СОНОГРАФИЧЕСКИЕ ИЗМЕНЕНИЯ ОРГАНОВ БРЮШНОЙ ПОЛОСТИ У ДЕТЕЙ С РАЗЛИЧНЫМ ТЕЧЕНИЕМ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

In order to determine the frequency and nature of sonographic changes in abdominal organs in children with tuberculosis infection, 192 patients at the age of 6 months -14 years were examined on the basis of the tuberculosis department of City Children’s Infectious Hospital №3 for the period 2019-2021. 3 groups of patients were identified: group 1 - 92 children with active respiratory tuberculosis; group 2 – 52 children with residual post-tuberculosis changes; group 3 – 48 children with latent tuberculosis infection at risk of tuberculosis. Sonographic liver changes (reactive and/or intrahepatic cholestasis and/or hepatomegaly) were observed in children with active tuberculosis in 40.2±5.1% of cases, in children of group 3 - in 35.4±6.9% of cases and less often in children of group 2 - in 17.3±5.3% of cases (p<0.05). Changes of the gallbladder (violations of bile outflow and/or shape changes) were visualized in children with active tuberculosis in 73.9±4.6% of cases, in children of group 3 (60.4±7.1% of cases), less often in children of group 2 (55.8±6.7% of cases, p<0.05 for group 1). Changes of the pancreas were reactive and were more often observed in children of group 1 - in 14.1± 3.5% of cases than in children of group 2 (5.8±3.2% of cases, p<0.05) and group 3 (4.2± 2.9% of cases). Also, ultrasound changes of the spleen were more often detected in children with active tuberculosis - in 17.4±4.0% of cases than in children of group 2 (5.8±3.2% of cases, p<0.05) and group 3 (2.1±2.1% of cases, p<0.05).Pentru a determina frecvența și natura modificărilor ecografice în organele abdominale la copiii cu infecție tuberculoasă, au fost examinați 192 de pacienți cu vârsta cuprinsă între 6 luni - 14 ani din secția de tuberculoză a Spitalul Municipal de infecții pentru copii Nr. 3 pentru perioada 2019-2021. Au fost identificate 3 loturi de pacienţi: lotul 1 - 92 copii cu tuberculoză activă a organelor respiratorii; grupa 2 - 52 copii cu sechele post-tuberculoase; grupa 3 - 48 de copii cu infecție tuberculoasă latentă din grupele cu risc de tuberculoză. Modificări ecografice la nivelul ficatului (colestază reactivă și/sau intrahepatică și/sau hepatomegalie) au fost observate la copiii cu tuberculoză activă în 40,2 ± 5,1% din cazuri, la copiii din grupa a 3-a - în 35,4 ± 6,9% din cazuri și mai rar în copiii din grupa a 2-a – în 17,3±5,3% din cazuri (p<0,05). Modificări ale vezicii biliare (afectarea fluxului biliar și/sau modificări ale formei) la copiii cu tuberculoză ac- tivă au fost vizualizate în 73,9 ± 4,6% din cazuri, la copiii din grupa a 3-a (60,4 ± 7,1% din cazuri), mai rar la copiii dun grupul 2 (55,8±6,7% din cazuri, p<0,05 pentru grupul 1). Modificările pancreasului au fost reactive și s-au observat mai des la copiii din grupa 1 - în 14,1±3,5% din cazuri decât la copiii din grupul 2 (5,8±3,2% din cazuri, p<0,05) și grupul 3 (4,2±2,9% din cazuri). De asemenea, modificări ale splinei au fost depistate mai des la copiii cu tuberculoză activă - în 17,4±4,0% din cazuri decât la copiii din loturile 2 (5,8±3,2% din cazuri, p<0,05) și 3 loturi (2,1±2,1% din cazuri, p<0,05).С целью определения частоты и характера сонографических изменений органов брюшной полости у детей с туберкулезной инфекцией обследованы 192 пациента в возрасте 6 месяцев -14 лет туберкулезного отделения СПГБУЗ ДИБ№3 за период 2019-2021гг. Выделено 3 группы пациентов: 1 группа - 92 ребенка с активным ту- беркулезом органов дыхания; 2 группа – 52 ребенка с остаточными посттуберкулезными изменениями; 3 группа – 48 детей с латентной туберкулезной инфекцией из групп риска по туберкулезу. Сонографические изменения печени (реактивные и/или внутрипеченочный холестаз и/или гепатомегалия) наблюдались у детей с активным туберкулезом в 40,2±5,1% случаев, у детей 3 группы - в 35,4±6,9% случаев и реже у детей 2 группы - в 17,3±5,3% случаев (р<0,05). Изменения желчного пузыря (нарушения оттока желчи и/или изменения формы) у детей с ак- тивным туберкулезом визуализировались в 73,9±4,6% случаев, у детей 3 группы (60,4±7,1% случаев), реже у детей 2 группы (55,8±6,7% случаев, р<0,05 для 1 группы). Изменения поджелудочной железы были реактивными и чаще наблюдались у детей 1 группы - в 14,1±3,5% случаев, чем у детей 2 группы (5,8±3,2% случаев, р<0,05) и 3 группы (4,2±2,9% случаев). Также изменения селезенки чаще определялись у детей с активным туберкулезом  в 17,4±4,0% случаев, чем у детей 2 группы (5,8±3,2% случаев, р<0,05) и 3 группы (2,1±2,1% случаев, р<0,05)

