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Journal Infectology

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Vol 14, No 5 (2022)
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https://doi.org/10.22625/2072-6732-2022-14-5

Original Research

5-13 773
Abstract

   Objective. To study the features of invasive aspergillosis (IA) due to A. non-fumigatus versus A. fumigatus in adult (≥ 18 years) recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2016-2021.
   Materials and methods. The study included 33 patients with IA caused by A. non-fumigatus (n = 20) and A. fumigatus (n = 13). A comparative analysis of cases of IA, the results of therapy and outcomes in patients after allo-HSCT in the RM Gorbacheva Research Institute was performed. Diagnostic criteria EORTC / MSGERC 2020 were used.
   Results. Invasive aspergillosis caused by A. non-fumigatus made up the majority (60.6 %) of IA cases with an identified pathogen registered in patients after allo-HSCT in the period from 2016 to 2021. The main etiological agents in the A. non-fumigatus group were A. niger in 13 (65 %) patients, A. flavus – in 4 (20 %). The median day of diagnosis of A. non-fumigatus IA
was + 110 days (17–2093), for A. fumigatus it was + 46 days (2–866) (p = 0.171). Overall 12-week survival was 55 % and 59.2 % in the A. non-fumigatus and A. fumigatus groups, respectively (p = 0.617). The majority of patients in both the A. fumigatus (n = 10, 77 %) and A. non-fumigatus (n = 16, 80 %) groups received voriconazole as initial antifungal therapy. Second-line
therapy was required in 2 (10 %) patients with A. non-fumigatus IA: liposomal amphotericin B and echinocandins with or with-out posaconazole, and 2 (15 %) patients in the A. fumigatus group: liposomal amphotericin B and voriconazole in combination with echinocandins. A comparative analysis showed that in patients from the two groups, none of the assessed signs (gender, age, underlying disease, disease status at the time of transplantation, time from diagnosis to allo-HSCT, source of hematopoietic stem cells, conditioning regimen, donor type, antifungal prophylaxis, cytomegalovirus reactivation, severe acute and chronic graft-versus-host disease) did not differ significantly.
   Conclusions. A. niger is the main causative agent of IA caused by A. non-fumigatus. Patients characteristics, their treatment and outcomes did not differ significantly between the A. non-fumigatus and A. fumigatus groups.

14-25 830
Abstract

   Aim: to build a predictive model for severe COVID-19 prediction in young adults using deep learning methods.
   Materials and methods: data from 906 medical records of patients aged 18 to 44 years with laboratory-confirmed SARS-CoV-2 infection during 2020–2021 period was analyzed. Evaluation of laboratory and instrumental data was carried out using the Mann-Whitney U-test. The level of statistical significance was p≤0,05. The neural network was trained using the Pytorch framework.
   Results: in patients with mild to moderate SARS-CoV-2 infection, peripheral oxygen saturation, erythrocytes, hemoglobin, total protein, albumin, hematocrit, serum iron, transferrin, and absolute peripheral blood eosinophil and lymphocyte counts were significantly higher than in patients with severe СOVID-19 (p< 0,001). The values of the absolute number of neutrophils, ESR, glucose, ALT, AST, CPK, urea, LDH, ferritin, CRP, fibrinogen, D-dimer, respiration rate, heart rate, blood pressure in the group of patients with mild and moderate severity were statistically significantly lower than in the group of severe patients (p < 0.001). Eleven indicators were identified as predictors of severe COVID-19 (peripheral oxygen level, peripheral blood erythrocyte count, hemoglobin level, absolute eosinophil count, absolute lymphocyte count, absolute neutrophil count, LDH, ferritin, C-reactive protein, D-dimer levels) and their threshold values. A model intended to predict COVID-19 severity in young adults was built.
   Conclusion. The values of laboratory and instrumental indicators obtained in patients with SARS-CoV-2 infection upon admission significantly differ. Among them eleven indicators were significantly associated with the development of a severe COVID-19. A predictive model based on artificial intelligence method with high accuracy predicts the likelihood of severe SARS-CoV-2 course development in young adults.

