Barriers and facilitators to viral hepatitis testing in Uzbekistan: scoping qualitative study among key stakeholders, healthcare workers, and the general population.

INTRODUCTION: In the World Health Organization European Region, an estimated 14 million people live with a chronic hepatitis B virus infection (HBV), and 12 million are affected by a hepatitis C virus infection (HCV). Uzbekistan bears a major burden of HBV and has one of the highest HCV prevalence in the region. Following a presidential decree in May 2022, significant funds were allocated to the viral hepatitis (VH) elimination program in Uzbekistan. The program expands VH testing to reach 500,000 people annually during 2022-2025 as part of the VH elimination strategy that includes the provision of free testing and affordable treatment. Exploring the existing barriers and facilitators to VH testing is pivotal for informing these interventions. METHODS: This study uses a cross-sectional qualitative design to identify and explore the barriers and facilitators to VH testing among the general population in Uzbekistan. We collected data during October-November 2022 through semi-structured interviews with 12 key informants (KIs) and 7 focus group discussions with two target populations: the general population and healthcare workers (HCW) in Tashkent, Uzbekistan. RESULTS: Following the capability-opportunity-motivation-behavior model (COM-B model) as a framework for the analysis, we identified major capability barriers to VH testing primarily linked to low health literacy and limited knowledge about VH types, symptoms, transmission, testing and treatment. Physical opportunity barriers included the time and financial costs associated with testing, diagnostics, and treatment. Sociocultural opportunity barriers involved anticipated negative reactions and stigmatization, particularly affecting women. Motivational barriers included a reluctance to be tested when asymptomatic and a general fear of receiving positive test results. The involvement of healthcare workers in promoting VH awareness and motivating the general population emerged as a facilitator. CONCLUSIONS: A multi-pronged approach is recommended to achieve VH testing goals among the general population, focusing on raising awareness and health literacy and creating an enabling environment that ensures easy accessibility and minimizing VH testing-associated costs.

Identification of CXCL9 chemokine as a potential biomarker for assessing clinical severity in COVID-19 patients.

INTRODUCTION: The severity and clinical outcome of COVID-19 depend on virus-specific factors and the host's inflammatory response. Identifying biomarkers of severe COVID-19 is a crucial condition and predicts disease severity. METHODOLOGY: This study enrolled a total of 167 patients with COVID-19. These patients were categorized into three groups based on the severity of the disease: moderate course - 78 individuals, severe course - 52 individuals, and extremely severe course - 37 individuals. We analyzed chemokines (IP-10, CXCL9, CCL17) and cytokine IL28B levels using the enzyme immunoassay (EIA) method. RESULTS: CXCL9 levels were increased in severe and extremely severe cases compared to moderate ones. The CCL17 chemokine demonstrated significant elevation in severe cases. However, there was no significant difference in the level of IP-10, and IL28B in the compared groups. CONCLUSIONS: Our findings suggest that CXCL9 and CCL17 chemokines could be used as biomarkers to assess the clinical status of patients with COVID-19 and can relate to disease severity. These biomarkers could aid in identifying patients at high risk for severe disease and help guide clinical decision-making for the effective management of COVID-19.

Therapeutic potential of natural products in schistosomiasis-associated liver fibrosis.

Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.

Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo.

Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production. Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein. Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway. Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

The History of Controlling and Treating Infectious Diseases in Ancient China.

Infectious diseases are the common enemies of mankind. In the course of historical development, they persistently threaten human health and safety. Even today, despite the developments in medical science, we cannot escape the fear and suffering caused by infectious diseases. Whether in ancient or modern times, the source of infection, route of transmission, and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases. All factors closely related to these three conditions can affect the prevalence of infectious diseases. China is one of the cradles of world civilization. The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases. In the face of the current threat posed by widespread infectious disease, it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease. The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights, especially for impoverished and medically underserved regions.

Repurposing of Rutan showed effective treatment for COVID-19 disease.

