Evolution of insecticide resistance and its mechanisms in Anopheles stephensi in the WHO Eastern Mediterranean Region

Abstract

Background: While Iran is on the path to eliminating malaria, the disease with 4.9 million estimated cases and 9300 estimated deaths in 2018 remains a serious health problem in the World Health Organization (WHO) Eastern Mediterranean Region. Anopheles stephensi is the main malaria vector in Iran and its range extends from Iraq to western China. Recently, the vector invaded new territories in Sri Lanka and countries in the Horn of Africa. Insecticide resistance in An. stephensi is a potential issue in controlling the spread of this vector. Methods: Data were collated from national and international databases, including PubMed, Google Scholar, Scopus, ScienceDirect, SID, and IranMedex using appropriate search terms. Results: Indoor residual spaying (IRS) with DDT was piloted in Iran in 1945 and subsequently used in the malaria eradication programme. Resistance to DDT in An. stephensi was detected in Iran, Iraq, Pakistan, and Saudi Arabia in the late 1960s. Malathion was used for malaria control in Iran in 1967, then propoxur in 1978, followed by pirimiphosmethyl from 1992 to 1994. The pyrethroid insecticide lambda-cyhalothrin was used from 1994 to 2003 followed by deltamethrin IRS and long-lasting insecticidal nets (LLINs). Some of these insecticides with the same sequence were used in other malaria-endemic countries of the region. Pyrethroid resistance was detected in An. stephensi in Afghanistan in 2010, in 2011 in India and in 2012 in Iran. The newly invaded population of An. stephensi in Ethiopia was resistant to insecticides of all four major insecticide classes. Different mechanisms of insecticide resistance, including metabolic and insecticide target site insensitivity, have been developed in An. stephensi. Resistance to DDT was initially glutathione S-transferase based. Target site knockdown resistance was later selected by pyrethroids. Esterases and altered acetylcholinesterase are the underlying cause of organophosphate resistance and cytochrome p450s were involved in pyrethroid metabolic resistance. Conclusions: Anopheles stephensi is a major malaria vector in Iran and many countries in the region and beyond. The species is leading in terms of development of insecticide resistance as well as developing a variety of resistance mechanisms. Knowledge of the evolution of insecticide resistance and their underlying mechanisms, in particular, are important to Iran, considering the final steps the country is taking towards malaria elimination, but also to other countries in the region for their battle against malaria. This systematic review may also be of value to countries and territories newly invaded by this species, especially in the Horn of Africa, where the malaria situation is already dire.

An update on the distribution, bionomics, and insecticide susceptibility of Anopheles stephensi in Ethiopia, 2018–2020

“…Widespread pyrethroid resistance in An. stephensi has been reported from Asia [ 19 ] and resistance has also been reported in Ethiopia [ 20 ]. However, to combat and control this invasive vector, a fuller understanding of insecticide resistance profiles is necessary.…”

“…pharoensis , indicating potential to cause increases in malaria in urban areas. As vector control measures are considered, high levels of resistance to many of the insecticides used on ITNs and for IRS may render these interventions less effective [ 19 ], and therefore alternative interventions, such as new types of nets (PBO and bi-treated), and larviciding, may need to be considered.…”

Gene drives gaining speed

“…Many naturally occurring desired traits result from allelic variants of essential genes. For example, resistance to insecticides 104 is often conferred by allelic variants of genes encoding proteins targeted by these chemicals such as ion channels 105 , 106 , neurotransmitter receptors 107 , 108 or enzymes modifying neurotransmitter activity 109 . The wild-type alleles of these genes thus confer susceptibility to standard vector-control measures.…”

Current Epidemiological Characteristics of Imported Malaria, Vector Control Status and Malaria Elimination Prospects in the Gulf Cooperation Council (GCC) Countries

“…These include widespread insecticide resistance in An. stephensi that is prevalent in the WHO Eastern Mediterranean Region, including countries bordering or in the near vicinity of GCC countries [ 97 ], and temperature-dependent expansion of the range of mosquito species into new geographic areas and their interaction with resident mosquito species (e.g., expansion of An. stephensi in the Middle East and North Africa where Ae.…”