An estimate of the burden of serious fungal diseases in Greece.

Data on the epidemiology of serious fungal infections in Greece are scarce. Our aim was to calculate the burden of serious fungal diseases in Greece. A thorough literature search for papers reporting epidemiological data on serious fungal diseases in Greece was performed. Where no Greek data existed, we used a structured set of assumptions to estimate fungal disease burden, based on specific high-risk populations. Of the 10.8 million population, 85.5 % are adults and 27 % are over 60 years of age. The annual fungal disease estimates are as follows: 142,337 Greek women get recurrent vaginal thrush (2,632 cases/100,000 females); there are 889 cases of esophageal candidiasis (8.2 cases/100,000); annual incidence of Pneumocystis pneumonia is 112 cases; chronic pulmonary aspergillosis prevalence is 386 cases; there are 20,843 patients with allergic bronchopulmonary aspergillosis and 27,744 with severe asthma with fungal sensitization; candidaemia incidence is 541 cases (5.0/100,000); there are 81 cases of Candida peritonitis; invasive aspergillosis occurs in 1,125 patients. According to our calculations, 194,067 individuals (1.79 cases/100,000) in Greece suffer from serious fungal diseases each year. This is the first attempt to determine the burden of fungal diseases in Greece, and provides a crude estimate on its impact on public health.

Infectious complications following allogeneic stem cell transplantation by using anti-thymocyte globulin-based myeloablative conditioning regimens in children with hemoglobinopathies.

BACKGROUND: Anti-thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo-SCT) for hemoglobinopathies; however, epidemiology data for transplant-related infections in this population are scarce. METHOD: We retrospectively analyzed the epidemiology of bacterial, fungal, viral, and parasitic infections in a cohort of 105 children and adolescents with ß-thalassemia (n = 100) or sickle cell disease (n = 5) who underwent allo-SCT using human leukocyte antigen (HLA)-identical sibling (n = 96) or HLA-compatible unrelated donors (n = 9) in a single institution. All patients received an ATG-based conditioning regimen. RESULTS: The cumulative incidence of cytomegalovirus (CMV) viremia was 45.7% (95% confidence interval [CI] 33-55%), developing at a median of 48 (range 12-142) days without evidence of overt CMV disease. Herpes zoster developed in 8 patients at a median of 12 months post transplant, while 10 patients presented with late onset hemorrhagic cystitis at a median of 35 days post transplant. The cumulative incidence of bacteremia was 17.1% (95% CI 10.6-25%), occurring at a median of 74 (range 24-110) days. No patient developed probable or definite invasive fungal infection. Four deaths were recorded; 2 of them were attributed to infections (toxoplasmosis and Pneumocystis jirovecii pneumonia, respectively). CONCLUSION: The rate of infections after allo-SCT, using an ATG-containing preparative regimen, in our population of pediatric patients with hemoglobinopathies is comparable to that reported elsewhere with the use of non-ATG containing regimens.

Dimorphic fungal osteoarticular infections.

The objective of this investigation was to review the clinical manifestations, management, and outcome of osteoarticular infections caused by dimorphic fungi. We exhaustively reviewed reports of bone and joint infections caused by dimorphic fungi published between 1970 and 2012. Underlying conditions, microbiological features, histological characteristics, clinical manifestations, antifungal therapy, and outcome were analyzed in 222 evaluable cases. Among 222 proven cases (median age 41 years [interquartile range (IQR) 26-57]), 73 % had no predisposing condition. Histopathology performed in 128 (57 %) cases and culture in 170 confirmed diagnosis in 63 % and 98 % of the cases, respectively. Diagnosis was obtained from an extra-osteoarticular site in 16 cases. The median diagnostic time was 175 days (IQR 60-365). Sporothrix schenckii was the most frequent pathogen (n = 84), followed by Coccidioides immitis (n = 47), Blastomyces dermatitidis (n = 44), Histoplasma capsulatum (n = 18), Paracoccidioides brasiliensis (n = 16), and Penicillium marneffei (n = 13). Arthritis occurred in 87 (58 %) cases and osteomyelitis in 64 (42 %), including 19 vertebral osteomyelitis. Dissemination was reported in 123 (55 %) cases. Systemic antifungal agents were used in 216 (97 %) patients and in combination with surgery in 129 (60 %). Following the Infectious Diseases Society of America (IDSA) guidelines, a successful initial medical strategy was observed in 97/116 (84 %) evaluable cases. The overall mortality was 6 %, and was highest for P. marneffei (38.5 %). This study demonstrates that dimorphic osteoarticular infections have distinctive clinical presentations, occur predominantly in apparently immunocompetent patients, develop often during disseminated disease, and may require surgical intervention.

