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Exploring the vexing world of malaria control

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Increasing collaboration between the ‘mosquito people’ and the ‘drug people’

December 5, 2017—Malaria is a complicated disease to tackle from a public health perspective. Its complexity stems in part from the two organisms that conspire to transmit the disease: the single-celled Plasmodium parasite and the mosquitoes that ferry them to their hosts. Thankfully, there are tools that can help control this two-pronged threat — insecticides for the mosquitoes and drugs for the parasites — but they too have vulnerabilities, and can be overcome.

“Two of the biggest challenges in malaria control are insecticide resistance and drug resistance,” explains Hilary Ranson, professor of medical entomology at the Liverpool School of Tropical Medicine in Liverpool, UK and a world-renowned expert in insecticide resistance in mosquitoes. While the scientists who study these areas stand to learn a lot from each other, they often work in distinct and non-overlapping spheres.

“When you go to meetings or conferences, you get the mosquito people in one session and the drug people in another,” says Ranson. “The scientific problems are almost identical, and yet we don’t spend enough time talking to each other.”

That’s why Ranson traveled to the Harvard T. H. Chan School for a six-month sabbatical, which ended in October. A visiting professor in the Chan School’s Department of Immunology and Infectious Diseases (IID), she immersed herself in the fundamental research unfolding within IID’s laboratories — studies of the malaria parasite and its abilities to outwit drugs, as well as basic studies of mosquitoes and their biology.

Finding research synergy

The idea for Ranson’s sabbatical first emerged 18 months ago, when she gave a seminar at the Chan School on her laboratory’s research, which focuses on field studies of mosquito-borne diseases, such as malaria, dengue, and Zika, and the use of insecticides and insecticide-treated bed nets. During that brief visit, IID chair Dyann Wirth recognized how complementary and synergistic Ranson’s research is with that of her own department — particularly the work of associate professor Flaminia Catteruccia, who studies mosquito biology as a means to uncover novel ways to combat the insects and ultimately, reduce malaria transmission.

“Hilary and I have known each other for many years in the mosquito community and although we’ve been discussing science as it relates to malaria, her sabbatical was the first opportunity we had to work together,” says Catteruccia.

She and Ranson are exploring two major questions: first, what are the biological mechanisms that underlie insecticide resistance in mosquitoes and second, how do they impact malaria control programs?

This latter question reflects a sort of sea change in malaria research, as insecticide resistance has generally been presumed to be a bad thing for malaria control programs — even in the absence of a detailed understanding of how insecticides and insecticide resistance alters mosquitoes, their biology, and the parasites inside them.

“You can imagine a scenario in which mosquitoes become resistant but at a biological cost — they’ll resist the insecticide but they’ll also be less fit,” explains Catteruccia. “So there may be fewer mosquitoes around or the malaria parasites may be at a disadvantage because of a change in mosquito physiology or some sort of stress response.”

Questioning the effectiveness of malaria control tools

These are just some of the possibilities that Ranson, Catteruccia, and their colleagues are now pursuing. Their explorations represent one of the first steps in a multidisciplinary, international effort that fuses wet-lab studies with field research to determine whether insecticide resistance is having a positive, negative, or neutral impact on malaria transmission.

Ultimately, their vision is to combine this research with epidemiological modeling to help predict how insecticides and insecticide resistance will affect public health.

“Within this program, we can address some really fundamental questions, including the most important ones — are our malaria control tools working? If they are, how long will they work, and if they aren’t, why not — and what can we do to improve them?” says Catteruccia.

For Ranson, this work represents an important coming together of researchers and disciplines that largely kept to themselves. It is also reflects a broader recognition that collaboration is more efficient, particularly for public health officials working in malaria-endemic countries to control the disease.

“We really should be working as a cohesive group that can offer advice on how best to treat the patient and control the mosquito, rather than multiple different groups — the mosquito experts, the drug experts, the parasite experts — going in separately,” says Ranson. “At best, we are occupying too much of the time of those at the front line of malaria control and at worst we are giving conflicting advice.”

How best to utilize scarce resources is a predominant theme in Ranson’s line of work. The recent Zika outbreak as well as ramped up malaria eradication efforts have helped focus attention on the lack of entomologists, particularly in countries where mosquito-borne diseases are surging. Many countries have only one or two people — some have none — within their borders who know anything about controlling insects. “It has been a dying discipline, really,” says Ranson.

A critical need for entomologists

Unfortunately, the problems that entomologists seek to address are not fading. Consider yellow fever, a disease also carried by mosquitoes. Although there is a vaccine available, there are critical shortages in its global supply. In the event of an outbreak — like those recently in Angola (which subsequently spread to the Democratic Republic of Congo), Brazil, and Uganda — the only effective disease control measure is to prevent mosquitoes from biting.

“If you want to develop vaccines for these diseases, you need one for every disease,” says Ranson. “But when you target the mosquito vectors, you control all the diseases they transmit — even the ones we don’t know about yet.”

She believes part of the entomologist shortage lies in misperceptions about what these professionals do and the type of training required. To address these challenges, she hopes universities will consider embedding relevant courses and modules into their biology and public health degree programs, and inviting experts who are passionate about their work to speak to students.

Ranson urges those who are considering careers in global health to keep an open mind. “Consider this as a possible option. It ticks so many of the boxes — it is largely unexplored, there are great opportunities for overseas work, and the community is very open and collaborative.”

It also stands in stark contrast to many other areas of science that are being squeezed by tight budgets. “Funding is not the key issue,” she says. “It’s finding the best people.”

–Nicole Davis