Intermittent screening and treatment or intermittent preventive therapy for control of malaria in pregnancy in Indonesia
Lead Research Organisation:
Liverpool School of Tropical Medicine
Department Name: UNLISTED
Abstract
FIGHTING MALARIA IN PREGNANCY IN INDONESIA
The control of malaria in pregnancy in Indonesia, where approximately 10% of pregnant women get infected with malaria, could receive a potential boost through a new study conducted by the Eijkman Institute for Molecular Biology and the Timika Research Facility in Indonesia. Together with experts from the Liverpool School of Tropical Medicine in the UK, they are going to test two new methods of preventing malaria and the harmful effects in pregnancy.
When pregnant women contract malaria this can have devastating consequences for pregnancy, resulting in fever which may trigger preterm onset of labour or even pregnancy loss. It is also possible for women to be infected without showing any outward signs or symptoms, yet if these infections are undetected and left untreated, they can cause anaemia in the mother and can interfere with the growth of the fetus leading to low birth weight, which increases the risk of babies dying during infancy.
The new project will provide malaria testing to women with or without the symptoms of malaria on every scheduled antenatal visit using a rapid diagnostic test (RDT). The RDT is simple to perform, uses a single drop of blood and gives results within 15 minutes. Those women testing positive will be treated with an artemisinin combination drug called dihydroartemisinin-piperaquine (DHP), which is the treatment of choice in the 2nd and 3rd trimester of pregnancy in Indonesia. A second method called intermittent preventive treatment, which is used in most countries in Africa but not yet in Asia, will also be tested. With this method women without symptoms of malaria will be selected to receive the same drug but without prior blood testing.
Both methods will be compared with the existing policy in Indonesia, where all pregnant women are tested for malaria on the first antenatal visit only, and those with a positive result are treated with DHP. During subsequent antenatal visits, women are only tested if they have symptoms of malaria such as fever. This means that some infections will go undetected. It is anticipated that the two new methods will either detect infections much earlier than the current approach, or prevent them altogether.
The findings of this study, together with an assessment of feasibility and cost effectiveness of each method, will be used to inform malaria prevention policy for pregnant women in Indonesia and other parts of South East Asia.
The control of malaria in pregnancy in Indonesia, where approximately 10% of pregnant women get infected with malaria, could receive a potential boost through a new study conducted by the Eijkman Institute for Molecular Biology and the Timika Research Facility in Indonesia. Together with experts from the Liverpool School of Tropical Medicine in the UK, they are going to test two new methods of preventing malaria and the harmful effects in pregnancy.
When pregnant women contract malaria this can have devastating consequences for pregnancy, resulting in fever which may trigger preterm onset of labour or even pregnancy loss. It is also possible for women to be infected without showing any outward signs or symptoms, yet if these infections are undetected and left untreated, they can cause anaemia in the mother and can interfere with the growth of the fetus leading to low birth weight, which increases the risk of babies dying during infancy.
The new project will provide malaria testing to women with or without the symptoms of malaria on every scheduled antenatal visit using a rapid diagnostic test (RDT). The RDT is simple to perform, uses a single drop of blood and gives results within 15 minutes. Those women testing positive will be treated with an artemisinin combination drug called dihydroartemisinin-piperaquine (DHP), which is the treatment of choice in the 2nd and 3rd trimester of pregnancy in Indonesia. A second method called intermittent preventive treatment, which is used in most countries in Africa but not yet in Asia, will also be tested. With this method women without symptoms of malaria will be selected to receive the same drug but without prior blood testing.
Both methods will be compared with the existing policy in Indonesia, where all pregnant women are tested for malaria on the first antenatal visit only, and those with a positive result are treated with DHP. During subsequent antenatal visits, women are only tested if they have symptoms of malaria such as fever. This means that some infections will go undetected. It is anticipated that the two new methods will either detect infections much earlier than the current approach, or prevent them altogether.
The findings of this study, together with an assessment of feasibility and cost effectiveness of each method, will be used to inform malaria prevention policy for pregnant women in Indonesia and other parts of South East Asia.
Technical Summary
BACKGROUND:
Malaria in Pregnancy (MiP) can have devastating consequences to mother and newborn, yet the harmful effects are entirely preventable. Annually, 70% of 125.2 million pregnancies in malaria endemic regions occur in the Asia-Pacific region, and cost-effective prevention strategies are urgently needed in this region which has predominantly low-intensity falciparum and vivax transmission. Indonesia is the first country in Asia to introduce systematic screening at first antenatal visit (Single Screening and Treatment: SSTp). SSTp may not detect subsequent infections. A proposed extension is intermittent screening and treatment (ISTp) consisting of repeated screening with rapid diagnostic tests (RDTs) as part of focused antenatal care and treating the RDT positive women with long-acting drugs that also provides several weeks of post-treatment prophylaxis. Screening strategies however may miss low density PCR-positive infections, not detectable by RDT or microscopy. Recently completed surveys in Asia have shown an unexpectedly high prevalence of these infections in asymptomatic pregnant women. Under these circumstances, intermittent preventive therapy (IPTp) is another approach, not yet evaluated in Asia though widely used in sub-Saharan Africa.
