Clinical characteristics of hospitalized adults and adolescents with herpes zoster in Croatia: more than 20 years of a single-center experience.

AIM: To evaluate the clinical characteristics of adult and adolescent Croatian patients hospitalized for herpes zoster over a period of 21 years in the largest national center for infectious diseases (catchment area approximately 25% of the Croatian population). METHODS: This retrospective chart review included all patients older than 15 years hospitalized for herpes zoster at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" between January 1, 1996 and December 31, 2016. RESULTS: The study enrolled 1755 patients (uniform annual hospitalizations), 50% of whom suffered from complicated forms of herpes zoster, mostly generalized zoster (22.0%), infected lesions (14.8%), and meningitis/encephalitis (10.4%). A low percentage of patients experienced Ramsey-Hunt syndrome (3.0%), keratitis (1.5%), and visceral dissemination (0.2%). The majority of patients were older than 55 years (80%, median 70 years). Overall, 61.6% of patients suffered from at least one comorbidity (most frequent: diabetes 14.6%, cardiovascular incidents 24.4%, malignancy 13.0%, other infection 12.9%), and 28.2% suffered from ≥2 comorbidities. All-cause in-hospital mortality was 0.9%. The proportion of patients with any complicated form and of patients with meningitis/encephalitis steadily decreased over time, while the proportion of patients with comorbidities increased. This coincided also with steadily increasing age. No association was observed between comorbidities and complicated forms of zoster. Pharmacological immunosuppression was associated with generalized zoster; younger age was associated with meningitis/encephalitis; and older age was associated with generalized zoster and infected lesions. CONCLUSION: The patients most frequently hospitalized for herpes zoster are elderly people burdened with comorbidities, not necessarily patients with complicated forms of the disease.

A case report of severe recurrent varicella in an ankylosing spondylitis patient treated with adalimumab - a new side effect after 15 years of usage.

BACKGROUND: Tumor necrosis factor-α (TNF-α) antagonists, most of which are monoclonal antibodies, became a widespread treatment for autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis, psoriatic arthritis, hidradenitis suppurativa and uveitis. Their use is based on the blockage of TNF-α, which plays an important role in granulomas formation, development of phagosomes, activation and differentiation of macrophages, immune response against viral pathogens. The multiple adverse effects of TNF-α inhibition have been identified, including a two-to four-fold increased risk of active tuberculosis and other granulomatous conditions and an increased occurrence of some other serious bacterial, fungal and certain viral infections. CASE PRESENTATION: A 34-year-old male patient with disseminated varicella and pneumonitis was admitted to our hospital. The diagnosis of varicella was established serologically by enzyme immunoassay (EIA) and by polymerase chain reaction confirmation of the virus in vesicular fluid. The patient has been receiving adalimumab and methotrexate for the last 3 years due to ankylosing spondylitis and was seropositive to varicella zoster virus prior to the introduction of TNF-α antagonists. Acyclovir was administered for 10 days with the resolution of clinical illness and radiological signs of pneumonitis. CONCLUSION: Due to the use of biological agents, particularly TNF-α inhibitors, as a well-established therapy for some autoimmune diseases, new potential adverse events can be expected in the future and we wanted to point out one of them. To our knowledge this is the first case of recurrent disseminated varicella in a patient taking TNF-α antagonists.

Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data.

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)-the first-line anthelminthic drug for medical treatment of CE-is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = -0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 µg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 µg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 µg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (ß = -17.2 µg/L/cm; 95th CI, -35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.

Albendazolesulphoxide concentrations in plasma and hydatid cyst and prediction of parasitological and clinical outcomes in patients with liver hydatidosis caused by Echinococcus granulosus.

AIM: To investigate the relationship between plasma and cyst concentrations of albendazolesulphoxide (ASO) and their effects on parasitological findings and disease recurrence in patients with liver hydatidosis. METHODS: The study was conducted at the University Hospital for Infectious Diseases Dr. Fran Mihaljevic, Zagreb, Croatia, between August 2006 and January 2011. Consecutive patients (N=48, age 6-77 years) were treated with albendazole (3×5 mg/kg/d) over 28 days before surgical cyst removal (n=34) or percutaneous evacuation (PAIR) (n=14). Plasma ASO was determined on days 10 and 28 of treatment and cyst concentrations at surgery/PAIR. RESULTS: Disease recurred in 3 surgically treated patients. Variability of ASO concentrations was substantial. Plasma concentrations on day 10 were higher than on day 28 (geometric means ratio [GMR] 2.00; 95%CI 1.38-2.91, P<0.001) and higher than cyst concentrations at the time of treatment (GMR=1.58, 1.01-2.34, P=0.045). Higher cyst (but not plasma) concentrations were independently associated with lower odds of protoscolex motility (OR=0.23, 0.01-0.70, P<0.001) and higher odds of protoscolex destruction (OR=1.17, 1.04-1.46, P<0.001). With adjustment for age and protoscolex motility, higher day 10 plasma concentrations (but not cyst concentrations) were associated with lower odds of disease recurrence (OR=0.49, 0.09-0.97, P=0.035). Plasma concentrations did not predict cyst concentrations. CONCLUSION: Viability of protoscolices progressively decreased with increasing ASO concentrations in the cyst. Data strongly suggested that higher plasma concentrations reduced the risk of disease recurrence.

