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.

Factor XI deficiency is not associated with an increased risk of pneumonia and pneumonia-related mortality.

INTRODUCTION: Drugs targeting factor XI (FXI) shows promising results in reducing postoperative VTE. Recently, researchers have shown that FXI knockout mice had a worse outcome when infected with pathogens for pneumonia, raising concerns about the safety of these drugs. AIM: To investigate the effect of FXI deficiency on the incidence of pneumonia and outcomes of pneumonia in humans. METHODS: Using the computerized database of the largest healthcare provider in Israel, we identified adults who were tested for FXI activity between January of 2002 and December of 2014 (n = 10 193). Patients were followed up until December of 2016 for the occurrence of pneumonia and pneumonia requiring hospitalization as a proxy of severe pneumonia. RESULTS: A total of 8958 (87.9%) had normal FXI activity, 804 (7.9%) had partial deficiency and 431 (4.2%) had severe deficiency; 722 individuals had pneumonia during 70 881 person-years of follow-up (incidence rate: 10.2 per 1000 person-years). Compared to those with normal FXI activity, the adjusted HR for pneumonia was 0.87 (95% CI, 0.67-1.14), and 0.95 (0.69-1.30) for those with partial and severe FXI deficiency, respectively. Overall, 256 individuals were hospitalized for pneumonia during 72 209 person-years of follow-up (incidence rate: 3.5 per 1000 person-years). The corresponding HR for severe pneumonia was 1.0 (0.70-1.48) and 0.86 (0.53-1.40) in those with partial and severe FXI deficiency, respectively. FXI deficiency was not significantly associated with 30-day and 90-day mortality among patients with pneumonia. CONCLUSION: FXI deficiency was not associated with an increased risk of pneumonia, pneumonia severity or short-term mortality among patients with pneumonia.

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.

Assessment of the role of small mammals in the transmission cycle of tegumentary leishmaniasis and first report of natural infection with Leishmania braziliensis in two sigmodontines in northeastern Argentina.

To contribute to the knowledge of the role of small mammals in the transmission cycle of tegumentary leishmaniasis caused by Leishmania braziliensis, we studied the small mammal community and its temporal and spatial association with phlebotominae, as well as small mammal infection by Leishmania spp. by PCR-RFLP analyses in an endemic area of northeastern Argentina. Ten small mammal samplings were conducted (2007-2009, 7506 Sherman trap nights and 422 cage trap nights). In two of these samplings, 16 capture stations each one consisting of a CDC light trap to capture phlebotominae, two to four Sherman traps and two cage traps were placed. We found co-occurrence of phlebotominae and small mammal captures in four stations, which were all the stations with small mammal captures and yielded 97% (2295 specimens, including 21 gravid females) of the total phlebotominae captures, suggesting that small mammals may provide a potential source of blood for phlebotominae females. One Didelphis albiventris and two Rattus rattus were associated with high captures of Nyssomyia whitmani, vector of L. braziliensis in the study area. The PCR-RFLP analyses confirm the presence of L. braziliensis in two sigmodontine small mammals (Akodon sp. and Euryoryzomys russatus) for the first time in Argentina, to our knowledge.

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.

Rare bleeding disorders - bleeding assessment tools, laboratory aspects and phenotype and therapy of FXI deficiency.

Rare bleeding disorders (RBDs) are inherited deficiencies of coagulation factors such as fibrinogen, factor (F) II, FV, FVII, combined FV+FVIII, FX, FXI and FXIII. These disorders usually have a low prevalence in the general population and constitute approximately 3-5% of all coagulation disorders. However, in some countries they may have the same prevalence as haemophilia B due to the practice of consanguineous marriage. The clinical picture of RBDs is highly variable and can vary markedly from mild to severe, making both diagnosis and optimal treatment quite challenging. This review focuses on: (i) the efforts to establish a bleeding assessment tool adequate to RBDs, (ii) the optimal management of patients affected with FXI deficiency and (iii) the correlation between clinical severity and laboratory diagnosis when determining the minimum coagulant activity required to prevent bleeding in each RBD.

