Pre-exposure prophylaxis, a new approach for HIV prevention: experience from the HIV Center of the Military University Hospital Prague.

AIMS: To present our experience with pre-exposure prophylaxis (PrEP) at the HIV Center of the Military University Hospital Prague, to characterize a set of PrEP candidates, to assess the efficiency and safety of PrEP and to measure the incidence of sexually transmitted diseases (STDs) in the studied cohort. MATERIAL AND METHODS: In total, 99 PrEP candidates (98 men who have sex with men and one woman) were monitored during an 18-month period. An initial examination included acquiring a history, performing a physical examination, screening for HIV (serology) and other STDs and performing renal function tests. RESULTS: In total, 81 candidates (in the cohort of 99 candidates) received PrEP. During the course of the 18-month period, none of the clients were newly infected with HIV, and no side effects of the provided medication were recorded. A total of 21% of the 99 PrEP candidates were initially tested positive for STDs, including two clients with HIV. A total of 14% of the 81 PrEP clients contracted an STD during the monitoring period. CONCLUSIONS: Experience amassed at the HIV Center of the Military University Hospital Prague over an 18-month period documented the demand for PrEP, assessed PrEP efficacy, indicated good tolerance and suggested that PrEP played a role in the decline in the HIV incidence in the Czech Republic. In addition, several new HIV cases and cases of other asymptomatic STDs were also detected.

Data from the first wave of Covid-19 from the Central Military Hospital, Prague, Czech Republic.

AIMS: To process data from the first wave of Covid-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) collected in the Infectious Diseases Clinic (IDC) of the First Faculty of Medicine and Central Military Hospital, Prague. To analyse some clinical, diagnostic and therapeutic aspects of Covid-19 in the context of the Czech Republic and to compare them with the data from the most recent literature. PATIENTS AND METHODS: This retrospective study analysed data on patients admitted to the IDC between 12 March 2020 and 5 May 2020. The study cohort included 53 patients with Covid-19, 25 females and 28 males, with an average age of 57 years. The parameters analysed were clinical symptoms, average length of hospital stay, complications, and death. Additional data concerned the age, weight, smoking habits, history of comorbidities, and selected laboratory results.  These data were compared between groups of patients differing in severity of the course of Covid-19. Finally, imaging findings, serology results, and therapy outcomes were studied. Statistical analysis was performed using the SigmaStat software. RESULTS: Eleven (20.8%) patients had a mild course of the disease, 16 (30.2%) patients had a moderate course, 22 (41.5%) patients had a severe course, and four (7.5%) patients had a critical course. The study patients presented with the following clinical symptoms: fever in 88.5% of cases, cough in 84.6% of cases, difficulty breathing in 77.4% of cases, diarrhoea in 23.1% of cases, chest pain in 17.3% of cases, and anosmia in 11.5% of cases. The average length of hospital stay was eight days. The most common complication was a bacterial superinfection, reported in 17 (32.1%) study patients. The overall case fatality rate for Covid-19 in our study was 5.7%. The average age of the study cohort was 57 years, and patients with a severe course of the disease were of older average age than those with a less severe course of the disease (p < 0.05). The predominant comorbidities were hypertension and diabetes mellitus. The analysis of the baseline laboratory data showed significant differences between the groups of patients differing in severity of the course of Covid-19 in CRP, procalcitonin, and d-dimers but not in lymphocyte count. High resolution computed tomography (HRCT) scan of the lungs was performed in 22 patients, and 21 of them had typical findings for Covid-19. The average MuLBSTA score for Covid-19 pneumonia severity in our study cohort was 11.5 points and was not associated with the severity of the course of the disease. Serology tests were performed in 43 study patients, with 29 (67.4%) of them turning out positive in the first test and other five (11.6%) testing positive when retested. Hydroxychloroquine (HCQ) was given experimentally as monotherapy or in combination with azithromycin (AZI) to 24 (45.3%) patients. Two patients on HCQ therapy also received inosinum pranobexum (isoprinosine) for severe lymphopenia, one patient received convalescent plasma, six patients were given AZI alone, and one patient was treated with inosinum pranobexum alone. Altogether 37.7% of study patients were prescribed other antibiotics for confirmed or suspected bacterial superinfection. Standard clinical and pharmaceutical care was provided to patients with particular focus on the safety of off-label drug use. HCQ was with drawn in three patients due to a prolonged corrected QT interval (QTc). CONCLUSIONS: In the first wave of the SARS-CoV-2 epidemic, our study patients showed comorbidities and risk factors which are consistent with the international literature, but the course of the disease was mostly moderate to severe, with a low proportion of critically ill patients and fatal outcomes. As soon as new information became available, new diagnostic and therapeutic options were introduced into routine practice. Based on our experience, we are well prepared for a possible second wave of SARS-CoV-2 in terms of the diagnostics, but the therapeutic options still remain very limited.