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Hemorrhagic Fever with Renal Syndrome Patients Exhibit Increased Levels of Lipocalin-2, Endothelin-1 and NT-proBNP.

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by viruses of the Orthohantavirus genus. This syndrome is characterized by renal and cardiopulmonary implications detectable with different biomarkers. Here, we explored the role of serum and urine levels of lipocalin-2, endothelin-1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFRS pathology. A total of twenty-eight patients hospitalized due to a Puumala orthohantavirus infection were included, with serum and urine samples collected on patient admission (acute phase) and discharge (convalescent phase). In comparison to healthy individuals, patients exhibited significantly higher acute-phase serum and urine levels of lipocalin-2, serum levels of endothelin-1 and serum and urine levels of NT-proBNP. Patients in the convalescent phase showed a significant decrease in urine lipocalin-2, serum endothelin-1 and serum and urine NT-proBNP levels. We recorded a strong correlation between serum levels of lipocalin-2 and endothelin-1 and urine levels of lipocalin-2 with several kidney injury markers, such as serum creatinine, urea, urine white blood cell count and proteinuria. We also demonstrated an independent correlation of serum and urine lipocalin-2 levels with acute kidney injury in HFRS. All in all, our results show an involvement of NT-proBNP, lipocalin-2 and endothelin-1 in the renal and cardiac pathology of HFRS.

Analysis of Types of Skin Lesions and Diseases in Everyday Infectious Disease Practice-How Experienced Are We?

Rashes and skin lesions are a common reason for patient visits to emergency departments and physicians' offices. The differential diagnosis includes a variety of infectious and non-infectious diseases, some of which can be life-threatening. The aim of this retrospective study was to evaluate the quantity and type of skin lesions among outpatients and inpatients at a tertiary care university-affiliated teaching hospital for infectious diseases over a three-year period to assess disease burden and physicians' experience in diagnosing skin lesions. Diagnoses (by ICD-10 codes) were classified into three groups: infectious diseases that include skin lesions, non-infectious skin lesions and undiagnosed skin lesions. During the observed period, out of the total of 142,416 outpatients, 14.8% presented with some form of skin lesion. Among them, 68% had skin lesions inherent to infectious disease, 10.8% suffered from non-infectious skin lesions and 21.2% remained with undiagnosed skin lesions. The most common infectious diagnoses were chickenpox, herpes zoster and unspecified viral infections characterized by skin and mucous membrane lesions. The most common non-infectious diagnoses were urticaria and atopic dermatitis. Overall, the most common individual diagnosis (ICD-10 code) was "nonspecific skin eruption" (n = 4448, 21.1%), which was followed by chickenpox and herpes zoster. Among the 17,401 patients hospitalized over the observed period, 13.1% had skin lesion as the main reason for hospitalization, almost all (97.5%) of which were infectious in etiology. The most common diagnoses were cellulitis, erysipelas and herpes zoster. The presented data suggest that the burden of diseases presenting with skin lesions is significant in everyday infectious disease practice, but the overwhelming number of undiagnosed patients implies the need for further education in this area.

Unusual presentations of actinomycosis: a case series and literature review.

INTRODUCTION: To review unusual actinomycosis cases that appeared as a diagnostic and therapeutic challenge at our institution and to present a literature review on the usual clinical presentations. METHODOLOGY: This retrospective review included all patients hospitalized for actinomycosis in a 10-year period at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. RESULTS: A total of 15 patients were hospitalized during the observed period, 9 (60%) females and 6 (40%) males. The localizations of actinomycosis were: pelvis (5), lungs (3), blood stream (2), colon (1), penis (1), stomach (1), skin (1), cervicofacial region (1). We present four unusual cases: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft. CONCLUSIONS: Actinomycosis was a very rare clinical problem in our clinical practice (0.032% of all hospitalizations and 0.0034% of all outpatients) but among those cases classical clinical presentations were also very rare.

