A cross-sectional assessment of injection of "salts" and HIV transmission-related behaviours among a cohort of people who inject drugs in Kyrgyzstan.

INTRODUCTION: Despite the increasing availability of new psychoactive substances (hereafter referred to as "salts") in Eastern Europe and Central Asia, there is a dearth of epidemiological data on the relationship between injecting "salts" and HIV risk behaviours. This is particularly relevant in settings where injection drug use accounts for a substantial proportion of the HIV burden, such as in Kyrgyzstan, a former Soviet Republic. This study assessed whether injecting "salts" is associated with sexual and injection-related HIV risk behaviours among people who inject drugs in Kyrgyzstan. METHODS: The Kyrgyzstan InterSectional Stigma Study is a cohort of people who inject drugs in Kyrgyzstan's capital of Bishkek and the surrounding rural administrative division of Chuy Oblast. We conducted a cross-sectional analysis using survey data collected from cohort participants between July and November 2021, which included information on injection drug use (including "salts") and HIV risk behaviours. To minimize confounding by measured covariates, we used inverse-probability-weighted logistic and Poisson regression models to estimate associations between recent "salt" injection and HIV risk behaviours. RESULTS: Of 181 participants included in the analysis (80.7% men, 19.3% women), the mean age was 40.1 years (standard deviation [SD] = 8.8), and 22% (n = 39) reported that they had injected "salts" in the past 6 months. Among people who injected "salts," 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6). Injecting "salts" was significantly associated with a greater number of injections per day (adjusted relative risk [aRR] = 1.59, 95% confidence interval [CI] = 1.30-1.95) but lower odds of using syringe service programmes in the past 6 months (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.12-0.32). Injecting "salts" was also significantly associated with lower odds of condomless sex in the past 6 months (aOR = 0.42, 95% CI = 0.24-0.76) and greater odds of having ever heard of pre-exposure prophylaxis (aOR = 4.80, 95% CI = 2.61-8.83). CONCLUSIONS: (PWID) people who inject drugs who inject "salts" are a potentially emergent group with increased HIV acquisition risk in Kyrgyzstan. Targeted outreach bundled with comprehensive harm reduction and pre-exposure prophylaxis services are needed to prevent transmission of HIV and other blood-borne viruses.

[The lost years of potential life under cancer of neck of uterus in the Kyrgyz Republic].

One of modern methods of estimating health losses under malignant neoplasms in economic terms, characterizing number of deaths and age of death are lost years of potential life. The cumulative losses from premature cancer mortality made up to 29 217.5 man-years in 2013 and 39 710 man-years in 2021. The number of years lost over 9 years increased by 10 492.5 man-years despite decreasing of mortality across all ages. The rate of lost years of potential life during this period increased from 5.3 to 6.2 years. The maximal contribution to lost years of potential life was made by population groups 45-59 years old. Total losses from premature mortality from cervical cancer were 2682.5 man-years and 2411 man-years in 2013 in 2021. The number of years lost decreased by 271.5 man-years. The rate of lost years of potential life during this period increased from 0.5 to 3.7 years. The greatest contribution to lost years of potential life was made by population groups 60-64 and 40-49 years old. The calculation demonstrated that there are significant reserves for reducing population mortality from malignant neoplasms in most vulnerable age population groups that is important for organization of oncological care and planning of target prevention programs.

Work at high altitude and non-fatal cardiovascular disease associated with unfitness to work: Prospective cohort observation.

INTRODUCTION: Mining at high altitude exposes workers to hypoxic environment and cold climate in addition to conventional hazards in mining, but very little is known on how to define fitness to work in prospective candidates with pre-existing conditions. The aim of the current study was to define the incidence of cardiovascular diseases leading to unfitness to work as well as their predictors in a prospective observation. METHODS: A total of 569 prospective employees (median age 34 (interquartile range (IQR) 28;40) years, 95% men 85% mid-altitude residents) for a high-altitude gold mine in Kyrgyzstan operating at 3800-4500 meters above sea level were screened at pre-employment in 2009-2012 and followed by January 2022. Cox regression was used to quantify the association of baseline demographics and physiological variables with newly diagnosed cardiovascular diseases (CVD) leading to unfitness to work, expressed as hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: With 5190 person-years of observation, 155 (27%) workers have left work, of whom 23 had a newly identified CVD leading to unfitness to work (cumulative incidence 4%) with no difference between drivers and other occupations, despite greater blood pressure and body mass index (BMI) in the former at baseline. Age (HR 1.13 (95% CI 1.06;1.22) and BMI (HR 1.18 (95% CI 1.04;1.34)) were associated with a greater chance of having CVD, adjusted for lung function, baseline diagnoses, year of employment and baseline blood pressure. Narrowing the analysis to only men, drivers, smokers and even middle-altitude residents did not change the effect. CONCLUSION: These findings confirmed high efficacy of pre-employment screening limiting access of workers with advanced conditions to work which later yielded low CVD incidence. In addition to conventional contraindications to work at high altitude, age and high BMI should be considered when a decision is made.

Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017-2022.

In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).

Associations between different forms of intimate partner violence and posttraumatic stress among women who use drugs and alcohol in Kyrgyzstan.

Survivors of intimate partner violence (IPV) have an increased risk of experiencing posttraumatic stress, and the subsequently associated symptoms can vary by form of IPV exposure (i.e., physical, sexual, or psychological IPV). Related research among socially marginalized populations, however, is limited, including among women who use and misuse substances. Drawing on baseline data from a pilot study conducted among 213 women in Kyrgyzstan who reported using drugs or engaging in hazardous alcohol use, we examined the associations between different forms of IPV and severe posttraumatic stress symptoms (PTSS). The vast majority of participants reported lifetime (93.9%, n = 200) and past 3-month (65.3%, n = 139) IPV, and two thirds of participants (65.3%, n = 139) reported experiencing PTSS in the prior month. Multivariable logistic regression analyses indicated statistically significant associations between only some forms of IPV and PTSS, including physical IPV, adjusted odds ratio (aOR) = 3.24, 95% confidence interval (CI) [1.15, 9.14], and injurious IPV, aOR = 2.71, 95% CI [1.10, 6.65]. Additionally, experiencing any form of IPV was associated with 4.95 higher odds of reporting PTSS, 95% CI [1.16, 21.15]; no other results were significant. These results not only underscore the need for future research on the mechanisms that might explain the unique associations between different forms of IPV and posttraumatic stress, but also highlight an urgent need for trauma-informed mental health and psychosocial support interventions for women who use drugs and alcohol.

Molecular Detection and Phylogenetic Analysis of Tick-Borne Encephalitis Virus from Ticks Collected from Cattle in Kyrgyzstan, 2023.

Ticks are important vectors of the tick-borne encephalitis virus (TBEV). In Kyrgyzstan, the livestock farming trade and nomadic lifestyle enable tick-borne diseases to be imported from neighboring countries, but there are few relevant studies. In this study, we collected 40 ticks from cattle in Kyrgyzstan. Molecular marker analysis identified the ticks as Ixodes persulcatus (97.5%; n = 39) and Haemaphysalis punctata (2.5%; n = 1). Real-time PCR screening revealed two ticks to be positive for TBEV, but only one tick was amplified using nested PCR targeting the TBEV envelope (E) and non-structure 5 (NS5) gene. The obtained sequences belonged to the TBEV Siberian subtype and phylogenetic tree analysis results confirmed that the virus was related to the Bosnia strain. We also performed next-generation sequencing, which confirmed the TBEV Siberian subtype. Continuous research and surveillance of TBEV in Kyrgyzstan are required to provide further information on tick-borne diseases.

Financial Vulnerability and Its Association with HIV Transmission Risk Behaviors Among People Who Inject Drugs in Kyrgyzstan.

The Family Resource Scale (FRS) is a three-factor financial vulnerability (FV) measure. FV may impact HIV transmission risks. Cross-sectional data from 279 people who inject drugs (PWID) in Kyrgyzstan surveyed April-October 2021 was used to validate the FRS and estimate associations between FV on past 6-month injection and sexual HIV risk outcomes. The three-factor FRS reflected housing, essential needs, and fiscal independence, and had good internal reliability and structural validity. Greater cumulative, housing, and essential needs FRS scores were associated with increased relative risk on public injection (adjusted risk ratio [aRR], 95% confidence interval [95% CI]: 1.03 [1.01, 1.04]; aRR [95% CI]: 1.06 [1.02, 1.09]; aRR [95% CI]: 1.06 [1.03, 1.08], respectively, all p < 0.001) and preparing injections with unsafe water sources (aRR [95% CI]: 1.04 [1.02, 1.07]; aRR [95% CI]: 1.09 [1.04, 1.15]; aRR [95% CI]: 1.08 [1.03, 1.14], respectively, all p < 0.001). Results suggest that PWID housing- and essential needs-related FV may exacerbate injection HIV transmission risks. Reducing PWIDs' FV may enhance the HIV response in Kyrgyzstan.

