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Community-based scheduled screening and treatment of malaria in pregnancy for improved maternal and infant health: a cluster-randomized trial

Final Report Summary - COSMIC (Community-based scheduled screening and treatment of malaria in pregnancy for improved maternal and infant health: a cluster-randomized trial)

Executive Summary:
Malaria is by far the world’s most important tropical parasitic disease and around 250 million people become ill each year and 600.000 mainly young children die as a consequence of this disease. Importantly, also pregnant women are very susceptible to malaria infection and Malaria in Pregnancy is a major cause of maternal anaemia and low birth weight that leads to infant mortality, poor growth and development. Prevention measures such as, bed nets and intermittent preventive treatment with sulphadoxine-pyrimethamine, is cheap and cost-effective, but coverage achieved by these interventions is low. Therefore, the COSMIC project aimed at the implementation of scheduled intermittent screening at community level with Rapid Diagnostic Test deployed by Community Health Workers. This should enable rapid and effective treat with anti-malarials and prevents the negative effects of a malaria infection during pregnancy. In addition the Community Health Workers will encourage pregnant women to attend antenatal clinics for other pregnancy-targeted interventions, thereby improving its coverage. The specific project objectives were:
• Identify, both at the community and health facility level, potential bottlenecks for the implementation of scheduled intermittent screening targeting pregnant women at community level with Rapid Diagnostic Test by Community Health Workers;
• Determine the impact of introducing scheduled intermittent screening on the quality of Community Case Management of Malaria in the general population;
• Determine the impact of scheduled intermittent screening on antenatal care attendance and intermittent preventive treatment with sulphadoxine-pyrimethamine coverage;
• Determine the protective efficacy of scheduled intermittent screening on placenta malaria, anaemia and low birth weight;
• Estimate the incremental cost-effectiveness of scheduled intermittent screening when added to intermittent preventive treatment with sulphadoxine-pyrimethamine, measured in terms of cost per case of placental malaria, maternal anaemia and low birth weight averted.
• Formulate policy recommendations to implement this intervention in the West Africa region and other Sub-Saharan African countries.
The project was implemented in Benin, Burkina Faso and The Gambia and comprised 6 work packages: one dedicated to management, 4 research orientated work packages and one designed for dissemination activities and policy panels.
Although the intervention did not have the expected effect on placenta malaria, it clearly demonstrated the ability of Community Health Workers to follow up pregnant women between antenatal clinics, and to diagnose and treat malaria when needed. This is a very important finding with significant impact on maternal and child health. Also, the proposed intervention resulted in stimulating pregnant women to attend the antenatal clinics, where they received prophylactic sulphadoxine-pyrimethamine to protect them (and their unborn child) against malaria. It was noted that women in the intervention group significantly more frequently attended the antenatal clinics and received more doses of protective sulphadoxine-pyrimethamine. The fact that 3 or more doses of intermittent preventive treatment with sulphadoxine-pyrimethamine reduced significantly the risk of placenta malaria as compared to 1-2 doses indicates that the World Health Organizarion recommendation of providing IPTp-SP at each antenatal clinic must be widely implemented. Policy panels and interviews clearly revealed the appreciation of stakeholders and communities for the project (“We do not want to see the project coming to an end”). The project is perceived as providing significant increased health care for pregnant women and is in general considered as very beneficial for the communities. Therefore, the COSMIC consortium proposes that scheduled screening and treatment of malaria in the Community by Health Workers is a valuable intervention to be taken up in the health system. It will stimulate women to increase their antenatal clinic, which will have beneficial effects on both maternal as well as infant health.
Project Context and Objectives:
Malaria is by far the world’s most important tropical parasitic disease. An estimated 250 million people become ill each year. Malaria is due to infection with the parasite Plasmodium, a small single cell organism. There are 5 species of Plasmodium that cause human disease: P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. The disease kills an estimated 600.000 people per year, mainly young children in developing countries. Other important risk groups are pregnant women and non-immune travellers.
In general, transmission of the parasites from man to man occurs via the bite of infected blood-feeding female mosquitoes (Anopheles). Inside the human body, the malaria parasites multiply extremely rapidly in the liver. At a certain time point, they leave this organ and subsequently infect red blood cells (erythrocytes). A next wave of Plasmodium replication takes place in the erythrocytes, then the red blood cell bursts, followed by infection of new red blood cells by the parasites. Malaria begins as a flu-like illness 8 - 30 days after infection. Symptoms include fever, with or without other symptoms like headache, pain in the muscles, vomiting, diarrhoea and cough. Typical cycles of fever with shaking chills and drenching sweats may develop. Destruction of the erythrocytes leads to severe anaemia. Death may be due to infected red blood cells blocking blood vessels in the brain (cerebral malaria) or damage to other vital organs (e.g. liver and kidneys).

