Immunogenicity of the drug "Live intranasal vaccine for the prevention of pertussis" (GamLPV) with a single use in healthy volunteers

Introduction. A significant increase in the incidence of pertussis in the world, including among adolescents and adults, the prevalence of mild forms of the disease and asymptomatic carrier of bacteria B. pertussis, and the resulting need for mass revaccination of different age groups determine the demand for new vaccines against B. pertussis. In N.F. Gamaleya Federal Research Center for Epidemiology and Microbiology, a live intranasal pertussis vaccine for the prevention of pertussis (GamLPV) has been developed. The GamLPV vaccine underwent preclinical studies that proved its safety and effectiveness in experiments on small laboratory animals and nonhuman monkeys. Safety of vaccine is shown in clinical studies on healthy volunteers.The aim of the study is to assess the immunogenicity of different doses of the drug GamLPV when first used in healthy volunteers.Materials and methods. The study was conducted as randomized placebo-controlled, blind trial with consistent volunteer inclusion and dose escalation. Study ID in clinicaltrials.gov database: NCT03137927 (A Phase I Clinical Study of a GamLPV, a Live Intranasal Bordetella Pertussis Vaccine). The following parameters of humoral and cellular immune responses were assessed in dynamics: levels of specific IgM, IgG and IgA antibodies in blood serum of volunteers and the number of cytokines interleukin-17, tumor necrosis factor-α, interferon-γ produced after specific induction in vitro of blood mononuclears of vaccinated volunteers. Dynamics of attenuated bacteria persistence in nasopharynx of vaccinated volunteers was evaluated.Results. Intranasal vaccination of volunteers with the drug Gam LPV resulted in the formation of a specific humoral (IgG and IgA) and cellular immune response. The dose-dependent nature of immunoglobulin and cytokine production was shown. Attenuated bacteria persisted for a long time in the nose/oropharynx of vaccinated volunteers.Discussion. Good tolerability of all tested doses of the drug justifies the choice for further investigation of a vaccine dose equal to 4 × 109 CFU. At the next stage, the safety and immunogenicity of two-time vaccination of volunteers will be studied.

Fear of Medical Staff: The Importance of Stigmatization during the COVID-19 Pandemic: Letter to the Editor

Introduction: During the COVID-19 pandemic, although hospital staff cared for patients, they were recognized in the community as an asymptomatic carrier and people were afraid and anxious about them. To the extent thateven the families of hospital staff experienced this social stigma, and many people cut off contact with them. In addition to the stigma that medical staff received from people during the COVID-19 pandemic, many people were stigmatized and feared that as an asymptomatic carrier they would endanger the health of their families and those around them. For this reason, they tried to limit social communication and be more present at home and at work. Hospital staff were among the first to deal with the deadly virus and relinquish their physical health. Many nurses and physicians stay awake for long hours to save the lives of patients with COVID-19. Unfortunately, we have seen people fear and avoid the hospital staff, which has led to increased burnout and depression in the medical staff. For this purpose, it is necessary to take measures to socially motivate the medical staff of hospitals by the Ministry of Education and Health.

Numerical study of Zika model as a mosquito-borne virus with non-singular fractional derivative

Zika virus infection, which is closely related to dengue, is becoming a global threat to human society. The transmission of the Zika virus from one human to another is spread by bites of Aedes mosquitoes. Recent studies also reveal the fact that the Zika virus can be transmitted by sexual interaction. In this paper, we use the fractional derivative with Mittag–Leffler non-singular kernel to study Zika virus transmission dynamics. This fractional is also known as the Atangana–Baleanu Caputo (ABC) derivative which is employed for the resulting system of ordinary differential equations. We investigate the proposed Zika virus model by using the Legendre spectral method. The model parameters are estimated and validated numerically by investigating the effect of fractional order exponent on various cases such as Susceptible human, infected human, asymptomatic carrier, exposed human, and recovered human. Numerical results obtained with the proposed method have been compared with exact solutions, showing in all parameters a very satisfactory agreement.

Optimal strategies for carrier screening and prenatal diagnosis of α- and β-thalassemia

The thalassemias are inherited quantitative disorders of hemoglobin synthesis with a significant worldwide burden, which result in a wide spectrum of disease from the most severe transfusion-dependent form to the mildest asymptomatic carrier state. In this article, we discuss the importance of carrier, prenatal, and newborn screening for thalassemia. We examine the rationale for who should be screened and when, as well as the current methodology for screening. Deficiencies in the newborn screening program are highlighted as well. With the advent of inexpensive and rapid genetic testing, this may be the most practical method of screening in the future, and we review the implications of population-based implementation of this strategy. Finally, a case-based overview of the approach for individuals with the trait as well as prospective parents who have a potential fetal risk of the disease is outlined.