Bacteremia due to Staphylococcus aureus - the importance of appropriate management.

Staphylococcus aureus bacteremia (SAB) is the most common cause of severe bloodstream infections with high incidence and lethality. The diagnosis of SAB must be followed by an appropriate diagnostic and therapeutic management. The aim of the study was to identify clinical and epidemiological characteristics of SAB cases treated in the Central Military Hospital Prague and to assess compliance with the guidelines for diagnosis and thera-py. A total of 65 patients with S. aureus blood culture positivity were enrolled in the retrospective study. Sixty SAB cases (92%) were caused by MSSA strains, and MRSA strains were detected in five patients (8%). The source of the infection was confirmed in 83% of patients. The average case fatality rate in the study cohort was 28%. The analysis of the quality of care suggested both diagnostic and therapeutic insufficiencies in 65% of SAB patients. Overall, the result of the study supports the importance of the role of infectious disease specialists played in the bedside management of patients with SAB.

A new definition of sepsis (Sepsis-3) - aims, advantages, and controversies.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Over the last decades, the approach to sepsis is evolving dramatically, mainly as a result of a rapid increase in the knowledge of its epidemiology, physiopathology, and management. In this context, the new international criteria and definition for sepsis, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), were introduced in 2016. The criteria were established consensually by the Task Force which consisted of experts from the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. The main goal is the expansion of awareness of the professional public about this medical condition with a high fatality rate, particularly when not diagnosed and treated early. Sepsis-3 should also serve as a benchmark for future preclinical and clinical research, development of new diagnostic methods, and the terapy of patients with sepsis and septic shock.

Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis.

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA(2)) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA(2) and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA(2) were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA(2) activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA(2) activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA(2) activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

Incidence, immunological and clinical characteristics of reactivation of latent Toxoplasma gondii infection in HIV-infected patients.

To determine changes in incidence of reactivation of Toxoplasma gondii infection, manifesting as toxoplasmic encephalitis, and to assess the immunological mechanisms controlling reactivation in HIV-infected patients, a Czech cohort of 502 HIV/T. gondii co-infected patients was followed for 2909·3 person-years. The incidence of toxoplasmic encephalitis between the periods before and after the introduction of combination antiretroviral therapy (cART) was compared. Toxoplasmic encephalitis was diagnosed in 21 patients. In those patients the geometric mean value of CD4+ T lymphocytes was 12·6 times lower than in patients with non-reactivated T. gondii infection but an additionally significant decline in CD8+ T lymphocytes (3·3-fold) and natural killer cells (4·3-fold) was observed. This confirms the significance of these parameters. A twelvefold decrease in Toxoplasma reactivation incidence (40·2 vs. 3·4/1000 person-years) between monitored periods was seen. In the cART era, Toxoplasma reactivation was observed only in patients with unrecognized HIV infection or refusing therapy.

