University Hospital For Infectious Diseases Research Articles

Hepatitis A Outbreak in Men Who Have Sex with Men Using Pre-Exposure Prophylaxis and People Living with HIV in Croatia, January to October 2022.

The hepatitis A virus (HAV) is a highly hepatotropic virus transmitted mainly via the fecal-oral route. The purpose of this study is to describe a prolonged HAV outbreak in HIV-infected men who have sex with men (MSM) and pre-exposure prophylaxis (PrEP) users in Croatia in 2022. Croatia has a centralized system of HIV care and the PrEP service is only available at the University Hospital for Infectious Diseases (UHID), Zagreb. We reviewed all MSM living with HIV and MSM PrEP users at UHID and identified those diagnosed with HAV between January and October 2022. During this period, a total of 1036 MSM living with HIV and 361 PrEP users were followed, and 45 (4.4%) and 32 (8.9%) were diagnosed with HAV, respectively. Most cases were diagnosed in mid-February. A total of 70.1% (726/1036) MSM living with HIV and 82.3% (297/361) PrEP users were susceptible to HAV. Sequencing information was available for 34 persons; in all cases the HAV subtype IA was found. Our findings indicate that both MSM living with HIV and HIV-uninfected PrEP users are vulnerable to HAV infection and might be a potential source for a more widespread HAV epidemic.

1802. Off-label Use of Antimicrobial Agents at the University Hospital for Infectious Diseases, Zagreb, Croatia

Abstract Background Antimicrobial agents' (AMAs) off-label use can be associated with the prescriber's education. Little is known about the AMAs' off-label use by infectious disease (ID) specialists. We have conducted research at the University Hospital for Infectious Diseases (UHID), Zagreb, Croatia, a 230-bed tertiary center where ID specialists primarily prescribe AMAs. Methods A retrospective cross-sectional analysis was conducted on the day with the highest hospitalization number, January 17, 2019. Any use of AMA not complying with the SmPC was considered off-label and evaluated regarding modality (indication, dose, regimen, route of administration, and age) and justification by institutional or/and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines. Results The study included 155 patients, 63 (40.6%) adults and 92 (59.4%) children. 61 (96.8%) adult patients had at least one AMA. There were 134 AMA prescriptions in adults, 42 (31.3%) off-label. AMAs were most frequently prescribed off-label regarding regimen (21), dose (17), and indication (14). Institutional guidelines justified off-label in 5 cases regarding dose, 4 regarding indication, and 2 regarding regimen. ESCMID guidelines justified off-label prescriptions in 5 cases regarding indication. The rest of the off-label was not supported by the existing guidelines. 60 (65.2%) pediatric patients had at least one AMA. There were 73 prescriptions, 31 (42.5%) off-label. AMAs were most frequently prescribed off-label regarding indication (19), dose (12), and age (2). Institutional guidelines justified 3 off-label cases regarding indication and 1 regarding dose. ESCMID guidelines justified no off-label in children. The lack of guidelines was the leading cause of the off-label AMAs use in children. Conclusion One-third of AMAs are prescribed off-label regarding SmPC by ID specialists. However, institutional and international guidelines can justify part of this use. Disclosures All Authors: No reported disclosures.

COVID-19 and Pulmonary Thrombosis-An Unresolved Clinical Puzzle: A Single-Center Cohort Study.

Pulmonary thrombosis (PT) is a frequent complication of COVID-19. However, the risk factors, predictive scores, and precise diagnostic guidelines on indications for CT pulmonary angiography (CTPA) are still lacking. This study aimed to analyze the clinical and laboratory characteristics associated with PT in patients with COVID-19. We conducted a cohort study of consecutively hospitalized adult patients with COVID-19 who underwent CTPA at the University Hospital for Infectious Diseases in Zagreb, Croatia between 1 April and 31 December 2021. Of 2078 hospitalized patients, 575 (27.6%) underwent CTPA. PT was diagnosed in 178 (30.9%) patients (69.6% males, median age of 61, IQR 50-69 years). The PT group had a higher CRP, LDH, D-dimer, platelets, and CHOD score. PT was more frequent in patients requiring ≥15 L O2/min (25.0% vs. 39.7%). In multivariable analysis, only D-dimer ≥ 1.0 mg/L (OR 1.78, 95%CI 1.12-2.75) and O2 ≥ 15 L (OR 1.89, 95%CI 1.26-2.84) were associated with PT. PT was not associated with in-hospital mortality. In conclusion, our data confirmed a high incidence of PT in hospitalized patients with COVID-19, however, no correlation with traditional risk factors and mortality was found. CTPA should be performed in patients requiring high-flow supplemental oxygen or those with increased D-dimer levels.

