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Background The country of Georgia initiated its hepatitis C virus (HCV) elimination program in 2015, at which point a serosurvey showed the adult prevalence of HCV antibody (anti-HCV) and HCV RNA to be 7.7% and 5.4%, respectively. This analysis reports hepatitis C results of a follow-up serosurvey conducted in 2021, and progress towards elimination. Methods The serosurvey used a stratified, multistage cluster design with systematic sampling to include adults and children (aged 5–17 years) providing consent (or assent with parental consent). Blood samples were tested for anti-HCV and if positive, HCV RNA. Weighted proportions and 95% confidence intervals (CI) were compared with 2015 age-adjusted estimates. Results Overall, 7237 adults and 1473 children were surveyed. Among adults, the prevalence of anti-HCV was 6.8% (95% CI, 5.9–7.7). The HCV RNA prevalence was 1.8% (95% CI, 1.3–2.4), representing a 67% reduction since 2015. HCV RNA prevalence decreased among those reporting risk factors of ever injecting drugs (51.1% to 17.8%), and ever receiving a blood transfusion (13.1% to 3.8%; both P < .001). No children tested positive for anti-HCV or HCV RNA. Conclusions These results demonstrate substantial progress made in Georgia since 2015. These findings can inform strategies to meet HCV elimination targets.

Antimicrobial resistance remains a public health concern globally. This study presents antimicrobial resistance by microdilution and genetic diversity by the whole-genome sequencing of

Anthrax is endemic in Georgia, as are multiple zoonotic poxviruses. Poxvirus-associated infections share some clinical manifestations and exposure risks with anthrax, and so it is important to distinguish between the two. With this in mind, an archived collection of anthrax-negative DNA samples was retrospectively screened for poxviruses, and of the 148 human samples tested, 64 were positive. Sequence analysis confirmed the presence of orf virus, bovine papular stomatitis virus, and pseudocowpox virus. This study provides evidence of previously unrecognized poxvirus infections in Georgia and highlights the benefit of the timely identification of such infections by improving laboratory capacity.

Mammal-associated coronaviruses have a long evolutionary history across global bat populations, which makes them prone to be the most likely ancestral origins of coronavirus-associated epidemics and pandemics globally. Limited coronavirus research has occurred at the junction of Europe and Asia, thereby investigations in Georgia are critical to complete the coronavirus diversity map in the region. We conducted a cross-sectional coronavirus survey in bat populations at eight locations of Georgia, from July to October of 2014. We tested 188 anal swab samples, remains of previous pathogen discovery studies, for the presence of coronaviruses using end-point pan-coronavirus RT-PCR assays. Samples positive for a 440 bp amplicon were Sanger sequenced to infer coronavirus subgenus or species through phylogenetic reconstructions. Overall, we found a 24.5% positive rate, with 10.1% for Alphacoronavirus and 14.4% for Betacoronavirus. Albeit R. euryale, R. ferrumequinum, M. blythii and M. emarginatus were found infected with both CoV genera, we could not rule out CoV co-infection due to limitation of the sequencing method used and sample availability. Based on phylogenetic inferences and genetic distances at nucleotide and amino acid levels, we found one putative new subgenus and three new species of Alphacoronavirus, and two new species of Betacoronavirus.

The recent emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an ongoing global COVID-19 pandemic and public health crisis. Detailed study of human immune response to SARS-COVIS-2 infection is the important topic for a successful treatment of this disease. Our study was aimed to characterize immune response on the level of antibody profiling in convalescent plasma of patients in Georgia. Antibodies against the following SARS-COV-2 proteins were studied: nucleocapsid and various regions of Spike (S) protein: S1, S2 and Receptor binding domain (RBD). Convalescent plasma of patients 6-8 weeks after initial confirmation of SARS-COV-2 infection were tested. Nearly 80% out of 154 patients studied showed presence of antibodies against nucleocapsid protein. The antibody response to three fragments of S protein was significantly less and varied in the range of 20-30%. Significantly more females as compared to males were producing antibodies against S1 fragment, whereas the difference between genders by the antibodies against nucleocapsid protein and RBD was statistically significant only by one-tailed Fisher exact test. There were no differences between the males and females by antibodies against S2 fragment. Thus, immune response against some viral antigens are stronger in females and we suggest that it could be one of the factors of less female fatality after SARS-COVID-2 infection.

Zoonotic diseases are endemic in the country of Georgia. Using the non-linear canonical correlation (NCC) method, the aim of this study was to examine the relationship between thirteen epidemiological risk factors and seropositivity to five zoonotic infections (anthrax, Q fever, tularemia, leptospirosis, and Crimean-Congo hemorrhagic fever [CCHF]) among Georgian military recruits during 2014-2016. According to this multivariate statistical technique, which is suitable for the analysis of two or more sets of qualitative variables simultaneously, two canonical variables were identified. These variables accounted for 68% of the variation between the two sets of categorical variables ("risk factors" and "zoonotic infections"). For the first canonical variable, there was a relationship among CCHF (canonical loading, which is interpreted in the same way as the Pearson's correlation coefficient, [cl] = 0.715), tick bites (cl = 0.418) and slaughter of animals (cl = 0.351). As for the second canonical variable, Q fever (cl = -0.604) and leptospirosis (cl = -0.486) were related to rodents inside and outside home (cl = -0.346) and sweeping in or around home (cl = -0.317). The NCC method allows researchers to obtain additional insights into the complex relationship between epidemiological risk factors and multiple zoonotic infections.

