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The barriers to eliminating disease

Researchers find a common killer can slip through the net

13 October 2011

In the temperate western hemisphere, we take going to sleep for granted. But in tropical climates biting insects carry deadly diseases and a peaceful slumber could lead to death by a small but silent killer.

Killer culprit: Phlebotomus argentipes transmits visceral leishmaniasis. Image: Dr François Chappuis, Kalanet

Killer culprit: Phlebotomus argentipes transmits visceral leishmaniasis.
Image: Dr François Chappuis, Kalanet

The use of mosquito nets laced with insecticide is a proven winner in the battle against malaria. They are so effective at providing a safe haven for people to sleep that their use has extended to other insect-borne diseases, such as visceral leishmaniasis (VL). But do these deadly screens work for non-malarial diseases?

Research supported by the EU and BBSRC has shown only minor 10 per cent reductions in the prevalence of VL when using insecticide-impregnated nets. Consequently, the whole strategy of where and when to use them on the whole Indian subcontinent needs a rethink, says BBSRC Fellow and senior researcher on the project Dr Matthew Rogers of the London School of Hygiene and Tropical Medicine. "Efforts should be made to characterize the basic biology and behaviour of this important disease vector so that we can devise better control strategies in the future."

Although the results on the surface are disappointing, it's equally important to know that something doesn't work than merely assuming it does – especially when lives are at stake. Knowing that nets are of limited effectiveness means a new starting point for developing effective control strategies, and a re-examination of the fundamental biology and ecology of the insect in question.

In addition, the study developed new immunological techniques to gauge people's exposure to bites that could be used for other insect-borne diseases. "I developed, validated and applied an antibody test (ELISA) to measure the amount of antibodies individuals had to the saliva of the sand fly, as a measure of the numbers of bites," says Dr Rogers.

Chemical world

A neglected tropical disease, VL is the World's second largest vector-borne disease and is prevalent in poor communities throughout India, Nepal, and Bangladesh. This life-threatening condition is transmitted by the bite of a small sand fly, Phlebotomus argentipes, and infected people suffer with high fever, weight loss and weakness that can lead to death if left untreated. According to the WHO, 2.5M people are currently affected by 500,000 news new cases arise each year including around 60,000 fatalities in India (ref 1).

A long-lasting insecticidal net: but how well do they work? Image: Dr Bart Ostyn, Kalanet.

A long-lasting insecticidal net: but how well do they work? Image: Dr Bart Ostyn, Kalanet

Elimination in the Indian subcontinent is considered feasible because there is only one species of insect carrying the disease from person-to-person. In 2005 the governments of India, Bangladesh and Nepal signed a memorandum of understanding for the elimination of the disease at the World Health Assembly in Geneva, aiming to reduce the yearly incidence of VL to less than one per 10 000 population by 2015.

A crucial part of this eradication plan is to control the insects by strategic use of insecticides. Indoor residual spraying (IRS) has been used for more than two decades, including in India using the long-lasting and controversial chemical DDT, which has been implicated in bioaccumulation in the environment and food chain. In Nepal, other more recent synthetic pyrethroid insecticides, which are derived from Chrysanthemum flowers, have been used since 1995 which are stronger but less long-lasting than DDT, and not associated with the same environmental problems.

Either way, as the spraying takes place in people's homes, there is a need for alternatives "To date, indoor spraying campaigns have been unable to control the disease," says Dr Rogers. "The use of long-lasting insecticidal nets has been postulated as an alternative or complement to spraying."

Action plan

A field worker collects blood samples from villagers in India. Image: Dr François Chappuis, Kalanet

A field worker collects blood samples from villagers in India.
Image: Dr François Chappuis, Kalanet

The Kalanet community trial was set up to test the impact of comprehensive distribution of long-lasting insecticidal nets (LNs) on transmission and incidence of VL. Largely funded by the EU under its 6th Framework Program, the Kalanet community trial was part of a large project conducted by the Kalanet consortium of European, Indian and Nepalese scientists, of which individuals such as Dr Rogers are funded by BBSRC, this case a David Phillips Fellowship.

Villages in the Muzaffarpur district in India, and the Saptari, Sunsari, and Morang districts in Nepal were randomly assigned with LNs to sleep under, or used as control clusters with their predominantly untreated nets. "Over three years and involving approximately 20,000 participants, data were collected to assess the acceptability, cost-effectiveness and efficacy of LNs against both the sand fly vector and the disease," says Dr Rogers.

Unfortunately, the results were disappointing. LNs led to a 9-12% reduction in sand fly bites, and while that percentage across hundreds of thousands of people is significant to their lives, on a population-wide basis the data show that alone it's not a means of controlling disease transmission (ref 1).

Another paper, also part of the same project, found similar results (ref 2). "It showed a small 10% drop in VL incidence during the three year LN intervention," says Dr Rogers. "The papers complement each other and report that the LNs were largely ineffective against P. argentipes and transmission of VL."

Net gain

Although the results are initially disappointing, during the study Rogers and colleagues worked on new techniques to gauge infections in individuals – new techniques that could be developed and applied to the study of other diseases.

There is only one insect vector for visceral leishmaniasis, so scientists believe the disease could be eradicated. Image: Ray Wilson

There is only one insect vector for visceral leishmaniasis, so scientists believe the disease could be eradicated. Image: Ray Wilson

The scientists used individual's immunological reactions to sand fly bites to gauge infection across the population. Dr Rogers says that sand fly saliva is a complex cocktail of pharmacologically active compounds which prevents blood from clotting and widens capillaries in the skin to supply the biting fly with larger volumes of blood. "Our immune systems can readily make antibodies to these salivary proteins, and we and others have shown this to correlate with the exposure risk and actual numbers of bites."

But what's to stop other insect bites from messing up the results? Dr Rogers adds that there is usually enough species-specificity to identify the bites of particular sand fly vectors, but this is far from ideal since cross-reaction between closely-related insect species can often occur. "This epidemiological tool is still in its infancy," says Dr Rogers. "Improved information on the genetics of these insect vectors will tailor this tool to the vector species in question."

Overall, the Kalanet project has revealed much about the impact on the current elimination effort against VL in the Indian subcontinent – in that spraying and LNs in their current format offer little protection. "It is generally accepted that elimination of VL can only be achieved through effective vector control, improved rapid case detection – including detection of asymptomatic people – and treatment," says Dr Rogers. "Therefore, efforts should be made to characterize the basic biology and behaviour of this important disease vector so that we can devise better control strategies in the future."

References

  1. Serological Markers of Sand Fly Exposure to Evaluate Insecticidal Nets against Visceral Leishmaniasis in India and Nepal: A Cluster-Randomized Trial (external link)
  2. Longlasting insecticidal nets for prevention of Leishmania donovani infection in India and Nepal: paired cluster randomised trial (external link)

Contact

Arran Frood

tel: 01793 413329