Современные возможности диагностики туберкулеза у пациентов с ВИЧ-инфекцией

The problem of the steady growth of HIV-associated tuberculosis has become increasingly urgent in recent years in Russia. Diagnosis of tuberculosis is particularly difficult at the stage of severe immunodeficiency. Objective. to evaluate the effectiveness of the T-SPOT ® method.TB in the diagnosis of tuberculosis infection in patients with HIV infection. Materials and methods. in the period for 2019-2020, the T-SPOT®.TB results were analyzed in 396 patients. The criteria for inclusion in this study were the age of 18 years and older, the diagnosis of HIV infection, follow-up at the AIDS center. Results. in the group with a positive T-SPOT®.TB and changes on the computed tomogram, the verified diagnosis of tuberculosis was 90.7% of the group with both signs and 75.5% of those with a positive result T-SPOT®.TB. The group with a positive result T-SPOT®.TB and no changes on the CT scan is 16.8% of those with a positive result T-SPOT®.TB,such patients were diagnosed with „latent tuberculosis infection”. Conclusion. T-SPOT®.TB can be used in the diagnostic complex of monitoring patients with HIV infections — as a screening method that allows not only to verify the diagnosis, but also to detect latent tuberculosisProblema creşterii constante a tuberculozei asociate cu HIV a devenit din ce în ce mai urgentă în ultimii ani în Rusia. Diagnosticul tuberculozei este deosebit de dificil în stadiul imunodeficienţei severe. Obiectiv. Evaluarea eficacităţii metodei T-SPOT®.TB în diagnosticul infecţiei cu tuberculoză la pacienţii cu infecţie HIV. Materiale si metode. În perioada 2019-2020, rezultatele T-SPOT®.TB au fost analizate la 396 de pacienţi. Criteriile pentru includerea în acest studiu au fost vârsta de 18 ani şi peste, diagnosticul infecţiei cu HIV, monitorizarea la centrul SIDA. Rezultate. În grupul cu T-SPOT®.TB pozitiv şi modificări ale tomogramei computerizate, diagnosticul verificat de tuberculoză a constituit 90,7% din grupul cu ambele semne şi 75,5% dintre cei cu rezultat pozitiv T-SPOT®.TB. Grupul cu un rezultat pozitiv T-SPOT®.TB şi fără modificări ale scanării CT constituie 16,8% dintre cei cu un rezultat pozitiv T-SPOT®.TB, astfel de pacienţi au fost diagnosticaţi cu „infecţie cu tuberculoză latentă”. Concluzie. T-SPOT®.TB poate fi utilizat în complexul de diagnosticare şi monitorizare a pacienţilor cu HIV infecţie — ca metodă de screening care permite nu numai verificarea diagnosticului, ci şi detectarea tuberculozei latenteПроблема неуклонного роста ВИЧ-ассоциированного туберкулеза становится все более актуальной в последние годы в России. Диагностика туберкулеза особенно затруднена на стадии выраженного иммунодефицита. Цель исследования, оценить эффективность метода T-SPOT®.TB в диагностике туберкулезной инфекции у пациентов с ВИЧ-инфекцией. Материалы и методы, В период за 2019-2020 гг.. обследовано 396 пациентов, состоящих на учете в СПИД-центре. Критериями включения в данное исследование были возраст 18 лет и старше, диагноз ВИЧ-инфекция, диспансерное наблюдение в СПИД-центре. Результаты. Установлено, что в группе с положительным T-SPOT®.TB и изменениями на КТ верифицированный диагноз туберкулеза составил 90,7% от группы с наличием обоих признаков и 75,5% из лиц с положительным результатом T-SPOT®.TB. Среди лиц с положительным результатом T-SPOT®.TB. отсутствие изменений на КТ составило 16,8%, таким пациентам поставлен диагноз «латентная туберкулезная инфекция». Заключение. в диагностическом комплексе наблюдения пациентов с ВИЧ-инфекций T-SPOT®.TB может использоваться как скрининг метод, позволяющий в последующем не только верифицировать диагноз, но и выявить латентный туберкуле

Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality-a multicentre prospective cohort study

Background: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). Methods: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan-Meier estimates and Cox models. Findings: 480/740 patients (64.9%; 95% CI 61.3-68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18-5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21-2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24-2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10-2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18-2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04-1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95-1.70; p = 0.103). Conclusion: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe

Features of hematological and hemostasiological parameters in Coronavirus infection COVID-19 and community-acquired pneumonia

Against the background of priority attention paid to the COVID-19 pandemic, there are also cases of community-acquired pneumonia of a different genesis. Identification of the features of lung lesions in such diseases is relevant during the spread of seasonal respiratory infections. The comparative study of the dynamics of hematological and hemostasiological parameters of blood in patients with pneumonia of various origins is of interest in terms of searching for predictors of the prognosis of the diseases development. Aim. To compare the features of clinical symptoms, hematological and hemostasiological parameters in patients with pneumonia caused by COVID-19 and in patients with community-acquired pneumonia. Materials and methods. During cross-sectional study two groups were formed: group 1 consisted of 92 patients diagnosed with moderate community-acquired pneumonia caused by COVID-19 infection; group 2 included 40 patients diagnosed with moderate community-acquired bilateral polysegmental pneumonia. Results. It was found that patients with COVID-19 had an older age (69 vs 39.3 years), a lower body temperature at admission (37.5 vs 38.85 °C), a lower percentage of reduced oxygen saturation (less than 89 % in 5.4 % of cases vs 10 % of cases). In most cases, the average values of some hematological parameters in patients with COVID-19 did not go beyond the reference range. Leukopenia (below 4 × 109 cells/l) and lymphopenia (below 1.1 × 109 cells/l) were observed in 26 % and 38 % of cases respectively; thrombocytopenia (less than 100 × 109 cells/l) - in 12.2 % of cases; hyperfibrinogenemia (more than 4 g/l) - in 65.3 % of cases. A direct correlation was found between platelet levels and leukocytes (R = 0.53; p < 0.001) and lymphocytes (R = 0.29; p = 0.06). Compared with the patients of the group 2, on average, patients with COVID-19 had significantly lower levels of leukocytes and lymphocytes (2.5 times each; p < 0.001) and an increased level of fibrinogen (by 45 %; p < 0.001). Conclusion. In patients with pneumonia caused by COVID-19, we revealed the particular features of clinical symptoms, hematological and hemostasiological blood parameters compared to community-acquired nonspecific pneumonia

Pulmonary tuberculosis in clinical practice

Pulmonary tuberculosis has a lot of clinical manifestations, and it complicates the diagnosis of tuberculosis in the general clinical practice. We studied the clinical manifestations of tuberculosis detected in the pulmonary department and compared them with the significancy of diagnostic methods. Material and methods. People with a verified diagnosis of lung tuberculosis (n=109) were examined using the GeneXpert MTB/RIF method if Ziehl Nielsen bacterioscopy has negative results or if there was no effect of treatment for two weeks. Results. All patients had complaints of both intoxication and bronchitis as with pneumonia on admission. Infiltrative tuberculosis (57,1 %; n=68), disseminated tuberculosis (16,8 %; n=20) were most often diagnosed. We looked for correlations between dyspnea and the prevalence of the process (p=0,24), dyspnea with temperature (p=0,24), the presence of pain in the chest (p=0,405), the results of immunodiagnostics and sputum examination (p=0,133). We found out that there are no such correlations in tuberculosis. The term for diagnosing tuberculosis was 7,97±3,9 days in the presence of cough with sputum and 9,04±4,3 days in the case of dry cough. The term for diagnosing tuberculosis was 12,31±4,9 days in patients without cough. Mycobacterium tuberculosis was detected using GeneXpert MTB/RIF molecular genetic methods with nonproductive cough in 84,5 % (60 people out of 71), while in the first days of hospitalization in 46,6 % of patients (28 people out of 60, p <0,001). Conclusion. It was found that the period of hospitalization is little related to the characteristics of patients and depends on organizational measures to identify mycobacterium tuberculosis. It is recommended to immediately apply the GeneXpert MTB / RIF method to patients with mild tuberculosis

