bims-mosdis Biomed News
on Mosquito distribution and disease
Issue of 2021‒06‒13
twenty-five papers selected by
Richard Halfpenny
Staffordshire University

  1. Parasit Vectors. 2021 Jun 09. 14(1): 314
      BACKGROUND: The Aedes aegypti mosquito is responsible for the transmission of several medically important arthropod-borne viruses, including multiple serotypes of dengue virus (DENV-1, -2, -3, and -4). Competition within the mosquito between DENV serotypes can affect viral infection dynamics, modulating the transmission potential of the pathogen. Vector control remains the main method for limiting dengue fever. The insect endosymbiont Wolbachia pipientis is currently being trialed in field releases globally as a means of biological control because it reduces virus replication inside the mosquito. It is not clear how co-infection between DENV serotypes in the same mosquito might alter the pathogen-blocking phenotype elicited by Wolbachia in Ae. aegypti.METHODS: Five- to 7-day-old female Ae. aegypti from two lines, namely, with (wMel) and without Wolbachia infection (WT), were fed virus-laden blood through an artificial membrane with either a mix of DENV-2 and DENV-3 or the same DENV serotypes singly. Mosquitoes were subsequently incubated inside environmental chambers and collected on the following days post-infection: 3, 4, 5, 7, 8, 9, 11, 12, and 13. Midgut, carcass, and salivary glands were collected from each mosquito at each timepoint and individually analyzed to determine the percentage of DENV infection and viral RNA load via RT-qPCR.
    RESULTS: We saw that for WT mosquitoes DENV-3 grew to higher viral RNA loads across multiple tissues when co-infected with DENV-2 than when it was in a mono-infection. Additionally, we saw a strong pathogen-blocking phenotype in wMel mosquitoes independent of co-infection status.
    CONCLUSION: In this study, we demonstrated that the wMel mosquito line is capable of blocking DENV serotype co-infection in a systemic way across the mosquito body. Moreover, we showed that for WT mosquitoes, serotype co-infection can affect infection frequency in a tissue- and time-specific manner and that both viruses have the potential of being transmitted simultaneously. Our findings suggest that the long-term efficacy of Wolbachia pathogen blocking is not compromised by arthropod-borne virus co-infection.
    Keywords:  Aedes aegypti; Co-infection; Dengue; Infection dynamics; Serotype; Wolbachia
  2. Front Immunol. 2021 ;12 660873
      Aedes aegypti mosquitoes are vectors for arboviruses of medical importance such as dengue (DENV) and Zika (ZIKV) viruses. Different innate immune pathways contribute to the control of arboviruses in the mosquito vector including RNA interference, Toll and Jak-STAT pathways. However, the role of cellular responses mediated by circulating macrophage-like cells known as hemocytes remains unclear. Here we show that hemocytes are recruited to the midgut of Ae. aegypti mosquitoes in response to DENV or ZIKV. Blockade of the phagocytic function of hemocytes using latex beads induced increased accumulation of hemocytes in the midgut and a reduction in virus infection levels in this organ. In contrast, inhibition of phagocytosis by hemocytes led to increased systemic dissemination and replication of DENV and ZIKV. Hence, our work reveals a dual role for hemocytes in Ae. aegypti mosquitoes, whereby phagocytosis is not required to control viral infection in the midgut but is essential to restrict systemic dissemination. Further understanding of the mechanism behind this duality could help the design of vector-based strategies to prevent transmission of arboviruses.
    Keywords:  Aedes aegypti; Zika virus; cellular immunity; dengue virus; hemocytes; macrophage-like cells; vector mosquitoes
  3. Parasit Vectors. 2021 Jun 08. 14(1): 312
      BACKGROUND: Diseases transmitted by invasive Aedes aegypti and Aedes albopictus mosquitoes are public health issues in the tropics and subtropics. Understanding the ecology of mosquito vectors is essential for the development of effective disease mitigation programs and will allow for accurate predictions of vector occurrence and abundance. Studies that examine mosquito population dynamics are typically focused on female presence or total adult captures without discriminating the temporal and spatial distribution of both sexes.METHODS: We collected immature and adult mosquitoes bimonthly for 2 years (2018-2019) in the Medellín Botanical Garden. Collection sites differed in proximity to buildings and nearby vegetation, and were classified by their overhead vegetation cover. We used linear mixed models (LMMs) and Spatial Analysis by Distance Indices (SADIE) to assess the spatial distribution of Ae. aegypti and Ae. albopictus. Using our Ae. albopictus captures exclusively, we assessed (1) the spatial and temporal distribution of males and females using SADIE and a generalized linear mixed model (GLMM), (2) the relationship between climatic variables/vegetation coverage and adult captures using GLMMs and LMMs, and (3) the correlation of male and female size in relation to climatic variables and vegetation coverage using LMMs.
