Interview Dr. Lee Han Lim

Keeping Ahead of Threats: A Lifetime Researcher’s Perspective

How can we safely, effectively and affordably stop vector-borne diseases in Asia and globally? In the 40 years since Dr. Lee Han Lim began working with the Institute of Medical Research (IMR) in Kuala Lumpur, he has found some answers. It is due to his research that Malaysia has almost completely eradicated malaria since 1995; WHO has now classified the country in the pre-elimination phase for the disease[1]. However, Malaysia, is still combating other vector-borne diseases such as dengue, Zika, chikungunya and simian (monkey) malaria – and Dr. Lee continues his hunt for solutions.

7,456,000 people live in Kuala Lumpur, Malaysia. In this urban environment, the late monsoon season occurs from October through February – and with it, risk increases for the transmission of neglected tropical diseases via mosquitoes.
 

From your perspective, why is prevention of tropical diseases important?
This can be viewed from several aspects. First, there are humanitarian considerations, whereby human suffering and deaths due to tropical diseases can and should be prevented or eliminated. There is also the economic impact of tropical diseases, in terms of costs of healthcare such as treatment and prevention, and its effects on work productivity, since many such diseases affect physically active people in the work force. And there are social effects, where several tropical diseases, such as filariasis, cause severe deformities that are associated with social stigma and can result in denial of marriage and inability to work.

 
In 1978, Dr. Lee Han Lim joined the Institute of Medical Research, Malaysia, as a Research Officer with the Medical Entomology Unit in Kuala Lumpur. In 1993, he was appointed as Head of the Unit and also the Head of the WHO Collaborating Centre for the Ecology, Taxonomy and Control of Vectors of Malaria, Filariasis and Dengue.

 

How have you and your research team contributed to public health?
I am convinced that prevention is a crucial first step to protecting public health. This is why my research focuses on developing and evaluating various mosquito vector control measures to suppress mosquito-associated diseases. In malaria control, our research on insecticide-impregnated bed nets was translated into the National Malaria Control Policy since 1993. And the findings from our trial of indoor residual spraying of deltamethrin have led to it replacing the insecticide DDT since 1998. Recently we are testing the use of outdoor residual spraying of the rain-resistant deltamethrin formulation in Sabah to control the outdoor biting simian malaria anopheline vectors, which is the first test of its type in the world.

 

“I am convinced that prevention is a crucial first step to protecting public health. This is why my research focuses on developing and evaluating various mosquito vector control measures to suppress mosquito-associated diseases.”

Dr. Lee Han Lim

 

If effective, a formulation like this can make a significant difference in the fight against mosquito-borne diseases since tropical countries like Malaysia see a lot of rainfall throughout the year.

 

In dengue vector control, we are working on a few approaches. One is developing genetically modified Aedes aegypti, Wolbachia-infected Aedes aegypti and Aedes albopictus. We also continue development of sterile insect technique and the area-wide application of the microbial control agent, Bacillus thuringiensis H-14 (Bti). Other supportive research includes development of biochemical test kits for the rapid detection of insecticide resistance and kits for detection of dengue and chikungunya virus in mosquitoes. We also conduct molecular studies on insecticide resistance.
 

 

Key Concepts in the Fight against Mosquitoes

 

With every blood meal, mosquitoes can transfer bacteria and viruses that cause neglected tropical diseases and malaria. Science strongly focuses on preventing these diseases through vector control and resistance management.

 

 

Wolbachia Replacement Approach

Wolbachia are bacteria that live inside insect cells, occurring naturally in up to 60 percent of all insect species, including butterflies, dragonflies and moths, as well as many mosquito species that bite people. Despite the broad range of insects carrying Wolbachia, it is not infectious, and it cannot be transmitted to warm-blooded animals, including humans.

In Wolbachia replacement approach, Wolbachia-infected Aedes mosquitoes are released to intermingle with, and ultimately outnumber, wild mosquitoes. Infecting an Aedes population with Wolbachia reduces the mosquitoes’ ability to transmit dengue (and other diseases) to humans. [2]

 

Sterile Insect Technique

The mass-rearing and sterilization, using radiation, of a target pest, followed by the systematic area-wide release of the sterile males by air over defined areas. These sterile males mate with wild female insects, but the result is no offspring and a declining pest population. [3]

 

What is the current state of insecticide resistance among mosquitoes in Asia?

Globally, WHO estimated that since 2010, 61 countries have reported malaria vector resistance to at least one class of insecticide, with 50 of those countries reporting resistance to two or more classes. Similarly, insecticide resistance in mosquitoes is quite widespread in Asian countries. Resistance to major groups of chemical insecticides, notably pyrethroids and organophosphates, has been reported in the anopheline malaria and filariasis vectors. Resistance has also been detected in Aedes – specifically aegypti and albopictus – vectors for dengue, chikungunya and Zika virus; in the Culex vectors, which are nuisance pests, as well as vectors of Japanese encephalitis and filariasis.

