Challenges in Reducing Dengue Burden

Diagnostics, Control Measures and Vaccines

Sai Kit Lam

Disclosures

Expert Rev Vaccines. 2013;12(9):995-1010. 

In This Article

Current Control Measures

In the absence of drugs or a licensed vaccine, vector control is currently the only measure capable of limiting the spread of dengue. Aedes mosquitoes use a range of man-made and natural materials as breeding sites, which are targeted in vector control strategies.[216]

Vector control methods involve environmental, chemical and biological management approaches.[216] The WHO promotes the strategy known as Integrated Vector Management (IVM) to control mosquito vectors.[217] This strategy aims to improve the efficacy, affordability and sustainability of vector control, as well as reducing its environmental impact.

The removal of existing and potential vector breeding sites to prevent vector proliferation and human–vector contact is an important part of environmental management.[205] Important strategies include the installation of pipes to provide a reliable water supply to communities, which requires heavy investments in infrastructure, and the frequent emptying and thorough cleaning of containers for water storage. In addition, the cleaning of gutters, and removal or recycling of rubber tires and abandoned containers to prevent them from collecting rainwater, as well as the removal of plants that collect water in their leaves, are also vital in controlling mosquito breeding sites. Human behavioral changes, such as the installation of mosquito screens in windows and entry points and the use of mosquito nets, may also have an impact on reducing human contact with the vector, although as Aedes are day-biting mosquitoes, the use of nets is not considered as efficient as for malaria. Studies have shown that community participation can facilitate vector eradication, but this requires a sustained approach with a long-term shift in human behavior toward improved sanitation.[20,81] The requirements to maintain vector control efforts are evident from experiences in Latin America, where a relaxation of vector control measures resulted in resurgence in dengue incidence that was worse than outbreaks that occurred before such measures were implemented.[218] Similarly, in Singapore the adoption of a case-reactive approach to vector control has been held partially responsible for the sudden increase in dengue over the last decade.[82]

Chemical control involves targeting the larval and adult stages of the mosquito. Larvicides are used widely and also added to water storage containers, although a major limitation with their use is that many common mosquito breeding sites, such as leaf axils, tree holes and deep wells, are inaccessible for their application.[205] There are also concerns over the toxicity of larvicides such as methoprene, pyriproxyfen and temephos. Despite toxicity assessments of drinking water by the International Programme on Chemical Safety (IPCS), the addition of chemicals to domestic water can be viewed suspiciously by communities. Adulticides are sprayed either as residual surface treatments on walls and roofs of homes and buildings, or as space treatments in emergency situations during epidemics. Insecticides targeting both adult and larval stages may have limited efficacy beyond 2 years due to the development of insecticide resistance.[83,84] In fact, epidemiological and economic assessments of vector control strategies carried out by Luz et al. found that all 43 insecticide-based approaches tested resulted in the development of resistance, with potential to increase the size of future epidemics.[83]

For biological control of Aedes mosquitoes, a selection of fish species have been used to eliminate mosquito larvae from containers used to store potable water and wells, while predatory copepods (small freshwater crustaceans) are also effective against immature larvae.[85,86] However, control organisms often need to be reintroduced into the environment, while the success of the method depends on community participation and acceptance of the introduction of control organisms into water containers.

Novel vector control measures are also being investigated. The intracellular and maternally inherited insect bacterium, Wolbachia pipientis, has been introduced into the Aedes population in order to reduce the potential for dengue transmission both indirectly by reducing the lifespan of infected mosquitoes and also by directly interfering with dengue virus transmission.[87]Wolbachia strains such as wMel invade uninfected mosquito populations by inducing cytoplasmic incompatibility, which causes embryos from female mosquitoes not infected with the bacterium to die, while those of infected females are unaffected.[88] The wMel Wolbachia population has been released in Australia, successfully invading the natural population.[89] Other novel control mechanisms include the development and release of a genetically modified Ae. aegypti strain carrying a repressible female-specific dominant lethal gene that causes a flightless phenotype.[90,91] Tet-repressible expression of the promoter and first intron of Ae. Aegypti Actin-4 (AeAct-4) produces a sex-specific, alternatively spliced transcript, which is abundant in female pupae, predominantly in the indirect flight muscles.[90] The flightless phenotype produced is effectively lethal in the field and prevents mating. Under laboratory conditions, weekly introductions of transgenic males at ratios of 8.5–10.0:1 (transgenic:target) eliminated genetically diverse target populations within 10–20 weeks,[91] supporting further testing in contained field trials. However, manipulation of mosquito populations raise ethical and biosafety concerns due to their potential effects on biodiversity and risks to human health, and are recommended as last resorts.[92] In future, it will be necessary to combine and integrate vector control measures and preventive measures such as vaccination to increase the control of dengue.

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