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Lutzomyia longipalpis is the main vector of Leishmania infantum, the causative agent of visceral leishmaniasis in the Neotropical realm. Its taxonomic status has been widely discussed once it encompasses a complex of species. The knowledge about the genetic structure of insect vector populations helps the elucidation of components and interactions of the disease ecoepidemiology. Thus, the objective of this study was to genotypically analyze populations of the Lu. longipalpis complex from a macrogeographic perspective using Next Generation Sequencing. Polymorphism analysis of three molecular markers was used to access the levels of population genetic structure among nine different populations of sand flies. Illumina Amplicon Sequencing Protocol® was used to identify possible polymorphic sites. The library was sequenced on paired-end Illumina MiSeq platform. Significant macrogeographical population differentiation was observed among Lu. longipalpis populations via PCA and DAPC analyses. Our results revealed that populations of Lu. longipalpis from the nine municipalities were grouped into three clusters. In addition, it was observed that the levels of Lu. longipalpis population structure could be associated with distance isolation. This new sequencing method allowed us to study different molecular markers after a single sequencing run, and to evaluate population and inter-species differences on a macrogeographic scale. [ABSTRACT FROM AUTHOR]

Leishmania (Leishmania) infantum is the zoonotic agent of visceral leishmaniasis (VL), a disease with a global distribution. The transmission scenario of VL has been undergoing changes worldwide, with the biologic cycle invading urbanized areas and dispersing the parasites into other previously free areas. The epidemiological cycle in Brazil has dispersed from the Northeast to other regions of the country. In this study, an integrative approach, including genotyping Brazilian strains of L. (L.) infantum for 14 microsatellite markers and reviewing historical records of the disease, was used to assess dispersion routes throughout central-southern Brazil. Our results support three L. (L.) infantum dispersion routes: A) dispersion from Bolivia to the states of Mato Grosso, Mato Grosso do Sul and São Paulo via the Bolivia-Brazil gas pipeline from 1998 to 2005; B) VL dispersion from Paraguay to the Brazilian side of the triple border (Foz do Iguaçu and Santa Terezinha de Itaipu) during after 2012; and C) emergence of a new L. (L.) infantum cluster in western Santa Catarina State and its dispersion to southern Paraná State (municipality of Pato Branco), after 2013. Hypotheses regarding possible entries of Leishmania (L.) infantum into the area of the triple border are presented and discussed. Understanding how VL has dispersed is vital to the development of control measures for this disease and to avoid future dispersion events. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a zoonosis caused by the protozoan Leishmania infantum and in Brazil is transmitted mainly by the bite of Lutzomuyia longipalpis sand flies. Data about the presence, distribution, natural infection rate, seasonal and monthly dynamics of the vector population are important for optimizing the measures to control VL in endemic areas. This study aimed to identify sand fly fauna in an endemic area for VL to detect the prevalence of L. infantum infection in the Lu. longipalpis population and to elucidate the influence of bioclimatic factors on the monthly fluctuations of this vector. HP light traps were monthly set in the intradomicile and peridomicile of residences located in the central and beachfront areas of Camaçari, a VL endemic area. The sand fly collection was conducted in two periods: i) period 1—between December 2011 and November 2012 and ii) period 2—August 2014 and July 2015. Sand fly species were identified and detection of L. infantum infection by qPCR was performed in pools of female Lu. longipalpis. For the first time, the parasite load of positive pools was correlated with the number of Lu. longipalpis captured per month in both periods. Correlation analyses between the monthly fluctuation of the sand fly population and bioclimatic indices of the municipality in both collection periods were also performed. In both evaluated periods, more than 98% of the collected sand flies were Lu. longipalpis, confirming the predominance of this species in the region. It was captured mostly in the beachfront area in all months evaluated (99%). For the period 1, Leishmania DNA was detected in 81% of tested pools representing a minimal infection rate of 9.6%. In the period 2, 40% of the pools were positive with a minimal infection rate of 10.2%. Infected sand flies were only detected in the beachfront area in both periods. The parasite load was low and did not vary in the evaluated months despite the number of collected sand flies. No correlation was observed for climatic factors in both areas of Camaçari. These findings emphasize the high risk of Leishmania transmission in Camaçari regardless of the season and that other factors, aside from bioclimatic elements, are influencing the sand fly population monthly fluctuation. [ABSTRACT FROM AUTHOR]