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

Strongyloidiasis - diagnostic and therapeutic dilemmas in hyperinfection patients: a case series.

The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases 'Dr. Fran Mihaljević' in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.

311. Impact of Non-alcoholic Fatty Liver Disease on Clinical Outcomes in Patients with COVID-19

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease with a prevalence up to 30%. NAFLD is strongly associated with components of metabolic syndrome, already recognized as risk factors for worse outcomes in COVID-19. However, the impact of NAFLD on COVID-19 is not well characterized. The aim of this study was to investigate a possible association between NAFLD and COVID-19 severity and outcomes.MethodsA prospective observational study included consecutively hospitalized adult patients with severe COVID-19 at the University Hospital for Infectious Diseases in Zagreb, Croatia between March and June 2021. On admission patients were screened for fatty liver by the ultrasound and subsequently diagnosed with NAFLD according to current guidelines. Demographic, clinical and laboratory data was collected and correlated to clinical outcomes. ResultsOf the 112 patients included in the study, 77 (68.7%) had NAFLD (59.7% males; median age of 62, IQR 54-66 years). Except for higher prevalence of obesity in NAFLD group (61.0% vs 17.1%) there were no differences in other comorbidities. NAFLD group had higher inflammatory markers CRP (96, IQR 51-138 vs 59, IQR 29-99mg/L) and IL-6 (129, IQR 44-169 vs 25, IQR 8-56pg/mL). Steatosis stage showed positive correlation with BMI, waist/hip ratio, CRP, PCT, IL-6, AST, ALT, LDH and fibrinogen. Steatosis stage correlated with clinical status at the 7-category scale on admission and at days 7, 14 and 28. Patients with NAFLD had longer duration of hospitalization (9, IQR 6-15 vs 6, IQR 5-11 days, p=0.024), more frequently required noninvasive ventilation or high-flow oxygen (24.7% vs 5.7%, p=0.018) and had higher rate of pulmonary embolism (22.1% vs 5.7%, p=0.024). There was no difference in mortality. The median value for clinical status on the ordinal scale at day 7 was significantly higher in NAFLD group at days 7 and 14, as presented in Fig. 1. Multivariable analysis identified age > 65 (OR 3.6, 95%CI 1.3-10.9), LDH > 350 (OR 8.1, 95%CI 2.7-29.4), NAFLD (OR 3.9, 1.1-20.5) and pulmonary embolism (OR 10.4, 2.7-48.3) associated with adverse outcomes at day 28. The figure shows the patients’ clinical status as assessed on the seven-category ordinal scale on admission and at day 7, 14 and 28, according to the presence of NAFLD. Categories on the ordinal scale were as follows: 1, discharged or ready for discharge; 2, hospitalization in a non–intensive care unit (ICU) without supplemental oxygen; 3, non–ICU hospitalization with supplemental oxygen; 4, ICU or non–ICU hospitalization with noninvasive ventilation or high-flow oxygen; 5, ICU hospitalization with mechanical ventilation; 6, ICU hospitalization with extracorporeal membrane oxygenation or mechanical ventilation and additional organ support; and 7, death.ConclusionOur data suggests that NAFLD is associated with COVID-19 severity and might be linked to adverse outcomes in hospitalized patients. Disclosures All Authors: No reported disclosures

The cost of care for people living with stable HIV in Croatia and the efficiency of EmERGE