Timing of last COVID-19 vaccine dose and SARS-CoV-2 breakthrough infections in fully (boosted) vaccinated healthcare personnel.

AIM: To estimate the incidence, timing and severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) breakthrough infections in fully vaccinated healthcare personnel (HCP). METHODS: In total, 6496 fully vaccinated HCP were analysed prospectively from 15th November 2021 to 17th April 2022. Full coronavirus disease 2019 (COVID-19) vaccination was defined as a complete primary vaccination series followed by a booster dose at least 6 months later. RESULTS: Overall, 1845 SARS-CoV-2 breakthrough infections occurred (28.4 episodes per 100 HCP), of which 1493 (80.9%) were COVID-19 cases and 352 (19.1%) were asymptomatic infections. Of the 1493 HCP with COVID-19, four were hospitalized for 3-6 days (hospitalization rate among HCP with COVID-19: 0.3%). No intubations or deaths occurred. SARS-CoV-2 breakthrough infections occurred at a mean of 16.2 weeks after the last vaccine dose. Multi-variable regression analyses showed that among the 1845 HCP with a breakthrough infection, the administration of a COVID-19 vaccine dose ≥16.2 weeks before the infection was associated with increased likelihood of developing COVID-19 rather than asymptomatic SARS-CoV-2 infection [odds ratio (OR) 1.58, 95% confidence interval (CI) 1.01-2.46; P=0.045] compared with administering a vaccine dose later. The likelihood of developing COVID-19 compared with asymptomatic infection increased by 7% weekly after the last COVID-19 vaccine dose (OR 1.07, 95% CI 1.03-1.11; P=0.001). CONCLUSION: SARS-CoV-2 breakthrough infections are common among fully (boosted) vaccinated HCP. However, full COVID-19 vaccination offered considerable protection against hospitalization. These findings may contribute to defining the optimal timing for booster vaccinations. More efficient COVID-19 vaccines that will also confer protection against SARS-CoV-2 infection are needed urgently.

Effective control of an acute gastroenteritis outbreak due to norovirus infection in a hospital ward in Athens, Greece, April 2011.

In April 2011, an acute gastroenteritis outbreak due to norovirus infection occurred in a hospital ward in Athens, Greece, affecting 28 people: 16 staff members, 10 inpatients and two relatives of symptomatic inpatients. The attack rate among the patients and staff was 16.4% (10/61) and 31.4% (16/51), respectively. The outbreak lasted eight days and the clinical symptoms were mild. Effective infection control measures prevented the spread of the virus to other hospital wards.

Costs associated with COVID-19 in healthcare personnel in Greece: a cost-of-illness analysis.

