Report on insecticide resistance in Aedes mosquitoes (Aedes aegypti, Ae. albopictus, Ae. vittatus) in WHO South-East Asia Region countries

Overview

The WHO South-East (SE) Asia Region comprises 11 countries, namely Bangladesh, Bhutan, the Democratic People’s Republic of Korea (DPR Korea), India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand and Timor-Leste.

Globally, 3.5 billion people are at risk of contracting dengue fever and 1.3 billion live in dengue-endemic areas in 10 countries, except in DPR Korea. Four serotypes, DENV 1, 2, 3, 4, are reported. Ae. aegypti is reportedly the predominant vector species responsible for transmission of dengue. In the absence of effective vaccines and drugs, vector control is the only strategy for disease control. Continued use of insecticides results in the development of resistance though. Biochemical and molecular studies have provided information on resistance mechanisms.

This report was developed on the basis of a thorough literature review and included general information on insecticides, insecticide resistance and mechanism of resistance and standard test procedures. The search for literature was carried out on PubMed, Google, Google Scholar and Sci-Hub databases, using such search terms as “SE Asia”, “country”, “Aedes”, “Aedes aegypti”, “Aedes albopictus”, “Aedes vittatus”, “insecticide susceptible”, “insecticide resistance”, “pyrethroid resistance” and “organophosphate resistance”. We retrieved more than 300 articles and 121 of them were used for preparing this report that provides information from various studies with a brief on the method and interpretation. Relevant data were tabulated and presented on respective country maps.

The insecticide resistance data from the 11 countries were asymmetric both within the country and between the countries. Data from Bhutan, DPR Korea, Maldives, Myanmar and Nepal were very limited and did not match the epidemiological situation evidenced in the countries to suggest effective disease abatement vector control strategies, which, presently, are mostly reliant on synthetic chemical insecticides. Data from the remaining countries seem to be better quantum-wise, but not longitudinal in nature to help understand the trends of disease transmission for planning suitable vector control methods. Thus, in spite of the continued use of vector control interventions in different countries, the transmission remained unabated and fluctuated between different parts of the country.

Although standard vector control interventions are suggested by WHO, the countries adopted different interventions. The insecticide resistance data was generated using different methods – both standard WHO methods and non-standard methods – deploying varied dosage of insecticides. This led to inaccurate estimates and trends. Many countries of the Region had data on biochemical enzymes and knockdown resistance (kdr) mutations that confer resistance mechanisms but were from a handful of regions. Most of the data on insecticide resistance were from a few scientific studies, and not from the respective public health agencies, unlike other vector-borne diseases (VBDs).

The way forward is as follows:

There is a need for conducting longitudinal studies across the country to assess trends of resistance, using standard WHO methods, and to prescribed dosages of insecticides and alternative methods for detection of resistance.

• Emphasis should be on determining the mechanism of insecticide resistance in countries where data is scanty and other countries that have reasonable facilities should conduct longitudinal phenotypic studies, followed by mechanistic studies.
• Countries should conduct studies for determining biochemical and molecular markers that confer insecticide resistance using which suitable vector control strategies can be designed in conjunction with the phenotypic resistance data in the vectors for control and resistance management.
• Insecticide resistance database repositories need to be established for the countries of the Region. Data need to reach the respective decision-making agencies of the countries and consultations should be held between contiguous countries, especially with common borders, for concerted efforts towards control and elimination of the diseases.
• Use of insecticides with a novel mode of action should be introduced for vector control for insecticide resistance management. Use of non-chemical methods will be advantageous and studies need to be conducted on the effectiveness of such methods.

Salient observations on insecticide resistance in vectors in the countries concerned are summarized below.

Bangladesh

Dengue was first reported in 1964 with intermittent transmission in later years. Ae. aegypti was resistant to permethrin but not to deltamethrin. Increased enzyme levels of esterases, mixed-function oxidases (MFOs) and kdr mutations, V1016G and F1534C, were reported. Data limited only to urban areas prompts a need for extensive studies in all regions.

Bhutan

The first outbreak of dengue was reported in 2004 with more than 2500 cases. Deltamethrin space spray has been the vector control intervention since then. Information on insecticide resistance is scarce. A single study reported Ae. aegypti, resistant to deltamethrin, cyfluthrin and propoxur, and kdr mutation, V1016G. There is a need for extensive studies on insecticide resistance in the vectors for effective vector and disease control.

