As One Type of Malaria Declines, New Map Reveals Another Strain Holding Steady

With signs of declining malaria deaths in Africa raising hopes of eradicating the disease worldwide, researchers unveiled today at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) a new malaria map that is the first to identify on a global scale where the long-lasting and potentially deadly form of malariaa parasite known as Plasmodium vivaxhas a firm foothold in large swaths of South Asia and parts of Latin America.

This map helps us understand just how difficult it is going to be to eradicate malaria, says Peter Gething, PhD, who led the University of Oxfords Malaria Atlas Project (MAP) team that produced the study of vivax burden. It shows that in substantial parts of the world, vivax malaria is endemic and transmission is significant. Unfortunately, the tools for fighting this type of malaria range from ineffective to non-existent.

Other studies being discussed at ASTMHthe worlds largest gathering of public and private sector malaria scientists, clinicians and program professionalsand published in the December issue of the American Journal of Tropical Medicine and Hygiene, add to mounting evidence that vivax malaria may be killing people far more often than previously thought; confirm that existing treatments are inadequate and potentially toxic to millions; and shed light on the level of precaution that travelers should take when visiting these regions (see Backgrounder for further information).

While not as deadly as the Plasmodium falciparum malaria parasite that is predominant in Africa, vivax is more common throughout the world, with an estimated 2.85 billion people at risk of infection. And with its unique ability to relapse by hiding in the liver for months or even years, vivax is harder to detect and cure.

 

The MAP team produced an analysis last year depicting only where vivax is known to exist. Malaria experts immediately called for a map pinpointing where the disease is most prevalent, noting that such a tool is essential to mounting an effective fight against this form of malaria.

Hotspots for vivax malaria highlighted by MAP include substantial parts of India. Rates are high even in urban areas like Mumbai, where malariaonce thought of largely as a disease of rural areaswas previously uncommon. Papua New Guinea also has a high rate of infections and transmission, as do significant parts of Indonesia and Myanmar (including Yangon). In the Americas, the area of greatest concern is a large but sparsely populated portion of the Northern Amazon, most of which is in Brazil. But the hotspot also includes parts of Peru, Colombia and Venezuela. In Central America, almost all of Nicaragua is a hotspot for vivax malaria, as are parts of Honduras and Guatemala.

In Africa, Gething said that while vivax is known to exist, infection rates appear to be very, very low for most of the continent, though the map indicates a moderate but stable level of vivax transmission in parts of the Horn of Africa and throughout Madagascar.

Stealth Disease Burden: Large Reservoir of Vivax Infections Hiding in the Liver

Researchers considered an area to be a vivax malaria hot spot if the data analysis yielded infection rates that exceeded 7 percent. Gething noted that this threshold might be considered relatively low for falciparum infections. But he said its high for vivax in part because the figure accounts only for parasites that are detectable in the blood, and also because vivax disease rates have proven hard to reduce.  

He noted that in areas where vivax is endemic, at any given time, there are many people carrying vivax parasites only in their liver, from which they periodically emerge to cause new infections in the blood stream. But, he said, this large reservoir of vivax is difficult to quantify with existing surveillance tools, chiefly because there is currently no simple test for detecting the liver parasites.

One person with vivax actually can represent multiple malaria infections over many years in a single community and each time the parasite moves from the liver to the blood, it contributes anew to disease burden and transmission, Gething says.

The disease burden caused by vivax relapse, he said, is exacerbated by a lack of treatment options. Medicines such as the artemisinin combination therapies (ACTs) that are used to cure falciparum infections can help treat acute bloodstream vivax infections. But only one drugprimaquinecan clear vivax parasites from the liver and thus provide a long-term cure to this type of malaria.

However, in a cruel twist of evolution, a hereditary condition that may have evolved in response to malaria exposures can make the drug toxic, sometimes fatally so, to some people who live in vivax-endemic areas. At ASTMH, another team of researchers from the Malaria Atlas Project will present a map depicting the prevalence of the condition, known as G6PD deficiency, within malaria-endemic countries. Preliminary data indicate that this condition is relatively common in vivax-endemic Southeast Asia, though the highest rates are found in sub-Saharan Africa. The condition is also observed in the Americas, though at lower rates. 

We hope that by mapping the prevalence of G6PD deficiency we can provide evidence that will help contribute towards determining the risks and benefits of using primaquine, which is an important, yet potentially dangerous drug, says Rosalind Howes, the lead investigator on the project.

Even when primaquine is not toxic, the fact that it requires a 14-day regimen has made it impractical for areas where people have little or no access to even modest levels of healthcarewhich is the majority of the malaria-endemic regions of the world.

Meanwhile, bednets and indoor spraying, which, coupled with ACTs, have helped reduce malaria deaths in Africa, appear to have had little impact on vivax. One reason is that the mosquitoes that transmit vivax typically bite outdoors, rather than indoors in the home. And RTS,S, the malaria vaccine candidate in Phase 3 trials that may soon be commercially available, does not target vivax.

This persistence of the vivax parasite in the face of a massive global campaign to eliminate malaria has prompted some malaria fighters to dub it the last parasite standing.

Malaria experts say even though vivax still appears to be less deadly than falciparum, growing evidence of its link to fatalities warrant giving it a higher profile in the global malaria eradication campaign.

Its time to step-up the fight against vivax malaria and stop looking at this form of the disease as relatively mild and tolerable, says Peter J. Hotez, MD, PhD, an infectious disease expert and president of ASTMH. We expect to emerge from this years conference with a far better view of the state of vivax infections around the world and with new knowledge on treatment challenges that can guide a global strategy focused on eradicating all forms of malaria.