The iDEM consortium project team with locality managers
Pinpointing New Approaches

Intervention for Dengue Epidemiology in Malaysia: iDEM consortium

The economic and public health effects of Aedes diseases such as dengue are enormous. But what if affected regions could move from treatment-focused programs to ones that are increasingly prevention-based? Scientists in Malaysia aim to find this out in a new program to pinpoint the best approach via targeted integrated vector management trials.

Danau Kota lake in Kuala Lumpur, Malaysia
Credit: Mitra Saadatian-Elahi, Bayer AG
The iDEM consortium met in Kuala Lumpur, which has a view over the Danau Kota lake in the city center. It is bodies of water like these, in warm and humid settings, which can be a breeding ground for disease vectors like mosquitoes.

 

The Economic and Public Health Burden of Dengue in Malaysia

Over the past decades, the global incidence of dengue has been on an upward trend due to various factors including urbanization, increased human mobility and trade, and climate change. This increasing dengue incidence has caused a tremendous economic burden on society worldwide.

In Malaysia, the high estimated economic toll imposed by dengue illness amounts to US 102 million dollars per year, or US 3.72 dollars per capita. This includes direct costs to the healthcare system (such as public and private hospital services) and indirect costs (such as productivity losses and premature deaths). Including the expenditures incurred by dengue surveillance, research and development, and vector control activities administered by the Ministry of Health and other local health agencies, costs are estimated to reach a substantial US 133 million dollars per year.

The iDEM consortium project team with locality managers
Credit: Mitra Saadatian-Elahi, Bayer AG

 

The project team alongside locality managers. The project will carry out IVM using a cluster (locality) randomized controlled trial design. 

 

Objectives and Timelines

The evidence base for vector control activities on dengue incidence is limited because the randomized controlled trials (RCT) published thus far were not designed to investigate epidemiological impact as the primary endpoint. Scientists aim to address this gap with this cluster RCT that will measure the effectiveness of Integrated Vector Management (IVM) on dengue incidence in urban settings in the Federal Territories of Kuala Lumpur and Putrajaya in Malaysia. The intervention will consist of targeted outdoor residual spraying cycles with K-othrine polyzone every four months, deployment of autodissemination traps, and public engagement activities. The planned start date is the third quarter of 2019, and the trial is expected to be accomplished by June 2022. Epidemiological and entomological data will be collected at baseline, before the introduction of IVM and during the two years of IVM deployment.

 

Rational for Integrated Vector Management

WHO defines IVM as a “rational decision-making process for the optimal use of resources for vector control.” In the face of the current challenges to vector control, in particular resistance to insecticides, IVM is vital. Vector control cannot rely on a single solution; there is no silver bullet. For sustainable impact, vector control needs to span and integrate multiple sectors and disciplines, linking efforts in environmental management, health education, governance, and vector control interventions in order to control new and emerging threats.

The Ministry of Health of Malaysia routinely practices IVM using combinations of source reduction, providing education about dengue, larviciding, space spraying, ecosystem or environmental management. The current project will complement and enhance this approach by looking at a more proactive, preventive IVM program with innovations in both application and control. The program will use both chemicals and biologicals with different modes of action, targeting various mosquito life-cycle stages in conjunction with community participation and education.

Water reservoir on a roof in Kuala Lumpur, Malaysia
Credit: Mitra Saadatian-Elahi, Bayer AG

 

Dr. Jason Richardson inspecting water reservoirs on a roof in Kuala Lumpur. Individual sites such as these are receiving attention in this trial. 

 

Why Cluster Randomized Controlled Trial?

In this trial, the unit to be randomized, i.e. the cluster, will be locality, which is usually a development of several neighboring buildings with individuals sharing the same facilities such as parking lots and food courts. Clusters will be randomly allocated to receive the modified IVM interventions (treatment localities) or the usual IVM interventions (control localities) carried out by the Ministry of Health and Municipality staff.

