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Mosquitoes Are Winning, But There May Be Solutions

November 8, 2023

Mosquitos November Commentary

What is the world’s deadliest animal?

No, it isn’t sharks or tigers.

It’s  mosquitoes, responsible for about 725,000 human deaths a year. (Incidentally, humans are the second deadliest, killing about 400,000 annually. Sharks don’t make it into the top ten).

 Mosquitoes accomplish their deadly mission mainly by infecting people and other animals with a wide variety of microorganisms. These diseases include West Nile virus, Zika, yellow fever, chikungunya, dengue, and malaria.  Malaria alone kills about 600,000 people annually, mostly in Africa. Nearly 80% of those deaths occur in children under five years of age. Malaria is spread by the female Anopheles mosquito when it bites a human and injects a parasite of the Plasmodium species. Of the five types of Plasmodium parasites, P. falciparum is the deadliest.

Those figures are staggering, but cases and deaths of malaria were actually rapidly  declining between 2000 and 2015 because of the “widespread use of insecticides in homes, insecticide-coated bed nets, and better treatments.” Deaths from malaria continued to decline after 2015, hitting a low in 2019. But then they began to rise again. Cases of dengue are also increasing in countries in Latin America and in Pakistan.

The reasons for increasing malaria cases and deaths are several. Mosquitoes are evolving and adapting, so that they are now more likely to bite people outside and during the day when they aren’t protected by insecticide-coated bed nets. They are also becoming resistant to many of the insecticides in current use. Climate change is also expanding the regions where mosquitoes can thrive, putting more people at risk for mosquito-borne diseases. At the same time, the malaria parasite is becoming resistant to some of the available treatments for malaria. Taken together, these factors have wiped out gains made in the early 21st century in controlling malaria. Some of these factors also explain why other mosquito-borne illnesses are increasing or showing up in new places around the world. Dengue is now seen in Florida and locally transmitted cases of malaria have been reported in Texas, Florida, and Maryland. Although malaria is not predicted to be a serious problem in the U.S. for the foreseeable future, it continues to be a scourge in Africa.

In short, mosquitoes are continuing to gain the upper hand on humans. Two technologies offer us a chance to fight back. Two new malaria vaccines have now been approved and there is promise that biological modifications may represent a strategy for wiping out whole populations of disease-carrying mosquitoes. Both strategies face challenges, however, some of which come from fear and misinformation.

Effective Vaccines Available Against Malaria

Two vaccines against malaria are now available and recommended by the World Health Organization (WHO). The first, known as  RSS,S, was piloted in 2019 in Ghana, Kenya, and Malawi and recommended for widespread use in children who live in vulnerable areas in 2021. It requires four injections. RSS,S has an estimated efficacy for reducing cases of malaria in children that begins at about 75% but wanes quickly over time. This means that many children who get the vaccine will still get malaria and that seasonal booster doses will probably be necessary.

The  second, R21/Matrix-M, was developed by scientists at the University of Oxford and recommended earlier this year by the WHO for children between 5 and 36 months, an age-group particularly vulnerable to dying from malaria infection. It requires a three-dose series and, with the addition of a fourth shot one year later, also has an efficacy of about 75% for reducing cases.

 Vaccine hesitancy is a growing problem in the U.S. and has also affected Africa. While demand for the RSS,S malaria vaccine has been high (and supply relatively low), there are concerns that vaccine misinformation could be a factor in limiting the uptake of the new R21 malaria vaccine. Critica’s CEO Sara Gorman and Chief Medical Officer David Scales co-authored a paper in the journal  Lancet Infectious Diseases anticipating this problem, along with Critica’s Chief Scientific Advisor Boghuma K. Titanji of Emory University, Shalom Tchokfe Ndoula and Judith Seungue of the Ministry of Public Health of Cameroon, and Isabelle Makone of the pediatrics faculty at University of Yaounde, Cameroon.. We can anticipate that in addition to cost and supply issues, malaria vaccines could face pushback because they are intended for children, require multiple injections, and do not provide 100% protection against getting malaria or, if infected, becoming seriously ill. The paper authors urge African public health authorities to learn all they can about potential misinformation and parental fears about the vaccines. This information can then be used to tailor communication campaigns aimed at counteracting misinformation and increasing vaccine acceptance. Countless lives could be saved by the malaria vaccines, so it is imperative that we do all we can to allay groundless fears and encourage vaccine uptake.

