Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Implications of highly suppressive treatment HIV infection.

Treatment of HIV infection has modified the initially fatal infection into a typically chronic disease requiring lifelong treatment. However, there is no complete normalization of immune activation, signs of inflammation and prothrombotic state in treated patients. This condition is the result of many factors, but the main cause is thought to be the residual production of HIV-1 RNA and viral proteins by infected cells in cellular reservoirs. Persistence of immune activation/inflammation/prothrombotic state leads to the pathophysiology of "sterile inflammation" and so-called non-AIDS diseases, which manifest one to two decades earlier in those infected. Despite all the pitfalls and unwanted secondary manifestations of antiretroviral drugs, the treatment of HIV infection has managed to reverse the trajectory of a fatal pandemic and has made it possible to approach therapeutic modalities that were absolutely unimaginable just a few years ago. Solid organ transplantation is now a completely legitimate therapeutic method for patients living with HIV, and highly suppressive treatment even allows transplantation from an HIV-infected donor. The text below presents a brief overview of the basic pitfalls, but also of the successes, of the current highly suppressive treatment of HIV infection.

Current hepatitis C therapy.

Hepatitis C virus (HCV) infection is still a major cause of chronic liver diseases, with approximately 71 million chronically infected persons worldwide. People who inject drugs currently or in the past (PWID), mostly intravenously, are the main risk group among HCV chronically infected persons. The efficacy of therapy with direct acting antivirals (DAA) is almost 100 %. Currently, the main mission is to diagnose HCV infection in the most possible number of infected persons; it is in collision with poor adherence of PWID in particular.

The first case of periorbital human dirofilariasis in the Czech Republic.

Dirofilaria repens and Dirofilaria immitis are the most common filarial species affecting humans in Europe. Dirofilaria repens causes subcutaneous or ocular infection, whereas D. immitis is responsible mainly for the pulmonary form. In this report, we present the first human case of periorbital dirofilariasis in the Czech Republic. A 58-year-old woman suffered from an eyelid oedema, redness and pain in the left eye. After excising the parasite from her eyelid, all clinical symptoms disappeared. Based on the morphology and cytochrome oxidase I sequencing, the parasite was identified as D. repens. Histology revealed that the excised worm was female with absent microfilariae in uteri. With respect to the length of the incubation period and the sequence identity with a known Czech isolate, we concluded that D. repens was most likely of autochthonous origin.

[Impact of outreach testing on elimination of hepatitis C].

OBJECTIVES: Analysis of changes in a group of patients with chronic hepatitis C (CHC) treated with direct-acting antivirals (DAAs) with a special focus on risk factors for transmission. Evaluation of cooperation with organizations working with people who inject drugs (PWID) including the impact of outreach testing. METHODS: A retrospective analysis and interannual comparison of CHC patients treated with DAAs at the Department of Infectious Diseases, University Hospital Brno, Czech Republic between 2018 and 2020. RESULTS: A total of 291 (101 in the year 2018, 111 in 2019 and 79 in 2020) patients with CHC have been treated. Comparison of results from the years 2018, 2019 and 2020 demonstrated a significant rise in the proportion of PWID (46.5 %, 64.9 % and 65.8 %, respectively). Also the proportion of genotype 3a infection (23.8 %, 30.6 % and 35.4 %) increased at the expense of genotype 1b infection (52.5 %, 46.9 % and 38.0 %). By contrast, the median age (43, 40 and 38 years) and the proportion of patients with liver cirrhosis decreased (20.8 %, 15.3 % and 12.7 %). The percentage of patients started on DAA therapy within one year of diagnosis increased (47.5 %, 53.2 % and 62.0 %). And so did the proportion of patients receiving therapy as a result of cooperation with organizations and facilities working with PWID (5.9 %, 25.2 % and 25.3 %). The downside was high numbers of patients lost to follow-up (19.8 %, 23.4 % and 22.3 %). Those were mostly patients who completed their therapy as planned and were only lost to after receiving the final dose of DAAs. CONCLUSIONS: The fact that PWID have gradually become the dominant group of CHC patients is accompanied by a younger age of treated patients, a higher proportion of those with genotype 3a and less advanced liver damage. The changing spectrum of CHC patients makes medical professionals change their approach. Outreach testing and cooperation with organizations working with PWID have proved an effective way of improving the diagnosis and treatment of CHC.

[Hepatitis D screening is important in the Czech Republic as well].

Only patients infected with hepatitis B virus (HBV) can contract hepatitis D virus (HDV) infection, either simultaneously (co-infection) or as a superinfection in those already infected with HBV. The routes of HDV transmission are contaminated needles or transfusion; sexual and vertical transmissions are relatively rare. Chronic hepatitis D is the most serious form of chronic viral hepatitis due to more rapid progression to decompensated cirrhosis and hepatocellular carcinoma (HCC). Liver cirrhosis may develop within five years and HCC within 10 years of dual infection. In the vast majority of cases, HDV replication suppresses HBV replication. Therefore, most patients are positive for HDV RNA in plasma while showing no or low levels of HBV DNA. At present, there is no routine screening for HDV in persons with chronic HBV infection in the Czech Republic. One of the reasons the absence of approved treatment op-tions, with the only possibility being administration of pegylated interferon alpha for 48 weeks or even longer. This approach does not provide long-term efficacy in most cases. Therapy with bulevirtide seems to be promising according to available data.

