Primrose Tanachaiwiwat

Haiti is a Caribbean country of about 11 million people with a high burden of mosquito-transmitted disease and limited vector control, thereby making effective operational mosquito control of high importance. Previous studies have examined vector-borne disease burden and insecticide resistance markers in Haitian Aedes and Anopheles mosquitoes, but not Culex species. In this study, we examined collections of Culex quinquefasciatus from 12 locations in northern and southern Haiti for the presence of markers of insecticide resistance (using a variety of target-site mutations and biochemical assays) and pathogens (using a deep-sequencing microbiome workflow). The metagenomic analysis identified Wolbachia, Rhabdoviridae, and Plasmodium infections in all sample pools at relatively high levels, along with less frequent detections of other potential pathogens. Insecticide resistance marker examination identified variable frequencies of knockdown resistance and acetylcholinesterase resistance mutations, as well as variation in resistance-associated enzymatic activities in these populations. These findings indicate that insecticide resistance to pyrethroid and organophosphate insecticides is likely. Although there was variation among Culex mosquito populations and no clear activity pattern, enzymatic activity was significantly higher at the southern sites than at the northern sites. Similar findings in Cx. quinquefasciatus populations in other locations in the Americas strongly suggest that vector control with pyrethroid and organophosphate adulticides may be of limited efficacy.

Haiti is a Caribbean country of about 11 million people with a high burden of mosquito-transmitted disease and limited vector control, thereby making effective operational mosquito control of high import. Previous studies have examined vector-borne disease burden and insecticide resistance markers in Haitian Aedes and Anopheles mosquitoes but not Culex species. In this study, we examined collections of Culex quinquefasciatus from 12 locations in northern and southern Haiti for the presence of markers of insecticide resistance (using a variety of target site mutations and biochemical assays) and pathogens (using a deep sequencing microbiome workflow). The metagenome analysis identified Wolbachia, Rhabdoviridae and Plasmodium infection in all sample pools at relatively high levels along with less frequent findings of other potential pathogens. Resistance marker examination identified variable frequencies of knockdown resistance and acetylcholinesterase resistance mutations, as well as variation in resistance-associated enzymatic activities in these populations, which indicate that insecticide resistance to the primary pyrethroid and organophosphate insecticides is likely. Though there was variation between Culex mosquito populations and no clear activity pattern, enzymatic activity was significantly higher in the southern sites compared to the northern sites. Similar findings in Cx. quinquefasciatus populations in other locations in the Americas strongly suggest that vector control with pyrethroid and organophosphate adulticides may be of limited efficacy.

Adeno-associated viral vectors (AAV) are the leading gene therapy in the clinic. AAV9 has been of particular interest due to its wide tropism for multiple tissue types as well as being able to cross the blood-brain barrier and transduce central nervous system tissues. However, effectively and safely targeting extrahepatic tissue following the systemic administration of AAV9 remains a challenge due to high rates of liver transduction and liver toxicity. Thus, a crucial first step in developing a safe AAV9-based vector is to reduce liver targeting. Here we utilized rational design techniques to make five point mutations in the AAV9 capsid. In doing so, we developed a novel AAV9 variant, AAV9-DM, that is characterized by reduced liver tropism as compared to AAV9 and other liver de-targeted AAV9 mutants. We show that AAV9-DM is effective at transducing cells in vivo, resulting in robust transgene expression over a 9-week period. Importantly, the AAV9-DM capsid maintains the ability to transduce non-hepatic tissues with a biodistribution similar to AAV9. This new mutant represents a novel AAV capsid that may be the basis for developing safer therapeutics to target extrahepatic tissue while reducing adverse side effects related to liver transduction.

With ongoing global efforts to eliminate malaria, several countries have entered a pre-elimination stage, in which populations of the primary mosquito vector are reduced and the rates of malaria transmission are low. Efforts to eliminate malaria have changed the dynamics of disease transmission, causing a shift in anopheline community composition in some regions. One of the most abundant species of Anopheles found in pre-elimination areas, such as southern Africa, is Anopheles squamosus (Theobald, 1901; Diptera: Culicidae). Although An. squamosus has been documented across the African continent, limited information is available about its biology. Knowing what, when, and where the malaria vector bites humans can help develop effective malaria control strategies. The aim of this review is to compile the information available on An. squamosus’s biology, ecology, distribution, behavior, and potential role in disease transmission. The review of current literature suggested that An. squamosus is abundant throughout the African continent. Studies indicate that this species occupies the same range and exhibits similar behaviors to primary malaria vectors in southern and eastern African countries, like Zambia. In conclusion, An. squamosus continues to be an understudied species that has circumvented disease control measures and further studies are needed to develop effective control strategies.

With ongoing global efforts to eliminate malaria, many countries have entered a pre-elimination stage, in which populations of the primary mosquito vector are reduced and the rates of malaria transmission are low. Efforts to eliminate malaria have changed the dynamics of disease trans-mission, causing a shift in anopheline community composition in some regions. One of the most abundant species of Anopheles found in pre-elimination areas, such as southern Africa, is Anopheles squamosus. Though An. squamosus has been documented across the African continent, limited in-formation is available about their biology. The aim of this review is to compile the information available for An. squamosus biology, ecology, distribution, behavior, and potential role in disease transmission. The review of current literature suggested that An. squamosus is abundant throughout the African continent. Studies indicate that this species occupies the same range and exhibits similar behaviors to primary malaria vectors in southern and eastern African countries like Zambia. Anopheles squamosus continues to be an understudied species that has circumvented disease control measures. Further studies are needed to develop resources to accurately identify this species from morphologically cryptic, closely related species and to effectively assess its role in malaria parasite transmission.