This is the first cross-sectional study of the seroprevalence and risk factors for Coxiella burnetii in Jordan. A total of 781 individuals from 11 governorates of Jordan were tested by SERION ELISA classic C. burnetii IgG Phase 2. A validated and pretested questionnaire was used to collect risk factors and demographic data. The overall seroprevalence for C. burnetii was 24.2% (95% CI; 21.3–27.3%). Unadjusted odds ratios showed that governorate of residence, consumption of raw milk, and ownership of sheep, goats, and dogs were significantly (P ≤ 0.05) associated with C. burnetii seropositivity. The multivariate logistic regression showed that individuals who own small ruminants had three times greater odds of seropositivity than those who do not own a small ruminant, after controlling for age, gender, raw milk consumption, and ownership of dogs. In addition, individuals who live in Al-Karak, Az-Zarqa, and Al-Tafilah had significantly greater odds of seropositivity compared with individuals who live in the capital city, Amman (OR = 3.6, 4.8, and 2.7, respectively). This study suggests that preventive measures should be practiced in ruminant farms in Jordan to avoid C. burnetii infection. Coxiella burnetii should also be considered in the differential diagnosis of febrile-like illnesses in Jordan, especially among farmers and veterinarians.

BackgroundBetween February and June 2020, 917 COVID-19 cases and 14 COVID-19-related deaths were reported in Georgia. Early on, Georgia implemented non-pharmaceutical interventions (NPI) including extensive contact tracing and restrictions on movement.AimTo characterize the demographics of those tested and infected with COVID-19 in Georgia; to evaluate factors associated with transmission between cases and their contacts; and to determine how transmission varied due to NPI up to 24 June 2020.MethodsWe use data gathered by the Georgian National Center for Disease Control on all polymerase chain reaction tests conducted (among symptomatic patients, through routine testing and contact tracing); hospitalization data for confirmed cases, and contact tracing data. We calculated the number of contacts per index case, the secondary attack rate (% contacts infected), and effective R number (new cases per index case), and used logistic regression to estimate how age, gender, and contact type affected transmission.ResultsMost contacts and transmission events were between family members. Contacts 50 were more likely to die than younger patients. Contact tracing identified 917 index cases with mean 3.1 contacts tested per case, primarily family members. The overall secondary attack rate was 28% (95% confidence interval [CI]: 26-29%) and effective R number was 0.87 (95%CI 0.81-0.93), peaking at 1.1 (95%CI 0.98-1.2) during the period with strongest restrictions.ConclusionGeorgia effectively controlled the COVID-19 epidemic in its early stages, although evidence does not suggest transmission was reduced during the strict lockdown period.Research in ContextEvidence before this studyWe searched PubMed and MedRxiv for papers reporting research using contact tracing data to evaluate the characteristics of the COVID-19 epidemic in any country. A number of analyses were identified from Asia, including China, Taiwan, Maldives, Thailand, South Korea, and India, but none from other regions other than one previous analysis conducted in Europe, focusing on the first two months of the COVID-19 epidemic in Cyprus. Studies evaluated number of contacts and different contact types, secondary attack rate, and effective R number. However, none of these studies compared characteristics between different time periods or under varied levels of non-pharmaceutical interventions or restrictions on social mixing.Added value of this studyIn this study, we use contact tracing data from Georgia from all cases identified in the first four months of the epidemic, as well as testing and hospitalization data, to evaluate the number and type of contacts, effective R number (new cases per index case), and secondary attack rate (proportion of contacts infected) in this population, and whether these measures changed before, during, and after the lockdown period. We also evaluated how the chance of transmission varied by type of index case and contact. Our results indicate that number of contacts remained relatively low throughout the study period, so although the secondary attack rate was relatively high (28%) compared to that seen in studies in Asia (10-15%), the effective R number was less than one overall, peaking at 1.1 (0.98-1.2) during the strictest lockdown period, with easing of restrictions corresponding to a lower effective R of 0.87 (0.77-0.97). Most transmission occurred between family members with transmission very low between co-workers, friends, neighbours, and medical personnel, indicating that the restrictions on social mixing were effective at keeping the epidemic under control during this period.Implications of all the available evidenceOur study presents the first analysis of the successful control of a COVID-19 epidemic in a European country, indicating that despite a high secondary attack rate, reduction in contacts outside the home, and a well-timed lockdown, were able to keep transmission under control.

This is the first study on campylobacteriosis carried out in Georgia. It targeted 382 hospitalized children with acute inflammatory diarrhea. The study was conducted between July 2020 to July 2021 based on the main infection clinic of the capital city. Culture-based bacteriological methods were followed by phenotypic and Real-time PCR tests for bacterial confirmation and identification. The data revealed recent epidemiologic prevalences of the three main causative bacteria in the target population. Shigella sonnei with 19.1% (95% CI: 15.2–23.4%) was the most frequently detected pathogen followed by Campylobacter spp. with 12.3% (95% CI: 9.2–16.0%) and Salmonella spp. with 4.9% (95% CI: 3.0–7.6%). However, in 63.6% of the samples, the causative agent remained unknown. Species differentiation of Campylobacter spp. revealed 81% Campylobacter jejuni and 19% Campylobacter coli. An epidemiological pyramid with estimated magnification factors may give more insights into the burden of campylobacteriosis among the studied population, resulting in a putative annual incidence of 6 per 1000 children in Tbilisi. Children with campylobacteriosis were younger (median age 40 months (interquartile range (IQR) 22−95)) than with shigellosis (median age 92 months (interquartile range (IQR) 52−140)). However, no statistically significant difference was found with the age range of patients with campylobacteriosis and salmonellosis as well as with salmonellosis and shigellosis. In conclusion, Campylobacter spp. may be suspected to be the second most frequent bacterial causative agent of acute inflammatory diarrhea in hospitalized children and the primary cause in the 0–3 age group in Georgia. In addition, Campylobacter CROMagar showed better selectivity in comparison to mCCDA selective agar of stool samples in our study.

