bims-mosdis Biomed News
on Mosquito distribution and disease
Issue of 2021–12–19
25 papers selected by
Richard Halfpenny, Staffordshire University



  1. Acta Trop. 2021 Dec 08. pii: S0001-706X(21)00447-2. [Epub ahead of print] 106269
      Monte Verde, a peri-urban squatter community near San Pedro Sula virtually eliminated Aedes aegypti production in all known larval habitats: water storage containers (concrete tanks used for water storage and laundry, drums, cisterns, buckets), wells, and objects collecting rainwater. The project began in 2016 when Monte Verde was overrun with dengue, Zika, and chikungunya. During more than a year of experimentation, Monte Verde residents crafted an effective, sustainable, and environmentally friendly toolkit that was inexpensive but required full community participation. Biological control with copepods, turtles, and tilapia was at the core of the toolkit, along with a mix of other methods such as getting rid of unnecessary containers, scrubbing them to remove Ae. aegypti eggs, and covering them to exclude mosquitoes or rainwater. Environmentally friendly larvicides also had a limited but crucial role. Key design features: (1) toolkit components known to be virtually 100% effective at preventing Ae.aegypti production when used properly in appropriate larval habitats; (2) using Ae. aegypti larval habitats as a resource by transforming them into "egg sinks" to drive Ae. aegypti population decline; (3) dedicated community volunteers who worked with their neighbors, targeting 100% coverage of all known Ae. aegypti larval habitat with an appropriate control method; (4) monthly monitoring in which the volunteers visited every house to assess progress and improve coverage as an ongoing learning experience for both volunteers and residents. From September 2018 to the end of the record in October 2021 (except for a brief lapse during COVID lockdown in 2020), the total number of Ae.aegypti larvae each month in approximately 2000 monitored containers fluctuated between 0.1% and 2.4% of the 57,148 larvae in the baseline survey at the beginning of the project. Taking pupae as an indicator of Ae.aegypti production, the only pupae seen in Monte Verde after August 2018 were in the concrete water storage tanks, the monthly count fluctuating between zero and 0.6% of the 22,984 pupae counted in Monte Verde at the baseline survey. Ae. aegypti adults declined to low numbers but did not disappear completely. There were no recognizable cases of dengue, Zika, or chikungunya after June 2018, though the study design did not provide a basis for concluding whether Monte Verde's Ae. aegypti control program was responsible. Ingredients for success were outside stimulation and facilitation to foster shared community awareness and commitment regarding the problem and its solution, enduring commitment of local leadership, compatibility of the toolkit with the local community, social and ecological diversity, overcoming social obstacles, powerful symbols, rapid results with "success breeding success," and building resilience. Severe external disturbances during the project offered an opportunity to learn how mosquito production responded to strains on monthly monitoring. Monte Verde can serve as a model for extending this approach to other communities. Community management of Aedes aegypti larval habitats reduced the number of pupae (reflecting all known adult Aedes aegypti production) virtually to zero.
    Keywords:  Aedes aegypti; Zika; biological control; chikungunya; community participation; copepods; dengue fever; tilapia; turtles
    DOI:  https://doi.org/10.1016/j.actatropica.2021.106269
  2. BMC Genomics. 2021 Dec 14. 22(1): 894
       BACKGROUND: Wolbachia wMel is the most commonly used strain in rear and release strategies for Aedes aegypti mosquitoes that aim to inhibit the transmission of arboviruses such as dengue, Zika, Chikungunya and yellow fever. However, the long-term establishment of wMel in natural Ae. aegypti populations raises concerns that interactions between Wolbachia wMel and Ae. aegypti may lead to changes in the host genome, which could affect useful attributes of Wolbachia that allow it to invade and suppress disease transmission.
    RESULTS: We applied an evolve-and-resequence approach to study genome-wide genetic changes in Ae. aegypti from the Cairns region, Australia, where Wolbachia wMel was first introduced more than 10 years ago. Mosquito samples were collected at three different time points in Gordonvale, Australia, covering the phase before (2010) and after (2013 and 2018) Wolbachia releases. An additional three locations where Wolbachia replacement happened at different times across the last decade were also sampled in 2018. We found that the genomes of mosquito populations mostly remained stable after Wolbachia release, with population differences tending to reflect the geographic location of the populations rather than Wolbachia infection status. However, outlier analysis suggests that Wolbachia may have had an influence on some genes related to immune response, development, recognition and behavior.
    CONCLUSIONS: Ae. aegypti populations remained geographically distinct after Wolbachia wMel releases in North Australia despite their Wolbachia infection status. At some specific genomic loci, we found signs of selection associated with Wolbachia, suggesting potential evolutionary impacts can happen in the future and further monitoring is warranted.
    Keywords:  Aedes aegypti; Evolve-and-resequence; Genome-wide association study; Population replacement; Wolbachia
    DOI:  https://doi.org/10.1186/s12864-021-08200-1
  3. Malar J. 2021 Dec 13. 20(1): 461
       BACKGROUND: Molecular diagnostic tools have been incorporated in insecticide resistance monitoring programmes to identify underlying genetic basis of resistance and develop early warning systems of vector control failure. Identifying genetic markers of insecticide resistance is crucial in enhancing the ability to mitigate potential effects of resistance. The knockdown resistance (kdr) mutation associated with resistance to DDT and pyrethroids, the acetylcholinesterase-1 (ace-1R) mutation associated with resistance to organophosphates and carbamates and 2La chromosomal inversion associated with indoor resting behaviour, were investigated in the present study.