BACKGROUND: Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the aetiological agent of coronavirus disease 2019 (COVID-19). AIM: To estimate the costs related to SARS-CoV-2 exposure and infection among HCP in Greece. METHODS: Data were retrieved from the national database of SARS-CoV-2 infections and from the database of HCP exposed to patients with COVID-19. A cost-of-illness analysis was performed to estimate total, direct and indirect costs. RESULTS: In total, 254 HCP with COVID-19 and 3332 HCP exposed to patients with COVID-19 during the first epidemic wave were studied. Of the 254 HCP with COVID-19, 49 (19.3%) were hospitalized (mean length of hospitalization 11.6 days) and four were admitted to intensive care units (mean duration 10.8 days). Overall, 1332 (40%) exposed HCP had a mean duration of absenteeism of 7.5 days, and 252 (99.2%) HCP with COVID-19 had a mean duration of absenteeism of 25.8 days. The total costs for the management of the two groups were estimated at €1,735,830 (€772,890 Euros for HCP with COVID-19 and €962,940 for exposed HCP). Absenteeism accounted for a large proportion of the total costs (80.4% of all expenditures), followed by costs for reverse transcriptase polymerase chain reaction and hospitalization (10.2% and 6.5% of all expenditures, respectively). CONCLUSION: COVID-19 is associated with increased rates and duration of absenteeism among HCP. Indirect costs, particularly absenteeism, are the major driver of total costs among exposed HCP and HCP with COVID-19. The estimated total costs are conservative. Studies are needed to explore the impact of COVID-19 vaccination of HCP on absenteeism and COVID-19-associated costs.

Hospital factors associated with SARS-CoV-2 infection among healthcare personnel in Greece.

Healthcare workers (HCWs) have been recognized as a high-risk group for infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study estimated their risk of infection based on hospital characteristics. Factors significantly associated with increased risk for SARS-CoV-2 infection were: working in a non-referral hospital compared with a coronavirus disease 2019 (COVID-19) referral hospital, working in a hospital with a high number of employees, and working in a hospital with an increased number of patients with COVID-19. This study revealed gaps in infection control in the non-referral hospitals. There is an urgent need for continuous training in infection control practices. Compliance of HCWs with the use of personal protective equipment should also be addressed.

Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1.

Characterization of the cytotoxic T lymphocyte (CTL) response against HIV-1 has been limited by the use of target cells expressing viral proteins from laboratory isolates of HIV-1. This approach has favored identification of group-specific CTL responses and precluded assessment of the extent of type-specific CTL responses directed against HIV-1. Using cells expressing viral proteins from the HIV-1 IIIB strain, we performed a detailed characterization of HIV-1-specific CTL response in three laboratory workers accidentally infected with HIV-1 IIIB. Eight of the epitopes identified were group specific, lying in relatively conserved regions of Gag, reverse transcriptase, and envelope. Three type-specific epitopes were identified, two of them in highly variable regions of envelope. In longitudinal studies in one subject, seven different epitopes and five different restricting HLA class I alleles were identified, with a progressive increase in the number of CTL epitopes recognized by this subject over time. Our data demonstrate that type-specific CTL responses make up a significant proportion of the host cellular immune response against HIV-1 and that a broadening of epitope specificity may occur.

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

Echocardiographic findings in patients with temporal arteritis: apropos of one case of temporal arteritis-associated verrucous (Libman-Sachs) endocarditis.

We report the case of a 70-year-old patient who presented with fever of unknown origin. The initial diagnosis was infective endocarditis as a mitral valve vegetation was found in a transesophageal echocardiogram. Lack of response to empiric antibiotic treatment and further diagnostic work-up established the correct diagnosis of marantic endocarditis due to temporal arteritis. Treatment with steroids and aspirin led to rapid clinical improvement and disappearance of the vegetation. Apropos of this case, we reviewed the records of 25 patients with a new diagnosis of temporal arteritis and analyzed the echocardiographic findings in comparison to those of 40 age- and sex-matched controls. Abnormal echocardiographic findings were present in 13 (52%) out of 25 patients with temporal arteritis and in 5 (12.5 %) out of 40 controls (p < 0.001, chi-square test).

Extranodal non-Hodgkin lymphoma presenting as a soft tissue mass in the proximal femur in a HIV(+) patient.

Primary soft tissue non-Hodgkin lymphomas (NHL) are very rare especially among HIV-1 infected patients. We describe a patient with HIV-1 infection who presented with acute pain of the right proximal femur. The clinical and laboratory investigation revealed a high grade centroblastic B-cell lymphoma of soft tissue. The patient was treated by surgical resection of the tumor, chemotherapy and local radiotherapy with no serious side effects. After 36 mdnths of follow up he is in excellent clinical condition, with his lymphoma in complete remission.

