3. rfMDA only

4. rfMDA with RAVC

A rapid reporting surveillance system will capture confirmed, passively identified cases at all study health facilities, and those cases will trigger an intervention by the study team if located in one of the study EAs. ;

Related Conditions & MeSH terms

• Malaria

• NCT number: NCT02610400
• Study type: Interventional
• Source: University of California, San Francisco
• Status: Completed
• Phase: Phase 3
• Start date: February 2016
• Completion date: December 2017