[Dual or triple combination antiretrovirals?]

Since the beginning of the antiretroviral therapy (ART) era, its extraordinary effect in terms of morbidity and mortality has been linked to a three-drug combination HIV treatment strategy, which has been perceived as a constant paradigm for many years. However, epidemiological studies over the past decade have clearly shown that ART does not result in complete normalization of all biomarkers, and some degree of systemic immune activation and inflammation, including endothelial dysfunction, persist. It is generally accepted that these pathophysiological processes are the cause of non-AIDS diseases, which are clinically manifested in people living with HIV on average 10 years earlier than in the general HIV-negative population. HIV treatment is not eradicative but only inhibitive and requires regular daily medication. This increases the risk of the cumulative impact of side effects and drug toxicity. In addition, it is expected that there will be a significant increase in the number of patients with various other non-AIDS comorbidities that will require multiple medication in the coming years. In particular, the higher genetic barrier of the new generation of drugs and an improved safety profile have raised the question of the effectiveness of two-drug combination regimens with the fundamental goal of reducing the burden on the human body by different drugs while maintaining high efficacy fully comparable to the current three-drug combination strategy. However, the question of whether dual combination regimens can sufficiently suppress the persistence of chronic inflammation and immune activation remains unanswered. To answer such a question, robust data from large prospective randomized studies are needed, which are still lacking. This review discusses the principle of systemic immune activation, its regenerative potential in ART, the expected causes leading to systemic immune activation, intervention options to influence it, as well as the limitations of studies to date.

[COVID-19: diagnosis and treatment].

The guidelines provide evidence-based recommendations for the management of COVID-19. The clinical manifestations of the disease are described and indication criteria for hospital admission of patients with COVID-19 are listed. Polymerase chain reaction and antigen testing are used in direct diagnostics. Indirect detection of infection by antibodies is currently of limited value. There are a number of hematological and biochemical laboratory test used to diagnose COVID-19. Pathological values of some laboratory parameters are associated with severity of COVID-19. Of the imaging studies, chest X-ray, chest computer tomography and lung ultrasound are used. COVID-19 therapy includes symptomatic and specific therapy (antivirals, immunotherapeutics and anticoagulants) and intensive care in the severe and critical forms of the disease. Remdesivir and favipiravir are available as antiviral agents. Immunotherapeutics include monoclonal antibodies (casirivimab/imdevimab, bamlanivimab/etesevimab), dexamethas one, baricitinib and tocilizumab. Low-molecular-weight heparin is a dominant form of anticoagulant therapy. The guidelines provide specific therapeutic recommendations for each stage of the disease. Antibiotics are recommended only if bacterial superinfection is suspected or demonstrated, which is not common in the early stages of the disease.

Current view on hepatitis B diagnosis and therapy.

Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors predominantly vaccination policy and migration. Chronic hepatitis B is a dynamic process reflecting the interaction between HBV replication and the host immune response and not all patients with chronic HBV infection have chronic hepatitis B. Stopping of nucleotide or nucleoside analogues (NA) therapy is a serious resolution due the danger of reactivation of viral replication associated with increasing HBV DNA level, ALT activity and inflammatory activity in the liver histology. The safest stopping rule for NA therapy is HBsAg loss what is the sign of immune control of HBV infection.

Acute searching and early diagnosis of HCV infected persons.

Hepatitis C virus (HCV) infection is still a major cause of chronic liver diseases, with approximately 71 million chronically infected persons worldwide. People who inject drugs currently or in the past (PWID), mostly intravenously, are the main risk group among HCV chronically infected persons. The efficacy of therapy with direct-acting antivirals (DAA) is almost 100 %. Currently, the main mission is to diagnose HCV infection in the most possible number of infected persons; it is in collision with poor adherence of PWID in particular. Changing the spectrum of chronic hepatitis C patients forces medical professionals to change their approach to diagnosis and treatment of HCV infection. Outreach testing and cooperation with support organizations showed to be an effective way to set a course to eliminate HCV in the PWID population.

Clostridium difficile Infection: an update on treatment and prevention.

Disruption of the colonic microflora is one of the most significant adverse effects of antibiotic (ATB) therapy. Excessive multiplication of toxigenic Clostridioides difficile strains is responsible for about 20 % of cases of post-antibiotic diarrhoea. The global trend of Clostridium colitis incidence, severity, mortality and in particular therapeutic failure keeps rising. At the Department of Infectious Diseases we work on long-term monitoring of the most important colitis-associated risk factors and evaluation of individual therapeutic and preventive procedures (selective ATB therapy, faecal bacteriotherapy). A diligent analysis of risk factors and knowledge of pathogenesis are a prerequisite to practical implementation of effective and rational precautions to curb spreading of this illness. In the future, we anticipate increased use of fecal microbiota transplant, improvements in faecal transplant administration, wider use of probiotics and selective ATBs and further introduction of passive and active immunization into practice.