Aedes albopictus is an invasive mosquito species that has spread globally and can transmit several arboviruses, including dengue, chikungunya and yellow fever. The species was first reported in Brazil in 1986 and since then has been found in 24 of the 27 Brazilian states, often in peri-urban environments close to highly urbanized areas. To date, population genetics of this important mosquito in areas in the city of São Paulo has not been investigated. In this study, we used 12 microsatellite loci to investigate the microgeographic population genetics of Ae. albopictus, which is present throughout the city of São Paulo. All the analyses revealed structuring of the populations studied, divided into two groups with restricted gene flow between them and without evidence of isolation by distance. We propose two hypotheses to explain the results: (i) low dispersal capability—limited gene flow between populations is due to the low dispersal capability inherent to Ae. albopictus; and (ii) multiple introductions—the structure identified here results from multiple introductions, which led to different dispersal patterns within the city and more genetic heterogeneity. The ability of Ae. albopictus to invade new areas and expand may explain why these mosquito populations appear to be well established and thriving in the city of São Paulo. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) genotype D (HBV/D) is globally widespread, and ten subgenotypes (D1 to D10) showing distinct geographic distributions have been described to date. The evolutionary history of HBV/D and its subgenotypes, for which few complete genome sequences are available, in the Americas is not well understood. The main objective of the current study was to determine the full-length genomic sequences of HBV/D isolates from Brazil and frequency, origin and spread of HBV/D subgenotypes in the Americas. Complete HBV/D genomes isolated from 39 Brazilian patients infected with subgenotypes D1 (n = 1), D2 (n = 10), D3 (n = 27), and D4 (n = 1) were sequenced and analyzed together with reference sequences using the Bayesian coalescent and phylogeographic framework. A search for HBV/D sequences available in GenBank revealed 209 complete and 926 partial genomes from American countries (Argentina, Brazil, Canada, Chile, Colombia, Cuba, Haiti, Martinique, Mexico, USA and Venezuela), with the major circulating subgenotypes identified as D1 (26%), D2 (17%), D3 (36%), D4 (21%), and D7 (1%) within the continent. The detailed evolutionary history of HBV/D in the Americas was investigated by using different evolutionary time scales. Spatiotemporal reconstruction analyses using short-term substitution rates suggested times of the most recent common ancestor for the American HBV/D subgenotypes coincident with mass migratory movements to Americas during the 19th and 20th centuries. In particular, significant linkages between Argentina and Syria (D1), Brazil and Central/Eastern Europe (D2), USA and India (D2), and Brazil and Southern Europe (D3) were estimated, consistent with historical and epidemiological data. [ABSTRACT FROM AUTHOR]

High-energy freshwater environments such as rapids and waterfalls in the Upper-Paraná Atlantic Forest are home to highly endemic minute freshwater snails of the genus Acrorbis. Only one species, Acrorbis petricola, is currently included within this genus, whose geographical distribution is restricted to three known populations, one in Brazil and the other two in Argentina. Because of habitat specificity and limited geographical distribution, the species is considered vulnerable in Argentina and endangered in Brazil. In this work, we identify five new populations of A. petricola in southern Upper-Paraná Atlantic Forest, exclusively found on waterfalls from the Misiones Province, Argentina. Based on these populations and on specimens of one of the two historical populations from the Misiones Province, we explored the morphological features of shells and reproductive system of specimens from each location and provide the first molecular data on the species. We used DNA sequences from cytochrome c oxidase subunit I (COI) and 16S-rRNA genes to investigate the molecular diversity, genetic distances and genealogical relationships among populations. We verified the existence of intra- and interpopulation morphological variability, with the greatest variation being found in spire, spiral sculpture, penis sheath, flagella, prostatic diverticula and bursa copulatrix. We found interpopulation genetic diversity, with no intrapopulation variation, and identified six geographically structured genetic lineages with maximum genetic distances of up to 2.3%. Different combinations of morphological characters with the same genetic background within each locality were observed. The finding of new populations genetically differentiated not only broadens the known distribution of the species, but also illustrates that waterfall environments in the Atlantic Forest harbour a hidden diversity of Acrorbis that still remains to be discovered. This scenario suggests a complex evolutionary history that needs to be unveiled and taken into account for future development of conservation strategies in this endemic genus. [ABSTRACT FROM AUTHOR]