The first reason for this cluster design is to facilitate the implementation by the public health team. The interventions have been designed to be applied at the level of a building or locality and not at the level of an individual person, or even a single housing unit (apartment). The second reason is that we expect the interventions to have a mass beneficial effect; For example, the impact on mosquitoes in one spot in a building will be affected by the interventions that are taking place elsewhere in the same corridor, or even on different floors of the same building. Randomizing localities will allow measurement of the effects of the interventions including such a mass effort.

 

Epidemiological Investigation: e-Dengue

Dengue incidence in Malaysia is controlled under the national surveillance notification systems mandated by the Prevention and Control of Infectious Diseases Act 1988 and overseen by the Ministry of Health. The e-Dengue database is the formal reporting or notification system for further management of cases, epidemic, vector control, and statistics reporting. Once the clinical criteria of dengue patients are confirmed by the laboratory, the information must be entered into the e-Dengue database.

Following case notifications, further investigations by trained environmental health officers are conducted. The reported cases will be reviewed at state and national level for epidemic management protocols. The areas where cases are registered will be managed for 14 days under the protocols to conduct vector control activities. The epidemiological impact data for this trial will be extracted from the Ministry of Health’s e-Dengue surveillance system.

Bayer research team in front of the Batu Caves, Kuala Lumpur
Credit: Mitra Saadatian-Elahi, Bayer AG

 

A battle for public health: the research team in Kuala Lumpur at the Batu Caves. Fittingly, they stand in front of a statue of Kartikeya, the Hindu god of war. 

 

Entomological Monitoring

In Malaysia, Aedes aegypti and Aedes albopictus are respectively the primary and the secondary vectors for dengue transmission. Active entomological surveillance in the country is routinely performed by health workers to reduce the risk of human exposure to dengue viruses and to assess the impact of the intervention on vector densities. The main monitoring device for our trial will be ovitraps placed outdoors (near bushes and small plants) and semi-indoors (along corridors, such as near shoe racks and flower pots). The ovitrap index is defined as the proportion of ovitraps where we find that adult female mosquitoes have laid their eggs. This will be estimated over the baseline and intervention period. Surveys of adult and larval mosquitoes will also be carried out.

One of the most persistent challenges in vector control management is insecticide resistance. We will test the level of mosquito resistance to the insecticides used in the study area before and during the trial.

 

Biostatistics

The main objective of the trial is to quantify the effect of the modified IVM on the incidence rate of dengue infection in comparison to conventional IVM. The expected effect is a one-third reduction on the incidence rate. If this assumption holds, then we have enough localities to give a 90 percent probability of establishing the effectiveness of the interventions.

At the end of the two years of follow-up, the incidence rate will be estimated and compared between the localities having received the modified IVM interventions (treatment arm) and those having received the conventional IVM (control arm), taking into account the variation in incidence between localities.

The entomological effect of the interventions will also be quantified by comparing the ovitrap and larval indices between a subset of the treatment and control localities.

 

Expected Scientific Impact

We believe that co-application of several vector control techniques together with community engagement would further enhance the vector control efficacy to ensure favorable outcomes, such as the decrease of the incidence of Aedes-borne diseases, and in particular, dengue. Furthermore, the project will offer a better understanding of proactive IVM in the control of dengue and can provide more information on the relationship between the epidemiological and entomological endpoints. The results of this trial will help shift the conception of policies to handle Aedes-borne diseases from treatment to prevention, thus saving public funding, increasing impact, and ultimately benefitting public health.

 

Project Authors:

Professor Neal Alexander, Dr. Nurulhusna Ab Hamid, Frederic Baur, Dr. Rahmat Dapari, Dr. Rose Nani Mudin, Dr. Jason H Richardson, Dr. Muriel Rabilloud, Dr. Mitra Saadatian-Elahi, Dr. Frederic Schmitt, Dr. Remco Suer, Dr. Nazni Wasi Ahmad.


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