Dengue vaccine acceptance and willingness to pay: a systematic review and meta-analysis.

OBJECTIVE: Dengue is the most important human vector-borne disease in terms of disease burden. A first dengue vaccine has recently been licenced, and others are in advanced stages of development. However, to date, none of these vaccines has achieved balanced efficacy and safety for all dengue serotypes. The aim of this systematic review and meta-analysis was to assess the global acceptance and willingness to pay for unspecified dengue vaccines. METHODS: This systematic review and meta-analysis included cross-sectional and cohort studies that reported values for vaccine acceptance (percentage) and willingness to pay for currently available or hypothetical vaccines. These values were pooled using random-effects models for the acceptance, while weighted linear regression was chosen for willingness to pay. Heterogeneity between studies was assessed using prediction intervals (PIs), and a domain-based tool was used to assess the risk of bias. Subgroup and sensitivity analyses were performed where appropriate. This study was registered with PROSPERO (CRD42021255784). RESULTS: We included 19 studies from the Americas and Asia in the quantitative meta-analysis. The risk of bias was mainly related to the selection of participants and to the assumptions about the safety and efficacy of the vaccines. The percentage of vaccine acceptance was 88.3% (95% CI: 81.0%-93.0%), with some heterogeneity between studies (80% PI: 52.9%-98.1%). Willingness to pay was US$ 46.7 (95% CI: 25.9-67.5) per vaccine recipient. There were differences between continents, with higher acceptance in the Americas. CONCLUSIONS: We were able to obtain global estimates of vaccine acceptance and willingness to pay and identify the associated factors that influence these values. This knowledge is relevant for the planning of future vaccination strategies.

A rural-urban latitudinal study of the distributions of Culex quinquefasciatus and Culex pipiens bioforms in their southernmost sympatric fringe.

Mosquitoes grouped in the complex Culex pipiens L. (Diptera: Culicidae) are important vectors of medical and veterinary diseases. In the South American sympatric region, Cx. pipiens and Culex quinquefasciatus Say coexist and potentially hybridize. To identify key drivers of their geographical distribution, mosquito immatures were collected from flower vases of eight urban/rural cemetery pairs within a 5° latitudinal transect along Buenos Aires Province, Argentina. The specimens were identified by molecular methods and their relative proportion modelled as a function of environmental variables. At the beginning of the warm season, northern and southern cemeteries presented exclusively Cx. quinquefasciatus and Cx. pipiens, respectively, with different proportions of both at mid latitudes. By the end of the summer, Cx. quinquefasciatus was present throughout the study area, exclusively in 11 of the 16 cemeteries both rural and urban, whereas Cx. pipiens was predominant only in the southernmost pair. Mean annual temperature, photoperiod variability and time of the season were key drivers of their distributions. All specimens of Cx. pipiens were identified as form molestus and no hybrids were recognized. The reported distribution patterns and the potential absence of Cx. pipiens f. pipiens and hybrids are discussed, along with their implications in disease transmission.

Past, present and future of Aedes aegypti in its South American southern distribution fringe: What do temperature and population tell us?

Aedes aegypti (Diptera: Culicidae) (Linnaeus) is currently the major threat among arbovirus vectors in the Americas. We examined its past, present, and future distribution patterns in the South American fringe in association with environmental and demographic variables at two spatial scales. We updated the database of the occurrence of Ae. aegypti per locality and modelled by GLMM the past occurrence (until 2000) and its expansion (2001-2017) as a function of air temperature, precipitation, altitude, and population. We also conducted a field survey in 7 pairs of urban/rural cemeteries along the entire temperature range within the expansion region. At both scales, mean annual air temperature and human population were significantly associated with the distribution of Ae. aegypti. Projection of the expansion models for 2030 under two climatic change scenarios showed a vast infestation, mainly driven by the shift of the 16 °C isotherm. We postulate a quantitative compromise between air temperature and human population associated with vector occurrence, along with potential thresholds for their mutual favourability.

Heterogeneous distribution of Culex pipiens, Culex quinquefasciatus and their hybrids along the urbanisation gradient.