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.

Objectives The burden of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections is unknown in Georgia. This analysis describes the prevalence of hepatitis B and coinfection with HDV and the demographic characteristics and risk factors for persons with HBV infection in Georgia. Study design This is a cross-sectional seroprevalence study. Methods A cross-sectional, nationwide survey to assess hepatitis B prevalence among the general adult Georgian population (age ≥18 years) was conducted in 2015. Demographic and risk behavior data were collected. Blood specimens were screened for anti–hepatitis B core total antibody (anti-HBc). Anti-HBc–positive specimens were tested for hepatitis B surface antigen (HBsAg). HBsAg-positive specimens were tested for HBV and HDV nucleic acid. Nationally weighted prevalence estimates and adjusted odds ratios (aORs) for potential risk factors were determined for anti-HBc and HBsAg positivity. Results The national prevalence of anti-HBc and HBsAg positivity among adults were 25.9% and 2.9%, respectively. Persons aged ≥70 years had the highest anti-HBc positivity (32.7%), but the lowest HBsAg positivity prevalence (1.3%). Anti-HBc positivity was associated with injection drug use (aOR = 2.34; 95% confidence interval [CI] = 1.46–3.74), receipt of a blood transfusion (aOR = 1.68; 95% CI = 1.32–2.15), and sex with a commercial sex worker (aOR = 1.46; 95% CI = 1.06–2.01). HBsAg positivity was associated with receipt of a blood transfusion (aOR = 2.72; 95% CI = 1.54–4.80) and past incarceration (aOR = 2.72; 95% CI = 1.25–5.93). Among HBsAg-positive persons, 0.9% (95% CI = 0.0–2.0) were HDV coinfected. Conclusions Georgia has an intermediate to high burden of hepatitis B, and the prevalence of HDV coinfection among HBV-infected persons is low. Existing infrastructure for hepatitis C elimination could be leveraged to promote hepatitis B elimination.

Tularemia has sustained seroprevalence in Eurasia, with estimates as high as 15% in endemic regions. The purpose of this report is to characterise the current epidemiology of Francisella tularensis subspecies holarctica in Georgia. Three surveillance activities are summarised: (1) acute infections captured in Georgia's notifiable disease surveillance system, (2) infectious disease seroprevalence study of military volunteers, and (3) a study of seroprevalence and risk factors in endemic regions. Descriptive analyses of demographic, exposure and clinical factors were conducted for the surveillance studies; bivariate analyses were computed to identify risk factors of seropositivity using likelihood ratio χ2 tests or Fisher's exact tests. Of the 19 incident cases reported between 2014 and August 2017, 10 were confirmed and nine met the presumptive definition; the estimated annual incidence was 0.12/100 000. The first cases of tularemia in Western Georgia were reported. Seroprevalences of antibodies for F. tularensis were 2.0% for military volunteers and 5.0% for residents in endemic regions. Exposures correlated with seropositivity included work with hay and contact with multiple types of animals. Seroprevalence studies conducted periodically may enhance our understanding of tularemia in countries with dramatically underestimated incidence rates.

Aim Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes. Methods The study included 148 patients with HCV genotype 2 as determined by 5-untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non-structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV. Results Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P

Background The country of Georgia launched the world’s first Hepatitis C Virus (HCV) Elimination Program in 2015 and set a 90% prevalence reduction goal for 2020. We conducted a nationally representative HCV seroprevalence survey to establish baseline prevalence to measure progress toward elimination over time. Methods A cross-sectional seroprevalence survey was conducted in 2015 among adults aged ≥18 years using a stratified, multi-stage cluster design (n = 7000). Questionnaire variables included demographic, medical, and behavioral risk characteristics and HCV-related knowledge. Blood specimens were tested for antibodies to HCV (anti-HCV) and HCV RNA. Frequencies were computed for HCV prevalence, risk factors, and HCV-related knowledge. Associations between anti-HCV status and potential risk factors were calculated using logistic regression. Results National anti-HCV seroprevalence in Georgia was 7.7% (95% confidence interval (CI) = 6.7, 8.9); HCV RNA prevalence was 5.4% (95% CI = 4.6, 6.4). Testing anti-HCV+ was significantly associated with male sex, unemployment, urban residence, history of injection drug use (IDU), incarceration, blood transfusion, tattoos, frequent dental cleanings, medical injections, dialysis, and multiple lifetime sexual partners. History of IDU (adjusted odds ratio (AOR) = 21.4, 95% CI = 12.3, 37.4) and blood transfusion (AOR = 4.5, 95% CI = 2.8, 7.2) were independently, significantly associated with testing anti-HCV+ after controlling for sex, age, urban vs. rural residence, and history of incarceration. Among anti-HCV+ participants, 64.0% were unaware of their HCV status, and 46.7% did not report IDU or blood transfusion as a risk factor. Conclusions Georgia has a high HCV burden, and a majority of infected persons are unaware of their status. Ensuring a safe blood supply, implementing innovative screening strategies beyond a risk-based approach, and intensifying prevention efforts among persons who inject drugs are necessary steps to reach Georgia’s HCV elimination goal.