ВИЧ-ИНФЕКЦИЯ И ВНЕБОЛЬНИЧНАЯ ПНЕВМОНИЯ. ПРИЧИНЫ СМЕРТИ

The aim was to study the characteristics of community-acquired pneumonia in patients with HIV infection, depending on the outcome of the disease and to identify significant predictors of death.Materials and methods. The study included 80 patients with community-acquired pneumonia and HIV-infection. Two groups were formed in accordance with the outcome of community-acquired pneumonia. 1 group (study group) - 40 deceased patients, 2 group (comparison group) - 40 patients discharged from the hospital with improvement. Inclusion criteria: patients over 18 years of age, diagnosis of community-acquired pneumonia, diagnosis of HIV infection, informed consent of the patient. Patients with diagnosed pulmonary tuberculosis were excluded at the stage of examination and treatment.Results. Patients with HIV-infection entered the hospital with community-acquired pneumonia of severe degree in 65% of cases, 71.25% of cases with respiratory insufficiency of II and III degrees, in 16.25% of cases with critically low oxygen saturation (less than 85%). The majority of patients had bilateral pneumonia (78.75%), in 28.75% of cases complicated by pleural effusion. Patients needed respiratory support at different levels-the chambers of the pulmonology ward in 36.25% of cases, indications for noninvasive ventilation (NIV) in the intensive care unit (ICU) were noted in 80% of cases, ventilation in the ICU in 56.25% of cases. Deceased patients were significantly more likely to be injecting drug users, reported weight loss of more than 10% in six months, CD4 + cells did not exceed 50/μl, bilateral lung damage, pleural effusion, oxygen saturation less than 90%.The conclusion. Treatment and diagnosis of comorbid patients with community-acquired pneumonia and HIV-infection is complex, in the stage of pronounced immunosuppression can lead to death. Early onset of NIV in the presence of severe respiratory failure may improve the survival prognosis.Целью работы было изучение особенностей внебольничной пневмонии у больных ВИЧ-инфекцией в зависимости от исхода заболевания и выявить значимые предикторы смерти.Материалы и методы исследования. В исследование включено 80 пациентов с внебольничной пневмонией и ВИЧ-инфекцией. Сформировано две группы в соответствии с исходом внебольничной пневмонии. 1 группа (группа изучения) - 40 умерших пациентов, 2 группа (группа сравнения) - 40 пациентов, выписанных из стационара с улучшением. Критерии включения: пациенты старше 18 лет, диагноз внебольничной пневмонии, диагноз ВИЧ-инфекции, информированное согласие пациента. Исключались пациенты с диагностированным туберкулезом легких на этапе обследования и лечения.Результаты. Больные ВИЧ-инфекцией поступали в стационар с внебольничной пневмонией тяжелой степени в 65% случаев, в 71,25% случаев – с дыхательной недостаточностью II и III степеней, в 16,25% случаев - с критически низкой сатурацией кислорода (менее 85%). Большинство пациентов имели пневмонию двусторонней локализации (78,75%), в  28,75%  случаев осложненную плевральным выпотом. Пациенты нуждались в респираторной поддержке различного уровня – ресурсами палаты пульмонологического отделения в 36,25% случаев, показания к неинвазивной вентиляции легких (НВЛ) в ОРИТ отмечены в 80% случаев, ИВЛ в ОРИТ – в 56,25% случаев. Умершие  пациенты достоверно чаще были потребителями инъекционных наркотиков, отмечали потерю веса более 10% за полгода, количество CD4+клеток у них не превышало50кл/мкл,чаще отмечались двустороннее поражение легких, наличие плеврального выпота, сатурация кислорода крови меньше 90%.Заключение. Лечение и диагностика коморбидных больных с внебольничной пневмонией и ВИЧ-инфекцией отличается сложностью, в стадии выраженной иммуносупрессии может приводить к летальному исходу. Раннее начало НВЛ при наличии выраженной дыхательной недостаточности может улучшить прогноз выживаемости.</p

