Hepatitis C Virus in people with experience of injection drug use following their displacement to Southern Ukraine before 2020.

BACKGROUND: Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine. METHODS: In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships. RESULTS: Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement. CONCLUSIONS: Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

Alternative genotyping of drug-resistant Mycobacterium tuberculosis strains.

The aim of the present research was to study the capability of a genotyping method for M. tuberculosis through detection of six VNTR-loci (MIRU10, MIRU26, MIRU31, MIRU39, MIRU40, ETR-A). Loci MIRU10, MIRU26, MIRU40 and ETR-A have exhibited high polymorphism in group non-Beijing, while loci MIRU26 and MIRU31 - in the Beijing family. A combined detection of all six loci for fingerprinting of the isolates both from Beijing and non-Beijing was highly effective (Hunter-Gaston index was 0.88 and 0.93 correspondently), especially in areas with limited financial resources and high prevalence of multidrug resistant M. tuberculosis strains.

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/µCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

The Impact of IgG administration on the cellular immunity status in the patients with multidrug-resistant tuberculosis/HIV with CD4 + lymphocyte cells below 50 cells/ µl.

Background: Treatment of the patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection in a state of severely suppressed immune system remains unsatisfactory. Methods: The study involved 52 HIV-positive patients with MDR-TB and CD4+ lymphocyte cells below 50 cells/µCL. Patients in control group (Group 1) and in basic group (Group 2) received standard treatment with second-line antituberculosis agents and antiretroviral agents. In addition, the patients in basic group were treated by immunoglobulin G (IgG) intravenously. Immunological diagnostics with the determination of the level of lymphocytes subgroups (CD3+, CD4+, CD8+, CD4+/CD8+) was carried out using an AQUIOS™ CL flow cytometry device at the beginning and after 3-20 months of treatment. Statistical analysis was performed using the Statistica 10.0 software (Stat. Soft Inc., USA). Results: In the patients of Group 2, the absolute number of CD3+ and CD4+ cells at the end of the 20th month of the treatment normalized in 26.9% (absolute amount) and 42.3% (relative amount) of subjects, while in Group 1, this indicator remained below the normal level (P < 0.05). The addition of IgG into standard therapy caused normalization of CD8+ count in 76.9% of patients, while in the control group-only in 46.2% of patients (P < 0.05). Conclusions: The administration of IgG in combination with standard anti-tuberculosis and antiretroviral therapy (ART) contributes to the normalization of the cellular immunity status in patients with MDR-TB/HIV coinfection and severe immunosuppression and allows you to start ART earlier than in patients with single standard therapy.

Biochemical value dynamics in patients with multidrug-resistant tuberculosis/hiv with CD4+ lymphocyte cells below 50 cells/µCL and its variability in the application of adjuvant immunoglobulin therapy.

Context: Treatment of the patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection in a state of severely suppressed immune system remains under efficient. Aims: The aim of this study was to assess the effectiveness of adjuvant immunoglobulin therapy in TB/HIV patients. Settings and Design: The relationship between biochemical indexes in the patients with MDR-TB/HIV co-infection and adjuvant immunoglobulin therapy. Materials and Methods: The study involved 52 HIV-positive patients with MDR-TB and CD4+ lymphocyte cells below 50 cells/µCL. Patients in control group (Group 1) and in basic group (Group 2) received standard treatment with second-line antituberculosis agents and antiretroviral agents. In addition patients in basic group were treated by immunoglobulin G intravenously. The evaluation of biochemical parameters such as bilirubin level, thymol test, the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) was carried out on automatic analyzer HumaStar 300 at the beginning and after 0.5-8 months of treatment. Statistical analysis was performed using the Statistica 10.0 software (Stat. Soft Inc., USA). Kruskal-Wallis, ANOVA, and Chi-square tests were used in this study. Results: After 8 months of treatment, studied biochemical indexes were lower in Group 2 than in patients from Group 1. For example, the number of patients in Group 2 with increased bilirubin level was 1.7 times more than in Group 1 (p < 0.05), with increased ALT, AST, or GGT activity in 2.5 times (p < 0.01), 2.7 times (p < 0.01), or 2.4 times (p < 0.05) correspondently, comparatively with Group 1. Conclusion: The usage of immunoglobulins intravenously in the group of patients with MDR-TB associated with HIV infection, with CD4+ level <50 cells/µCL, is appropriate and essential because it improves treatment outcome.

Association between effectiveness of tuberculosis treatment and cytochrome P-4502E1 polymorphism of the patients.

CONTEXT: The risk of antituberculosis (TB) drug-induced liver injury could be determined by patients' genotype polymorphism of the xenobiotic-metabolizing enzymes. To find the meaning of cytochrome P-4502E1 (CYP2E1) polymorphism in TB patients. Corresponding of CYP2E1 polymorphism in TB patients with the level of isoniazid and rifampicin as well as for the outcome and toxicity development during inpatient TB treatment. METHODS: CYP2E1 genotype was detected with the help of polymerase chain reaction and endonuclease analysis. The level of rifampicin, isoniazid, diene conjugates (DC), and catalase activity in the blood was determined spectrophotometrically. We have considered medical records at the beginning and at the end of inpatient treatment. STATISTICAL ANALYSIS USED: Kruskal-Wallis, ANOVA, and Chi-square tests were used in this study. RESULTS: The concentration of rifampicin 6 h after its intake was 17.6% higher in carriers of slow metabolizer (SM) CYP2E1 genotype than in patients with rapid metabolizer (RM) genotype that proved a participation of hepatic enzyme CYP2E1 in metabolism of rifampicin. According to obtained results in TB patients with RM genotype, the indexes of cytolysis (alanine aminotransferase, aspartate aminotransferase) and bile stasis (gamma-glutathione transferase) were higher comparatively to SM genotype both before and after inpatient treatment. This correlated with a higher concentration of DC in the blood (+8.6%) and lower plasma catalase activity (-50.0%) in the patients with RM genotype comparatively with the patients with SM genotypes. CONCLUSION: Polymorphism of CYP2E1 genotype is an important criterion for the development of hepatotoxicity before and during TB treatment while increased rifampicin level has no influence on it.