RESUMEN: La Escala de Recursos Familiares (FRS, por sus siglas en inglés) es una medida de vulnerabilidad financiera (FV, por sus siglas en inglés) de tres factores. La FV puede afectar los riesgos de transmisión del VIH. Se utilizaron datos transversales de 279 personas que se inyectan drogas (PWID, por sus siglas en inglés) en Kirguistán encuestadas de abril a octubre de 2021 para validar la FRS y estimar las asociaciones entre la FV en la inyección y los resultados de riesgo sexual del VIH en los últimos seis meses. La FRS de tres factores reflejaba la vivienda, las necesidades esenciales y la independencia fiscal, y presentaba una buena confiabilidad interna y validez estructural. Mayores puntajes acumulativos de la FRS en vivienda y necesidades esenciales se asociaron con un mayor riesgo relativo en la inyección pública (Riesgo relativo ajustada [aRR], Intervalo de Confianza del 95% [IC95%]: 1.03 [1.01, 1.04]; aRR [IC95%]: 1.06 [1.02, 1.09]; aRR [IC95%]: 1.06 [1.03, 1.08], respectivamente, todos p < 0.001) y la preparación de inyección con fuentes de agua no seguras (aRR [IC95%]: 1.04 [1.02, 1.07]; aRR [IC95%]: 1.09 [1.04, 1.15]; aRR [IC95%]: 1.08 [1.03, 1.14], respectivamente, todos p < 0.001). Los resultados sugieren que la FV relacionada con la vivienda y las necesidades esenciales de las PWID puede exacerbar los riesgos de transmisión del VIH por la inyección. Reducir la FV de las PWID puede mejorar la respuesta al VIH en Kirguistán.

Environmental distribution of Echinococcus- and Taenia spp.-contaminated dog feces in Kyrgyzstan.

Recently, there have been epidemics of human cystic echinococcosis (CE) and alveolar echinococcosis (AE) in Kyrgyzstan. This study investigated 2 districts for the presence of Echinococcus granulosus s.l. and Echinococcus multilocularis eggs; species identity was confirmed by polymerase chain reaction in dog feces and the level of environmental contamination with parasite eggs in 2017­2018 was also investigated. In the Alay district 5 villages with a high reported annual incidence of AE of 162 cases per 100 000 and 5 villages in the Kochkor district which had a much lower incidence of 21 cases per 100 000 were investigated. However, the proportion of dog feces containing E. granulosus s.l. eggs was ~4.2 and ~3.5% in Alay and Kochkor respectively. For E. multilocularis, the corresponding proportions were 2.8 and 3.2%. Environmental contamination of Echinococcus spp. eggs was estimated using the McMaster technique for fecal egg counts, weight and density of canine feces. The level of environmental contamination with E. multilocularis eggs was similar at 4.4 and 5.0 eggs per m2 in Alay and Kochkor respectively. The corresponding values for E. granulosus s.l. were 8.3 and 7.5 eggs per m2. There was no association between village or district level incidence of human AE or CE and the proportion of dog feces containing eggs of Echinococcus spp. or the level of environmental contamination. Increased contamination of taeniid eggs occured in the autumn, after the return of farmers with dogs from summer mountain pastures.

An epidemiological survey of vector-borne pathogens infecting cattle in Kyrgyzstan.

Cattle production is a major contributor to the national economy of Kyrgyzstan. Most cattle in Kyrgyzstan are managed via extensive systems and graze in communal pastures. As a result, infestations with ectoparasites are widespread, implying that various vector-borne diseases might be common in cattle. However, methods to control such infectious diseases are not available in Kyrgyzstan because the epidemiology of vector-borne pathogens (VBPs) infecting cattle remains unclear. The present study was therefore designed to survey Kyrgyz cattle for VBPs. We prepared blood DNA samples from 319 cattle in Kyrgyzstan and screened them with specific PCR assays for detecting Babesia bovis, Babesia bigemina, Babesia naoakii, Theileria annulata, Theileria orientalis, Trypanosoma evansi, Trypanosoma theileri, and Anaplasma marginale infections. Our findings indicated that the surveyed cattle were infected with six of the eight pathogens targeted, with the exceptions being B. naoakii and Try. evansi. The most common pathogen was T. orientalis (84.3%), followed by B. bigemina (47.6%), T. annulata (16.6%), A. marginale (11.6%), Try. theileri (7.2%), and B. bovis (2.5%). Additional screening of the B. bovis- and B. bigemina-negative samples with a Babesia genus-specific 18S rRNA PCR identified two positive samples, and sequencing analysis confirmed that each of them was infected with either Babesia major or Babesia occultans. To the best of our knowledge, this is the first report of B. bovis, B. bigemina, B. occultans, Try. theileri, and A. marginale infections in cattle in Kyrgyzstan. Our findings suggest that cattle in Kyrgyzstan are at high risk of infectious diseases caused by VBPs.