AimTo estimate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV (PLHIV) at the University Hospital for Infectious Diseases (UHID), Zagreb. The Pathway includes a mobile application enabling individuals to communicate with their caregivers.MethodsThis study involving 293 participants collected data on the use of HIV outpatient services one year before and after EmERGE implementation. In departments supporting HIV outpatients, a micro-costing exercise was performed to calculate unit costs. These were combined with mean use of HIV services per patient year (MPPY) to estimate average annual costs. Primary outcomes were CD4 count, viral load, and secondary outcomes were patient activation, PAM13; and quality of life, PROQOL-HIV. Information on out-of-pocket expenditures was also collected.ResultsOutpatient visits decreased by 17%, from 4.0 (95% CI 3.8-4.3) to 3.3 MPPY (95% CI 3.1-3.5). Tests, including CD4 count, decreased, all contributing to a 33% reduction of annual costs: 7139 HRK (95% CI 6766-7528) to 4781 HRK (95% CI 4504-5072). Annual costs including anti-retroviral drugs (ARVs) decreased by 5%: 43 101 HRK (95% CI 42 728-43,490) to 40 743 HRK (95% CI 40 466-41,034). ARVs remain the main cost driver in stable PLHIV. Primary and secondary outcomes did not change substantially between periods.ConclusionEmERGE Pathway was a cost-saving intervention associated with changes in management, and a reduction in outpatient visits, tests, and costs. ARV costs dominated costs. Future efficiencies are possible if EmERGE is introduced to other PLHIV across the UHID and if ARV prices are reduced.

Clinical Manifestations of Bartonella henselae Infection Among Children

Objectives: The aim of this study was to analyze clinical manifestations, epidemiology and laboratory parameters of B. henselae infection among children treated at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević”, Zagreb from January 2014 until June 2019. Materials and methods: We retrospectively analyzed the epidemiology, clinical and laboratory characteristics among children with positive indirect immunofluorescence assay for B. henselae IgM and IgG or positive B. henselae polymerase chain reaction from lymph node aspirate. Results: A total of 104 patients, 47 (45,1%) female and 57 (54,8%) male were enrolled. The median age was 9,7 (range, 1,1 to 17,3 years). A history of cat contact was present in 101 (97,1%) children. Acute infection was serologically confirmed in 87 (83,6%), in 5 (4,8%) with PCR while both methods were positive in 12 (11,5%) patients. The presentation on B. henselae infection were regional lymphadenopathy , disseminated disease, encephalopathy and fever of unknown origin. Suppurative inflammation was the most common complication in patients with lymphadenopathy 12/92 (13%). Full recovery was the most frequent outcome (96,1%). Conclusion lesion: B. henselae infection among children is usually a mild disease presented as regional lymphadenopathy. Serology and polymerase chain reaction are useful tests for diagnosis. Treatment duration and choice of therapy depend on clinical manifestation and developed complications.

Enteroadsorbent Polymethylsiloxane Polyhydrate vs. Probiotic Lactobacillus reuteri DSM 17938 in the Treatment of Rotaviral Gastroenteritis in Infants and Toddlers, a Randomized Controlled Trial

Purpose: The aim of this study was to compare two adjunct therapies in the treatment of childhood rotavirus gastroenteritis (RVGE). We compared the recommended treatment, probiotic Lactobacillus reuteri DSM 17938 (BioGaia®), vs. a novel treatment, enterosorbent polymethylsiloxane polyhydrate (Enterosgel®).Methods: This was an open-label, randomized, clinical controlled trial at the University Hospital for Infectious Diseases (UHID) in Zagreb, Croatia. A total of 149 children aged 6–36 months with acute rotaviral gastroenteritis over a period of <48 h, with no significant chronic comorbidity, were randomized to receive the standard therapy with L. reuteri DSM 17938 (hereafter L. reuteri) or polymethylsiloxane polyhydrate (hereafter PMSPH) therapy, during 5 days. The primary end point was time to recovery in days in both groups. The recovery was defined as absence of fever and vomiting and either the first firm stool, absence of stool for more than 24 h, or return of usual bowel habit.Results: A total of 75 children were randomized into the L. reuteri group and 74 were randomized into the PMSPH group; after excluding missing data, the data from 65 children in each group were analyzed. There was no significant difference in the treatment efficacy between the two regimens with an estimated median time of recovery of 6 days in both groups (p = 0.754). No significant side effects were observed in either group.Conclusion: Novel enterosorbent PMSPH had a similar efficacy to probiotic L. reuteri in the treatment of rotaviral gastroenteritis in preschool children.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04116307 [October 3, 2019] (retrospectively registered). https://clinicaltrials.gov/show/NCT04116307.

