Extracellular vesicles in infectious diseases - importance and perspectives.

Extracellular vesicles (EVs) are mother cell derived transport units released into the extracellular environment. They are a new pillar of intercellular communication as they carry nucleic acids, proteins, and other signalling molecules, protecting them from degradation in the extracellular environment until fusion of the vesicle with the target cell. The transport mechanism relies on surface structures involved in cell adhesion. It is well known that all cellular organisms are capable of producing EVs. Most human cells have this capability, and EVs can be detected in all body compartments. At the time of their discovery, EVs were considered as useless waste vesicles of marginal interest. Thanks to the newly described transport mechanisms of biologically active molecules, EVs are currently known to participate in a variety of homeostatic mechanisms. In infectious diseases, the most studied area is the modulation of the immune response, where they are seen as potential biomarkers, as their production or the content they carry can be altered under pathological conditions. For microbes, interactions at the pathogen-pathogen and pathogen-host level are at the forefront of attention. EVs also have potential for use as drug delivery systems and novel targets for pharmacotherapy.

Decreasing neutralization antibody levels following vaccination against SARS-CoV-2 in the elderly: an observational study in Southern Moravia, Czech Republic.

INTRODUCTION: Understanding the immune response after SARS-CoV-2 vaccination is essential to control the COVID-19 pandemic. Recent studies indicate that vaccine-induced humoral immunity may not be long-lasting and is weaker in the elderly. METHODOLOGY AND SAMPLE: At the turn of June and July 2021, 653 seniors (426 women and 197 men with a mean age of 74 years) were tested once for antibodies against SARS-Cov-2 in the South Moravian Region between 9 and 161 days after the second dose of vaccine (558 Pfizer -BioNTech, 28 Moderna, 36 AstraZeneca, 1 Johnson & Johnson). Samples of the whole capillary blood were tested in two point-of-care iCHROMA II immunofluorescence assays: (1) COVID-19 Ab against mix of SARS-CoV-2 nucleocapsid and spike proteins (IgM Ab, IgG Ab) and (2) COVID-19 nAb against S1-RBD protein (nAb). Results were analysed in relation to gender, age, vaccine type, and past COVID-19 disease. RESULTS: Our results show high variability in the antibody response but indicate an overall relatively weak and decreasing antibody response in the first six months after vaccination. Only 58.4% (95% CI: 54.6-62.3) of subjects had virus neutralizing antibodies (nAb). The level of nAb decreased with time from vaccination - at post-vaccination months 4 and 5, nAb were only detected in 41.1% (95% CI: 30.9-51.3) and 15.4% (95% CI: 1.5-29.3) of subjects, respectively. Vaccinees in older age groups, those vaccinated with AstraZeneca, and naive individuals showed a lower antibody response. CONCLUSION: The antibody response to SARS-CoV-2 vaccine in the elderly was relatively weak and decreased in the first six months after vaccination. Although humoral immunity is complex and cellular immune memory is a key element of the humoral response after exposure to the wild virus, our results suggest that vaccine-induced humoral immunity may not be long-lasting. The oldest koncenage groups who have not acquired natural SARS-CoV-2 infection are particularly at risk. This finding is relevant for adjusting vaccination strategies in selected population groups to include a booster dose. More research into the antibody response and the complex immune response after vaccination against SARS-CoV-2 over longer time is needed.

Progressive multifocal leukoencephalopathy - epidemiology, immune response, clinical differences, treatment.

Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system with very high mortality. It is caused by the JC virus with high seroprevalence, at up to 80%. Development of PML is typically opportunistic, particularly in acquired immunodeficiency syndrome, and usually affects patients with profound immunodeficiency. Furthermore, as a result of highly efficient immunosuppressive and immunomodulatory treatments in recent years, the number of PML cases has increased in the general population. In this article, the authors mention virological and epidemiological relationships and characteristic manifestations of PML. Possible relationships of humoral and cellular immunity are discussed and limited treatment options including prophylaxis are mentioned.