[Analysis of resistance-associated substitutions in hepatitis C virus sequences from Kyrgyzstan].

INTRODUCTION: The countries of Central Asia, including Kyrgyzstan, are characterized by high prevalence and morbidity of HCV infection. Identification of HCV genotype and mutations associated with resistance to direct-acting antiviral (DAA) plays an important role either in conducting molecular epidemiological studies or choosing the treatment tactics. The aim of the work was to research of the genotype diversity of HCV variants circulating in Kyrgyzstan and the identification among them the mutations associated with the development of resistance to DAA. MATERIALS AND METHODS: 38 serum samples from HCV-infected residents of Kyrgyzstan were analyzed in this study. The nucleotide sequences of viral gene fragments (NS3, NS5A, NS5B) were determined by Sangers sequencing and deposited in the international GenBank database under the numbers ON841497ON841534 (NS5B), ON841535ON841566 (NS5A), and ON841567ON841584 (NS3). RESULTS: The HCV subtypes 1b (52.6%; 95% CI 37.367.5%), 3a (44.8%; 95% CI 30.260.2%) and 1a (2.6%; 95% CI 0.513.4%) are circulating in Kyrgyzstan. 37% (95% CI 1959%) of subtype 1b isolates had C316N mutation in the NS5A gene; 46% (95% CI 2370%) had F37L mutation in the NS5A gene; 45% (95% CI 2272%) had Y56F mutation in the NS3 gene. Among subtype 3a isolates, resistance-associated mutations in NS5B fragment were not found. 22% (95% CI 945%) of subtype 3a sequences had a Y93H mutation in the NS5A gene. A combination of Y56F + Q168 + I170 mutations was identified among all sequences of NS3 gene. DAA resistance mutations were not found in NS3, NS5A, NS5B genes of subtype 1a sequence. CONCLUSION: A rather high prevalence of mutations associated with resistance or significant decrease in sensitivity to DAA among HCV sequences from Kyrgyzstan was shown. Updating of data on HCV genetic diversity is necessary for timely planning of measures to combat epidemic.

First record of the human infection of Brucella melitensis in Kyrgyzstan: evidence from whole-genome sequencing-based analysis.

BACKGROUND: Brucellosis, a zoonosis mainly transmitted by consumption of unpasteurized dairy products as well as direct contact with infected animals, is endemic in Kyrgyzstan. However, Brucella species in humans have not been investigated and the origin of the disease remains poorly known in wide parts of Сentral Asia. Thus, molecular characterization of the circulating strains is a critical first step in understanding Brucella diversity in the country. METHODS: In this study, isolates were collected from patients with suspected brucellosis from different regions in Kyrgyzstan between 2019 and 2020. The detection and identification of Brucella was carried out by Bruce-ladder PCR. Next generation sequencing was used to sequence the 89 Brucella isolates, which were genotyped by cgSNP and cgMLST to identify epidemiological connection between Brucella isolates as well as placing them in the context of the global Brucella phylogeny. RESULTS: The Brucella strains isolated from all regions of Kyrgyzstan were identified as B. melitensis. Based on cgSNP analysis, 18 sequence types were differentiated. The highest numbers of different sequence types were found in Batken (n = 8), Osh (n = 8) and Jalal-Abad (n = 6) oblasts. According to cgSNP and cgMLST analyses, different B. melitensis lineages circulate in Kyrgyzstan, all of them belonging to the Eastern Mediterranean group of the global Brucella phylogeny with the highest similarity to strains from Turkmenistan, Iran and Turkey. CONCLUSION: In the present study, B. melitensis was identified as a causative agent of human brucellosis in Kyrgyzstan and different lineages could be identified. Since this study focused on isolates of human origin, the identity of Brucella species and lineages circulating among animal populations remains elusive. Implementing culture techniques and use of most recent molecular, bioinformatic and epidemiological tools are needed to set up a One Health approach to combat brucellosis in Kyrgyzstan. Further, other Сentral Asian countries need to take part in this effort as brucellosis is a transboundary disease in these regions.