    METHODS: Anopheles mosquitoes sampled from different sites in Kenya and collected within the context of malaria vector surveillance were analysed. Mosquitoes were collected indoors using light traps, pyrethrum spray and hand catches between August 2016 and November 2017. Mosquitoes were identified using morphological keys and Anopheles gambiae sensu lato (s.l.) mosquitoes further identified into sibling species by the polymerase chain reaction method following DNA extraction by alcohol precipitation. Anopheles gambiae and Anopheles arabiensis were analysed for the presence of the kdr and ace-1R mutations, while 2La inversion was only screened for in An. gambiae where it is polymorphic. Chi-square statistics were used to determine correlation between the 2La inversion karyotype and kdr-east mutation.
    RESULTS: The kdr-east mutation occurred at frequencies ranging from 0.5 to 65.6% between sites. The kdr-west mutation was only found in Migori at a total frequency of 5.3% (n = 124). No kdr mutants were detected in Tana River. The ace-1R mutation was absent in all populations. The 2La chromosomal inversion screened in An. gambiae occurred at frequencies of 87% (n = 30), 80% (n = 10) and 52% (n = 50) in Baringo, Tana River and Migori, respectively. A significant association between the 2La chromosomal inversion and the kdr-east mutation was found.
    CONCLUSION: The significant association between the 2La inversion karyotype and kdr-east mutation suggests that pyrethroid resistant An. gambiae continue to rest indoors regardless of the presence of treated bed nets and residual sprays, a persistence further substantiated by studies documenting continued mosquito abundance indoors. Behavioural resistance by which Anopheles vectors prefer not to rest indoors may, therefore, not be a factor of concern in this study's malaria vector populations.
    Keywords:  2La inversion; Ace-1 R mutation; Insecticide resistance; Kdr mutation
    DOI:  https://doi.org/10.1186/s12936-021-03997-4
  4. Parasit Vectors. 2021 Dec 11. 14(1): 606
       BACKGROUND: Entomological surveillance is an important means of assessing the efficacy of insect vector management programs and estimating disease transmission thresholds. Among baited traps, Biogents' BG-Sentinel (BGS) trap baited with BG-Lure is considered to have the most similar outcome to, and be a possible replacement for, human-landing catches for the epidemiologically relevant monitoring of adult Aedes aegypti and Culex quinquefasciatus. In contrast to the BGS trap, the Black Hole ultraviolet (UV) light trap, which is widely used to catch nocturnal flying insects, is not baited with synthetic human odor-mimicking lures.
    METHODS: We evaluated the L-lactic acid-based Kasetsart University (KU)-lures nos. 1-6 as novel candidate chemical lures for the diurnal species Ae. aegypti and the nocturnal species Cx. quinquefasciatus using two commercial traps (the BGS trap and the Black Hole UV light trap) in a semi-field screen (SFS) house. Firstly, we optimized the dose of each KU-lure in an SFS house (140 m3). Secondly, six different candidate KU-lures were screened by comparing their percent attraction using a single discriminating dose (0.5 g). Finally, we evaluated the synergism of the KU-lures selected in this way with commercially available traps.
    RESULTS: BGS traps baited with KU-lure no. 1 exhibited the greatest percent attraction for Ae. aegypti (29.5% ± 14.3%), whereas those baited with KU-lure no. 6 most strongly attracted Cx. quinquefasciatus (33.3% ± 10.7%). Interestingly, BGS traps treated with 10 g BG-Lure did not significantly attract more Ae. aegypti or Cx. quinquefasciatus than the untreated BGS traps. CO2 at a flow rate of 250 ml/min most strongly attracted both Ae. aegypti and Cx. quinquefasciatus (42.2% ± 14.2% and 75.1% ± 16.9%, respectively). BGS and Black Hole UV light traps with KU-lure no. 6 exhibited a stronger attraction for Cx. quinquefasciatus than untreated traps, and the percent attraction did not differ between the treated traps.
    CONCLUSIONS: Synergistic effects of KU-lures nos. 1 and 6 with the mosquito traps were demonstrated for both the diurnal and nocturnal species in the SFS house assays. However, further studies are urgently needed for the development of species-specific lures to increase trap efficacy in the field for local vector mosquitoes in Thailand.