Emergence of Invasive Fungal Rhinosinusitis in Recently Recovered COVID-19 Patients

Objective: The risk of invasive fungal rhinosinusitis is increased in Coronavirus disease 2019 (COVID-19) because of its direct impact in altering innate immunity and is further exacerbated by widespread use of steroids/antibiotics/monoclonal antibodies. The study aims to describe this recently increased clinical entity in association with COVID-19. Method: A prospective, longitudinal study including patients diagnosed with acute invasive fungal rhinosinusitis (AIFRS) who recently recovered from COVID-19 infection or after an asymptomatic carrier state. A single-center, descriptive study investigating demographic details, clinical presentation, radio-pathological aspects, and advocated management. Result: A total of 21 patients were included with a mean age of 49.62 years (SD: 14.24). Diabetes mellitus (DM) was the most common underlying disorder (90.48%), and 63.16% of all patients with DM had a recent onset DM, either diagnosed during or after COVID-19 infection. Nineteen patients (90.48%) had recently recovered from active COVID-19 infection, and all had a history of prior steroid treatment (oral/parenteral). Remaining 2 patients were asymptomatic COVID-19 carriers. Surprisingly, 2 patients had no underlying disorder, and 5 (23.81%) recently received the Covishield vaccine. Fungal analysis exhibited Mucor (95.24%) and Aspergillus species (14.29%). Most common sign/symptom was headache and facial/periorbital pain (85.71%), followed by facial/periorbital swelling (61.90%). Disease involvement: sinonasal (100%), orbital (47.62%), pterygopalatine fossa (28.58%), infratemporal fossa (14.29%), intracranial (23.81%), and skin (9.52%). Exclusive endoscopic debridement and combined approach were utilized in 61.90% and 38.10%, respectively. Both liposomal amphotericin B and posaconazole were given in all patients except one. Conclusion: A high suspicion of AIFRS should be kept in patients with recent COVID-19 infection who received steroids and presenting with headache, facial pain, and/or facial swelling. Asymptomatic COVID-19 carriers and COVID-19 vaccinated candidates are also observed to develop AIFRS, although the exact immuno-pathogenesis is still unknown. Prompt diagnosis and early management are vital for a favorable outcome.

Experience in genetic testing of hypertrophic cardiomyopathy using nanopore DNA sequencing

Aim. To investigate the application of the Oxford Nanopore Technologies’ third generation sequencing for the genetic testing of hypertrophic cardiomyopathy.Material and methods. The study involved 12 patients with hypertrophic cardiomyopathy aged 18 to 67 years (women, 9; men, 3). Using the PCR barcoding amplicons (SQK-LSK109) protocol, DNA libraries were created which contained long-range PCR fragments of the MYH7, MYBPC3, TNNT2, TNNI3 and TPM1 genes. The sequencing was performed using the MinION system by Oxford Nanopore Technologies (UK). Bioinformatic algorithms for data analysis included Guppy v.5.0.7, Nanopolish and Clairvoyante. The identified genetic variants were confirmed by Sanger sequencing.Results. Data on the complete sequence of the five major sarcomeric genes for hypertrophic cardiomyopathy were obtained. We found eight potentially disease-causing sequence variants in MYH7, MYBPC3 and TNNT2 genes by monomolecular sequencing. However, only three mutations p.Arg243Cys, p.Tyr609Asn, p.Arg870His in the MYH7 gene, and one mutation p.Lys985Asn in the MYBPC3 were confirmed by Sanger sequencing. Cascade screening of pathogenic variant p.Arg870His in the MYH7 gene was performed. We found one asymptomatic carrier.Conclusion. It appears that monomolecular sequencing technology is a feasible approach to identify mutations in patients with hypertrophic cardiomyopathy. Although improvement in accuracy of DNA sequencing, as well as optimization and simplification of bioinformatic algorithms for identification of the genetic variants are needed.

