Clinical and laboratory predictors of antitoxic immunity against diphtheria and tetanus in adults with HIV infection

Antiretroviral therapy has made HIV infection a chronic controlled disease, where aspects of the immunoprophylaxis of infectious diseases have acquired important clinical significance. The goal of the study was to determine the clinical and laboratory predictors of antitoxic immunity against diphtheria and tetanus in HIV-infected adults. The study included 90 HIV-infected patients aged 22 to 60 years (main group). The control group consisted of 49 immunocompetent volunteers of the corresponding age. The levels of anti-diphtheria and anti-tetanus antibodies were determined by ELISA using the diagnostic test systems RIDASCREEN Diphtheria IgG and RIDASCREEN Tetanus IgG (R-Biopharm AG, Germany). Statistical processing was performed using the licensed software product STATISTICA v.6.1. Significant differences were found between the titers of antitoxic antibodies in HIV-infected and immunocompetent adults. According to the correlation analysis, the decrease in the titers of antidiphtheria antibodies was revealed with an increase in the age of the HIV-infected patient (rs=-0.21; p=0.05). The fact of smoking (rs=-0.31; p=0.003), lowered body weight (BMI<18.5 kg/m2) (rs=-0.29; p=0.006), the presence of arterial hypertension (rs=-0.38; p<0.001), a history of bone fractures over the past 5 years (rs=-0.38; p<0.001), anemia (rs=-0.21; p=0.049), thrombocytopenia (rs=-0.44; p<0.001), accelerated ESR (rs=-0.61; p<0.001), the presence of hairy leukoplakia of the tongue (rs=-0.23; p=0.027), frequent infections caused by herpes simplex (rs=-0.52; p=0.003) and varicella zoster virus (rs=-0.34; p=0.013) are associated with low levels of antidiphtheria antibodies. A direct relationship was found between the intensity of anti-diphtheria immunity and patients receiving OST (rs=+0.54; p=0.003) and with a history of injuries with impaired skin integrity (rs=+0.31; p=0.003). Decreased anti-tetanus immunity in HIV-infected patients was also associated with smoking (rs=-0.48; p<0.001), decreased BMI (rs=-0.71; p<0.001), anemia (rs=-0.33; p=0.002), thrombocytopenia (rs=-0.75; p<0.001), a history of bone fractures over the past 5 years (rs=-0.67; p<0.001); the total number of HIV-associated opportunistic diseases (rs=-0.42; p<0.001), including the presence of oropharyngeal candidiasis (rs=-0.23; p=0.032) and hairy leukoplakia of the tongue (rs=-0.57; p<0.001), history of Herpes Zoster in the past (rs=-0.48; p<0.001), with frequent relapses of diseases caused by herpes simplex viruses (rs=-0.78; p<0.001) and repeated episodes of herpes zoster (rs=-0.74; p<0.001), as well as with pathology of the skin (rs=-0.55; p<0.001). Protective predictors of anti-tetanus antitoxic immunity strength were established: male gender (rs=+0.22; p=0.039), parenterally acquired HIV infection (rs=+0.21; p=0.05), HIV-infected patients receiving OST (rs=+0.40; p=0.041). A direct relationship was found with the decreased level of hemoglobin (rs=+0.41; p<0.001), the increase of relative number of lymphocytes in the blood (rs=+0.21; p=0.05), as well as with living in rural areas (rs=+0.40; p<0.001) and the presence of injuries with impairment of skin integrity (rs=+0.84; p<0.001). Clinical and laboratory predictors of strength of antitoxic immunity against diphtheria and tetanus in HIV-infected adults were identified, which allows us to create an individual “vaccination roadmap” for patients in this category

