Sensitivity, uncertainty and identifiability analyses to define a dengue transmission model with real data of an endemic municipality of Colombia.

Dengue disease is a major problem for public health surveillance entities in tropical and subtropical regions having a significant impact not only epidemiological but social and economical. There are many factors involved in the dengue transmission process. We can evaluate the importance of these factors through the formulation of mathematical models. However, the majority of the models presented in the literature tend to be overparameterized, with considerable uncertainty levels and excessively complex formulations. We aim to evaluate the structure, complexity, trustworthiness, and suitability of three models, for the transmission of dengue disease, through different strategies. To achieve this goal, we perform structural and practical identifiability, sensitivity and uncertainty analyses to these models. The results showed that the simplest model was the most appropriate and reliable when the only available information to fit them is the cumulative number of reported dengue cases in an endemic municipality of Colombia.

An alternative model to explain the vectorial capacity using as example Aedes aegypti case in dengue transmission.

Vectorial capacity (VC), as a concept that describes the potential of a vector to transmit a pathogen, has had historical problems related to lacks in dimensional significance and high error propagation from parameters that take part in the model to output. Hence, values estimated with those equations are not sufficiently reliable to consider in control strategies or vector population study. In this paper, we propose a new VC model consistent at dimensional level, i.e., the definition and the equation of VC have same and consistent units, with a parameter estimation method and mathematical structure that reduces the uncertainty in model output, using as a case of study an Aedes aegypti population of the municipality of Bello, Colombia. After a literature review, we selected one VC equation following biological, measurability and dimensional criteria, then we rendered a local and global sensitivity analysis, identifying the mortality rate of mosquitoes as a target component of the equation. Thus, we studied the Weibull and Exponential distributions as probabilistic models that represent the expectation of mosquitoes infective life, intending to include the best distribution in a selected VC structure. The proposed mortality rate estimation method includes a new parameter that represents an increase or decrease in vector mortality, as it may apply. We noticed that its estimation reduces the uncertainty associated with the expectation of mosquitoes' infective life expression, which also reduces the output range and variance in almost a half.

Vector competence analysis of two Aedes aegypti lineages from Bello, Colombia, reveals that they are affected similarly by dengue-2 virus infection.

Dengue is the second most prevalent vector-borne disease after malaria in Colombia. It is caused by dengue virus, an arbovirus that exhibits high epidemic power, which is evidenced by its occurrence in more than 80% of the country, largely because of the extensive dispersion of the mosquito vector Aedes aegypti. The existence of two lineages of Ae. aegypti has been proposed based on genetic differences at the mitochondrial level, and they have been reported to circulate in similar proportions in the municipality of Bello (Colombia). It has been suggested that the differentiation of these lineages could influence features such as vector competence (VC) and life table. With the aim of testing this hypothesis, female mosquitoes from both lineages collected from Bello were orally challenged with dengue virus serotype 2 (strain D2-HAN) to measure infection, dissemination, survival and fecundity. Analysis of VC showed an increase in viral titer over time; however, no significant differences were observed between the lineages. The survival rate was not different between the infected lineages, but comparing lineages, it was lower in infected mosquitoes, which may affect the intensity of transmission. Finally, we conclude that the genetic differentiation of Ae. aegypti into lineages did not confer differences in epidemiological status when the mosquitoes were infected with this D2 serotype strain.

Risk Factors Associated with Dengue Transmission and Spatial Distribution of High Seroprevalence in Schoolchildren from the Urban Area of Medellin, Colombia.