Human anthrax has increased dramatically in Georgia and was recently linked to the sale of meat in an urban market. We assessed epidemiological trends and risk factors for human anthrax at the urban–rural interface. We reviewed epidemiologic records (2000–2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). To estimate risk, we used a negative binomial regression. The average incidence per 1 million population in peri-urban areas (24.5 cases) was > 2-fold higher compared with rural areas and > 3-fold higher compared with urban area. Risk from handling or purchasing meat was nearly 2-fold higher in urban areas and > 4-fold higher in peri-urban areas compared with rural area. Our findings suggest a high risk of anthrax in urban and peri-urban areas likely as a result of spillover from contaminated meat and animal by-products. Consumers should be warned to purchase meat only from licensed merchants.

Military personnel are at an increased risk for exposure to arthropod- borne and zoonotic pathogens. The prevalence of these pathogens has not been adequately described in the country of Georgia. As the Georgian military moves toward an increased level of capability and the adoption of European Union and North Atlantic Treaty Organization standards, international field exercises will become more frequent and will likely involve an increasing number of international partners. This study was undertaken with the goal of defining the arthropod-borne and zoonotic pathogen threat in Georgia so force health protection planning can proceed in a rational and data-driven manner. To estimate disease burden, blood was taken from 1,000 Georgian military recruits between October 2014 and February 2016 and screened for previous exposure to a set of bacterial and viral pathogens using a antibody-based, serologic procedure. The highest rate of exposure was to Salmonella enterica serovar Typhi, and the lowest rate of exposure was to Coxiella burnettii (the causative agent of Q fever). These data provide insight into the prevalence of arthropod-borne infections in Georgia, fill a critical knowledge gap, will help guide future surveillance efforts, and will inform force health protection planning.

Yersinia pestis, the causative agent of plague, is a recently evolved clone of the enteropathogenic bacterium Yersinia pseudotuberculosis. Y. pestis has been extensively studied for decades; however, there are insufficient data about the intra-species diversity of this microorganism in certain parts of the world, including the Caucasus region. Using a high-density single-nucleotide polymorphism (SNP) microarray, we genotyped a total of 46 Y. pestis isolates from two plague foci in Georgia and neighboring Caucasus countries together with 12 Y. pseudotuberculosis isolates from Georgia. The genotyping microarray captured a total of 13,525 SNP positions across the Y. pestis and Y. pseudotuberculosis genomes and plasmids with high-throughput capability and superior reproducibility. From this analysis, we confirmed the presence of two independent and relatively distant phylogenetic groups of Y. pestis in the Caucasus region. The signature SNP patterns identified from this study will allow assay development for plague surveillance and pseudotuberculosis diagnostics.

This study compared three local cluster detection methods to identify local hotspots of human cutaneous anthrax (HCA) transmission in the country of Georgia where cases have been steadily increasing since the dissolution of the Soviet Union. Recent reports have indicated that the disease has reached historical levels in 2012 highlighting the need for better informed policy recommendations and targeted control measures. The purpose of this paper was to identify spatial clusters of HCA to aid in the implementation of targeted public health interventions. At the same time, we compared the utility of different statistical tests in identifying hotspots. We used the Getis-Ord ( G i ∗ ( d ) ) , a multidirectional optimal ecotope-based algorithm (AMOEBA) – a cluster morphology statistic, and the spatial scan statistic in SaTScan™. Data on HCA cases from 2000 to 2012 at the community level were aggregated to an 8 × 8 km grid surface and population data from the Global Rural and Urban Mapping Project (GRUMP) were used to calculate local incidence. In general, there was agreement between tests in the locations of HCA hotspots. Significant local clusters of high HCA incidence were identified in the southern, eastern and western regions of Georgia. The G i ∗ ( d ) and spatial scan statistics appeared more sensitive but less specific than the AMOEBA algorithm. The scan statistic identified larger geographic areas as hotspots of transmission. In general, the spatial scan statistic and G i ∗ ( d ) performed well for spatial clusters with lower incidence rates, whereas AMOEBA was well suited for defining local spatial clusters of higher HCA incidence. In resource constrained areas, efficient allocation of public health interventions is crucial. Our findings identified hotspots of HCA that can be used to target public health interventions such as livestock vaccination and training on proper outbreak management. This paper illustrates the benefits of evaluating statistical approaches for defining disease hotspots and highlights differences in these clustering approaches applicable beyond public health studies.

