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.

Ecology of fleas and their hosts in the trifinio of north-east Argentina: first detection of Rickettsia asembonensis in Ctenocephalides felis felis in Argentina.

Fleas are important in public health due to their role as parasites and vectors of pathogens, including Rickettsia. The aim of this study was to evaluate the diversity, abundance and prevalence of fleas and the presence of Rickettsia in the trifinio of north-east Argentina. Fleas from household and synanthropic animals were obtained from urban and periurban areas. They were taxonomically identified and samples of 227 fleas in 86 pools were analysed by polymerase chain reaction targeting the gltA and ompB genes of Rickettsia spp. The study revealed that Ctenocephalides felis felis was dominant on dogs, cats and opossums, with higher prevalence in the periurban area. The Shannon-Wiener and Morisita-Horn indices expressed differences in the diversity and similarity values of the absolute abundances of the species between the areas compared. DNA amplifications revealed 30.8% C. f. felis pools positive for Rickettsia spp. Phylogenetic analysis showed that the haplotype obtained was identical to Rickettsia asembonensis from Peru and Brazil. This is the first detection in Argentina of R. asembonensis that infects C. f. felis, and we emphasize the importance of conducting research from a 'One Health' perspective on the role of opossums and rodents in the integration of the transmission cycles of rickettsial bacteria.

Description of Evandromyia cristacapita sp. nov., a new sand fly species of the Argentinian Chaco.

A new species of phlebotomine sand fly collected in the rural and peri-urban areas of wet and dry subregions of the Chaco Province, Argentina, is described. Illustrations of male and female adults are presented. Morphological characters allow the inclusion of the new species within the Evandromyia genus, Barrettomyia subgenus, Cortelezzii series (Diptera: Psychodidae). Furthermore, we present an identification key for the Cortelezzii series of the Barrettomyia subgenus with a new distinct species complex for its correct identification. The species was denominated as Evandromyia cristacapita sp. nov.

Temperature and photoperiod effects on dormancy status and life cycle parameters in Aedes albopictus and Aedes aegypti from subtropical Argentina.

Aedes albopictus (Diptera: Culicidae) distribution is bounded to a subtropical area in Argentina, while Aedes aegypti (Diptera: Culicidae) covers both temperate and subtropical regions. We assessed thermal and photoperiod conditions on dormancy status, development time and mortality for these species from subtropical Argentina. Short days (8 light : 16 dark) significantly increased larval development time for both species, an effect previously linked to diapause incidence. Aedes albopictus showed higher mortality than Ae. aegypti at 16 °C under long day treatments (16 light : 8 dark), which could indicate a lower tolerance to a sudden temperature decrease during the summer season. Aedes albopictus showed a slightly higher percentage of dormant eggs from females exposed to a short day, relative to previous research in Brazilian populations. Since we employed more hours of darkness, this could suggest a relationship between day-length and dormancy intensity. Interestingly, local Ae. aegypti presented dormancy similar to Ae. albopictus, in accordance with temperate populations. The minimum dormancy in Ae. albopictus would not be sufficient to extend its bounded distribution. We believe that these findings represent a novel contribution to current knowledge about the ecophysiology of Ae. albopictus and Ae. aegypti, two species with great epidemiological relevance in this subtropical region.

Phlebotominae in peri-domestic and forest environments inhabited by Alouatta caraya in northeastern Argentina.

Multiple species of Phlebotominae are vectors of Leishmania (Protozoa: Trypanosomatidae), which causes visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL). To describe the Phlebotominae (Diptera: Psychodidae) related to the environments of black and gold howler monkeys Alouatta caraya (Humbodlt, 1812) (Primates: Atelidae), potential vectors were sampled in different landscapes and vertical strata of sleeping trees. Phlebotomine captured between December 2011 and March 2012 (2365 individuals) belonged to eight species, of which Nyssomyia neivai (Pinto, 1926) (61.4%) and Migonemyia migonei (França, 1920) (18.73%) were the most abundant, and Ny. withmani was recorded for the first time in the Chaco province. In the 'peri-domestic' landscape, the phlebotomine were mainly captured in henhouses (78.7%), whereas the tree canopy in 'rural' and 'wild' landscapes yielded 31.2% and 29.1% of the phlebotomine, respectively. A significant association between the type of landscape and the species of phlebotomine was observed by multivariate analysis. Lutzomyia longipalpis (Lutz & Neiva, 1912) and Mg. migonei were associated with 'peri-domestic' landscape, and Ny. neivai was associated with the 'wild' landscape. The results of this prospective study suggest that the interaction between phlebotomine and A. caraya could be a key factor with respect to understanding the epidemiology of leishmaniasis.

