EastBay Today

Feature
Posted December 5, 2016

Blood Link

Assistant Professor Nazzy Pakpour researches the link between
malaria transmission and a rising global epidemic

Nazzy Pakpour’s fascination with insects began when she was a child in Iran. She used to catch big, slow, winged, cockroach-like bugs and glue a string to their backs so she could keep them as her pets.

Assistant Professor Nazzy Pakpour says many scientists are studying various factors that might increase malaria transmission, but the look at diabetes is new — and could be critical to prevention efforts in developing countries.

“I was a weird child,” she says.

By the time she immigrated to the United States and entered high school, her interest in the creepy-crawly was full-blown. It was then that she put together her first insect collection, and the summer before college, she worked at the Smithsonian Insect Museum, where she held tarantula feedings for swarms of morbidly curious museum-goers.

Today, she no longer keeps insects on leashes or conducts demonstrations of their carnage. But as an assistant professor of biology at Cal State East Bay, Pakpour still loves bugs, having become an expert on parasites and immunology.

“They’re so weird,” she says. “It’s like living with aliens. You can look at the biology of any species and [each is] so unique and different.”

And she surrounds herself with them. Her office holds wooden cases filled with a variety of critters, and several (live) Vietnamese walking sticks hang out in a tank above her desk. Take a walk a couple floors down to her lab and you’ll find fruit flies breeding for research in jars of sticky brown fly food (see Still Hungry? below).

Bizarre and fascinating, yes. But for the entomologist, insects are also serious business.

Deadly Bite

Take the mosquito, which is one of the deadliest animals in the world thanks to its role as a powerful vector for malaria. The disease threatens nearly half the world’s population, and although prevention efforts have lowered illness and death rates in recent years, malaria remains a killer in 95 countries — primarily those in sub-Saharan Africa. The World Health Organization reported that in 2015, 214 million people became sick with malaria and 438,000 died of the disease.

The fever, headache, chills, vomiting — and sometimes coma and death — that occur with the illness happen when the malaria parasite reproduces inside the body, having invaded the host via the saliva of a biting, infected mosquito. When other mosquitoes bite the person, they can become infected too and then spread the disease.

But scientists still have much to learn about what increases infection rates for the mosquitoes themselves. For example, scientists are now studying how a variety of outside factors can boost or impede transmission — including other diseases or infections within the host, such as HIV.

And Pakpour wants to understand the role of one particular disease that’s becoming a global epidemic: diabetes. 

Early Results

Pakpour’s recent research suggests that diabetes may in fact make malaria transmission more prevalent. Experiments involving two different malaria strains, the lethal Plasmodium berghei and nonlethal Plasmodium yoelii, found that Type 2 diabetic mice infected with malaria transferred the parasites to mosquitoes at a rate about one-third times higher than healthy mice.

do mosquitoes really bite?

No. Although it’s how we commonly refer to the way these pests stage their attack, the assault of a mosquito is more like a stab wound. A mosquito pierces the skin through a sharp, sword-like body part called a proboscis, which functions similar to a mouth. The proboscis has thin tubes inside of it, one of which injects saliva into the mosquito’s victim. The saliva does double-duty, as it contains a mild painkiller that buys the mosquito the time it needs to feed, and also an anticoagulant enzyme that thins the blood, ensuring it flows smoothly through the other tube in the proboscis.              Dinner is served.

This study, published this year with two colleagues at UC Davis, could have critical implications for controlling the spread of malaria where it is already most dangerous — Africa. 

Diabetes afflicts 422 million adults throughout the world, according to World Health Organization. But the disease is rising even faster in the areas most vulnerable to malaria. The International Diabetes Federation predicts that the number of adults with Type 2 diabetes in Africa will more than double by 2040, reaching 34.2 million. The IDF also estimates that more than two-thirds of people with diabetes are undiagnosed (and some people with malaria don’t show symptoms), meaning up to 22.8 million Type 2 diabetics could start spreading malaria at a higher rate without knowing it in the next two decades. 

That’s the worst-case scenario, though, and Pakpour’s research is still preliminary. But if diabetes does have a hand in spreading malaria, the big question is, how?

“There’s a certain beauty in the complexity of malaria transmission — it’s this intricate dance between three organisms,” the professor says. “You have the parasite, the mosquito and the human host all interacting at the same time at the same place. That’s a really fascinating kind of biology that’s happening.”

This complex nexus is where Pakpour — if she can determine what increases infection rates for the mosquitoes — may be able to find ways to disrupt transmission.

Future Testing

The professor already has a few hypotheses that could explain the connection.