Healthcare delivery for HIV-positive people with tuberculosis in Europe

Background: In a 2013 survey, we reported distinct discrepancies in delivery of tuberculosis (TB) and HIV services in eastern Europe (EE) vs. western Europe (WE). Objectives: To verify the differences in TB and HIV services in EE vs. WE. Methods: Twenty-three sites completed a survey in 2018 (EE, 14; WE, nine; 88% response rate). Results were compared across as well as within the two regions. When possible, results were compared with the 2013 survey. Results: Delivery of healthcare was significantly less integrated in EE: provision of TB and HIV services at one site (36% in EE vs. 89% in WE; P = 0.034), and continued TB follow-up in one location (42% vs. 100%; P = 0.007). Although access to TB diagnostics, standard TB and HIV drugs was generally good, fewer sites in EE reported unlimited access to rifabutin/multi-drug-resistant TB (MDR-TB) drugs, HIV integrase inhibitors and opioid substitution therapy (OST). Compared with 2013, routine usage of GeneXpert was more common in EE in 2018 (54% vs. 92%; P = 0.073), as was access to moxifloxacin (46% vs. 91%; P = 0.033), linezolid (31% vs. 64%; P = 0.217), and bedaquiline (0% vs. 25%; P = 0.217). Integration of TB and HIV services (46% vs. 39%; P = 1.000) and provision of OST to patients with opioid dependency (54% vs. 46%; P = 0.695) remained unchanged. Conclusion: Delivery of TB and HIV healthcare, including integration of TB and HIV care and access to MDR-TB drugs, still differs between WE and EE, as well as between individual EE sites

Hydrophobic Rose Bengal Derivatives Exhibit Submicromolar-to-Subnanomolar Activity against Enveloped Viruses

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment.

BACKGROUND A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. METHODS People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). RESULTS There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. CONCLUSIONS Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD

The hepatitis C cascade of care in HIV/HCV-coinfected individuals in Europe- regional and intra-regional differences.

BACKGROUND Following the introduction of direct-acting antiviral therapy in 2013, WHO launched the first Global Health Sector Strategy on Viral Hepatitis. We describe a hepatitis C virus (HCV) cascade of care in people with HIV (PWH) across Europe in terms of reaching the WHO elimination targets of diagnosing 90% and treating 80% of HCV-infected individuals. METHODS HIV/HCV-coinfected participants in the EuroSIDA cohort under prospective follow-up at October 1, 2019, were described using a nine-stage cascade of care. Care cascades were constructed across Europe, on a regional (n = 5) and country (n = 21) level. RESULTS Of 4773 anti-HCV positive PWH, 4446 [93.1%, 95% confidence interval (CI) 92.4-93.9)] were ever tested for HCV RNA, and 19.0% (95% CI 16.4-21.6) were currently HCV RNA positive, with the highest prevalence in Eastern and Central-Eastern Europe (33.7 and 29.6%, respectively). In Eastern Europe, 78.1% of the estimated number of chronic infections have been diagnosed, whereas this proportion was above 95% in the other four regions. Overall, 3116 persons have ever started treatment (72.5% of the ever chronically infected, 95% CI 70.9-74.0) and 2404 individuals (55.9% of the ever chronically infected, 95% CI 53.9-57.9) were cured. Cure proportion ranged from 11.2% in Belarus to 87.2% in Austria. CONCLUSION In all regions except Eastern Europe, more than 90% of the study participants have been tested for HCV-RNA. In Southern and Central-Western regions, more than 80% ever chronically HCV-infected PWH received treatment. The proportion with cured HCV infection did not exceed 80% in any region, with significant heterogeneity between countries. SUMMARY In a pan-European cohort of PWH, all regions except Eastern Europe achieved the WHO target of diagnosing 90% of chronic HCV infections, while the target of treating 80% of eligible persons was achieved in none of the regions