Chronic hepatitis C in the Czech Republic: Forecasting the disease burden.

OBJECTIVE: Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown. METHODS: Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets. RESULTS: The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030. CONCLUSIONS: Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.

Current view on hepatitis B diagnosis and therapy.

Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors predominantly vaccination policy and migration. Chronic hepatitis B means the duration of HBV infection for more than 6 months. It is a dynamic process reflecting the interaction between HBV replication and the host immune response and not all patients with chronic HBV infection have chronic hepatitis B. All patients with chronic HBV infection are in increased risk of progression to liver cirrhosis and hepatocellular carcinoma. The long-term administration of potent nucleos(t)ide analogue with high barrier of resistance (tenofovir, entecavir) represents the treatment of choice. Pegylated interferon-α can also be considered in mid to moderate chronic hepatitis B patients.

Current knowledge of hepatitis E virus related disease.

Hepatitis E virus (HEV) infection is one of the most common causes of acute hepatitis worldwide. The Czech Republic is also a region with a natural occurrence of HEV genotype 3. Diseases caused by different genotypes have distinct clinical and epidemiological characteristics. In industrialized countries, numerous local animal reservoirs have been described and infection is considered to be zoonotic disease in these areas. The most significant route of transmission is through ingestion of insufficiently cooked meat of reservoir animals. In addition, numerous extrahepatic manifestations, even without dominant liver disease, and the possibility of chronic hepatitis in immunocompromised patients have been described. The review summarizes the current knowledge of HEV related disease and current approaches to the treatment of acute and chronic hepatitis E.

[Guideline for fecal bacteriotherapy to treat recurrent Clostridium difficile colitis].

We present a case of a 17-year-old female with anti-NMDAR encephalitis probably associated with vaccination against yellow fever. Her symptoms occurred 27 days after vaccination against yellow fever. Anti-NMDAR encephalitis manifested as acute psychosis, memory loss and catatonia following fever with complex partial epileptic seizures. Interictal electroencephalogram showed slow-wave delta background activity with "delta brushes". The diagnosis was confirmed by NMDAR antibody positivity in serum and cerebrospinal fluid. Since ovarian teratoma, as the most common cause of anti-NMDAR encephalitis, did not develop within five years from its onset, the association with vaccination against yellow fever seems to be highly probable.

Tenofovir disoproxil fumarate (TDF) vs. emtricitabine (FTC)/TDF in lamivudine resistant hepatitis B: A 5-year randomised study.

BACKGROUND & AIMS: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB). METHODS: LAM-R CHB patients were randomised 1:1 to receive TDF 300mg or FTC 200mg and TDF 300mg once daily in a prospective, double blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA<69IU/ml (<400copies/ml) at week 96 (primary efficacy endpoint) was reported previously. Here we present week 240 follow-up data. RESULTS: Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240weeks of treatment. At week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA<69IU/ml (p=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (p=0.41 and p=0.97 respectively). Hepatitis B e antigen loss and seroconversion at week 240 were similar between groups, (p=0.41 and p=0.67 respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by week 240. No TDF resistance was observed up to week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at week 240 was -0.98% and -2.54% at the spine and hip, respectively. CONCLUSIONS: TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240weeks. LAY SUMMARY: The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240weeks. Clinical trial number: NCT00737568.

[First experience with elbasvir/grazoprevir fixed-dose combination in real-life practice in the Czech Republic].

Hepatitis C virus infection (HCV) is one of the leading causes of chronic liver disease worldwide. The new fixed-dose combination of the highly potent second wave first generation NS5A inhibitor elbasvir (50 mg) and the second generation protease inhibitor grazoprevir (100 mg) is contained in the drug Zepatier. This combination is indicated for the treatment of patients chronically infected with HCV genotypes 1 or 4. Between June and August 2017, the treatment was initiated in 22 patients with chronic viral hepatitis C, with 17 patients being treated in the Department of Infectious Diseases University Hospital Brno and five patients in the Center of Cardiovascular and Transplant Surgery in Brno. All patients were infected with HCV subtype 1b. In all cases, the duration of Zepatier monotherapy (without simultaneous ribavirin administration) was 12 weeks. At the moment, only preliminary results are available. All 22 patients achieved end-of-treatment virologic response. In nine patients, it was already possible to evaluate the virologic response at four weeks after the end of treatment, with sustained virological response (SVR12) was observed in all these patients. The most common complaints were fatigue (3 patients, 14 %) and headache (2.9 %). These problems were not serious and did not interfere with normal daily activities of treated persons.