The trial will be conducted in five African countries, three in west Africa (Burkina-Faso, Mali and The Gambia), where malaria transmission is highly seasonal, and higher in Burkina Faso and Mali than in The Gambia, one Southern Africa (Mozambique), where malaria is moderate and HIV is highly prevalent, and one Central Africa (Democratic Republic of the Congo, DRC), where malaria transmission is intense and across the whole year. The Mozambican and Congolese sites will carry out the study component on Pyronaridine-Artesunate’s (PA) interactions with antiretroviral treatment.
Burkina Faso: Nanoro and Bousse
The study will be conducted by the Clinical Research Unit of Nanoro (CRUN), in central- west Burkina Faso, 90 Km from Ouagadougou, the capital city. Malaria is the main public health problem and represents a significant burden, particularly for pregnant women and children. It is the first cause of consultation (35.1%), hospitalization (40.8%) and death (37.5%). The communities in which the trial will be implemented are easily accessible and cooperative, and there is a long-standing collaboration between the CRUN and the local stakeholders. CRUN has a Health and Demographic Surveillance System (HDSS) which covers a population of about 60,000 people in 24 villages, including the study catchment area, facilitating the identification, selection, and follow-up of the study participants.
Mali: Bougoula-Hameau and San
The recruitment will be at two sites: Bougoula-Hameau, about 400 Km south of Bamako and San about 440 Km north-east of Bamako. Bougoula-Hameau has a population of about 80,000 people and has been the site of several trials such as the PA efficacy trials in non-pregnant adults and children, the EDCTP-funded trial on repeated PA treatment (www.wanecam.org), and other research projects. Malaria transmission is more intense during the rainy season from May-June to November, with a seasonal peak in October. San health centre serves a population of about 160,000 inhabitants. Several studies on malaria in pregnancy were carried out in this site. The most recent ones include an EDCTP-funded trial on the safety and efficacy of intermittent screening and treatment versus intermittent preventive treatment in pregnant women (IPTp) with sulfadoxine-pyrimethamine (SP) and an in vivo efficacy study on IPTp with SP (IPTp-IST, NCT01084213).
The Gambia: Basse, Demba Kunta Koto, Fatoto, Gambissara and Koina
The trial will be carried out in the Upper River Region (eastern part of the country), where the Medical Research Council, (MRCG) has a field station in Basse. A Health and Demographic Surveillance System (HDSS) is ongoing in the south bank and covers a population of approximately 180,000 people. There are five health facilities (Basse, Demba Kunta Koto, Fatoto, Gambissara and Koina) from which pregnant women can be recruited. A recently implemented cluster randomized trial (community-based scheduled screening and treatment of malaria in pregnancy for improved maternal and infant health) has recruited in 18 months 1,852 pregnant women and followed them up until delivery, with minimal loss to follow up (about 6%). Though malaria transmission in The Gambia has decreased significantly over the last decade there is still substantial transmission in this region, mainly between September and December, with malaria prevalence in the general population of about 30-40%.
The trial will be carried out at Lisungi health centre, an 81-beds health facility, located in Kinshasa suburb, where malaria transmission is perennial. Asymptomatic carriage of Plasmodium falciparum is estimated at 23.1% in children of less than 5 years. In 2016, over 15.3 million malaria cases and 33,997 related deaths were registered. On average, 60 deliveries are registered each month in Lisungi. This site has benefited from the support of EDCTP through the Quinact trial (grant reference MS.2010.10800.004).
Mozambique: Manhiça District
Manhiça is located in southern Mozambique, 80 Km north of Maputo city. The district is under Health and Demographic Surveillance System (HDSS) covering around 178.000 inhabitants which registers vital events (pregnancies, deaths, migrations). The district has a 153-bed District Hospital (Manhiça District Hospital (HDM) and a 148-bed Rural Hospital (Xinavane Rural Hospital (HRX) with a 24-hour emergency room, radiology facilities, maternity ward, small surgery room, in-patient ward, and basic laboratory and outpatient consultations. The hospitals also offer maternity and child health services with caesarean section (5/24 hour and on alternate weekends). Malaria is endemic with perennial transmission, mainly by P. falciparum which represents one of the top five causes of mortality in under-five. A recent community-based surveillance reports a malaria prevalence of 6.10% by RDT and 7.95% by qPCR. The prevalence of HIV in women attending the ANC clinic was 29.4% in 2010. The Manhiça Health Research Centre (CISM) works in collaboration with the HDM and HRX where the study will take place. At antenatal clinics, pregnant women receive health talks about nutrition, malaria and HIV/AIDS prevention and treatment. Routine screening tests are also offered for HIV, syphilis, anaemia, and urinary infection. Approximately 85% of all deliveries in the district occur at HDM. CISM conducts a wide spectrum of research including epidemiology and clinical trials in maternal and child health. CISM also participates in other EDCTP funded studies in maternal health and malaria as MAMAH (RIA2016MC-1613, www.mamahproject.net).