Interview: Mohammad Shafiul Alam

It will take a few years to market the dengue vaccines

Mohammad Shafiul Alam

The dengue situation in the country has turned into a critical public health concern. Mohammad Shafiul Alam, a scientist at the Department of Infectious Diseases at the International Center for Disease Research, Bangladesh (icddr,b), spoke to Prothom Alo about the spread of dengue, changes in the behaviour of Aedes mosquitoes, the status of insecticides used to eradicate mosquitoes, and vaccine trials to prevent dengue. He was interviewed by Partha Shankar Saha.

Q:

The number of dengue cases and deaths in the first seven months of this year is more than any time in the past. How did the situation become so critical?

The dengue outbreak in this year is basically the continuation of last season. In the last season the outbreak was mostly in October and November which normally happens in July-August. Generally, density of Aedes mosquito decreases as temperature drops in the winter. Then the density of mosquito started to increase immediately after the rain. But even in December last year the number of infected was high. During this whole period there was dengue infection. As a result, a large number of Aedes mosquito came into contact with dengue patients and turned into vector. As a result, the dengue situation has exacerbated.

Q :

Has the behaviour of Aedes mosquitoes changed? The common belief is that Aedes mosquito bites during the day, not at night. Again, it breeds in clean water, not sewer or sink water. Now it is said that the mosquito bites at night too. It also breeds in relatively dirty water. What did you see in your research?

Aedes mosquitoes are highly adaptable. One must remember that dengue outbreak season is currently ongoing. This mosquito can make many behavioural changes to survive in such cases. As a result, it is not surprising that the mosquito changes its behaviour at such times and reproduces in relatively dirty water or bites at night. However, we do not have detailed research on this.

Q:

There are four types of dengue: Den-1, Den-2, Den-3 and Den-4. It is said this year Den-2 affected are the most in numbers. What are your observations? What is the main reason for death this year?

Den-2 and Den-3 prevalence has been high in the country for several years. We haven’t observed it as yet. But we have plans. The risk of death is usually higher if a person is exposed to another form of dengue a second time and has other serious physical complications or immune deficiency.

Q :

What is the percentage of Aedes among the mosquitos? Is dengue inevitable if Aedes bites?

There are around 3,500 mosquito species in the world and one fourth of them are Aedes. We have found 126 species of mosquitoes in Bangladesh. Among them there are 26 species of Aedes. But two of the species among them - Aedes Aegypti and Aedes Albopictus carry dengue virus and infect human beings. The density of Aedes mosquitoes depends on favourable conditions such as precipitation. The density of this mosquito does not remain the same throughout the year. By using BG Sentinel (a kind of trap) over the last three months we found 2-10 per cent aedes mosquitoes on a weekly basis during our small scale survey.

Dengue is not inevitable if Aedes mosquito bites. In our own laboratory the germ of dengue was found up to 80 per cent in the salivary gland of Aedes Aegypti. But normally in the natural environment this rate is much lower. For example, in India the infection rate was around 18 per cent, in Singapore seven and in Indonesia less than one per cent. The Aedes mosquito may uptake the blood of more than one person. So, the chances of one affected mosquito biting several persons remain.

Q :

Are mosquitoes becoming resistant to insecticides or larvicides? Is this happening because of long-term use of the same insecticide?

We have not yet got any evidence that proves Aedes mosquito becomes larvicide resistant. In our country generally the larvicides are used by targeting culex mosquito that means those living in drains, bushes or outside the house. The breeding geounds of Aedes mosquito are different from common breeding sites. As a result, though this larvicide is effective in case of Aedes it cannot play a big role. However, studies have shown that adult Aedes mosquitoes have become resistant to pyrethroid insecticides. Due to this, there was an outbreak of dengue in Dhaka in 2019. As per our advice, use of Malathion insecticides was then started and the dengue outbreak brought under control.

In recent studies, we have seen that Aedes has become resistant to many of the mosquito insecticides available in the form of spray bottles in the market. No single pesticide formulation should be used for long periods of time.

Q:

What effective measures may be taken to eradicate the Aedes mosquito?