Foodborne botulism is a severe, paralytic illness caused by ingestion of preformed neurotoxins produced by Clostridium botulinum. In 2003, we conducted a population-based household survey of home canning practices to explore marked regional variations in botulism incidence in the Republic of Georgia (ROG). We designed a cluster sampling scheme and subdivided each of the 10 regions of the ROG into a variable number of strata. Households were selected from each stratum using a two-step cluster sampling methodology. We administered a questionnaire about home canning practices to household members responsible for food preparation. Using multivariate logistic regression analysis, we modeled high (eastern ROG) against low (western ROG) incidence areas. Overall, we surveyed 2,742 households nationwide. Home canning with a capping device hermetically sealing the lid covering the jar was practiced by 1,909 households (65.9%; 95% confidence interval [CI]: 59.8 to 72.1%). Canning was more prevalent in regions of low botulism incidence (34 versus 32%; P < 0.01). When compared with low-botulism areas, the following practices were associated with an increased risk in high-botulism areas: ≥6 months between canning vegetables and consuming them (adjusted odds ratio [aOR] = 2.1; 95% CI: 1.3 to 3.5) and adding any of the following ingredients to the jar at time of preparation: >1 tablespoon of salt per liter (aOR = 5.1; 95% CI: 1.2 to 22.6); vinegar (aOR = 2.2; 95% CI: 1.3 to 3.7), and greens (aOR = 5.6; 95% CI: 1.7 to 18.2). The following practices were associated with a decreased risk in high-botulism areas: >57 jars canned per household annually (aOR = 0.5; 95% CI: 0.3 to 0.9), covering or immersing vegetables in boiling water before placing them into the jar (aOR = 0.3 95% CI: 0.2 to 0.6), covering or immersing vegetables in boiling water after placing them into the jar (aOR = 0.4; 95% CI: 0.2 to 0.9), or adding garlic (aOR = 0.2; 95% CI: 0.1 to 0.5) or aspirin (aOR = 0.1; 95% CI: 0.1 to 0.2) to the jar at the time of preparation.

Rickettsial pathogens cause diseases that vary in severity and clinical presentation. Rickettsia species transmitted by ticks are mostly classified within the spotted fever group of rickettsiae (SFGR) and are often associated with febrile diseases. Preliminary studies have detected three human-pathogenic SFGR from ticks in Georgia: Rickettsia aeschlimannii, Rickettsia raoultii, and Rickettsia slovaca. To more broadly assess the presence of tick-borne rickettsiae from Georgia we examined 1594 ticks, representing 18 species from five genera (Ixodes, Hyalomma, Haemaphysalis, Dermacentor, and Rhipicephalus), collected from eight regions of Georgia. A total of 498 tick DNA samples extracted from single ticks or pooled ticks were assessed by molecular methods. Genus-specific Rick17b and species-specific qPCR assays were used to identify six rickettsiae: R. aeschlimannii, R. raoultii, R. slovaca, Rickettsia conorii subsp. conorii, Rickettsia massiliae, and Rickettsia monacensis. Tick samples that were positive for Rickettsia, but not identified by the species-specific assays, were further evaluated by multi-locus sequence typing (MLST) using sequences of four protein-coding genes (gltA, ompA,ompB, sca4). Three additional Rickettsia species were identified by MLST: Candidatus Rickettsia barbariae, Rickettsia helvetica, and Rickettsia hoogstraalii. Overall, nine species of Rickettsia (six human pathogens and three species with unknown pathogenicity) were detected from 12 tick species of five different genera. A distribution map for the tick-borne rickettsiae revealed six newly identified endemic regions in Georgia.

Anthrax is a widely spread zoonotic disease found on nearly every continent. To control the disease in humans and animals, annual livestock vaccination is recommended. However, in 2007, the country of Georgia ended its policy of compulsory annual livestock anthrax vaccination. Our objective was to assess how the epidemiology of human anthrax has evolved from 2000-2013 in Georgia, in the wake of this cessation. We used passive surveillance data on epidemiological surveys of human anthrax case patients. Risk factors and rates of self-reported sources of infection were compared, before and after the change in livestock vaccination policy. We mapped ethnicity-adjusted incidence during the two periods and assessed changes in the spatial pattern of risk. The overall risk of human anthrax increased >5-fold, from 0.7 cases per 100,000 in 2000 to 3.7 cases per 100,000 by 2013. Ethnic disparities in risk became pronounced; from 2000 to 2013, incidence increased >60-fold in Azerbaijanis from 0.35 to 21.1 cases/100,000 Azerbaijanis compared to 0.61 to 1.9 cases/100,000 among ethnic Georgians. Food-borne exposures from purchasing meat increased from 11% in 2000-2006 to 21% in 2007-2013. Spatial analyses revealed a shift from a random pattern of reporting pre-policy change to clustering among district municipalities following the change in policy. Our findings indicate there were unintended human health consequences associated with changing livestock vaccination policy. Following a reduction in the immunizations administered, there was a major shift in the epidemiology of human anthrax in Georgia. Current infection risk is now highest among ethnic minorities. Increased reporting among individuals uncharacteristically at risk for anthrax from foodborne exposures suggests spillover from modes of agricultural production. Given the importance of human-livestock health linkages, careful evaluations of policy need to be undertaken before changes to animal vaccination are made.

Bacillus anthracis causes the acute fatal disease anthrax, is a proven biological weapon, and is endemic in Georgia, where human and animal cases are reported annually. Here, we present whole-genome sequences of 10 historical B. anthracis strains from Georgia.

Brucellosis, which is among the most widespread global zoonotic diseases, is endemic in the nation of Georgia and causes substantial human morbidity and economic loss. Here, we report whole-genome sequences of three Brucella melitensis and seven Brucella abortus isolates from cattle, sheep, and humans that represent genetic groups discovered in Georgia.

