Category Archives: Monkeys

Biology and Malaria Eradication: Are there Barriers?

During a press conference prior to the release of the executive summary of 3-year study of trends and future projections for the factors and determinants that underpin malaria by its Strategic Advisory Group on Malaria Eradication (SAGme), WHO outlined some hopeful signs emanating from the SAGme including

  1. Lack of biological barriers to malaria eradication
  2. Recognition of the massive social and economic benefits that would provide a return on investment in eradication, and
  3. Megatrends in the areas of factors such as land use, climate, migration, urbanization that could inhibit malaria transmission

Concerning the first point, the executive summary notes that, “We did not identify biological or environmental barriers to malaria eradication. In addition, our review of models accounting for a variety of global trends in the human and biophysical environment over the next three decades suggest that the world of the future will have much less malaria to contend with.”

The group did agree that, “using current tools, we will still have 11 million cases of malaria in Africa in 2050.” So one wonders whether there are biological barriers or not.

Interestingly the group did identify, “Potential biological threats to malaria eradication include development of insecticide and antimalarial drug resistance, vector population dynamics and altered vector behaviour. For example, Anopheles vectors might adapt to breeding in polluted water, and mosquito vector species newly introduced to Africa, such as Anopheles stephensi, could spread more widely into urban settings.”

This discussion harkens back to an important conceptual article by Bruce Aylward and colleagues that raised the question in the American Journal of Public Health, “When Is a Disease Eradicable?” They outlined three important criteria that had been proposed at two international conferences in 1997 and 1998.

  1. biological and technical feasibility
  2. costs and benefits, and
  3. societal and political considerations

Their further expansion on the biological issues using smallpox as an example is instructive. They noted that not only are humans essential for the life cycle of the organism, but that there was no other reservoir for the causative virus, and the virus could not amplify in the environment. In short, there were no vectors, as in the case of malaria. The relatively recent documentation of transmission of malaria between humans and other primates of different plasmodium species is another biological concern. At this point, Malaysia, for example, is reporting more cases of Plasmodium knowlesi in humans that either P vivax or P falciparum.

Another biological issue identified by Aylward and colleagues was the fact that smallpox had one effective and proven intervention, the vaccine. Application of the vaccine could be targeted using photograph disease recognition cards as the signs were quite specific to the disease. Malaria has several effective interventions, but most strategies emphasize the importance of using a combination of these, and implementation is met with a number of management and logistical challenges. The signs and symptoms of malaria are confused with a number of febrile illnesses.

Finally, two other issues raised concern. Insecticide resistance was recognized in the first malaria eradication effort, and is raising its head again, as pointed out by SAGme. Comparing smallpox and yaws, the challenge of latent or sub-clinical/asymptomatic infection was mentioned. Malaria too, is beleaguered with this problem.

Clearly, we must not lose momentum in the marathon (not a race) to eliminate malaria, but we must, as WHO stressed at the press conference, increase our research and development efforts to strengthen existing tools and develop new once to address the biological and logistical challenges.

The Monkey on the Back of Malaria Elimination

Concerning malaria elimination, “WHO grants this certification when a country has proven, beyond reasonable doubt, that the chain of local transmission of all human (emphasis added) malaria parasites has been interrupted nationwide for at least the past 3 consecutive years.” This target is challenging enough, but becomes more complicated when we consider that zoonotic transmission of malaria among monkeys and humans has been documented in Brazil and Southeast Asia. We cannot expect monkeys to sleep under bednets, so creative and realistic solutions are needed.

The Malaria Eradication Research Agenda (malERA) recognizes this problem. Plasmodium knowlesi, originally found in macaque monkeys in Southeast Asia has been dubbed the fifth human malaria due to its spread to people as deforestation has disturbed the habitat of the monkeys. In particular malERA addresses the challenge of understanding the upward trend of this malaria infection in that region and the need for better understanding of transmission dynamics and proper diagnosis.

The danger of P. knowlesi is heightened by difficulties in diagnosing it and distinguishing it from other malaria species. “Recently, the prevalence of human infection with a simian malaria parasite, P. knowlesi, has become an important issue in a wide area of Southeast Asia. The identification of this parasite by microscopy is very difficult because it resembles the P. malariae parasite. However, the symptoms caused by P. malariae and P. knowlesi are very different, with only P. knowlesi causing severe and life-threatening malaria” (Komaki-Yasuda et al.)

Reports from Brazil highlight another ‘simian hotspot.’ While P. Knowlesi represents monkey infections reaching humans, the opposite may have happened to establish a reservoir in the New World. “P. vivax lineages appearing to originate from Melanesia that were putatively carried by the Australasian peoples who contributed genes to Native Americans. Importantly, mitochondrial lineages of the P. vivax-like species P. simium are shared by platyrrhine monkeys and humans in the Atlantic Forest ecosystem, but not across the Amazon, which most likely resulted from one or a few recent human-to-monkey transfers.”  But looking even further back in natural history, Escalante and colleagues found, “compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia.”

A recent study in this area found the worrying results that, “The low incidence of cases and the low frequency of asymptomatic malaria carriers investigated make it unlikely that the transmission chain in the region is based solely on human hosts, as cases are isolated one from another by hundreds of kilometers and frequently by long periods of time, reinforcing instead the hypothesis of zoonotic transmission.”

In Africa, Linda Duval and co-researchers, who found P. falciparum in blood samples from two chimpanzees belonging to two different subspecies, warn that, “If malignant malaria were eradicated from human populations, chimpanzees, in addition to gorillas, might serve as a reservoir for P. falciparum,”

It appears that the dynamics between monkeys, malaria and humans has a long history. Even once certified malaria-free countries face the threat of imported malaria from people crossing borders. Now we must recognize that the threat may already live within borders. So since existing malaria interventions to protect humans from malaria cannot be applied to monkeys, accelerated research on the genetics of the parasite and the mosquito is needed to prevent both primate groups from getting malaria.