Modified vector attack on dengue

Abstract

Genetically modified mosquitoes are showing promise in reducing the occurrence of a serious disease. Nigel Williams reports. Genetically modified mosquitoes are showing promise in reducing the occurrence of a serious disease. Nigel Williams reports. There is long history of using the release of laboratory-modified insects to reduce the impact of diseases, some with considerable effect, and a novel modification is showing promise in the fight against dengue fever. Researchers at the Oxford-based company Oxitec announced last month that a small-scale trial using male mosquitoes that had been genetically modified to be dependent on an antibiotic had cut numbers of the insect in the Cayman Islands by 80 per cent in six months. The modified mosquitoes mate as normal but die quite quickly in the absence of access to tetracycline. Their offspring inherit the trait and perish quickly too. “By giving them tetracycline in the lab, we can keep them alive and breed large numbers of them, but when we release them into the environment and they mate with wild females, all the offspring inherit a copy of the gene that kills them if they don't get the antidote… so they die,” says Luke Alphey, co-founder of Oxitec. The mosquito is Aedes aegypti, which spreads dengue fever when females bite humans. Dengue fever causes severe flu-like symptoms and can be lethal. The World Health Organisation estimates there are 50 million cases of dengue fever a year, of which 25,000 are fatal. About 2.5 billion people are at risk, mostly in Africa and south-east Asia. There is no vaccine or treatment and experts say new ways of controlling the disease are urgently needed because of a sharp rise in global infection rates over recent years. Angela Harris of the Mosquito Research and Control Unit in the Cayman Islands said she was encouraged by the trial, conducted between April and October this year. “This kind of technology really has a place for reducing dengue and having an impact on human health,” she said. Alphey said that his company was in talks with officials in several countries about further and larger trials. Modified male insects have been used to control populations several times before. Most early attempts were with the release of sterile males created by irradiation. One of the first successes was against the screwworm fly before the second world war in the south-east US. The war disrupted experiments but, by 1952, laboratory and field experiments suggested the approach had promise. A large-scale experiment on the Caribbean island of Curacao demonstrated a spectacular success of the sterile-male technique — the island was completely rid of the screwworm fly in 1954–1955. The technique was then used in the south-east US which led to the eradication of the fly in the region by 1959 and the substantial depression of it over vast grazing lands in Texas starting in 1962. Successes obtained with the sterile-male technique plus the considerable positive experience with insecticides led Ed Knipling of the US Department of Agriculture and colleagues to construct a formal theory of the principles for insect control by the mid-1960s. He presented his theory to the Entomological Society of America in 1965. Knipling argued that the core of a sound system of insect control was based upon attack against the total population of the pest, not isolated pockets occurring in individual fields. He also argued that single suppression techniques were subject to limitations, but that combinations of different techniques could compensate for the individual weaknesses and allow the combined package to overcome the law of diminishing returns. Insecticides were efficient in killing insects when the populations were large but inefficient when the numbers were small. The sterile male technique, in contrast, was inefficient in killing large populations but highly effective when numbers of individuals were small. A sequential use of insecticides and the sterile male technique could reduce a large population to a small one and then continue to a miniscule population or zero, he argued. The antibiotic-dependence strategy could see a new approach to achieving disease vector control.