Brucellosis, which is among the most widespread global zoonotic diseases, is endemic in the nation of Georgia and causes substantial human morbidity and economic loss. Here, we report whole-genome sequences of three Brucella melitensis and seven Brucella abortus isolates from cattle, sheep, and humans that represent genetic groups discovered in Georgia.

Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes.The study included 148 patients with HCV genotype 2 as determined by 5-untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non-structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV.Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients.High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.

Multiple factors help shape the infant intestinal microbiota early in life. Environmental conditions such as the presence of bioactive molecules from breast milk dictate gut microbial growth and survival. Infants also receive distinct, personalized, bacterial exposures leading to differential colonization. Microbial exposures and gut environmental conditions differ between infants in different locations, as does the typical microbial community structure in an infant’s gut. Here we evaluate potential influences on the infant gut microbiota through a longitudinal study on cohorts of breast-fed infants from the neighboring countries of Armenia and Georgia, an area of the world for which the infant microbiome has not been previously investigated. Marker gene sequencing of 16S ribosomal genes revealed that the gut microbial communities of infants from these countries were dominated by bifidobacteria, were different from each other, and were marginally influenced by their mother’s secretor status. Species-level differences in the bifidobacterial communities of each country and birth method were also observed. These community differences suggest that environmental variation between individuals in different locations may influence the gut microbiota of infants.

The authors report isolation and identification of two strains of bacteria belonging to the genus Janibacter from a human patient with aortic stenosis from a rural area of the country of Georgia. The microorganisms were isolated from aortic heart valve. Two isolates with slightly distinct colony morphologies were harvested after sub-culturing from an original agar plate. Preliminary identification of the isolates is based on amplification and sequencing of a fragment of 16SrRNA. Whole genome sequencing was performed using the Illumina MiSeq instrument. Both isolates were identified as undistinguished strains of the genus Janibacter. Characterization of whole genome sequences of each culture has revealed a 15% difference in gene profile between the cultures and confirmed that both strains belong to the genus Janibacter with the closest match to J. terrae. Genomic comparison of cultures of Janibacter obtained from human cases and from environmental sources presents a promising direction for evaluating a role of these bacteria as human pathogens.

We describe here a strain of Yersinia pestis, G1670A, which exhibits a baseline mutation rate elevated 250-fold over wild-type Y. pestis. The responsible mutation, a C to T substitution in the mutS gene, results in the transition of a highly conserved leucine at position 689 to arginine (mutS(L689R)). When the MutSL 689R protein of G1670A was expressed in a ΔmutS derivative of Y. pestis strain EV76, mutation rates observed were equivalent to those observed in G1670A, consistent with a causal association between the mutS mutation and the mutator phenotype. The observation of a mutator allele in Yersinia pestis has potential implications for the study of evolution of this and other especially dangerous pathogens.

The country of Georgia has a high prevalence of hepatitis C virus (HCV) infection, associated with exposures to HCV in health care settings with inadequate infection control and unsafe injections among persons who inject drugs (1). In April 2015, in collaboration with CDC and other partners, Georgia embarked on a program to eliminate HCV infection, subsequently defined as achieving a 90% reduction in prevalence by 2020. The initial phase of the program focused on providing HCV treatment to infected persons with advanced liver disease and at highest risk for HCV-associated morbidity and mortality. By April 27, 2016, a total of 27,392 HCV-infected persons registered for the program, 8,448 (30.8%) started treatment, and 5,850 patients (69.2%) completed HCV treatment. Among patients completing treatment who were eligible for posttreatment testing, 2,398 received polymerase chain reaction (PCR) testing for HCV at least 12 weeks after completion of treatment; 1,980 (82.6%) had no detectable virus, indicative of a sustained virologic response* (i.e., cure). Major challenges to achieving elimination remain, including the need to increase access to care and treatment services and implement a comprehensive approach to prevention and control of HCV infection. As a global leader in this effort, the Georgia HCV Elimination Program can help pave the way for other countries experiencing high rates of HCV infection to undertake similar initiatives.

Anthrax is an endemic infection in Georgia. More than 2,000 affected foci exist in the country with approximately 10% being active. Since 2003, an active surveillance program across pipeline construction sites has been ongoing. This study reports the results of soil samples tested from 2003-2014, which revealed a number of Bacillus anthracis isolates thereby indicating their presence at several sites. The construction sites have since been decontaminated. These results highlights the utility and importance of active surveillance campaigns on such especially dangerous pathogens.

Bartonella infections are widespread and highly prevalent in rodents. Several rodent-associated Bartonella species have been related to human diseases. Recently, Bartonella species was reported as the etiology of a human case in the country of Georgia (Caucasus). However, information on Bartonella in rodents in Georgia is absent. Rodent hearts were collected from Georgia to investigate the presence and diversity of Bartonella species. Bartonella bacteria were cultured from 37.2% (16/43) of rodents examined, while Bartonella DNA was detected in 41.2% (28/68) of rodents by polymerase chain reaction targeting citrate synthase (gltA) gene. Sequences of gltA showed that rodents in this region harbored multiple Bartonella strains, including Bartonella elizabethae, Bartonella tribocorum, Bartonella grahamii, and an unknown genogroup. The first three Bartonella species, known to be rat-associated and human cases linked, were commonly observed in wood mice (Apodemus [Sylvaemus] uralensis) (5/8 positive with B. elizabethae and B. tribocorum) and social voles (Microtus socialis) (4/6 positive with B. grahamii and B. elizabethae) in this study. The frequent distribution of these Bartonella species suggests that they may contribute to unidentified clinical infections. The unknown genogroup was observed in 24 Bartonella isolates and/or DNA extracts from heart tissues, all of which were obtained from Libyan jirds (Meriones libycus). Further characterization of the bacterial cultures based on sequence analysis of four additional genes (ftsZ, nuoG, rpoB, and ssrA) supported that the jird-associated Bartonella strains comprise a distinct monophyletic clade. The impact of this bacterium on wildlife and human health needs to be determined.

