Chemical control and insecticide resistance status of sand fly vectors worldwide

Abstract

Background: Phlebotomine sand flies are prominent vectors of Leishmania parasites that cause leishmaniasis, which comes second to malaria in terms of parasitic causative fatalities globally. In the absence of human vaccines, sand fly chemical-based vector control is a key component of leishmaniasis control efforts.

Methods and findings: We performed a literature review on the current interventions, primarily, insecticide-based used for sand fly control, as well as the global insecticide resistance (IR) status of the main sand fly vector species. Indoor insecticidal interventions, such as residual spraying and treated bed nets are the most widely deployed, while several alternative control strategies are also used in certain settings and/or are under evaluation. IR has been sporadically detected in sand flies in India and other regions, using non-standardized diagnostic bioassays. Molecular studies are limited to monitoring of known pyrethroid resistance mutations (kdr), which are present at high frequencies in certain regions.

Conclusions: As the leishmaniasis burden remains a major problem at a global scale, evidence-based rational use of insecticidal interventions is required to meet public health demands. Standardized bioassays and molecular markers are a prerequisite for this task, albeit are lagging behind. Experiences from other disease vectors underscore the need for the implementation of appropriate IR management (IRM) programs, in the framework of integrated vector management (IVM). The implementation of alternative strategies seems context- and case-specific, with key eco-epidemiological parameters yet to be investigated. New biotechnology-based control approaches might also come into play in the near future to further reinforce sand fly/leishmaniasis control efforts.

Fig 1. Global geographical distribution of IR bioassay reports in Lutzomyia and Phlebotomus sand fly vector species.

The global map focuses in regions with data coverage since 2000: (A) Latin America, (B) Mediterranean basin and north-central Africa, and (C) the Middle East and southeastern Asia. The sand fly species analyzed per region are (A) L. longipalpis, L. evansi, and L. peruensis, (B) mainly, P. papatasi, P. sergenti, and P. tobbi, and (C) mainly, P. papatasi, P. sergenti, and P. argentipes. Data correspond to WHO tube or CDC bottle bioassays in adult field-caught sand fly populations, against compounds of the 4 main insecticide classes. For WHO and CDC bioassay experiments using insecticide discriminating doses, the resistance status is determined by the mortality percentage (%) recorded 24 hours post-exposure (1 hour of exposure), as follows: ≥98% shows susceptibility (green), 90%–97% indicates the possibility of resistance (yellow), and <90% denotes resistance (red). Regarding the cases where (i) KD rates (%) at 1 hour of exposure are given; (ii) other than discriminating doses were tested; or (iii) dose–or time–response KD/mortality curves were provided, the susceptibility/resistance status is presented as defined by the respective authors. The symbol size varies depending on the number of insecticides of the same class tested against a specific population. In cases of differences in the population’s response against these insecticides, the less sensitive condition is presented. A detailed dataset for each bioassay experiment is provided in S1 Table. Maps were obtained from USGS (https://apps.nationalmap.gov/viewer/). DDT, dichloro-diphenyltrichloroethane; IR, insecticide resistance; USGS, US Geological Survey.

Fig 2. Global geographical distribution and respective allelic frequencies (%) of the kdr mutations at VGSC locus 1014 in sand fly populations.

Molecular analyses refer to (A) P. argentipes populations from India and Sri Lanka and (B) mixed Phlebotomus spp. populations from Greece and P. papatasi populations from Turkey. The size of the pie charts is proportional to the number of specimens genotyped per population. Red dots denote the sampling regions in the 4 countries. Genotyping data correlated with results of bioassay experiments are marked with a black circle. The allelic frequencies, the number of total specimens analyzed per population, and the species included are given in detail in S2 Table. Maps were obtained from USGS (https://apps.nationalmap.gov/viewer/). kdr, knockdown resistance; Leu, leucine (wild-type allele); Phe, phenylalanine (mutant allele); Ser, serine (mutant allele); USGS, US Geological Survey; VGSC, voltage-gated sodium channel.