26-34 488
Abstract

   SARS-CoV-2 pandemic is now a global medical and social problem. Little is known about its impact on some vulnerable subgroups, such as immunocompromised patients. Therefore, there is still a strong interest in exploring the impact of SARS-CoV-2 infection among HIV-positive individuals worldwide.
   Aim of the study: to analyze immunological aspects of the deceased patients with HIV/COVID-19 coinfection.
   Materials and methods. We provided retrospective analysis of 258 patient’s electronic medical records. All patients were admitted to the Infectious diseases hospital № 2 with HIV / COVID-19 coinfection and died in May 2020 – February 2022. Standard immunological parameters were analyzed like CD4+, CD8+ counts and immunoregulatory index for different patient’s subgroups. Statistical data processing was provided by SPSS 17 version (allowable error E = 5 %).

   Results and discussion. The study demonstrated CD4+ and CD8+ reduction in HIV-infected with COVID-19. Late HIV-presenters didn’t display such phenomenon probably because of immune system exhaustion. COVID-19 itself in some cases could lead to immunodeficiency worsening due to depletion of T cell populations in HIV-patients on effective antiretroviral therapy.
   Conclusion. Comprehension of different immunological characteristics in HIV / COVID-19 coinfected patients could improve therapeutic approaches for this challenging cohort.

35-40 3303
Abstract

   Objective: to assess the efficacy of COVID-19 vaccination against in organized group.
   Materials and methods: A total of 122 adults, employees of a higher education institution participated in the study. Study participants were observed prospectively and filled out a questionnaire where they indicated their age, presence of chronic diseases, history of COVID-19 and vaccination status.
   Findings: the study participants were divided into two groups: 59 vaccinated (48.36 %) and 63 unvaccinated (51.64 %) individuals with no differences in age between the groups. There were significantly fewer confirmed cases of COVID-19 in the vaccinated group (р = 0,0008457, df = 1; χ2 = 11,138), significant differences (p = 0.0084; df = 4; χ2 =13.678) were observed in the number of cases among study participants based on their vaccination status.
   Conclusion: participants diagnosed with pneumonia were 75 % unvaccinated (p = 0,00729; df = 1; χ2 = 7,2). All hospitalized study participants were unvaccinated (p = 0,004678; χ2 =8,0). None of the vaccinated participants needed respiratory support (p = 0,0455; df = 1; χ2 = 4,0). Chronic disease in vaccinated subjects made a significant (p = 0,04563; df = 2; χ2 = 6,1743) impact on COVID-19 severity.

41-50 493
Abstract

   Objective. To assess the impact of CMV and HHV-6 reactivation on the course of early post-transplant period in patients with hematologic malignancies.
   Materials. Retrospective analysis of medical records of 339 patients with hematologic malignancies who received hematopoietic stem cell transplantation (HSCT) was performed, and markers of CMV and HHV-6 infections were detected (specific IgG, EIA). Blood and other materials from HSCT recipients were tested (PCR) for viral DNA in early post-transplant period (up to Day 100).

   Results. Reactivation of viral infections after HSCT was discovered in 177 patients (52,2 %): CMV-infection was detected in 23 %, HHV-6 in 17,4 %, CMV+HHV-6 in 11,6 % of HSCT recipients. CMV DNA was predominantly identified in blood, while HHV-6 DNA was more frequently discovered in GIT mucosa and bone marrow. 40 % of 99 patients with HHV-6 reactivation had concomitant CMV+HHV-6 reactivation. In this group, the clinical manifestation of infections was registered significantly more frequently. Febrile neutropenia was more frequent in HSCT recipients with CMV reactivation, sepsis and graft hypofunction were diagnosed more frequently in presence of HHV-6 and predominantly HHV-6+CMV infections. The direct correlation (using Spearman’s method) between CMV and HHV-6 reactivation and terms of leukopoiesis recovery, engraftment terms, and transplant hypofunction was revealed. An impact of herpetic infections reactivation on the graft hypofunction and late recovery of leukopoiesis was confirmed using the logistic regression; its impact on the chimerism was revealed. In 72 % of cases, the graft failure in early post-transplant period occurred in patients with herpetic infections reactivation.
   Conclusion. HHV-6 and CMV reactivation in the early period after HSCT correlates with terms of leukopoiesis recovery, contributes to development of complications, and is an additional factor aggravating the course of the post-transplant period.