Lactobacillus rhamnosus endocarditis complicating colonoscopy.

We report the first case of endocarditis caused by Lactobacillus after an uneventful colonoscopy. The initial empiric treatment with the standard regimen of penicillin-aminoglycoside failed; subsequent treatment with a combination of antibiotics, selected according to the in vitro studies, was successful.

Eosinophilic granuloma of the femur in an HIV-1-positive patient.

A case of eosinophilic granuloma in the right femur of an HIV-1-infected patient is described, and the possible pathogenetic role of HIV infection in eosinophilic granuloma formation is discussed.

An unusual case of brucellar spondylitis involving both the cervical and lumbar spine.

We report an unusual case of brucellar spondylitis, involving both the cervical and lumbar spine. Diagnosis was established using magnetic resonance imaging (MRI). An initial plain radiograph of the lumbar spine, showing mild degenerative lesions, was misleading. Therefore, institution of a proper treatment was delayed.

A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies.

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.

Nutritional risk as predictor for healthcare-associated infection among hospitalized elderly patients in the acute care setting.

BACKGROUND: Poor nutritional status is associated with high rates of healthcare-associated infections (HCAIs) among hospitalized elderly patients. Early recognition of patients at risk for HCAIs is important. The Geriatric Nutritional Risk Index (GNRI) is a screening tool able to predict nutrition-related complications. AIM: To examine the use of GNRI as a predictor of HCAIs in the acute care setting. METHODS: A total of 248 consecutive patients aged >65 years, admitted as emergencies to the medical ward of an acute care hospital, were enrolled. On admission, clinical and laboratory assessment, anthropometric measurements, performance status, and GNRI score estimation were performed. HCAIs were recorded during admission. FINDINGS: On admission, 53.8% of the patients were not at risk, 37.2% at low or medium risk and 8.9% at high risk for nutrition-related complications, as stratified by using the GNRI. During hospitalization 23.7% of the patients developed HCAIs. Patients with HCAIs had higher mortality (P < 0.001) and longer hospital stay (P < 0.001). In multivariate analysis, a performance status >1 [hazard ratio (HR): 2.08; 95% confidence interval (CI): 1.07-4.02; P = 0.03] and diabetes (HR: 2.57; 95% CI: 1.37-4.84; P = 0.003) were associated with increased risk for HCAIs, whereas GNRI score (per unit increase) had a protective effect (HR: 0.97; 95% CI: 0.95-0.99; P = 0.01). Well-nourished patients (GNRI >98) were significantly more likely to remain free from HCAIs during hospitalization (P = 0.003). CONCLUSION: GNRI can accurately stratify hospitalized elderly patients according to risk for developing HCAIs.

Efficacy of prolonged antimicrobial chemotherapy for brucellar spondylodiscitis.

The standard treatment of brucellar spondylitis with a combination of two antibiotics for 6-12 weeks is associated with high rates of treatment failure and relapse. The present study aimed to assess the safety and efficacy of a treatment strategy based on the prolonged administration of a triple combination of suitable antibiotics. Eighteen patients with brucellar spondylitis were treated with a combination of at least three suitable antibiotics (doxycycline, rifampin, plus intramuscular streptomycin or cotrimoxazole or ciprofloxacin) until the completion of at least 6 months of treatment, when clinical, radiological and serology re-evaluation was performed. If necessary, the treatment was continued with additional 6-month cycles, until resolution or significant improvement of clinical and radiological findings, or for a maximum of 18 months. At presentation, the median age was 66 years (range, 42-85 years) with male predominance. The median duration of therapy was 48 weeks (range 24-72 weeks). Treatment was discontinued early because of side-effects in only one patient. Surgical intervention was required for three patients. At the end of treatment all patients had a complete response. After completion of treatment, all patients were followed up with regular visits. During the follow-up period (duration 1-96 months, median 36.5 months), no relapses were observed. In conclusion, prolonged (at least 6 months) administration of a triple combination of suitable antibiotics appears to be an effective treatment for brucellar spondylitis.