PRB

(April 2009) Malaria threatens close to one-half of the world’s population, and more than 1 million children die each year of malaria-related complications. In sub-Saharan Africa, nearly 250,000 pregnant women die annually: Up to 30 percent of these deaths are due to hemorrhage, with malaria often an important contributing factor. Eliminating malaria has proved elusive given the inadequate infrastructure and health systems in many of the countries where the disease is most prevalent. But there are effective ways to combat malaria even in low-income countries.

During a PRB Discuss Online, malaria expert and epidemiologist Joel Breman of the Fogarty International Center, U.S. National Institutes of Health, answered participants’ questions about the challenge of eradicating malaria: What countries are most at risk? What are cost-effective ways to reduce exposure? What breakthrough research is needed to break the back of malaria?

April 23, 2009 1 PM EST

Transcript of Questions and Answers

Mary Kent: How might climate change affect efforts to reduce malaria?
Joel Breman: The most important change would be an increase in warm and wet areas allowing malaria-transmitting Anopheles mosquitoes to flourish. Warm and humid temperatures favor a shortened time for the parasite to develop within the mosquito—and a longer life for the mosquito to live, bite and infect people. Of course, more rainfall increases places where Anophelines can lay their eggs. A recent example is the increasing elevation where malaria is transmitted in the Kenya highlands and on Mount Kilimanjaro in Tanzania.

Gauthier MUSENGE MWANZA: J’aaprends que des scientifiques s’attèlent au développement d’une méthode s’appuyant sur un poisson mangeur de larves pour contrôler les populations de moustiques, afin de lutter contre le paludisme. Pour ce, quelle est l’efficacité de cette méthode de lutte contre le paludisme?
Joel Breman: The use of fish that eat Anopheles larva for malaria control has been widely studied and used in many pilot projects. Experiences in India and nearby countries have shown that the approach works best in urban areas and elswhere where there are large ponds or other mosquito breeding sites. Use of local fish species that adapt to and replicate easily in the environment is better than importing the fish. Care is needed as some types of larvivorous fish eat other fish—and humans also like to eat some species of the fish! In Africa, Anopheles msosquito breeding sites are many, small, and widely dispersed providing a challenge to this type of approach.

Rahat Bari Tooheen: What is the most pragmatic solution to the malaria issue, givem the political, social, and environmental conditions of developing nations?
Joel Breman: This question is key, Rahat. Despite the challenges, there are scientific, operational, financial, and political solutions to malaria control and elimination, and they are being implemented. Communities at risk must participate in malaria programs—assuring compliance by taking their drugs, using and maintaining their bed nets, participating in spraying of houses and understanding why. Presidents of endemic countries and ministers have met to establish global and national goals. Is essential that the current tools for malaria are affordable—free in many low-income countries—and that research for new drugs, insecticides, and vaccines is well supported financially. Perhaps most importantly, we need to train many more malariologists and others—in clinical, service delivery, managerial, laboratory, and research disciplines to confront the huge malaria problem.

Kakaire Kirunda: The Uganda Government and Development partners have tried to up the fight against malaria and this is good. But in one of the policies, every febrile illness is taken as malaria and people are given antimalarial treatment without laboratory diagnosis. There are fears that this is wrong because the potent drugs [ACTs] are going to become useless and bring about resistance problems. What is the way forward on this? There is talk of introducing rapid tests but the costs are still high.
Joel Breman: Great, Kakaire. Each African child has 4 to 12 fever episodes a year—about half or more due to malaria in some areas, but variable, especially with the success of control programs. We would soon run out of the artemisinin combination treatments (ACTs) and other drugs if every such event received treatment—resistance would also be a concern. Microscopic exam of blood is good in health units with careful supervision, but not readily available or precise in most endemic communities. Rapid diagnostic tests (RDTs) for malaria parasites are simple to do and give immediate results. Yes we need to get the price lower than about $1 per test. Most importantly, major efforts need to be made to improve the lab and clinical diagosis to find out what causes all the febrile conditions—many of which are life threatening—and treat them properly.

Esther Nakkazi: It seems finally malaria has caught the attention of the developed world. 1. Why at this point in time is the developed world interested in malaria? 2. What new approach should we use to eliminate malaria? 3.What are your thoughts on subsidizing malaria treatment from NGOs. Is it wise?
Joel Breman: There are many reasons why high-income countries are getting interested in malaria because it is mutually beneficial to do so. On a basic level, ten of millions of travelers go from rich to poor malarious countries for visits or to work. A healthy workforce in endemic countries provides opportunity for successful investments. Successful malaria and other disease control programs add to social and political stability. The fact that 1-2 million children die yearly from malaria–perhaps 150 to 300 an hour, has finally got some attention. I think it is very wise to subsidize malaria treatments. The new Affordable Medicines Facility for Malaria (AMFm) advised by a committee convened by the U.S. Institute of Medicine is finally getting off the ground.