 

 

Far away from the crowded city, workers on the fields sow and grow rice, one of the main crops in Malaysia.

 

What are the main reasons for this situation?

This is due to over-use and long-term application of chemical insecticides to control the mosquito vectors and the diseases they carry. Over-reliance on chemical insecticides also accounts for the evolution of resistance in mosquitoes.

 

How can insecticide resistance be avoided more effectively? 

The judicious use of chemical insecticides is the key to avoid development of insecticide resistance. This should include proper dosing, timing and application, the rotation of insecticides of different modes of action, use of synergists and the use of non-chemical control strategies.

 

In Malaysia, landscapes are extremely diverse – but whether big city, farmland or natural forest, wherever it’s damp or wet, mosquitoes might be nearby.

 

In your opinion, what one recent innovation has made a difference in the fight against NTDs and dengue in Malaysia and Asia? 

We have developed outdoor residual spraying for the control of dengue by depositing a long-lasting pyrethroid formulation onto the outer walls of premises. Any mosquitoes landing and coming into contact with the treated surface will be killed. We are fortunate in that Bayer has developed a new rain-resistant deltamethrin formulation which fulfills our requirement of long lasting bio-efficacy on building walls. Numerous field trials have attested to the effectiveness of the method, especially in high rise buildings, where most of the dengue outbreaks occur today. Outdoor Residual Spraying is especially used when there is a sudden outbreak and under emergency situations. Dengue has been shown to abate quickly with the implementation of Outdoor Residual Spraying. The method is now adopted as a new policy of the Ministry of Health for the emergency control of dengue outbreaks.

 

To prevent NTDs even more effectively, what innovation is on your ‘wishlist’?
With our present state of knowledge, Wolbachia replacement approach seems to be the most effective, affordable and sustainable method to control dengue, chikungunya and Zika. Although field testing is still at the early stage, hopefully the large-scale, area-wide releases of Wolbachia carrying Aedes could be rolled out soon. In addition, since chemical insecticides still play a pivotal role in vector control, and there are widespread incidents of resistance to existing insecticides, I hope new compounds with novel modes of action to counter resistance could be available in the near future. The potential use of the sterile insect technique to suppress mosquito vectors should also be looked into.

 

Prioritizing prevention for children and adults is important in urban and suburban areas to halt dengue fever, a viral infection, which occurs nationwide in Malaysia.

 

Personally, why did you choose this research path? What motivates your work?

I have been very interested in various sciences since high school and later developed a particular interest with the biological research, especially the biomedical aspects. In university, I took up the Entomology & Parasitology double major as my core subjects, since both contained elements of biomedicine. Upon graduation, I joined the Medical Entomology Unit of the Institute for Medical Research, and this is where I participated in research. At the time, malaria and filariasis were still major health problems in Malaysia, and my task was to focus on research into various methods of vector control as key to preventing these diseases. 

 

The subsequent resurgence of dengue and later chikungunya and Zika shifted our priority to research for solutions to control the mosquito vectors since there’s no vaccine nor specific drugs to treat these diseases. Biomedical research, such as medical entomology, is actually an important component of disease control.

 

Top tips: What can you do to prevent the spread of vector-borne diseases? [4]

Vector-borne neglected tropical diseases and malaria are serious illnesses, but everyone can take common-sense steps to avoid being bitten by an infected mosquito, sandfly or tick. The World Health Organization suggests the following:

  1. Ensure your vaccinations are up to date for diseases prevalent in areas you may visit or move to.
  2. Wear light-colored, long-sleeved shirts and long trousers, tucked into socks or boots, and use insect repellent on exposed skin and clothing to protect yourself from being bitten.
  3. Install window screens in your home or workplace to keep mosquitoes outside.
  4. Sleep under an insecticide-treated bed net if you live in an area with a risk of malaria.
  5. Use safety-tested and regulated indoor residual sprays with long-lasting insecticides on internal walls, eaves and ceilings to reduce biting. 
  6. Get rid of stagnant water (for example, in containers, flower pots and used tires) in areas where mosquitoes breed.
  7. Check your body regularly for ticks. If you find one, remove it with tweezers and apply a skin disinfectant. In tick-infested areas, examine your clothing, luggage and other belongings thoroughly before entering your home.
  8. Avoid contact with blood, secretions, organs or other bodily fluids of infected people or animals.
  9. Make sure you keep strict hygiene control of food, and avoid unpasteurized dairy products in areas where tick-borne encephalitis can be transmitted.

Further information here!

 

 

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