The mosquitoes of the Culex pipiens complex, hereafter referred to as the Pipiens Assemblage, are vectors of arbovirus of worldwide concern including West Nile and St. Louis encephalitis. Given their distinct eco-physiology and vectorial capacity, accurate specimen identification and insight in the environmental drivers of their distribution are essential for the understanding of disease transmission patterns. Using a PCR-based identification protocol, we characterized the spatial distribution of Cx. pipiens, Cx. quinquefasciatus and their hybrids developing in used tyres located within the overlapping region in South America as a function of different estimators of the urbanisation gradient. Out of 84 samples collected from tyre piles of 20 sites, we identified 369 larvae which corresponded predominantly to Cx. quinquefasciatus (76.4% of immatures) all along the gradient but more frequent at the urban end. Cx. pipiens (21.4%) was more conspicuous at the low urbanised end but was also present in highly urbanised sites, whereas hybrids were collected in very low numbers (2.2%). The urbanisation estimator best associated with the heterogeneous occurrence of the Pipiens Assemblage members was the proportion of impervious surface 1km around each tyre pile, which explained 41.7% of the variability in the data, followed closely by the distance to the Capital City (38.3%). Cumulative annual precipitation, population number in a 1km radius around each pile and distance to the de la Plata River were significantly associated with the distribution of the Pipiens Assemblage at lower explanation percentages (20-23%). A thorough understanding of the ecological basis and environmental associations of the distribution of Pipiens Assemblage members will enable forecasting population trends in changing environments to develop effective control measures for mosquitoes and the diseases they transmit.

Imperviousness as a predictor for infestation levels of container-breeding mosquitoes in a focus of dengue and Saint Louis encephalitis in Argentina.

Dengue and Saint Louis encephalitis virus are among the most important emerging viruses transmitted by mosquitoes at the global scale, and from 2009 onward both diseases have reached temperate Argentina. To test whether the urbanization level can be used as a predictor for the infestation levels of container-breeding mosquito vectors, we searched for Aedes aegypti and Culex pipiens in 8400 water-filled containers from 14 cemeteries of Buenos Aires Province and we used generalized linear models to relate positive containers with the impervious area quantified inside (internal PIA) and outside (external PIA) cemeteries. The best model for Ae. aegypti explained 91% of the variability and included the season, the internal PIA and the external PIA at 1km as a quadratic function, showing a parabolic response peaking in ∼75%. Regarding the infestation levels of Cx. pipiens, the final model explained 75% of the variability and included only the season. In view of these results, the percentage of impervious area efficiently predicted the infestation levels of Ae. aegypti but not of Cx. pipiens. Considering the worldwide relevance of the former in dengue transmission, the simple quantification of imperviousness proposed herein provides a helpful basis for vector surveillance and control in urbanized areas.

Oviposition strategies of temporary pool mosquitoes in relation to weather, tidal regime and land use in a temperate wetland.

Wetlands have traditionally been associated with harbouring mosquitoes, a well-known nuisance and vectors of diseases. Within mosquito life cycle, oviposition is a determinant event by shaping their individual fitness and vectorial capacity. The study was conducted in one of the main temperate wetlands in South America. We used Generalized Linear Models to study the relation between temperature, precipitation, tidal regime, land use, microenvironment, and the occurrence of floodwater (Ochlerotatus and Psorophora spp.) and raft-laying (Culex and Uranotaenia spp.) mosquitoes using temporary pools as larval habitats. Pool occurrence was negatively associated with temperature, and positively related to precipitation and high tides. As regards the land use, it was lowest in domestic areas and plantations, intermediate in secondary forests, and highest in marshes. Each oviposition strategy was best modelled as a function of different environmental factors. The occurrence of floodwater mosquitoes was positively associated with high cumulative precipitation and low tide records. Raft-laying mosquitoes were related to low temperature records, while the effect of flooding varied with the land use. In view of these results, physical (water inputs and movement), chemical, and biological (egg and larval flushing, and predatory interactions) considerations are given to provide insight in the oviposition patterns of mosquitoes occurring in this complex wetland. We finally propose the generation of a tidal flow as a control measure against floodwater mosquitoes, which are the most anthropophilic in the study area.

Environmental predictors of the occurrence of ground water mosquito immatures in the Paraná Lower Delta, Argentina.

