PLOS Medicine Specialty Consulting Editor, Lorenz von Seidlein, reports research highlights and his own reflections from the Malaria session at last week’s Epicentre/MSF Scientific Day in Paris.
On 8th June Epicentre’s 27th Scientific Day took place in Institute du Monde Arabe, a spectacular building on the Seine in Paris by Jean Nouvel & Architecture-Studio that won the 1989 Aga Khan Award for Architectural Excellence. Epicentre was created in 1986 by doctors from Médecins Sans Frontières (MSF) and MSF-France holds the majority of votes on its Board. With over 30,000 personnel globally and an annual budget of about USD $1.6 billion, MSF is the single most important institution that responds to outbreaks and humanitarian disasters such as the large Ebola outbreak in 2015. Epicentre conducts mostly epidemiologic and operational research in settings where MSF operates. The annual Scientific Day is opportunity for the MSF community to discuss research in and around operations. The topics of the four sessions this year were HIV, antibiotic resistance, malaria, epidemiology in emergency settings and one session with mixed topics. Each session consisted of presentations by researchers affiliated with epicentre followed by plenary or round table discussions with contributions from the audience. The sessions illustrated the recent achievements of Epicentre and MSF including the roll out of antiretroviral drugs and the provision of health care in emergency settings that includes rather impressive mental health assessments of refugees in Mosul, Iraq and several camps in Greece.
Of particular interest to me was a session discussing current work on malaria in sub-Saharan Africa, in which I had the opportunity to participate. There is a range of interventions that help to control malaria, the most basic of which is the provision of an accurate diagnosis (RDT) and an appropriate treatment using artemisinin-containing therapy (ACT). Aditya Nadimpalli presented a study from Aweil, South Sudan where malaria is a major contributing factor to mortality showed how difficult it can be for clients to get access to such basic health care. In Aweil town, under 5 mortality was 3.7 deaths per 100,000 children per day compared to 9.0/100,000 in rural Aweil, where access to appropriate healthcare is more difficult. One strategy to deliver malaria treatment, which MSF has early on implemented in multiple sites, is seasonal malaria chemoprophylaxis (SMC). SMC consists of three monthly doses of SP-amodiaquine administered to children under 5yo during the malaria season. This regimen works in regions with seasonal malaria, generally those where >60% of the annual rainfall occurs over a 3 month period. It has been estimated that 39 million children would be eligible for such a programme: 24.9 north of the equator (Sahel region) and 14.1 south of the equator (East and South Africa). A Cochrane analysis from 2012 concluded SMC prevents approximately three quarters of all uncomplicated and severe malaria episodes. Matthew Coldiron presented a series of studies in Magaria district, Niger to assess the protective efficacy of SMC. One time saving, pragmatic approach is to provide SMC doses to the parents and allow the parents to administer the doses. The findings of this home-based approach were not promising, though; the protective efficacy of SMC was significantly higher when the administration of at least of the first dose was directly observed, suggesting doses that were sent home were not administered. Thus, the sustained roll out of SMC in rural Africa in the absence of a functioning health infrastructure such a village health post is a major challenge.
There is no reason why SMC should not work in older children. A large study by Milligan and co-workers published recently in PLOS Medicine used a step-wedge, cluster randomised design in central Senegal to evaluate the effectiveness of SMC in children up to 10 years of age. 780,000 doses SP+AQ were administered and the investigators observed a 60% reduction in uncomplicated malaria and 45% reduction in severe malaria in treated compared to control clusters. In another recently published study Coldiron and co-workers from epicentre/MSF adapted the SMC approach in a refugee camp in Uganda in response to a malaria outbreak. They extended intermittent treatment to children from 6 months to 15 years of age and administered DP, not SP+AQ in 8-week intervals (March, May, July). The intervention was popular exceeding 90% coverage during all three distributions with a total of 40,611 participants. There was no control group and the investigators compared the data in the intervention year with that the year before. They found a statistically significant reduction in malaria incidence in children participating in SMC while the incidence in the non-participating camp population increased. (IRR 0.73, 95% CI 0.69–0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67–0.72 among children aged 5–14 years). Among controls 15 years or older (who did not receive DP in 2015), the malaria incidence between the 2 years increased (IRR 1.49, 95% CI 1.42–1.56). Four surveys were conducted. The disappointing finding is the increase in parasite prevalence during the last survey in September after the completion of SMC in July.
Following the presentations the benefits and shortcomings of SMC were discussed. The study in Uganda shows that the effect of SMC is strictly time limited. There is no indication that this intervention makes a permanent impact on the parasite reservoir and would therefore have to be repeated every year in perpetuity. In areas like Senegal where the drug administration precisely coincides with the malaria season the impact is maximal. In contrast, Uganda is outside the seasonal malaria belt and it seems likely that more than 3 rounds will be needed. The intervention has only a little indirect benefit for the rest of the community who are not treated.
These observations lead to the larger question what interventions are being implemented in regions with perennial malaria transmission such as the Democratic Republic of Congo (DRC) or Central African Republic (CAR) where they are arguably most urgently needed? A sobering answer was suggested by Adam Bennett and co-workers earlier this year. They used data from publicly available national population-based surveys that measured the 2- week history of fever and malaria treatment for children younger than 5 years, the malaria indicator surveys (MIS), demographic health surveys (DHS), and multiple indicator cluster surveys (MICS). Data on ACT doses distributed comes from the WHO world malaria report. Over three-quarters (80·3%) of children with malaria did not get a potentially life-saving ACT in 2015. By 2017 1,266 billion long lasting insecticide treated bednets have been distributed in sub-Saharan Africa. It has been suggested that much of the decline in malaria burden observed since the beginning of the century has been due to LLINs. This claim becomes more comprehensible if you consider the 80% of malaria episodes in DAR and CAR that go untreated in children; it would be surprising if treatment rates in older children and adults are higher. There has been considerable progress in the distribution of ACTs and ITN in east Africa but in Central Africa large underserved areas remain.
Why is it so difficult to provide even the most basic health provision, treatment for acute malaria and distribution of ITNs where they are most needed? Providing much-needed interventions requires the establishment of village health posts with a village health worker who has received at least basic training. There has to be a supply line of diagnostic tests (RDTs) and antimalarials (ACTs) in all villages. For a country like DRC with a population of 77.2 million and 90% of the population living in rural areas, there may be roughly 100,000 villages that require a health worker. It would be reasonable to suggest that the government should provide such service to its citizens. But the government is in turmoil, travel advisories currently bar international visitors, and it seems unlikely that international donors will take on this urgent task any time soon. Who but MSF can take on such a challenge?
Lorenz von Seidlein has also worked for 20 years on malaria and other issues in global health. Lorenz is currently coordinating a malaria elimination project with the Mahidol Oxford Research unit In Bangkok, Thailand. He receives a stipend from PLOS Medicine for his contributions as a Specialty Consulting Editor.
Featured image credit: US Army Africa, Flickr.