51-59 677
Abstract

   According to the World Health Organization, sustained virological suppression of 90 % should be achieved among children and adolescents living with HIV / AIDS, which makes it important to assess the prevalence of virological failure of antiretroviral therapy.
   The aim of this study was to determine the prevalence of virological failure and the clinical factors associated with it, as well as therapeutic drug monitoring in groups divided by the viral load level among children and adolescents with HIV.
   Materials and Methods: A retrospective analysis of the medical records of 184 children and adolescents receiving antiretroviral therapy and registered at the Irkutsk Regional Center for the Prevention and Control of AIDS and Infectious Diseases, Irkutsk, was carried out. The study included 172 children aged 1-18 years with perinatal HIV infection. Patients were divided into groups depending on the level of viral load: group 1 – 21 patients with viral load > 1000 copies/ml of plasma, group 2 – 42 patients with viral load 50– 1000 copies/ml of plasma, group 3 – 109 patients with undetectable viral load (< 50 copies/ml). All patients underwent standard tests in accordance with clinical guidelines for the treatment of HIV infection in children, as well as therapeutic drug monitoring.
   Results. Against the background of ongoing antiretroviral therapy, a significant number of patients 21 / 172 (12,2 %) experienced virological failure. The proportion of children and adolescents with incomplete suppression of HIV replication is 42 / 172 (24,4 %). Statistically significant differences were obtained by changing the ART regimen (p = 0,031). In the first group, the proportion of patients who changed the therapy regimen is 7 / 21 (33,3 %), which is two times less than in the group with a zero viral load of 70 / 109 (64,2 %). There are differences in the proportion of children and adolescents with zero concentrations of ritonavir and lopinavir (p = 0,020 and p = 0,012) in the three compared groups. The distribution of patients with zero concentrations was as follows: for ritonavir in the first group 3 / 17 (17,6 %), in the second – 8/37 (21,6 %), in the third group – 4/80 (5 %); for lopinavir – 4/17 (23,5 %), 6/36 (16,7 %), 3/80 (3,8 %), respectively.
   Conclusion. This study demonstrates that the prevalence of virological failure among children and adolescents receiving ART remains high. To achieve sustained virological suppression in children and adolescents taking a protease inhibitor regimen, adherence to therapy must be increased. As one of the methods for assessing adherence, therapeutic drug monitoring can be used.

60-68 695
Abstract

   The aim of the analysis was to describe the results of administration of pan-genotype antiviral therapy (glecaprevir / pibrentasvir, GLE / PIB) in real-world setting in three clinical centers in St. Petersburg within the city program for the treatment of chronic hepatitis C.
   Materials and methods. A retrospective analysis of the GLE / PIB usage of in the period from 2019 to 2022 within the city program for the treatment of chronic hepatitis C in St. Petersburg was carried out.
   Results. The analysis included 464 patients treated in three clinical centers of St. Petersburg: St. Petersburg State Medical Institution “Clinical Infectious Diseases Hospital named after S. P. Botkin”, St. Petersburg State Medical Institution “Center for the Prevention and Control of AIDS and Infectious Diseases” and the Clinic of Infectious Diseases of the Military Medical Academy named after S. M.Kirov”. Overall 452 out of 464 patients (97 %) achieved SVR12. According to the duration of treatment, SVR12 rates were the following: 8 weeks – 97.7 % (419 / 429), 12 weeks – 92.9 % (26 / 28) and 16 weeks – 100 % (7 / 7). The effectiveness according to fibrosis stage was as follows: F0 – 97 % (142 / 146), F1 – 100 % (74 / 74), F2 – 100 % (59 / 59), F3 – 98 % (57 / 58), F4 (CP-A, B) – 94 % (118 / 125). SVR12 according to HCV genotypes and subtypes was the following: genotype 1b – 100 % (63 / 63), genotype 1a – 91 % (21 / 23), genotype 1 unspecified – 100 % (23 / 23), genotype 2 – 98 % (50 / 51), genotype 3 – 97 % (292 / 301). In patients with an indeterminate genotype, the efficacy was 100 % (7 / 7). Antiviral therapy was well tolerated, there were no cases of discontinuation of therapy, as well as cases of the development of serious adverse events.