Characterizing mosquito larval habitats is essential for understanding the complex interactions between immatures and the biotic and abiotic components of their environment. Using generalized linear mixed models, we studied the environmental predictors of the presence of three ubiquitous mosquito species breeding in ground water habitats in the Paraná Lower Delta, Argentina. During a year-round survey, 34.1% of the 419 ground water habitats inspected were positive for either Culex dolosus s.l. (Lynch Arribálzaga 1891), Aedes crinifer (Theobald 1903), or Culex intrincatus Brèthes 1916. Univariate analysis showed that the former two occurred throughout the year, whereas the latter during the summer and fall. Ae. crinifer and Cx. intrincatus were more frequently collected in secondary forests, whereas Cx. dolosus s.l. was homogeneously distributed among land uses. Best generalized linear mixed models included the sampling period and landscape variables in different combinations for each species. Spatial dependence of the data was evident for Cx. dolosus s.l. and Ae. crinifer. Our results showed that the most widespread species presented different spatio-temporal distribution patterns, related with land use, anthropic intervention, and seasonality, highlighting the complexity of the wetland under study. This methodological approach could aid in the selection of priority areas for vector control and disease risk management.

The effect of shade on the container index and pupal productivity of the mosquitoes Aedes aegypti and Culex pipiens breeding in artificial containers.

The aim of this study was to assess whether certain attributes of larval breeding sites are correlated with pupal productivity (i.e. numbers of pupae collected per sampling period), so that these could be used as the focus for control measures to enhance control efficiency. Therefore, the objectives were to identify the months of highest pupal productivity of Aedes aegypti (L.) and Culex pipiens L. (Diptera: Culicidae) in an urban temperate cemetery in Argentina where artificial containers of < 6 L (flower vases) were the predominant breeding habitats, to compare various measures of the productivity of sunlit and shaded containers and to determine whether the composition of the containers affected pupal productivity. Over a period of 9 months, 200 randomly chosen water-filled containers (100 sunlit and 100 shaded), out of approximately 3738 containers present (approximately 54% in shade), were examined each month within a cemetery (5 ha) in Buenos Aires (October 2006 to June 2007). In total, 3440 immatures of Cx pipiens and 1974 of Ae. aegypti were collected. The larvae : pupae ratio was 10 times greater for the former, indicating that larval mortality was greater for Cx pipiens. Both mosquito species showed a higher container index (CI) in shaded than in sunlit containers (Ae. aegypti: 12.8% vs. 6.9% [chi(2) = 17.6, P < 0.001]; Cx pipiens: 6.3% vs. 1.8% [chi(2) = 24, P < 0.001]). However, the number and the density of immatures per infested container and the number of pupae per pupa-positive container did not differ significantly between sunlit and shaded containers for either species. Therefore, the overall relative productivity of pupae per ha of Ae. aegypti and Cx pipiens was 2.3 and 1.8 times greater, respectively, in shaded than in sunlit areas as a result of the greater CIs of containers in shaded areas. Neither the CI nor the number of immatures per infested container differed significantly among container types of different materials in either lighting condition. The maximum CI and total pupal counts occurred in March for Ae. aegypti and in January and February for Cx pipiens. The estimated peak abundance of pupae in the whole cemetery reached a total of approximately 4388 in the middle of March for Ae. aegypti and approximately 1059 in the middle of January for Cx pipiens. Spearman's correlations between monthly total productivity and monthly CI were significant at P < 0.001 for Ae. aegypti (r(s) = 0.975) and P < 0.01 for Cx pipiens (r(s) = 0.869). Our findings indicate that the efficacy of control campaigns against the two most important mosquito vectors in temperate Argentina could be improved by targeting containers in shaded areas, with maximum effort during species-specific times of year when pupal productivity is at its peak.

Are antigen test kits efficient for detecting heartworm-infected dogs at the southern distribution limit of the parasite in South America? Preliminary results.