    RESULTS: Spatial analysis showed that Ae. aegypti and Ae. albopictus were distributed at different locations within the surveilled area. However, Ae. albopictus was the predominant species in the park during the study period. Adult Ae. albopictus captures were positively correlated with precipitation and relative humidity, and inversely correlated with temperature and wind speed. Moreover, we observed a spatial misalignment of Ae. albopictus males and females-the majority of males were located in the high vegetation coverage sites, while females were more evenly distributed. We observed significant associations of the size of our adult Ae. albopictus captures with precipitation, temperature, and wind speed for both sexes and found that overhead vegetation cover influenced male size, but observed no effect on female size.
    CONCLUSIONS: Our work elucidates the differential dynamics of Ae. albopictus males and females, which is pivotal to develop accurate surveillance and the successful establishment of vector control programs based on the disruption of insect reproduction.
    Keywords:  Aedes aegypti; Aedes albopictus; Male–female distribution; Population ecology
  4. N Engl J Med. 2021 06 10. 384(23): 2177-2186
      BACKGROUND: Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis are less susceptible than wild-type A. aegypti to dengue virus infection.METHODS: We conducted a cluster-randomized trial involving releases of wMel-infected A. aegypti mosquitoes for the control of dengue in Yogyakarta, Indonesia. We randomly assigned 12 geographic clusters to receive deployments of wMel-infected A. aegypti (intervention clusters) and 12 clusters to receive no deployments (control clusters). All clusters practiced local mosquito-control measures as usual. A test-negative design was used to assess the efficacy of the intervention. Patients with acute undifferentiated fever who presented to local primary care clinics and were 3 to 45 years of age were recruited. Laboratory testing was used to identify participants who had virologically confirmed dengue (VCD) and those who were test-negative controls. The primary end point was symptomatic VCD of any severity caused by any dengue virus serotype.
    RESULTS: After successful introgression of wMel into the intervention clusters, 8144 participants were enrolled; 3721 lived in intervention clusters, and 4423 lived in control clusters. In the intention-to-treat analysis, VCD occurred in 67 of 2905 participants (2.3%) in the intervention clusters and in 318 of 3401 (9.4%) in the control clusters (aggregate odds ratio for VCD, 0.23; 95% confidence interval [CI], 0.15 to 0.35; P = 0.004). The protective efficacy of the intervention was 77.1% (95% CI, 65.3 to 84.9) and was similar against the four dengue virus serotypes. The incidence of hospitalization for VCD was lower among participants who lived in intervention clusters (13 of 2905 participants [0.4%]) than among those who lived in control clusters (102 of 3401 [3.0%]) (protective efficacy, 86.2%; 95% CI, 66.2 to 94.3).
    CONCLUSIONS: Introgression of wMel into A. aegypti populations was effective in reducing the incidence of symptomatic dengue and resulted in fewer hospitalizations for dengue among the participants. (Funded by the Tahija Foundation and others; AWED number, NCT03055585; Indonesia Registry number, INA-A7OB6TW.).
  5. Malar J. 2021 Jun 06. 20(1): 251
      BACKGROUND: Better understanding of the distribution of Plasmodium vivax and its risk factors could be used to prevent and control malaria infection. Therefore, the aim of this study was to characterize the distribution and risk factors of P. vivax, and to compare them with Plasmodium falciparum occurrence in south-central Ethiopia.METHODS: A cohort of 34,548 individuals were followed for 121 weeks between 2014 and 2016 as part of larger cluster randomized controlled trial to evaluate the effect of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) on malaria prevention in Ethiopia. Weekly home visit (active search) and patient self- report to health post (passive search) between the weekly home visits were used to register malaria cases. A blood sample was collected by finger prick and malaria was diagnosed using rapid diagnostic test (RDT). Generalized estimating equation (GEE) Poisson model that accounts for repeated measure of malaria episodes was applied to assess the risk factors of P. vivax episode.
    RESULTS: The overall incidence rate of P. vivax was 7.4 episodes per 1000 person-years of observation. The study showed households closer to the lake Zeway and Bulbula river (potential mosquito breeding sites) were more at risk of P. vivax infection (incidence rate ratio (IRR): 1.33; 95% CI = 1.23-1.45). Furthermore, the age group under 5 years (IRR: 1.40, 95% CI = 1.10-1.79), the age group 5-14 years (IRR: 1.27, 95% CI = 1.03-1.57), households with less educated household head (IRR: 1.63, 95% CI = 1.10-2.44) and house roof made of thatch/leaf (IRR: 1.35, 95% CI = 1.11-1.65) were at higher risk for P. vivax. Similar explanatory variables such as distance from the breeding sites, age group (under 5 years but not 5-14 years old), educational status and type of housing were also found to be the predictors of P. falciparum incidence.