Phlebotominae of epidemiological importance in cutaneous leishmaniasis in northwestern Argentina: risk maps and ecological niche models.

In Argentina, 58.2% out of the 8126 Cutaneous Leishmaniasis (CL) incident cases accumulated from 1954 to 2006 were reported in the provinces of Salta and Jujuy. The aim of this study was to develop an exploratory risk map and a potential distribution map of the vector, in order to offer recommendations for CL prevention. A total of 12 079 Phlebotominae (Diptera: Psychodidae) belonging to the species Lutzomyia neivai (Pinto), Lu. migonei (França), Lu. cortelezzii (Brèthes), Lu. shannoni (Dyar), Lu. quinquefer (Dyar) and Brumptomyia spp. (França & Parrot) were captured. Potential distribution models were created for two species, Lu. neivai (incriminated vector of Leishmania braziliensis) and Lu. migonei, associated with domestic animals in Argentina and that in turn could be involved as a link between zoonotic transmission cycles and anthropozoonotic. The Maximum Entropy Modeling System (MaxEnt) was used. The Jackknife test was performed, and the 'rainfall of the driest month' was the variable that best generalized the models. Accuracy was evaluated by the area under the curve (AUC) and validated by the Cohen's kappa index. This approximation provides a new analytical resource of high potential for the prevention of the disease, in order to allocate resources properly and to develop the most suitable strategies for action.

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.

Ecological characterization of a cutaneous leishmaniasis outbreak through remotely sensed land cover changes.

In this work we assessed the environmental factors associated with the spatial distribution of a cutaneous leishmaniasis (CL) outbreak during 2015-2016 in north-eastern Argentina to understand its typical or atypical eco-epidemiological pattern. We combined locations of human CL cases with relevant predictors derived from analysis of remote sensing imagery in the framework of ecological niche modelling and trained MaxEnt models with cross-validation for predictors estimated at different buffer areas relevant to CL vectors (50 and 250 m radii). To account for the timing of biological phenomena, we considered environmental changes occurring in two periods, 2014-2015 and 2015-2016. The remote sensing analysis identified land cover changes in the surroundings of CL cases, mostly related to new urbanization and flooding. The distance to such changes was the most important variable in most models. The weighted average map denoted higher suitability for CL in the outskirts of the city of Corrientes and in areas close to environmental changes. Our results point to a scenario consistent with a typical CL outbreak, i.e. changes in land use or land cover are the main triggering factor and most affected people live or work in border habitats.

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.

Testing agonist-induced platelet aggregation by the Impact-R [Cone and plate(let) analyzer (CPA)].

The Impact-R [Cone and plate(let) analyzer (CPA)] is useful to assess platelet adhesion in different diseases and to monitor antiplatelet therapy. The purpose of the present study was to adapt this system to test agonist-induced platelet aggregation. Blood samples were tested by light transmission platelet aggregometry (LTA), Impact-R regular test and Impact-R agonist-response test. In the latter, samples were pre-incubated for 1 min with an agonist leading to platelet activation, micro-aggregates formation and reduced adhesion. Impact-R regular test of ten healthy volunteers demonstrated platelet adhesion (surface coverage, SC) of 11.2 +/- 2.6% while LTA induced by ADP, ristocetin, epinephrine, collagen and arachidonic acid (AA) yielded maximal aggregation (81% to 93%). In the Impact-R agonist-response test, SC was reduced to 2.2 +/- 1.0%, 1.2 +/- 0.9%, 2.3 +/- 1.0%, 2.2 +/- 0.8% and 2.4 +/- 0.4%, respectively. Prostaglandin E(1) treatment weakened SC reduction in response to ADP and epinephrine (SC of 8.8 +/- 1.8% and 9.5 +/- 2.0%, respectively). Inhibition of P2Y(12) receptor with 2MeSAMP resulted in a dose-dependent decrease in maximal aggregation in the ADP-induced test, which inversely correlated to SC in the Impact-R ADP-response test. The Impact-R agonist-response tests detected aggregation defects in patients with storage pool disease, severe von Willebrand disease and epinephrine response deficiency, and may be useful to assess the effect of different agonists on platelet aggregation.