3,5-Dimethyladamantan-1-amine Restores Short-term Synaptic Plasticity by Changing Function of Excitatory Amino Acid Transporters in Mouse Model of Spinocerebellar Ataxia Type 1

Introduction. Memantine is an agent that used for treatment of Alzheimer's type dementia. Memantine considerably reduces the effects of neurodegeneration, may potentially slow down the neurodegenerative changes in the cerebellum and may act as treatment of choice for spinocerebellar ataxia type 1 (SCA 1). Our objective was to study molecular mechanisms of the short-term synaptic plasticity improvement associated with long-term memantine use in SCA 1 transgenic mice. Materials and methods. The experiments were performed on 12-week-old CD1 mice. We created a mouse model of cerebellar astrogliosis after expression of mutant ataxin-1 (ATXN1[Q85]) in the Bergmann glia (BG). To model the astrocyte-mediated neurodegeneration in the cerebellum, the mice were injected with LVV GFAP-Flag-ATXN1[Q85] lentiviral vector (LVV) constructs intracortically. Some of the mice received 0.35 mg/kg memantine dissolved in drink water once daily for 9 weeks. The control animals were administered LVV GFAP-ATXN1[Q2]-Flag. Changes of the excitatory postsynaptic currents amplitudes from Purkinje cells (PC) were recorded by patch clamp. Expression of anti-EAAT1 in the cerebellar cortex was assessed using immunohistochemistry. Results. The reactive glia of the cerebellar cortex in SCA1 mice is characterized by a decrease in the immunoreactivity of anti-EAAT1, while chronic memantine use restores this capacity. The decay time of the excitatory postsynaptic current amplitude in the parallel fiber-Purkinje cell (PF-PC) synapses of the SCA1 mice is considerably longer, which indicates the slowing of glutamate reuptake and EAAT1 dysfunction. The prolonged presence of increased neurotransmitter levels in the synaptic cleft facilitates activation of the mGluR1 signaling and restoration of mGluR1-dependent synaptic plasticity in Purkinje cells of the SCA1 mice. Conclusions. The slowing of neurotransmitter reuptake associated with long-term memantine treatment improves mGluR1-dependent short-term synaptic plasticity of the Purkinje cells in the SCA1 mice. Restoration of synaptic plasticity in these animals may underlie partial reduction of ataxic syndrome

Supporting National Immunization Technical Advisory Groups in the WHO European Region in developing national COVID-19 vaccination recommendations through online communication platform.