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

AimTo 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).MethodsThis retrospective chart review included all patients older than 15 years hospitalized for herpes zoster at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević” between January 1, 1996 and December 31, 2016.ResultsThe 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.ConclusionThe patients most frequently hospitalized for herpes zoster are elderly people burdened with comorbidities, not necessarily patients with complicated forms of the disease.

Profile of invasive group A and group B Streptococcal infections in patients hospitalized at the University Hospital for Infectious Diseases „Dr. Fran Mihaljević“ during the period from 2011 to 2018

Aim: Beta-haemolytic streptococci (BHS) rarely cause invasive disease (ID). Usually the most common cause of ID is group B BHS (BHS-B). However, in our recent routine work higher number of group A BHS (BHS-A) isolates from blood was noted. The aim of this study was to report trends and findings by group BHS-A and BHS-B causing laboratory confirmed disease from 2011 to 2018 at the University Hospital for Infectious Diseases „Dr. Fran Mihaljević”. Methods: Data on patients from the electronic database of microbiological laboratory at UHID for the period 2011-2018 was collected and analysed. Results: During the period 2011-2018, 151 BHS A and B were identified from normally sterile body sites. Most isolates were from blood cultures (96.7%). BHS-A and BHS-B were isolated almost equally. The highest number of isolates was recorded in 2012 and 2017. The number of BHS A isolates peaked in 2012, 54% more than BHS-B, and 50% more in 2016. Children presented 19.9% of patients, and were mostly isolated with BHS-A. 80.1% patients were adults. Adults predominated in the age group &amp;gt;65 years. 12 children and 18 adults were hospitalised in intensive care unit. Conclusion: Invasive group A and group B streptococcal infections predominantly affect most vulnerable age groups, children and elderly. In this study invasive BHS disease is most common among adults above 65 years of age. BHS-A was most common cause of invasive disease among paediatric patients as well as in the age group above 65 years. Typing and characterization of BHS-A isolates due to its characteristics should be foreseen as important diagnostic tool, especially to monitor changes in virulence and to prevent potential outbreaks.

The epidemiological and clinical features of odontogenic infective endocarditis.

Antibiotic prophylaxis (AP) of infective endocarditis (IE) in dental practice is a controversial topic. We evaluated the characteristics of the odontogenic IE and assessed the practice and sources of information pertaining to the topic utilized by the Croatian dentists. We conducted a retrospective review of consecutive medical charts of adult patients with IE, admitted to the University Hospital for Infectious Diseases in Zagreb, Croatia, between January 2007 and December 2017. In addition, a cross-sectional, self-reporting questionnaire survey was conducted with participation of 348 Croatian dentists. Of the 811 admissions for suspected IE (40.3% of all Croatian and 92.1% of all Zagreb hospitals), 386 patients were confirmed as definite IE: 68 with odontogenic IE and 318 with IE of other origin. Their first hospital admissions were analyzed. Definite odontogenic IE was defined as a positive echocardiographic result in conjunction with two separate positive blood cultures showing exclusive oral cavity pathogen or Streptococcus viridans associated with current or recent (< 1month) dental, periodontal, or oral cavity infection. The annual number of new odontogenic IE patients appeared constant over time. In 91.2% of the cases, odontogenic IE was not preceded by a dental procedure; poor oral health was found in 51.5% of patients, and 47.1% had no cardiac condition that increases the IE risk. In-hospital mortality was 5.1% with conservative treatment and 4.5% with cardiac surgery and was much lower for odontogenic IE than in non-odontogenic IE (14.6% and 34.4%, respectively). An increasing number of admissions for non-odontogenic IE were observed in parallel with an increasing number of staphylococcal IE. Surveyed dentists (500 invited, 69.6% responded) were aware of the AP recommendations, but were largely reluctant to treat patients at risk. In people with poor oral health, AP should be considered regardless of cardiac risk factors. Improvement of oral health should be the cornerstone of odontogenic IE prevention.

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.

PANDEMIC INFLUENZA A (H1N1) 2009 PRESENTING AS A MILD DISEASE IN CHILDREN IN A CROATIAN CLINICAL CENTRE.