    CONCLUSION: Households living closer to a mosquito breeding site, age group under 15 years, less educated household heads and thatch/leaf roof housing were the risk factor for P. vivax. The result of this study can be used for tailored interventions for malaria control and prevention by prioritizing those living close to potential mosquito breeding site, enhancing bed net use of children less than 15 years of age, and improving housing.
    Keywords:  Cohort; Ethiopia; Mosquito breeding site; Plasmodium vivax; Risk
  6. Parasit Vectors. 2021 Jun 08. 14(1): 311
      BACKGROUND: Mosquito control has the potential to significantly reduce malaria burden on a region, but to influence public health policy must also show cost-effectiveness. Gaps in our knowledge of mosquito population dynamics mean that mathematical modelling of vector control interventions have typically made simplifying assumptions about key aspects of mosquito ecology. Often, these assumptions can distort the predicted efficacy of vector control, particularly next-generation tools such as gene drive, which are highly sensitive to local mosquito dynamics.METHODS: We developed a discrete-time stochastic mathematical model of mosquito population dynamics to explore the fine-scale behaviour of egg-laying and larval density dependence on parameter estimation. The model was fitted to longitudinal mosquito population count data using particle Markov chain Monte Carlo methods.
    RESULTS: By modelling fine-scale behaviour of egg-laying under varying density dependence scenarios we refine our life history parameter estimates, and in particular we see how model assumptions affect population growth rate (Rm), a crucial determinate of vector control efficacy.
    CONCLUSIONS: Subsequent application of these new parameter estimates to gene drive models show how the understanding and implementation of fine-scale processes, when deriving parameter estimates, may have a profound influence on successful vector control. The consequences of this may be of crucial interest when devising future public health policy.
    Keywords:  Gene drive; Malaria; Modelling; Mosquitos; Parameter estimation; Population biology; Public health; Vector control
  7. Curr Biol. 2021 Jun 07. pii: S0960-9822(21)00573-X. [Epub ahead of print]31(11): R738-R740
      Wolbachia bacteria are being widely released for suppression of dengue transmitted by Aedes mosquitoes. Walker, Quek, Jeffries and colleagues present robust evidence for natural Wolbachia infections in malaria-vectoring Anopheles mosquitoes, paving the way for new Wolbachia-based interventions.
  8. Malar J. 2021 Jun 09. 20(1): 263
      BACKGROUND: Anopheles stephensi, an invasive malaria vector, was first detected in Africa nearly 10 years ago. After the initial finding in Djibouti, it has subsequently been found in Ethiopia, Sudan and Somalia. To better inform policies and vector control decisions, it is important to understand the distribution, bionomics, insecticide susceptibility, and transmission potential of An. stephensi. These aspects were studied as part of routine entomological monitoring in Ethiopia between 2018 and 2020.METHODS: Adult mosquitoes were collected using human landing collections, pyrethrum spray catches, CDC light traps, animal-baited tent traps, resting boxes, and manual aspiration from animal shelters. Larvae were collected using hand-held dippers. The source of blood in blood-fed mosquitoes and the presence of sporozoites was assessed through enzyme-linked immunosorbent assays (ELISA). Insecticide susceptibility was assessed for pyrethroids, organophosphates and carbamates.
    RESULTS: Adult An. stephensi were collected with aspiration, black resting boxes, and animal-baited traps collecting the highest numbers of mosquitoes. Although sampling efforts were geographically widespread, An. stephensi larvae were collected in urban and rural sites in eastern Ethiopia, but An. stephensi larvae were not found in western Ethiopian sites. Blood-meal analysis revealed a high proportion of blood meals that were taken from goats, and only a small proportion from humans. Plasmodium vivax was detected in wild-collected An. stephensi. High levels of insecticide resistance were detected to pyrethroids, carbamates and organophosphates. Pre-exposure to piperonyl butoxide increased susceptibility to pyrethroids. Larvae were found to be susceptible to temephos.
    CONCLUSIONS: Understanding the bionomics, insecticide susceptibility and distribution of An. stephensi will improve the quality of a national response in Ethiopia and provide additional information on populations of this invasive species in Africa. Further work is needed to understand the role that An. stephensi will have in Plasmodium transmission and malaria case incidence. While additional data are being collected, national programmes can use the available data to formulate and operationalize national strategies against the threat of An. stephensi.
