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Summer 2023 saw the identification of two episodes of local transmission of malaria -- seven cases in Florida and one in Texas -- and these were the first of locally acquired mosquito-borne malaria in the U.S. since 2003, according to the . Of course, the main vector for the disease is the mosquito bite, and antimalarials are the go-to treatment. But researchers in the U.K. have reported that they may have found a way to stop malaria infection before it even starts.

Joseph D. Challenger, MPhys, PhD, of the Medical Research Council Centre for Global Infections Disease Analysis/Imperial College in London, and co-authors said that they developed a vaccine that relies on a Plasmodium falciparum transmission-blocking monoclonal antibody (mAb). The vaccine, TB31F, reduced the number of malaria-infected mosquitoes and substantially lower the incidence of malaria at the community level, they stated in the .

Their study, done in Gambia (low malaria endemicity) and Burkina Faso (high endemicity), demonstrated that, over a 3-year period, a single annual weight-based dose of TB31F substantially cut the incidence of seasonal malaria by 54% in a high-transmission setting, and by 74% in a low-transmission setting.

"A transmission-blocking mAb used alongside established interventions could play a crucial role in decreasing the global burden of malaria," the authors said. "If TB31F is implemented alongside seasonal malaria chemoprevention, we predict an even larger impact."

Findings indicated that the most efficient per-dose reduction in malaria transmission was in those ages 5-15 years. However, a much larger impact on the incidence of malaria was seen when TB31F was given to 80% of people in all age groups, and combined with other seasonal malaria interventions such as chemoprevention and the use of insecticide-treated nets.

Below are some highlights from the study by Challenger's group

What is the current status of efforts to reduce the global malaria burden?

Considerable progress has been made in reducing the , and recent recommendations from the World Health Organization [WHO] to implement the , RTS,S/AS01, have fuelled optimism this will continue. In spite of this, the pace of improving malaria control has slowed. With now threatening the efficacy of interventions responsible for much of current progress, malaria remains a major health problem.

How do transmission-blocking vaccines work?

elicit antibodies that interfere with the transmission of malaria to mosquitoes. Instead of inducing antibodies by active immunization, mAbs targeting the same antigens achieve a similar reduction in the incidence of malaria, but through a delayed, rather than a direct, benefit.

How does TB31F fit in?

Transmission-blocking vaccines based on prefertilization gametocyte antigens Pfs230 and Pfs48/45 are currently in clinical trials and TB31F is one of them. This humanized version of the targets a highly conserved epitope on Pfs48/45, expressed on Plasmodium falciparum mature gametocytes and gametes.

How long is the transmission-blocking activity of TB31F expected to last?

It is significant that only a single dose of TB31F is needed to achieve prolonged activity, and the authors predict >80% reduction in transmission activity for a median duration of 5 months. Extrapolation from the estimated TB31F half-life suggests that a single administration could span much of the malaria transmission season in many regions, and existing technologies could extend its half-life even further, lowering cost.

What is the take-home message?

should not be withheld from populations in sub-Saharan African regions, where it achieves a very high level of personal protection against clinical malaria. The findings demonstrate the large public health impact a malaria transmission-blocking intervention can have, and that combining seasonal malaria chemoprevention and TB31F may considerably increase the number of cases averted.

Challenger's group evaluated an in vitro prevention method, but what about devices that go over a body? In a 2023 University of California San Francisco (UCSF) Global Child Health presentation, Paul Krezanoski, MD, of UCSF, discussed the purpose and value of bednets and bednet-use monitoring. Krezanoski is the inventor of Smartnet, a .

What are bednets?

Krezanoski: [The] long-lasting insecticide treated bednets [LLIN]...are meant to be put around your bed at night and they have some insecticide within them so that when mosquitoes lay down on them, it kills the mosquitoes and also provides a barrier of protection...200 million bednets were distributed [in 2021]...but the WHO has recommended that for all 3.2 billion people worldwide, everybody should have access to a bednet.

