Mediastinal Mass, Cancer, or Infection, Atypical Paraesophageal Actinomycosis Infection, Clinical and Surgical Approach.

Actinomyces israelii (AI) is a Gram-positive, rod-shaped bacterium that lives commensally on and within humans as a typical colonizer within the gastrointestinal tract, including the mouth. As an opportunistic pathogen, infection often results from tissue injury or breach of the mucosal barrier (ie, during various dental or GI procedures, aspiration, or specific pathologies such as diverticulitis). Symptoms generally present slowly as a non-tender, indurated mass that evolves into multiple abscesses, fistulae, or draining sinus tracts without regard for anatomical barriers, including fascial planes or lymphatic drainage. However, it may also present as an acute suppurative infection with pain and rapid progression to abscess formation.

Malaria in Venezuela: changes in the complexity of infection reflects the increment in transmission intensity.

BACKGROUND: Malaria incidence has reached staggering numbers in Venezuela. Commonly, Bolívar State accounted for approximately 70% of the country cases every year. Most cases cluster in the Sifontes municipality, a region characterized by an extractive economy, including gold mining. An increase in migration to Sifontes, driven by gold mining, fueled a malaria spillover to the rest of the country and the region. Here samples collected in 2018 were compared with a previous study of 2003/2004 to describe changes in the parasites population structures and the frequency of point mutations linked to anti-malarial drugs. METHODS: A total of 88 Plasmodium falciparum and 94 Plasmodium vivax isolates were collected in 2018 and compared with samples from 2003/2004 (106 P. falciparum and 104 P. vivax). For P. falciparum, mutations linked to drug resistance (Pfdhfr, Pfdhps, and Pfcrt) and the Pfk13 gene associated with artemisinin delayed parasite clearance, were analysed. To estimate the multiplicity of infection (MOI), and perform P. falciparum and P. vivax population genetic analyses, the parasites were genotyped by using eight standardized microsatellite loci. RESULTS: The P. falciparum parasites are still harbouring drug-resistant mutations in Pfdhfr, Pfdhps, and Pfcrt. However, there was a decrease in the frequency of highly resistant Pfdhps alleles. Mutations associated with artemisinin delayed parasite clearance in the Pfk13 gene were not found. Consistent with the increase in transmission, polyclonal infections raised from 1.9% in 2003/2004 to 39% in 2018 in P. falciparum and from 16.3 to 68% in P. vivax. There is also a decrease in linkage disequilibrium. Bayesian clustering yields two populations linked to the time of sampling, showing that the parasite populations temporarily changed. However, the samples from 2003/2004 and 2018 have several alleles per locus in common without sharing multi-locus genotypes. CONCLUSIONS: The frequency of mutations linked with drug resistance in P. falciparum shows only changes in Pfdhps. Observations presented here are consistent with an increase in transmission from the previously circulating parasites. Following populations longitudinally, using molecular surveillance, provides valuable information in cases such as Venezuela with a fluid malaria situation that is affecting the regional goals toward elimination.

Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum.

Mutations in the Plasmodium falciparumk13 (Pfk13) gene are linked to delayed parasite clearance in response to artemisinin-based combination therapies (ACTs) in Southeast Asia. To explore the evolutionary rate and constraints acting on this gene, k13 orthologs from species sharing a recent common ancestor with P. falciparum and Plasmodium vivax were analyzed. These comparative studies were followed by genetic polymorphism analyses within P. falciparum using 982 complete Pfk13 sequences from public databases and new data obtained by next-generation sequencing from African and Haitian isolates. Although k13 orthologs evolve at heterogeneous rates, the gene was conserved across the genus, with only synonymous substitutions being found at residues where mutations linked to the delayed parasite clearance phenotype have been reported. This suggests that those residues were under constraint from undergoing nonsynonymous changes during evolution of the genus. No fixed nonsynonymous differences were found between Pfk13 and its orthologs in closely related species found in African apes. This indicates that all nonsynonymous substitutions currently found in Pfk13 are younger than the time of divergence between P. falciparum and its closely related species. At the population level, no mutations linked to delayed parasite clearance were found in our samples from Africa and Haiti. However, there is a high number of single Pfk13 mutations segregating in P. falciparum populations, and two predominant alleles are distributed worldwide. This pattern is discussed in terms of how changes in the efficacy of natural selection, affected by population expansion, may have allowed for the emergence of mutations tolerant to ACTs.