Відділення інформатики Національної академії наук України

Item does not contain fulltext8 p

Could species-focused suppression of Aedes aegypti, the yellow fever mosquito, and Aedes albopictus, the tiger mosquito, affect interacting predators? An evidence synthesis from the literature

The risks of Aedes aegypti and Aedes albopictus nuisance and vector-borne diseases are rising and the adverse effects of broad-spectrum insecticide application have promoted species-specific techniques, such as sterile insect technique (SIT) and other genetic strategies, as contenders in their control operations. When specific vector suppression is proposed, potential effects on predators and wider ecosystem are some of the first stakeholder questions. These are not the only Aedes vectors of human diseases, but are those for which SIT and genetic strategies are of most interest. They vary ecologically and in habitat origin, but both have behaviorally human-adapted forms with expanding ranges. The aquatic life stages are where predation is strongest due to greater resource predictability and limited escape opportunity. These vectors' anthropic forms usually use ephemeral water bodies and man-made containers as larval habitats; predators that occur in these are mobile, opportunistic and generalist. No literature indicates that any predator depends on larvae of either species. As adults, foraging theory predicts these mosquitoes are of low profitability to predators. Energy expended hunting and consuming will mostly outweigh their energetic benefit. Moreover, as adult biomass is mobile and largely disaggregated, any predator is likely to be a generalist and opportunist. This work, which summarizes much of the literature currently available on the predators of Ae. aegypti and Ae. albopictus, indicates it is highly unlikely that any predator species depends on them. Species-specific vector control to reduce nuisance and disease is thus likely to be of negligible or limited impact on nontarget predators. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Natural plant diet impacts phenotypic expression of pyrethroid resistance in Anopheles mosquitoes

Success in reducing malaria transmission through vector control is threatened by insecticide resistance in mosquitoes. Although the proximal molecular mechanisms and genetic determinants involved are well documented, little is known about the influence of the environment on mosquito resistance to insecticides. The aim of this study was to assess the effect of plant sugar feeding on the response of Anopheles gambiae sensu lato to insecticides. Adults were fed with one of four treatments, namely a 5% glucose control solution, nectariferous flowers of Barleria lupulina, of Cascabela thevetia and a combination of both B. lupulina+C. thevetia. WHO tube tests were performed with 0.05% and 0.5% deltamethrin, and knockdown rate (KD) and the 24 h mosquito mortality were measured. Plant diet significantly influenced mosquito KD rate at both concentrations of deltamethrin. Following exposure to 0.05% deltamethrin, the B. lupulina diet induced a 2.5 fold-increase in mosquito mortality compared to 5% glucose. Species molecular identification confirmed the predominance of An. gambiae (60% of the samples) over An. coluzzii and An. arabiensis in our study area. The kdr mutation L1014F displayed an allelic frequency of 0.75 and was positively associated with increased phenotypic resistance to deltamethrin. Plant diet, particularly B. lupulina, increased the susceptibility of mosquitoes to insecticides. The finding that B. lupulina-fed control individuals (i.e. not exposed to deltamethrin) also displayed increased 24 h mortality suggests that plant-mediated effects may be driven by a direct effect of plant diet on mosquito survival rather than indirect effects through interference with insecticide-resistance mechanisms. Thus, some plant species may weaken mosquitoes, making them less vigorous and more vulnerable to the insecticide. There is a need for further investigation, using a wider range of plant species and insecticides, in combination with other relevant environmental factors, to better understand the expression and evolution of insecticide resistance

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

Identification of malaria transmission and epidemic hotspots in the western Kenya highlands: its application to malaria epidemic prediction

<p>Abstract</p> <p>Background</p> <p>Malaria in the western Kenya highlands is characterized by unstable and high transmission variability which results in epidemics during periods of suitable climatic conditions. The sensitivity of a site to malaria epidemics depends on the level of immunity of the human population. This study examined how terrain in the highlands affects exposure and sensitivity of a site to malaria.</p> <p>Methods</p> <p>The study was conducted in five sites in the western Kenya highlands, two U-shaped valleys (Iguhu, Emutete), two V-shaped valleys (Marani, Fort-Ternan) and one plateau (Shikondi) for 16 months among 6-15 years old children. Exposure to malaria was tested using circum-sporozoite protein (CSP) and merozoite surface protein (MSP) immunochromatographic antibody tests; malaria infections were tested by microscopic examination of thick and thin smears, the children's homes were georeferenced using a global positioning system. Paired t-test was used to compare the mean prevalence rates of the sites, K-function was use to determine if the clustering of malaria infections was significant.</p> <p>Results and Discussion</p> <p>The mean antibody prevalence was 22.6% in Iguhu, 24% in Emutete, 11.5% in Shikondi, 8.3% in Fort-Ternan and 9.3% in Marani. The mean malaria infection prevalence was 23.3% in Iguhu, 21.9% in Emutete, 4.7% in Shikondi, 2.9% in Fort-Ternan and 2.4% in Marani. There was a significant difference in the antibodies and malaria infection prevalence between the two valley systems, and between the two valley systems and the plateau (P < 0.05). There was no significant difference in the antibodies and malaria infection prevalence in the two U-shaped valleys (Iguhu and Emutete) and in the V-shaped valleys (Marani and Fort Ternan) (P > 0.05). There was 8.5- fold and a 2-fold greater parasite and antibody prevalence respectively, in the U-shaped compared to the V-shaped valleys. The plateau antibody and parasite prevalence was similar to that of the V-shaped valleys. There was clustering of malaria antibodies and infections around flat areas in the U-shaped valleys, the infections were randomly distributed in the V-shaped valleys and less clustered at the plateau.</p> <p>Conclusion</p> <p>This study showed that the V-shaped ecosystems have very low malaria prevalence and few individuals with an immune response to two major malaria antigens and they can be considered as epidemic hotspots. These populations are at higher risk of severe forms of malaria during hyper-transmission seasons. The plateau ecosystem has a similar infection and immune response to the V-shaped ecosystems. The U-shaped ecosystems are transmission hotspots.</p

