Malaria: Things are getting better … or not
Malaria has been one of the most important infectious diseases of man through human history. Local successes in malaria control led to elimination of the disease in most of the non-tropical world, but success stalled after the 1960s. More recently, with increased political will, funding from public and private donors, and some valuable new tools, advances in malaria control have been seen in many areas.
Indeed, our conversation has changed, with many openly discussing the audacious goal of eradicating malaria. However, we have a long way to go. Malaria remains deeply entrenched in much of the tropics, especially most of sub-Saharan Africa, with WHO estimating 219 million episodes and 660,000 deaths from malaria in 2010. A recent report shows that, even in the United States, we are not yet seeing improvements.
Improved disease prevention needed
The CDC recently released its latest annual summary of malaria in the United States, which covered all cases reported in the country in 2011. The report showed that malaria incidence is increasing. A total of 1,925 cases were reported in 2011, a 14% increase from 2010, and the largest number of cases reported in the country since 1971. The epidemiology of malaria in the United States was similar to that seen in recent years. Nearly all cases were presumed to be imported (five were listed as laboratory-acquired, transfusion-related, congenital or cryptic). About half were caused by Plasmodium falciparum, the most virulent human malaria parasite; one-quarter caused by P. vivax, the other common human malaria parasite; and the species was not identified for most of the remainder.
Of imported cases, about two-thirds were acquired in Africa, the region with the highest level of malaria transmission in the world. Most of those who acquired malaria were not typical tourists, but rather listed their reason for travel as visiting friends or relatives. Remarkably, among US civilians with malaria for whom information on chemoprophylaxis was available, only 6% reported adhering to an appropriate regimen. Among all cases, 14% were reportedly severe and five patients died.
Clearly, malaria is not going away any time soon in the United States, and we can do better in preventing and managing the disease. The CDC continues to recommend use of atovaquone/proguanil hydrochloride (Malarone, GlaxoSmithKline), mefloquine or doxycycline as chemoprophylaxis for those at risk of malaria during travel; specific geographic and dosing recommendations are complicated but well described on the CDC’s website and many other travel-related websites.
Treatment of malaria has changed, with the advent of artemisinin-based combination therapy (ACT) for uncomplicated P. falciparum malaria. One ACT, artemether/lumefantrine (Coartem, Novartis), is available in the United States — and IV artesunate to treat complicated disease. Older drugs also appropriate for therapy include atovaquone/proguanil, mefloquine, and quinine plus doxycycline or clindamycin for uncomplicated disease and IV quinidine for complicated disease.
Areas at-risk remain
Worldwide, malaria messages are mixed. A major push toward malaria elimination began after a landmark meeting in 2007, and impressive advances have been seen in many countries with relatively low malaria transmission, including areas of the South Pacific, Southeast Asia and South Africa. Major efforts are underway to shrink the malaria map, with hopes to eliminate the disease in countries toward the outside of the malaria map over the coming years. However, malaria remains deeply entrenched in many areas, including most of sub-Saharan Africa, but also large areas of South Asia and Southeast Asia, as well as parts of Oceania and South America. It will be a long time before we can seriously consider malaria elimination in these areas. Meanwhile, how should we divide limited available resources between malaria elimination along the borders of transmission and control efforts to limit morbidity and mortality in the heartland? This question is not easy to answer. Hopefully, with continued political will and donor enthusiasm, robust efforts to both “shrink the map” and “strike the heartland” will offer meaningful advances in the coming years.
Priorities for control of malaria
What are our tools for the control of malaria? First, control of insect vectors is a priority, but is challenged by varied biology of different anopheline mosquito vectors in different parts of the world. In Africa, key vectors bite in homes, and strategies are directed toward control of household mosquitoes. Both indoor residual spraying of insecticides (IRS) and insecticide-impregnated bed nets (ITNs) have shown excellent success, although the sustainability of interventions are challenged by the high cost of IRS, insecticide resistance and changes in mosquito behaviors that circumvent ITN protections.
Second, effective antimalarial drugs play a critical role. Each episode of disease must be treated to limit progression to severe disease, and with each treatment transmission to mosquitoes, and subsequently to other humans, is decreased. ACTs offer an enormous advance, as they are rapidly active and highly efficacious in most parts of the world. However, resistance to malaria drugs has been a problem for decades, and recently, early signs of artemisinin resistance have been seen in Southeast Asia, with delayed parasite clearance after treatment.
There are now signs that artemisinin resistance is spreading from initially identified foci in Cambodia; this is a worrisome development. Beyond treatment, effective malaria drugs offer excellent opportunities for malaria control. Chemoprophylaxis in travelers is highly effective, but expensive and impractical for developing world populations. However, simpler intermittent preventive therapy and mass drug administration approaches are now being studied and already implemented in some regions, and these offer important control tools.
Lastly, a highly effective malaria vaccine will be of enormous benefit. A partially effective vaccine, RTS,S (GlaxoSmithKline), has shown modest efficacy for the protection of African children against malaria, and if continued trials are positive, it may be available in a few years. But, no single control approach currently on the horizon is a silver bullet; rather, a combination of vector control, appropriate use of drugs for treatment and control, and possibly a new vaccine will be required to move malaria from control to elimination around the world over the coming decades.
The malaria burden in the United States is a drop in the bucket compared with that in highly endemic areas, but nonetheless, as shown in the recent CDC update, the disease remains an important concern in travelers. Recent increases in malaria in the United States will hopefully spur us to improve our vigilance in advising appropriate chemoprophylaxis for at-risk travelers and in appropriately diagnosing and treating malaria when it occurs.
CDC. Malaria. Available at: www.cdc.gov/malaria/.
Cullen KA. MMWR Surveill Summ. 2013;62(Suppl 5):1-17.
WHO. World Malaria Report 2012. World Health Organization, Geneva, 2012.
For more information:
Philip J. Rosenthal, MD, is a professor in the department of medicine, division of infectious diseases, at the University of California, San Francisco. He can be reached at email@example.com.
Disclosure: Rosenthal has served as a consultant for Novartis.