Weapons in the War Against Zika

May 11, 2016

Since 2007, Zika virus transmission has been documented in 62 countries and territories.1 It’s spreading fast through Latin America and the Caribbean, and may soon threaten the southeastern United States.

What is being done to stop Aedes aegypti, the mosquitoes that spread this dangerous virus? Below, we breakdown some current approaches to fighting this mosquito and the diseases it transmits.

Oxitec OX513A Mosquitoes

How does it work? Genetically engineered male Aedes aegypti mosquitoes, which do not bite or transmit disease and have life spans of less than a week, mate with wild female mosquitoes. Their offspring inherit a gene that causes them to die.

When will it be ready? Now. Oxitec mosquitoes were released in five efficacy trials in three countries. In all of these trials, Oxitec mosquitoes reduced local Aedes aegypti populations by more than 90%.2 The approach is in use in the city of Piracicaba, Brazil.

Is it safe? With more than 150 million Oxitec mosquitoes released to date, regulators have found the approach to be safe, with no harm done to human health or the environment. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) have offered their support to this approach. The U.S. Food and Drug Administration (FDA) is considering a field trial in the Florida Keys. OX513A has been approved by Brazil’s National Biosafety Technical Commission (CTNBio) for releases throughout the country.3

Wolbachia

How does it work? To put it simply, scientists insert bacteria called Wolbachia into mosquito eggs. There are two main approaches for this method.

Incompatible Insect Approach
For the first, known as an incompatible insect approach, Wolbachia-infected males are released into a population not infected with Wolbachia. When they mate with a female mosquito, they lead to changes in the reproduction system. This results in a reduction in offspring.

Population Replacement Approach
For the second, known as a population replacement approach, both males and females, which bite and carry disease, are released. They then spread the bacteria through mating with the mosquito population in which they’ve been released. This approach is not being used in the U.S.

When will it be ready? Field trials are taking place in Australia and other countries for the population replacement approach.4 Some field studies have also been performed for the incompatible insect technique. Publication of the results is pending.

Is it safe? Wolbachia-infected Aedes aegypti may still be able to transmit diseases like dengue, chikungunya and Zika. Also, with the population replacement approach, Wolbachia-infected female Aedes aegypti– the ones that bite – can persist in the environment.5

Vaccines

How does it work? Vaccines stimulate the body’s production of antibodies. This allows immune cells to make antibodies that fight the disease when exposed at a later time.

When will it be ready? There are no available vaccines for the Zika virus,6 and a WHO official recently said vaccines are “at least 18 months away from large-scale trials.”

Is it safe? Vaccines have no environmental effects and undergo rigorous clinical trials.7

Chemical Insecticides

How does it work? Insect-killing chemicals are sprayed in infested areas.

When will it be ready? Now. Chemical insecticides have been used for years all over the world, but Aedes aegypti mosquitoes have developed resistance to many of them.8

Is it safe? Although this approach has been rigorously tested,9 pesticides are potentially toxic to other organisms, including humans, and can indiscriminately kill beneficial insects that are crucial to a healthy ecosystem, such as bees and butterflies.10

Radiation-based Sterile Insect Technique (SIT)

How does it work? Scientists expose male mosquitoes to radiation, which causes genetic mutations that make them sterile.11

When will it be ready? The concept for SIT was first developed in the 1950s. While SIT has been used successfully against some insect pests, mosquitoes are easily damaged by the process of irradiation, in particular Aedes aegypti mosquitoes.  To date there have not been any successful programs of Aedes aegypti population control using radiation-based SIT.12

Is it safe? It’s impossible to control exactly what mutations occur, and if male mosquitoes aren’t completely sterilized, they could theoretically pass on harmful mutations. Furthermore, research has been done on the irradiation of mosquitoes, but no successful control campaign has been achieved with irradiating mosquitoes to date.

RNA interference (RNAi)

How does it work? RNA interference can silence particular genes – including, potentially, those that control fertility.

When will it be ready? The RNAi approach has been successfully tested in the lab, but to date there is no data for field efficacy.

Is it safe? This technique alters the biology of a mosquito and has only been tested in the laboratory. We don’t know whether it works in the field.13

Gene Drive

How does it work? Scientists would insert genes that would make Aedes aegypti mosquitoes resistant to contracting Zika.14 These genes would be driven through the population to replace the wild population with one incapable of transmitting disease.

When will it be ready? The gene drive method has not been tested in the field, and inserted genes are frequently unstable in insects.15

Is it safe? Scientists don’t yet know how or if a gene drive would affect the way mosquitoes transmit the Zika virus – or even change the virus itself.16 The approach relies on driving a new gene through the population, with irreversible and potentially unpredictable effects.

The Bottom Line

All things considered, Oxitec’s genetically engineered mosquito is the most environmentally friendly vector control method. Vaccines won’t be available for some time, and all the other approaches have the potential to change the natural environment.

 


5 Alphey L. (2009) Natural and engineered mosquito immunity. J Biol 8, 40.

8 Marcombe S, Darriet F, Tolosa M, Agnew P, Duchon S, et al. (2011) Pyrethroid resistance reduces the efficacy of space sprays for dengue control on the island of Martinique (Caribbean). PLoS Negl Trop Dis 5, e1202.

10 Hidayati H, Nazni WA, Lee HL, and Sofian-Azirun M. (2011) Insecticide resistance development in Aedes aegypti upon selection pressure with malathion. Trop Biomed 28, 425-437.

13 Whyard S, Erdelyan CN, Partridge AL, Singh AD, Beebe NW, et al. (2015) Silencing the buzz: a new approach to population suppression of mosquitoes by feeding larvae double-stranded RNAs. Parasit Vectors 8, 96.

14 DeFrancesco L. (2015) Gene drive overdrive. Nat Biotech 33, 1019-1021.

15 Franz AW, Sanchez-Vargas I, Raban RR, Black WCt, James AA, et al. (2014) Fitness impact and stability 
of a transgene conferring resistance to dengue-2 virus following introgression into a genetically 
diverse Aedes aegypti strain. PLoS Negl Trop Dis 8, e2833.

16 DeFrancesco L. (2015) Gene drive overdrive. Nat Biotech 33, 1019-1021.