SUMMARYPandemic influenza A virus (H1N1) 2009 causes a disease that is epidemiologically and clinically not significantly different from seasonal influenza, but there are differences. The aim of the study was to display and compare epidemiological and clinical characteristics of pandemic influenza in children. At Dr. Fran Mihaljević University Hospital for Infectious Diseases in Zagreb, in the first two seasons, the incidence of pandemic influenza virus A (H1N1) in particular was exhaustively analyzed only in patients with laboratory-confirmed pandemic influenza A virus (H1N1) 2009. In hospitalized children with documented influenza pandemic, moderate form of the disease predominated, which ultimately meant shorter hospital stay and fewer complications. Otitis media was the rarest complication in children in both seasons. In conclusion, children younger than 5 years, especially boys, were vulnerable groups for pandemic influenza, presenting as a mild disease with low mortality and few complications. Most of the affected children with influenza did not have important risk factors such as asthma and obesity, highlighted by other authors as significant risk factors.

Clinical and Laboratoy Characteristics of Parvovirus B19 Infection During 2013/2014 Outbreak in Zagreb, Croatia

BackgroundHuman Parvovirus B19 (HPV-B19) occurs worldwide and causes mild, acute exanthematous disease that occurs in a form of cyclic local epidemics. The aim of this study was to analyze clinical features and complication rates of acute HPV-B19 infection in different age groups.MethodsWe retrospectively reviewed the charts of 718 consecutive patients clinicaly diagnosed with acute HPV-B19 infection who visited outpatient department at the University Hospital for Infectious Diseases in Zagreb, Croatia during 2013–2014 outbreak. In 212 patients (of 298 tested) diagnosis was confirmed by positive IgM antibodies and/or HPV-B19 DNA in peripheral blood.ResultsOutbreak started in June 2013 and had a peak in April 2014, with highest prevalence in schoolchildren. There were no difference in clinical presentation or laboratory findings between clinicaly and serologicaly diagnosed patients. Biphasic presentation, fever, myalgia, arthralgia, headache and peripheral edema were more frequent in adults, but „slapped cheeks” was found predominantly in children. Complications were more common in adults, most commonly hematological disordes (mild anemia, thrombocytopenia and leukopenia), vasculitis, hepatitis and aseptic meningitis. There were no deaths in our cohort.Children (n = 52)Adults (n = 160) P-valueAge, years8.8 ± 4.139 ± 10.7Male sex31 (59.6%)26 (12.3%)0.0001Clinical presentationBiphasic presentation8 (15.4%)48 (30.0 %)0.0460Fever26 (50.0%)110 (68.7%)0.0194Rash51 (98.1%)127 (79.4%)0.0008Myalgia5 (9.6%)50 (31.2%)0.0017Arthralgia9 (17.3%)100 (62.5%)0.0001Headache3 (5.8%)34 (21.2%)0.0107“Slapped cheeks”29 (55,8%)24 (15.0%)0.0001Peripheral edema6 (11.5%)63 (39.4%)0.0001Anemia4 (7.7%)19 (11.8%)0.6076Leukopenia1 (1.9%)23 (14.5%)0.0111Thrombocytopenia4 (7.7%)35 (21.8%)0.0231Hepatitis1 (1.9%)11 (6.87%)0.3011Vasculitis1 (1.9%)2 (1.25%)0.5721Other2 (3.8%)3 (1.9%)0.5982Conclusion Parvovirus B19 infection has different clinical presentation, laboratory findings and complications in children and adults. Since the diversity of the clinical manifestations in adults may be misleading, the infection in adults should be suspected when disease is prevalent in children.Disclosures `All authors: No reported disclosures.

High Prevalence of Q80K Among NS3 Resistance-Associated Substitutions in Subtype 1a Patients with Chronic Hepatitis C Prior to Treatment with Direct Acting Antivirals: The Croatian Data