Association between gender-based violence and hypertension among women in the Kyrgyzstan Republic.

BACKGROUND: Gender-based violence (GBV) is a significant global public health problem and the most prominent human rights violation severely impacting women's health and wellbeing. Therefore, the aim of this study is to evaluate the association between gender-based violence and hypertension in Kyrgyzstan Republic. METHODS: This study was conducted using population-based data of women from the 2018 Kyrgyzstan Demographic and Health Survey. The odds ratio was calculated to measure the association between GBV and hypertension, and p-values < 0.005 was considered statistically significant. RESULT: We included data of 4793 participants, and 621 (13%) of them had hypertension. Participants exposed to GBV were 24% more likely to have hypertension than unexposed participants (OR = 1.24, 95% CI: 1.03-1.48). Of all women with hypertension, 206 (33.0%) were exposed to GBV. Participants with secondary education or higher exposed to GBV were 24% more likely to be hypertensive than GBV unexposed women with the same education levels OR = 1.24, 95% CI: 1.04-1.49). Unemployed participants exposed to GBV were 45% more likely to develop hypertension than their unexposed counterparts (OR = 1.45, 95%CI: 1.15-1.81). Rural residents exposed to GBV were also 29% more likely to have hypertension than those unexposed to GBV (OR = 1.29, 95% CI: 1.04-1.59). The odds of hypertension among those exposed to GBV increase with age. CONCLUSION: The study revealed that GBV is a significant factor of having hypertension among Kyrgyz women.

Risk Factors for Severe Cutaneous Anthrax in a Retrospective Case Series and Use of a Clinical Algorithm to Identify Likely Meningitis and Evaluate Treatment Outcomes, Kyrgyz Republic, 2005-2012.

BACKGROUND: US Centers for Disease Control and Prevention guidelines currently recommend triple-therapy antimicrobial treatment for anthrax meningitis. In the Kyrgyz Republic, a country with endemic anthrax, cutaneous anthrax patients are routinely hospitalized and treated successfully with only monotherapy or dual therapy. Clinical algorithms have been developed to identify patients with likely anthrax meningitis based on signs and symptoms alone. We sought to retrospectively identify likely meningitis patients in the Kyrgyz Republic using a clinical algorithm and evaluate risk factors and their outcomes by type of treatment. METHODS: We conducted a retrospective chart review of cutaneous anthrax patients in the Kyrgyz Republic from 2005 through 2012. Using previous methods, we developed a highly specific algorithm to categorize patients by meningitis status. We then evaluated patient risk factors, treatments, and outcomes by disease severity and meningitis status. RESULTS: We categorized 37 of 230 cutaneous anthrax patients as likely having meningitis. All 37 likely meningitis patients survived, receiving only mono- or dual-therapy antimicrobials. We identified underlying medical conditions, such as obesity, hypertension, and chronic obstructive pulmonary disease, and tobacco and alcohol use, as potential risk factors for severe anthrax and anthrax meningitis. CONCLUSIONS: Based on our analyses, treatment of anthrax meningitis may not require 3 antimicrobials, which could impact future anthrax treatment recommendations. In addition, chronic comorbidities may increase risk for severe anthrax and anthrax meningitis. Future research should further investigate potential risk factors for severe anthrax and their impact on laboratory-confirmed meningitis and evaluate mono- and dual-therapy antimicrobial regimens for anthrax meningitis.

SARS-CoV-2 herd immunity of the Kyrgyz population in 2021.

