ABSTRACT
The Beijing genotype comprises a highly disseminated strain type that is frequently associated with multidrug resistant (MDR) tuberculosis (TB) and increased transmissibility but, countries such as Portugal and Guinea-Bissau fall outside the regions phylogeographically associated with this specific genotype. Nevertheless, recent data shows that this genotype might be gradually emerging in these two countries as an underlying cause of primary MDR-TB. Here, we describe the emergence of Mycobacterium tuberculosis Beijing strains associated with MDR-TB in Portugal and Guinea-Bissau demonstrating the presence of the well described superclusters 100-32 and 94-32 in Portugal and Guinea-Bissau, respectively. Genome-wide analysis and comparison with a global genomic dataset of M. tuberculosis Beijing strains, revealed the presence of two genomic clusters encompassing isolates from Portugal and Guinea-Bissau, GC1 (n = 121) and GC2 (n = 39), both of which bore SNP signatures compatible with the 100-32/B0/W148 and 94-32/Central Asia Outbreak clades, respectively. Moreover, GC2 encompasses a cross-border cluster between Portugal, Guinea-Bissau and Brazil thus supporting migration-associated introduction of MDR-TB and subsequent clonal expansion at the community-level. The comparison with global Beijing datasets demonstrates the global reach of the disease and its complex dissemination across multiple countries while in parallel there are clear microevolutionary trajectories towards extensively drug resistant TB.
Subject(s)
DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Mycobacterium tuberculosis/classification , Tuberculosis, Multidrug-Resistant/microbiology , Whole Genome Sequencing/methods , Beijing , Brazil , Guinea-Bissau , High-Throughput Nucleotide Sequencing , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Phylogeny , Phylogeography , PortugalABSTRACT
Zika virus infections can cause a range of neurologic disorders including congenital microcephaly. However, while Zika infections have been notified across all regions in Brazil, there has been an unusual number of congenital microcephaly case notifications concentrated in the Northeast of the country. To address this observation, we investigated epidemiological data (2014-2016) on arbovirus co-distribution, environmental and socio-economic factors for each region in Brazil. Data on arbovirus reported cases and microcephaly were collected from several Brazilian Ministry of Health databases for each Federal unit. These were complemented by environmental management, social economic and Aedes aegypti infestation index data, extracted from multiple databases. Spatial time "ecological" analysis on the number of arboviruses transmitted by Aedes mosquitoes in Brazil show that the distribution of dengue and Zika was widespread in the whole country, with higher incidence in the West-Central region. However, reported chikungunya cases were higher in the Northeast, the region also with the highest number of microcephaly cases registered. Social economic factors (human development index and poverty index) and environmental management (water supply/storage and solid waste management) pointed the Northeast as the less wealthy region. The Northeast is also the region with the highest risk of Aedes aegypti house infestation due to the man-made larval habitats. In summary, the results of our ecological analysis support the hypothesis that the unusual distribution of microcephaly might not be due to Zika infection alone and could be accentuated by poverty and previous or co-infection with other pathogens. Our study reinforces the link between poverty and the risk of disease and the need to understand the effect on pathogenesis of sequential exposure to arboviruses and co-viral infections. Comprehensive large-scale cohort studies are required to corroborate our findings. We recommend that the list of infectious diseases screened, particularly during pregnancy, be regularly updated to include and effectively differentiate all viruses from ongoing outbreaks.
Subject(s)
Aedes/growth & development , Databases, Factual , Ecosystem , Poverty , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Zika Virus , Animals , Brazil , Female , Humans , Incidence , Infant , Infant, Newborn , Larva/growth & development , Male , MicrocephalyABSTRACT
During the past three decades there has been a notable increase in dengue disease severity in Venezuela. Nevertheless, the population structure of the viruses being transmitted in this country is not well understood. Here, we present a molecular epidemiological study on dengue viruses (DENV) circulating in Aragua State, Venezuela during 2006-2007. Twenty-one DENV full-length genomes representing all of the four serotypes were amplified and sequenced directly from the serum samples. Notably, only DENV-2 was associated with severe disease. Phylogenetic trees constructed using Bayesian methods indicated that only one genotype was circulating for each serotype. However, extensive viral genetic diversity was found in DENV isolated from the same area during the same period, indicating significant in situ evolution since the introduction of these genotypes. Collectively, the results suggest that the non-structural (NS) proteins may play an important role in DENV evolution, particularly NS1, NS2A and NS4B proteins. The phylogenetic data provide evidence to suggest that multiple introductions of DENV have occurred from the Latin American region into Venezuela and vice versa. The implications of the significant viral genetic diversity generated during hyperendemic transmission, particularly in NS protein are discussed and considered in the context of future development and use of human monoclonal antibodies as antivirals and tetravalent vaccines.