Background: Therapy for chronic hepatitis C is based on direct-acting antiviral drugs (DAA) that include protease inhibitors, polymerase inhibitors, as well as inhibitors of NS5A protein. Resistance-associated substitutions (RAS) can be associated with inadequate treatment outcomes with DAA. People with HCV subtype 1a infection carrying Q80K polymorphism could have a reduced treatment response to a protease inhibitor simeprevir. The data on the prevalence of Q80K polymorphism and other RAS worldwide are quite variable. Objectives: The study goal was to analyze the frequency of Q80K polymorphism and other substitutions associated with HCV resistance to NS3 inhibitors in patients previously not treated with simeprevir infected with HCV subtype 1a from Croatia. Methods: The study included 136 people with chronic hepatitis C and infected with HCV subtype 1a receiving clinical care at the department of viral hepatitis of the University hospital for infectious diseases, Zagreb and Croatian reference center for viral hepatitis from July 2015 to April 2016. All participants were not previously treated with simeprevir and not co-infected with HIV. Detection of Q80K polymorphism and other substitutions associated with resistance to NS3 inhibitors was performed by population-based sequencing on ABI PRISM® 3100 genetic analyzer. Phylogenetic tree was constructed using the Maximum Likelihood method and supported with a bootstrap test of 1000 replicates. Geno2Pheno algorithm was used for the interpretation of sequences, detection of resistance associated substitutions and determination of the clade of the sequence. Results: The prevalence of Q80K polymorphism was observed in 42.6% of patients while resistance to simeprevir (mediated by other RAS as well) was detected in 46.3% of patients. Phylogenetic analysis of subtype 1a sequences showed the separation into 2 clades and Q80K polymorphism was exclusively present in clade I isolates. Other RAS detected in the patients included V36L, T54S, V55A, S122R, and I170T. Conclusions: In conclusion, the prevalence of Q80K polymorphism was found to be rather high in patients with chronic hepatitis C infected with clade I subtype 1a while other substitutions associated with resistance to protease inhibitors were rarely found in Croatian cohort. The results of this study confirm the need for pre-treatment screening for Q80K in subtype 1a patients considered for simeprevir treatment.

Different features of influenza A H1N1pdm09 virus infection among adults in 2009/10 and 2010/11.

Influenza A H1N1pdm09 virus infection causes an epidemiologically and clinically severe disease mostly characterized by pneumonia, resulting in a high mortality rate. The purpose of this study was to investigate and compare epidemiological and clinical characteristics of influenza A H1N1pdm09 virus infection in patients hospitalized during the pandemic (2009/10) and post-pandemic seasons (2010/11). The data of patients with laboratory-confirmed influenza A H1N1pdm09 virus infection hospitalized and treated at the University Hospital for Infectious Diseases Dr. Fran Mihaljevic in Zagreb, Croatia in the first two seasons of appearance were analyzed. Compared to the pandemic season, in the post-pandemic season, patients were hospitalized longer, had higher values of inflammatory parameters, and were more often treated with antibiotics. The total number of risk factors in patients did not vary significantly between the two seasons. In the pandemic season, a significantly higher number of obese patients and patients with chronic lung disease was observed, whereas in the post-pandemic season, a statistically significant number of patients presented with symptoms of chronic cardiac and neuromuscular diseases. Primary viral pneumonia was frequently registered in younger adults during the pandemic season, whereas in the post-pandemic season, there were more cases of bacterial pneumonia. During the pandemic season, the influenza A H1N1pdm09 virus infection caused a severe disease with rare bacterial complications, especially in adult patients. The common characteristics of the influenza A H1N1pdm09 virus were lost in the post-pandemic season, assuming the shape and characteristics of the seasonal influenza A virus.

Fever of unknown origin--diagnostic methods in a European developing country.

Fewer of unknown origin (FUO) remains amongst the most difficult diagnostic dilemmas in contemporary medicine. The aim of this study was to determine the causes of FU and to identify the methods of diagnosis in patients with FUO in a tertiary care setting in the Republic of Macedonia. Retrospectively histories of 123 immunocompetent patients older than 14 years with classical FUO that had been examined at the University Hospital for Infectious Diseases and Febrile Conditions in the city of Skopje, during the period 2006-2012 were evaluated. FUO was defined as axillary fever of ≥ 37.5 °C on several occasions, fever duration of more than 21 days and failure to reach the diagnosis after the initial diagnostic workup comprised of several defined basic investigations. Infections were the cause of FUO in 51 (41.5%) of the patients, followed by non-infective inflammatory disorders (NIID) in 28 (22.8%), miscellaneous in 12 (9.7%) and neoplasm in 11 (8.9%) of the patients. Twenty one of the patients (17.1%) remained undiagnosed. The most common causes for FUO were visceral leishmaniasis, abscesses, urinary tract infections, subacute endocarditis, polymyalgia rheumatica and adult onset of Still disease. The final diagnosis was reached with histology in 24 (23.5%), imaging and endoscopic procedures in 21 (20.6%), clinical course and empiric therapy response in 20 (19.6%), serology in 18 (17.6%) and cultures in 16 (15.7%) of the cases. In the Republic of Macedonia infections are the leading cause of FUO, predominately visceral leishmaniasis. In the future in patients with prolonged fever, physicians should think more often of this disease, as well as of the possibility of atypical presentation of the common classical causes of FUO.