One possibility, Pakpour explains, is the presence of excess insulin, the hormone that regulates blood sugar. Some diabetics don’t process insulin well, so high levels can stay in their blood. It turns out that insulin affects a mosquito’s immune system. “The mosquito has an immune response, and a lot of the time it can fight off the malaria infection,” she explains. “But insulin seems to dampen that down and make them more susceptible [to contracting malaria].”

Another possibility is that diabetes may somehow affect the transition between two particular stages of the parasite’s life cycle. At one point while in a human host, the parasite faces a decision: An individual organism either reproduces by replicating itself asexually within the body — this is the stage that causes malaria symptoms — or becomes a gametocyte, which can leave the body and infect a mosquito. Less than 1 percent of the parasites become gametocytes.

But diabetes might change that. “One idea is that there are more [gametocytes], so the mosquito is more likely to be infected,” Pakpour says. Diabetes often causes low-grade inflammation, a source of stress that might provoke more gametocytes to form. The stress may also induce those gametocytes to congregate in the skin or blood, where a mosquito is more likely to pick them up. “Maybe it’s not a difference in numbers but a difference in location,” she says.

It turns out that insulin affects a mosquito’s immune system.

Both scenarios would result in the parasites spreading.

Pakpour is starting further experiments at Cal State East Bay to see whether these ideas, or a combination of them, are right. The university also plans to finish building an insectary by 2017, a facility that will house specimens for research and teaching. There, Pakpour will be able to grow her mosquitoes and do all her research on campus — and involve more students.

Which shouldn’t be too hard. After all, her enthusiasm for insects is infectious, whether she’s telling you how swimming larval dragonflies shoot liquid from their backsides to propel them through water, or the time she saw a parasitic wasp carry a paralyzed spider to its nest. The wasp laid its eggs inside the spider, and the larval wasps hatched and ate the spider alive from the inside out. “It’s like crazy zombie stuff happening in your garden!” Pakpour exclaims.

That fascinating weirdness is what drives the professor. But she finds extra motivation in understanding, a bit at a time, how the insect world affects humans. “I’m adding my little drops to the bucket,” she says. And someday, her work may help save lives. 


Still Hungry?  Pakpour’s Interest in Insatiable Pests Includes Student-led Research 

In a spare, humble lab on the campus of Cal State East Bay, fruit flies proliferate and buzz around inside beakers and test tubes. Here, several undergraduate students are trying to put the bugs on a diet, treating them with a drug that inhibits serotonin, a biological chemical important for a variety of functions, including mood and circadian rhythm.

The goal is to get the flies to eat less, reproduce less and die sooner. If successful, this drug could eventually lead to new ways to control what’s become a menace to fruit farmers across North America and Europe: the spotted-wing fruit fly.

Student Anthony Salvato prepares fruit fly food called agar, which the flies lay their eggs in. The lab dies the agar green so that the eggs are more visible and can easily be counted.

Native to Asia, the spotted-wing fruit fly first appeared in the U.S. and Italy in 2008. It immediately devastated crops. The Invasive Species Compendium (an encyclopedic resource that aggregates science-based data worldwide) estimates that in California, Washington and Oregon the fly caused more than $500 million in losses after destroying cherries, strawberries, blueberries, raspberries and blackberries. Today, the fly continues to threaten berries and other fruits like apples, plums and peaches.

The fly owes its proliferation to a sharp competitive edge. All fruit flies have an ovipositor under their abdomen, a tube-like organ they use to deposit eggs into the soft flesh of rotting fruit. For farmers, losing already rotten fruit littered on the ground isn’t a big deal. But in the spotted-wing variety, the ovipositor is serrated, which enables it to pierce the skin of fresh fruit in trees — and ruin crops.

“The problem now is that the fly is prevalent in the U.S. from the East Coast to the West Coast,” Anthony Salvato, one of two students to help pioneer the research, says. But no one’s developed a sustainable pesticide yet — which is where the researchers come in.

Flies feed on brown, sticky food spiked with serotonin-inhibiting drugs in a Cal State East Bay lab. If the treatment works, agriculture may have a new way to fight the insurgent spotted-wing fruit fly.

The students have already shown that a serotonin-inhibitor drug can reduce the lifespan of and decrease the number of laid eggs by the common species of fruit fly, reproducing the results of a previous study. “The idea is that they’ll stop eating and they’ll just fall over and die,” Chris Tat, Salvato’s counterpart, says. “Or, they’ll stop eating and not have energy to lay eggs or do anything.” With this groundwork done, the undergraduates will soon begin experiments with the spotted-wing fruit fly.

“They’ve really taken this project a lot further than I was expecting it to go, and they’ve generated really nice data,” says Pakpour, who had originally put the project under a “crazy” file she keeps of speculative ideas. But if the researchers can show their concept is sound, a new method for controlling the pests may not be too far off, to which fruit farmers will be able to give thanks.  

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