Spatiotemporal dynamics of Lutzomyia longipalpis and macro-habitat characterization using satellite images in a leishmaniasis-endemic city in Argentina.

The spatiotemporal population dynamics of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae) were evaluated in a city in Argentina in which visceral leishmaniasis is endemic. Over 14 sampling sessions, 5244 specimens of five species of Phlebotominae (Diptera: Psychodidae) were captured, of which 2458 (46.87%) specimens were L. longipalpis. Generalized linear models were constructed to evaluate the associations between L. longipalpis abundance and explanatory variables derived from satellite images. The spatial variable 'stratum' and the temporal variable 'season' were also included in the models. Three variables were found to have significant associations: the normalized difference vegetation index; land surface temperature, and low urban coverage. The last two of these were associated with L. longipalpis abundance only during summer and winter, respectively. This variation between seasons supports the development of models that include temporal variables because models of distributions of the abundance of a species may show different critical variables according to the climatic period of the year. Abundance decreased gradually towards the downtown area, which suggests that L. longipalpis responds to a meta-population structure, in which rural-periurban source populations that persist over time may colonize adjacent areas. This information allows for a spatiotemporal stratification of risk, which provides public health authorities with a valuable tool to help optimize prevention measures against visceral leishmaniasis.

Co-occurrence and seasonal and environmental distributions of the sandflies Lutzomyia longipalpis and Nyssomyia whitmani in the city of Puerto Iguazú, northeastern Argentina.

The aim of this work was to study the distribution of Phlebotominae (Diptera: Psycodidade) abundance in time and space in an area in northeastern Argentina with vector transmission of visceral and tegumentary leishmaniasis. For this, 51 households were selected using a 'worst scenario' criterion where one light trap was set during two consecutive nights in peridomiciles in the transitions between the four seasons, and the environment was surveyed simultaneously. The relationships of phlebotomine assemblage structure and the most abundant species with seasonality and environmental variables were evaluated using a canonical correspondence analysis and generalized linear mixed models, respectively. A total of 5110 individuals were captured. Lutzomyia longipalpis (Lutz & Neiva, 1912) and Nyssomyia whitmani (Antunes & Coutinho, 1939) were the most abundant species captured in all samplings (98.3% of the total capture). The period of highest abundance of Lu. longipalpis was early autumn, and it was distributed in the most urbanized areas. Nyssomyia whitmani occupied mainly the less urbanized areas, showing peaks of abundance in early spring and summer. Other species were captured in low numbers and showed seasonal-spatial variations similar to those of Ny. whitmani. We confirmed Leishmania spp. vector persistence throughout the year in spatial patches of high abundance even during the less favorable season.

Temporal distribution of, and effect of anthropic modifications on, phlebotomine populations in the Chaco Bioregion, Argentina.

Migonemyia migonei is the predominant species in the dry ecoregion and Nyssomyia neivai in the humid region, although co-dominance in humid highly modified areas could be observed. Vector abundance seems to be modulated by environmental anthropization, as the abundance and predominance of Ny. neiviai and Mg. migonei increased in highly modified areas. In Humid Chaco, the risk of human-vector contact would be present throughout the year, being particularly high in spring/summer, and in Dry Chaco, the risk would be restricted to temperate and humid months.

Evaluation of efficacy of impregnated curtains in experimental hen houses as a phlebotomine control tool in northeast Argentina.

The aim of this study was to evaluate the effectiveness of insecticide-impregnated curtains against the entry of phlebotomine (Diptera: Psychodidae) flies into experimental slatted hen houses in an area endemic for American cutaneous leishmaniasis (ACL). Three treatments in experimental dwellings containing three chickens each were applied using, respectively, an impregnated curtain (IC), a non-impregnated curtain (NIC) and no curtain (NC). A control site without chickens (WC) was included. The study used permethrin at 0.05 g/m2 . During each month for 1 year, each experimental hen house randomly received all treatments. Phlebotomine sandflies were captured using REDILA BL traps placed inside the hen house. Significant differences in abundances of phlebotomine flies/trap/night were observed between treatments (χ2 = 17853.58, d.f. = 3, P < 0.0001): 59.7% of phlebotomines were captured in the NC treatment, 26.3% in the NIC treatment, 8.0% in the IC treatment and 6.1% in the WC condition. Nyssomyia whitmani (Antunes & Coutinho) was the most abundant species in all collections (89.9%). These results showed a lower abundance of phlebotomines in the experimental hen house in the IC condition than in the hen house in the NC condition (P < 0.05) and that the presence of NIC represents an effective physical barrier against phlebotomines (P < 0.05). Therefore, the use of curtains may be an alternative eco-friendly method for the prevention of indoor ACL transmission in slatted dwellings, which represent a common house type in northeast Argentina.

