ASU researchers receive NIH awards for studies of malaria and emergent disease

[Source: Bio-Medicine.org] - An Arizona State University research team headed by School of Life Sciences Associate Professor Ananias Escalante will share in more than $6.3 million in awards from the National Institutes of Health for three related studies. Two of the studies will examine the ecology and evolution of malaria and a third will delve into the genetic mysteries behind the host shift of retroviral disease from primates to humans.

Escalante, lead investigator of the malarial studies, will undertake a global comparative study of the evolution of malarial drug resistance, with support from Yuseob Kim, assistant professor, and Maria Pacheco-Delgado, faculty research associate, in ASU's School of Life Sciences. The researchers focus will be on the malarial parasite Plasmodium falciparum.

Worldwide, malaria ranks with tuberculosis and HIV-AIDS among the most important causes of disease and death. Malaria kills a child from somewhere in the world every 30 seconds and is responsible for 350 million to 500 million clinical cases and 1 million deaths each year. According to Escalante, human malaria is endemic in most tropical and subtropical ecosystems worldwide, a burden that poses a significant barrier to global development. Of the four human malarial parasites, P. falciparum and Plasmodium vivax are responsible for most malaria morbidity and mortality.

Escalante and his colleagues seek to understand which types of P. falciparum populations are most prone to the emergence of drug resistance or to the reemergence of drug sensitivity. Investigating how antimalarial drug use selects for resistance is a matter of great interest in evolutionary biology and public health, Escalante says.

"This work will provide good theoretical population genetics models to allow scientists to analyze advantageous mutations and the dynamics of mutations under natural selection in a geographically structured population, " Escalante explains. Such models help the international public health community to better evaluate potential drug policies such as combination therapy or drug rotation in situations likely to be encountered in different endemic areas.

The second study led by Escalante will look at the evolution of P. vivax and Asian macaque malarias. Although this parasite is the most prevalent malarial parasite outside of sub-Saharan Africa, Escalante says that little information presently exists with regard to its genetic diversity. Targeting parasite proteins, either by vaccination or chemotherapeutic drugs, requires an understanding of how the parasites have evolved and the extent and maintenance of their variation.

"Our long-term goal is to link population-level research with comparative genome approaches to understand the origin, demographic history, and genetic diversity of P. vivax at those genes encoding proteins that are involved in the invasion of the red blood cell, a crucial step in the parasite life cycle," Escalante explains. "Our research considers nonhuman primate malarias an important element of the puzzle. We are studying not only well characterized P. vivax and nonhuman primate malaria isolates, but also field isolates from human and nonhuman primate malarias in order to assess the demographic history of the extant populations, explore host-specificity, and assess putative genetic variation that may be under positive selection by the host immune system."

Escalante says that he is "particularly interested in how host switches may lead to molecular adaptations in parasites and pathogens and how the demographic history of parasite and pathogen affects its adaptive variation."

Host shifts are the focus of the third study where Escalante is the ASU principal investigator. This is a project involving multiple investigators and institutions coordinated by Escalante and Lisa Jones-Engel, a field biological anthropologist from University of Washington working on human-primate interactions. In this work, Jones-Engels and Escalante, together with researchers from University of California at Davis and the Fred Hutchinson Cancer Center in Seattle, will examine the evolution, recombination, emergence and exchange of simian retroviruses between human and nonhuman primates. Escalante will also explore the dynamics of nonhuman malarial parasites as part of his vivax-macaque malaria project.

This project will provide valuable information for assessing how human society influences the ecological contexts in which cross-species disease transmission occurs. To date, most research on emerging primate-borne disease has focused on perceived high-risk human populations, such as bushmeat hunters in Africa, and zoo and primate laboratory workers in Western countries. In contrast, little is known about the pathogen exchange between primates in close contact with humans in Asia.

According to Escalante, humans in Asia come into contact with primates in many different ecological contexts besides bushmeat hunting and consumption. There are urban primates, temple primates and wildlife and pet markets. Primates, such as macaques, are also used to harvest coconuts. These complex human-primate interactions increase the potential for cross-species shifts in disease. Jones-Engel and Escalante will be based in Bangladesh with an accessory field site in Indonesia for this work.

Prior to joining ASU, Escalante was a researcher with the Division of Parasitic Diseases at the Center for Disease Control and Prevention in Atlanta, where he still maintains strong ties. His research has had global implications, involving a network of partners in the United States and international collaborators in Bangladesh, Cameroon, India, Indonesia, Kenya, Peru, Tanzania, and Venezuela.

"My long-term goal is to establish bridges among the epidemiological, ecological and evolutionary biology perspectives to address infectious diseases," says Escalante.

"Events such as the Severe Acute Respiratory Syndrome or SARS epidemic and the spread of antimicrobial resistance have increased awareness about the need for incorporating laboratory-based research in decision-making processes that involve public health," Escalante explains.

"Molecular information, together with concepts from ecology and evolutionary biology allows the public health community to test hypotheses and explore scenarios that otherwise could not be investigated by traditional epidemiological approaches."