An integrated approach should be adopted to control Aedes mosquitoes because a single approach can never control it. Aedes breeding sites should be destroyed or modified, larviciding and fogging should be strengthened, and people should be motivated to combat dengue. Indoor residual sprays, Bacillus Thuringiensis Israelensis (BTI -- a type of bacteria) and new pest control methods should be included. In cities, we mostly use larvicidal sprays and insecticide fogging to control adult mosquitoes. We know that Dhaka North City Corporation (DNCC) has brought in BTI, it is a good initiative. As dengue has spread across the country, integrated vector control management (IVM) plans should be developed and implemented for regular mosquito control.

Q :

Many discussions are rife about dengue vaccine. It is heard that already the trial of the dengue vaccine in the country is done or going to happen. Tell us something about that vaccine.

Only two dengue vaccines are being produced commercially. Dengvaxia is the only vaccine approved by the US Food and Drug Administration (FDA) for people who have had dengue and are 9 to 16 years old. Three doses of this vaccine should be given at 6-month intervals. Another vaccine is called Qdenga. This vaccine is given in two doses three months apart. It can also be given to those who have not been infected with dengue before. However, both vaccines have some limitations.

We have been researching a live attenuated tetravalent vaccine (TV-005). This vaccine is developed by the US National Institutes of Health (NIH). It protects against all four types of dengue. People of all ages can get this vaccine. We have completed Phase II trials of this vaccine. The process of publishing its results is underway. Another formulation of this vaccine, codenamed TV-003, is given in two doses 6 months apart. Phase III trial of TV-003 completed in Brazil. A phase III trial will soon begin in India as well. We are trying to start a phase III trial of this vaccine in the country. This vaccine will take several years to reach the market.

Q:

Is there any relation between the change of climate with the spread of Aedes or being affected by dengue?

Yes, the relationship exists. In our study from 2011-13, we found that air humidity is associated with an increase in the number of Aedes mosquitoes. As we saw last year, there was quite a lot of rain in September and October. It had many dengue patients from October to December. Its continuity is still maintained. Increased rainfall increases Aedes breeding grounds. Other studies have shown that adult mosquitoes bite more at higher temperatures. Warm temperatures increase the number (replication) of the dengue virus in the mosquito's body.

Q :

We have a close history of dengue with Kolkata, West Bengal, India. Dengue is under control there. Does this difference of experience in two geographically close areas occupy your mind as a researcher?

I think the main difference is the experience of the mosquito control authorities and the state of public awareness. Kolkata has a long history in the fight against dengue. Dengue was first recorded in Calcutta in 1824. Later there were several epidemics in 1836, 1906, 1911 and 1972. The last large-scale dengue outbreak in Kolkata was seen in 2005. Where we first saw large outbreaks in 2000 and later in 2019. However, the first documented case of dengue occurred in Dhaka in 1964.

Q :

Dengue has become a reality in tropical countries like ours. Many believe that it may increase in the future as well. So, what can we do to bring it to a tolerable level?

We need to adopt concerted strategic action. It can be divided into three parts. In the short term, all potential breeding sites of Aedes mosquitoes should be destroyed through combing operations involving the general public and normal mosquito control activities should be strengthened. Conduct regular pesticide resistance testing to determine effective pesticides and expedite necessary approvals for their use. Bottled spray insecticides available for general public use should be tested for efficacy to ensure availability. Because the flight range of Aedes aegypti is very short, only 100-200 meters. They usually bite and rest indoors.

In the medium term, the use of insect growth regulators (IGRs) such as pyriproxyfen and methoprene and microbial insecticides such as BTI should be considered as alternative larvicides. Surveys should be conducted throughout the year to determine the prevalence of mosquitoes.

In the long term, non-chemical Aedes control methods, which may be somewhat expensive (Rs. 50-100 crore) in the initial phase—such as Wolbachia-infected mosquitoes or sterile insect techniques (Sterile Insect Technique or SIT)—can be considered. Many dengue-prone countries including Australia, Indonesia, Malaysia, Singapore, Brazil have been successful by applying these methods. However, trials are needed to assess feasibility and potential impact before implementing such methods. We are doing some research on Wolbachia with a university in Australia. In the laboratory, Wolbachia was introduced into Bangladeshi Aedes mosquitoes and we got promising results.

Besides, the development of the dengue vaccine should be financed. So that later in the case of a production license the opportunity to get  cheap vaccines can be taken.

After the 2019 dengue outbreak, an initiative was taken to set up a separate directorate for mosquito control and research. Undoubtedly, the initiative is commendable. But that initiative was not implemented. It is important to have such effective institutions to control dengue and other mosquito-borne diseases.