Summary: Brucellosis is an ancient disease that still remains a significant threat to humans and is typically linked to exposure to infected animals and/or consumption of unpasteurized animal products. Despite this history, we have a relatively limited understanding of the host characteristics of this disease; consequently, further research is necessary. In this study, we examined the humoral immune response in 43 Georgian individuals that had been diagnosed with brucellosis 3–12 months before enrollment in the study, many of whom still had symptoms after the completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34 of 38 (89%) patients had demonstrable specific antibodies to Brucellergene™ antigens; the results from the two ELISAs were highly correlated (p = 0.031, r = 0.851). We also studied the cellular immune responses in 15 patients. All of the patients generated interferon (IFN)-γ in response to ex vivo stimulation with Brucella protein antigens, and the majority of the patients maintained measurable humoral responses to both LPS and protein antigens. From this initial study, we conclude that measurement of antibody and of cellular (IFN-γ) responses to brucellergene OCB protein epitopes may be worthy of further investigation as an alternative or adjunct to current diagnostics. Keywords: Brucella, Immune response, ELISPOT, ELISA, Brucellin, LPS

Summary Objectives Helicobacter pylori causes gastritis, duodenal ulcers, and gastric cancer. Although household crowding, low socioeconomic status (SES), and poor sanitation are associated with infection elsewhere, risk factors of infection in the Republic of Georgia (ROG), a country with a high prevalence rate (>70%), remain unknown. In this study we explored potential risk factors of infection among symptomatic patients in ROG. Methods During 2007–2008, we prospectively recruited 390 subjects with gastrointestinal symptoms referred to five tertiary care centers for diagnostic upper endoscopy. We administered a questionnaire on potential risk factors and tested patients using three diagnostic tests: gastric biopsies underwent histological evaluation and rapid urease test (CLO test), and an ELISA was used to detect IgG against H. pylori in serum. We defined a case as having two or more positive results from the three available tests. Univariate and multivariate logistic regression analyses were performed. Results Overall, 217 (56%) patients met the study case definition. Subjects diagnosed with cancer had the highest rate of H. pylori infection (62%), followed by those with gastritis (55%), and ulcer (54%). Age >30 years (adjusted odds ratio (aOR 2.6, 95% confidence interval (CI) 1.6–4.3) and residing in the capital city (aOR 0.6, 95% CI 0.4–0.9) were significantly associated with infection. Conclusions In this large cohort with gastrointestinal symptoms, only age >30 years and living in the capital were significant factors associated with infection. Lower SES, less education, and crowding did not confer an increased risk, in contrast to the findings of previous studies. Population-based studies are needed to identify potential routes and risk factors of H. pylori infection in ROG.

Context Brucellosis is endemic in the country of Georgia, with the highest incidence of disease in the east of Georgia, in the Kakheti region – which is also home to the majority of sheep and a large portion of the national cattle herd (two species that are natural hosts of zoonotic Brucella spp.). Objective Our purpose was to understand the ruminant livestock management and dairy production as well as the sociological factors in order to relate it to the disease ecology of brucellosis and to understand the framework that contributes too brucellosis transmission in the region. Methods In 2010, we examined the aspects of livestock management and production through the use of a semi-structured questionnaire that was administered to 198 villagers and 41 key informants (physicians, veterinarians, dairy production specialists, and laboratory personnel) who were identified by convenience sampling. Results were primarily qualitative, but some were quantified to reveal trends and compared with non-parametric tests. Results We found that animals are managed at the village level. Male villagers take turns shepherding and herding on both summer pastures (highlands) and winter pastures (lowlands or around the village). Men also do all the sheep-dairy production. Women care for milk cattle as well as make the dairy products from cow milk. Of the households that own livestock, 28% own sheep (50 per flock) and 96% own cattle (3 per herd). The northern-most part of Kakheti (Akhmeta) has the widest distribution of its cheese; the guda cheese from this area is sold all over Kakheti and central Georgia. Typically, cheese is aged in 20% brine for 3 d (white cheeses) or 21 d (guda cheeses). In addition, raw milk is used for cheese production and heating the milk is believed to decrease the quality of the final product. Conclusions Interventions at the animal level will be best carried out in the fall when animals return to winter pastures. Under-employed private veterinarians would be available for extension work and contact with local villagers. Control will be best achieved at the animal level because the local people have a social and cultural resistance to the use of heated or pasteurized milk for cheese production.

Minimal information is available on the incidence of Crimean–Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia.

