The complexity of dengue pathogenesis has contributed to the difficulty in searching for dengue antivirals
The World Health Organisation (WHO) has acknowledged the growing prominence of dengue infections globally in the past decade. It estimates that 3.9 billion people are at risk, with 70 per cent of the actual burden in Asia.
In Malaysia, dengue is endemic and has a seasonal pattern of dengue fever outbreaks. To date, dengue control and surveillance remain the key dengue prevention strategies.
In conjunction with the ASEAN Dengue Day on June 15, the IMR- SEAMEO Webinar series featured a webinar presentation titled ‘Dengue in Malaysia: An Endemic Amidst Covid-19 Pandemic.’
Dr Nazni Wasi Ahmad from the Medical Entomology Unit at the Infectious Disease Research Centre moderated the webinar.
Dengue prevention study amidst the pandemic
Dr Nurulhusna Ab Hamid, research officer from the Medical Entomology Unit at Infectious Disease Research Centre, shared the experience of working with the randomised control trial for vector control during the pandemic.
“iDEM (Intervention for Dengue Epidemiology in Malaysia) is a collaborative project under the public-private partnership scheme, known as the Consortium of Public and Private Partner.”
The objective of iDEM, she shared, was to quantify the effectiveness of the proactive Integrated Vector Management (IVM) approach on the incidence of dengue in the Federal Territory of Kuala Lumpur and Putrajaya and to evaluate the effectiveness of the IVM approach on the population density of mosquitoes and insecticide resistance.
The iDEM project involved community engagement, vector control activities, entomological endpoints and epidemiological endpoints.
The vector control activities in iDEM used a combination of the Outdoor Residual Spray (ORS) technique, and Auto-dissemination (ADD) traps.
She noted challenges in conducting a controlled study, which required setting up traps at selected localities and regular visits for monitoring and data extraction during the pandemic.
“The trial began with community engagement back in December 2019, but it stopped in March 2020 due to the pandemic.”
There was a communication limitation between the Community Engagement Team with the building managers and the head of the community.
It also limited the engagement with the community in helping the team maintain the water in ADDs, which led to the ADDs being misused and mistreated as an illegal breeding site.
Added Dr Nurulhusna: “Up until June 2021, we have had three phases of Movement Control Order (MCO). There were travel restrictions and standard operating procedure (SOP) protocols.
“Although the vector control activities could continue, there was a delay in the process of obtaining approval for the teams. Also, due to a limitation of passengers in vehicles, the downsized units could not cover more than two localities in a day.
“Meanwhile, for entomological endpoint data collection, we used modified methods to collect indoor samples collection to avoid direct contact.
“There were times when some of us had to quarantine ourselves due to close contact with the community.
“Preliminary entomological endpoints were inconsistent, but we saw decreasing trends in certain parameters.”
Dr Nurulhusna shared the iDEM project was ongoing and in strict compliance with the SOPs. She noted the preliminary data presented might differ from the final result later on.
Dengue drug discovery
It has been solely focused on dengue patient management when it comes to treating dengue patients. Patients with severe dengue are closely monitored for fluid management.
There is no such specific drug to treat dengue patients. There is a dengue vaccine called Dengvaxia. However, the use of this vaccine is limited to those infected with the dengue virus.
Dr Mohd Ridzuan Mohd Abd Razak, a researcher from the Bioassay Unit at Herbal Medicine Research Centre, shared the dengue drug discovery process. He holds a PhD in Structural and Molecular Biology, and his recent research interest is on drug discovery for dengue.
According to Dr Mohd Ridzuan, understanding dengue pathogenesis is fundamental to find a correct and potent target to attack the dengue virus.
“The complexity of dengue pathogenesis has contributed to the difficulty in searching for dengue antivirals.”
The drug discovery process involves three stages: hit discovery, preclinical studies, and clinical trials.
He shared those reports showed that in the early stages, there were many hit discoveries. However, the numbers gradually reduced.
“There were many potential antiviral compounds reported at the early drug discovery stage. The number of reported hit discoveries of anti-dengue candidates drops after the evaluation and screening process.
“Therefore, a continuous effort in searching for new dengue drug treatment is the need to fill in the drug discovery pipeline for dengue,” he pointed out.
Based on dengue drugs in development and the clinical trial stage, Dr Mohd Ridzuan said: “Combination of antiviral and anti-inflammatory agents’ treatments might be a promising initiative in dengue drug discovery.” — The Health