In the fight against coronavirus infection, control of the immune response is of decisive importance, an important component of which is the seroprevalence of antibodies to SARS-CoV-2. Immunity to SARS-CoV-2 is formed either naturally or artificially through vaccination. The purpose of this study was to assess the seroprevalence of antibodies to SARS-CoV-2 in the population of Kyrgyzstan. A cross-sectional randomized study of seroprevalence was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the Association of Preventive Medicine (Kyrgyzstan) and the St. Petersburg Pasteur Institute (Russia) approved the study. Volunteers (9471) were recruited, representing 0.15% (95% CI 0.14-0.15) of the total population, randomized by age and region. Plasma antibodies (Abs) to the nucleocapsid antigen (Nag) were determined. In vaccinated individuals, Abs to the SARS-CoV-2 receptor-binding domain antigen (RBDag) were determined. Differences were considered statistically significant at p < 0.05. The SARS-CoV-2 Nag Ab seroprevalence was 48.7% (95% CI 47.7-49.7), with a maximum in the 60-69 age group [59.2% (95% CI 56.6-61.7)] and a minimum in group 1-17 years old [32.7% (95 CI: 29.4-36.1)]. The highest proportion of seropositive individuals was in the Naryn region [53.3% (95% CI 49.8-56.8)]. The lowest share was in Osh City [38.1% (95% CI 32.6-43.9)]. The maximum SARS-CoV-2 Nag seropositivity was found in the health-care sector [57.1% (95% CI 55.4-58.8)]; the minimum was seen among artists [38.6% (95% CI 26.0-52.4)]. Asymptomatic SARS-CoV-2 Nag seropositivity was 77.1% (95% CI 75.6-78.5). Vaccination with Sputnik V or Sinopharm produced comparable Ab seroprevalence. SARS-CoV-2 Nag seropositivity in the Kyrgyz population was 48.75% (95% CI 47.7-49.7), with the mass vaccination campaign undoubtedly benefitting the overall situation.

Global Distribution and Natural Recombination of Hepatitis D Virus: Implication of Kyrgyzstan Emerging HDVs in the Clinical Outcomes.

Discrepancies in human hepatitis delta virus (HDV) genotypes impact the virus' biological behavior, clinical manifestation, and treatment response. Herein, this report aims to explore the role of recombination in the worldwide genotypic distribution and genetic diversity of HDV. Three-hundred-forty-eight human HDV full-length genomic sequences of ~1678 nt in length, isolated in twenty-eight countries worldwide between 1986 and 2018, were analysed. Similarity analysis and recombination mapping were performed, and forty-eight recombination events were identified, twenty-nine of which were isolated from Kyrgyzstan and determined to be involved in the diversity and extension of HDV sub-genotypes. HDV recombination occurred only between the genetically close genotypes (genotype 5 and genotype 2) or mainly within genotype 1, suggesting the complex replicative molecular mechanisms of HDV-RNA. The global distribution and classification of HDV genotypes have been updated, indicating that HDV recombination is one of the driving forces behind the biodiversity and the evolution of human HDV genomes. The outcome analysis suggests that the expansion of HDV sub-genotypes and the complex recombination networks might be related to the genomic character of Kyrgyzstan circulating strains and extensive mobility within countries and across borders. These findings will be of great importance in formulating more effective public health HDV surveillance strategies and guiding future molecular and epidemiological research to achieve better clinical outcomes.

Ancient DNA reveals Black Death source.

Graves in Kyrgyzstan hold early victims of plague that swept medieval Europe.

The source of the Black Death in fourteenth-century central Eurasia.

The origin of the medieval Black Death pandemic (AD 1346-1353) has been a topic of continuous investigation because of the pandemic's extensive demographic impact and long-lasting consequences1,2. Until now, the most debated archaeological evidence potentially associated with the pandemic's initiation derives from cemeteries located near Lake Issyk-Kul of modern-day Kyrgyzstan1,3-9. These sites are thought to have housed victims of a fourteenth-century epidemic as tombstone inscriptions directly dated to 1338-1339 state 'pestilence' as the cause of death for the buried individuals9. Here we report ancient DNA data from seven individuals exhumed from two of these cemeteries, Kara-Djigach and Burana. Our synthesis of archaeological, historical and ancient genomic data shows a clear involvement of the plague bacterium Yersinia pestis in this epidemic event. Two reconstructed ancient Y. pestis genomes represent a single strain and are identified as the most recent common ancestor of a major diversification commonly associated with the pandemic's emergence, here dated to the first half of the fourteenth century. Comparisons with present-day diversity from Y. pestis reservoirs in the extended Tian Shan region support a local emergence of the recovered ancient strain. Through multiple lines of evidence, our data support an early fourteenth-century source of the second plague pandemic in central Eurasia.

Management of type 1 diabetes in low- and middle-income countries: Comparative health system assessments in Kyrgyzstan, Mali, Peru and Tanzania.

AIMS: To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. METHODS: The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. RESULTS: Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. CONCLUSIONS: People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.