Triatoma infestans, to be or not to be autogenic?

Autogeny, the ability to develop eggs without a meal in the adult stage, has been described in several groups of arthropods, especially hematophagous Diptera Nematocera. In obligate hematophagous hemimetabolous insects that feed on blood in all their instars, such as Triatominae, this concept gives rise to species with apparently facultative autogeny, such as Triatoma infestans. Generalized linear models were applied to explain egg production by the predictor variables molting weight as a proxy of nymphal accumulated reserves and digested blood weight as an indicator of adult reserve in fasted, incompletely fed and engorged at repletion females. The relationship between these indicators of nutritional status and egg development turned out to be a continuous function in which, with molting weights greater than 254 mg, the insects are autogenic, but for the first batch of eggs with molting weights between 132 and 253 mg, they require one adult meal of at least 202 mg, and with molting weights less than 131 mg at least two meals are required. Both molting weight and blood intake could determine oocyte production in an additive manner, thus the concept of autogeny as a switch on-off phenomenon is not directly applicable to Triatominae. Nevertheless, autogenic ability would allow Triatominae with relatively long cycles to accelerate population growth under favorable or low competition conditions during colonization or recovery after a control intervention.

Lutzomyia longipalpis, Gone with the Wind and Other Variables.

Lutzomyia longipalpis (Lutz & Neiva) is the main vector of Leishmania infantum (Nicolle) in America, associated in turn with the current spread and urbanization of American visceral leishmaniasis (AVL). The vector distribution in AVL foci shows a spatial-temporal clustering despite the different epidemiological contexts. The factors associated with the macroscale distribution of Lu. longipalpis as a landscape stratification are discussed in the framework of the process of their adaptation to anthropized environments. On the other hand, the fact that Lu. longipalpis is clustered in only a few hot spots or critical sites suggests that microscale approaches that describe the trap surrounding environment and the availability of refuges and food sources are better at explaining the uneven distribution of this vector, and should contribute, together with macroscale variables, to design operational control strategies. With regard to temporal distribution and climatic or vegetation data obtained by remote sensing as variables to explain and forecast the abundance of Lu. longipalpis, it is necessary to take into account the time lags in relation to the life cycle of the vector, the difference between the level of daily activity and actual abundance, and the differences in critical variables and thresholds according to the region or season. In conclusion, this review shows that it is feasible to characterize the distribution of Lu. longipalpis at focus level and within it to identify the main critical sites, proposing a sequential cost-effectivity strategy for urban AVL surveillance and control.

First Evidence of Akodon-Borne Orthohantavirus in Northeastern Argentina.

Orthohantaviruses (genus Orthohantavirus, family Hantaviridae) are the etiologic agents of Hantavirus Pulmonary Syndrome in the Americas. In South America, orthohantaviruses are highly diverse and are hosted by sigmodontine rodents (subfamiliy Sigmodontinae, family Cricetidae), an also diverse group of rodents. The aims of this work were to (1) identify orthohantavirus hosts and (2) to study the spatial and temporal variations in the prevalence of infection and their associations with community, environmental and individual characteristics, in different environments of Misiones province, northeastern Argentina. Live-capture sessions were carried out during two years in different land uses, with a trapping effort of 31,653 trap nights. We captured 719 individuals from the species Akodon montensis, Rattus rattus, Mus musculus, Calomys tener, Thaptomys nigrita, Oligoryzomys nigripes, Euryoryzomys russatus, Oligoryzomys flavescens, Brucepattersonius sp., and Juliomys pictipes. Antibodies against orthohantavirus were detected in Akodon montensis in one natural protected and one periurban areas, and it was the most abundant species in almost every study sites. We observed the presence of spatial focality of orthohantavirus infection and a positive association with host abundance suggesting the existence of a threshold density. At the individual level, large, reproductively active, and male individuals were more likely to have antibodies against orthohantavirus. This is the first record of orthohantavirus infection in A. montensis in Argentina, which shows the importance of investigations about emerging diseases.

Distribution of phlebotomine sand flies (Diptera: Psychodidae) in a primary forest-crop interface, Salta, Argentina.