    Keywords:  Attractant; BG-Lure; BG-Sentinel trap; Black Hole ultraviolet light trap; Kasetsart University-lure; Semi-field screen house assay
    DOI:  https://doi.org/10.1186/s13071-021-05108-3
  5. Front Microbiol. 2021 ;12 775078
      The potential use of bacteria for developing novel vector control approaches has awakened new interests in the study of the microbiota associated with vector species. To set a baseline for future malaria research, a high-throughput sequencing of the bacterial 16S ribosomal gene V3-V4 region was used to profile the microbiota associated with late-instar larvae, newly emerged females, and wild-caught females of a sylvan Anopheles atroparvus population from a former malaria transmission area of Spain. Field-acquired microbiota was then assessed in non-blood-fed laboratory-reared females from the second, sixth, and 10th generations. Diversity analyses revealed that bacterial communities varied and clustered differently according to origin with sylvan larvae and newly emerged females distributing closer to laboratory-reared females than to their field counterparts. Inter-sample variation was mostly observed throughout the different developmental stages in the sylvan population. Larvae harbored the most diverse bacterial communities; wild-caught females, the poorest. In the transition from the sylvan environment to the first time point of laboratory breeding, a significant increase in diversity was observed, although this did decline under laboratory conditions. Despite diversity differences between wild-caught and laboratory-reared females, a substantial fraction of the bacterial communities was transferred through transstadial transmission and these persisted over 10 laboratory generations. Differentially abundant bacteria were mostly identified between breeding water and late-instar larvae, and in the transition from wild-caught to laboratory-reared females from the second generation. Our findings confirmed the key role of the breeding environment in shaping the microbiota of An. atroparvus. Gram-negative bacteria governed the microbiota of An. atroparvus with the prevalence of proteobacteria. Pantoea, Thorsellia, Serratia, Asaia, and Pseudomonas dominating the microbiota associated with wild-caught females, with the latter two governing the communities of laboratory-reared females. A core microbiota was identified with Pseudomonas and Serratia being the most abundant core genera shared by all sylvan and laboratory specimens. Overall, understanding the microbiota composition of An. atroparvus and how this varies throughout the mosquito life cycle and laboratory colonization paves the way when selecting potential bacterial candidates for use in microbiota-based intervention strategies against mosquito vectors, thereby improving our knowledge of laboratory-reared An. atroparvus mosquitoes for research purposes.
    Keywords:  16S rRNA; Anopheles atroparvus; European mosquitoes; field-caught; laboratory colonization; microbiota
    DOI:  https://doi.org/10.3389/fmicb.2021.775078
  6. Iran J Public Health. 2021 Aug;50(8): 1668-1677
       Background: Mosquito species are highly considering as disease transmission as well as nuisance insects. One of the principal strategy to protect human from the mosquito bites is repellent agents. This study aimed to assess repellency of two organic essential oils, Eucalyptus globulus and Syzygium aromaticum from bites of malaria vector, Anopheles stephensi.
    Methods: The study was conducted in 2019-2020. The components of essential oils of E. globulus and S. aromaticum was determined using gas chromatography/mass spectrometry. The unfed female mosquitoes aged 2-5 d old were used in all experiments. In vivo Klun and Debboun module bioassays were utilized on human-volunteer skin. The essential oils at serial concentrations were used to find repellent efficacy against Anopheles landings and bites. To find the synergistic effect, four combinations of the essential oils were tested.
    Results: The main composition of E. globulus essential oil was 1,8-Cineol (78.20%), whereas that of S. aromaticum essential oil was 2-methoxy-3-(2-propenyl) (77.04%). Based on minimum effective dose (≤1% biting), 10% (v/v) of E. globulus showed high landing repellency (77.78%), whereas minimum effective dose of S. aromaticum at concentration of 1% had high landing repellency (88.89%). Among four combinations, the ratio of 1:1 of E. globulus (10%):S. aromaticum (1%) showed the most landing repellency (94.44%).
    Conclusion: The combinations of two essential oils had the most potential repellency effect against landing of mosquitoes. As essential oils are eco-friendly with less irritation for human skin, E. globulus and S. aromaticum essential oils are recommended as effective and safe mosquito repellents.
    Keywords:  Anopheles stephensi; Eucalyptus globulus; Repellent activity; Syzygium aromaticum
    DOI:  https://doi.org/10.18502/ijph.v50i8.6813
  7. PLoS Negl Trop Dis. 2021 Dec 14. 15(12): e0010001
       INTRODUCTION: In Colombia, organochloride, organophosphate, carbamate, and pyrethroid insecticides are broadly used to control Aedes aegypti populations. However, Colombian mosquito populations have shown variability in their susceptibility profiles to these insecticides, with some expressing high resistance levels.
    MATERIALS AND METHODS: In this study, we analyzed the susceptibility status of ten Colombian field populations of Ae. aegypti to two pyrethroids; permethrin (type-I pyrethroid) and lambda-cyhalothrin (type-II pyrethroid). In addition, we evaluated if mosquitoes pressured with increasing lambda-cyhalothrin concentrations during some filial generations exhibited altered allelic frequency of these kdr mutations and the activity levels of some metabolic enzymes.
    RESULTS: Mosquitoes from all field populations showed resistance to lambda-cyhalothrin and permethrin. We found that resistance profiles could only be partially explained by kdr mutations and altered enzymatic activities such as esterases and mixed-function oxidases, indicating that other yet unknown mechanisms could be involved. The molecular and biochemical analyses of the most pyrethroid-resistant mosquito population (Acacías) indicated that kdr mutations and altered metabolic enzyme activity are involved in the resistance phenotype expression.
    CONCLUSIONS: In this context, we propose genetic surveillance of the mosquito populations to monitor the emergence of resistance as an excellent initiative to improve mosquito-borne disease control measures.
    DOI:  https://doi.org/10.1371/journal.pntd.0010001
  8. iScience. 2021 Dec 17. 24(12): 103416
      The microbiota of Anopheles mosquitoes influences malaria transmission. Antibiotics ingested during a blood meal impact the mosquito microbiome and malaria transmission, with substantial differences between drugs. Here, we assessed if amoxicillin affects the gut mosquito microbiota. We collected Anopheles larvae in Burkina Faso, kept them in semi-field conditions, and offered a blood meal to adult females. We tested the impact of blood supplementation with two alternative amoxicillin preparations on microbiota composition, determined by high-throughput sequencing in individual gut samples. Our analysis detected four major genera, Elizabethkingia, Wigglesworthia, Asaia, and Serratia. The antibiotic treatment significantly affected overall microbiota composition, with a specific decrease in the relative abundance of Elizabethkingia and Asaia during blood digestion. Besides its interest on the influence of amoxicillin on the mosquito microbiota, our study proposes a thorough approach to report negative-control data of high-throughput sequencing studies on samples with a reduced microbial load.