Previously, from the tannic sumac plant (Rhus coriaria), we developed the Rutan 25 mg oral drug tablets with antiviral activity against influenza A and B viruses, adenoviruses, paramyxoviruses, herpes virus, and cytomegalovirus. Here, our re-purposing study demonstrated that Rutan at 25, 50, and 100 mg/kg provided a very effective and safe treatment for COVID-19 infection, simultaneously inhibiting two vital enzyme systems of the SARS-CoV-2 virus: 3C-like proteinase (3CLpro) and RNA-dependent RNA polymerase (RdRp). There was no drug accumulation in experimental animals' organs and tissues. A clinical study demonstrated a statistically significant decrease in the C-reactive protein and a reduction of the viremia period. In patients receiving Rutan 25 mg (children) and 100 mg (adults), the frequency of post-COVID-19 manifestations was significantly less than in the control groups not treated with Rutan tablets. Rutan, having antiviral activity, can provide safe treatment and prevention of COVID-19 in adults and children. Clinical Trial Registration: ClinicalTrials.gov, ID NCT05862883.

Assessment of the Impact of the Rotavirus Vaccine Against Severe Rotaviral Diarrhea in Uzbekistan.

BACKGROUND: This article presents the results of a long-term study of the impact of rotavirus vaccination in Uzbekistan. Uzbekistan is the first country in the Central Asian region to introduce rotavirus vaccination into the national compulsory vaccination calendar. The study aimed to evaluate the impact of rotavirus vaccination on hospitalizations due to all-cause AGE and RVGE in children < 5 years of age in Uzbekistan. METHODS: Detection of rotavirus antigen was performed using Rotavirus-Antigen-IFA-BEST "Vector Best" kit (Novosibirsk, Russia). RESULTS: The total of 20,128 children under 5 years of age were hospitalized in sentinel hospitals with a diagnosis of acute gastroenteritis during the study period (2019-2020). Of this number of children, 4481 children (22.2%) were included in the study. Of 4481 children, 367 (8.2%) children tested positive for rotavirus. In our study, decrease in the rotavirus rate was noted in all age groups. The peak of rotavirus positivity occurred in the months of January and February. CONCLUSION: The average rotavirus-positive rate in the period (2019-2020) was 8.2% and the absolute percentage decrease was 18.1% compared to the pre-vaccination period (2005-2009) where the rotavirus-positive rate was 26.3%. The percentage of prevented cases averaged 68.8%.

Viral hepatitis elimination challenges in low- and middle-income countries-Uzbekistan Hepatitis Elimination Program (UHEP).

BACKGROUND & AIMS: Chronic infection with hepatitis B and C viruses (HBV & HCV) is a major contributor to liver disease and liver-related mortality in Uzbekistan. There is a need to demonstrate the feasibility of large-scale simplified testing and treatment to implement a national viral hepatitis elimination program. METHODS: Thirteen polyclinics were utilized to screen, conduct follow-up biochemical measures and treat chronic HBV and HCV infection in the general adult population. Task shifting and motivational interviewing training allowed nurses to provide rapid screening and general practitioners (GPs) to treat individuals on-site. An electronic medical system tracked individuals through the cascade of care. RESULTS: The use of rapid tests allowed for screening of 60 769 people for HCV and HBV over 6 months and permitted outdoor testing during the COVID-19 pandemic along with COVID testing. 13%-14% of individuals were lost to follow-up after the rapid test, and another 62%-66% failed to come in for their consultation. One stop testing and treatment did not result in a statistically increase in retention and lack of patient awareness of viral hepatitis was identified as a key factor. Despite training, there were large differences between GPs and patients initiating treatment. CONCLUSIONS: The current study demonstrated the feasibility of large-scale general population screening and task shifting in low- and middle-income countries. However, such programs need to be proceeded by awareness campaign to minimize loss to follow up. In addition, multiple trainings are needed for GPs to bolster their skills to talk to patients about treatment.

Identifying HIV-1 Transmission Clusters in Uzbekistan through Analysis of Molecular Surveillance Data.