[Immune response in the pathogenesis of hepatitis C virus infection]. / Imunitní odpoved v patogenezi infekce virem hepatitidy C.

The pathogenesis of hepatitis C virus (HCV) infection is regulated by the host immunity and several metabolic factors affecting liver metabolism, including oxidative stress, insulin resistance, and hepatic steatosis. Both innate and adaptive immunity play an important role in HCV infection. Cytotoxic lymphocytes have a crucial role in viral eradication or viral persistence. Major cause of viral persistence during HCV infection could be the development of a weak antiviral immune response to the viral antigens, with corresponding inability to eradicate infected cells.

[A case of tuberculous meningitis associated with persistently reduced CD4+ T lymphocyte counts]. / Prípad tuberkulózní meningitidy provázené perzistujícím snízením CD4+ T lymfocytu.

A case history is presented of a 35-year-old man admitted to the hospital with tuberculous meningitis complicated by caseous necrosis of cervical lymph nodes and thrombosis of the left jugular vein. Another complication, malignant brain edema, appeared more than one year after discharge from hospital and was managed at the neurosurgery department. The most probable cause was a post-inflammatory obstruction of the cerebrospinal fluid pathways. A challenging finding, observed repeatedly while in hospital and at follow ups after discharge, was medium significant CD4+ T cell lymphopenia, with the lowest CD4+ T cell count of 308 cells/µl of peripheral blood. For this reason, the patient was screened several times for anti-HIV antibodies, but always with a negative result. Active tuberculous infection was considered as another possible reason behind persistent CD4+ T cell lymphopenia. However, imaging and laboratory analyses were not suggestive of tuberculosis. The patient is currently in good condition and his CD4+ T lymphocyte counts returned to normal at seven years of follow-up. It is underlined that patients after tuberculous meningitis need a long-term follow-up.

[Toxic shock syndrome]. / Syndrom toxického soku.

The authors present an up-to-date review of toxic shock syndrome (TSS) - a life-threatening condition where toxins of the Gram-positive bacteria Staphyloccocus aureus and Streptococcus pyogenes play a key role in the pathogenesis. The authors provide insight into the epidemiology and pathogenesis of the disease and point out the relevant patient history data and clinical signs and symptoms that may indicate progression of TSS. Last but not least, the state of the art diagnostic and therapeutic approaches to early and full blown TSS are summarized. Case reports are presented to illustrate two different etiological forms of this relatively rare nosological entity.

Impact of the COVID-19 pandemic on competitive swimming performance.

OBJECTIVE: This article aims to conduct a comparison of swimming performance during short course national championships (25-m) from 2019 and 2020 (before and during the pandemic). MATERIALS AND METHODS: The data points from the championships will be compared for 5 European countries: Poland, Spain, Russia, Turkey, and Denmark. Times achieved in the finals were calculated by the analysis of variance. Post hoc pairwise comparison analysis was performed using Tukey's test. The analysis plan included the assessment of the main effects and the effect of interactions in the groups of women and men. The strength of the effect was expressed by the partial eta-squared ratio. RESULTS: Two main trends were observed in the results. The first was a greater variation in the results in the group of men than in women (12-5 differences). The second was the development and improvement of sports performance in symmetrical strokes (69% improvement in recorded times measured during the pandemic, e.g., in Poland, women on 50-m breaststroke and butterfly Δ = 0.52, p <0.001 and Δ = 0.32, p = 0.034, men on 50-m and 100-m butterfly Δ = 0.34, p = 0.003 and Δ = 1.21, p <0.001). CONCLUSIONS: The main conclusion of our analysis is that the pandemic influenced the development of sports performance in symmetrical techniques, i.e., in breaststroke and butterfly.

Evaluation of potential biomarkers for the discrimination of bacterial and viral infections.