ПОРУШЕННЯ ФУНКЦІЇ В-ЛІМФОЦИТІВ ПРИ ВІЛ-ІНФЕКЦІЇ

Aim – on the basis of literary information to analyse the parafunction of B-limphocytes at HIV infection.HIV causes a chronic infection, which is not destroyed by the immune system of the body. Besides progressive decline and dysfunction of CD4+ T cells, HIV infection leads to intensive phenotypic and functional abnormalities in a pool of B-lymphocytes. Although B cells are not the primary target for HIV, there are enough studies that show significant damage specifically in subpopulation of B lymphocytes.Conclusions. Besides apparent lymphopenia, which is caused by CD4+ T lymphocytopenia, there are functional disorders, first of all, in populations of B cells, namely hipergammaglobuliemia, polyclonal abnormal activation of B cells, expansion of immature/transitional B cells, induction of terminal differentiation of B cells, increased levels of autoantibodies, abnormal predisposition to apoptosis, increased frequency of B-cell malignancies, as well, which is also quite important, low humoral immune response to vaccine antigens. In addition, HIV infection is associated with a decrease of CD27 memory B cell may not be negated, even with the early appointment of antiretroviral therapy. Both cellular and humoral immunity are not capable of controlling the infection, which leads to a significant depletion of lymphocytes function and increases susceptibility to opportunistic infections. Deeper understanding of the pathogenic mechanisms of B-lymphocyte dysfunction could potentially lead to new strategies for treatment and creating preventive vaccine. This review presents the mechanisms involved in the dysfunction of B cells in HIV infection, which are least studied in the immunopathogenesis of HIV infection.Мета роботи – на підставі літературних відомостей проаналізувати порушення функції В-лімфоцитів при ВІЛ-інфекції.ВІЛ спричинює хронічну інфекцію, що не знищується імунним захистом організму. Крім прогресуючого зниження та дисфункції CD4+ Т-клітин, ВІЛ-інфекція призводить до інтенсивних фенотипічних та функціональних порушень у пулі В-лімфоцитів. Хоча В-клітини не є основною мішенню для ВІЛ, є достатня кількість досліджень, що свідчать про суттєві порушення саме у субпопуляції В-лімфоцитів. Висновки. Крім явної лімфопенії, що обумовлена CD4+ Т-лімфоцитопенією, відбуваються функціональні порушення, насамперед, у популяції В-клітин, а саме: гіпергаммаглобулінемія, поліклональна аномальна активація В-клітин, збільшення незрілих/перехідних В-лімфоцитів, індукція термінального диференціювання В-клітин, підвищення рівнів автоантитіл, патологічна схильність до апоптозу, збільшення частоти В-клітинних злоякісних пухлин, а також, що досить важливо, низька гуморальна імунна відповідь на вакцинні антигени. Враховуючи останній аспект, необхідно буде направити зусилля на вдосконалення імунопрофілактики ВІЛ-інфікованих осіб, що зменшить ризик виникнення «вакцинокерованих» інфекційних захворювань. Також з ВІЛ-інфекцією асоційовано зменшення CD27 В-клітин пам’яті, що можливо, не буде нівелюватись, навіть при ранньому призначенні антиретровірусної терапії. І клітинний, і гуморальний імунітет не в змозі контролювати цю інфекцію, що призводить до суттєвого виснаження функції лімфоцитів та збільшує сприйнятливість до опортуністичних інфекцій. Більш глибоке розуміння патогенних механізмів дисфункції В-лімфоцитів зможе потенційно привести до нових стратегій щодо лікування, створення профілактичної вакцини. У даному огляді представлені механізми, що беруть участь у порушенні функції В-клітин при ВІЛ-інфекції, що менш за все вивчені в імунопатогенезі ВІЛ-інфекції.