The CRF02_AG and sub-subtype A6 are currently the predominant HIV-1 variants in the Republic of Uzbekistan, but little is known about their time-spatial clustering patterns in high-risk populations. We have applied molecular evolution methods and network analyses to better understand the transmission patterns of these subtypes by analyzing 316 pol sequences obtained during the surveillance study of HIV drug resistance. Network analysis showed that about one third of the HIV infected persons were organized into clusters, including large clusters with more than 35 members. These clusters were composed mostly of injecting drug users and/or heterosexuals, with women having mainly high centrality within networks identified in both subtypes. Phylogenetic analyses of the 'Uzbek' sequences, including those publicly available, show that Russia and Ukraine played a role as the main sources of the current subtype A6 epidemic in the Republic. At the same time, Uzbekistan has been a local center of the CRF02_AG epidemic spread in the former USSR since the early 2000s. Both of these HIV-1 variants continue to spread in Uzbekistan, highlighting the importance of identifying transmission networks and transmission clusters to prevent further HIV spread, and the need for HIV prevention and education campaigns in high-risk groups.

Prevalence of HIV-1 drug resistance in Eastern European and Central Asian countries.

BACKGROUND: Eastern Europe and Central Asia (EECA) is one of the regions where the HIV epidemic continues to grow at a concerning rate. Antiretroviral therapy (ART) coverage in EECA countries has significantly increased during the last decade, which can lead to an increase in the risk of emergence, transmission, and spread of HIV variants with drug resistance (DR) that cannot be controlled. Because HIV genotyping cannot be performed in these countries, data about HIV DR are limited or unavailable. OBJECTIVES: To monitor circulating HIV-1 genetic variants, assess the prevalence of HIV DR among patients starting antiretroviral therapy, and reveal potential transmission clusters among patients in six EECA countries: Armenia, Azerbaijan, Belarus, Russia, Tajikistan, and Uzbekistan. MATERIALS AND METHODS: We analyzed 1071 HIV-1 pol-gene fragment sequences (2253-3369 bp) from patients who were initiating or reinitiating first-line ART in six EECA counties, i.e., Armenia (n = 120), Azerbaijan (n = 96), Belarus (n = 158), Russia (n = 465), Tajikistan (n = 54), and Uzbekistan (n = 178), between 2017 and 2019. HIV Pretreatment DR (PDR) and drug resistance mutation (DRM) prevalence was estimated using the Stanford HIV Resistance Database. The PDR level was interpreted according to the WHO standard PDR survey protocols. HIV-1 subtypes were determined using the Stanford HIV Resistance Database and subsequently confirmed by phylogenetic analysis. Transmission clusters were determined using Cluster Picker. RESULTS: Analyses of HIV subtypes showed that EECA, in general, has the same HIV genetic variants of sub-subtype A6, CRF63_02A1, and subtype B, with different frequencies and representation for each country. The prevalence of PDR to any drug class was 2.8% in Uzbekistan, 4.2% in Azerbaijan, 4.5% in Russia, 9.2% in Armenia, 13.9% in Belarus, and 16.7% in Tajikistan. PDR to protease inhibitors (PIs) was not detected in any country. PDR to nucleoside reverse-transcriptase inhibitors (NRTIs) was not detected among patients in Azerbaijan, and was relatively low in other countries, with the highest prevalence in Tajikistan (5.6%). The prevalence of PDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was the lowest in Uzbekistan (2.8%) and reached 11.1% and 11.4% in Tajikistan and Belarus, respectively. Genetic transmission network analyses identified 226/1071 (21.1%) linked individuals, forming 93 transmission clusters mainly containing two or three sequences. We found that the time since HIV diagnosis in clustered patients was significantly shorter than that in unclustered patients (1.26 years vs 2.74 years). Additionally, the K103N/S mutation was mainly observed in clustered sequences (6.2% vs 2.8%). CONCLUSIONS: Our study demonstrated different PDR prevalence rates and DR dynamics in six EECA countries, with worrying levels of PDR in Tajikistan and Belarus, where prevalence exceeded the 10% threshold recommended by the WHO for immediate public health action. Because DR testing for clinical purposes is not common in EECA, it is currently extremely important to conduct surveillance of HIV DR in EECA due to the increased ART coverage in this region.

