Transmitted HIV Drug Resistance in Bulgaria Occurs in Clusters of Individuals from Different Transmission Groups and Various Subtypes (2012-2020).

Transmitted HIV drug resistance in Bulgaria was first reported in 2015 using data from 1988-2011. We determined the prevalence of surveillance drug resistance mutations (SDRMs) and HIV-1 genetic diversity in Bulgaria during 2012-2020 using polymerase sequences from 1053 of 2010 (52.4%) antiretroviral therapy (ART)-naive individuals. Sequences were analyzed for DRM using the WHO HIV SDRM list implemented in the calculated population resistance tool at Stanford University. Genetic diversity was inferred using automated subtyping tools and phylogenetics. Cluster detection and characterization was performed using MicrobeTrace. The overall rate of SDRMs was 5.7% (60/1053), with 2.2% having resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 1.8% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 2.1% to protease inhibitors (PIs), and 0.4% with dual-class SDRMs. We found high HIV-1 diversity, with the majority being subtype B (60.4%), followed by F1 (6.9%), CRF02_AG (5.2%), A1 (3.7%), CRF12_BF (0.8%), and other subtypes and recombinant forms (23%). Most (34/60, 56.7%) of the SDRMs were present in transmission clusters of different subtypes composed mostly of male-to-male sexual contact (MMSC), including a 14-member cluster of subtype B sequences from 12 MMSC and two males reporting heterosexual contact; 13 had the L90M PI mutation and one had the T215S NRTI SDRM. We found a low SDRM prevalence amid high HIV-1 diversity among ART-naive patients in Bulgaria during 2012-2020. The majority of SDRMs were found in transmission clusters containing MMSC, indicative of onward spread of SDRM in drug-naive individuals. Our study provides valuable information on the transmission dynamics of HIV drug resistance in the context of high genetic diversity in Bulgaria, for the development of enhanced prevention strategies to end the epidemic.

High Rate of Hepatitis B and C Coinfections Among People Living with HIV-1 in Bulgaria: 2010-2014.

In a representative nationwide study, we have determined the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfections among HIV-positive patients diagnosed during the period 2010-2014 in Bulgaria. Despite a relatively low rate of new HIV diagnoses, the rates of hepatitis B and C coinfections among these patients fell within the upper range reported in Europe. HBsAg and HCV antibodies (Ab) were found in 10.4% and 25.6% of the tested individuals, respectively. Importantly, high rates of active hepatitis infections were confirmed by detection of HBV DNA in 51.1% and HCV RNA in 78.1% of the tested individuals. Hepatitis coinfections affected mostly high risk groups and persons with multiple risk behavior, including people who inject drugs, men who have sex with men, prisoners, and Roma people.

Antimicrobial therapy of salmonelloses--current state and perspectives.

Salmonellosis in humans is most often manifested as a self-limiting gastroenteritis. Antimicrobial therapy is superfluous in the milder forms of the disease and in Salmonella carriage but can be life saving for patients with septic salmonellosis and patients at risk of extraintestinal dissemination of the infection. The therapeutic approach is based on the clinical course of the disease and the patient's immune reactivity. Antimicrobial therapy is usually initiated before the in vitro susceptibility tests of the isolate become available. Currently, the drugs of choice for empiric treatment of acute infectious diarrhea, in which Salmonella spp are etiologically implicated, are fluoroquinolones in adults and third generation cephalosporins in children. Alternative treatment may use azithromycin and imipenem in life-threatening systemic Salmonella infections. Aminoglycosides are considered ineffective in gastrointestinal salmonelloses. The emerging resistance to fluoroquinolones, production of extended-spectrum beta-lactamases, and the increase of multidrug resistant Salmonella strains are major problems in the search for efficient antimicrobial therapy of Salmonella infection.

Immunophenotyping characteristic of the major lymphocyte populations and subpopulations in patients during salmonella infection.

AIM: To study the quantitative changes in the major lymphocyte populations and subpopulations in the peripheral blood of patients during salmonellosis and find correlations of these changes with disease severity and bacterial clearance. MATERIAL AND METHODS: The study included 24 adult patients with culture-proven gastrointestinal salmonellosis. Flow-cytometry was used to identify CD19+ (B lymphocytes), CD2+ (total T lymphocytes), CD3(+)CD4+ (helper T cells), CD3(+)CD8+ (suppressor/cytotoxic T lymphocytes), CD4(+)CD29+ and CD4(+)CD45(-)RA+ (helper/ inducer subpopulation and naive Tlymphocytes) in the acute and the convalescent phases of disease. The absolute number and percentage of cells in 1 microl of peripheral blood were also determined. Immunophenotype analysis was conducted on an EPICS XL-MCL flow cytometer, Coulter, USA using monoclonal antibodies produced by the same firm. RESULTS: T and B lymphocytes and the immunocompetent T cells were slightly decreased transiently in the acute phase of the disease. Helper T lymphocytes were slightly increased with a significant increase observed of helper/inducer cells and decrease of the naive T lymphocytes. CONCLUSION: The increase of B lymphocytes at the height of salmonellosis bears additionally a diagnostic significance in determining the severity of the disease while the increase of the helper T lymphocytes can be a prognostic marker of early bacterial clearance.

Fatal outcome of coinfection of Crimean-Congo hemorrhagic fever and malaria.

Here, we report a case of a Bulgarian patient with imported falciparum malaria that manifested 6 days after his arrival in Bulgaria, which was complicated by bloody diarrhea 2 days later. Blood smear revealed high parasitemia, with annular forms and gametocytes of Plasmodium falciparum. In addition, RNA of the Crimean-Congo hemorrhagic fever (CCHF) virus was detected in the blood sample by real-time reverse transcription (RT)-PCR and nested RT-PCR. The obtained sequence was found to be clustered within the Europe 1 lineage close to the other Bulgarian strains. Notably, the two infectious diseases may appear with many similar symptoms that are difficult to distinguish.

Cytokines in Salmonella infections.

Cytokines are intercellular signal molecules involved in the immune pathogenesis of infectious diseases. Cytokine mediated pathological alterations are mainly attributable to an imbalance in cytokine production. Experimental and clinical studies have documented the fact that Salmonella infections induce a Th1 dependent immune response and interferon-gamma and interleukin-12 are central to its genesis. Salmonella endotoxins, flagellins and porins are among the chief mediators of cytokine release. Lectin binding proteins, Toll-like receptors, transcription factors and various cells also contribute to this process. Serum and local (fecal) cytokine determination in salmonellosis provides evidence on the immune events occurring after antigen challenge. They might also serve as clinical and prognostic markers of disease severity and outcome. Recent studies are focused on the effect and interaction between pro-inflammatory (interleukin-1, interferon-gamma and tumor necrosis factor) and anti-inflammatory cytokines (interleukin-10).