    Keywords:  Entomology; Microbiome
    DOI:  https://doi.org/10.1016/j.isci.2021.103416
  9. Sci Rep. 2021 Dec 13. 11(1): 23865
      The areas where dengue virus (DENV) is endemic have expanded rapidly, driven in part by the global spread of Aedes species, which act as disease vectors. DENV replicates in the mosquito midgut and is disseminated to the mosquito's salivary glands for amplification. Thus, blocking virus infection or replication in the tissues of the mosquito may be a viable strategy for reducing the incidence of DENV transmission to humans. Here we used the mariner Mos1 transposase to create an Aedes aegypti line that expresses virus-specific miRNA hairpins capable of blocking DENV replication. These microRNA are driven by the blood-meal-inducible carboxypeptidase A promoter or by the polyubiquitin promoter. The transgenic mosquitoes exhibited significantly lower infection rates and viral titers for most DENV serotypes 7 days after receiving an infectious blood meal. The treatment was also effective at day 14 post infection after a second blood meal had been administered. In viral transmission assay, we found there was significantly reduced transmission in these lines. These transgenic mosquitoes were effective in silencing most of the DENV genome; such an approach may be employed to control a dengue fever epidemic.
    DOI:  https://doi.org/10.1038/s41598-021-03229-4
  10. Mol Ecol. 2021 Dec 14.
      In animals with distinct life stages such as holometabolous insects, adult phenotypic variation is often shaped by the environment of immature stages, including their interactions with microbes colonizing larval habitats. Such carry-over effects were previously observed for several adult traits of the mosquito Aedes aegypti after larval exposure to different bacteria, but the mechanistic underpinnings are unknown. Here, we investigated the molecular changes triggered by gnotobiotic larval exposure to different bacteria in Ae. aegypti. We initially screened a panel of 16 bacterial isolates from natural mosquito breeding sites to determine their ability to influence adult life-history traits. We subsequently focused on four bacterial isolates (belonging to Flavobacterium, Lysobacter, Paenibacillus, and Enterobacteriaceae) with significant carry-over effects on adult survival and found that they were associated with distinct transcriptomic profiles throughout mosquito development. Moreover, we detected carry-over effects at the level of gene expression for the Flavobacterium and Paenibacillus isolates. The most prominent transcriptomic changes in gnotobiotic larvae reflected a profound remodeling of lipid metabolism, which translated into phenotypic differences in lipid storage and starvation resistance at the adult stage. Together, our findings indicate that larval exposure to environmental bacteria trigger substantial physiological changes that impact adult fitness, uncovering a possible mechanism underlying carry-over effects of mosquito-bacteria interactions during larval development.
    Keywords:   Aedes aegypti ; Microbiota; gnotobiotic; transcriptome; triglyceride; vector competence
    DOI:  https://doi.org/10.1111/mec.16327
  11. Toxicol Rep. 2021 ;8 1883-1891
      Temephos, an organophosphate insecticide, is widely accepted for the control of Aedes aegypti, vector of infectious diseases such as dengue, chikungunya, yellow fever, and zika. However, there are claims that repeated and indiscriminate use of temephos has resulted in resistance development in exposed mosquito populations. The present study attempts to evaluate the continuous performance of temephos on the Ae. aegypti population, in laboratory conditions, in terms of toxicity and the effect on marker enzymes associated with metabolic resistance. Results of the toxicity bioassay showed that after the initial exposure, toxicity increased till F4 generation by 1.65 fold, and continuous exposure resulted in a 7.83 fold reduction in toxicity at F28 generation. Percent mortality result showed a marked reduction in mortality with the passage of generations while using the same series of concentrations, viz. 2 ppm, which was 100 % lethal at the initial nine generations, could kill only 22.66 % at F28. Resistance to organophosphates is mainly governed by metabolic detoxifying enzyme families of esterases, glutathione-s-transferase, and cytochrome P450. Analysis of these metabolic detoxifying enzymes showed an inverse trend to toxicity (i.e. toxicity increased in early generations as enzyme activity dropped and then dropped as enzyme activity increased). At the initial exposure, enzyme activity decreased in 2-4 generations, however, repeated exposure led to a significant increase in all the metabolic detoxifying enzymes. From the toxicity level as well as marker enzyme bioassay results, it can be inferred that mosquitoes showed increased detoxification in generational time with an increase in enzymes associated with metabolic detoxification. In conclusion, repeated application of temephos led to resistance development in Ae. aegypti which may be associated with the increase in metabolic detoxifying enzyme activities.