Risk factors for coronary artery abnormalities in children with Kawasaki disease: a 10-year experience.

Kawasaki disease (KD) is an acute systemic vasculitis of childhood. Due to development of coronary artery aneurysms (CAA) it is considered the most common cause of acquired heart disease in children. The clinical and laboratory features of patients with complete and incomplete KD were compared in order to identify the possible predictors of CAA development. A cross-sectional study of children with KD treated at the University Hospital for Infectious Diseases, Zagreb, between January 2003 and December 2012 was conducted. A total of 111 KD patients were included; 70.3% patients had complete KD. Patients with complete KD had more frequently rash, changes on extremities and mucous membranes, as well as higher serum bilirubin, aminotransferases, gamma-glutamyl transferase and lactate dehydrogenase levels. Patients with incomplete KD had longer duration of fever before the diagnosis (8 vs. 7 days) and delayed IVIG treatment (day 8 vs. 7). CAA was detected in seven children (6.3%). Disease duration before hospitalization >6 days (OR 7.16, 95% CI 1.51-100.35), age <6 months (OR 25.86, 95% CI 1.68-398.35) and platelet count >771 after the 7th day of disease (OR 13.33, 95% CI 2.19-80.87) were independently associated with CAA development. The diagnosis and treatment in incomplete KD can be delayed due to the absence of major criteria. Age, duration of symptoms prior hospitalization and platelet count were identified as independent predictors of CAA development.

Cardiovascular markers of inflammation and serum lipid levels in HIV-infected patients with undetectable viraemia.

IntroductionSuccessfully treated HIV-infected patients may still have an increased risk for cardiovascular morbidity and mortality, which might be related not only to traditional risks, but also to inflammation and dyslipidemia induced by HIV and/or antiretroviral therapy [1, 2]. We examined the relationship of serum lipid levels with plasma biomarkers of inflammation using a composite inflammatory burden score (IBS) from the following seven markers of inflammation: CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin.Materials and MethodsSubjects were selected among consecutive HIV-infected males ≥18 years of age with an undetectable viral load (<50 copies/mL of HIV1-RNA), seen at the University Hospital for Infectious Diseases, Zagreb, Croatia, in the period from January 2012 to March 2013. Plasma inflammatory biomarkers (CD40L, tPA, MCP-1, IL-8, IL-6, hCRP and P-selectin, quantified by bead-based cytometry) >75th percentile were considered elevated and an IBS was constructed as the presence of zero, one, two, or three or more elevated biomarkers. Correlations between the IBS and lipid parameters were examined using Spearman's Rho and by ordered logistic regression proportional odds model to estimate the odds of more elevated (>75th percentile) biomarkers.Results181 male patients were included into the study, the median age was 46.7 (Q1–Q3, 39.9–55.0) years and the median current CD4 cell count was 553.0 (Q1–Q3, 389–729) per microliter. The patients were mainly treated with two nucleoside reverse transcriptase inhibitor (NRTI) plus one non-NRTI (NNRTI) (N=100, 60.8%) or two NRTI plus lopinavir (N=50, 27.6%). There was a significant correlation between the IBS and serum cholesterol (Rho=0.23, 95% CI, 0.09–0.37), triglycerides (Rho=0.30, 95% CI, 0.16–0.42) and cholesterol/HDL-cholesterol ratio (Rho=0.25, 95% CI 0.11–0.38). In the multivariable model a one unit increase in cholesterol/HDL-cholesterol ratio was associated with a 1.72-fold (95% CI, 1.27–2.33) increased odds of having a greater IBS. One unit increase (mmol/L) of cholesterol and triglycerides was associated with a 1.41-fold (95% CI, 1.13–1.76) and 1.37-fold (95% CI, 1.18–1.60) increased odds of having a greater IBS, respectively.ConclusionsOur study suggests that in virologically suppressed patients there is a significant association between markers of inflammation and serum levels of cholesterol and triglycerides as well as the cholesterol/HDL-cholesterol ratio.