Biodegradable Larvicide may help control spread of Zika, Dengue Fever, Yellow Fever and Malaria

 

On 1 February 2016, the World Health Organization (WHO) declared Zika virus an international public health emergency due to its possible link with birth defects in Brazil. The development of a potent but biodegradable, earth-friendly larvicide against the mosquitoes that carry the virus could offer a much-needed control strategy, generating excitement across the research community.

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Biodegradable larvicide may help control spread of Zika, Dengue Fever, Yellow Fever and Malaria

The deadliest animals in the world are not sharks, lions or venomous snakes but mosquitoes. This hundred-million-year old family of flies act as vectors for killer pathogens including malaria, which is responsible for killing more people than any other disease, dengue and yellow fever--together leading to the death of several million people every year.

The latest mosquito-transmitted virus to reach pandemic levels is Zika. First discovered in Uganda in 1947 and common across Africa, it began to spread rapidly west in May 2015, when an outbreak took hold in Brazil. It has now reached pandemic levels across South America, and spread to several countries in the Caribbean and Central America. Its arrival in Brazil has attracted media attention not least because the Olympics will open in Rio this summer.

Most infections are asymptomatic and, at worst, sufferers develop fever and a rash. However, there is a more concerning connection with rising numbers of babies being born with microcephaly, a condition that leaves babies with an abnormally small head size and possible developmental problems. The virus has now been found in the brains of babies with the condition and has also been linked to miscarriages. Zika has also been linked to a rise in the number of cases of Guillain-Barré syndrome, a rare neurological disorder that can cause paralysis. With no treatment for the disease, there is a pressing need for new control strategies.

Prevention strategies

A number of preventive approaches have been suggested. The most obvious is vaccination, but this will take time (current estimates are at least 18 months) and money. This solution has limited potential as, like any virus, Zika can mutate. There are also more novel approaches, such as genetically modifying ‘self-limiting’ mosquitoes. However, these are also expensive and not yet feasible on a large scale.

A more traditional approach is the use of a larvicide, a type of pesticide used in mosquito control programmes. Larvicides target the mosquito at the immature stages of its life cycle: the egg stage; the larva; and the pupa (the non-feeding stage prior to the mosquito becoming an adult).

Crucially, all of these stages are found in water environments where the immature mosquito cannot disperse. This makes them relatively easy targets for control strategies. Spraying of larvicides can rapidly reduce the mosquito population in an affordable way and has been used extensively in the past.

A novel larvicide

The problem with existing larvicides is that they are almost all toxic. “Many insecticides are neurotoxic to humans and non-target organisms,” explains Dr Catherine Hill, medical entomologist at Purdue University, West Lafayette, Indiana. Indeed, included in the list of WHO-recommended larvicides is temephos, an organophosphate larvicide widely used in the developing world to treat mosquito-infested water. It is hazardous to the environment and has been classified as ‘very toxic’ to aquatic organisms by the US Centers for Disease Control and Prevention (CDC).

Included in the same list is diflubenzuron – a metabolite of which is a ‘probable human carcinogen’, according to the United States Environmental Protection Agency – and fenthion, which is toxic to fish, birds and already vulnerable bees. “Almost none of the currently approved larvicides for mosquitoes are biodegradable,” says Mary Skelly, CEO of Dublin-based antimicrobial biotech company Microbide.

Alternative mosquito control

Alongside this, mosquitoes are evolving resistance against many existing larvicides, and new ones are expensive to develop. “We need alternative methods of control, and there is increasing awareness that integrated approaches combining different techniques are more likely to provide sustainable results,” says Dr Guy Hendrickx, CEO of Avia-GIS, a Belgian company that has developed maps to track mosquitoes. He agrees with Dr Hill, that there is a "desperate need" for new and safer larvicides.

Microbide is testing an alternative solution: a class of organic chemicals called 'aldehydes.' These compounds, dubbed ‘old-fashioned chemicals’ by Skelly, are ubiquitous in nature. Most are derived from sugars and they are frequently found in essential oils. They are also highly reactive and excellent candidates for killing pathogens. But aldehydes also evaporate easily, which is a problem if you want to harness their antibacterial properties.

To exploit the biocidal properties of aldehydes, Skelly has developed a way to hold them in solution. By associating the aldehyde with surfactants, the aldehyde is protected within micelles--tiny lipid spheres, which form naturally when oil is mixed with water. The micelles coat and protect the aldehyde, anchoring it in solution and stopping it from evaporating. Micelles also orient the active part of the aldehydes towards the surface of the solution, making them even more effective as biocides. “When you spray the solution onto standing water or at the edge of a mosquito-infested stream or pond, the equilibrium changes, and the chemical is forced out [of the micelle] where it irreversibly binds with, and kills, immature mosquitoes on contact,” says Skelly.

A chemical with potential

Skelly first filed a patent for the technology in 2008. One year on, following successful antimicrobial tests on bacteria and spores, she decided to trial it on mosquitoes. The formula was tested on Anopheles arabiensis, one of the mosquito species that carries malaria, and Aedes aegypti, the major culprit in Zika transmission. The results showed that the micellized aldehyde solutions were highly effective at killing the immature stages of both species of mosquito.

The complexed aldehydes have outperformed non-complexed market leaders in head-to-head studies of hospital high level disinfectants. But the true advantage is the environmentally friendly nature of the solution. The product is entirely biodegradable – after use it breaks down into CO2 and water. The Microbide solutions are pH neutral and studies show the active aldehydes have no effect on larger organisms found in water, such as fish, plants and even adult mosquitoes. “If we were to get approval as an insecticide, we would be the sixth and only biodegradable chemical on the market for that purpose,” Skelly says. However, the mechanism is non-specific, and other small aquatic organisms like water fleas may be affected. Such costs will have to be weighed up against the potential benefits to public health.

Microbide hope to conduct a field trial to confirm their results in the lab, followed by stringent safety tests. “It’s important to ensure that the toxicity and environmental safety profiles of Microbide’s product meet requirements,” Hill explains. Due to its affordability and ecologically friendly profile, it could complement more expensive treatments used for clean water. “We see it as part of an integrated approach, with a focus on grey water,” says Hendrickx. Grey water is household wastewater, from baths, sinks and washing machines for example, which can be major breeding sites for mosquitoes.

For now, Microbide will be making its data public in line with a joint declaration from the Wellcome Trust, the Bill and Melinda Gates Foundation, the CDC and others, to share data on Zika. Hopefully, increasing access to such data like will accelerate efforts to combat this devastating, expanding outbreak.

Eleanor Bird.

 
Miriam Murphy