Biologically Modified Mosquitoes Are Controversial

A second, more controversial approach to controlling malaria and other mosquito-borne diseases is to modify the mosquitoes that carry the malaria parasite. One approach is to create-genetically modified Anopheles mosquitoes that are immune to the malaria parasite. Another is to introduce mosquitoes that produce only sterile females or male mosquitoes whose offspring are mostly male (only female mosquitoes bite, so this would effectively eliminate the chance of infecting humans with the malaria parasite). These biologically modified mosquitoes are created in the laboratory, then released into the wild where they mate with other mosquitoes and pass on their modified genes, ultimately either making the population of mosquitoes incapable of transmitting disease or of wiping them out altogether.

We have seen all kinds of misinformation about the genetically modified mosquito research projects on social media, including the false claim that the  Gates Foundation is responsible for the handful of malaria cases reported in the U.S. According to this claim, the foundation first funded research to develop malaria vaccines, then released genetically modified mosquitoes carrying the disease to infect Americans and increase vaccine sales. Of course, none of this remotely true (except that the Gates Foundation has indeed funded malaria vaccine research, for which we are grateful). The Gates Foundation did not fund U.S. mosquito release projects and the mosquitoes that are released anywhere do not carry the malaria parasite. It does demonstrate, however, the extremes to which some misinformation purveyors go to scare people about potentially life-saving new technologies.

More important than misinformation myths about the Gates Foundation are concerns about the genetically modified mosquito projects from Africans and African governments. As Stephanie Nolen wrote last month in the  New York Times, “Governments are hesitant and few in Africa have laws to regulate the use of the technology. Its risks lie in the unknowns: Could the modified mosquito evolve in some way that has harmful effects on the rest of the ecosystem? Could it prompt a dangerous mutation in the malaria parasite, which will find a new way to spread to survive?”

One could counter these arguments by reminding that some risks are worth taking if it would mean saving 600,000 lives annually. Of course, data showing that the release of genetically modified mosquitoes is safe would be the most reassuring, and some have already emerged. The U.S. Environmental Protection Agency (EPA) has authorized the release of a genetically modified version of the Aedes aegypti mosquito into Florida and Texas. The Ae. aegypti mosquito carries the viruses that cause dengue, Zika, and chikungunya and is common in many parts of the U.S. The females of the genetically modified version cannot survive into adulthood and are therefore incapable of transmitting disease. According to the  U.S. Centers for Disease Control and Prevention (CDC), “The EPA evaluated the potential risk of releasing GM [genetically modified] mosquitoes into communities and determined that there is no risk to people, animals, or the environment.” Over one billion of these mosquitoes have been released in several countries since 2019, showing clear signs of reducing disease but no untoward outcomes.

Although it is hard to know exactly what positive role mosquitoes play in the ecosystem, proponents of genetically modified mosquitoes point out that only one species of mosquito is targeted in these efforts, while most areas have multiple species of mosquito. Hence, harm to the environment from biologically modified mosquitoes may not be a real concern. It is also unclear what mechanism would be involved in Nolen’s fear that biologically modifying a mosquito could lead to a dangerous mutation in the parasite that causes malaria. Still, this is the reason we need aggressively funded research into this promising strategy to ensure its safety.

The death toll wrought by mosquitoes is substantial, and it appears that this is only getting worse as mosquitoes evolve to resist pesticides and climate change pushes them into new areas of the globe. We desperately need solutions to mosquito-borne diseases and both vaccines and biological modification are clearly potential ways to solve the problem. We now have two vaccines, although getting them to enough children is a challenge. We could have an even more definitive solution if we develop the technology to eliminate the ability of whole species of mosquitoes to transmit disease. While great care is needed in studying and implementing this technology and regulations clearly appropriate, it is important that we not let fear stand in the way of solutions that could save millions of lives. Misinformation about malaria and all other vaccines should be vigorously addressed, and research into genetically modified mosquitoes should be well funded and supported so that we can assess the safety, viability, and effectiveness of this approach. One way or another, we are going to have to use technology if we are going to win the war with Earth’s deadliest animal.

Categories: GMOs, Malaria, Vaccines