Pregnant women are very susceptible to malaria infection and Malaria in Pregnancy (MiP) is a major cause of maternal anaemia and low birth weight (LBW) that leads to infant mortality, poor growth and development. In low transmission areas, malaria can become severe, resulting in maternal and fetal death. In sub-Saharan Africa (SSA) MiP is responsible for 8–14% of LBW, 3–8% of infant deaths, higher risk of post-partum haemorrhage and >10,000 maternal deaths/year. Prevention like, bed nets and intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp/SP), is cheap and cost-effective, but coverage achieved by these interventions is low. Therefore, we propose Community Health Workers (CHW) to implement scheduled intermittent screening at community level with RDT of pregnant women and if positive treat with anti-malarials (SST). In addition CHWs will encourage pregnant women to attend antenatal clinics (ANC) for other pregnancy-targeted interventions and IPTp/SP, thereby improving its coverage.
This approach combines existing IPTp/SP with SST at village level as an extension of Home based management of malaria (HMM). This low cost (based on existing practice) and simple (diagnosis by RDTs) intervention improves maternal and newborn health and capitalize on an already existing intervention (HMM). The aim of this proposal is to determine the added value (as compared to IPTp/SP alone implemented in health facilities) of community SST of pregnant women implemented through the CHW involved in HMM.

The specific project objectives were:
• Identify, both at the community and health facility level, potential bottlenecks for the implementation by CHW involved in CCMm of CSST targeted at pregnant women;
• Determine the impact of introducing CSST on the quality of CCMm in the general population;
• Determine the impact of CSST on ANC attendance and IPTp/SP coverage;
• Determine the protective efficacy of CSST on placenta malaria, anaemia and low birth weight;
• Estimate the incremental cost-effectiveness of CSST when added to IPTp/SP, measured in terms of cost per case of placental malaria, maternal anaemia and LBW averted.
• Formulate policy recommendations to implement this intervention in the West Africa region and other SSA countries.


Project Results:
A total of 4,731 pregnant women were recruited between November 2013 and November 2015 across the three study sites (WP 2). Loss to follow up was low in the Gambia (113/1960=5.8%) and in Burkina Faso (62/1800=3.4%). However, loss to follow up was high in Benin (290/971=29.9%). In Benin, recruitment was significantly lower than expected and loss to follow up for women recruited was high (290/971=29.9%). In total, 4,266 (90.2%) women completed follow up and delivered with the study team, of which, 88% have primary outcome data.

In all countries, the mean number of slides (for each scheduled visit, a RDT was performed and a blood slide collected) per woman was significantly higher in the intervention than in the control group indicating the community Health workers (CHWs) followed closely the instructions of screening women between antenatal visits. In all countries, the percentage of positive slides tended to be higher in the intervention group.
Antenatal clinic attendance (scheduled visits) was significantly higher in the intervention arm in Burkina Faso but not in The Gambia and Benin. However, coverage of IPTp-SP in terms of number of doses taken by each woman or the mean number of doses given at village level, was not significantly different between intervention and control arms.

