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%.

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.

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.

Dynamic modeling of cost-effectiveness of rotavirus vaccination, Kazakhstan.

The government of Kazakhstan, a middle-income country in Central Asia, is considering the introduction of rotavirus vaccination into its national immunization program. We performed a cost-effectiveness analysis of rotavirus vaccination spanning 20 years by using a synthesis of dynamic transmission models accounting for herd protection. We found that a vaccination program with 90% coverage would prevent ≈880 rotavirus deaths and save an average of 54,784 life-years for children <5 years of age. Indirect protection accounted for 40% and 60% reduction in severe and mild rotavirus gastroenteritis, respectively. Cost per life year gained was US $18,044 from a societal perspective and US $23,892 from a health care perspective. Comparing the 2 key parameters of cost-effectiveness, mortality rates and vaccine cost at

Rotavirus genotype distribution in Kyrgyzstan and Kazakhstan, 2007-2009.

This is the first study to present rotavirus genotype distribution in children admitted to a hospital with acute gastroenteritis in Kyrgyzstan and Kazakhstan from January 2007 through December 2009. In total, 858 rotavirus ELISA-positive samples were characterized by RT-PCR, with a considerable geographical and seasonal variation in genotype distribution observed during the study. The globally common genotypes (G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], G12P[8] and G12P[6]) accounted for 81.5-88.2% of the infections in Kyrgyzstan and 72.3-79.3% of the infections in Kazakhstan. The predominant genotypes were G1P[8], G2P[4] and G3P[8]. G1P[8] was the dominating genotype in Kyrgyzstan, detected in 51-64.7% of the samples. A similar predominance was not seen for G1P[8] in Kazakhstan, with a shift to G2P[4] predominance being seen in 2008. G9P[8] was a rare genotype in both countries, whereas G12 was detected in between 2.2% and 7.6% of the samples. The surveillance period was characterized by many co-circulating genotypes, and eight unusual combinations (G1P[4], G2P[8], G2P[6], G3P[4], G9P[4], G12P[4], G9P[9] and G10P[4]) were detected. This study provides important baseline data on rotavirus genotypes in Kyrgyzstan and Kazakhstan in the pre-vaccine era, and the results may indicate that the two licensed vaccines can be expected to prevent rotavirus disease in these countries.

Epidemiology and burden of rotavirus disease in Central Asia.

BACKGROUND: Rotavirus infection is the most common cause of severe gastroenteritis in children worldwide. New rotavirus vaccines are not currently used in the five countries that make up the Central Asian region. Three of these countries, Kazakhstan, Uzbekistan, and Kyrgyzstan, have a combined total population of 48 million and an estimated 1 million annual births. METHODS: We conducted prospective hospital-based surveillance for rotavirus diarrhea in three Central Asian countries (Kazakhstan, Uzbekistan, and Kyrgyzstan) during 2005-2009 to estimate the burden of rotavirus. We calculated the proportion of rotavirus among children aged <5 years hospitalized with acute diarrhea and estimated numbers of rotavirus-associated deaths, hospitalizations, outpatient visits, and home care episodes. RESULTS: Of 20 780 children hospitalized with diarrhea and enrolled in the study, 26% (95% confidence interval (CI) 25-27) were positive for rotavirus antigen by ELISA. On an annual basis, 4007 (2.6 per 1000 child-years) rotavirus hospitalizations occur in Kazakhstan, 5491 (2.1 per 1000 child-years) in Uzbekistan, and 3883 (6.8 per 1000 child-years) in Kyrgyzstan. Rotavirus is also estimated to cause 68 (0.04 per 1000 child-years) deaths in children aged <5 years in Kazakhstan, 662 (0.25 per 1000 child-years) in Uzbekistan, and 156 (0.27 per 1000 child-years) in Kyrgyzstan. CONCLUSION: This study presents an epidemiological picture of rotavirus disease in Central Asia and illustrates a substantial rotavirus burden, which is preventable with rotavirus vaccination.

Economic burden of rotavirus disease in children under 5 years in Kazakhstan.

BACKGROUND: We aimed to estimate the societal costs of rotavirus cases among children less than 5 years in Kazakhstan, an upper-middle income country in Central Asia. METHODS: Data on medical, non-medical and indirect costs were collected for 190 patients less than 5 years, hospitalized with severe diarrhea in 2009 in two pediatric hospitals. Data on resource use for moderate and mild diarrhea cases were obtained from published sources. A probabilistic sensitivity analysis was performed to explore uncertainty in cost estimates. RESULTS: Approximately 4,000 severe, 30,700 moderate, and 122,900 mild rotavirus cases were estimated annually in children <5 years old. The mean societal cost of a severe, moderate and mild rotavirus case was estimated at US$ 454, 82, and 21, respectively. The total annual cost of rotavirus disease was $37.53 million or on average $107.36 for a child under 5 years old in Kazakhstan. Ninety-four percent of total costs (35.13 million) are indirect costs (productivity losses) from fatal cases and parents' job absenteeism, while direct medical costs account for 2.04 million (5.4%), and direct non-medical for 0.46 million (1.2%). CONCLUSIONS: Rotavirus-associated diarrhea represents a significant economic burden in Kazakhstan, largely due to indirect costs. The costs of rotavirus infections should be considered when planning further preventive actions, including the introduction of rotavirus vaccination.