Transmission and Colonization of Pneumocystis jirovecii

Pneumocystis spp. was discovered in 1909 and was classified as a fungus in 1988. The species that infects humans is called P. jirovecii and important characteristics of its genome have recently been discovered. Important advances have been made to understand P. jirovecii, including aspects of its biology, evolution, lifecycle, and pathogenesis; it is now considered that the main route of transmission is airborne and that the infectious form is the asci (cyst), but it is unclear whether there is transmission by direct contact or droplet spread. On the other hand, P. jirovecii has been detected in respiratory secretions of hosts without causing disease, which has been termed asymptomatic carrier status or colonization (frequency in immunocompetent patients: 0–65%, pregnancy: 15.5%, children: 0–100%, HIV-positive patients: 20–69%, cystic fibrosis: 1–22%, and COPD: 16–55%). This article briefly describes the history of its discovery and the nomenclature of Pneumocystis spp., recently uncovered characteristics of its genome, and what research has been done on the transmission and colonization of P. jirovecii. Based on the literature, the authors of this review propose a hypothetical natural history of P. jirovecii infection in humans.

Identification of modifying copy number variations in healthy carriers of pathogenetically significant CNVs

Присутствие дополнительных хромосомных вариантов в геноме пациента или бессимптомное носительство аберрации может приводить к фенотипической вариабельности проявлений патогенетически значимой CNV. Высказана гипотеза, что сочетанное действие CNV оказывает модифицирующий эффект, который может быть кумулятивным или компенсаторным, и, соответственно, изменять риск, связанный с определённой CNV, что имеет принципиальное значение для медико-генетического консультирования. The presence of concomitant chromosomal variants in the genome of a patient or an asymptomatic carrier of aberrations may lead to phenotypic variability of pathogenetically significant CNV. It is supposed, that multiple CNVs has a modifying effect, which can be cumulative or compensatory. The risk associated with a particular CNV changes accordingly. This is of fundamental importance for genetic counseling.

Covid Reinfection versus Asymptomatic Carrier State: A Case Report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first discovered in China in December 2019, has been implicated in the current coronavirus disease 2019 (COVID-19) pandemic. Although much has been learned about the virus which peaked with the development of the vaccine, there is still a lot of unanswered questions. Maximum duration of positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) from symptom onset may be up to 3 months [1], however it is not known if the continued detection of the viral genome implies prolonged infectivity or presence of a non-viable virus [2]. Most people with COVID-19 develop antibodies after resolution of acute infection [2]. The exact duration of these antibodies in the body is unknown, but some studies have shown that both memory T-cells and B-cells can persist up to 6 to 8 months after acute SARS-CoV-2 infection [3]. These SARS-CoV-2 antibodies may confer some immunity to the person after the acute infection and have been associated with protection against subsequent infection in nonhuman primates by the same viral strain during the early recovery phase [4]. In humans, however, it is unknown to what extent this immune response indicates a protective immunity to subsequent infection with SARS-CoV-2 [5]. Few cases of reinfection have been documented worldwide with varying symptom severity; the first case in the US was published in January 2021 (reinfection occurred in June 2020) [5]. None of the initial cases reported the presence of SARS-CoV-2 antibodies at the time of reinfection. We present a patient who tested positive to SARS-CoV-2 RT-PCR twice in 10 months (Table 1). At both times, she was asymptomatic and the second time, she had coexisting SARS-CoV-2 antibodies.

Parental Origin of the RB1 Gene Mutations in Families with Low Penetrance Hereditary Retinoblastoma

Our aim was to identify RB1 alterations causing hereditary low penetrance retinoblastoma and to evaluate how the parental origin of an RB1 mutation affects its phenotypic expression. By NGS and MLPA, RB1 mutations were found in 191 from 332 unrelated retinoblastoma patients. Among patients with identified RB1 mutations but without clinical family history of retinoblastoma, 7% (12/175) were found to have hereditary disease with one of the parents being an asymptomatic carrier of an RB1 mutation. Additionally, in two families with retinoblastoma history, mutations were inherited by probands from unaffected parents. Overall, nine probands inherited RB1 mutations from clinically unaffected fathers and five, from mothers. Yet, we gained explanations of maternal “unaffectedness” in most cases, either as somatic mosaicism or as clinical presentation of retinomas in involution, rendering the proportion of paternal to maternal truly asymptomatic mutation carriers as 9:1 (p = 0.005). This observation supports an assumption that parental origin of an RB1 mutation influences the likelihood of developing retinoblastoma. Additionally, our study revealed a relatively high frequency of asymptomatic carriage of the RB1 mutations among the parents of retinoblastoma patients, highlighting the utmost necessity of molecular analysis among the probands’ relatives irrespective of their clinical status and family history of retinoblastoma.