    Keywords:  ANOVA, analysis of variance; BSA, bovine serum albumin; CDNB, 1-chloro-2,4-dinitrobenzene; CPCSEA, committee for the purpose of control and supervision of experiments on animals; DEET, NN-diethyl-meta-toluamide; DEM, diethyl maleate; DMSO, dimethyl sulfoxide; Dengue vector; GSH, reduced glutathione; GST, glutathione-s-transferase; IAEC, institutional animal ethical committee; LC50, lethal concentration 50; Larvicide; MAPK, mitogen-activated protein kinases; NADPH, nicotinamide adenine dinucleotide phosphate hydrogen; OD, optical density; OP, organophosphate; Organophosphates; PBO, piperonyl butoxide; PPM, parts per million; Pesticide resistance; SE, standard error; SPSS, statistical package for the social sciences; TMBZ, 3, 3, 5, 5-tetramethyl benzidine; TPP, triphenyl phosphate; Temephos; WHO, World Health Organization; ºC, degree celsius
    DOI:  https://doi.org/10.1016/j.toxrep.2021.11.013
  12. PLoS Negl Trop Dis. 2021 Dec 16. 15(12): e0009261
       BACKGROUND: During 2017, twenty health districts (locations) implemented a dengue outbreak Early Warning and Response System (EWARS) in Mexico, which processes epidemiological, meteorological and entomological alarm indicators to predict dengue outbreaks and triggers early response activities. Out of the 20 priority districts where more than one fifth of all national disease transmission in Mexico occur, eleven districts were purposely selected and analyzed. Nine districts presented outbreak alarms by EWARS but without subsequent outbreaks ("non-outbreak districts") and two presented alarms with subsequent dengue outbreaks ("outbreak districts"). This evaluation study assesses and compares the impact of alarm-informed response activities and the consequences of failing a timely and adequate response across the outbreak groups.
    METHODS: Five indicators of dengue outbreak response (larval control, entomological studies with water container interventions, focal spraying and indoor residual spraying) were quantitatively analyzed across two groups ("outbreak districts" and "non-outbreak districts"). However, for quality control purposes, only qualitative concluding remarks were derived from the fifth response indicator (fogging).
    RESULTS: The average coverage of vector control responses was significantly higher in non-outbreak districts and across all four indicators. In the "outbreak districts" the response activities started late and were of much lower intensity compared to "non-outbreak districts". Vector control teams at districts-level demonstrated diverse levels of compliance with local guidelines for 'initial', 'early' and 'late' responses to outbreak alarms, which could potentially explain the different outcomes observed following the outbreak alarms.
    CONCLUSION: Failing timely and adequate response of alarm signals generated by EWARS showed to negatively impact the disease outbreak control process. On the other hand, districts with adequate and timely response guided by alarm signals demonstrated successful records of outbreak prevention. This study presents important operational scenarios when failing or successding EWARS but warrants investigating the effectiveness and cost-effectiveness of EWARS using a more robust designs.
    DOI:  https://doi.org/10.1371/journal.pntd.0009261
  13. PLoS Negl Trop Dis. 2021 Dec 13. 15(12): e0010004
       BACKGROUND: Culex mosquitoes are vectors for a variety of pathogens of public health concern. New indicators of exposure to Culex bites are needed to evaluate the risk of transmission of associated pathogens and to assess the efficacy of vector control strategies. An alternative to entomological indices is the serological measure of antibodies specific to mosquito salivary antigens. This study investigated whether the human IgG response to both the salivary gland extract and the 30 kDa salivary protein of Culex quinquefasciatus may represent a proxy of human exposure to Culex bites.
    METHODOLOGY/PRINCIPAL FINDINGS: A multidisciplinary survey was conducted with children aged 1 to 14 years living in neighborhoods with varying exposure to Culex quinquefasciatus in the city of Bouaké, Côte d'Ivoire. Children living in sites with high exposure to Cx quinquefasciatus had a significantly higher IgG response to both salivary antigens compared with children living in the control site where only very few Culex were recorded. Moreover, children from any Culex-high exposed sites had significantly higher IgG responses only to the salivary gland extract compared with children from the control village, whereas no difference was noted in the anti-30 kDa IgG response. No significant differences were noted in the specific IgG responses between age and gender. Sites and the use of a bed net were associated with the level of IgG response to the salivary gland extract and to the 30 kDa antigen, respectively.
    CONCLUSIONS/SIGNIFICANCE: These findings suggest that the IgG response to Culex salivary gland extracts is suitable as proxy of exposure; however, the specificity to the Culex genus needs further investigation. The lower antigenicity of the 30 kDa recombinant protein represents a limitation to its use. The high specificity of this protein to the Culex genus makes it an attractive candidate and other specific antibody responses might be more relevant as a biomarker of exposure. These epidemiological observations may form a starting point for additional work on developing serological biomarkers of Culex exposure.
    DOI:  https://doi.org/10.1371/journal.pntd.0010004
  14. Parasit Vectors. 2021 Dec 11. 14(1): 602
       BACKGROUND: The recent detection of the South Asian malaria vector Anopheles stephensi in the Horn of Africa (HOA) raises concerns about the impact of this mosquito on malaria transmission in the region. Analysis of An. stephensi genetic diversity and population structure can provide insight into the history of the mosquito in the HOA to improve predictions of future spread. We investigated the genetic diversity of An. stephensi in eastern Ethiopia, where detection suggests a range expansion into this region, in order to understand the history of this invasive population.
    METHODS: We sequenced the cytochrome oxidase subunit I (COI) and cytochrome B gene (CytB) in 187 An. stephensi collected from 10 sites in Ethiopia in 2018. Population genetic, phylogenetic, and minimum spanning network analyses were conducted for Ethiopian sequences. Molecular identification of blood meal sources was also performed using universal vertebrate CytB sequencing.
