The Fogarty International Center of the National Institutes of Health has recently awarded $1.25 million to scientists at Case Western Reserve University's School of Medicine and the Center for Global Health and Diseases to renew an educational program in infectious disease research training with collaborating institutions in Papua New Guinea.
This program, co-directed by Peter Zimmerman, professor of international health, biology and genetics, and Peter Siba, director, Papua New Guinea Institute of Medical Research (PNGIMR), extends a 29-year history of productive ID research collaborations between CWRU and PNGIMR initiated by James Kazura and former PNGIMR Director Michael Alpers. CWRU collaborators on this renewed Fogarty Training grant include Christopher Cullis, chairman of the Department of Biology, and Scott Frank, director of the Masters of Public Health Program. The program adds expertise in entomology through collaboration with Edward Walker and Ernest Delfosse, chairman of the Department of Entomology at Michigan State University. Renewal of this training program was announced at PNG's National Medical Research Symposium in early September.
The School of Medicine and College of Arts and Sciences, as well as MSU's Department of Entomology, have contributed significant institutional support to this ID Training Program.
Phase I of the Program (2005-2010) supported one-year undergraduate honors thesis projects on infectious disease research including mosquito resistance to insecticides, malnutrition, drug resistant tuberculosis and a range of studies focused on malaria. During this time 23 students finished their Bachelor of Science Honors thesis projects; 5 completed or are nearing completion of Masters of Medical Science requirements. Results of the students' research have been published in the Malaria Journal, the American Journal of Tropical Medicine and Hygiene and Clinical Infectious Diseases. Many of these students have received awards to present their ID research findings at international scientific meetings and scholarships to continue their graduate education in Europe, Australia, Japan and the United States.
Three of these students received Fulbright International Scholarships to pursue master's degrees in the United States: two at CWRU and one at Michigan State University. These students provided the inspiration for the renewal proposal submitted in November 2010. In Phase II of this ID Research Training Program (2011-2016) students will receive two years of support to pursue graduate degrees in biology or public health at CWRU or in entomology at MSU.
PNG students who are part of the first in-take cohort include Krufinta Bun and Barne Willie at CWRU and John Keven at MSU.
New funding from the National Institute of Health's Fogarty International Center and the National Institute of Nursing Research will support three post-doctoral trainees in anthropology, epidemiology and nursing from Case Western Reserve University. Over the next year, the trainees will undertake behavioral science research in Papua New Guinea to study self management of potential drug treatments for lymphatic filariasis.
As part of the training, they will collaborate on a trial of potential drugs to destroy the lymphatic filariasis parasite that causes blockages in the lymphatic system.
James Kazura and Christopher King from the Center for Global Health and Disease at Case Western Reserve School of Medicine direct the drug study. The principal investigators on the new, one-year $228,000 grant are Elizabeth Madigan, professor at the Frances Payne Bolton School of Nursing; Janet McGrath in the Department of Anthropology in the College of Arts and Sciences; and Daniel Tisch in the Department of Epidemiology and Biostatistics in the School of Medicine.
The post-doc trainees represent three schools participating in the Global Health Framework project at Case Western Reserve University's Center for Global Health and Disease.
Started in 2007, the Framework is a collaboration to design interdisciplinary courses, provide mentored international opportunities and support a certificate program in global health.
The funds were made possible through federal stimulus money to jumpstart the economy and provide salaries and living abroad expenses.
Lymphatic filariasis causes a form of elephantiasis or gross enlargement of limbs and body parts, Madigan said. Afflicted individuals suffer from stigma and limited job and social opportunities.
Because this disease is not transmitted in the United States, sending trainees to places where the disease is endemic to learn from local science experts and see the disease's impact in the broader context of the community is important, Tisch said.
The university has been working in Papua New Guinea since 1983 and has long-standing research projects in the country, making it an ideal setting to train post-doc students in global health issues.
"The post-doctoral students will each have unique and valuable skills from their respective disciplines to contribute to the implementation of the drug trial," Tisch said.