DPR Korea

Dengue is not reported. Ae. albopictus was the reported vector of dengue but data on insecticide resistance is needed. Deltamethrin is the only insecticide approved for public health sprays. There is a need for generation of data on different aspects of insecticide resistance.

India

The first epidemic of clinical dengue-like illness was recorded in Madras (now Chennai). Most of the studies (~30) were on phenotypic resistance but sparse. Both Ae. aegypti and Ae. albopictus were reported to be resistant to DDT, Ae. aegypti to malathion, deltamethrin and permethrin. Both species were variable susceptible to temephos. kdr mutations, V1016G and F1534C, were detected in some states, but could not be correlated to phenotypic resistance to pyrethroids. F1534C was correlated to DDT resistance in some studies. Concerted studies on insecticide resistance are needed routinely along with mechanistic studies.

Indonesia

The first outbreak of dengue was recorded in 1968–1970 in Jakarta, Indonesia. Organophosphates were introduced in the 1970s and pyrethroids in the 1980s. Ae. aegypti as found to be resistant to multiple insecticides. In biochemical enzyme assays, esterases, monooxygenases and acetylcholinesterase (AChE) reportedly conferred resistance to temephos. kdr mutations, V1016G and F1534C, were identified in some provinces and showed a strong association with pyrethroid resistance in Ae. aegypti.

Maldives

The first outbreak of dengue was reported in 1979 and more cases were found in subsequent years. A major vector control method in implementation involves environmental management and includes larvicides and space spraying. However, there is an urgent need for structured vector surveillance and insecticide resistance studies for effective vector and disease management. Information on vector prevalence and insecticide susceptibility is lacking; it is needed to formulate effective vector control strategies.

Myanmar

During the five-year period of 2010–2015, a total of 89 832 cases and 393 deaths were reported. Chemical larviciding, adulticidal and biological control and environmental management were the vector control methods being employed. Simplified larval bioassay, using d-T80 allethrin, reported Ae. aegypti resistance to pyrethroids. kdr mutations, V1016G, F1534C and S982P, were detected that correlated with phenotypic resistance. There is a need for extensive surveys for detection of insecticide resistance in vectors, following standard methods, in order to suggest vector control strategies for disease containment in the country.

Nepal

The first case of dengue was reported in 2004 followed by outbreaks in 2010, 2013, 2016 and 2018. The largest outbreak so far, with >10 000 cases, was reported in 2019. Deltamethrin space spray and chemical and bacterial larvicides are suggested for vector management and are in use. Simplified larval bioassay, using d-T80 allethrin with Ae. aegypti, showed variable susceptibility, correlated with kdr mutation V1016G but not with F1534C. There is a need for extensive surveys for detection of insecticide resistance in vectors, following standard methods, to suggest vector control strategies for disease containment in this epidemic-prone country.

Sri Lanka

Dengue was confirmed serologically in 1962, followed by outbreaks of dengue and chikungunya in 1965. Outbreaks of DENV serotypes 1, 2 and 3 continued. Temephos larviciding and malathion and pyrethroid/pyrerthroid + synergist space spraying are the major interventions for vector control. Routine insecticide resistance surveillance is needed in different geographies.

Thailand

The first case of dengue was reported in 1949. Larvicide temephos and ULV spraying, including household insecticides, are in use. Aedes in Thailand was reported to be resistant to DDT with varied susceptibility to other insecticides. High enzyme activities of monooxygenases, GST and esterases in Ae. aegypti in urban areas were more due to increased selection by insecticides owing to the compactness of households, when compared to outdoor prevalent Ae. albopictus. Mutations V1016G and F1534C, attributed to pyrethroid resistance, including double mutations, were identified. There is a need for continued and routine studies in different provinces to formulate appropriate vector control strategies for vector and disease management.

Timor-Leste

Dengue was first reported in 2003, followed by an outbreak in 2005. Studies in 2016 reported Ae. aegypti to be resistant to pyrethroids, permethrin, resmethrin and lambdacyhalothrin but susceptible to bio-resmethrin and deltamethrin and the organophosphate, malathion. Biochemical enzymes MFOs and GST that confer resistance did not show a significant increase while esterases have shown significant increases in field populations. Information is very scant and the results available so far are from a single study. Extensive studies are needed in different geographies of the country to generate data for formulating effective vector control strategies in this country.