Aksoy Labs combats the tsetse fly to protect Africa from sleeping sickness
Nearly everyone has been pestered by a housefly — a dilemma easily solved with the quick deployment of a flyswatter. However, not all species of flies are so harmless or so easily dispatched.
In sub-Saharan Africa there is a vastly different, much more dangerous species of fly that threatens the lives of millions of people and livestock herds across the entire continent. The tsetse fly (pronounced set see) is an insect slightly larger than the common housefly that transmits Human African Trypanosomiasis, commonly known as sleeping sickness, a parasitic disease found throughout the rural areas of 36 African countries.
Sleeping sickness is spread through the painful bite of infected tsetse flies, which transmit the African trypanosome into both humans and animals. Symptoms of the disease include itchiness, high fevers, severe head and muscle aches, swelling of the face, swollen lymph nodes, and severe weight loss. According to the World Health Organization (WHO), sleeping sickness has killed hundreds of thousands of people in several major epidemics throughout the continent in the last century, with the latest one taking its toll in the 1980s.
It is due to the grave nature of this threat that the tsetse fly has been in the cross hairs of Serap Aksoy, professor of epidemiology at the Yale School of Public Health, for quite some time. Aksoy came to Yale as a postdoctoral fellow in 1982. She led the Division of Epidemiology of Microbial Diseases from 2002 to 2010, and is currently principal investigator of the Aksoy Lab. In 2014 she worked doggedly with an international team of researchers to successfully sequence the genetic code of the tsetse fly, thereby opening the door for scientific breakthroughs that could reduce or end sleeping sickness.
“The vast genomic data now accumulated on tsetse flies and trypanosome parasites from the sequencing work empowered us and other researchers to find new paths to explore for ultimately defeating the disease,” said Aksoy.
The study of Aksoy’s team’s sequencing work was published in the journal Science, published by the America Association for the Advancement of Science, and in a series of manuscripts published in a Special Collection in the Public Library of Sciences (PLOS).
Since the sequencing of the genetic code, Aksoy has continued to work closely with others to find ways to improve current control methods of sleeping sickness, and develop strategies to reduce or eliminate its transmission in sub-Saharan Africa. Her work with colleagues has spanned a broad range of projects including close studies of tsetse immunity, reproduction and symbiosis, tsetse-symbiont and trypanosome interactions, tsetse genomics and population genetics, trypanosome developmental processes in tsetse, and tsetse olfaction.
Sleeping sickness is endemic to Africa and generally infects extremely poor people who live in remote regions. According to Aksoy, the sick often suffer from the disease for years before seeking treatment, causing them and those caring for them to miss work and spend their savings on traditional medicines. In the case of the most recent epidemics, incidence of disease, particularly in West Africa was reduced to less than 3,000 cases thanks to an ambitious campaign led by WHO, many nongovernmental organizations, and a public–private partnership with Sanofi-Aventis and Bayer that donated the necessary drugs for distribution in affected countries.
“It is due to the success of control campaigns like this that we are hoping to eliminate sleeping sickness as a public health problem by 2020 in West Africa,” said Aksoy. “However, while we work toward this goal, the presence of tsetse in disease-endemic areas will continue to place an estimated 70 million people in sub-Saharan Africa at risk.
“In particular, unlike West Africa, in East Africa the disease can be spread from both domestic and wild animals to humans, which greatly increases the risk and requires greater incorporation of tsetse control methods,” explained Aksoy.
For this reason, Aksoy and her team here at Yale continue to research an additional control strategy called para-transgenic expression, where they introduce and synthesize proteins that target trypanosomes in microbes cultivated from the gut of tsetse flies. By repopulating the fly’s guts with such organisms, they hope to interfere with parasite development in the gut — which will, in turn, block transmission of the disease to humans and animals. Through implementation of this approach and others still being explored they hope to find a cost-effective method to reduce parasite transmission in tsetse populations in areas where disease transmission risk is high.
In addition to her and her team’s efforts to investigate ways to control sleeping sickness, Aksoy has been a strong advocate for building research capacity in Africa to combat the disease. Support from the Fogarty International Center, part of the United States National Institutes of Health, has enabled her and her collaborators at Yale to work to help train the next generation of African scientists and scholars with their peers at the Biotechnology Research Center of Kenya Agricultural & Livestock Research Organization, Kenya Medical Research Institute, International Center for Insect Ecology and Physiology, Makere University, Gulu University, and The South Africa National Bioinformatics Institute, among others.
According to research scientist Paul Mireji who is visiting the Aksoy lab this month from Kenya, training in tsetse biology at Yale University has helped improve tsetse and trypanosomiasis control initiatives in Kenya and was critical for building a cohort of doctoral and postdoctoral students in East Africa studying this disease. “It is very fulfilling to see that most of our mentees from this program are on their way to establish their own independent research in tsetse and trypanosomiasis control,” said Mireji.
Together Aksoy and her many colleagues have also developed workshops spanning vector and parasite biology, epidemiology, genomics/bioinformatics, and ecology and evolutionary biology. These workshops have been instrumental in helping train dozens of graduate students and Ph.D.-level scientists in disease-endemic countries (DECs) in Africa. Support from Fogarty has also resulted in the training of 12 Ph.D. students who conducted part of their thesis projects in the Yale labs.
“Both here in the United States and overseas in Africa, our hope is that the next generation of scientists will carry the torch for realizing the opportunities recent genomics and genetics research has unraveled in vector biology,” said Aksoy. “The development of local research capacity is particularly vital for the control of neglected tropical diseases in disease-endemic countries as elimination efforts begin.”
Aksoy is also passionate about incorporating DEC researchers into the global scientific network as editors and peer reviewers, because these practices provide scientists with opportunities to exchange ideas and establish global collaborations with peers, she said.
She believes strongly that global publishing houses should play a major role in building strong scientific communities in DECs by including scientists and scholars from these communities on their editorial boards, recruiting reviewers from DECs when appropriate, and providing support for disseminating information on good manuscript writing practices and the publication process. In fact, in her role as the editor-in-chief of PLOS Neglected Tropical Diseases, a prominent journal devoted to the world’s most-neglected tropical diseases, she often lectures on the value of good publication skills at various international meetings and throughout her various travels.
“It’s only through close, honest collaboration with colleagues and a deliberate, ongoing practice of willingly sharing knowledge that we can all expect to succeed in our efforts to eradicate threats like the tsetse fly, a scourge of rural Africa,” added Aksoy.