"This is an unusual opportunity to fund post-docs fellows for overseas research," Madigan said, explaining funds usually are made available to support foreign students coming into the country.
"The opportunity to work in a cross-disciplinary team to address a serious health issue in underserved populations is exciting and prepares the trainees for careers in global health in their respective disciplines," McGrath said, noting that the post-doctoral project is an important new expansion of the Global Health Framework project.
A mutation on the surface of human red blood cells provides protection against malaria caused by the parasite Plasmodium vivax, research led by Case Western Reserve University School of Medicine shows. The minute change, at a single position of red blood cell surface protein called the Duffy blood-group antigen, has been known for years. But the researchers found this mutation makes it harder for the parasite to lock onto the red cell surface and gain entry. No entry, no infection.
The research is now published in the advanced online edition of the Proceedings of the National Academy of Sciences. "The findings has practical implications as medical researchers continue attempts to develop vaccine for vivax malaria," said Christopher King, a professor of international health, medicine and pathology at the Center for Global Health and Diseases at Case Western Reserve University School of Medicine, and lead author.
The protective aspect of the mutation was discovered in campus labs and confirmed through a population study in the Amazon region of Brazil.
Malaria is caused by four different parasites, the majority of cases in Asia and the Americas are caused by P. vivax.
"Plasmodium vivax carries a Duffy binding protein that binds to the Duffy antigen on the surface of the red cell- a critical step to invading the cell," King explained. "Both parasite and human proteins appear to be needed for the parasite to invade the cell."
King's lab had been studying the parasite's protein as a target for a vaccine. He teamed with Peter A. Zimmerman, a professor of international health, genetics and biology, also at the Center for Global Health and Diseases. Zimmerman's lab was studying the mutation in the DNA sequence of Duffy blood group gene.
While investigating the binding process, they found that Duffy binding protein interaction with red blood cells varied between samples.
They performed the genetic tests for the single-point mutation. Antigens with the mutation are called Duffy 'A' and those without, Duffy 'B.'
They found the parasite bound to red blood cells expressing Duffy 'B' about twice as often as the parasite bound to cells expressing Duffy 'A.'
The researchers then wanted to see if the finding translated to real life.
They collaborated with Marcelo U. Ferreira, an investigator at the Department of Parasitology, Institute of Biomedical Sciences, University of Sao Paulo, to analyze data from 400 individuals tracked for malaria infections for more than a year in northwest Brazil.
In northwestern Brazil, where a mixture of Duffy 'A' and 'B' variants are inherited, the researchers found that people expressing the Duffy 'B' variant experience P. vivax malaria more often than those who expressed the Duffy 'A' variant.
"Therefore, stronger binding to Duffy 'B' leads to greater success at red cell invasion and more vivax malaria," Zimmerman said. "Seen from the other side of this relationship, weaker binding to Duffy 'A' appears to reduce red cell invasion and is therefore protective against vivax malaria."
The analysis showed that those with the Duffy 'A'/Duffy 'A' genotype had a 29 percent reduced risk of vivax malaria. Those who had the Duffy 'A'/Duffy 'B-negative' (a variant that has no antigen) genotype, had an 80 percent reduced risk. Reduced risk was not associated with an increase in antibodies in either case.
Those with Duffy 'B'/Duffy 'B' or Duffy 'B'/Duffy 'B-negative' genotypes had an increased risk of 220 to 270 percent for vivax malaria.
A vaccine's effectiveness therefore may depend on whether a recipient carries one or two copies of the Duffy 'A' or 'B' mutation in his DNA, King said.
"The Duffy 'B' variant is ancestral to Duffy 'A.' We know this because all non-human primates carry the Duffy 'B' variant," Zimmerman said. "So a case can be made for the Duffy 'A' variant arising as protection frm vivax malaria."
In a further analysis, the researchers found no association with the Duffy 'A' variant and Plasmodium falciparum, the parasite that causes the majority of infections in sub-Saharan Africa and the cause of 66 cases among the 400 individuals studied.