PURPOSE: Timely knowledge of the bacterial etiology and localization of infection are important for empirical antibiotic therapy. Thus, the goal of this study was to evaluate routinely used biomarkers together with novel laboratory parameters in the diagnosis of infection. METHODS: In this prospective study, 54 adult patients with bacterial infections admitted to the Department of Infectious Diseases were included. For comparison, 27 patients with viral infections were enrolled. In these patients, white blood cell (WBC) counts, differential blood counts, serum levels of procalcitonin (PCT), IL-1ß, IL-6, IL-8, IL-10, IL-12, TNF-α, IFN-γ, soluble CD14 (sCD14), heparin-binding protein (HBP), cortisol (Cort), and monocyte surface expression of TLR2, TLR4, HLA-DR, and CD14 were analyzed. Also, these biomarkers were evaluated in 21 patients with acute community-acquired bacterial pneumonia (CABP), as well as in 21 patients with pyelonephritis and urosepsis. RESULTS: The highest sensitivity and specificity (expressed as the area under the curve [AUC]) for bacterial infection were observed in serum concentration of PCT (0.952), neutrophil and lymphocyte counts (0.852 and 0.841, respectively), and serum levels of HBP (0.837), IL-6 (0.830), and Cort (0.817). In addition, the serum levels of IFN-γ and Cort were significantly higher and IL-8 levels were lower in CABP when compared to pyelonephritis or urosepsis. CONCLUSIONS: From the novel potential biomarkers, only PCT demonstrated superiority over the routine parameters in the differentiation of bacterial from viral infections. However, some of the novel parameters should be further evaluated in larger and better characterized cohorts of patients in order to find their clinical applications.

Gangrenous herpes zoster with multidermatomal involvement in a patient after kidney transplantation.

We present the case of a 66-year-old female after renal transplant with severe course of herpes zoster (HZ). Although HZ represents a common infectious complication of transplant patients, its variable manifestation and ability to disseminate warrants serious consideration. Prompt diagnosis and treatment are essential in preventing further spread and disastrous complications.

[Infectious complications of biological therapy]. / Infekcní komplikare biologické lécby.

Biological treatment represents a significant progress in the therapy of many serious diseases. Together with the growing knowledge of pathophysiology and subsequent development of new therapeutic agents, this progress will definitely lead to further expansion of biologics. Since biologics interfere with many mechanisms of host defence, which may sometimes be compromised by them, increased risk of infectious complications must be taken into account. Patients treated with biologics are prone to classical virulent infections (e.g. listeriosis, legionellosis and tuberculosis) and opportunistic infections such as progressive multifocal leukoencephalopathy. Furthermore, suppression of the immune response that is caused by biologics may lead to reactivation of latent infections such as tuberculosis or viral hepatitis B. Therefore, the knowledge of basic mechanisms by which biologics modify the immune response is important for a rapid clinical diagnosis of possible aetiology of infectious complications.

[Viral hepatitis B in a patient with follicular lymphoma treated with biological therapy]. / Virová hepatitida B u pacientky s folikulárním lymfomem lécené biologickou terapií.

Reactivation, recurrence or acute infection with hepatitis B virus (HBV) represent severe complications of biological therapy. Reported is a case of a 58-year-old female treated in the past with cytostatics and rituximab for follicular lymphoma, in whom HBV infection was detected during a follow-up of the contacts of her partner diagnosed with acute viral hepatitis B. At the beginning, the patient had a very high serum level of HBV DNA (4.3 × 108 IU/mL) and therefore she was treated with combined antiviral therapy (lamivudine and tenofovir). After 10 months, the serum level of HBV DNA decreased significantly (3,100 IU/mL) and the combined antiviral therapy was switched to monotherapy with tenofovir. Another 5 months later, the serum level of HBV DNA was only 950 IU/mL. This case demonstrates important clinical problems connected with HBV infection in immunocompromised persons.

Antiviral prophylaxis of neonatal herpes infection.

