HPV-associated oropharyngeal carcinomas in patients living with HIV on long-term antiretroviral therapy: Case reports.

In the 1970s, human papillomaviruses (HPV) were ascertained as the aetiologic agents of cervical carcinoma. Subsequently, an association with HPV was established in other epithelial tumours, including squamous cell carcinoma of the head and neck (HNSCC). HPV has demonstrated a high potential for inducing oropharyngeal tumours, with HPV-16 infection posing a significant oncogenic risk. People living with HIV (PLWH) are identified as being at a higher risk of HPV infection and the subsequent development of HPV-associated tumours of the oropharynx. We present two patients under the care of the Department of AIDS with long-term HIV infections who were newly diagnosed with HPV-associated carcinomas of the tonsils. Both patients had been on antiretroviral therapy (ART) for over 15 years, achieving optimal viral suppression for more than 10 years. Chemotherapy and radiation therapy were employed in the treatment of the carcinomas. Throughout the neoplastic disease treatment, both patients maintained optimal viral suppression for HIV. The presented cases underscore the fact that despite achieving long-term optimal viral suppression of HIV, people living with HIV remain susceptible to the development of HPV-associated neoplasms.

Autochthonous and Imported Visceral Leishmaniasis in Bulgaria-Clinical Experience and Treatment of Patients.

Visceral leishmaniasis (VL) is a severe endemic disease with a fatal outcome if left untreated. The symptoms of patients are diverse and atypical. Against the background of anemia and pancytopenia, the condition of the patients gradually worsens with marked cachexia. Through sharing our experience, we aim to draw attention to this deadly disease. Clinical and laboratory data for 58 patients with VL treated over a forty-five-year period are presented. The diagnosis was established within a duration of 1 to 28 months of illness. Continuous fever (38-42 °C), splenomegaly, hepatomegaly, severe anemia (decreased hemoglobin to lowest values of 31 g/L), leucopenia (lowest values of leucocytes et 0.5 g/L), and thrombocytopenia (reduced thrombocyte count to 29 g/L) were observed. The diagnosis was made on the basis of microscopic evidence of amastigote forms in bone marrow smears and serological tests. The patients were treated with Glucantime for 17 to 21 days. Relapses were observed in seven patients (12.1%) and fatal outcome was observed in two patients (3.5%) during treatment, who developed acute respiratory and cardiovascular failure. In Bulgaria, Visceral leishmaniasis is primarily endemic in the southern regions and should be suspected not only in patients who have returned from tropical and subtropical countries, but also in those who have not traveled abroad. The challenges associated with VL stem from delayed diagnosis of patients, as this disease remains unrecognized by physicians.

Molecular Analysis of Dihydropteroate Synthase Gene Mutations in Pneumocystis jirovecii Isolates among Bulgarian Patients with Pneumocystis Pneumonia.

Pneumocystis jirovecii pneumonia (PCP) is a significant cause of morbidity and mortality in immunocompromised people. The widespread use of trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment and prophylaxis of opportunistic infections (including PCP) has led to an increased selection of TMP-SMZ-resistant microorganisms. Sulfa/sulfone resistance has been demonstrated to result from specific point mutations in the DHPS gene. This study aims to investigate the presence of DHPS gene mutations among P. jirovecii isolates from Bulgarian patients with PCP. A total of 326 patients were examined via real-time PCR targeting the P. jirovecii mitochondrial large subunit rRNA gene and further at the DHPS locus. P. jirovecii DNA was detected in 50 (15.34%) specimens. A 370 bp DHPS locus fragment was successfully amplified in 21 samples from 19 PCP-positive patients, which was then purified, sequenced, and used for phylogenetic analysis. Based on the sequencing analysis, all (n = 21) P. jirovecii isolates showed DHPS genotype 1 (the wild type, with the nucleotide sequence ACA CGG CCT at codons 55, 56, and 57, respectively). In conclusion, infections caused by P. jirovecii mutants potentially resistant to sulfonamides are still rare events in Bulgaria. DHPS genotype 1 at codons 55 and 57 is the predominant P. jirovecii strain in the country.

Study on the Prevalence of Pneumocystis jirovecii as a Causative Agent of Lung Pathology in People with Different Immune Status.

BACKGROUND: Pneumocystis pneumonia (PCP) commonly affects immunocompromised individuals, whereas in immunocompetent persons, it occurs relatively rarely, and in most cases, the Pneumocystis infection is detected as an asymptomatic colonization. The present study aimed to establish the prevalence of Pneumocystis jirovecii infection in human hosts with different immune status (immunocompromised and immunocompetent), using molecular diagnostic methods, and to compare their diagnostic value with that of classical staining methods. METHODS: We used the collected-to-this-moment data from a prospective study on the prevalence of pneumocystosis among the Bulgarian population. Clinical specimens (including throat secretions, induced sputum, tracheal aspirates, and bronchoalveolar lavage) collected from 220 patients suspected of PCP (153 immunocompetent and 67 immunocompromised patients) were examined with microscopic staining methods and real-time PCR for detection of P. jirovecii. Results: DNA of the pathogen was detected in 38 (17%) specimens (32 immunocompromised patients and 6 immunocompetent subjects). From all 220 clinical samples examined by staining methods, only five (2%) P. jirovecii cysts were detected by the Gomori stain. All patients with PCP were treated with trimethoprim-sulfamethoxazole, but in ten of them (HIV-positive patients), the disease had a fatal outcome. CONCLUSIONS: This study is the first in Bulgaria including the main available laboratory methods for diagnosis of human pneumocystosis. Regarding the etiological diagnosis of PCP, in our study the sensitivity of real-time PCR was higher compared to the staining methods. The choice of a method for sample collection and examination has an important role in the efficiency of the laboratory diagnostics.