  9. Malar J. 2021 Jun 09. 20(1): 259
      BACKGROUND: Despite increasing documentation of insecticide resistance in malaria vectors against public health insecticides in sub-Saharan Africa, there is a paucity of information on the potential fitness costs of pyrethroid resistance in malaria vectors, which is important in improving the current resistant management strategies. This study aimed to assess the fitness cost effects of insecticide resistance on the development and survival of immature Anopheles gambiae from western Kenya.METHODS: Two-hour old, first instar larvae (L1) were introduced and raised in basins containing soil and rainwater in a semi-field set-up. Each day the number of surviving individuals per larval stage was counted and their stage of development were recorded until they emerged as adults. The larval life-history trait parameters measured include mean larval development time, daily survival and pupal emergence. Pyrethroid-resistant colony of An. gambiae sensu stricto and susceptible colony originating from the same site and with the same genetic background were used. Kisumu laboratory susceptible colony was used as a reference.
    RESULTS: The resistant colony had a significantly longer larval development time through the developmental stages than the susceptible colony. The resistant colony took an average of 2 days longer to develop from first instar (L1) to fourth instar (L4) (8.8 ± 0.2 days) compared to the susceptible colony (6.6 ± 0.2 days). The development time from first instar to pupa formation was significantly longer by 3 days in the resistant colony (10.28 ± 0.3 days) than in susceptible colony (7.5 ± 0.2 days). The time from egg hatching to adult emergence was significantly longer for the resistant colony (12.1 ± 0.3 days) than the susceptible colony (9.6 ± 0.2 days). The pupation rate (80%; 95% (CI: 77.5-83.6) vs 83.5%; 95% (CI: 80.6-86.3)) and adult emergence rate (86.3% vs 92.8%) did not differ between the resistant and susceptible colonies, respectively. The sex ratio of the females to males for the resistant (1:1.2) and susceptible colonies (1:1.07) was significantly different.
    CONCLUSION: The study showed that pyrethroid resistance in An. gambiae had a fitness cost on their pre-imaginal development time and survival. Insecticide resistance delayed the development and reduced the survivorship of An. gambiae larvae. The study findings are important in understanding the fitness cost of insecticide resistance vectors that could contribute to shaping resistant management strategies.
    Keywords:  Anopheles gambiae; Fitness; Insecticide resistance; Larval life-traits
  10. Trans R Soc Trop Med Hyg. 2021 Jun 09. pii: trab087. [Epub ahead of print]
      BACKGROUND: Understanding the human malaria infectious reservoir is important for elimination initiatives. Here, we implemented mosquito membrane feeding experiments to prepare for larger studies to quantify the transmission potential and relative contribution of the human infectious reservoir.METHODS: Patients with clinical malaria attending four health facilities with at least 16 Plasmodium falciparum gametocytes per μL were recruited during the 2018 transmission season. Infectiousness to mosquitoes was assessed by direct membrane feeding assay (DMFA). We compared our results with a Bayesian predictive model to investigate the relationship between infectiousness and gametocyte density and explore the impact of fever on gametocyte infectivity.
    RESULTS: A total of 3177 suspected malaria cases were screened; 43.3% (1376) had microscopically patent P. falciparum parasites and 3.6% (114) of them had gametocytes. Out of 68 DMFAs, 38 (55.9%) resulted in at least one infected mosquito, with a total of 15.4% (1178/7667) of mosquitoes infected with 1-475 oocysts per gut. The relationship between mosquito infection prevalence and gametocytaemia was similar to other African settings and negatively associated with fever (OR: 0.188, 95% CI 0.0603 to 0.585, p=0.0039).
    CONCLUSIONS: Among symptomatic malaria patients, fever is strongly associated with transmission failure. Future studies can use DMFA to better understand the human malaria reservoir in settings of low endemicity in The Gambia and inform malaria elimination initiatives.
    Keywords:   Anopheles coluzzii ; Plasmodium falciparum ; The Gambia; direct membrane feeding assays; gametocytes
  11. J Econ Entomol. 2021 Jun 12. pii: toab107. [Epub ahead of print]
      Organized mosquito control programs (MCP) in the United States have been protecting public health since the early 1900s. These programs utilize integrated mosquito management for surveillance and control measures to enhance quality of life and protect the public from mosquito-borne diseases. Because much of the equipment and insecticides are developed for agriculture, MCP are left to innovate and adapt what is available to accomplish their core missions. Unmanned aerial systems (UAS) are one such innovation that are quickly being adopted by MCP. The advantages of UAS are no longer conjectural. In addition to locating mosquito larval habitats, UAS affords MCP real-time imagery, improved accuracy of aerial insecticide applications, mosquito larval detection and sampling. UAS are also leveraged for applying larvicides to water in habitats that range in size from multi-acre wetlands to small containers in urban settings. Employing UAS can reduce staff exposure to hazards and the impact associated with the use of heavy equipment in sensitive habitats. UAS are utilized by MCP nationally and their use will continue to increase as technology advances and regulations change. Current impediments include a dearth of major UAS manufacturers of equipment that is tailor-made for mosquito control, pesticides that are optimized for application via UAS and regulations that limit the access of UAS to national airspace. This manuscript highlights the strengths and weaknesses of UAS within MCP, provides an update on systems and methods used, and charts the future direction of UAS technology within MCP tasked with public health protection.