Herpes simplex virus (HSV) is considered to be one of the most frequent viral infectious agents in humans. Transmission of HSV from mother to foetus during pregnancy is uncommon with about 85% of transmission occurring perinatally, when neonates acquire HSV during vaginal birth from infected genital tract secretions. For women, who present with an episode of recurrent genital herpes several weeks before the expected delivery date, suppressive therapy with acyclovir or valacyclovir is recommended during the last 4 weeks of pregnancy. The study group consists of 21 women with recurrent genital tract herpes, who delivered between the years 2007-2009 at the Department of Obstetrics and Gynaecology, University Hospital Na Bulovce. Women in the last month of pregnancy were administered prophylactic viralstatic treatment with acyclovir 3 x 400 mg per day orally until delivery. In this study, no patient showed signs of acute lesions and viral DNA was not detectable on PCR in vaginal secretions. One woman delivered by acute caesarean section following signs of foetal hypoxia during the first stage of labour, two women were delivered by forceps. No newborns showed signs of HSV neonatal infection. Antiviral prophylaxis in the last month of pregnancy in women with recurrent genital herpes infection is considered to be safe and effective in the prevention of vulvar lesions and in decreasing the incidence of caesarean sections in this group of women.

Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease.

The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1 ra) on admission. Furthermore, the CSF levels of IL-1 beta, IL-1 ra, IL-6, IL-8, macrophage inflammatory protein-1 beta (MIP-1 beta), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1 beta and IL-1 ra, IL-6, IL-8, and MIP-1 beta, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1 beta, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction.

[A case of acute hepatitis E acquired in the Czech Republic]. / Prípad akutní virové hepatitidy E získané v Ceské republice.

We report a case of 54-year-old female, who was diagnosed with acute viral hepatitis E with uncomplicated anicteric course of the infection. The patient did not have a specific travel history to endemic areas and the infection has been acquired in the Czech Republic. The epidemiologic history was remarkable only because she consumed undercooked pork meat. A differential diagnostic process of acute viral hepatitis in our conditions as well as problems of acute viral hepatitis E as an autochtonous infection in Western and Central Europe are discussed.

[Guidelines for the diagnosis and treatment of genital herpes in women]. / Doporucený postup pro diagnostiku a terapii genitálního herpesu u zen.

Presented are draft guidelines for genital herpes (GH) in women. The text is concerned with the incidence, clinical picture, diagnosis, prevention, prophylaxis and therapy of genital HSV infection. The aim is to provide valuable information on the approach to both initial and relapsing GH, with attention being paid to risk factors such as immunosuppression or pregnancy. Also mentioned are procedures to decrease the risk of vertical transmission of HIV infection and adequate measures to prevent disseminated neonatal herpes infection.

Antithrombin as a marker of severe acute hepatitis B.

BACKGROUND: Acute hepatitis B (AHB) can run a severe course, which sometimes leads to a fulminant disease with acute liver failure (ALF). Pro-coagulation factors are well-established markers of AHB severity, but less is known about the levels of anti-coagulation parameters in AHB. METHODS: In this study, we demonstrate that antithrombin (AT) plasma levels were associated with AHB severity in 161 patients. RESULTS: Nine (6%) patients had severe AHB (i.e. international normalized ratio [INR] ≥ 1.6 and total bilirubin ≥ 10 mg/dL). Coagulopathy (i.e. INR > 1.2 and/or AT < 80%) was observed in 65 (40%) AHB patients on admission. Low initial plasma AT levels (i.e. < 80%) were observed in 56 (35%) patients. In all, plasma AT levels decreased in 91 (57%) patients during their hospital stay. Both baseline and nadir AT levels were significantly lower in severe than in mild and moderate AHB. Moreover, the concentration of AT negatively correlated with INR, aspartate aminotransferase, and total and conjugated bilirubin levels. Interestingly, nadir AT levels positively correlated with the duration of hospitalization. CONCLUSIONS: These results indicate that plasma AT levels can be used as an additional marker of AHB severity.