    RESULTS: Six An. stephensi COI-CytB haplotypes were observed, with the highest number of haplotypes in the northeastern sites (Semera, Bati, and Gewana towns) relative to the southeastern sites (Kebridehar, Godey, and Degehabur) in eastern Ethiopia. We observed population differentiation, with the highest differentiation between the northeastern sites compared to central sites (Erer Gota, Dire Dawa, and Awash Sebat Kilo) and the southeastern sites. Phylogenetic and network analysis revealed that the HOA An. stephensi are more genetically similar to An. stephensi from southern Asia than from the Arabian Peninsula. Finally, molecular blood meal analysis revealed evidence of feeding on cows, goats, dogs, and humans, as well as evidence of multiple (mixed) blood meals.
    CONCLUSION: We show that An. stephensi is genetically diverse in Ethiopia and with evidence of geographical structure. Variation in the level of diversity supports the hypothesis for a more recent introduction of An. stephensi into southeastern Ethiopia relative to the northeastern region. We also find evidence that supports the hypothesis that HOA An. stephensi populations originate from South Asia rather than the Arabian Peninsula. The evidence of both zoophagic and anthropophagic feeding support the need for additional investigation into the potential for livestock movement to play a role in vector spread in this region.
    Keywords:  Horn of Africa; Invasive species; Malaria; Phylogeography; Sequencing; Vector-borne
    DOI:  https://doi.org/10.1186/s13071-021-05097-3
  15. BMC Infect Dis. 2021 Dec 14. 21(1): 1248
       BACKGROUND: While the overall burden of malaria is still high, the global technical strategy for malaria advocates for two sets of interventions: vector control-based prevention and diagnosis and prompt effective treatment of malaria cases. This study aimed to assess the performance of malaria interventions on malaria infection and anaemia in irrigated areas in Sudan.
    METHODS: Based on the Sudan 2016 national malaria indicator survey, data for two states (Gezira and Sennar), characterized by large-irrigated schemes, were analysed. Four community-level malaria interventions were used as contextual variables: utilization of malaria diagnosis, utilization of Artemisinin-based combination therapy (ACT), utilization of long-lasting insecticidal nets (LLINs) and coverage with indoor residual spraying (IRS). Association between these interventions and two outcomes: malaria infection and anaemia, was assessed separately. Malaria infection was assessed in all age groups while anaemia was assessed in children under 5 years. Multilevel multiple logistic regression analysis were conducted.
    RESULTS: Among 4478 individuals involved in this study distributed over 47 clusters, the overall malaria infection rate was 3.0% and 56.5% of the children under 5 years (total = 322) were anaemic. Except for IRS coverage (69.6%), the average utilization of interventions was relatively low: 52.3% for utilization of diagnosis, 33.0% for utilization of ACTs and 18.6% for LLINs utilization. The multi-level multiple logistic regression model showed that only IRS coverage was associated with malaria infection (Odds ratio 0.83 per 10% coverage, 95%Confidence Interval (95%CI) 0.74-0.94, p = 0.003) indicating that a higher level of IRS coverage was associated with less malaria infection. Anaemia was not associated with any intervention (all p values larger than 0.1).
    CONCLUSIONS: Malaria transmission in Gezira and Sennar areas is low. IRS, with insecticide to which vectors are susceptible, is an effective malaria control intervention in irrigated schemes. Community utilization of other interventions was not associated with malaria infection in this study. This may be due to the low utilization of these interventions. However, individual use of LLINs provide personal protection. This study failed to establish an association between anaemia and malaria control interventions in low transmission areas. The higher level of malaria infection in urban areas is a cause for concern.
    Keywords:  Anaemia; Irrigated schemes; Low transmission; Malaria indicator survey; Malaria infection; Malaria interventions; Multilevel logistic regression; Sudan
    DOI:  https://doi.org/10.1186/s12879-021-06929-4
  16. Nat Commun. 2021 Dec 16. 12(1): 7320
      The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development.
    DOI:  https://doi.org/10.1038/s41467-021-27578-w
  17. Parasitol Int. 2021 Dec 08. pii: S1383-5769(21)00244-0. [Epub ahead of print]87 102526
      Plasmodium vivax is the most geographically widespread human malaria parasite. Global malaria efforts have been less successful at reducing the burden of P. vivax compared to P. falciparum, owing to the unique biology and related treatment complexity of P. vivax. As a result, P. vivax is now the dominant malaria parasite throughout the Asia-Pacific and South America causing up to 14 million clinical cases every year and is considered a major obstacle to malaria elimination. Key features circumventing existing malaria control tools are the transmissibility of asymptomatic, low-density circulating infections and reservoirs of persistent dormant liver stages (hypnozoites) that are undetectable but reactivate to cause relapsing infections and sustain transmission. In this review we summarise the new knowledge shaping our understanding of the global epidemiology of P. vivax infections, highlighting the challenges for elimination and the tools that will be required achieve this.