КЛІНІКО-ЕКОНОМІЧНИЙ АНАЛІЗ ВИТРАТ НА ФАРМАКОТЕРАПІЮ ГОСТРОГО ТОНЗИЛІТУ В УМОВАХ СТАЦІОНАРУ

IntroductionAcute tonsillitis (J03 for ICD-10) is one of the most common respiratory diseases in children [1]. According to the medical protocol approved by the Ministry of Health ofUkraine, patients with catarrhal form of acute tonsillitis are provided ambulatory care, but patients with follicular and lacunar tonsillitis forms are treated in a hospital [2].In the latest data of the State Committee of Statistics, 41.1% of the funds in the structure of health care costs are citizens’ private funds [3]. These funds covered 99.6% of the costs for the purchase of pharmaceutical products for outpatient treatment, and 86.7% costs for treatment in a hospital [4]. In addition, it should take note of the low purchasing power of patients, as 36.1% of them are unable to buy the medicines prescribed by a doctor [5].In view, the high rates of morbidity, constantly growing treatment costs and low purchasing power of patients, the purpose of our research was to investigate the expediency of the financial expenses for pharmacotherapy of acute tonsillitis based on the results of retrospective clinical and economic analysis of hospital medical history forms.Materials and methodsThe material of our study were doctors’ prescription sheets (form №003-4/o) of 290 patients with acute tonsillitis aged 2–18 years who were hospitalized in healthcare institutions of Dnipropetrovsk region for the period 2013–2015. Overall, we analyzed 1709 medications. Propriety of medical prescriptions was determined by comparing them to the current Ukrainian medical protocol of care for patients with acute tonsillitis [2] and the Ukraine State Drug Formulary [6]. The expediency of the financial costs for pharmacotherapy of acute tonsillitis was assessed by method the integrated frequency/VEN/ABC analysis [7].Results and discussionThe criterions for classifying medicines to category «V» (vital) were their presence in the medical protocol of care for patients with acute tonsillitis [2] and the the Ukraine State Drug Formulary [6]. The category of «N» (non-essential) included medicines that have been absent at any of the above regulatory documents.Results of the integrated frequency/VEN/ABC-analysis showed that the most costly group A included 15.04% (257 of 1709) medicines category V and 11.29% (193 of 1709) medicines category N. It was found that the basic financial funds had been used for ceftriaxone (J01DD04), local antiseptics (R02AA20) and cefuroxime (J01DC02), among which the most costly ceftriaxone had been prescribed for the largest number of patients. Despite the fact that ceftriaxone is recommended by national standard treatment of acute tonsillitis [2], but it is not the drug of choice for the treatment of this nosology. Ceftriaxone is rational to replace by penicillin or cephalosporin first generation, which have the same clinical efficacy against Streptococcus pyogenes and less cost [11].The frequency of non-essential medicine prescriptions were dominated by the vital medicines. However, the financial costs for vital medicines were slightly greater than for the non-essential medicines, which amounted to 55.66% and 44.34% respectively. Excessive costs for the third-generation cephalosporin pharmacotherapy of acute tonsillitis can be explained by the doctors' intention to protect their patients from clinical failures associated with the penicillin destruction by β-lactamases of tonsils co-pathogenic microorganisms [12].ConclusionsBasic funds were not spent for essential medicines for the treatment of acute tonsillitis. The most often prescribed costly medicine may have been replaced by cheaper ones with similar clinical efficacy.Economically more rational begin pharmacotherapy of acute tonsillitis with penicillins. Сephalosporins second- or third generation and inhibitor-protected penicillins, as antibiotics for second-line therapy, should be prescribed only in cases of recurrent tonsillitis [5].Local antiseptics, probiotics, corticosteroids and dietary supplements had been widely used by doctors. Removal these pharmaceutical products from doctors’ prescription sheets would reduce the financial expenses for pharmacotherapy of acute tonsillitis without affecting its quality.У статті наведено результати інтегрованого частотного^ЕМАВС-аналізу доцільності фінансових витрат на проведення фармакотерапії гострого тонзиліту. Встановлено суттєву перевагу частоти лікарських призначень другорядних засобів (^ над життєво важливими (V) у кількісному вираженні та незначну перевагу життєво важливих засобів над другорядними у вартісному вираженні. З отриманих результатів можна зробити висновок, що основні фінансові кошти не витрачались на необхідні та важливі лікарські засоби для лікування гострого тонзиліту

Рівень протеїну S100b у сироватці крові хворих з ко-інфекцією ВІЛ /туберкульоз як нейроспецифічний біомаркер ятрогенної нейротоксичності