Yersinia pestis was introduced to Brazil during the third plague pandemic and currently exists in several recognized foci. There is currently limited available phylogeographic data regarding Y. pestis in Brazil. We generated whole genome sequences for 411 Y. pestis strains from six Brazilian foci to investigate the phylogeography of Y. pestis in Brazil; these strains were isolated from 1966 to 1997. All 411 strains were assigned to a single monophyletic clade within the 1.ORI population, indicating a single Y. pestis introduction was responsible for the successful establishment of endemic foci in Brazil. There was a moderate level of genomic diversity but little population structure among the 411 Brazilian Y. pestis strains, consistent with a radial expansion wherein Y. pestis spread rapidly from the coast to the interior of Brazil and became ecologically established. Overall, there were no strong spatial or temporal patterns among the Brazilian strains. However, strains from the same focus tended to be more closely related and strains isolated from foci closer to the coast tended to fall in more basal positions in the whole genome phylogeny than strains from more interior foci. Overall, the patterns observed in Brazil are similar to other locations affected during the 3rd plague pandemic such as in North America and Madagascar. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti, commonly known as “the yellow fever mosquito”, is of great medical concern today primarily as the major vector of dengue, chikungunya and Zika viruses, although yellow fever remains a serious health concern in some regions. The history of Ae. aegypti in Brazil is of particular interest because the country was subjected to a well-documented eradication program during 1940s-1950s. After cessation of the campaign, the mosquito quickly re-established in the early 1970s with several dengue outbreaks reported during the last 30 years. Brazil can be considered the country suffering the most from the yellow fever mosquito, given the high number of dengue, chikungunya and Zika cases reported in the country, after having once been declared “free of Ae. aegypti”. Methodology/Principal findings: We used 12 microsatellite markers to infer the genetic structure of Brazilian Ae. aegypti populations, genetic variability, genetic affinities with neighboring geographic areas, and the timing of their arrival and spread. This enabled us to reconstruct their recent history and evaluate whether the reappearance in Brazil was the result of re-invasion from neighboring non-eradicated areas or re-emergence from local refugia surviving the eradication program. Our results indicate a genetic break separating the northern and southern Brazilian Ae. aegypti populations, with further genetic differentiation within each cluster, especially in southern Brazil. Conclusions/Significance: Based on our results, re-invasions from non-eradicated regions are the most likely scenario for the reappearance of Ae. aegypti in Brazil. While populations in the northern cluster are likely to have descended from Venezuela populations as early as the 1970s, southern populations seem to have derived more recently from northern Brazilian areas. Possible entry points are also revealed within both southern and northern clusters that could inform strategies to control and monitor this important arbovirus vector. [ABSTRACT FROM AUTHOR]

Cryptococcosis is an important fungal infection in immunocompromised individuals, especially those infected with HIV. In Brazil, despite the free availability of antiretroviral therapy (ART) in the public health system, the mortality rate due to Cryptococcus neoformans meningitis is still high. To obtain a more detailed picture of the population genetic structure of this species in southeast Brazil, we studied 108 clinical isolates from 101 patients and 35 environmental isolates. Among the patients, 59% had a fatal outcome mainly in HIV-positive male patients. All the isolates were found to be C. neoformans var. grubii major molecular type VNI and mating type locus alpha. Twelve were identified as diploid by flow cytometry, being homozygous (AαAα) for the mating type and by PCR screening of the STE20, GPA1, and PAK1 genes. Using the ISHAM consensus multilocus sequence typing (MLST) scheme, 13 sequence types (ST) were identified, with one being newly described. ST93 was identified from 81 (75%) of the clinical isolates, while ST77 and ST93 were identified from 19 (54%) and 10 (29%) environmental isolates, respectively. The southeastern Brazilian isolates had an overwhelming clonal population structure. When compared with populations from different continents based on data extracted from the ISHAM-MLST database (mlst.mycologylab.org) they showed less genetic variability. Two main clusters within C. neoformans var. grubii VNI were identified that diverged from VNB around 0.58 to 4.8 million years ago. [ABSTRACT FROM AUTHOR]