National Immunization Technical Advisory Groups are groups of multi-disciplinary experts that provide scientific advice to policy makers to enable them to make informed immunization policy and programme decisions. NITAGs faced challengesusing their routine approach to develop recommendations for COVID-19 vaccines during the pandemic. In response, the WHORegional Office for Europe (Regional Office), with the support of theRobert Koch Institute, developedan innovative approach of a series of webinars, provision of materials, and remote technical assistance to address these challenges. Polls conducted during webinars were used to tailor future webinars and evaluate the effectiveness of these interventions. According to poll results, 76% of participants found the webinars and resources shared very useful in their work on COVID-19 vaccination.The Regional Office plans to build further upon the scope of online communication and establish a regional online platform for NITAGs to further support NITAGs and build capacity

HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010–2019

WHO/UNICEF estimates for HPV vaccination coverage from 2010 to 2019 are analyzed against the backdrop of the 90% coverage target for HPV vaccination by 2030 set in the recently approved global strategy for cervical cancer elimination as a public health problem. As of June 2020, 107 (55%) of the 194 WHO Member States have introduced HPV vaccination. The Americas and Europe are by far the WHO regions with the most introductions, 85% and 77% of their countries having already introduced respectively. A record number of introductions was observed in 2019, most of which in low- and middle- income countries (LMIC) where access has been limited. Programs had an average performance coverage of around 67% for the first dose and 53% for the final dose of HPV. LMICs performed on average better than high- income countries for the first dose, but worse for the last dose due to higher dropout. Only 5 (6%) countries achieved coverages with the final dose of more than 90%, 22 countries (21%) achieved coverages of 75% or higher while 35 (40%) had a final dose coverage of 50% or less. When expressed as world population coverage (i.e., weighted by population size), global coverage of the final HPV dose for 2019 is estimated at 15%. There is a long way to go to meet the 2030 elimination target of 90%. In the post-COVID era attention should be paid to maintain the pace of introductions, specially ensuring the most populous countries introduce, and further improving program performance globally

Comparative Economic Evaluation of Haemophilus influenzae Type b Vaccination in Belarus and Uzbekistan

BACKGROUND: Hib vaccine has gradually been introduced into more and more countries during the past two decades, partly due to GAVI Alliance support to low-income countries. However, since Hib disease burden is difficult to establish in settings with limited diagnostic capacities and since the vaccine continues to be relatively expensive, some Governments remain doubtful about its value leading to concerns about financial sustainability. Similarly, several middle-income countries have not introduced the vaccine. The aim of this study is to estimate and compare the cost-effectiveness of Hib vaccination in a country relying on self-financing (Belarus) and a country eligible for GAVI Alliance support (Uzbekistan). METHODS AND FINDINGS: A decision analytic model was used to estimate morbidity and mortality from Hib meningitis, Hib pneumonia and other types of Hib disease with and without the vaccine. Treatment costs were attached to each disease event. Data on disease incidence, case fatality ratios and costs were primarily determined from national sources. For the Belarus 2009 birth cohort, Hib vaccine is estimated to prevent 467 invasive disease cases, 4 cases of meningitis sequelae, and 3 deaths, while in Uzbekistan 3,069 invasive cases, 34 sequelae cases and 341 deaths are prevented. Estimated costs per discounted DALY averted are US$9,323 in Belarus and US$ 267 in Uzbekistan. CONCLUSION: The primary reason why the cost-effectiveness values are more favourable in Uzbekistan than in Belarus is that relatively more deaths are averted in Uzbekistan due to higher baseline mortality burden. Two other explanations are that the vaccine price is lower in Uzbekistan and that Uzbekistan uses a three dose schedule compared to four doses in Belarus. However, when seen in the context of the relative ability to pay for public health, the vaccine can be considered cost-effective in both countries

The cost-effectiveness of rotavirus vaccination in Armenia.