   Conclusion. GLE / PIB has demonstrated high effectiveness in the real-world setting in patients infected with prevalent genotypes of HCV, including those with genotype 3 and compensated liver cirrhosis. The results of our analysis fully correspond to the data obtained earlier in clinical trials and
real-world setting.

Pharmacoeconomics

69-77 567
Abstract

   One of the main causes of acute gastroenteritis in children under 5 years of age is rotavirus infection (RVI). Vaccines against RVI significantly reduce the incidence.
   Aim. To evaluate the cost-effectiveness of mass vaccination of children with a 5-valent RVI vaccine in the Russian Federation.
   Materials and methods. The assessment was carried out using modeling based on published data on the effectiveness of the vaccine and epidemiological indicators in the Russian Federation. The analysis was carried out from the perspective of the health care system and society as a whole with a 5-year horizon. The cost of RVI therapy corresponded to the compulsory health insurance tariffs for St. Petersburg for 2022, the price of 1 dose of the vaccine was the registered price, including VAT. Costs and life expectancy, taking into account quality, were discounted at 3.5 % per year.
   Results. Given the assumptions made, routine vaccination will prevent an average of 468,637 cases of RVI over 5 years. Avoided direct medical costs, i. e. RVI treatment costs will amount to 53,4 %, and lost income due to temporary disability – 46,6 % of the total avoided costs. At the same time, the volume of avoided costs is 61,4 % due to a decrease in morbidity in the vaccinated population, and 38.6 % due to the development of a indirect effect. The predicted avoided costs per 1 vaccinated person is 2,975 thousand rubles. From a societal perspective, the cost-effectiveness of the Rota-V-Aid vaccine will be 364,813 thousand rubles / QALY (quality-adjusted life year), and from a healthcare perspective – 1726,399 thousand rubles / QALY. Thus, in both cases, the cost-effectiveness of RVI vaccination will not exceed the generally accepted threshold of willingness to pay, equal to three times the gross domestic product per capita in the Russian Federation (according to data for 2021 – ~2,7 million rubles). The predicted cost-effectiveness of selective vaccination is significantly lower than that of mass vaccination.
   Conclusions. Mass vaccination of children with a 5-valent vaccine against RVI will not only reduce the incidence in the Russian Federation, but, taking into account the assumptions made, can also be considered as a cost-effective intervention.

Clinical Case

78-84 491
Abstract

   The clinical case describes the difficulties of differential diagnosis of polyneuropathy that developed after Gam-Covid-Vac vaccination on the background of combined infectious pathology (HIV infection, tick-borne borreliosis, COVID-19) in a young woman. It is shown that various infectious and non-infectious diseases with similar clinical symptoms (peripheral nervous system affliction) occurring simultaneously in one patient can significantly affect each other’s course and complicate the establishment of the true cause of polyneuropathy. It should be noted that in this example, the establishment of a final diagnosis was carried out collectively, by consensus, and was based on the effectiveness of etiotropic (antibacterial) treatment, which in fact was an ex juvantibus therapy option, which made it possible to establish the most probable etiology of polyneuropathy – tick-borne borreliosis. In turn, HIV infection and possibly vaccination, according to the authors, could cause immunosuppression, which affected the degree of dissemination of Borrelia burgdorferi. It is also likely that the insufficient immune response in combination with the cascade plasma filtration session affected the initial dubious results of the serological tests, which further complicated the diagnosis.