Fecal bacteriotherapy in the treatment of Clostridium difficile infection.

AIM: Using a prospective analysis to assess the success of faecal bacteriotherapy (FBT) in antibiotic-associated colitis due to Clostridium difficile. To analyse whether any of the factors according to which the treated patients can be categorized has a statistically significant effect on the therapeutic outcome. MATERIALS AND METHODS: During the 2-year study period (2015-2016), 71 patients received FBT. After treatment, the patients were followed up by means of clinic visits or by phone. If colitis did not recur within eight weeks of follow-up, the treatment was considered successful. RESULTS: The overall success rate was 76%, with statistically insignificant decline in recurrences. Subgroup analysis did not show any statistically significant difference in the success rate between the routes of administration, i.e. through a naso-enteral feeding tube and rectal enema. Likewise, there were no statistically significant differences in the success rate between the types of prior antibiotic therapy or between using fresh and cryo-stored stool suspension. No unexpected adverse event or lethality occurred during the study period. CONCLUSIONS: Faecal bacteriotherapy is a successful and safe therapeutic alternative for recurrent C. difficile infections.

[Hepatitis E--overview of the latest knowledge]. / Hepatitida E--prehled soucasných poznatku.

Hepatitis E (HE) is a ubiquitous infection, occurring both in developing and in developed countries. It is caused by the hepatitis E virus (HEV), a small, non-enveloped RNA virus. The reported incidence in the Czech Republic in 2013 was 2 cases per 100,000 inhabitants and the number of HE cases has been growing over the past years. Besides the long known fecal-oral transmission, zoonotic and blood product transmission of HEV has recently been observed in industrialized countries. Most infections are asymptomatic. Symptomatic infection may present as acute hepatitis with nonspecific flu-like symptoms and liver enzymes elevation. In immunocompromised patients, HEV can lead to chronic hepatitis E and can even cause acute liver failure in pregnant women. Several extrahepatic manifestations have also been reported. Antiviral therapy has been successfully used in chronic hepatitis E. The first vaccine available for clinical use is licensed in China so far.

[Campylobacteriosis at the Department of Infectious Diseases of the University Hospital Brno in 2011-2013: a retrospective study]. / Kampylobakteriózy na Klinice infekcních chorob Fakultní nemocnice Brno v letech 2011-2013: retrospektivní studie.

OBJECTIVE: To provide basic clinical, laboratory, and microbiological characteristics of adult patients with campylobacteriosis admitted to the Department of Infectious Diseases University Hospital Brno (UHB), in 2011-2013. MATERIALS AND METHODS: A retrospective analysis of clinical and laboratory parameters of 160 patients hospitalized with campylobacteriosis at the Department of Infectious Diseases, UHB from 1 January 2011 to 31 December 2013. RESULTS: There was no lethality or bacteremia reported in the study group of 160 adult patients (n=160) with campylobacteriosis. A more severe form of the disease with signs of systemic inflammatory response syndrome (SIRS) occurred in 24 patients, i.e. 15% of the study population. Transient mild to moderate leukocytopenia and thrombocytopenia were seen in 16 (10.0%) and 24 patients (15.0%), respectively, and seven patients (4.4%) had bicytopenia. The following factors correlated statistically significantly with the intestinal form of the disease and SIRS: age under 70 years (p=0.037), absence of arterial hypertension (p=0.044), immunosuppressive treatment (p=0.008), leukocyte count in the peripheral blood over 12.0×10(9)/l (p=0.023), and body temperature over 38.0 °C (p<0.001). Antibiotic treatment was used in 96.3% of patients with the intestinal form and in 100.0% of patients with SIRS. The average duration of antibiotic treatment was 8.8 and 9.3 days, respectively. Postantibiotic colitis due to Clostridium difficile occurred in seven patients (4.4%). There were no organ or autoimmune complications observed. CONCLUSIONS: Campylobacteriosis with SIRS occurs preferentially in persons under 70 years of age. Empirical antibiotic treatment is used too frequently without being adequately deescalated.