Introduction Anthrax is endemic in the country of Georgia. The most common cutaneous anthrax form accounts for 95% of anthrax cases and often is self-resolving. Humans are infected from processing contaminated animal products, contacting sick animals, or by insect bites. Objective We aimed to describe the burden of human cutaneous anthrax and associated risk factors using the national surveillance data. Methods We extracted all human cutaneous anthrax cases from Electronic Integrated Disease Surveillance System (EIDSS) from 1 January 2008 to 31 December 2015. We conducted descriptive analyses to characterize the number of confirmed, probable and suspected cases by age groups, gender, ethnicity, year and geographic area. Results Out of 911 reported cutaneous anthrax cases, 299 (33%) were rejected. Out of remaining 612 cases, 437 (71%), 172 (28%), and 3 (

Complete sequences of 9.5-kb pPCP1 plasmids in threeYersinia pestisstrains from the former Soviet Union (FSU) were determined and compared with those of pPCP1 plasmids in three well-characterized, non-FSUY. pestisstrains (KIM, CO92, and 91001). Two of the FSU plasmids were from strains C2614 and C2944, isolated from plague foci in Russia, and one plasmid was from strain C790 from Kyrgyzstan. Sequence analyses identified four sequence types among the six plasmids. The pPCP1 plasmids in the FSU strains were most genetically related to the pPCP1 plasmid in the KIM strain and least related to the pPCP1 plasmid inY. pestis91001. The FSU strains generally had larger pPCP1 plasmid copy numbers compared to strain CO92. Expression of the plasmid'splagene was significantly (P≤.05) higher in strain C2944 than in strain CO92. Givenpla's role inY. pestisvirulence, this difference may have important implications for the strain's virulence.

In November 2006, an outbreak of waterborne tularemia occurred in an eastern region in the Republic of Georgia. Outbreak investigation revealed 26 cases: 21 oropharyngeal and 5 glandular tularemia cases. The presentation of the index case triggered an outbreak investigation involving the collection of clinical/ epidemiological data, application of tularine skin test, and laboratory confirmation of the possible cases using the tube agglutination test and polymerase chain reaction (PCR) testing. Serology results were verified by enzyme-linked immunosorbent assay (ELISA) and Western blot. A case– control study along with follow-up was conducted 4 months after the index case presentation. Exudative pharyngitis, predominantly laterocervical adenitis, fever, and headache were the most prevalent clinical signs/symptoms observed. Depressed mood, concentration difficulties, and sleep disturbance were also detected. Bubo aspirates tested by PCR were positive in 4/4 cases and pharyngeal swabs also tested by PCR were positive in 2/3 cases. Francisella tularensis was isolated from the water samples. Comparison of the cases and controls did not reveal any statistically significant risk factors. A follow-up investigation revealed cases with protracted symptoms of fatigue, headache, and sleep disturbance. Additionally, 8/26 cases still had cervical adenopathy of prominent size. A delay in diagnosis was associated with persistent lymphadenopathy on follow-up examination (p = 0.05). We observed unique features of persistent neuropsychiatric symptoms and lymphadenopathy 5 months after tularemia infection which were associated with delayed diagnosis and the lack of prompt response to therapy. This outbreak of oropharyngeal tularemia emphasizes the importance of a rapid diagnostic and investigative response to tularemia. This type of response can prevent ongoing exposure, as well as provide expeditious treatment to mitigate persistent symptoms.

Forty Yersinia pestis isolates from endemic foci of plague in the Republic of Georgia, and six Y. pestis isolates from neighbouring former Soviet Union countries, were analysed for their biochemical and phenotypic properties, and their genetic relatedness was compared with Y. pestis strains KIM and CO92 by pulsed-field gel electrophoresis (PFGE). In addition, 11 Y. pestis isolates from the USA, together with published nucleotide sequences from Y. pestis strains KIM, CO92 and 91001, were compared with the 46 isolates in the present collection using multilocus sequence typing (MLST), based on sequence data for the 16S rRNA, hsp60, glnA, gyrB, recA, manB, thrA and tmk loci. Four virulence gene loci (caf1, lcrV, psaA and pla) were also sequenced and analysed. Two sequence types (ST1 and ST2), which differed by a single nucleotide, were identified by MLST. With the exception of a single isolate (771G), all of the Georgian Y. pestis isolates belonged to ST2. PFGE also grouped the Georgian Y. pestis isolates separately from the non-Georgian isolates. Overall, PFGE discriminated the Y. pestis isolates more effectively than MLST. The sequences of three of the four virulence genes (lcrV, psaA and pla) were identical in all Georgian and non-Georgian isolates, but the caf1 locus was represented by two allele types, with caf1 NT1 being associated with the non-Georgian isolates and caf1 NT2 being associated with the Georgian isolates. These results suggest that Georgian Y. pestis isolates are of clonal origin.

Background. The acute paralytic syndrome of botulism has been well-described; however, little is known about its long-term consequences.Methods. We conducted a case-control study in the Republic of Georgia to evaluate the health of patients ⩾6 months after they had experienced an episode of botulism. Case patients were selected on the basis of who had had a clinical diagnosis of foodborne botulism reported to the national surveillance system from 1998 through 2003. Three control subjects were randomly selected from each patient's community.Results. We located 217 patients who had had botulism from surveillance records, with a median time since onset of illness of 4.3 years. The median age was 37 years, and 49% of the patients were female, similar to the control subjects. Most of the patients (68%) had acquired botulism from home-conserved vegetables (probably containing toxin type B), 15% had been hospitalized for