The aim of this study was to evaluate the performance of commercial heartworm antigen tests in dogs harbouring Dirofilaria immitis microfilariae near its distribution limit in South America. A total of 4934 blood samples of adult dogs from Southern Greater Buenos Aires were examined to detect circulating microfilariae in the buffy coat interface between December 2005 and April 2006. Microfilariae were detected in 88 (1.8%) blood samples and all the microfilariae observed were identified as D. immitis by acid phosphatase stain technique. In a first trial, 69 (78.4%) out of the 88 serum were positive by Speed((R)) Diro. Then, a new test was performed over 25 microfilariae-positive serum samples randomly selected among the 88 previously tested samples and using simultaneously Speed((R)) Diro, Witness((R)) Dirofilaria and Snap((R)) 3dx. This second trial showed identical results for the three different tests, in which 19 (76%) samples were positive. Therefore, more than 20% of microfilaremic dogs were antigen negative. The main hypothesis that could explain our finding is a low worm burden in the study area. According to our preliminary results, it is highly recommendable the complementary use of antigen tests and other procedures to obtain an accurate diagnostic near the distribution limit of the parasite.

Detailed assessment of microhabitat suitability for Aedes aegypti (Diptera: Culicidae) in Buenos Aires, Argentina.

Little information is available on the ecology of Aedes aegypti Linnaeus at the southern extreme of its distribution (Buenos Aires, Argentina), particularly on microhabitat suitability. The aim of our study was to identify at a detailed scale, microhabitat factors that correlate with the presence of preimaginal stages of the mosquito. In March 2001, we performed a spatial census of all containers located in a 1 ha patch within a cemetery in Buenos Aires City. On a reference map (1:700) we plotted the position of graves and surrounding corridors, the location of containers, the shade projected by each plant between 10:00 and 16:00 h and vegetation cover. We classified vegetation by height, substrate by composition and shadow by level of exposure to sunlight. We performed univariate and multivariate logistic regression analyses with nine constructed independent variables, some of them at scales of 0.5, 1, 2, 3, and 10 m. Of 850 receptacles examined, 101 contained preimaginal stages of Ae. aegypti. Level of exposure to sunlight, type of substratum, vegetation height and distance of containers to vegetation were significantly associated with the presence of breeding sites at the studied scales. Final multivariate models were significant at scales of 2 m (chi(3)2=25.693, p<0.001) and 3m (chi(3)2=26.440, p<0.001), and 65.9 and 66.8% of our data were correctly classified, respectively, for each scale. Our results suggest that sites less exposed to sunlight, with taller and closer vegetation, and in shaded and vegetated neighbourhoods were the most favourable microhabitats for Ae. aegypti breeding.

Characterization of Triatoma guasayana biotopes in a hardwood forest of Santiago del Estero, Argentina.

Triatoma guasayana is a silvatic triatomine species distributed in Argentina, Bolivia and Paraguay. The study was performed in a secondary forest of Santiago del Estero, Argentina. The abundance of T. guasayana was evaluated by census in the following wild biotopes: quimiles (Opuntia quimilo), chaguares (dry bromeliads), logs and underground burrows. Ten biotopes of each type were dismantled in winter (August) and another 40 in summer (January); all fauna was recorded. The biotopes most infested by T. guasayana were quimiles (65%), followed by chaguares (55%), and logs (25%). Quimiles and chaguares were infested in both seasons, whereas logs were positive only in summer and burrows were never infested. Infestation and abundance were higher in summer than in winter. The biotope structure is a key factor for T. guasayana colonization. The larger number of refuges, the constant presence of blood sources and suitable inner microclimatic conditions offered by quimiles may favour the persistence of T. guasayana colonies. The richness of invertebrate fauna per type of biotope was ranked in the same order as that of T. guasayana, suggesting similar microhabitat requirements for all studied arthropods.

Environmental characteristics of the cemeteries of Buenos Aires City (Argentina) and infestation levels of Aedes aegypti (Diptera: Culicidae).

Cemeteries with many water-filled containers, flowers, sources of human blood, and shade are favorable urban habitats for the proliferation of Aedes aegypti, a vector of yellow fever and dengue. A total of 22,956 containers was examined in the five cemeteries of the city of Buenos Aires, Argentina. The vector was found in four cemeteries that showed an average infestation level of 5.5% (617 positive out of 11,196 water-filled containers). The four cemeteries positive for Ae. aegypti showed significantly different (p<0.01) infestation levels. Vegetation cover and percentage of infestation were significantly correlated (p<0.01), but neither cemetery area nor number of available containers were significantly related to the proportion of positive vases. Our results suggest that the cemeteries of Buenos Aires represent a gradient of habitat favorableness for this vector species, some of which may act as foci for its proliferation and dispersal.