There was studied the influence of antiretroviral and antimycobacterial chemotherapy on releasing from the gliacell marker lesions – S100b protein in the context of possible iatrogenic. It was established that a slight increase inthe concentration of S100b protein in blood serum of patients with co-infection of HIV /TB after starting HAART wasnot associated with the occurrence of symptoms of the central nervous system.Было изучено влияние препаратов антиретровирусной и антимикобактериальной химиотерапии навысвобождение из клеток нейроглии маркера поражения протеина S100b, в разрезе возможной ятрогении.Установлено, что незначительное повышение концентрации белка S100b в сыворотке крови больныхc ко-инфекцией ВИЧ/туберкулез после начала высокоактивной антиретровирусной терапии не былосвязано с возникновением симптомов со стороны центральной нервной системы.Вивчено вплив препаратів антиретровірусної та антимікобактеріальної хіміотерапії на вивільненняз клітин нейроглії маркера ураження протеїну S100b з огляду на можливу ятрогенію. Встановлено, щонезначне підвищення концентрації білка S100b у сироватці крові хворих з ко-інфекцією ВІЛ/туберкульозпісля початку високоактивної антиретровірусної терапії не було пов’язане з виникненням симптомів збоку центральної нервової системи

Measles (lecture)

The article provides comprehensive review of different aspects of measles. Definition of disease, historical overview, measles in the world epidemiology and in the countries bordering Ukraine over the recent years, particularities of measles epidemiology in Ukraine are given in details. Etiology of measles virus including known genomic structure and viral proteins list, genetic changeability of the virus. Particularities of measles epidemiological process are discussed, criteria of determination of morbidity level and contagiosity of the given disease are outlined. Detailed pathogenesis of measles in different periods of disease is provided, reciprocal influence of the disease and vitamin A metabolism is given. Particularities of humoral and cellular immunological response, including those in early-aged and in patients with immune deficiency are described. Possibility of development of subacute sclerosing panencephalitis is pointed out; currently accepted causes of this complication development, its immunological and virological particularities are summarized. Pathogenetic mecha­nisms of rash development, com­plications as well as morphological changes in different organs and systems are given. The article gives both international and different clinical classifications of measles. Clinical manifestations of typical and atypical measles course are described in details by syndromes and according to disease periods. Particularities of measles course at different premorbid conditions are described. The article provides colored photos which illustrate clinical mani­festations of measles manifestation on the skin and mucosa at different disease periods

Корь (лекция)

The article provides comprehensive review of different aspects of measles. Definition of disease, historical overview, measles in the world epidemiology and in the countries bordering Ukraine over the recent years, particularities of measles epidemiology in Ukraine are given in details. Etiology of measles virus including known genomic structure and viral proteins list, genetic changeability of the virus. Particularities of measles epidemiological process are discussed, criteria of determination of morbidity level and contagiosity of the given disease are outlined. Detailed pathogenesis of measles in different periods of disease is provided, reciprocal influence of the disease and vitamin A metabolism is given. Particularities of humoral and cellular immunological response, including those in early-aged and in patients with immune deficiency are described. Possibility of development of subacute sclerosing panencephalitis is pointed out; currently accepted causes of this complication development, its immunological and virological particularities are summarized. Pathogenetic mecha­nisms of rash development, com­plications as well as morphological changes in different organs and systems are given. The article gives both international and different clinical classifications of measles. Clinical manifestations of typical and atypical measles course are described in details by syndromes and according to disease periods. Particularities of measles course at different premorbid conditions are described. The article provides colored photos which illustrate clinical mani­festations of measles manifestation on the skin and mucosa at different disease periods