The Human immunodeficiency virus type-1 (HIV-1) epidemic in Brazil is mainly driven by the subtype B pandemic lineage (BPANDEMIC), while Caribbean non-pandemic subtype B clades (BCAR) seem to account for a very low fraction of HIV-infections in this country. The molecular characteristics of the HIV-1 subtype B strains disseminated in the Northern and Northeastern Brazilian regions, however, have not been explored so far. In this study, we estimate the prevalence of the HIV-1 BPANDEMIC and BCAR clades across different Brazilian regions and we reconstruct the spatiotemporal dynamics of dissemination of the major Brazilian BCAR clades. A total of 2,682 HIV-1 subtype B pol sequences collected from 21 different Brazilian states from the five country regions between 1998 and 2013 were analyzed. Maximum Likelihood phylogenetic analyses revealed that the BCAR strains reached 16 out 21 Brazilian states here analyzed. The BCAR clades comprise a low fraction (<10%) of subtype B infections in most Brazilian states analyzed, with exception of Roraima (41%), Amazonas (14%) and Maranhão (14%). Bayesian phylogeographic analyses indicate that BCAR strains originally from the Hispaniola and Trinidad and Tobago were introduced at multiple times into different states from all Brazilian regions and a few of those strains, probably introduced into Roraima, Maranhão and São Paulo between the late 1970s and the early 1980s, established secondary outbreaks in the Brazilian population. These results support that the HIV-1 subtype B epidemics in some Brazilian states from the Northern and Northeastern regions display a unique molecular pattern characterized by the high prevalence of BCAR lineages, which probably reflects a strong epidemiological link with the HIV-1 epidemics in the Caribbean region. [ABSTRACT FROM AUTHOR]

Background: Aedes aegypti is the most important vector of dengue fever in Brazil, where severe epidemics have recently taken place. Ae. aegypti in Brazil was the subject of an intense eradication program in the 1940s and 50s to control yellow fever. Brazil was the largest country declared free of this mosquito by the Pan-American Health Organization in 1958. Soon after relaxation of this program, Ae. aegypti reappeared in this country, and by the early 1980s dengue fever had been reported. The aim of this study is to analyze the present-day genetic patterns of Ae. aegypti populations in Brazil. Methodology/Principal Findings: We studied the genetic variation in samples of 11 widely spread populations of Ae. aegypti in Brazil based on 12 well-established microsatellite loci. Our principal finding is that present-day Brazilian Ae. aegypti populations form two distinct groups, one in the northwest and one in the southeast of the country. These two groups have genetic affinities to northern South American countries and the Caribbean, respectively. This is consistent with what has been reported for other genetic markers such as mitochondrial DNA and allele frequencies at the insecticide resistance gene, kdr. Conclusions/Significance: We conclude that the genetic patterns in present day populations of Ae. aegypti in Brazil are more consistent with a complete eradication of the species in the recent past followed by re-colonization, rather than the alternative possibility of expansion from residual pockets of refugia. At least two colonizations are likely to have taken place, one from northern South American countries (e.g., Venezuela) that founded the northwestern group, and one from the Caribbean that founded the southeastern group. The proposed source areas were never declared free of Ae. aegypti. [ABSTRACT FROM AUTHOR]

Germline TP53 mutations predispose individuals to multiple cancers and are associated with Li-Fraumeni/Li-Fraumeni-Like Syndromes (LFS/LFL). The founder mutation TP53 p.R337H is detected in 0.3% of the general population in southern Brazil. This mutation is associated with an increased risk of childhood adrenal cortical carcinoma (ACC) but is also common in Brazilian LFS/LFL families. Breast Cancer (BC) is one of the most common cancers diagnosed in TP53 mutation carriers. We have assessed the prevalence of p.R337H in two groups: (1) 59 BC affected women with a familial history (FH) suggestive of hereditary cancer syndrome but no LFS/LFL features; (2) 815 BC affected women unselected for cancer FH, diagnosed with BC at or before age 45 or at age 55 or older. Among group 1 and group 2 patients, 2/59 (3.4%, CI95%: 0.4%–11.7%) and 70/815 (8.6%, CI95%: 6.8%–10.7%), respectively, were p.R337H carriers in the germline. The prevalence of p.R337H was higher in women diagnosed with BC at or before age 45 (12.1%, CI95%: 9.1%–15.8%) than at age 55 or older (5.1%, CI95%: 3.2%–7.7%), p<0.001). The Brazilian founder p.R337H haplotype was detected in all carriers analysed. These results suggest that inheritance of p.R337H may significantly contribute to the high incidence of BC in Brazil, in addition to its recently demonstrated impact on the risk of childhood ACC. [ABSTRACT FROM AUTHOR]