Prevalence of Antiretroviral Drug Resistance Mutations Among Pretreatment and Antiretroviral Therapy-Failure HIV Patients in Uzbekistan.

To evaluate the national prevalence of antiretroviral therapy (ART)-resistant HIV-1 viruses among both ART-initiators (pretreatment drug resistance, PDR) and ART-failure HIV patients in Uzbekistan. A nation-wide, cross-sectional active HIV-1 PDR surveillance was conducted in Uzbekistan from 2015 to 2016. In total, 713 blood plasma samples from adults were collected, including samples from ART-naive patients initiating ART and ART-failure HIV patients. HIV-1 genome polregion viral sequences were obtained from 309 patients, of those 106 on ART and 203 on ART-initiators. Analysis of HIV-1 subtypes and drug resistance mutations (DRMs) to HIV protease and reverse transcriptase inhibitors was performed. Among all the viruses studied, HIV-1 CRF 02_AG recombinant was the most common-57% (176/309). The second major group was represented by A1-40.5% (125/309). Two viruses were found to be recombinants formed by subtypes A1 and CRF02_AG sequences. ART-naive cohort I (PDR) included six samples that contained at least one surveillance drug resistance mutation (SDRM) (2.96%), with the most common being K103N mutation (4/6). In ART-experienced patients, cohort II, 77.4% (82/106) of viruses contained at least one mutation against PIs, NRTIs, or NNRTIs, with the most common mutations of M184V/I (49.1%; 52/106), K65R (18.9%; 20/106), K103N (23.6%; 25/106), and G190S (22.6%; 24/106). The significant difference in frequency of mutations was found between two dominant subtypes, A1 and CRF02_AG. The molecular epidemiological profile of HIV infection in Uzbekistan has changed toward a predominance of CRF02_AG viruses. In the first national-scale study of the PDR prevalence, it was found to be relatively low (2.96%). The DR mutations in failure patients correspond to the main therapy regimens (NRTI/NNRTI) adopted in the country. The observations provide new evidence for differences in ART efficacy and resistance profiles for different subtypes.

Rotavirus vaccine effectiveness and impact in Uzbekistan, the first country to introduce in central Asia.

Uzbekistan, the most populous country in central Asia, was the first in the region to introduce rotavirus vaccine into its national immunization program. Rotarix (GlaxoSmithKline Biologicals, RV1) was introduced in June 2014, with doses recommended at age 2 and 3 months. To evaluate vaccine impact, active surveillance for rotavirus diarrhea was reestablished in 2014 at 2 hospitals in Tashkent and Bukhara which had also performed surveillance during the pre-vaccine period 2005-2009. Children aged <5 y admitted with acute diarrhea had stool specimens collected and tested for rotavirus by enzyme immunoassay. Proportions testing rotavirus-positive in post-vaccine years were compared with the pre-vaccine period. Vaccine records were obtained and effectiveness of 2 RV1 doses vs 0 doses was estimated using rotavirus-case and test-negative design among children enrolled from Bukhara city. In 2015 and 2016, 8%-15% of infants and 10%-16% of children aged<5 y hospitalized with acute diarrhea at the sites tested rotavirus-positive, compared with 26% of infants and 27% of children aged<5 y in pre-vaccine period (reductions in proportion positive of 42%-68%, p <.001). Vaccine effectiveness of 2 RV1 doses vs 0 doses in protecting against hospitalization for rotavirus disease among those aged ≥6 months was 51% (95% CI 2-75) and is based on cases predominantly of genotype G2P[4]. Vaccine effectiveness point estimates tended to be higher against cases with higher illness severity (e.g., clinical severity based on modified Vesikari score ≥11). Our data demonstrate that the monovalent rotavirus vaccine is effective in reducing the likelihood of hospitalization for rotavirus disease in young children in Uzbekistan.

Progress Toward Hepatitis B and Hepatitis C Elimination Using a Catalytic Funding Model - Tashkent, Uzbekistan, December 6, 2019-March 15, 2020.