[Bednets] provide an individual level of protection but also a community-wide protection in that they kill mosquitoes and, if you have an effective insecticide, they can actually reduce the population of vectors that spread malaria in a community.

What factors affect ownership and use of LLINs?

Krezanoski: Possibly that people don't understand what causes malaria so we can think of doing things like education campaigns, which are...these days...ongoing all the time. Another barrier could be availability; maybe people don't know where to get bednets...so we can think about better delivery systems...to make sure everybody gets a bednet delivered to their door or gets a bednet after an immunization visit. Maybe there's cost [barrier]...so maybe we should think about making sure that [LLINs] are free.

Back in the early 2000s, I did...some work in Madagascar. One of the first questions that came up was whether bednets should be given for free or a price should be charged for them...at the time, it was thought that if you charged a price for the bednets, people might value the bednets more, and might be more likely to use them. We randomized to varying prices of the bednets, and then we looked at...how likely people were to go and get a bednet and how likely they were to report using them.

[In the study] at baseline, only 4% owned a bednet...and 1% reported using it...unsurprisingly, if we gave a bednet coupon to get a bednet for free, 100% of households went and got it...the ownership of bednets...decreased as the price [market price of about $5] increased...once someone had paid...for a bednet, they were pretty likely to use it. However, people who got their bednets for free didn't use them as much as people who had paid a small fee for them.

This [data] provided some evidence that charging a small amount of money -- it's not clear exactly how much -- might help induce people use their bednets. These days, most bednets are distributed for free.

How can people be incentivized to use bednets?

Krezanoski: We developed another [in Madagascar] to look at how these household-level incentives could help us to increase the use of bednets...behavioral incentives have been used in developing countries for weight loss and tobacco cessation...but no one had looked at using behavioral incentives encouraging the use of bednets.

We had 520 houses and essentially every house got a free bednet...intervention households were told that, a month later, we would do an unannounced visit to the house to see if the bednet was being used [via visual insection] and if it was being used, they'd get an unspecified bonus. We ended up giving some household goods like some rice, beans, and sugar, but [participants] didn't know that at the time.

At baseline, 6% of households were reporting bednet use every night. Within 1 month, the intervention households, when we did these surprise visits, 99% had a bednet hanging over a bed...that was our definition of use, and only 78% of the households in the control group used bednets. We went back at 6 months, you do see some regression...93% in the intervention group, and almost 90% in the control group [stopped using bednets]. There does seem to be an immediate impact of the incentives...and you can push behaviors, but over time, those incentives tend to revert to the mean.

What is SmartNet?

Krezanoski: SmartNet [uses] conductive fabric...that when the bednet is folded up on itself, [it] detects the completion of the circuit and then you can log that measurement time, and you know whether the bednet is being used or not being used.

When you are coming up with new tools, one of the most important things to think about are. We did some studies back in 2016, showing these bednets to women and family members, asking them what they thought about it...there were some concerns about the electronics washing the net; being monitored while asleep; removal of device components...we also did some qualitative research...where we did interviews with actual users of the [SmartNet] and, again similar concerns [as the other study] but in general, positive comments about being OK with having their bednet use measured.

What lessons can be learned from bednet monitoring?

Krezanoski: There are a lot of ways that we can improve bednet education and malaria prevention. One thing we found is that when people don't think they're being exposed [to malaria], there's a tendency to not use bednets as frequently.

Age is a really significant factor in bednet use. There's some really interesting implications about how children share bednets with their parents...we found that school-age children [5-17 years] use bednets for almost 2 fewer hours per night and are three times as likely to miss a night of use. Children would go to bed earlier than the parents and the bednets would not go down until the parents went to bed. That's the kind of information that we get from [Smartnet]. We could do education campaigns to get people to put their bednets down when the kids get into bed.

Additional reporting by Shalmali Pal.

You can read the study abstract here.