    Keywords:  Elimination; Hidden reservoirs; Hypnozoites; Malaria; Plasmodium vivax; Transmission
    DOI:  https://doi.org/10.1016/j.parint.2021.102526
  18. PLoS One. 2021 ;16(12): e0261283
      The present study aims to analyze the effectiveness of ovitraps in the capture of Hg leucocelaenus eggs and evaluate the influence of the dry and rainy seasons on their abundance and hatching rates. The eggs were collected in the Atlantic Forest of State of Rio de Janeiro, Brazil, an area in which the yellow fever virus is known to circulate. We distributed 15 ovitraps in three sampling points, with five ovitraps per point. We distributed 15 ovitraps in three sampling points on trees within a forested area, which were sequentially numbered, monitored, and replaced every two weeks from October 2016 to April 2018. There was a high dominance of Hg. leucocelaenus eggs (98.4%) and a variation in egg hatching rates between the wet and dry seasons. These rates were 1.5 times higher in the rainy season than in the dry season. The rainy season also showed a greater abundance of eggs and higher values of ovitrap positivity and egg density indexes in the installed ovitraps. The abundances of Hg. leucocelaenus eggs were positively correlated with mean monthly temperature and air humidity but not significantly correlated with accumulated precipitation. These results, as well as their implications for the possible use of ovitraps to monitor vector mosquitoes of yellow fever in the study region, are discussed.
    DOI:  https://doi.org/10.1371/journal.pone.0261283
  19. BMC Infect Dis. 2021 Dec 14. 21(1): 1246
       BACKGROUND: Cross-border malaria in Laiza City of Myanmar seriously affected Yingjiang County of China and compromised reaching the goal of malaria elimination by 2020. Since 2017, a pilot project on 3 + 1 strategy of joint cross-border malaria prevention and control was carried out for building a malaria buffer in these border areas. Here, 3 were the three preventive lines in China where different focalized approaches of malaria elimination were applied and + 1 was a defined border area in Myanmar where the integrated measures of malaria control were adopted.
    METHODS: A 5-year retrospective analysis (2015 to 2019) was conducted that included case detection, parasite prevalence and vector surveillance. Descriptive statistics was used and the incidence or rates were compared. The annual parasite incidence and the parasite prevalence rate in + 1 area of Myanmar, the annual importation rate in Yingjiang County of China and the density of An. minimus were statistically significant indictors to assess the effectiveness of the 3 + 1 strategy.
    RESULTS: In + 1 area of Myanmar from 2015 to 2019, the averaged annual parasite incidence was (59.11 ± 40.73)/1000 and Plasmodium vivax accounted for 96.27% of the total confirmed cases. After the pilot project, the annual parasite incidence dropped 89% from 104.77/1000 in 2016 to 12.18/1000 in 2019, the microscopic parasite prevalence rate dropped 100% from 0.34% in 2017 to zero in 2019 and the averaged density of An. Minimus per trap-night dropped 93% from 1.92 in June to 0.13 in September. The submicroscopic parasite prevalence rate increased from 1.15% in 2017 to 1.66% in 2019 without significant difference between the two surveys (P = 0.084). In Yingjiang County of China, neither indigenous nor introduced case was reported and 100% cases were imported from Myanmar since 2017. The averaged annual importation rate from 2015 to 2019 was (0.47 ± 0.15)/1000. After the pilot project, the annual importation rate dropped from 0.59/1000 in 2016 to 0.28/1000 in 2019 with an overall reduction of 53% in the whole county. The reduction was 67% (57.63/1000 to 18.01/1000) in the first preventive line, 52% (0.20/1000 to 0.10/1000) in the second preventive line and 36% (0.32/1000 to 0.22/1000) in the third preventive line. The averaged density of An. Minimus per trap-night in the first preventive line dropped 94% from 2.55 in June to 0.14 in September, without significant difference from that of + 1 area of Myanmar (Z value = - 1.18, P value = 0.24).
    CONCLUSION: The pilot project on 3 + 1 strategy has been significantly effective in the study areas and a buffer zone of border malaria was successfully established between Laiza City of Myanmar and Yingjiang County of China.
    Keywords:  China–Myanmar border; Control; Cross; Elimination; Joint; Malaria; Strategy
    DOI:  https://doi.org/10.1186/s12879-021-06920-z
  20. Health Policy Plan. 2021 Dec 17. pii: czab140. [Epub ahead of print]
      Universal coverage with effective vector control remains the mainstay of malaria vector control in sub-Saharan Africa Tanzania has utilized a number of mechanisms for the maintenance of long-lasting insecticidal net (LLIN) coverage over time. Schools have been identified as one potential channel for continuous distribution of LLIN. This research aims to evaluate an annual school based LLIN distribution programme in Tanzania which began in 2013, called the School Net Programme (SNP). Following each of the first four rounds of SNP distribution, a household survey was conducted in intervention and comparison districts in Southern and Lake zones of Tanzania (N = 5083 households). Measures of ownership, access, and use were compared between intervention and comparison districts. Determinants of reach were assessed in intervention districts. Population access to an LLIN increased from 63.1% (95% CI: 58.8, 67.5) to 76.5% (95% CI: 72.9, 80.0) in the intervention districts between the first and last surveys. Access also rose in the comparison districts from 51.4% (95% CI: 46.9, 55.9) to 79.8% (95% CI: 77.3, 82.0) following a mass distribution and implementation of school-based distribution during the study period. LLIN use increased in intervention districts from 44.9% (95% CI: 40.5, 49.3) to 65.6% (95% CI: 59.4, 71.8) and from 57.2% (95% CI: 49.7, 64.7) to 77.4% (95% CI: 69.3, 85.5) specifically amongst primary school-aged children. Households reached by the SNP were wealthier households with children enrolled in school. The SNP in Tanzania was able to maintain population level LLIN ownership, use, and access in the absence of a mass distribution. The SNP successfully reached households which housed school-aged children. Alternative delivery strategies may need to be considered to reach households without children enrolled in school which experienced less benefit from the program.