    Keywords:  adulticide; drone; integrated mosquito management; larvicide; unmanned aerial vehicle; vector surveillance
  12. Future Microbiol. 2021 Jun 08.
      Drawing of host blood is a natural phenomenon during the bite of blood-probing insect vectors. Along with the blood meal, the vectors introduce salivary components and a trail of microbiota. In the case of infected vectors, the related pathogen accompanies the aforementioned biological components. In addition to Anopheles gambiae or Anopheles stephensi, the bites of other nonmalarial vectors cannot be ignored in malaria-endemic regions. Similarly, the bite incidence of Phlebotomus papatasi cannot be ignored in visceral leishmaniasis-endemic regions. Even the chances of getting bitten by uninfected vectors are higher than the infected vectors. We have discussed the probability or possibility of uninfected, infected, and/or nonvector's saliva and gut microbiota as a therapeutic option leading to the initial deterrent to pathogen establishment.
    Keywords:  infectious diseases; insect vector; microbiota; mosquito; saliva; sandfly; uninfected bite; vaccine
  13. Parasitol Res. 2021 Jun 10.
      Arthropod vectors are frequently exposed to a diverse assemblage of parasites, but the consequence of these infections on their biology and behavior are poorly understood. We experimentally evaluated whether the ingestion of a common protozoan parasite of avian hosts (Haemoproteus spp.; Haemosporida: Haemoproteidae) impacted the survivorship of Culex quinquefasciatus (Say) (Diptera: Culicidae). Blood was collected from wild northern cardinals (Cardinalis cardinalis) in College Station, Texas, and screened for the presence of Haemoproteus spp. parasites using microscopic and molecular methods. Experimental groups of Cx. quinquefasciatus mosquitoes were offered Haemoproteus-positive cardinal blood through an artificial feeding apparatus, while control groups received Haemoproteus-negative cardinal blood or domestic canary (Serinus canaria domestica) blood. Culex quinquefasciatus mosquitoes exposed to Haemoproteus infected cardinal blood survived significantly fewer days than mosquitoes that ingested Haemoproteus-negative cardinal blood. The survival of mosquitoes fed on positive cardinal blood had a median survival time of 18 days post-exposure and the survival of mosquitoes fed on negative cardinal blood exceeded 50% across the 30 day observation period. Additionally, mosquitoes that fed on canary controls survived significantly fewer days than cardinal negative controls, with canary control mosquitoes having a median survival time of 17 days. This study further supports prior observations that Haemoproteus parasites can be pathogenic to bird-biting mosquitoes, and suggests that Haemoproteus parasites may indirectly suppress the transmission of co-circulating vector-borne pathogens by modulating vector survivorship. Our results also suggest that even in the absence of parasite infection, bloodmeals from different bird species can influence mosquito survivorship.
    Keywords:  Birds; Mosquito; Pathogen; Survivorship; Vectorial capacity
  14. J Med Entomol. 2021 Jun 09. pii: tjab100. [Epub ahead of print]
      A cue for long-range vision allows mosquitoes to identify hosts and differentiate the ecological niches (e.g., habitats). However, the visual factors involved in attracting mosquitoes to a host are complex and have not been fully understood. Therefore, we assessed color preference to Aedes albopictus (Skuse) and Culex pipiens (Conquillett) as diurnal and nocturnal species, respectively, using seven fundamental colors including black, white, red, yellow, green, blue, and purple with each trap at 100 lux in a laboratory. We used a binary behavioral assay using the Mosquito Preference Index (MPI) as a preference ratio with a range of 0-1. Our analyses showed that Ae. albopictus had a greater response to black (MPIs, 0.7), followed closely by red, blue, and purple (MPIs, 0.6). We also found that red, blue, and purple were significantly higher (P < 0.05) than those of green (MPI, 0.5), white (MPI, 0.3), and yellow (MPI, 0.2). Similarly, the MPIs for Cx. pipiens were significantly higher at black and red (MPIs, 0.7; P < 0.05) compare to those of white and yellow (MPIs, 0.3; P < 0.05). The color preference of Ae. albopictus showed significant correlation to luminous intensities (L-value) (r = -0.640; P = 0.000) and blue intensities (b-value) (r = -0.372; P = 0.000) for all seven colors. In addition, Cx. pipiens negatively correlated (r = -0.703; P = 0.000) between color preference and L-value. Our analyses provide a greater understanding of how color plays a role in visual sensory stimuli, and how that could potentially affect mosquito host-seeking behavior.