VISCERAL MIGRATING LARVA. CLINICAL CASES. UKRAINIAN BURDEN

Introduction. The work highlights the problematic issues of diagnosis and treatment of toxocariasis infection in people in Ukraine, which become even more acute and urgent due to the migration of the population and animals, and the destruction of the country's infrastructure as a result of the war unleashed by Russia. The aim of the study. Improvement of aspects of clinical, laboratory and instrumental diagnostics, as well as treatment of VML in humans Materials and methods. A literature research of the state of the problem of primary and differential diagnosis of the migrating larva in Ukraine and the world has been conducted. 2 clinical cases of diagnosis and treatment of migrating larva in are described. Results. The article describes two clinical cases of visceral migrating larva. The differences of these cases, in addition to the migrating formations in the lungs, were the asymptomatic course, the absence of eosinophilia, and the simultaneous determination of blood class G antibodies by ELISA to Toxocar and human roundworm (A. lumbricoide), which persisted even after treatment. Patients at the stage of diagnosis were examined in an oncology hospital, were consulted by thoracic surgeons and oncologists to exclude lung cancer. Both women were immunocompetent, one patient had a history of cervical cancer. From the epidemiological anamnesis, both women kept cats, and one of them, during chemotherapy for the treatment of a tumor, had a propensity for carnivorous raw-eating. Before prescribing systemic antiparasitic chemotherapy, the patients were examined by an ophthalmologist to exclude parasitic chorioretinitis. The patients were prescribed a 20-day course of albendazal 800 mg/day in two doses. Support therapy consisted of a 5-day course of prednisolone at a dose of 30 mg/day orally in two doses, which started one day before the appointment of albendazole. A control CT scan of the lungs after therapy did not reveal any formations, fibrosis, or calcifications. Discussion. This case proves that tocoscarosis in humans is a multidisciplinary medical and social problem. Conclusions were made on the need to restore the national registration of the disease, adopt national consensuses on treatment and diagnosis, and implement into clinical practice modern methods of verification of specific antibodies to nematodes based on immunoblotting. Conclusions. The registration of cases of VML and T. in the system of control and prevention of infectious diseases in Ukraine should be resumed. It is expedient to introduce specific studies on nematodes in clinical laboratory practice

ІННОВАЦІЙНІ МЕТОДИ НАВЧАННЯ У ПІДГОТОВЦІ УЧАСНИКІВ ПРОФЕСІЙНО-ОРІЄНТОВАНИХ ОЛІМПІАД

The aim of the work – to present our own experience in using different forms of simulation technology in preparing professionally oriented оlympiad participants on the infectious diseases course. The main body. Innovative methods of teaching the course of infectious diseases in the higher medical school introduced by the authors for the purpose of increasing the efficiency of education are considered. The issues of conducting medical student’s olympiads on professional disciplines are elucidated in detail. The authors’ own experience of using the variants of imitation technology (case-study methods, role-playing games, “brain attack”) has been analyzed. Over the past five years, 53 undergraduate students have been teached on the basis of a student’s scientific course at the Department of Infectious Diseases in Dnipropetrovsk Medical Academy. Of these, 14 students directly participated in professionally oriented Olympiad at the annual Ukrainian Olympiads on infectious diseases. The result of productive training was taking of six prize-places in individual competitions and eight prize-places in team competitions. Сonclusions. Unlike the traditional forms of study, the implementation of active methods, on example of training for an Olympiad, allows to form the professional skills and active realization of acquired knowledge, model the integral content of individual work, thus shifting the center of significance from the process of transferring, processing and assimilating information to independent creative activity. Such an approach can allow a student to achieve high results both during the competition at the student’s olympiad, and in the future in the practical activity of forming the person of a competitive specialist.Мета роботи – представити власний досвід застосування різних варіантів імітаційної технології при підготовці учасників студентських олімпіад з професійного циклу “інфекційні хвороби”. Основна частина. Розглянуто інноваційні методики викладання курсу інфекційних хвороб у вищій медичній школі, впроваджені авторами з метою підвищення ефективності навчання. Докладно висвітлені питання проведення медичних студентських олімпіад з навчальних дисциплін професійного циклу. Проаналізовано власний досвід застосування варіантів імітаційної технології: методів case-study, рольових ігор, “мозкової атаки”. За останні 5 років на базі студентського наукового гуртка кафедри інфекційних хвороб ДЗ “Дніпропетровська медична академя МОЗ України” пройшла підготовка 53 студентів-бакалаврів. З них 14 студентів брали безпосередню участь у змаганнях на щорічних всеукраїнських олімпіадах з інфекційних хвороб. Результатом плідної підготовки стало здобуття 6 призових місць в індивідуальних змаганнях і 8 призових місць у командних змаганнях. Висновки. На відміну від традиційних форм навчання, впровадження активних методів, на прикладі підготовки до олімпіади, дозволяє формувати професійні вміння і діяльну реалізацію набутих знань, моделювати цілісний зміст самостійної роботи, при цьому зміщується центр значущості з процесу передачі, переробки і засвоєння інформації на самостійну творчу діяльність. Саме такий підхід може дозволити студенту набути високих результатів як під час змагання на студентській олімпіаді, так і надалі у практичній діяльності при формуванні особистості конкурентоспроможного фахівця