A.Tiono, Centre National de Recherche et de Formation sur le Paludisme - Investigating the Human Malaria Reservoir of Transmission during Pregnancy

Malaria affects millions of individuals annually and is most harmful to children and pregnant women. However, in recent years there has been considerable success in controlling malaria reducing the levels of both infections and deaths. This has been achieved by high levels of use mosquito nets and the availability of effective drugs. This success has prompted many countries to think about eliminating malaria altogether. Eliminating malaria will require additional and different approaches in that it will be necessary to identify people who transmit the infection to mosquitoes. These may be different to those who are sick. A number of studies have shown that there are individuals with low levels of malaria parasites who are asymptomatic and a few studies show that these low level infections can be transmitted to mosquitoes. So, at the moment there is surprisingly little data on who might transmit the parasites to mosquitoes. This is important to know because it will help design approaches to control malaria that will be more effective both in terms of the speed they work and the cost to carry them out. For example, if we know who the main people or groups of people are then it would be easier to target them with specifically.

One group of individuals that realistically might infect mosquitoes more are pregnant women. Malaria is particularly harmful to pregnant women as the placenta provides a new environment for parasites to develop and grow in. It is because of this that pregnant women have higher chances of infection and when they are infected have higher numbers of parasites than non-pregnant women or men of the same age. Women in their first or second infections in pregnancy are most at risk. Anywhere between 1 and 5% of the population ae pregnant at one time and thus this is a substantial proportion of potentially infected and infectious individuals.

In this study we aim to calculate how much pregnant women contribute to malaria transmission. To do this we will describe the levels of stages of the malaria parasite that can infect mosquitoes in pregnant women compared with other members of the population. We will also see if these parasites are found in specialised locations in pregnant women. We will also check if pregnant women are bitten more by mosquitoes and infect mosquitoes more than non pregnant women and other members. Finally, we will combine these data in a series of simulations to work out what the best approaches to preventing transmission in pregnant women so that we can advise malaria control programmes if a focus on pregnant women is necessary and if so how this should be done.

Malaria is a major cause of morbidity and mortality worldwide, disproportionately affecting children and pregnant women. However, recent reductions in both deaths and infections have led to optimism and the implementation malaria elimination programmes. It is acknowledged that, to achieve elimination, malaria control programmes need also to focus on those who transmit infections to mosquitoes. Despite the recent advances, our knowledge of the human infectious reservoir of malaria, the proportion of the population that can transmit parasites to mosquitoes, remains limited. Understanding how different individuals in endemic populations contribute to disease transmission will enable specific targeting the most infectious individuals rather than blanket population coverage, reducing cost and logistical complexity. One group that has been largely overlooked as a potential reservoir of transmissible parasites are pregnant women. This is despite the 125 million pregnancies occurring in malaria-endemic countries every year, the increased susceptibility of pregnant women to malaria and prolonged infections with the parasite due to placental sequestration.

The research project is designed to describe gametocyte carriage in pregnant women and the infectiousness of these gametocytes to mosquitoes. We will characterise gametocyte populations in pregnant women in an attempt to elucidate specific physiological reasons for any increased infectiousness. We will compare estimates of infection and infectiousness with key comparator groups in the population. These parameters will also be assessed in different seasons and in areas of moderate and low transmission to provide estimates of the effect of season and endemicity on reservoir contributions from different groups. Finally, we will assimilate and incorporate these data in mathematical models to allow simulations of the effect of interventions with and without targeting of pregnant women.

The main goal of the proposed research is to evaluate to what extent pregnant women contribute to malaria transmission. We know that pregnant women suffer more infection and disease than non-pregnant women but we do not know if they are also more infectious to mosquitoes. This is important because malaria control and elimination programmes need to effectively prevent transmission to mosquitoes to be successful. If pregnant women are more infectious then will need to be specifically targeted.

To ensure that potential beneficiaries have the opportunity to engage with this research, we plan to build awareness, secure commitment, encourage participation and foster knowledge exchange with stakeholders at the local, national and global levels.

Who might benefit from this research?

Pregnant women living in malaria endemic areas and the communities in which they live will benefit from this research programme. Additionally the malaria research community and the stakeholders directly involved in designing control programmes will benefit from our findings.

How might they benefit from this research?

Pregnant women and other members of their community will directly benefit from educational exchanges on malaria during community engagement sessions. We aim to communicate and disseminate our work at all levels of the society: from primary school children to teenagers and adults, and from the lay public to malaria scientists. We will organise different activities for these various audiences. At the local community level, we will hold meetings with women to sensitise on malaria prevention with specific emphasis on malaria in pregnancy. We will communicate our interim findings during these meetings and explain the direct implications of these findings for the community in terms of behaviour (treatment seeking, use of prevention tools, etc). In a medium-term, our results will have an important impact on how we control malaria and increase the probability of successful malaria elimination: if we show that pregnant women can transmit malaria parasites to mosquitoes, appropriate measures to minimise this transmission will be developed and this might eventually lead to reduction in local transmission.
The malaria research community will also benefit from our research programme as this is a research topic that has been thus far neglected despite its importance for elimination strategies. An understanding of gametocyte dynamics in pregnant women will lead to a better comprehension of malaria transmission biology and will help understand who the individuals who sustain transmission in areas with markedly seasonal malaria are.

Public health professionals responsible for national and global malaria control programmes will directly benefit from our projects. Our links with multiple stakeholders in malaria research and control will maximise opportunities for them to use our research results and put them into practice. The data that will be generated will be used into mathematical models developed to inform malaria elimination programmes as well as the design of interventions targeting the infectious reservoir in pregnant women.

We are also planning to hold two seminars to share the findings of the proposed research project with specialists in the fields of malaria transmission, pregnancy malaria and malaria elimination. The first seminar will take place at year 3 and the second one, at year 5. These seminars will involve stakeholders in malaria control from the National Malaria Control Program, universities and other research institutions.