    Keywords:   Aedes albopictus ; Culex pipiens ; color; host-seeking behavior; mosquito
  15. Malar J. 2021 Jun 05. 20(1): 247
      BACKGROUND: Plasmodium knowlesi is now the major cause of human malaria in Malaysia, complicating malaria control efforts that must attend to the elimination of multiple Plasmodium species. Recent advances in the cultivation of P. knowlesi erythrocytic-stage parasites in vitro, transformation with exogenous DNA, and infection of mosquitoes with gametocytes from culture have opened up studies of this pathogen without the need for resource-intensive and costly non-human primate (NHP) models. For further understanding and development of methods for parasite transformation in malaria research, this study examined the activity of various trans-species transcriptional control sequences and the influence of Plasmodium vivax centromeric (pvcen) repeats in plasmid-transfected P. knowlesi parasites.METHODS: In vitro cultivated P. knowlesi parasites were transfected with plasmid constructs that incorporated Plasmodium vivax or Plasmodium falciparum 5' UTRs driving the expression of bioluminescence markers (firefly luciferase or Nanoluc). Promoter activities were assessed by bioluminescence, and parasites transformed with human resistant allele dihydrofolate reductase-expressing plasmids were selected using antifolates. The stability of transformants carrying pvcen-stabilized episomes was assessed by bioluminescence over a complete parasite life cycle through a rhesus macaque monkey, mosquitoes, and a second rhesus monkey.
    RESULTS: Luciferase expression assessments show that certain P. vivax promoter regions, not functional in the more evolutionarily-distant P. falciparum, can drive transgene expression in P. knowlesi. Further, pvcen repeats may improve the stability of episomal plasmids in P. knowlesi and support detection of NanoLuc-expressing elements over the full parasite life cycle from rhesus macaque monkeys to Anopheles dirus mosquitoes and back again to monkeys. In assays of drug responses to chloroquine, G418 and WR9910, anti-malarial half-inhibitory concentration (IC50) values of blood stages measured by NanoLuc activity proved comparable to IC50 values measured by the standard SYBR Green method.
    CONCLUSION: All three P. vivax promoters tested in this study functioned in P. knowlesi, whereas two of the three were inactive in P. falciparum. NanoLuc-expressing, centromere-stabilized plasmids may support high-throughput screenings of P. knowlesi for new anti-malarial agents, including compounds that can block the development of mosquito- and/or liver-stage parasites.
    Keywords:  Antimalarial drug response assays; Genetic transformation; Heterologous transfection; In vitro growth assays; Luciferase expression; Transgenic parasites
  16. Malar J. 2021 Jun 05. 20(1): 248
      BACKGROUND: The Solomon Islands has made significant progress in the control of malaria through vector control, access and use of improved diagnostics and therapeutic drugs. As transmission is reduced there is a need to understand variations in transmission risk at the provincial and village levels to stratify control methods.METHODS: A cross-sectional survey of malaria in humans was conducted in the Solomon Islands during April 2018. Nineteen villages across 4 provinces were included. The presence of Plasmodium species parasites in blood samples was detected using PCR.
    RESULTS: Blood samples were analysed from 1,914 participants. The prevalence of DNA of Plasmodium falciparum was 1.2 % (n = 23) and for Plasmodium vivax was 1.5 % (n = 28). 22 % (n = 5/23) of P. falciparum DNA positive participants were febrile and 17 % of P. vivax DNA positive participants (n = 5/28). The prevalence of both P. falciparum and P. vivax was extremely spatially heterogeneous. For P. falciparum, in particular, only 2 small foci of transmission were identified among 19 villages. Plasmodium falciparum infections were uniformly distributed across age groups. Insecticide-treated bed net use the night prior to the survey was reported by 63 % of participants and significantly differed by province.
    CONCLUSIONS: Malaria transmission across the Solomon Islands has become increasingly fragmented, affecting fewer villages and provinces. The majority of infections were afebrile suggesting the need for strong active case detection with radical cure with primaquine for P. vivax. Village-level stratification of targeted interventions based on passive and active case detection data could support the progress towards a more cost-effective and successful elimination programme.
