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Malaria in pregnancy in Burkina Faso & new ways of improving current interventions in Sub-Saharan Africa

Thesis summary

Malaria during pregnancy is a major public health problem, affecting the mother’s and infant’s health. Intra-uterine growth retardation, prematurity and anaemia increase the risk of low birth weight and infant morbidity/mortality during the first year of life. Controls interventions promoted and implemented in sub-Saharan African countries where the disease is endemic are organized around three major activities: prevention, diagnosis and treatment. For the prevention, National Malaria Control Programs have endorsed intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) across Africa as a standard two-dose regimen to replace the former chloroquine chemoprophylaxis. In the countries where this intervention has been implemented, it has achieved good results. Nonetheless, many pregnant wome n are not covered by the intervention, especially at the end of their pregnancy when the risk of acquiring a malaria infection may be substantial and needs to be addressed. We assessed the effect of an additional dose of SP to the standard two-dose regimen in a randomized trial comparing two-dose SP to three-dose SP. Thought at first sight the additional benefit of the third dose was not evident, the results were inconclusive as the study lacked power to show any difference or equivalence. In addition, recent publications provide robust evidence that a three-dose regimen offers a major advantage to all pregnant women and should therefore be promoted.

In the event that prevention fails, exposing women to infections, detection and fast and effective treatment of cases is crucial. Although parasitological confirmation of malaria infection by microscopy or rapid diagnosis test is recommended during pregnancy, health care providers usually only perform a diagnostic test if women presents with common malaria symptoms. This is problematic in high transmission settings as Burkina Faso as malaria infection is often asymptomatic. This also represents an important gap in the package of care offered to pregnant women. This requires to be addressed, as most infected women may not be detected and therefore not treated. We developed a model to estimate the impact of the scaling up the use of rapid diagnostic tests (RDT) as a tool for controlling malaria in pregnancy. In this model, RDT are offered to pregnant women in the health care system to replace the current situation where most of the diagnosis is based on symptoms which are non-specific to malaria. The model showed that, in a system where at least half of the pregnant women have access, introducing a RDT with 95% sensitivity and 95% specificity, would prevent 18.600 infant deaths. This figure would almost double with universal coverage.

When malaria infected women have been identified, they should be urgently treated with effective antimalarials. Current recommendations for treating malaria in pregnancy include artemisinin-based combination therapy as they have been shown to be effective and safe. However, evidence lacks whether a dose-adjustment for pregnant woman is needed as changes occurring during pregnancy may affect the pharmacokinetic parameters of the drugs. This was assessed in a pharmacokinetic (PK) study we carried out for the fixed-dose combination mefloquine-artesunate (MQAS), a promising candidate for rescue/alternative treatment of malaria in pregnancy. The results showed that there was little or no difference between the PK of the active compounds of MQAS in pregnant and non-pregnant women. Therefore, we esteem that no dose-adjustment is needed during pregnancy.

Current recommended intervention tools for the control of malaria in pregnancy can be improved to achieve better results in the reduction of malaria burden in pregnancy.