Dengue fever is an increasing health problem in tropical and subtropical regions. During 2010 in Medellin, the younger population presented a particularly high dengue incidence rate. This study estimated dengue virus (DENV) transmission in schoolchildren (aged 5-19 years) in Medellin from 2010 to 2012. A longitudinal serological survey (IgG) and spatial analysis were conducted to determine the distribution of DENV seroprevalence. A total of 4,385 schoolchildren participated for at least one year. Dengue seroprevalence significantly increased during the studied period (53.8% to 64.6%; p < 0.001). A significantly higher seroconversion rate was observed in 2010-2011 (16.8%) compared to 2011-2012 (7.8%). Multivariate regression analysis showed that the main factor associated with the seroprevalence was the aging. Furthermore, in 2010, patients with high socioeconomic status presented a lower risk. Predominant multitypic and DENV4 monotypic antibody responses were demonstrated. Geostatistical analysis evidenced a temporal clustering distribution of DENV seroprevalence in 2010. Population density and Ae. aegypti House Index were significantly correlated with the observed pattern. This study revealed high DENV transmission in schoolchildren determined as "sentinel population." High DENV risk was found in districts with combined poorly socioeconomic conditions and densest human and mosquito populations. These findings may allow to target population for effective prevention and vaccination campaigns.

Estimating Effects of Temperature on Dengue Transmission in Colombian Cities.

BACKGROUND: Dengue fever is a viral disease that affects tropical and subtropical regions of the world. It is well known that processes related to virus transmission by mosquitoes are highly influenced by weather. Temperature has been described as one of the climatic variables that largely governs the development and survival of mosquito eggs as well as the survival of all insect stages. Previously, we noted that high temperatures in the Colombian city of Riohacha negatively affect the establishment of dengue virus (DENV) infection in mosquitoes; in Bello and Villavicencio cities, which have lower average temperatures, DENV infection rates in mosquitoes are positively associated with a gradual increase in temperature. Here, we test the hypothesis that a similar effect of temperature can be detected in the incidence in the human population inhabiting dengue-endemic cities in Colombia. OBJECTIVE: Our objective was to evaluate the effect of climate variables related to temperature on DENV incidence in human populations living in DENV-endemic cities in Colombia. METHODS: Epidemiologic data from the Instituto Nacional de Salud from 2012-2015 and 7 variables related to temperature were used to perform Spearman rank sum test analyses on 20 Colombian cities. Additionally, locally estimated scatterplot smoothing analyses were performed to describe the relationship among temperatures and incidence. FINDINGS: Results indicated that Colombian cities with average and maximum temperatures greater than 28°C and 32°C, respectively, had an inversely related relationship to DENV incidence, which is in accordance with areas where higher temperatures are recorded in Colombia. CONCLUSION: Climatic variables related to temperature affect dengue epidemiology in different way. According to the temperature of each city, transmission might be positively or negatively affected.

Infection Rates by Dengue Virus in Mosquitoes and the Influence of Temperature May Be Related to Different Endemicity Patterns in Three Colombian Cities.

Colombia is an endemic country for dengue fever where the four serotypes of virus dengue (DENV1-4) circulate simultaneously, and all types are responsible for dengue cases in the country. The control strategies are guided by entomological surveillance. However, heterogeneity in aedic indices is not well correlated with the incidence of the disease in cities such as Riohacha, Bello and Villavicencio. As an alternative, molecular detection of dengue virus in mosquitoes has been proposed as a useful tool for epidemiological surveillance and identification of serotypes circulating in field. We conducted a spatiotemporal fieldwork in these cities to capture adult mosquitoes to assess vector infection and explain the differences between Breteau indices and disease incidence. DENV infection in females and DENV serotype identification were evaluated and infection rates (IR) were estimated. The relationship between density, dengue cases and vector index was also estimated with logistic regression modeling and Pearson's correlation coefficient. The lack of association between aedic indices and dengue incidence is in agreement with the weak associations between the density of the mosquitoes and their infection with DENV in the three cities. However, association was evident between the IR and dengue cases in Villavicencio. Furthermore, we found important negative associations between temperature and lag time from two to six weeks in Riohacha. We conclude that density of mosquitoes is not a good predictor of dengue cases. Instead, IR and temperature might explain better such heterogeneity.

Early Detection for Dengue Using Local Indicator of Spatial Association (LISA) Analysis.

