Malaria elimination in Sub-Saharan Africa: essential tools and identifiable targets

Though still affecting an important proportion of the world population, malaria has declined substantially in the last few years, thanks also to the scale up of interventions such as bed nets treated with insecticide. Such decrease has been observed also in sub-Saharan African countries, including The Gambia, where the malaria burden is the highest. The idea that malaria can be reduced at the point where it would not be a major public health problem anymore or would even be eliminated has been re-introduced again after the previous attempt in the 1950s. This was abandoned mainly for two reasons: lack of financial support and use of a single strategy that did not take into account the extreme variability of malaria transmission. It is now recognised that the knowledge needed to support any elimination effort is limited and that a new attempt in this direction should be supported by a strong research component. This proposed research program to be carried out in The Gambia aims at providing sub-Saharan African National Malaria Control Programs with the necessary knowledge and tools to move farther, towards malaria elimination. The Gambia is the ideal place to carry out the proposed research program because 1. The country has been extremely successful in reducing the malaria burden and aims at reducing it further; 2. The MRC laboratories have the required expertise, the advanced technological platform and the necessary international collaborations to achieve the program's objectives. The combination of these two factors is unique in West Africa and offers a golden opportunity to carry out a research programme that can have a profound influence on the way elimination efforts will be implemented in sub-Saharan Africa.

Activities are divided into two parallel and complementary sections: one section aims at understanding the dynamics of malaria transmission and the reasons why this can substantially differ within few kilometres; the other section will aim at improving diagnostic tests able to identify malaria infected but otherwise healthy people (malaria carriers).

For the former, the populations of 12 villages will be intensively followed up for 3 transmission seasons to understand who the malaria carriers are and how the infection spreads across the populations. Information on the vector population, including the presence of insecticide resistance, and on the human behaviour will be collected to partly explain the likely differences between the study villages. At the end of the study we will have a better understanding on how the malaria parasites spread and what are the important determinants that maintain transmission from one year to the other, despite the high coverage of preventive and curative measures.

Concerning diagnostic tests, the currently available tests that can be used in the field cannot detect a proportion of infected people that contributes in maintaining transmission. We will try two approaches, one aiming at developing easy-to-use molecular test that can detect most infected individuals, and the other looking at "markers" of infection by detecting parasite's or host's proteins that can be found only in infected individuals. The latter could provide the knowledge necessary to develop a more sensitive test.

The results of this research program will be important for any sub-Saharan African country willing to go towards elimination of malaria. They will be disseminated through international and regional conferences, and by international peer-reviewed publications and communications. In addition, through the Gambian National Malaria Control Program, results may be disseminated through the local press in a form accessible to a wider public.

Malaria elimination came recently back onto the global public health agenda when a substantial malaria decrease was observed worldwide, including in sub-Saharan Africa. In The Gambia, malaria has markedly decreased over the last few years, a result attributed to the interventions' scale-up. Transmission will further decrease but the impact will not be uniform and pockets of transmission will remain. The objectives of this proposed research program are both to understand the dynamics of malaria transmission in a context of high coverage of standard control interventions, and to provide the tools to identify the residual reservoir of infection.

Six areas where transmission is ongoing will be identified and 2 villages per area (lowest and highest malaria prevalence), will be selected and intensively followed up (monthly bleeds and passive case detection) for 3 transmission seasons. Blood samples will be screened for infection and then those positive genotyped. The human reservoir will be defined by membrane feeding assays and by detecting gametocytes with molecular methods. For the vector, target-site, metabolic and behavioural resistance will be determined. For human behavioural factors, a mixed methods study design (qualitative and quantitative) will be used. Modelling will synthesize information, quantify uncertainty and generate new hypotheses.
For the tools, two approaches will be followed: 1. Development of a simple, field-based molecular diagnostic test for identifying by mass screening asymptomatic carriers; 2. Identification of parasite's and host markers in uninfected and infected (with and without symptoms) individuals that may be later used for the development of diagnostic tests targeting sub-patent infections.

The results of this research program will be important for any sub-Saharan African country willing to go towards elimination of malaria. They will be disseminated through conferences, and by international publications and communications.

The proposed research program has the potential of having a large impact on the way malaria control and elimination are tackled in sub-Saharan Africa. The component on the dynamics of transmission will provide knowledge on the residual foci of malaria infection in a context of high coverage of control interventions. It will identify some or most of the determinants (related to the vector and to human behaviour) maintaining these foci. In addition, it will provide information on whether it is possible and how to identify asymptomatic carriers and individuals infectious to mosquitoes. Therefore, the primary beneficiary from the research will be the Gambian National Malaria Control Program (NMCP) and the Gambians still living in areas with ongoing transmission. Results of this program will help the NMCP to better target residual foci of transmission and to decrease the risk of malaria transmission for the local populations. Considering that the situation in The Gambia is similar to other countries in the West African region, the corresponding NMCP will also be able to use the information produced to better target their efforts. This research program will also provide valuable information to international agencies, e.g. World Health Organization, involved in the formulation of guidelines related to malaria elimination or in the funding of elimination efforts.

The component on tools will result in a simple, easy-to-use, molecular diagnostic test to identify asymptomatic parasite carriers. The NMCPs (in African and in other endemic continents) and any other organization involved in malaria control/elimination activities will benefit enormously from the availability of such test(s) as they will be able to identify and immediately treat asymptomatic carriers. This should reduce the human reservoir and reduce or eliminate transmission. Though asymptomatic carriers are not ill, the availability of the test will allow better targeting them in campaigns aiming at treating all infected individuals. By decreasing the risk of unnecessarily treating uninfected people, it will reduce the occurrence of adverse drug reactions. Commercial private sector could use the results for the mass production of the test. Similarly, the proteomics study will generate knowledge that could be used by the commercial private sector to develop a new diagnostic test.