    Keywords:  Heterogeneous transmission; Malaria elimination; Plasmodium falciparum; Plasmodium vivax; Solomon Islands
  17. PLoS One. 2021 ;16(6): e0252957
      Malaria incidence in Myanmar has significantly reduced over recent years, however, completeness and timeliness of incidence data remain a challenge. The first ever nationwide malaria infection and seroprevalence survey was conducted in Myanmar in 2015 to better understand malaria epidemiology and highlight gaps in Annual Parasite Index (API) data. The survey was a cross-sectional two-stage stratified cluster-randomised household survey conducted from July-October 2015. Blood samples were collected from household members for ultra-sensitive PCR and serology testing for P. falciparum and P. vivax. Data was gathered on demography and a priori risk factors of participants. Data was analysed nationally and within each of four domains defined by API data. Prevalence and seroprevalence of malaria were 0.74% and 16.01% nationwide, respectively. Prevalent infection was primarily asymptomatic P. vivax, while P. falciparum was predominant in serology. There was large heterogeneity between villages and by domain. At the township level, API showed moderate correlation with P. falciparum seroprevalence. Risk factors for infection included socioeconomic status, domain, and household ownership of nets. Three K13 P. falciparum mutants were found in highly prevalent villages. There results highlight high heterogeneity of both P. falciparum and P. vivax transmission between villages, accentuated by a large hidden reservoir of asymptomatic P. vivax infection not captured by incidence data, and representing challenges for malaria elimination. Village-level surveillance and stratification to guide interventions to suit local context and targeting of transmission foci with evidence of drug resistance would aid elimination efforts.
  18. Pak J Med Sci. 2021 May-Jun;37(3):37(3): 721-726
      Objective: To detect ZIKV using reverse transcription-polymerase chain reaction (RT-PCR) among clinical samples tested negative for Dengue virus (DENV) by RT-PCR in Punjab, 2016.Methods: A descriptive cross-sectional study was carried out for duration of two months. Total of 506 samples were collected within seven days from onset of illness from all over hospitals of Punjab, Pakistan of which 350 were selected simply randomly to test for presence of ZIKV by using "Trioplex Real-Time RT-PCR Assay (Trioplex)". Cohen's kappa coefficient (κ) and 95% confidence interval (CI) were used to assess the degree of concordance between DENV positive results of non-structural protein 1 (NS1) and IgM solid-phase enzyme immunoassay (ELISA).
    Results: No samples were positive for any ZIKV, DENV or Chikungunya virus (CHIKV) by Trioplex. Among the 350 samples, 26 samples were positive concordant and the degree of concordance between NS1- and IgM-ELISA was 13% and κ coefficient was -0.71 (95% CI -0.79, -0.63).
    Conclusion: At study time, no samples were positive for ZIKV. Strengthening laboratory capacity to confirm arboviruses for Punjab's laboratories is warranted. Trioplex RT-PCR has 100% sensitivity so there are nominal chances of false negative results. Establishing syndromic surveillance for Zika and conducting a sero-surveillance survey for Zika in areas with high human and Aedes mosquito density are recommended in Punjab.
    Keywords:  Dengue virus; Dengue-like Illness; Pakistan; Zika virus
  19. PLoS Negl Trop Dis. 2021 Jun 07. 15(6): e0009496
      Dengue is a viral disease transmitted by mosquitoes. The rapid spread of dengue could lead to a global pandemic, and so the geographical extent of this spread needs to be assessed and predicted. There are also reasons to suggest that transmission of dengue from non-human primates in tropical forest cycles is being underestimated. We investigate the fine-scale geographic changes in transmission risk since the late 20th century, and take into account for the first time the potential role that primate biogeography and sylvatic vectors play in increasing the disease transmission risk. We apply a biogeographic framework to the most recent global dataset of dengue cases. Temporally stratified models describing favorable areas for vector presence and for disease transmission are combined. Our models were validated for predictive capacity, and point to a significant broadening of vector presence in tropical and non-tropical areas globally. We show that dengue transmission is likely to spread to affected areas in China, Papua New Guinea, Australia, USA, Colombia, Venezuela, Madagascar, as well as to cities in Europe and Japan. These models also suggest that dengue transmission is likely to spread to regions where there are presently no or very few reports of occurrence. According to our results, sylvatic dengue cycles account for a small percentage of the global extent of the human case record, but could be increasing in relevance in Asia, Africa, and South America. The spatial distribution of factors favoring transmission risk in different regions of the world allows for distinct management strategies to be prepared.
  20. J Med Entomol. 2021 Jun 09. pii: tjab096. [Epub ahead of print]
      Indoor residual spraying (IRS) is one of the key vector control tools with a long history of use in the world. Ethiopia has set a goal to eliminate malaria from selected districts mainly by applying IRS and the distribution of long-lasting insecticidal nets. IRS is applied in low malaria transmission districts which are epidemic prone and in districts with high malaria transmission. Ethiopia uses insecticides that are recommended by World Health Organization; these insecticides must also be registered in Ethiopia. The registration of new and potential products requires confirmatory, local efficacy trials to be performed. Actellic 300CS, now registered, is one of such potential product. Actellic 300CS showed average mortalities of 99.6%, 99.6%, and 99.0% on the sprayed surfaces in the experimental huts, the top, middle, and bottom sections, respectively during the first 6 mo of the study period. Beyond 6 mo, (7, 8, and 9 mo) follow-up, mortalities for the top, middle, and bottom sections were 85.2%, 86.3%, and 85.2%, respectively. The results showed that the residual efficacy of Actellic 300CS was up to 9 mo with the first 6 mo exhibiting mortalities of greater than 99% while the next 3 mo showed mortalities exceeding 85%. Actellic 300CS was effective against fully susceptible laboratory-reared Anopheles arabiensis on all four surface types (rough, smooth, dung, and painted surfaces) tested in this study and could be used as one of the chemical insecticides of choice for the ongoing IRS programs in Ethiopia.
