Infectious Disease

Study shows “exciting potential” of Wolbachia-infected mosquitoes to combat dengue fever

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Hamer reports that he has received advisory fees for advisory boards from Takeda and a fellowship from the Travelers’ Health Branch of the CDC, outside of the editorial. Sharp and Utarini do not report any relevant financial information. Please refer to the studies for all relevant financial information from the other authors.

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The release of Wolbachia-infected mosquitoes resulted in a 77% reduction in the incidence of symptomatic dengue fever in an Indonesian city, according to researchers, who said the same approach could be used to control other mosquito-borne diseases.

The study tested a Wolbachia pipientis strain called wMel, which makes Aedes aegypti mosquitoes less susceptible to dengue virus infection. Wolbachia pipientis occurs naturally in many insects, but not in A. aegypti, the primary vector of dengue fever Adi Utarini, PhD, MPH, MSc, and colleagues in the non-profit World Mosquito Program, which has been releasing Wolbachia-infected mosquitoes into the wild since 2011.

Photo of the mosquito Aedes aegypti, 2018;  Photo credit: James Gathany

A study in Indonesia showed the potential of natural intervention to significantly reduce the incidence of dengue, the most common mosquito-borne disease worldwide. Source: CDC / James Gathany.

“Wolbachia facilitates introgression of its own population by manipulating reproductive results between wild-type and Wolbachia-infected mosquitoes: the only practicable mating results are those where the offspring are infected with Wolbachia,” they wrote in the new report, which was released on Wednesday in . The New England Journal of Medicine was published.

Dramatic increase in cases

The global incidence of dengue fever has risen dramatically over the past half century to an estimated 100 to 400 million infections per year, according to the WHO, which estimates that about half the world’s population is at risk from the mosquito-borne disease.

In an editorial on the new study Davidson H. Hamer, MD, A global health professor at Boston University School of Public Health said the incidence of dengue has doubled every decade since 1990.

“Rising global temperatures due to climate change, the widespread distribution of the Aedes aegypti mosquito vector, increasing urbanization, population growth, environmental conditions conducive to mosquito breeding, and limited or non-existent surveillance have all contributed to dengue a global threat.” to make, ”said Hamer wrote.

Protecting people largely depended on mosquito control. Developing a dengue vaccine has been challenging because an effective vaccine must protect against all four serotypes of the virus. People infected with one serotype are at a higher risk of developing more severe symptoms when infected with another.

There is an approved vaccine, Dengvaxia (Sanofi Pasteur), that protects against all four serotypes. The FDA approved the vaccine in 2019 for use in children 9-16 years old who live in areas where dengue is endemic, including Puerto Rico, but recommendations for its use are pending. (The CDC Advisory Committee on Immunization Practices is due to vote on recommendations later this month.) The vaccine is only approved for children with confirmation of a previous infection because it can act as an initial infection and put them at risk of more serious diseases if they do infected naturally.

Although dengue is widespread in U.S. territories such as Puerto Rico, the U.S. Virgin Islands, and American Samoa, most of the cases that occur in the adjacent U.S. are imported, according to the CDC. Local outbreaks sometimes occur, however, including one in Texas in 2013 that involved dozens of cases.

Hamer called the southern United States “an ideal environment” for dengue given its climate, the large number of travelers from Latin America and the Caribbean, and its population of A. aegypti mosquitoes.

A second report, published Wednesday in the New England Journal of Medicine, described a fatal case of dengue in a woman in Miami in 2019, according to the CDC epidemiologist Tyler M. Sharp, PhD, and colleagues, the woman was one of 18 people locally infected with dengue in Florida that year. Their infection was likely caused by a strain imported by travelers who had recently returned from Cuba, they said.

“This case shows the potential dangers of dengue – introduction by travelers from dengue endemic areas to areas where dengue is not endemic, local transmission and serious illnesses that lead to death,” Hamer wrote.

Considerable reduction

The results of a study presented at a tropical medicine conference in 2019 showed that cases of dengue have fallen sharply in areas of four countries, including Indonesia, where laboratory-grown mosquitoes containing Wolbachia have been released.

Wolbachia has been approved for use in the United States by the Environmental Protection Agency since 2017. Other novel methods of mosquito control, including the use of genetically modified mosquitoes, have been explored.

The study by Utarini and colleagues took place in Yogyakarta, Indonesia, an urban area of ​​about 26 square miles with a population of about 311,000 people. After getting parish approval from the heads of 37 urban villages, Utarini and colleagues divided the area into 24 clusters and assigned them in a 1: 1 ratio to have open Wolbachia-infected mosquito eggs or no mosquitos from March to December 2017 to use. .

“In intervention clusters,” they wrote, “most parishioners were unaware of the cluster assignment because release containers were discreetly placed in a minority of residential properties for a limited time.”

The researchers examined nearly 54,000 patients in 18 state primary care clinics between January 8, 2018 and March 18, 2020, and enrolled more than 8,000 participants in the study. The analysis included 6,306 people – 2,905 lived in the 12 clusters where treated mosquitoes were released and 3,401 lived in control clusters. The mean age of the study participants was 11.8 years.

According to Utarini and colleagues, 2.3% of the participants in the intervention clusters acquired virologically confirmed dengue fever compared to 9.4% of the participants in the control clusters (aggregated OR = 0.23; 95% CI, 0.15-0, 35) – a protective effectiveness of 77.1% (95% CI, 65.3% -84.9%. The researchers said the result was similar for all four dengue serotypes.

The incidence of dengue-related hospital admissions was also lower in intervention clusters – 0.4% versus 3%, a protective effectiveness of 86.2% (95% CI, 66.2% -94.3%), reported Utarini and colleagues .

“Future studies should investigate the multivalency of the intervention, as laboratory studies suggest that wMel could also mitigate the transmission of Zika, Chikungunya, yellow fever and Mayaro viruses by A. aegypti,” they wrote.

In his editorial, Hamer said the study showed Wolbachia’s potential to prevent dengue transmission.

“Although there is clearly a need for future research to assess the persistence of wMel-infected mosquito populations after the introduction and replication of these results in various contexts – possibly including areas in the southern United States where there is a risk of dengue introduction is high – The use of Wolbachia-infected mosquitoes has exciting potential to combat the harm associated with dengue, ”he wrote. “Predictions from mathematical models have shown that the reduced infectivity of wMel-infected A. aegypti could be sufficient to reduce the basic reproductive number to less than 1 and possibly lead to a local elimination of the disease.”

References:

Anders K. et al. There is growing evidence that the Wolbachia method of the World Mosquito Program reduces dengue transmission. Presented at: ASTMH 68th Annual Meeting; 20.-24. November 2019; National Port, Maryland.

Hamer DH. N Engl J Med. 2021; di: 10.1056 / NEJMe2107325.

Sharp ™ et al. N Engl J Med. 2021; doi: 10.1056 / NEJMc2023298.

Utarini A, et al. N Engl J Med. 2021; doi: 10.1056 / NEJMoa2030243.

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