Disordered urbanization and deforestation are the main activities proposed as causal factors of re-emergence of American cutaneous leishmaniasis caused by Leishmania braziliensis. The purpose of this work was to investigate, in the hyperendemic area of Argentina, the distribution of Phlebotomine sand flies at the modified primary vegetation-crop interface, as one of the potential sites where the effects of changing landscape on sand fly populations may be manifested. Twenty samplings were made between June 2004 and August 2005. The traps to catch sand flies were set on two consecutive nights every month (except in 5 mo, where it became every 15 d). The relationship between sand fly abundance and meteorological and landscape variables was analyzed using non-metric multidimensional scaling and Kendall's correlation coefficients. Lutzomyia neivai (Pinto) was the most abundant species, followed by Lutzomyia migonei (França), Lutzomyia cortelezzii (Brèthes), Lutzomyia shannoni (Dyar), and Lutzomyia punctigeniculata (Floch and Abonnenc). Traps located close to modified areas collected the greatest numbers of sand flies, whereas traps located in the least modified area (adjacent to the primary vegetation) collected the fewest. There was a strong negative correlation between the abundance of sand flies and precipitation. This study shows that even small modifications in the landscape led to an increase in sand fly abundance, mainly Lu. neivai, a Leishmania braziliensis vector. This underscores the need for recommendations about the risk of American cutaneous leishmaniasis before any environmental intervention is done in an endemic area, as well as for the monitoring of sand fly population dynamics at the site of intervention, before, during, and after the process.

Leishmania infantum DNA detected in phlebotomine species from Puerto Iguazú City, Misiones province, Argentina.

In Puerto Iguazú City, Argentina, human and canine Visceral Leishmaniasis cases have been recorded since the year 2010, with Leishmania infantum as the etiological agent and Lutzomyia longipalpis as its main vector. In the present study, polymerase chain reaction and sequencing were used to detect L. infantum DNA in 3.9% of the female sandflies captured in Puerto Iguazú City. This is the first report of L. infantum DNA detection in Micropygomyia quinquefer, and the second one in Lu. longipalpis and Nyssomyia whitmani for Argentina. Although the detection of Leishmania DNA itself is not enough to determine a Phlebotomine species as a vector, these results are significant in setting the direction of further investigations of vectorial competence and capacity, necessary to define the roles of different sandflies species as specific or permissive vectors in the transmission VL cycle.

Prevention of intestinal parasites in a tri-border area of Latin America: Children perceptions and an integral health education strategy.

To investigate knowledge of school-aged children and their perception on intestinal parasites, and to assess knowledge reconstruction on prevention practices after specific training in the subject. We performed an activity package that included the analysis of children's drawings of intestinal parasites, and information and communication technologies (ITCs) to transfer knowledge about these pathogens and prevention measures. Retrieval learning activities were performed to fixation of general and specific prevention and control measures.Overall, we found that there is a knowledge gap in many aspects of parasite biology and ecology, and therefore on the risk of infection and acquisition mechanisms. After ITCs, the children improved their knowledge over non-trained children.The approaches used to transfer knowledge and for learning, fixation were valuable tools for incorporating changes in misconceptions and in the deep-rooted habits that favour entero-parasitic diseases. This has important implications for the specific design of future education materials and campaigns. Understanding of perceptions helps to provide justifications and knowledge to achieve changes in unhealthy habits, and it constitutes the basis for the transformation of many risky practices.

Spatial and temporal patterns of phlebotomine sand flies (Diptera: Psychodidae) in a cutaneous leishmaniasis focus in northern Argentina.

Phlebotomine sand flies (Diptera: Psychodidae) were captured in an area of Argentina endemic for American cutaneous leishmaniasis (ACL). A total of 44,944 flies were collected during a 130-wk interepidemic period from 1990 through 1993. These sand flies included Lutzomyia neivai (Pinto) (97.8%), Lutzomyia migonei (Franca) (1.2%), Lutzomyia cortelezzii (Brèthes) (0.8%), Lutzomyia shannoni (Dyar) (0.1%), and Lutzomyia punctigeniculata (Floch and Abonnenc) (0.1%). Lutzomyia neivai was more abundant in secondary forests and peridomestic environments associated with human cases than in primary forest or xeric thorn scrub areas. Time series analyses of species densities suggested a bimodal or trimodal annual pattern related to rainfall peaks, a 5-wk reproductive cycle, and peridomestic local populations that were located adjacent to secondary forests. In general, sand fly abundance was correlated with the rainfall of the previous year. Lutzomyia neivai spatial distributions were consistent with ACL incidence patterns during the study and in the recent outbreaks in Argentina. However, Lu. migonei also may be involved in peridomestic transmission. Our results suggest that there is a need for improved, long-term surveillance of sand flies and ACL cases, as well as development of effective intervention strategies.

Comparison between two artificial shelter units and timed manual collections for detecting peridomestic Triatoma infestans (Hemiptera: Reduviidae) in rural northwestern Argentina.