In 2016, the World Health Organization (WHO) set hepatitis elimination targets of 90% reduction in incidence and 65% reduction in mortality worldwide by 2030 (1). Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection prevalences are high in Uzbekistan, which lacks funding for meeting WHO's targets. In the absence of large financial donor programs for eliminating HBV and HCV infections, insufficient funding is an important barrier to achieving those targets in Uzbekistan and other low- and middle-income countries. A pilot program using a catalytic funding model, including simplified test-and-treat strategies, was launched in Tashkent, Uzbekistan, in December 2019. Catalytic funding is a mechanism by which the total cost of a program is paid for by multiple funding sources but is begun with upfront capital that is considerably less than the total program cost. Ongoing costs, including those for testing and treatment, are covered by payments from 80% of the enrolled patients, who purchase medications at a small premium that subsidizes the 20% who cannot afford treatment and therefore receive free medication. The 1-year pilot program set a target of testing 250,000 adults for HBV and HCV infection and treating all patients who have active infection, including those who had a positive test result for hepatitis B surface antigen (HBsAg) and those who had a positive test result for HCV core antigen. During the first 3 months of the program, 24,821 persons were tested for HBV and HCV infections. Among those tested, 1,084 (4.4%) had positive test results for HBsAg, and 1,075 (4.3%) had positive test results for HCV antibody (anti-HCV). Among those infected, 275 (25.4%) initiated treatment for HBV, and 163 (15.2%) initiated treatment for HCV, of whom 86.5% paid for medications and 13.5% received medications at no cost. Early results demonstrate willingness of patients to pay for treatment if costs are low, which can offset elimination costs. However, improvements across the continuum of care are needed to recover the upfront investment. Lessons learned from this program, including the effectiveness of using simplified test-and-treat guidelines, general practitioners in lieu of specialist physicians, and innovative financing to reduce costs, can guide similar initiatives in other countries and help curb the global epidemic of viral hepatitis, especially among low- and middle-income countries.

The medical impact of hepatitis D virus infection in Uzbekistan.

BACKGROUND & AIMS: The hepatitis B virus (HBV) is endemic in Uzbekistan but the medical impact of infection with the HBV-dependent hepatitis D virus (HDV) is unknown in the Country. An Hepatology Center was recently established at the Institute of Virology in Tashkent, which has set up a database enlisting patients with chronic viral liver disorders from all over Uzbekistan; it provides an observatory on the current scenario of viral hepatitis in the Country. METHODS: The prevalence of HBV monoinfection, hepatitis C virus (HCV) infection and HDV superinfection on hepatitis B surface antigen (HBsAg)-positive cirrhosis was determined in 6589 patients with viral cirrhosis collected in the last 3 years. RESULTS: Of 1089, 1150 and 1455 carriers of the HBsAg with cirrhosis recruited in 2016, 2017 and 2018, 834 (76.5%), 926 (80.5%) and 1224 (84%) respectively, had antibody to the HDV. In 2016, 2017 and 2018, the prevalence of HDV infection has been 41%, 45% and 49.1% respectively, largely exceeding the prevalence of HBV monoinfection (12.5%, 11% and 9.3% respectively) and surpassing the prevalence of HCV in 2017 and 2018 (44% and 41.5% respectively). The median age of the patients with HDV cirrhosis was 39 years, distinctly lower than that of HBV and HCV patients (46 and 55). CONCLUSIONS: Superinfection with the HDV is present in over 80% of the HBsAg-positive cirrhosis in Uzbekistan. The HDV appears to be the major cause of advanced viral liver disease and of juvenile cirrhosis in the Country.

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions.

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.

IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.

AIMS: Genome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection. METHODS: One hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced. RESULTS: Of the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-α plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9-14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6-18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples. CONCLUSIONS: SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.

Rotavirus gastroenteritis in uzbekistan: implications for vaccine policy in central Asia.

