Measuring spatial co-occurrences of species potentially involved in Leishmania transmission cycles through a predictive and fieldwork approach.

The Leishmaniases are a group of neglected tropical diseases caused by different species of the protozoan parasite Leishmania, transmitted to its mammalian hosts by the bites of several species of female Phlebotominae sand flies. Many factors have contributed to shifts in the disease distribution and eco epidemiological outcomes, resulting in the emergence of Cutaneous Leishmaniasis outbreaks and the incrimination of vectors in unreported regions. New research development is vital for establishing the new paradigms of the present transmission cycles, hoping to facilitate new control strategies to reduce parasite transmission. Hereafter, this work aims to model and infer the current transmission cycles of Cutaneous Leishmaniasis in Colombia defined by vector and mammal species distributed and interacting in the different regions and validate them by performing sand fly and mammal collections. Vector-host co-occurrences were computed considering five ecoregions of the Colombian territory defined by the World Wide Fund for Nature (WWF) and downloaded from The Nature Conservancy TNC Maps website. Four validation sites were selected based on Cutaneous Leishmaniasis prevalence reports. Sand flies and mammals captured in the field were processed, and species were defined using conventional taxonomic guidelines. Detection of infection by Leishmania was performed to identify transmission cycles in the selected areas. This study uses predictive models based on available information from international gazetteers and fieldwork to confirm sand fly and mammalian species' sustaining Leishmania transmission cycles. Our results show an uneven distribution of mammal samples in Colombia, possibly due to sampling bias, since only two departments contributed 50% of the available samples. Bats were the vertebrates with the highest score values, suggesting substantial spatial overlap with sand flies than the rest of the vertebrates evaluated. Fieldwork allowed identifying three circulating Leishmania species, isolated from three sand fly species. In the Montane Forest ecosystem, one small marsupial, Gracilinanus marica, was found infected with Leishmania panamensis, constituting the first record of this species infected with Leishmania. In the same locality, an infected sand fly, Pintomyia pia, was found. The overall results could support the understanding of the current transmission cycles of Leishmaniasis in Colombia.

The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ'≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Admixture estimates obtained by a maximum likelihood method using HLA-A/-B/-DRB1 as genetic estimators revealed that the main genetic components in Mexico as a whole are Native American (ranging from 37.8% in the northern part of the country to 81.5% in the southeastern region) and European (ranging from 11.5% in the southeast to 62.6% in northern Mexico). African admixture ranged from 0.0 to 12.7% not following any specific pattern. We were able to detect three major immunogenetic clusters correlating with genetic diversity and differential admixture within Mexico: North, Central and Southeast, which is in accordance with previous reports using genome-wide data. Our findings provide insights into the population immunogenetic substructure of the whole country and add to the knowledge of mixed ancestry Latin American population genetics, important for disease association studies, detection of demographic signatures on population variation and improved allocation of public health resources.

Genetic diversity of HLA system in two populations from Nayarit, Mexico: Tepic and rural Nayarit.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 161 Mexicans from the state of Nayarit living in Tepic (N = 97) and rural communities (N = 64), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Nayarit include eight Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nayarit are Native American (50.79 ±â€¯5.03% by ML; 42.24% of Native American haplotypes) and European (37.04 ±â€¯6.21% by ML; 35.72% of European haplotypes), while African genetic component is less apparent but relatively high (12.17 ±â€¯2.50% by ML; 13.36% of African haplotypes).

Genetic diversity of HLA system in four populations from Baja California, Mexico: Mexicali, La Paz, Tijuana and rural Baja California.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 250 Mexicans from the states of Baja California Norte and Baja California Sur living in Mexicali (N = 100), La Paz (N = 75), Tijuana (N = 25) and rural communities (N = 50) to obtain information regarding allelic and haplotypic frequencies. The most frequent haplotypes for the Baja California region include nine Native American and five European haplotypes. Admixture estimates revealed that the main genetic components are European (50.45 ±â€¯1.84% by ML; 42.03% of European haplotypes) and Native American (43.72 ±â€¯2.36% by ML; 40.24% of Native American haplotypes), while the African genetic component was less apparent (5.83 ±â€¯0.98% by ML; 9.36% of African haplotypes).

Genetic diversity of HLA system in two populations from Sinaloa, Mexico: Culiacán and rural Sinaloa.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 286 Mexicans from the state of Sinaloa living in Culiacán (N = 103) and rural communities (N = 183) to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes for the state of Sinaloa include ten Native American most probable ancestry and five European most probable ancestry haplotypes. The admixture estimates revealed that the main genetic components in the state of Sinaloa are European (62.39 ±â€¯3.47%) and Native American (37.61 ±â€¯2.85%), while the African genetic component was estimated as virtually absent (0.00 ±â€¯1.86%).

Genetic diversity of HLA system in three populations from Guanajuato, Mexico: Guanajuato City, León and rural Guanajuato.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 262 Mexicans from the state of Guanajuato living in the cities of Guanajuato (N = 78), León (N = 22) and rural communities (N = 162), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes found in the state of Guanajuato include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Guanajuato are Native American (50.64 ±â€¯2.11% by ML, 43.35% of Native American haplotypes) and European (44.14 ±â€¯1.14% by ML; 39.35% of European haplotypes), while African genetic component is less apparent (5.22 ±â€¯2.08% by ML; 8.36% of African haplotypes).