A new artificial shelter unit was compared with segments of bamboo cane lined with pleated filter paper for detecting peridomestic Triatoma infestans Klug at Amamá and nearby rural villages in northwestern Argentina. The new shelter unit consisted of a black plastic, wide-mouthed jar with a screw cap on the top, and a removable central structure made of pleated corrugated paper. In devices exposed from February to December 1999 at 24 sites positive for T. infestans by timed manual collections with an irritant in April 1999, the cumulative percentage of sites with any sign of infestation detected by the shelter unit increased from 71% after 2 mo to 96% after 10 mo, whereas bamboo cane units concurrently detected only 12-42% of the sites. Sensitivity increased with time of exposure and the abundance of T. infestans per site. In 19 sites negative for T. infestans by inspection, shelters increasingly detected infestation at 16-63% of sites after 10 mo, whereas the bamboo canes only detected one infestation. Shelter units inspected three times over an 11-mo period were significantly more sensitive than a single manual search with an irritant performed in March 2000. Our study provided conclusive field evidence that the shelter unit was more sensitive for detecting peridomestic T. infestans than were timed manual searches, the standard reference method, or bamboo cane units. Rapid timed searches by skilled bug collectors during the early surveillance phase overlooked many peridomestic populations that, in the absence of control, inevitably would increase in abundance and repopulate treated areas.

Small-scale field trial of a sensing device for detecting peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in northwestern Argentina.

Two prototypes of sensing devices for detecting peridomestic populations of Triatoma infestans Klug were tested in paired trials with bamboo canes in Amamá and nearby rural villages under triatomine surveillance. In infested peridomestic structures housing domestic animals, 1-2 pairs of numbered devices were placed per test site, left for 3-9 nights, and inspected for evidence of infestation. Prototype A was a black plastic cylinder 19 cm high and 10 cm diameter, with a screw cap on the top, 2 openings in the bottom, and a removable central structure made of resistant plastic coated with leather. Prototype B had square leather pieces rolled into cylinders instead of the central structure. Prototype A was significantly more sensitive than the bamboo cane with pleated paper inside in 13 test sites in which 20 pairs were tried. In a smaller series involving 7 pairs, prototype B also detected infestations more frequently than the cane. Triatomine feces were the signs most frequently recorded by both prototypes, whereas the bamboo canes recorded no feces. Ten T. infestans and 1 Triatoma guasayana Wygodzinsky & Avalos were collected from the prototypes placed on the ground or walls, not beneath the thatched roofs of the animal shelters, whereas only 3 T. infestans were collected from the canes. This study describes an effective sensing device for detecting T. infestans populations in outdoor animal shelters and provides quantitative field data on its performance.

Study of a cutaneous leishmaniasis outbreak in General Vedia, Province of Chaco, 1996.

Between March and July 1996, a focalized epidemic outbreak of cutaneous leishmaniasis in General Vedia, province of Chaco, associated to the gallery forest of the Oro river was verified. The incidence rate in the area, which was 0-2/000 cases in preceding years, reached 8/000 cases in 1996. The risk of symptomatic infection was similar between sexes, but was different when analyzing the different age groups by sex, suggesting a greater relative importance of the peridomestic transmission for the females and of the transmission in the subtropical forest for the males. Specimens of Lutzomyia intermedia, a species already incriminated as a vector of Leishmaniasis in other provinces of northern Argentina, were captured and identified in the focus locality in May 1996. The possible causes of the outbreak related to the climatic variables and the vector abundance are analyzed and the results in the framework of possible preventive and control activities are discussed.

American cutaneous leishmaniasis outbreak, Tartagal city, province of Salta, Argentina, 1993.

An American cutaneous leishmaniasis outbreak, with cases clustering during 1993 in Tartagal city, Salta, was reported. The outbreak involved 102 individuals, 43.1% of them with multiple ulcers. Age (mean: 33 years old) and sex distribution of cases (74.5% males), as well as working activity (70 forest-related), support the hypothesis of classical forest transmission leishmaniasis, despite the fact that the place of permanent residence was in periurban Tartagal. Moreover, during July, sandflies were only collected from one of the 'deforestation areas'. Lutzomyia intermedia was the single species of the 491 phlebotomines captured, reinforcing the vector incrimination of this species. Most infections must have been acquired during the fall (April to June), a pattern consistent with previous sandfly population dynamics data. Based on the epidemiological and entomological results, it was advised not to do any vector-targeted periurban control measures during July. Further studies should be done to assess if the high rate of multiple lesions was due to parasite factors or to infective vector density factors.