Alberto Rizo, MD: What is the status of the Patarroyo’s Malaria vaccine?How did it test in SubSaharan countries? Any future for this vaccine?
Joel Breman: Dr. Manuel Pattaroyo and collaborators in Colombia have been working several decades on different types of vaccines against malaria. The early vaccines were synthetic peptides directed against the blood stage of falciparum malaria. After initial promising highly publicized results in the 1980s, the vaccine did not prove immunogenic or protective in Aotus monkeys, the animal model for P. falciparum. More recently, Dr. Pattaroyo is working on P. vivax vaccines and is again enthusiastic about a subunit-based, multi-antigen, multi-stage product.

Gayatri Singh: Where can we find information about (1) where are malaria medicines available in low income countries (particularly Africa) are imported from, and (2) who funds those medicines? We are interested both in malaria drugs that reach the public sector as well as the malaria drugs that reach the private market.
Joel Breman: This is not my area of expertise. For part 1. Obviously, within each country the malaria control program or central pharmaceutical office can give some guidance. To find which malaria medicines exist in which countries try UNICEF, the Roll Back Malaria (RBM) Partnership, and the U.S. President’s Malaria Initiative (PMI)websites. For part 2, major funders are the Global Fund For AIDS, Tuberculosis and Malaria (GFATM), and the PMI, along with bilateral support from USIAD and many other nations—and contributions from the Gates Foundations and many NGOs.

Ericka Moerkerken: What is your view on the use of biological larvicides (Bti and Bsph) as part of vector control strategies, in particular in the West African context? And what would it take for large donors to support support initatives with a strong biological control component and related operational research?
Joel Breman: Effective use of biological larvicides have been the major tools for the successful onchocerciasis control program where the black fly breeds near flowing rivers and streams. I am familiar with Bti but not Bsph. As mentioned above, Anopheles breeding sites in Africa are many and widely dispersed—some may be as small as “the hoof print of a cow”. I think that there may be some use in breeding sites near urban, periurban areas, refugee camps, construction sites. Research will be essential, not just on entomological indices of effectiveness and transmission, but on the impact on human infection and disease as well as on the social aspects of community acceptance, and toxicity if the product to fish, animals and humans if ingested. Develop a strong and clear hypothesis, Erica. Seems a good research project.

Dr. Josephine Alumanah: Curative is very vital, but we please could we step up on Preventive Measures. What do you think?
Joel Breman: Correct, Dr. Alumah. That is why bed nets, insecticide residual spraying, and environmental management (draining and filling pools of water), particularly in urban/periurban areas is crucial. Also, intermittent preventive treatment (IPT) of pregnant women (IPTp) (and, possibly, children) is an important prevention because this combats low birth weight due to malaria infection and maternal anemia and mortality from hemorrhage. Most countries have preventive policies for malaria and are trying to increase their coverage and use rates. Intensified research on drugs and vaccines to interrupt transmission is essential

Sophia Githinji: In Kenya, ITNs have been widely distributed in some districts resulting in impressive coverage. A recent study in western kenya found that 40% of the nets distributed less [than] 1 year before were badly holed due to sticks used to hand them around sleeping area or burnt by the open tin lamps commonly used in the poor settings. The rate of non-use or misuse of nets was high with 16% of the nets not used or diverted to other uses. 1. Are there measures to improve the physical quality of the nets? 2.what about sustainability of ITNs provisions, given that most of them are donor funded? 3. What about the simple environmental measures that eradicated malaria in the Americas and most parts of Europe long before the DDT? iS IN NOT THE HIGH TIME WE EMBACKED ON THESE MEASURES TO BACK UP THE TECHNOLOGICAL MEASURES IN USE TODAY?
Joel Breman: Important, questions, Sophia. 1. Work has gone into this by several manufacturers. The newer long-lasting insecticide treated nets (LLINs) should help respond to the need and be the only products now used. 2. Sustainability is always key and donors and countries and communities should have a long-term (more than 5 year) time frame to assure good nets. They are an essential public good—everyone benefits if one family uses the nets 3. 21 countries still have malaria in the Americas, but true, there is less of it and many countries are near elimination. Insecticide residual spray, prompt treatment of presumptive malaria cases, environmental management, and superior surveillance systems were/are important as well as continuing economic prosperity and political stability. I agree with your resounding call to arms!

laxman: what r the efective measures … applied by family to control malaria?
Joel Breman: Get, use, and maintain your long-lasting insecticide treated bednets, keep your compound and community free of mosquito breeding sites, respond to any fever episode by taking your family member to a health worker right away. Find out what your government and local non-governmental organizations are doing to combat malaria and ask how you can help them do a better job. If they are not doing anything demand that they do so with your village or community committee.