[Fecal bacteriotherapy for the treatment of recurrent Clostridium difficile colitis used in the Clinic of Infectious Diseases of the University Hospital Brno in 2010-2014 - a prospective study]. / Fekální bakterioterapie v lécbe rekurentní kolitidy zpusobené Clostridium difficile na Klinice infekcních chorob Fakultní nemocnice Brno v letech 2010-2014 - prospektivní studie.

INTRODUCTION: The aim of the study is to assess the efficacy of fecal bacteriotherapy in the treatment of Clostridium difficile colitis. MATERIALS AND METHODS: A prospective study of fecal bacteriotherapy in 80 adult patients hospitalized in the Clinic of Infectious Diseases, University Hospital Brno between 1 January 2010 and 31 December 2014. RESULTS: During the study period, 80 patients were treated with fecal bacteriotherapy. The majority of the study group received fecal bacteriotherapy via a nasojejunal tube (n=78) and two patients via a rectal enema. Six patients were instilled with 20 g of feces, with a success rate of 50 %. The outcomes of nine patients were unevaluable. In the rest of 65 patients, the success rate with 40 g of feces was 83.1 %. There were no severe adverse events or mortality associated with fecal bacteriotherapy. CONCLUSIONS: Fecal bacteriotherapy is a safe and effective treatment modality in Clostridium difficile colitis.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Epidemiological factors influencing the development of relapsing and severe Clostridium difficile infection.

INTRODUCTION: Clostridium difficile infection (CDI) is currently the most frequent cause of nosocomial infectious diarrhea in adults in the developed countries. The goal of the study was to evaluate risk factors for relapsing and severe CDI in a set of patients hospitalized at the Clinic of Infectious Diseases at the University Hospital Brno. MATERIALS AND METHODS: A retrospective analysis of epidemiological, clinical and laboratory data of 281 patients with proved CDI diagnosis hospitalized in the period from 1. 1. 2007 to 31. 12. 2010. RESULTS: Patient age over 65 is a risk for severe CDI (OR 2.95, p < 0.001) and extends hospitalization at the first episode of CDI by about 3.2 days on average. Patients with 2 or more comorbidities (p < 0.05) or with a history of recent hospitalization (p 0.001) are at risk for both relapsing CDI and severe CDI. The use of proton pump inhibitors may increase the number of relapses (OR 1.94, p < 0.05). If the CDI symptoms appear within 7 days of taking antibiotics, there is a greater risk of relapse (OR 2.32, p < 0.05). If the symptoms occur after a longer period, a mild or moderate course of the disease can be expected (OR 0.31, p < 0.05). CONCLUSIONS: To determine the risk level for development of relapsing or severe CDI, focus on risk factors from the patients medical history and their clinical and laboratory status is appropriate at the outset of CDI patients treatment. An early intensive monitoring of vital functions and administration of aggressive treatment can reduce complications, mortality and relapses of CDI.

[Infections caused by non-typhi serovars of Salmonella at the Infectious Diseases Clinic of the University Hospital Brno in 2011-2013]. / Infekce zpusobené netyfovými sérovary salmonel na Klinice infekcních chorob Fakultní nemocnice Brno v letech 2011-2013--retrospektivní studie.