Combined Albenazole-Praziquantel Treatment in Recurrent Brain Echinococcosis: Case Report.

We present a 40-year-old woman with a history of relapsing echinococcosis who had undergone a number of surgical procedures for cyst removal (right pulmectomy, cardiac surgery and 6 subsequent brain surgeries and two gamma knife procedures) and was admitted to University Hospital for Infectious Diseases "Fran Mihaljeviæ", Zagreb, Croatia in 2014 for pre-operative medical treatment of brain hydatidosis in the right parietal region. We aimed to attain a high cyst albendazole sulphoxide (ASO) concentration in order to achieve a more pronounced protoscolex inactivation and a high serum ASO concentration (reflecting the tissue concentrations) to reduce the risk of disease recurrence. The patient was treated with a higher dose of albendazole (15 mg/kg/day for 4 wk) that we had found effective in patients with liver hydatidosis, and combined with praziquantel over the last 14 d at a dose that is typically used to treat neurocysticercosis with an intention to improve ASO bioavailability. Neither serum nor cerebrospinal fluid concentrations on day 10 apparently differed from those on day 24 indicating a lack of an effect of praziquantel on ASO bioavailability. Intra-cystic ASO concentration was below the lower limit of quantification, but above the limit of detection. After the 7th episode of the disease and combined albendazole-praziquantel and surgery treatment, the patient achieved a 3-year remission. With the apparent lack of a meaningful pharmacokinetic praziquantel-albendazole interaction, this is most likely ascribable to the use of a higher albendazole dose than previously.

Repeated Percutaneous Treatment of Massive Hepatic Cystic Echinococcosis in a Child.

Because of mostly asymptomatic cyst growth and often-neglected nonspecific low-grade symptoms, many cases of cystic echinococcosis (CE) caused by Echinococcus granulosus in the pediatric population are diagnosed at school age, in an advanced and even complicated stage. In 2003, after 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old boy was diagnosed with massive liver CE, with ∼20 round-shaped double-walled medium-sized infective cysts, which permeated the whole liver. Because of their wide distribution across the liver tissue and the risky superficial position of some cysts, liver transplantation emerged as the optimal therapeutic option. Despite being described as only an exceptionally used method for CE, we subjected our patient on 4 occasions to a radiofrequency energy thermoablation (RFT) procedure similar to the one used for malignant neoplasms. In total, 9 superficially situated cysts were initially treated with RFT by using a 14-gauge outer needle and a temperature of 70°C for 8 minutes per cyst, and the remaining cysts were treated with the puncture-aspiration-instillation-reaspiration procedure, along with albendazole (15 mg/kg per day) therapy, for a period of 20 months. After 2 years of follow-up, 4 residual small-sized semisolidified cysts were seen in the liver, and the patient showed no signs of relapse. Although not routinely used, RFT, along with puncture-aspiration-instillation-reaspiration and prolonged albendazole therapy, has shown good tolerability and long-term efficacy in the treatment of multiple infective CE, which could suggest the usefulness of the RFT method beyond salvage situations in pediatric patients.

Septic abortion caused by Campylobacter jejuni bacteraemia.

A 20-year-old female patient, 14 weeks pregnant, was admitted to hospital with anamnestic and clinical features of acute pyelonephritis. Clinical signs of septic abortion developed and after obstetric examination the therapy was changed to ampicillin, gentamicin and clindamycin. Campylobacter jejuni was isolated from blood cultures. Pathohistological findings confirmed diagnosis of purulent chorioamnionitis. After 2 weeks of ciprofloxacin administration the patient fully recovered. Campylobacter jejuni was not isolated from stool culture and no signs of acute enteritis were registered during the illness. Invasive forms of Campylobacter disease without enteritis are not unusual in immunocompromised hosts but they are restricted to C. fetus rather than C. jejuni isolates.

The polymicrobial Actinomyces naeslundii and Pseudomonas aeruginosa sepsis in a patient with ulcerative colitis 2 months after colonoscopy.

We describe a case of an abrupt onset of polymicrobial Actinomyces naeslundii/Pseudomonas aeruginosa sepsis in a patient with a previously silent abdominal actinomycosis, developed 2 months after colonoscopy when the diagnosis of a left-sided ulcerative colitis was established. Prolonged high-dose ceftriaxone therapy was clinically effective, albeit accompanied by the development of a reversible pseudocholelithiasis that persisted for 5 months.