BACKGROUND: To determine the value of rotavirus vaccines in Central Asia, we conducted surveillance of rotavirus in Uzbekistan, the country with the largest birth cohort in the region. Uzbekistan is eligible for international funds to introduce new vaccines. METHODS: We screened stool samples for rotavirus that were collected from children aged <5 years with gastroenteritis in 2 hospitals during 2005-2006. Using surveillance information and other data, we estimated national numbers of rotavirus-associated events per year. RESULTS: Of 3537 enrolled children, 1046 (30%) had rotavirus detected in stool specimens. Children aged <2 years accounted for 841 (80%) of all rotavirus infections. The G1P[8] genotype was identified in 27 (52%) of 52 typed samples collected in 2005. Rotavirus is estimated to cause 1174-1857 deaths and 6394-6558 hospitalizations among children aged <5 years annually. The cumulative risk of hospitalization for rotavirus by age 5 years is 1 in 94-96 children, and the risk of rotavirus-related death is 1 in 330-524 children. CONCLUSIONS: One-third of all hospitalizations for gastroenteritis and almost 5% of all deaths among children aged <5 years in Uzbekistan may be attributable to rotavirus. Introduction of rotavirus vaccines into the national immunization program at the current subsidized prices could be cost-effective.

Hepatitis B virus transmission pattern and vaccination efficiency in Uzbekistan.

A national program of universal vaccination for the prevention of chronic hepatitis B virus (HBV) infection was launched in Uzbekistan since 1998. To evaluate the 6 years' outcome of the program, 567 children were enrolled in the study. Among those enrolled, 333 had immunized with adw2 type based Engerix-B (Glaxo Smith Kline Beechem, Rixensart, Belgium) and 48 with adr type based Hepavax-Gene (Green Cross Vaccine Corporation, Korea). A cohort of 186 children born before the immunization program, was also included in the study. When 45 vaccinated children were compared to age/sex-matched 45 unvaccinated children, the sero-prevalence of HBsAg was 0 versus 11% (P = 0.56), and of anti-HBc was 0% versus 44% (P < 0.0001), respectively. Loss of anti-HBs was observed in 18.4% after 5 years. Among 13 HBsAg carriers found in this study, genotype HBV/D was found in 69%, HBV/A in 23% (all in unvaccinated group) and HBV/C in 8% (in vaccinated group). No significant differences were observed in this study between groups which received different vaccine formulation. Phylogenetic analysis of the HBV isolates obtained from family members of the HBsAg-positive children, revealed evidence suggesting that transmission in the vaccinated group was exclusively perinatal, whereas in the unvaccinated group horizontal transmission pattern predominated. In conclusion, HBV universal vaccination is efficient in Uzbekistan irrespective of the vaccine formulation used, because the horizontal transmission pattern predominates currently in this endemic region.

Detection of hepatitis C virus natural recombinant RF1_2k/1b strain among intravenous drug users in Uzbekistan.

AIM: A series of recent studies have indicated the presence of natural intergenotypic recombinant hepatitis C virus (HCV) strains in distinct parts of the world. The majority of the current genotyping methods are based on analysis of either 5'UTR, structural (Core/E1/E2) or non-structural (NS5B) genomic regions of the virus. METHODS: In the present study, based on both structural and non-structural regions, we determined the genotype of 55 anti-HCV-positive intravenous drug users (IDUs) in Uzbekistan. RESULTS: HCV-3a (67.3%) was the most prevalent genotype in this cohort, followed by HCV-1b (27.3%). A discrepancy in results was observed between structural and non-structural regions in one case (1.8%). Phylogenetically this strain was related to the previously reported RF1_2k/1b variant. Based on accumulated sequences, specific primers were designed for polymerase chain reaction (PCR) spanning the tentative intergenotypic crossover point of RF1_2k/1b. The sensitivity and specificity of the method were assessed using generated template clones of HCV-1b, 2a, 2 k and RF1_2k/1b. The method was applied to 55 cases in the present study and only one case showed a positive result, indicating that in these individuals, the variant is not present as a minor quasispecies clone. CONCLUSION: In conclusion, the finding of RF1_2k/1b in Central Asia indicates that the variant has wide geographic distribution. The PCR-based screening method developed in this study should be useful in further epidemiological and clinical studies on the recombination phenomenon in HCV.