Maryland’s only locally acquired malaria case in 40 years was caused by a strain not seen in any other U.S.-contracted case, and likely came from a mosquito species rarely encountered in the state and not generally known to transmit that type of the disease.

Malaria, once common in some parts of the U.S., was considered eliminated in 1951. So what happened?

Research on the DNA of mosquitoes and malaria-transmitting parasites can help determine how this highly unusual case occurred, said Joana Carneiro da Silva, associate director of research and professor at the Institute for Genome Sciences at the University of Maryland School of Medicine.

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Maryland’s recent case was caused by a particular species of the plasmodium parasite not implicated in any other locally-acquired cases in the U.S. in recent memory, including a spate of cases in Texas and Florida this year.

It’s Plasmodium falciparum, by far the most lethal and one of the most common species. P. falciparum is responsible for 95% of malaria deaths worldwide, said Silva.

The Banner spoke with Silva about what this means and what to expect in the future. This interview has been edited for length and clarity.

First off, why is malaria a public health problem?

Malaria is an infectious disease that’s transmitted by mosquitoes. If left untreated, especially the cases caused by the most virulent species of Plasmodium, it can lead to death fairly quickly.

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Malaria still kills over half a million people each year, most of them young children under the age of 5 in Africa; that’s where most of the impact is felt.

How did Maryland’s locally acquired malaria case happen, and why now, for the first time in 40 years?

It can happen in one of two ways. One possibility is that an infected mosquito traveled in an airplane from an endemic area and it lands here and transmits malaria. Another, perhaps more likely possibility, is that someone came from one of these places, and perhaps unknown to this person, they were infected. If people have been exposed multiple times, they may have an asymptomatic infection, sort of like some COVID infections can be. And then the person, once here, got a mosquito bite and that mosquito transmitted the parasite to someone else.

So why here, why now? Well, there’s always the first time or a chance event. Another potential worry is that with climate change, some of the mosquito species are starting to expand their geographic ranges. In order for the Plasmodium parasite to transmit from one person to the other, the mosquito itself needs to be a particular species and often a particular strain of that species, because otherwise the immune system of the mosquito will be able to eliminate the plasmodium infection.

The mosquitoes that exist in Asia are different from the ones from Africa and they are different from the ones in the Americas. The Anopheles gambiae mosquito and the Anopheles funestus are the most common species that transmit malaria in Africa, but those do not exist here in the U.S. The parasites in each region had to adapt to being transmitted by these new mosquito species that exist in different continents. They have evolved in a lock-and-key kind of process such that, if you’re a parasite, you need to have the right key to work with the right mosquito lock.

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It’s uncommon for a parasite from a particular geographic region to be easily transmissible by a mosquito of a different geographic region. And so in order for P. falciparum to be transmissible here, there would have to be a mosquito here that is compatible with that particular parasite.

Does the type of mosquito that transmits malaria exist here in Maryland?

Anopheles mosquitoes [the genus that carries malaria] did exist here at some point, but they were eradicated from this area through mosquito control practices. They are common in Texas and possibly parts of the Southeast, but they are different species from those that circulate in Africa. Anopheles quadrimaculatus is the species that was primarily seen in eastern North America and existed all the way from Texas up to Maine at some point. But they’re not common in Maryland anymore at all.

Part of the fear is that with climate change, they’ll start moving farther north again.

What is the difference between the strain of malaria in the Maryland case, and the strain acquired in Texas and Florida?

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P. vivax [the strain of malaria acquired in Texas and Florida] is endemic in the Americas, in South and Central America in particular, so it still circulates in the natural population. So if you go to say, visit the Amazon, you need to take malaria pills. This species is also the one that existed natively in the U.S. until about 50 years ago.

P. vivax is much less virulent, so it doesn’t cause a lot of deaths; maybe in the order of 50 at most in Brazil, for example, every year. But it’s still very widespread throughout the region of the Amazon.

P. falciparum [the strain acquired in Maryland] is by far the most prevalent plasmodium parasite in Africa. It’s responsible for probably 95% of all deaths from malaria annually, and probably 75% of those occur in children under 5. But the parasite itself is still fairly widespread as well, so you can find it in Africa, South America, South and Southeast Asia, and Oceania.

Why is it important to study the genomes, or set of DNA, of malaria-transmitting parasites and mosquitoes? How does this help with malaria prevention?

We want to make sure we understand how to design drugs and vaccines that work against these parasite species. The parasite populations are continuously evolving to evade those drugs, so you need to look at their genomes to understand which genes and genetic mechanisms are responsible for those drug evasions, so that we can prevent that or design new drugs that are more effective.

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We need to understand why some vaccines that have been tried don’t seem to be effective. You design a vaccine based on the particular variant of the parasite, similar to what we do with the COVID virus. But in the parasite population, there are many different variants that differ from the one you’re targeting, and so the vaccine might prevent infection by some parasites but not others.

Through genomic research, we may be able to identify where this particular [locally-acquired] strain has come from, because we have studies that clearly show that the genome sequence of mosquitoes in different geographic regions is slightly different. And so by sequencing the genome of, for example, this particular infection, we will be able to tell what region this P. falciparum parasite came from.

How likely is it that we’ll see an increase in locally acquired malaria cases here in the future?

I can’t tell you how likely it is, but I can certainly say that it’s a worry that’s very much being addressed in, for example, the Southern U.S., and maybe now even farther north, and certainly Southern Europe, as well.

Malaria was eliminated by eliminating the mosquitoes that carry it from specific geographic regions, and those geographic regions might not have been optimal for those mosquitoes anyway. So it was possible to eradicate them from everywhere in the U.S. except maybe from the southern parts.

But now that the climate is getting warmer, it’s really changing. Those mosquito species that might still exist in the U.S. or Central America can start to migrate, expanding their range and the diseases they transmit farther north.

A previous version of this article misstated Joana Carneiro da Silva's title, the number of annual deaths caused by the P. vivax strain in Brazil, and the strains endemic in the Americas. Silva is a professor at the Institute for Genome Sciences; P. vivax causes roughly 50 deaths in Brazil annually; and both P. vivax and P. falciparum are endemic in the Americas, though falciparum is much less prevalent.

sarah.true@thebaltimorebanner.com

Sarah True was a public health reporter for the Baltimore Banner. She previously worked as a freelance journalist covering healthcare and health policy, and has been both a medical social worker and a health policy analyst in a past life. She holds dual Master’s degrees in public health and social work.

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