The cost-effectiveness of introducing infant rotavirus vaccination in Armenia in 2012 using Rotarix(R) was evaluated using a multiple birth cohort model. The model considered the cost and health implications of hospitalisations, primary health care consultations and episodes not leading to medical care in children under five years old. Rotavirus vaccination is expected to cost the Ministry of Health $220,000 in 2012, rising to$830,000 in 2016 following termination of GAVI co-financing, then declining to $260,000 in 2025 due to vaccine price maturity. It may reduce health care costs by$34,000 in the first year, rising to $180,000 by 2019. By 2025, vaccination may be close to cost saving to the Ministry of Health if the vaccine purchase price declines as expected. Once coverage has reached high levels, vaccination may prevent 25,000 cases, 3000 primary care consultations, 1000 hospitalisations and 8 deaths per birth cohort vaccinated. The cost per disability-adjusted life year (DALY) saved is estimated to be about$650 from the perspective of the Ministry of Health, $850 including costs accrued to both the Ministry and to GAVI,$820 from a societal perspective excluding indirect costs and $44 from a societal perspective including indirect costs. Since the gross domestic product per capita of Armenia in 2008 was$3800, rotavirus vaccination is likely to be regarded as "very cost-effective" from a WHO standpoint. Vaccination may still be "very cost-effective" if less favourable assumptions are used regarding vaccine price and disease incidence, as long as DALYs are not age-weighted

Strengthening national decision-making on immunization by building capacity for economic evaluation: Implementing ProVac in Europe.

BACKGROUND: For many years, low- and middle-income countries have made efforts to strengthen national decision-making on immunization. The Pan American Health Organization (PAHO) ProVac Initiative was established to help expedite the use of evidence-based decision-making around new vaccine introduction. This initiative provides training in user-friendly cost-effectiveness models and supports the development of country-led economic evaluations. Due to the success of the ProVac Initiative in the Americas, and following requests from countries from outside the Americas, the Bill & Melinda Gates Foundation funded a two-year pilot effort to expand the initiative to other world regions. Called the ProVac International Working Group (IWG), this endeavor took place in 2012 and 2013. It was coordinated by PAHO and carried out in collaboration with several international partners, including the Agence de Médecine Préventive (AMP), London School of Hygiene & Tropical Medicine (LSHTM), Program for Appropriate Technology in Health, Sabin Vaccine Institute, United States Centers for Disease Control and Prevention, and the World Health Organization (WHO). In the WHO European Region, technical support was provided by AMP, in close collaboration with the WHO Regional Office for Europe and other ProVac IWG partners. METHODS: In 2012, AMP, the WHO Regional Office for Europe, and other partners held a training workshop in Dubrovnik, Croatia, for 31 participants from four countries of the WHO European Region. The aim was to train health professionals in standard methods of economic evaluation and to assess regional demand for economic studies to support decision-making on immunization. AMP and the other organizations also supported four national cost-effectiveness studies in the WHO European Region. The assistance included country visits and support over a period of six months, the establishment of multidisciplinary teams of experts, ongoing training on the TRIVAC decision-support model for new-vaccine economic analysis, review of local evidence, recommending key data inputs, and support in presenting results to national decision makers. RESULTS: National cost-effectiveness studies were conducted in four countries: Albania (rotavirus vaccine [RV]), Azerbaijan (pneumococcal conjugate vaccine [PCV]), Croatia (PCV), and Georgia (PCV). All four countries improved their estimates of the burden of disease preventable by the new vaccines. National advisory bodies and ministries of health obtained economic evidence that helped Albania and Croatia to make decisions on introducing the new vaccines. Azerbaijan and Georgia used economic evidence to confirm previously made preliminary decisions to introduce PCV and make corresponding financial commitments. The study helped Albania to obtain access to affordable prices for rotavirus vaccines through participation in the UNICEF procurement mechanism for middle-income countries. Croatia was able to define the PCV price that would make its introduction cost-effective, and can use this figure as a basis for price negotiations. DISCUSSION: Despite some challenges due to competing national priorities, tight budgets for immunization, and lack of available national data, the ProVac IWG helped to build capacity of national health professionals, support decision-making for the introduction of new vaccines, and promote utilization of economic evidence for making decisions on immunization. This type of strong collaboration among international partners and countries should be scaled up, given that many other countries in the WHO European Region have expressed interest in receiving assistance from the ProVac IWG

Scenario analysis.

<p>Impact on discounted costs per DALY averted from univariate changes in parameter values.</p