For the analysis on placenta malaria, only Burkina Faso and The Gambia were included while for the analysis of peripheral infection the three countries were included. The large majority of placenta infections were classified as “past infection”, i.e. no parasites detected in the placenta biopsies, while the prevalence of active infection (acute or chronic) was only 4%, with no difference between study arms. Similarly, the prevalence of peripheral malaria infection at delivery was 11% in both arms. This probably indicates that treating only malaria infections detected by rapid diagnostic tests (RDT) between antenatal clinics visits is not sufficient to prevent placenta malaria as a substantial proportion of infections are probably not detected.

Adjusting the analysis to several confounding factors such as season of birth, parity, number of SP doses given as IPTp, and number of artemether-lumefantrine treatments received, did not change the overall results as the adjusted odds ratio was close to 1, indicating no difference between study arms. As expected, primi- and secundi-gravidae had a significantly higher risk of placenta malaria than multigravidae. The risk of placenta malaria was almost 2-fold higher for women who delivered during the dry (non-transmission) season and this probably indicates that they acquired a malaria infection during the previous transmission season and were unable to clear it. It is interesting to note that the number of artemether-lumefantrine treatments was significantly associated to an increased risk of placenta malaria, which simply reflects the fact that women found infected with malaria and treated accordingly had a higher risk of infection and hence of placenta malaria. It is also important to note that the risk of placenta malaria decreased with the increasing number of SP doses administered as IPTp. Such an effect is mainly due to Burkina Faso, where the WHO recommendation to provide IPTp-SP at each antenatal visit was implemented, while The Gambia and Benin did not implemented such policy. It is clear that 3 SP doses or more are significantly better than 1 or 2 doses, confirming that the WHO recommendation should be implemented.

The health system research analysed the local health policies in relation to prenatal care and community involvement in the provision of care in Benin, Burkina Faso and The Gambia. The data were collected in Benin (November – December 2013), Burkina Faso (November-December 2013) and in The Gambia (February - April 2014). Furthermore, it evaluated the integration of key sequences of work during the Clinical Trial (in existing care delivery systems) and the functionality of the new approach to malaria management in pregnant women. Importantly also barriers to health policy, care organization, and behavior of stakeholders throughout the clinical trial were identified. Based on this research recommendation for potential scaling up of the intervention were developed. These include:
• A concerted effort will be needed to overcome obstacles to scaling up the tested strategy related to the management of malaria in pregnancy.
• Plan a scaling-up protocol that includes all important steps, the provision and management of human, financial and material resources. Questions of availability of inputs to health facilities must be addressed ;
• Obtain the effective commitment of the actors at health system level and at community level so that they participate in lifting any bottlenecks ;
• Clarify the status and funding of community health workers in health policies in general and in the management of malaria during pregnancy ;
• Systematically assess the performance of the involved community health workers;
• Systematically report critical incidents and significant events occurring during prevention and management of malaria in pregnancy at the start of scaling up;


The medical anthropology research (WP 4) assessed local communities’ acceptability of Community SST (CSST) carried out by the CHW, and its feasibility and adequacy in the local context. Furthermore, potential bottlenecks, at community level, for the implementation of CSST (through the CSST-system) were identified. In addition, data on community acceptability was gathered in respective settings of Burkina Faso, Benin and The Gambia
In order to ensure comparative results qualitative data were collected during ethnographic fieldwork in all three countries. The following data collection techniques were used in order to enhance the reliability and validity of the results; interviews, group discussions and participant observation. Based on the literature review, interview and observation guides were developed and shared among the three countries. However, these were further adapted independently based on the preliminary data collected in the three countries. In the Gambia, fieldwork was carried out in 11 (4 control, 7 intervention) study villages located in The Upper River Region. Qualitative data collection in the communities was done through in-depth interviews (N=90), focus group discussions (N=5) and participant observations (N=29).
In Benin, fieldwork was conducted between May and August 2015 in the Atlantic Region. In total 17 villages were visited (15 intervention and 2 control villages). Data collection consisted of in-depth interviews (N=56), focus groups (N=5) and participant observations (N=9). Fieldwork in Burkina Faso was conducted between February and April 2015 in the Nanoro Health district. Data collection has been realized in 17 villages. ( 16 intervention and 1 control). In total In-depth interviews (N=21) and Focus group (N=5).
The acceptability of CSST at community level was in the Gambia widely accepted by both village health workers and community members. The acceptability of CSST by the community was very heterogeneous in Benin. In Burkina Faso the community widely accepted the implementation of the intervention. This community has frequently been exposed to research activities . The main difficulties were in following up with unmarried pregnant women and the unavailability of women at their homes for scheduled visits, especially during raining season.
ITPt uptake at ANC was also studied in the three countries. In The Gambia, the major
barriers for ANC visits are the distance, cost of travel, and language. A solution for this are mobile clinics in rural communities, women can visits these. Furthermore, some vulnerable populations are difficult to reach. A first group are pregnant teenagers (unmarried) are difficult to reach because they fear gossip. Often they have to go away from home and reside somewhere were there networks are less strong. This also implies that they drop out of school. Pregnant unmarried teenagers are reluctant to see the VHW/TBAs since they are part of the community. Going to ANC slightly better since health workers might not originate from their village. Some married women might also be vulnerable and be reluctant to go the ANC, if they have history of miscarriages; if they have pregnancies out of wedlock and if they are above forty years old because they might feel ashamed to be in the same space as younger pregnant women.