INTRODUCTION: The aim of the study is to describe the basic clinical, laboratory, and microbiological characteristics in adult patients with salmonellosis hospitalized at the Infectious Diseases Clinic of the University Hospital Brno in 2011-2013. MATERIALS AND METHODS: A retrospective analysis of clinical and laboratory parameters of 161 patients hospitalized at the Infectious Diseases Clinic of the University Hospital Brno from 1 January 2011 to 31 December 2013. RESULTS: Invasive salmonellosis was seen in 22.4% of the study group. The overall lethality rate reached 3.1%. Treatment with antibiotics was used in 93.8% of patients. Transient mild to moderate leukocytopenia was reported in 4.3% of patients and thrombocytopenia in 9.3% of patients. Transient changes in white blood cells as well as in the thrombocyte count were not clinically important. Long-term treatment with proton pump inhibitors is a risk factor for salmonellosis (p=0.128), but not for invasive salmonellosis. Long-term use of opioids (p=0.003) and/or acetylsalicylic acid (p=0.015) is a risk factor for invasive salmonellosis. Other risk factors for invasive disease are: age over 70 years (p=0.011), arterial hypertension (p=0.004), disease duration of less than three days (p=0.006), serum creatinine level above 250 µmol/l (p=0.01), peripheral leucocyte count above 12x10(9)/l (p=0.001), and body temperature above 38 °C (p=0.001). Hypokalemia does not represent a risk factor for invasive salmonellosis. CONCLUSIONS: Aged patients on long-term opioids or acetylsalicylic acid, with disease duration of less than three days, and meeting the criteria for systemic inflammatory response syndrome are at the highest risk for invasive salmonellosis. Empirical antibiotics are prescribed too often and the treatment is not properly de-escalated.

[Pathophysiology and pathogenesis of Salmonella sepsis]. / Patofyziologie a patogeneze salmonelové sepse

The authors present a review of current knowledge about complex pathogenetic and pathophysiologic mechanisms involved in the development of sepsis in salmonellosis. Mechanisms such as lipopolysacharide-induced NOD-like receptor activation, escaping lysosomal degradation, intracellular replication niche formation, cytoskeleton reorganization, proapoptotic mechanism induction, changes in cytokine levels (IL-1ß, TNF-α) and function of omptin proteases are discussed.

[A case report of ocular complications of leptospirosis]. / Kazuistika ocní komplikace leptospirózy.

Ocular complications are very frequent in leptospirosis and may develop in both the acute (bacteriemic) and the second (immunologic) phases of the disease. A delayed onset of these complications, even after months or years, is also possible. Keratoconjunctivitis and panuveitis belong to the most frequent signs. Targeted search for patients suspected of having leptospirosis and regular ophthalmological examinations even after cure of the acute illness may lead to early detection of ocular complications and to their specific treatment. Presented are a case report of complicated uveitis due to infection with Leptospira grippotyphosa and a literature overview.

[Colitis precipitated by Clostridium difficile -  a serious current problem]. / Kolitida vyvolaná Clostridium difficile -  závazný problém soucasnosti.

Clostridium difficile is currently considered a significant cause of nosocomial infection. The probability of a colonisation of hospitalised patients rises with the length of their stay in hospital and depends on the local epidemiologic situation. Interdisciplinary collaboration is the foundation of the effort to limit the development of this very serious, often fatal disease. The basic element is a rational antibiotic therapy which builds on the knowledge that the administration of antibiotics, even though based on a correct indication, may be fatal in an environment which is massively contaminated by spores of Clostridium difficile. Consequently, the high risk antibiotics (such as aminopenicillins, fluoroquinolones or cefalosporins) should be administered only in such cases where they cannot be substituted by antibiotics with a lower risk of CDI.

[Risk factors for relapsing and severe colitis caused by Clostridium difficile infection]. / Rizikové faktory rekurentního a tezkého prubehu kolitidy vyvolané infekcí Clostridium difficile.