85-89 623
Abstract

   The global outbreak of the new coronavirus infection COVID-19 is still ongoing, leading to coinfections such as malaria and COVID-19 and others. As evidenced by the increase in various reports of coinfections. In recent years, Uzbekistan has achieved epidemiological stability for malaria and in 2018 received an official World Health Organization certificate confirming the country’s “malaria-free” status. At the present stage during the COVID-19 pandemic, imported malaria from abroad is relevant for our republic and, therefore, there is a constant danger of renewed transmission from imported cases. In this article presented the clinical case of coinfection of COVID-19 and malaria in a patient. From the epidemiological data, the patient was a citizen of Cameroon. During treatment of coronavirus infection, the patient noted intermittent chills all over the body and sweating, clinical symptoms of tropical malaria began to appear. Microscopy of a thick drop and a thin blood smear confirmed the presence of Pl. falciparum. The patient was prescribed antimalarial therapy with mefloquine, resulting in clinical recovery.

90-100 546
Abstract

   The advent of the COVID-19, specialists are increasingly encountering previously unknown pathological conditions in their practice. For some time, we have believed that COVID-19 in children is most often mild and asymptomatic. However, with the passage of time and the accumulation of the experience, it became obvious that the new infectious disease it will be quite severe in children. Differential diagnosis of multiple organ disorders in children during the COVID-19 pandemic should be primary carried out with the Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C), as well as Long-COVID-19. According to published data, the manifestations of these conditions are due to frequent lesions of the gastrointestinal tract (60–100 %), cardiovascular (80 %), nervous (29–58 %) and respiratory (21–65 %) systems. At present, there is no exact idea of these pathological conditions, the criteria for their diagnosis and the tactics of managing children, not only at the stage of diagnosis, but also at the stage of observation. The authors present a diagnostically complex clinical case describing the development of multiple organ damage in a 7-year-old child after contact with a mother who was sick with COVID-19. The data on the course features, the results of the examination and the difficulties of differential diagnosis of this case with other diseases with a similar clinic are summarized.

101-108 550
Abstract

   The risk of severe type I diabetes mellitus in children with new coronavirus infection (COVID-19) is extremely high, which is associated with a high risk of intracranial hypertension, cerebral edema and multiple organ dysfunction syndrome. On the example of a clinical case, the features of the course of diabetic ketoacidosis and intensive care measures in children with COVID-19 were considered. The main data of the history and clinical and laboratory examination are reflected, special attention is paid to the applied aspects of therapy, it was noted that with a severe course of a new coronavirus infection and diabetic ketoacidosis, the risk of developing cerebral injury, acute kidney injury and thromboembolic complications is quite high, which may require artificial lung ventilation for the purpose of cerebral protection, renal replacement therapy and the use of anticoagulants. The new coronavirus infection is a risk factor for the severe course of diabetic ketoacidosis in children with type I diabetes, regardless of the age of the child, which is the basis for clinical alertness in order to timely identify and treat potential life-threatening complications.

109-115 2327
Abstract

   Whooping cough remains a life-threatening infection, especially for unvaccinated young children. The article describes a case of severe and non-smooth course of whooping cough in an unvaccinated girl of 4 months of life from the family hearth of whooping cough and COVID-19. There were cases of COVID-19 and whooping cough in adults in the family, occurring under the mask of a mild respiratory infection, not verified before they were detected in a child and did not require hospitalization. The combined course of two infectious diseases COVID-19 and whooping cough in a 4-monthold unvaccinated girl contributed to the prolongation of the duration of whooping cough, prolonged release of SARS-COV-2 RNA, the late appearance of hematological changes typical of whooping cough, the development of respiratory delays and re-hospitalization of a patient with prolonged respiratory support. In the context of the COVID-19 pandemic, the coverage of routine vaccination has significantly decreased, as a result of which children of the first years of life have become more vulnerable to vaccine-controlled infections, which causes the risk of combined infections.

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ISSN 2072-6732 (Print)