Genetic diversity of HLA system in two populations from Michoacán, Mexico: Morelia and rural Michoacán.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 498 Mexicans from the state of Michoacán living in the city of Morelia (N = 150) and rural communities (N = 348), to obtain information regarding allelic and haplotypic frequencies. We find that the ten most frequent haplotypes found in the state of Michoacán include 12 Native American and two European haplotypes. Admixture estimates revealed that the main genetic components in the state of Michoacán are Native American (48.79 ±â€¯1.44%) and European (43.10 ±â€¯0.86%), while African genetic component is less apparent (8.11 ±â€¯0.85%). Our findings add to the growing knowledge on the population genetics of Western Mexico and provide new HLA data on populations from Michoacán.

Genetic diversity of HLA system in six populations from Jalisco, Mexico: Guadalajara city, Tlajomulco, Tlaquepaque, Tonalá, Zapopan and rural Jalisco.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 2046 Mexicans from the state of Jalisco living in the city of Guadalajara (N = 1189), Tlajomulco (N = 30), Tlaquepaque (N = 39), Tonalá (N = 35), Zapopan (N = 168) and rural communities (N = 585), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes found in the state of Jalisco include nine Native American most probable ancestry and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Jalisco are European (48.45 ±â€¯1.18% by ML; 41.66% of European haplotypes) and Native American (44.02 ±â€¯1.24% by ML; 39.86% of Native American haplotypes), while African genetic component is less apparent (7.53 ±â€¯0.30% by ML; 9.62% of African haplotypes).

Genetic diversity of HLA system in two populations from Colima, Mexico: Colima city and rural Colima.

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 104 Mexicans from the state of Colima living in the city of Colima (N = 61) and rural communities (N = 43), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Colima include eight Native American, two European and one African haplotype. Admixture estimates revealed that the main genetic components in the state are Native American (52.74 ±â€¯3.88% by ML; 48.10% of Native American haplotypes) and European (37.52 ±â€¯8.94% by ML; 26.66% of European haplotypes), and a relatively high African genetic component (9.74 ±â€¯8.40% by ML; 11.91% of African haplotypes).

Diversity patterns, Leishmania DNA detection, and bloodmeal identification of Phlebotominae sand flies in villages in northern Colombia.

Leishmaniases are neglected tropical diseases exhibiting complex transmission cycles due to the number of parasite species circulating, sand fly species acting as vectors and infected mammals, including humans, which are defined in the New World as accidental hosts. However, current transmission scenarios are changing, and the disease is no longer exclusively related to forested areas but urban transmission foci occur, involving some species of domestic animals as suspected reservoirs. The aim of this study was to determine the transmission cycles in urban environments by evaluating sand fly diversity, detection of Leishmania DNA, and bloodmeal sources through intra and peridomestic collections. The study was carried out in Colombia, in 13 municipalities of Cordoba department, implementing a methodology that could be further used for the evaluation of vector-borne diseases in villages or towns. Our sampling design included 24 houses randomly selected in each of 15 villages distributed in 13 municipalities, which were sampled in two seasons in 2015 and 2016. Sand flies were collected using CDC light traps placed in intra and peridomestic habitats. In addition to the morphological identification, molecular identification through DNA barcodes was also performed. A total of 19,743 sand flies were collected and 13,848 of them (10,268 females and 3,580 males) were used in molecular procedures. Circulation of two known parasite species-Leishmania infantum and Leishmania panamensis was confirmed. Blood source analyses showed that sand flies fed on humans, particularly in the case of the known L. infantum vector, P. evansi; further analyses are advised to evaluate the reservoirs involved in parasite transmission. Our sampling design allowed us to evaluate potential transmission cycles on a department scale, by defining suspected vector species, parasite species present in different municipalities and feeding habits.

Spatial Distribution of Sand Fly Vectors and Eco-Epidemiology of Cutaneous Leishmaniasis Transmission in Colombia.

BACKGROUND: Leishmania is transmitted by Phlebotominae insects that maintain the enzootic cycle by circulating between sylvatic and domestic mammals; humans enter the cycles as accidental hosts due to the vector's search for blood source. In Colombia, leishmaniasis is an endemic disease and 95% of all cases are cutaneous (CL), these cases have been reported in several regions of the country where the intervention of sylvatic areas by the introduction of agriculture seem to have an impact on the rearrangement of new transmission cycles. Our study aimed to update vector species distribution in the country and to analyze the relationship between vectors' distribution, climate, land use and CL prevalence. METHODS: A database with geographic information was assembled, and ecological niche modeling was performed to explore the potential distribution of each of the 21 species of medical importance in Colombia, using thirteen bioclimatic variables, three topographic and three principal components derived from NDVI. Binary models for each species were obtained and related to both land use coverage, and a CL prevalence map with available epidemiological data. Finally, maps of species potential distribution were summed to define potential species richness in the country. RESULTS: In total, 673 single records were obtained with Lutzomyia gomezi, Lutzomyia longipalpis, Psychodopygus panamensis, Psathyromyia shannoni and Pintomyia evansi the species with the highest number of records. Eighteen species had significant models, considering the area under the curve and the jackknife results: L. gomezi and P. panamensis had the widest potential distribution. All sand fly species except for Nyssomyia antunesi are mainly distributed in regions with rates of prevalence between 0.33 to 101.35 cases per 100,000 inhabitants and 76% of collection data points fall into transformed ecosystems. DISCUSSION: Distribution ranges of sand flies with medical importance in Colombia correspond predominantly to disturbed areas, where the original land coverage is missing therefore increasing the domiciliation potential. We highlight the importance of the use of distribution maps as a tool for the development of strategies for prevention and control of diseases.