    Keywords:   Anopheles arabiensis ; Actellic 300CS; IRS; malaria; residual efficacy
  21. Clin Infect Dis. 2021 Jun 12. pii: ciab540. [Epub ahead of print]
      BACKGROUND: West Nile virus (WNV) is the leading cause of arboviral disease in the United States and is associated with significant morbidity and mortality. A previous analysis found that a vaccination program targeting persons aged ≥60 years was more cost effective than universal vaccination, but costs remained high.METHODS: We used a mathematical Markov model to evaluate cost-effectiveness of an age- and incidence-based WNV vaccination program. We grouped states and large counties (≥100,000 persons aged ≥60 years) by median annual WNV incidence rates from 2004 to 2017 for persons aged ≥60 years. We defined WNV incidence thresholds, in increments of 0.5 cases per 100,000 persons ≥60 years. We calculated potential cost per WNV vaccine-prevented case and per quality adjusted life years (QALYs) saved.
    RESULTS: Vaccinating persons aged ≥60 years in states with an annual incidence of WNV neuroinvasive disease of ≥0.5 per 100,000 resulted in approximately half the cost per health outcome averted compared to vaccinating persons aged ≥60 years in all the contiguous United States. This approach could potentially prevent 37% of all neuroinvasive disease cases and 63% of WNV-related deaths nationally. Employing such a threshold at a county-level further improved cost-effectiveness ratios while preventing 19% and 30% of WNV-related neuroinvasive disease cases and deaths, respectively.
    CONCLUSIONS: An age- and incidence-based WNV vaccination program could be a more cost-effective strategy than an age-based program while still having a substantial impact on lowering WNV-related morbidity and mortality.
    Keywords:  West Nile virus; cost-effectiveness; impact; vaccination
  22. Health Econ. 2021 Jun 08.
      In public health epidemiology, quasi-experimental methods are widely used to estimate the causal impacts of interventions. In this paper, we demonstrate the contribution the synthetic control method (SCM) can make in evaluating public health interventions, when routine surveillance data are available and the validity of other quasi-experimental approaches may be in question. In our application, we evaluate the short-term effects of a large-scale Mass Drug Administration (MDA) based malaria elimination initiative in Southern Mozambique. We apply the SCM to district level weekly malaria incidence data and compare the observed reduction in age group specific malaria incidence. Between August 2015 and April 2017, a total of 13,322 (78%) cases of malaria were averted relative to the synthetic control. During the peak malaria seasons, the elimination initiative resulted in an 87% reduction in Year 1 (December 2015-April 2016), and 79% reduction in Year 2 (December 2016-April 2017). Comparison with an interrupted time series approach shows the SCM accounts for pre-intervention trends in the data and post-intervention weather events influencing malaria cases. We conclude MDA brought about a drastic reduction in malaria burden and can be a useful addition to existing (or new) vector control strategies and tools in accelerating towards elimination.
    Keywords:  Mozambique; malaria elimination; surveillance data, synthetic control method, quasi-experimental evaluation
  23. PLoS Negl Trop Dis. 2021 Jun 11. 15(6): e0009465
      Dengue is steadily increasing worldwide and expanding into higher latitudes. Current non-endemic areas are prone to become endemic soon. To improve understanding of dengue transmission in these settings, we assessed the spatiotemporal dynamics of the hitherto largest outbreak in the non-endemic metropolis of Buenos Aires, Argentina, based on detailed information on the 5,104 georeferenced cases registered during summer-autumn of 2016. The highly seasonal dengue transmission in Buenos Aires was modulated by temperature and triggered by imported cases coming from regions with ongoing outbreaks. However, local transmission was made possible and consolidated heterogeneously in the city due to housing and socioeconomic characteristics of the population, with 32.8% of autochthonous cases occurring in slums, which held only 6.4% of the city population. A hierarchical spatiotemporal model accounting for imperfect detection of cases showed that, outside slums, less-affluent neighborhoods of houses (vs. apartments) favored transmission. Global and local spatiotemporal point-pattern analyses demonstrated that most transmission occurred at or close to home. Additionally, based on these results, a point-pattern analysis was assessed for early identification of transmission foci during the outbreak while accounting for population spatial distribution. Altogether, our results reveal how social, physical, and biological processes shape dengue transmission in Buenos Aires and, likely, other non-endemic cities, and suggest multiple opportunities for control interventions.