Conceptual framework and rationale

Malaria Journal Conceptual framework and rationale Alan S Robinson 2 Bart GJ Knols 1 Gabriella Voigt 0 Jorge Hendrichs 3 0 IAEA Laboratories , A-2444 Seibersdorf , Austria 1 Div. Infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center , F4-217, Meibergdreef 9, 1105 AZ Amsterdam , The Netherlands and K&S Consulting , Kalkestraat 20, 6669 CP Dodewaard , The Netherlands 2 Entomology Unit, FAO/IAEA Agriculture and Biotechnology Laboratory, IAEA Laboratories , A-2444 Seibersdorf , Austria 3 Joint FAO/IAEA Programme of Nuclear Techniques in Food and Agriculture , IAEA, Wagrammerstrasse 5, A-1400 Vienna , Austria The sterile insect technique (SIT) has been shown to be an effective and sustainable genetic approach to control populations of selected major pest insects, when part of area-wide integrated pest management (AW-IPM) programmes. The technique introduces genetic sterility in females of the target population in the field following their mating with released sterile males. This process results in population reduction or elimination via embryo lethality caused by dominant lethal mutations induced in sperm of the released males. In the past, several field trials have been carried out for mosquitoes with varying degrees of success. New technology and experience gained with other species of insect pests has encouraged a reassessment of the use of the sterility principle as part of integrated control of malaria vectors. Significant technical and logistic hurdles will need to be overcome to develop the technology and make it effective to suppress selected vector populations, and its application will probably be limited to specific ecological situations. Using sterile males to control mosquito vector populations can only be effective as part of an AW-IPM programme. The area-wide concept entails the targeting of the total mosquito population within a defined area. It requires, therefore, a thorough understanding of the target pest population biology especially as regards mating behaviour, population dynamics, dispersal and level of reproductive isolation. The key challenges for success are: 1) devising methods to monitor vector populations and measuring competitiveness of sterile males in the field, 2) designing mass rearing, sterilization and release strategies that maintain competitiveness of the sterile male mosquitoes, 3) developing methods to separate sexes in order to release only male mosquitoes and 4) adapting suppression measures and release rates to take into account the high reproductive rate of mosquitoes. Finally, success in area-wide implementation in the field can only be achieved if close attention is paid to political, socio-economic and environmental sensitivities and an efficient management organization is established taking into account the interests of all potential stakeholders of an AW-IPM programme. - Background Most insect control methods, both past and present, rely on the modification of some component of the insect's environment; in the majority of cases this means the use of insecticides. The realization that compromising the integrity of the hereditary machinery, through manipulation of the reproductive cells to induce genetic sterility, could also provide a method of pest control was a considerable conceptual leap [1]. Targeting the genome of pest insects to mitigate against their deleterious effects is currently undergoing a renaissance, especially in mosquitoes, with much attention being focused on using transgenesis to manipulate vector competence [2]. This approach, however, still has to overcome major regulatory hurdles and will require the identification of efficient effector genes and drive mechanisms to ensure the spread of any refractory gene. However, transgenic approaches may also contribute to the development of male-only strains [3] and provide alternative ways to sterilize mosquitoes [4]. When the concept of using sterility for insect control was first considered, entomologists were not aware of any treatment that could be given to insects, which following their release and mating with wild insects, would lead to the induction of sterility in individuals of the field population. Muller's discovery that ionizing radiation could induce dominant lethal mutations [5] was only appreciated by entomologists in the 1950's [6] and this led to the now well known and very impressive elimination of the New World screwworm Cochliomyia hominivorax, from the Southern States of the USA, Mexico and all of Central America and Panama [7], using what has come to be called the Sterile Insect Technique (SIT). This initial success for New World screwworm was quickly followed by many attempts to develop similar approaches for mosquitoes, with varying degrees of success [8]. Nevertheless, the release of sterile insects remains the only genetic technique that has been successfully implemented for the control of major insect pests over large areas [9]. What is a sterile male? The induction of genetic sterility in the females in the field population remains the key requirement for success of the SIT. Sterility is caused by dominant lethal mutations in the sperm of the released males resulting from radiation. A dominant lethal mutation is one that leads to the death of the developing zygote, in this case the embryo, irrespective of the genetic contribution of the other gamete. A sterile male has therefore to mate and transfer viable sperm and also accessory fluid of the appropriate quality and quantity to ensure appropriate female behaviour. This means that the definition of a sterile male, in terms of anopheline SIT, is very narrow and it does not include males that are aspermic, or which do not transfer viable sperm, or which do not elicit the correct behavioural response in the female, or which in any other way fail to convince the female that she has been mated by a "normal" male. In fact, the sterile male could be considered to be not sterile himself; the sterility must only be effective in the following generation when his sperm is used by the wild female to fertilize her eggs. The sterile male is simply a carrier of genetically compromised sperm from the rearing facility to the wild females in the field. Effectiveness of SIT at low insect densities and integrated approaches The first modellers to propose operational strategies for the use of sterile insects quickly realized that natural populations of pest insects can be present in such high numbers and often have such a high rate of population increase that it is very difficult to conceive the rearing of such high numbers of insects [10]. The SIT is clearly not a stand-alone technology and has to be integrated with other methods that are much more effective at suppressing pest populations that are at very high densities. However, sterile insects can be very effective at low pest densities where the technique exploits the ability of insects to find mates in the field. Seasonality (...truncated)