Vanhmany: LLINs are provided for local poor people in the malaria endemic area, but they are imported. How can we [sustain] the use of the LLIN if there is no international support for developing [countries] especially for the poor? Is there any research on the use of local product[s] that can be use[d] to control malaria?
Joel Breman: Tanzania has one of the most successful bed net producing factories and the manufacturing site is receiving support to assure a high grade product in large quantities. this can serve as a model. Research on local products as insect repellents and insecticides has occurred in many endemic countries and ICCIPE in Nariobi, Kenya is a leader in this area.

Gauthier MUSENGE MWANZA: Des chercheurs ont développé un nouvel antipaludique qui réactive les plus anciens et contribue à préserver l’efficacité de nouvelles molécules. Si je peux avoir plus d’informations sur ça.
Joel Breman: I am sorry I don’t know which “nouvel” drug you are referring to. Malariologists now agree that combining drugs for treatment (as done for HIV, tuberculosis and many cancers) is better than using a single drug. Each drug has a different chemical action on the parasite, thereby decreasing the chance of resistance developing to any of the drugs. This is the basis of ACT to treat malaria, where artemisinin (derived from a plant/Artemesia annua and known to the Chinese for centuries as a cure for “fever”) is combined with lumefantrine, sulfadoxine-pyrimethamine, amodiaquine or other drugs.

Lily: What are the most effective methods of distributing malaria medicines to rural areas and ensuring they are used properly? What prospects are there for newer and more effective drugs to come on the market anytime soon? What might be most effective in lowering the price/increasing the availability of current drugs?
Joel Breman: Exceedingly important, Lily—and I am not an expert by any means. UNICEF is. Creativity will be essential to getting the new antimalarials to “the end of the road” and “where there is no road”. I don’t have the answer… I usually go to the people in the country, in the community, in the household, and ask them how essential medicines get to them and, most importantly what motivates proper use. I would find out if and how oral rehydration salts, antipyretics, condoms, and other health needs are distributed. I would go to the local dispensaries, pharmacies, patent medicine stores, village markets, private/NGO/business clinics and see what they are using and how they receive their meds. There are different systems of distribution, formal and informal. Two problems, partial dosing and sham drugs need attention, the former could be addressed by having blister packets with all drugs combined in one tablet if possible and the daily regimen illustrated on the packet for dosing children and adults; for the second, control of quality needs building into the purchase, receipt, and distribution system. Newer drugs are being developed and tested: the process is long (the FDA just approved artemisinin-lumefantrine for in adults in the U.S.). The ominous finding of decreased sensitivity of falciparum malaria to artemisinin (not ACTs)in Cambodia mandates that the WHO ban on monotherapy/repeat monotherapy with artemisinin compounds be enforced more strictly and that development of newer antimalarial drugs be accelerated. In particular, drugs that interrupt transmission by acting on gametocytes and their maturation should receive priority. The new AMFm plans a novel approach to bring ACTs prices down by subsidizing bulk purchases and flooding markets with good products at fixed affordable prices for countries (perhaps free for patients). see above. The Clinton Foundation has been successful in negotiating lower prices for such essential drugs. We can learn from the HIV/AIDS, tuberculosis, diarrheal diseases and other programs on this one.

laxman: what r the latest [strategies] in the world to control malaria?
Joel Breman: Some of this was discussed above: The strategies are provision and use of: drugs to treat patients and prevent disease (IPT) in pregnant women and children (being evaluated); personal protection with LLINs; classical vector control with IRS, larviciding, drainage and filling of anopheline breeding sites, and other environmental management steps; research to develop new tools and assure the current ones are used optimally; for this, surveillance/monitoring of human disease and core entomological and parasite indices is needed, including resistance testing; and, long-term funding and collaboration. Sustainability requires training and support of large numbers of malariologists—for operations and research. Community understanding, and their active participation in every aspect of the control program is essential for elimation and eradication to be reached.

For More Information

Disease Control Priorities Project, “Malaria” (2006), accessed online at www.dcp2.org/file/9/DCPP-Malaria.pdf, on April 14, 2009.

Joel Breman et al., “Conquering Malaria,” in Disease Control Priorities in Developing Countries, 2d ed., ed. D.T. Jamison et al. (2006): 413-32, accessed online at http://www.dcp2.org/pubs/DCP/21/, on April 14, 2009

Florence Machio, “Will Africa Ever Get Rid of Malaria?” (2007), accessed online at http://www.dcp2.org/features/34/will-africa-ever-get-rid-of-malaria on April 14, 2009.