In Benin, the following barriers were identified. First, structural factors such as distance and road conditions make it difficult to access health centers. There are also some additional financial barriers. Moreover, the malaria season goes together with the rainy season, people don’t like to travel because it is cold then and they need to farm in order to have a livelihood. Importantly. many women did not understand the preventive nature of IPTp. Another barrier to go to public health center for ITPt, is the relationship between the women and the midwives working at the public health center. Most women prefer to go to ANC in afternoon but midwives do not attend to them. In addition, in contrast to The Gambia, Benin knows many legal and illegal private health centers. Therefore, this intervention also needs to take into account these private health. In addition, the distribution of IPTp proved to be problematic and there were often stock outs.

In Burkina Faso pregnant women faced the challenge of not having an approval of their husband when seeking for health services. To enable women to attend health service during their pregnancy, it is important that their husbands are sensitized and aware of importance of timely ANC.

The health economy component (WP5) focused its research on: (1) Costs associated with seeking malaria treatment during pregnancy and the role of financial support in Burkina Faso and Gambia, (2) Community-based screening and treating for malaria in pregnancy in Benin, Burkina Faso and Gambia: community health workers’ profiles, perceptions and time commitments.
The non-medical direct costs associated with health care seeking have been found to be a high component of total medical costs in both countries studies. Furthermore, it was found that community-based scheduled screening and treatment, adds to CHW workload, and needs to be carefully considered given the existing seasonal work commitments of CHWs and their challenging working conditions.

Potential Impact:
Although the intervention did not have the expected effect on placenta malaria, it showed that CHW were able to follow up pregnant women between antenatal clinics, and to diagnose and treat malaria when needed. This is a very important finding with significant impact on maternal and child health. Also, the proposed intervention resulted in stimulating pregnant women to attend the ANC. At ANC level they received prophylactic SP to protect them (and their unborn child) against malaria. It was noted that women in the intervention group significantly more frequently attended ANC and received SP. The fact that 3 or more IPTp-SP reduced significantly the risk of placenta malaria as compared to 1-2 doses indicates that the WHO recommendation of providing IPTp-SP at each antenatal clinic should be implemented as widely as possible.

Policy panels and interviews clearly revealed the appreciation of stakeholders and communities for the project (“We do not want to see the project coming to an end”). The project is perceived as providing significant increased health care for pregnant women and is in general considered as very beneficial for the communities.

Therefore, the COSMIC consortium proposes that scheduled screening and treatment of malaria in the Community by Health Workers is a valuable intervention to be taken up in the health system. It will stimulate women to increase their ANC attendance, which will have beneficial effects on both maternal as well as infant health.

List of Websites:
www.cosmicmalaria.eu

Henk Schallig (coordinator)
h.d.schallig@amc.uva.nl