BACKGROUND: Describe risk factors for relapsing and severe Clostridium difficile infection (CDI) in a set of patients hospitalized at the Clinic of infectious diseases the University Hospital Brno. MATERIAL AND METHODS: A retrospective study observing epidemiological, clinical and laboratory data of 281 patients with proven diagnosis of Clostridium difficile infection hospitalized in the period from 1. 1. 2007 to 31. 12. 2010. RESULTS: In the first part of the evaluation were enrolled 233 patients, 87 (37.3 %) patients had a record of relapsing CDI and 146 (62.7 %) patients had nonrelapsing CDI. Factors associated with relaps included 2 or more comorbidities, previous hospitalization during the 4 weeks before CDI, the use of proton pump inhibitors. In the second part of the evaluation were enrolled all 281 patients, severe CDI during any episode of the disease was observed in 181 (64.4 %) patients, while the remaining 100 (35.6 %) patients had mild or moderate CDI. The risk factors associated with severe CDI were age older than 65 years, history of coronary heart disease, chronic renal insufficiency, a combination of 2 or more comorbidities, previous hospitalization in a period of 4 weeks. CONCLUSIONS: Age older than 65 years is the risk for severe CDI. Patients with 2 or more comorbidities or with history of previous hospitalization are in a risk for both, relapsing and severe CDI. Use of proton pump inhibitors may lead to recurrence, probably on the basis of re-infection Clostridium difficile spores.

[Triple combination treatment of chronic hepatitis C]. / Trojkombinacní lécba chronické hepatitidy C.

The 2011 has brought about a significant change in the treatment of chronic hepatitis C virus (HCV) infection. This change has been enabled by commercial availability of new antiviral agents for treatment of chronic HCV infection - telaprevir and boceprevir - in combination with pegylated interferon (PEG-IFN) α and ribavirin (RBV). The triple combination is significantly more effective than the PEG-IFN and RBV combination alone in antiviral treatment-naive patients as well as in patients in whom the traditional PEG-IFN and RBV combination did not provide permanent HCV infection elimination. In treatment-naive patients, the triple combination is approximately 2-fold more effective than the standard treatment with PEG-IFN and RBV and the effect of the triple combination is 3-fold higher when used in pre-treated patients instead of repeated PEG-IFN and RBV treatment.

[Warning about risk of invasive infections in splenectomized patients. Experiences from University Hospital Brno, Czech Republic, in 2011]. / Upozornení na nebezpecí invazivních infekcí u splenektomovaných pacientu. Zkusenosti z FN Brno 2011.

Syndrome of fulminant sepsis in splenectomized (overwhelming postsplenectomy infection - OPSI) is feared and often fatal infectious complication in patients after splenectomy. The risk of syndrome of fulminant sepsis in splenectomized in these persons persists lifelong and doesn't diminish during the time. Etiologically, encapsulated bacterias like Streptococcus pneumoniae, Haemophilus influenzae group b and Neisseria meningitidis are involved. As the mortality of syndrome of fulminant sepsis in splenectomized is very high, it is indispensable to educate and vaccinate persons in risk. The authors present case reports of three splenectomized patients who were hospitalized for invasive pneumococcal infection in the University Hospital Brno, Czech Republic, in 2011.

[Febrile pancytopenia and hepatosplenomegaly as leading symptoms of visceral leishmaniasis]. / Febrilní pancytopenie a hepatosplenomegalie jako hlavní symptomy viscerální leishmaniózy.

The authors present a case report of a patient with febrile pancytopenia, hepatosplenomegaly and weight loss as main symptoms of visceral leishmaniasis. Standard treatment regimen with amphothericin B led to relapse of the disease after several weeks. The definitive cure of the disease was achieved with cytostatic miltefosin (Impavido©), which is not registered in the Czech Republic. The aim of this article is to point out this imported protozoan infection and its basic clinical and laboratory features.

[Liver diseases in internal medicine outpatient clinics]. / Nemoci jater v interní ambulanci.

Patients with a suspected or confirmed liver disease are frequent attendees at internal medicine outpatient clinics. Metabolic and toxic liver lesions are presently much more prevalent than infectious liver diseases. Liver steatosis and drug-induced liver impairment are the most frequent. The main task for internal medicine specialists in primary care with respect to chronic viral hepatitis B and C is to keep these diseases in mind and when an increased alaninaminotranspherase activity is detected, to perform blood tests for the presence of HBsAg as well as anti-HCV antibodies. Epidemiologically high-risk patients should always be tested for the presence of HBsAg and anti-HCV (even with normal ALT activity).