OBJECTIVES AND METHODS:
Open-label three-arm parallel-group multicentre cluster-randomised controlled superiority trial conducted in two rural sites in Eastern Indonesia comparing the efficacy, safety and cost-effectiveness of IPTp and ISTp with the current SSTp strategy. Dihydroartemisinin-piperaquine will be used in all three arms. The study is designed to detect 50% reduction in malaria infection at birth from 10% to 5%; Unit of randomization: antenatal clinics. Sample size: 23 clusters of 41 women per arm (N=3198) (Power 90%, alpha 0.025, ICC 0.002, allowing for 20% loss-to-follow-up and 13% efficiency loss due to varying cluster sizes). Secondary endpoints include clinical malaria, maternal anaemia, preterm birth, low birthweight and safety endpoints. Enrolled women of all parities in the 2nd trimester make 3 or 4 scheduled ANC visits 6-8 weeks apart. Infant follow-up is 42 days. Sub-studies of the cost-effectiveness, acceptability/feasibility studies will be conducted alongside the main clinical trial.
PARTNERS AND PRODUCT:
The project builds on an existing MiP research collaborations between the Liverpool School of Tropical Medicine (trial sponsor), the Eijkman Institute in Jakarta (coordinating Institute) and between the Timika Research Facility in Indonesia, and the Menzies School of Health Research, Australia and is designed to inform national, regional and global policy. It is designed in close collaboration with the policy makers and main implementers in Indonesia, notably the MoH, WHO and UNICEF-Indonesia.
The project will take 3.5 years.
Malaria in Pregnancy (MiP) can have devastating consequences to mother and newborn, yet the harmful effects are entirely preventable. Annually, 70% of 125.2 million pregnancies in malaria endemic regions occur in the Asia-Pacific region, and cost-effective prevention strategies are urgently needed in this region which has predominantly low-intensity falciparum and vivax transmission. Indonesia is the first country in Asia to introduce systematic screening at first antenatal visit (Single Screening and Treatment: SSTp). SSTp may not detect subsequent infections. A proposed extension is intermittent screening and treatment (ISTp) consisting of repeated screening with rapid diagnostic tests (RDTs) as part of focused antenatal care and treating the RDT positive women with long-acting drugs that also provides several weeks of post-treatment prophylaxis. Screening strategies however may miss low density PCR-positive infections, not detectable by RDT or microscopy. Recently completed surveys in Asia have shown an unexpectedly high prevalence of these infections in asymptomatic pregnant women. Under these circumstances, intermittent preventive therapy (IPTp) is another approach, not yet evaluated in Asia though widely used in sub-Saharan Africa.
OBJECTIVES AND METHODS:
Open-label three-arm parallel-group multicentre cluster-randomised controlled superiority trial conducted in two rural sites in Eastern Indonesia comparing the efficacy, safety and cost-effectiveness of IPTp and ISTp with the current SSTp strategy. Dihydroartemisinin-piperaquine will be used in all three arms. The study is designed to detect 50% reduction in malaria infection at birth from 10% to 5%; Unit of randomization: antenatal clinics. Sample size: 23 clusters of 41 women per arm (N=3198) (Power 90%, alpha 0.025, ICC 0.002, allowing for 20% loss-to-follow-up and 13% efficiency loss due to varying cluster sizes). Secondary endpoints include clinical malaria, maternal anaemia, preterm birth, low birthweight and safety endpoints. Enrolled women of all parities in the 2nd trimester make 3 or 4 scheduled ANC visits 6-8 weeks apart. Infant follow-up is 42 days. Sub-studies of the cost-effectiveness, acceptability/feasibility studies will be conducted alongside the main clinical trial.
PARTNERS AND PRODUCT:
The project builds on an existing MiP research collaborations between the Liverpool School of Tropical Medicine (trial sponsor), the Eijkman Institute in Jakarta (coordinating Institute) and between the Timika Research Facility in Indonesia, and the Menzies School of Health Research, Australia and is designed to inform national, regional and global policy. It is designed in close collaboration with the policy makers and main implementers in Indonesia, notably the MoH, WHO and UNICEF-Indonesia.
The project will take 3.5 years.