Dengue is a viral disease caused by a flavivirus that is transmitted by mosquitoes of the genus Aedes. There is currently no specific treatment or commercial vaccine for its control and prevention; therefore, mosquito population control is the only alternative for preventing the occurrence of dengue. For this reason, entomological surveillance is recommended by World Health Organization (WHO) to measure dengue risk in endemic areas; however, several works have shown that the current methodology (aedic indices) is not sufficient for predicting dengue. In this work, we modified indices proposed for epidemic periods. The raw value of the epidemiological wave could be useful for detecting risk in epidemic periods; however, risk can only be detected if analyses incorporate the maximum epidemiological wave. Risk classification was performed according to Local Indicators of Spatial Association (LISA) methodology. The modified indices were analyzed using several hypothetical scenarios to evaluate their sensitivity. We found that modified indices could detect spatial and differential risks in epidemic and endemic years, which makes them a useful tool for the early detection of a dengue outbreak. In conclusion, the modified indices could predict risk at the spatio-temporal level in endemic years and could be incorporated in surveillance activities in endemic places.

Trypanosoma cruzi transmission in a Colombian Caribbean region suggests that secondary vectors play an important epidemiological role.

BACKGROUND: Colombia, as part of The Andean Countries Initiative has given priority to triatomine control programs to eliminate primary (domiciliated) vector species such as Rhodnius prolixus and Triatoma dimidiata. However, recent events of Trypanosoma cruzi transmission in localities where R. prolixus and T. dimidiata are not present suggest that other species are involved in the T. cruzi transmission cycle. METHODS: We studied T. cruzi transmission on Margarita Island, located on the Magdalena River in the Colombian Caribbean region, where a high number of non-domiciliated triatomines infected with T. cruzi inside human dwellings have been observed. A cross-sectional survey including serological studies in humans and parasitological and molecular methods in vectors and reservoirs was conducted. We investigated risk factors for human infection and house infestation, and evaluated the association between abundance of wild triatomines in palm trees (Attalea butyracea) across municipalities, seasons and anthropogenic land use. RESULTS: The T. cruzi seroprevalence rate in humans was 1.7% (13/743) and autochthonous active T. cruzi transmission was detected. The infection risk was associated with the capture of triatomines in human dwellings. Five wild mammal species were infected with T. cruzi, where Didelphis marsupialis was the main reservoir host with an 86.3% (19/22) infection rate. TcIb was the only genotype present among vectors. Triatomine abundance was significantly higher in Ecosystem 2, as well as in the dry season. Despite the absence of triatomine domiciliation in this area, T. cruzi active transmission was registered with a human seroprevalence rate similar to that reported in areas with domesticated R. prolixus. CONCLUSIONS: This study illustrates the importance of secondary and household invading triatomines in Chagas disease epidemiology in the Caribbean lowlands of Colombia.

Geographical clustering of Trypanosoma cruzi I groups from Colombia revealed by low-stringency single specific primer-PCR of the intergenic regions of spliced-leader genes.

A low-stringency single-primer polymerase chain reaction (LSSP-PCR) typing procedure targeted to the intergenic regions of spliced-leader genes (SL) was designed to profile Trypanosoma cruzi I stocks from endemic regions of Colombia. Comparison between SL-LSSP-PCR profiles of parasite DNA from vector faeces and cultures isolated from those faeces showed more conservative signatures than profiles using LSSP-PCR targeted to the minicircle variable regions (kDNA). This was also observed by analysing 15 parasite clones from one stock as well as serial samples of a same stock after in vitro culturing or inoculation into mice. Thus, SL-LSSP-PCR appears more appropriate than kDNA-LSSP-PCR for reliable typing of major T. cruzi I groups from in vitro cultured stocks and triatomine faeces. SL-LSSP-PCR grouped 46 of 47 T. cruzi I Colombian stocks according to their geographical procedences in four clusters: Cluster Cas from Casanare Department, Cluster Mg from Northern Magdalena department, Cluster Mom from Momposina Depression in Southern Magdalena and finally Cluster NW from northwestern Colombia, including Sucre, Chocó, Córdoba and Antioquia departments. Sequence analysis identified punctual mutations among amplicons from each cluster. Within Cluster Mg, sequence polymorphism allowed association with different sylvatic vector species. Novel SL sequences and LSSP-PCR profiles are reported from T. cruzi I infecting Eratyrus cuspidatus, Panstrongylus geniculatus and Rhodnius pallescens vectors.