    Keywords:  Bednet; ITN; LLIN; Tanzania; continuous distribution; education; insecticide treated net; keep up; long-lasting insecticidal net; long-lasting insecticide treated bed net; malaria; net; schools
    DOI:  https://doi.org/10.1093/heapol/czab140
  21. Lancet Infect Dis. 2021 Dec 14. pii: S1473-3099(21)00557-0. [Epub ahead of print]
       BACKGROUND: Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin-piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions.
    METHODS: This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7-46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin-piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300-400 μg/kg per day for 3 consecutive days] and dihydroartemisinin-piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin-piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313.
    FINDINGS: Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin-piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention.
    INTERPRETATION: The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin-piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed.
    FUNDING: Joint Global Health Trials Scheme.
    TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
    DOI:  https://doi.org/10.1016/S1473-3099(21)00557-0
  22. Hastings Cent Rep. 2021 Nov;51 Suppl 2 S11-S18
      In the early 1970s, a World Health Organization-initiated and United States-funded project released lab-reared mosquitoes outside New Delhi in the first large-scale field trials of the genetic control of mosquitoes. Despite partnering with the Indian Council of Medical Research and investing significantly in outreach to local communities at the release sites, the project was embroiled in controversy and became an object of vehement debate within the Indian parliament and diplomatic contretemps between the United States and India. This early episode of genetic control research demonstrates how a scientific collaboration was entangled in geopolitics and shaped by the legacy of colonialism. This historical case study has implications for public deliberation in the present, pointing to the challenges of shared decision-making in the context of structural inequality, the way that a backdrop of military interest in a technology can impede trust, and the long-term consequences of projects that foster mistrust.
    Keywords:  Cold War science; bioethics; democratic deliberation; gene editing; genetic control; genetic modification; history of public health; international development; militarization of public health; postcolonial science; public deliberation; science and colonialism; securitization of public health; transnational/international research ethics; vector-borne disease
    DOI:  https://doi.org/10.1002/hast.1315
  23. Sci Rep. 2021 Dec 13. 11(1): 23867
      Insecticides have played a major role in the prevention, control, and elimination of vector-borne diseases, but insecticide resistance threatens the efficacy of available vector control tools. A global survey was conducted to investigate vector control insecticide use from 2010 to 2019. Out of 140 countries selected as sample for the study, 87 countries responded. Also, data on ex-factory deliveries of insecticide-treated nets (ITNs) were analyzed. Insecticide operational use was highest for control of malaria, followed by dengue, leishmaniasis and Chagas disease. Vector control relied on few insecticide classes with pyrethroids the most used overall. Results indicated that IRS programs have been slow to react to detection of pyrethroid resistance, while proactive resistance management using insecticides with unrelated modes of action was generally weak. The intensive use of recently introduced insecticide products raised concern about product stewardship regarding the preservation of insecticide susceptibility in vector populations. Resistance management was weakest for control of dengue, leishmaniasis or Chagas disease. Therefore, it will be vital that vector control programs coordinate on insecticide procurement, planning, implementation, resistance monitoring, and capacity building. Moreover, increased consideration should be given to alternative vector control tools that prevent the development of insecticide resistance.
    DOI:  https://doi.org/10.1038/s41598-021-03367-9
  24. Curr Pharm Biotechnol. 2021 Dec 15.
       OBJECTIVES: The Plasmodium parasite is transmitted directly to humans through the Anopheles mosquito bite and causes vector-borne Malaria disease, which leads to the transmission of the disease in Southeast Asia, including India. The problem of persistent toxicity, along with the growing incidence of insect resistance, has led to the use of green pesticides to control the spread of the disease in a cost-effective and environment-friendly manner. Based on this objective, this work investigated the larvicidal, pupicidal, and ovicidal activity of Mentha pipertia using a natural nanoemulsion technique.
    METHODS: GC-MS characterized essential oils of Mentha pipertia leaves were formulated as a nanoemulsion for herbal larvicidal, pupicidal, and ovicidal activities. Size of the nanoemulsion was analyzed by photon correlation spectroscopy. The herbal activities against Anopheles Stephensi of nanoemulsion were evaluated in terms of the lethal concentration for 50% (LC50) and 90% (LC90) to prove low cost, pollution free active effective formulation.
    RESULTS: Chiral, keto, and alcohol groups attached Mentha pipertia leaves essential oil nanoemulsions demonstrated good results in the larvicidal probit analysis, with values of LC50=09.67 ppm and LC90=20.60 ppm. Activity results of the most stable nano formulation with 9.89 nm size showed a significant increase when compared to the bulk.
    CONCLUSION: The nanoemulsion of Mentha pipertia leaves can be a promising eco-friendly widely available, low-cost herbicide against the Anopheles mosquito.
    Keywords:  Anopheles Stephensi; GC–MS; Larvicidal activity; Mortality; Nanoemulsion; Peppermint oil
    DOI:  https://doi.org/10.2174/1389201023666211215125621
  25. Malar J. 2021 Dec 11. 20(1): 460
       BACKGROUND: A detailed analysis of household and individual level Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India.
    METHODS: Socio-demographic and behavioural information from residents (aged 1-69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models.
    RESULTS: A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria.
    CONCLUSION: This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.
    Keywords:  Asymptomatic infection; Malaria elimination; Northeast India; Transmission intensity
    DOI:  https://doi.org/10.1186/s12936-021-03982-x