Childhood intussusception in Uzbekistan: analysis of retrospective surveillance data.

BACKGROUND: Estimates of baseline incidence of childhood intussusception could help safety monitoring after the introduction of rotavirus vaccines. We studied the incidence of intussusception in Uzbekistan, a GAVI-fund eligible state in Central Asia. METHODS: We retrospectively reviewed intussusception cases in children <2 years of age treated during 2004-2008 at 15 hospitals in the Bukhara region of Uzbekistan. Demographic and clinical data as well as information on diagnostic and treatment practices were obtained from hospital records. We categorized cases using the Brighton collaboration clinical case definition and calculated the national incidence rate. RESULTS: Over a 5-year study period, 67 confirmed cases were identified, of which 67% were boys. The median age was 12 months, and no seasonal trend in the distribution of cases was observed. The diagnostic methods used included abdominal radiography (87%) and ultrasonography (57%). Intussusception reduction by air enema was successful in 33 (49%) patients and 34 (50%) cases underwent surgery. A total of 4 deaths occurred, including 3 deaths in infants aged 0-6 months. The median length of hospital stay was 7.3 (range 0-37) days. The incidence of intussusception is estimated at 23 (95% CI 13.6-32.4) cases per 100,000 child-years, corresponding to approximately 237 cases annually. CONCLUSIONS: This is the first study to estimate the incidence of childhood intussusception prior to the introduction of the rotavirus vaccination in Uzbekistan. A prospective surveillance system using a standardized case definition is needed in order to better examine the occurrence of intussusception in developing countries.

Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in kyrgyzstan.

INTRODUCTION: We examined the cost-effectiveness of a rotavirus immunization program in Kyrgyzstan, a country eligible for vaccine funding from the GAVI Alliance. METHODS: We estimated the burden of rotavirus disease and its economic consequences by using national and international data. A cost-effectiveness analysis was conducted from government and societal perspectives, along with a range of 1-way sensitivity analyses. RESULTS: Rotavirus-related hospitalizations and outpatient visits cost US$580,864 annually, of which $421,658 (73%) is direct medical costs and $159,206 (27%) is nonmedical and indirect costs. With 95% coverage, vaccination could prevent 75% of rotavirus-related hospitalizations and deaths and 56% of outpatient visits and could avert $386,193 (66%) in total costs annually. The medical break-even price at which averted direct medical costs equal vaccination costs is $0.65/dose; the societal break-even price is $1.14/dose for a 2-dose regimen. At the current GAVI Alliance-subsidized vaccine price of $0.60/course, rotavirus vaccination is cost-saving for the government. Vaccination is cost-effective at a vaccine price $9.41/dose, according to the cost-effectiveness standard set by the 2002 World Health Report. CONCLUSIONS: Addition of rotavirus vaccines to childhood immunization in Kyrgyzstan could substantially reduce disease burden and associated costs. Vaccination would be cost-effective from the national perspective at a vaccine price $9.41 per dose.

Effect of hygiene promotion on the risk of reinfection rate of intestinal parasites in children in rural Uzbekistan.

A controlled prospective cohort study was designed to assess the effectiveness of hygiene promotion on the risk of reinfection by intestinal parasites in children in 276 rural Uzbek households over a 1-year period. The study included three groups: seasonality (no medicine, no hygiene promotion activity), treatment (medicine provided, no hygiene promotion activity) and hygiene promotion (medicine provided and hygiene promotion activity). The Participatory Hygiene and Sanitation Transformation methodology was utilized as the key tool in hygiene promotion activities. Three hygiene behaviors were targeted: hand washing with soap, safe feces disposal and boiling drinking water. On average, more than 80% of all children tested were infected with Enterobius vermicularis, Hymenolepis nana, Ascaris lumbricoides, Giardia lamblia or Entamoeba coli. There were statistically significant differences between the three groups for the risk of reinfection rate: the risk of reinfection by parasites was 30% lower in the hygiene promotion group than in the treatment group and 37% lower than in the seasonality group. If properly designed and carried out, hygiene promotion is an effective tool in reducing the risk of intestinal parasite reinfection in children, thus improving children's health in rural communities.