Plant-mediated effects on mosquito capacity to transmit human malaria

The ecological context in which mosquitoes and malaria parasites interact has received little attention, compared to the genetic and molecular aspects of malaria transmission. Plant nectar and fruits are important for the nutritional ecology of malaria vectors, but how the natural diversity of plant-derived sugar sources affects mosquito competence for malaria parasites is unclear. To test this, we infected Anopheles coluzzi, an important African malaria vector, with sympatric field isolates of Plasmodium falciparum, using direct membrane feeding assays. Through a series of experiments, we then examined the effects of sugar meals from Thevetia neriifolia and Barleria lupilina cuttings that included flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and mosquito traits that are key for determining the intensity of malaria transmission. We found that the source of plant sugar meal differentially affected infection prevalence and intensity, the development duration of the parasites, as well as the survival and fecundity of the vector. These effects are likely the result of complex interactions between toxic secondary metabolites and the nutritional quality of the plant sugar source, as well as of host resource availability and parasite growth. Using an epidemiological model, we show that plant sugar source can be a significant driver of malaria transmission dynamics, with some plant species exhibiting either transmission-reducing or -enhancing activities

Identification of Spiroplasma insolitum symbionts in Anopheles gambiae

Background: Insect symbionts have the potential to block the transmission of vector-borne diseases by their hosts. The advancement of a symbiont-based transmission blocking strategy for malaria requires the identification and study of Anopheles symbionts. Methods: High throughput 16S amplicon sequencing was used to profile the bacteria associated with Anopheles gambiae sensu lato and identify potential symbionts. The polymerase chain reaction (PCR) with specific primers were subsequently used to monitor symbiont prevalence in field populations, as well as symbiont transmission patterns. Results: We report the discovery of the bacterial symbiont, Spiroplasma, in Anopheles gambiae in Kenya. We determine that geographically dispersed Anopheles gambiae populations in Kenya are infected with Spiroplasma at low prevalence levels. Molecular phylogenetics indicates that this Anopheles gambiae associated Spiroplasma is a member of the insolitum clade. We demonstrate that this symbiont is stably maternally transmitted across at least two generations and does not significantly affect the fecundity or egg to adult survival of its host. Conclusions: In diverse insect species, Spiroplasma has been found to render their host resistant to infection by pathogens. The identification of a maternally transmitted strain of Spiroplasma in Anopheles gambiae may therefore open new lines of investigation for the development of symbiont-based strategies for blocking malaria transmission

Polymorphisms in Anopheles gambiae Immune Genes Associated with Natural Resistance to Plasmodium falciparum

Many genes involved in the immune response of Anopheles gambiae, the main malaria vector in Africa, have been identified, but whether naturally occurring polymorphisms in these genes underlie variation in resistance to the human malaria parasite, Plasmodium falciparum, is currently unknown. Here we carried out a candidate gene association study to identify single nucleotide polymorphisms (SNPs) associated with natural resistance to P. falciparum. A. gambiae M form mosquitoes from Cameroon were experimentally challenged with three local wild P. falciparum isolates. Statistical associations were assessed between 157 SNPs selected from a set of 67 A. gambiae immune-related genes and the level of infection. Isolate-specific associations were accounted for by including the effect of the isolate in the analysis. Five SNPs were significantly associated to the infection phenotype, located within or upstream of AgMDL1, CEC1, Sp PPO activate, Sp SNAKElike, and TOLL6. Low overall and local linkage disequilibrium indicated high specificity in the loci found. Association between infection phenotype and two SNPs was isolate-specific, providing the first evidence of vector genotype by parasite isolate interactions at the molecular level. Four SNPs were associated to either oocyst presence or load, indicating that the genetic basis of infection prevalence and intensity may differ. The validity of the approach was verified by confirming the functional role of Sp SNAKElike in gene silencing assays. These results strongly support the role of genetic variation within or near these five A. gambiae immune genes, in concert with other genes, in natural resistance to P. falciparum. They emphasize the need to distinguish between infection prevalence and intensity and to account for the genetic specificity of vector-parasite interactions in dissecting the genetic basis of Anopheles resistance to human malaria

Submicroscopic Gametocytes and the Transmission of Antifolate-Resistant Plasmodium falciparum in Western Kenya

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. METHODOLOGY/PRINCIPAL FINDINGS: Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. CONCLUSIONS/SIGNIFICANCE: In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites