Mali is a landlocked country located in Western Africa, highlighted in the map below.
Mali covers a great slice of sub-Saharan Africa and is one of the poorest countries in the world. Basic health care is a major problem, with four million annual cases of malaria presenting a crippling burden on its economy. With a population of over 14 million and over half of its population below the poverty line; its no surprise that the UN is focusing on rebuilding this nation.
Through government and private partnerships and initiatives, parts of Mali now have state of the art and world-class medical systems. What was once a hopeless scene is now a major success story.
Robert Gwadz a member of the National Institute of Allergy and Infectious Diseases (NIAID), was busy developing the “perfect mosquito” in 1989 — a genetically modified prototype of Anopheles gambiae in which the malaria parasite, the cause of major health issues, could not breed. The grand plan was to over run the local Anopheles mosquito population with the genetically engineered prototype and eliminate the malaria threat through interbreeding. But, Gwadz recalls, “We had no idea how to manage such a release.”
''Gwadz contacted Yéya Touré, a Malian researcher with whom he had previously worked. He received Rockefeller Foundation and World Health Organization (WHO) funding for the initial effort. Within two years, NIAID added its financial support and assigned entomologist Richard Sekai to coordinate the program inside Mali.'' A young Malian physician, Ogobara Duombo, working with Louis Miller, then head of the Malaria Section at the NIAID Laboratory of Parasitic Diseases, extended the research agenda into the treatment of Malaria. These efforts in 1992 became the Malaria Research and Training Center (MRTC) within the national medical school (now part of the University of Bamako).
Photo: Guindo Oumar (left), lab manager, and Professor Anatole Tounkara, scientific director, work together at the Center for HIV and TB
Research Program (SEREFO) in Mali.
Dr. Steve Smith, director of the NIAID Office of Global Research, stated the project’s success was initially due to the “strong commitment in NIAID and Mali by certain individuals.
You can’t do a project like this unless there are talented researchers with a mix of skills including science diplomacy.” Smith also noted that the Mali government’s constant supportive network has been pivotal. “It is a real partner,” he says. “Other countries don’t have this [key] piece.”
Influenced by popular demand for malaria preventative measures, the Mali Ministry of Health supported the MRTC’s creation at the nation’s only public university. It now works with MRTC researchers on joint projects. These include evaluation of mosquito control measures, malaria drug resistance and the training of laboratory technicians.
At first, the biggest problem was a lack of local resources and funding. For example Gwadz recalled that, after a fuse burst in one his original labs, there was not a single fuse available for sale in the entire country. He had to fly to Paris and collect a suitcase full and bring them back to Mali. “There were no supplies, no
basic laboratory chemicals. Everything had to be ordered from
overseas and imported,” he says. Electrical power was another major issue, with daily black outs as hydroelectrical plants failed as dams were low at the start of the rainy season.
These problems were largely overcome through the building of new, NIAID funded, research and training facilities. The development of reliable supply chains helped as well. The MRTC now boasts of seven fully equipped laboratory and office buildings in Bamako plus several field research sites, all equipped with emergency generators. Communications are assured by satellite dishes providing a direct Internet link to the NIAID computer network in Bethesda, Md. Most important is the laboratory equipment. “In some countries, we have to bring everything we need. This is not the case in Mali. We can do flow cytometry, PCR [polymerase chain reaction] and other advanced techniques,” says NIAID researcher Amy Klion. International research groups from other organizations now regularly make use of the MRTC facilities.
Expansion to Other Diseases...
Klion is an expert in filariasis, an infection of parasitic worms. The lymphatic form of the disease, which is common in Mali, causes severe swelling and ultimately elephantiasis. Lymphatic filariasis is transmitted by the same Anopheles mosquitoes that transmit malaria, leading to many coinfections.
The fact that Klion is working with the Mali project is indicative of how it has expanded. Klion relates, “One of Yéya Touré’s students, Yaya Coulibaly, came to work at NIAID. He was interested in filariasis, and that was the start of our collaboration.” The filariasis project led to a series of investigations on insect-borne diseases, among them leishmaniasis.
In 2002, the MRTC and the Entomology Unit of the University of Bamako medical school jointly formed a NIAID-sponsored International Center for Excellence in Research (ICER). NIAID designed the ICER program based on its experience with the MRTC. One of the ICER program’s goals is to create locally managed, sustainable research and training programs that build indigenous infectious disease research capacity and address shared scientific priorities. The main concern is diseases of local importance. (NIAID also formed ICERs in Uganda and India.)
An HIV/tuberculosis unit became a third part of the Mali ICER in 2002. The focus on HIV grew out of a proposal from the medical faculty dean. HIV prevalence in Mali is relatively low (about 1.5 percent in people 15 to 49), but TB is much more common. It, therefore, made scientific sense to include a concentration on HIV/TB coinfection. Gwadz notes, “Mali is also safe, cooperative and politically stable. The HIV/TB unit has proved a successful program.”
The increasing complexity of the Mali scientific program brought with it additional organizational complexity. NIAID now maintains two senior science administrators at its Mali office. Since 2004, a five-person Mali Service Center, run for now by outside contractors, provides accounting services for the researchers in Mali.
Decision Making Process.
The Mali staff has the status of a NIAID contractor; it is not an outside grantee. As contractors, staff members are paid directly by NIAID within the scope of specific research projects. The Americans and Malian consult on study designs, with Malians the primary executors. The American collaborators visit as needed. “I go to Mali every three months, when the data monitors go, and also to teach techniques such as PCR,” says Klion.
Of course, the U.S. researchers have a more America-centric view of the process than the Malians. “We have an idea, for example,about mosquito mating behavior, and the Malians figure out the details based on their local knowledge,” says Gwadz.
But for the Malian researchers, “Almost the entire study is done in Mali, including the lab work,” says Anatole Tounkara, present dean of the medical faculty and director of the HIV/TB research program. “It is a great thing for us that the NIAID considers us on the same level. This is not NIAID science but our science.”
Often the Malian scientists help determine research direction. Seydou Doumbia, deputy director of the MRTC entomology program, cites the example of leishmaniasis. “One of our colleagues was looking at leishmaniasis, but the NIAID people said that there was no leishmaniasis here. So we said here are the data. And they said, great, let’s see if we can do our vaccine study in Mali.” The HIV/TB program has formalized this process with a joint Mali-U.S. scientific review committee that approves research proposals from both countries. Once fully developed, all ICER protocols must receive final approval by Malian and NIAID Institutional Review Boards to ensure that protocols meet international standards.
Decisions cannot go in one direction because the Malians are the ones who have to cope with the local conditions. Hammering out an experimental protocol is, therefore, an iterative process. The NIAID scientists may propose a specific research idea, but the Malian scientists refine it according to local conditions. As Sekou Traoré, co-director of the MRTC recounts, “They [NIAID] say what they want to do, but we can say it is not feasible. We can say no at the initial phase, but when we have elaborated a protocol together, turning it down is no longer an option.”
Rick Fairhurst of NIAID’s Laboratory of Malaria and Vector Research illustrates the way the cooperation may evolve. His study relating human genetic mutations to malaria severity in 1,200 Malian children is yielding a treasure trove of data. Fairhurst is investigating the action of human mutations known to provide some protection. His Malian co-investigator, Mahamadou Diakité, is combing the same data set to find previously unrecognized protective mutations.
Further adjustments in research protocols occur at the village level, where studies are carried out. The Malian investigators first hold a meeting with the local chiefs, seeking their buy-in. These meetings are not pro forma as the chiefs usually ask very pointed questions. Once the chiefs have approved, the investigators call a villagewide meeting to explain the research. “We may have to alter the protocol based on what the villagers say,” notes Klion.
Villagers obtain concrete health benefits while participating in a study. They may receive health care that addresses the disease orcoinfection under study. Enhanced treatment for other diseases detected in the course of the study is another possibility. These services are provided either by the study personnel or nearby public clinics. There are also other types of limited assistance: Klion tells of a clinical trial in which participants received free breakfast because the study drug had to be taken with food. When the trial was over, the participants requested extending the free breakfasts for another month until harvest time. “But we were unable to do that,” recalls Klion. “It was heartbreaking.”
Next Steps
The Malian staff at Mali ICER now amounts to some 160 investigators, technicians and support staff. The original malaria project started out looking at mosquito behavior and control then expanded into epidemiology, treatment and vaccines. From 2006 to 2009, the MRTC/ICER initiated 39 human malaria studies. Fifteen involve malaria vaccines and the rest range from human protective factors to various drug regimens. There is also a study looking at the immunology of filaria-malaria coinfection.
Other recent filariasis investigations include two treatment trials. The HIV-TB unit meanwhile is conducting a long-term study of immune responses to TB, with and without HIV coinfection. It is now enrolling trials looking at HIV treatment response.
Among the projects at earlier stages of development are research on leishmaniasis (an epidemiologic study possibly leading to a vaccine trial) and the tick-borne disease, relapsing fever. Future directions include more involvement with national development. To relieve overcrowding at the University of Bamako, there are ongoing discussions about building a second national university. This would require significant expansion of the current faculty, and the ICER has a role to play here. “There is only one university in Mali, and I hope that we can generate more high quality researchers able to teach in new universities as we open them...This is my vision,” says Tounkara.
Malian researchers also mention their interest in further emphasizing “translational research.” This research would show how to apply scientific findings to improve community health. For example, it is not enough to discover a potent malaria treatment if it rapidly succumbs to drug resistance when put into clinical practice. Translational research would find ways of administering the drug that retain its efficacy. MRTC’s Traoré says, “We have to strike a balance between current research and what would be useful to the public in future. We want to be part of a new generation of scientists that uses new technology to respond to people’s needs.”
Traoré himself is back working on the original research concept, the genetically engineered malaria-proof mosquito. New gene manipulation techniques make the idea more promising, and Traoré received an independent grant from the University of Kiel (Germany) to further develop this mosquito.
The NIAID researchers welcome a move toward such independent research, which is a major goal of the collaboration. NIAID’s Klion, who first worked in Mali during the late 1980s, notes that the Malian education system historically has not encouraged self directed activity among its graduates. But, she says, “There has been a huge change in recent years. The Malians have more skills and autonomy, with the malaria group furthest along in becoming more independent.”
The Mali experience underscores the benefits from an international research collaboration based on mutual respect, common scientific objectives and shared responsibilities. The ICER is advancing to the point where its achievements will feed on themselves, setting the stage for further progress. The question remains as to the ultimate health, economic and cultural benefits for the country as a whole. These depend on Mali’s ability to apply what its scientists have learned. Mali faces a desperate lack of resources, but the intellectual vitality of its nascent scientific establishment promises to bring the country into the 21st century.
