Prosthetic joint infection due to Mycobacterium xenopi: a review of the literature with a new case report.

PURPOSE: Extrapulmonary infections due to M. xenopi, particularly osteoarticular localizations, are rare. The purpose of this paper is to describe a case of prosthetic hip infection and to review the published literature on cases of M. xenopi osteoarticular infections. METHODS: Literature search was performed in the following databases: MEDLINE (PubMed), Embase, Central (the Cochrane Library 2019, Issue 1), LILACS (BIREME) (Latin American and Caribbean Health Science Information database) and Clinical Trials databases (14th August 2018). We included all case reports and case series on adult patients diagnosed with bone or joint infection by M. xenopi for whom the treatment and outcome were specified. RESULTS: We retrieved 30 cases published between 1982 and 2012, among which 25 (83.3%) were reported from Europe. The two most common infection sites were spine (12/30, 40%) and knee (9/30, 30%). Risk factors for infection were previous invasive procedures (11/30, 36.7%), autoimmune disease (8/30, 26.7%), AIDS (4/30, 13.3%) and other comorbidities (2/30, 6.7%); five patients had no past medical history. All patients were treated with antibiotic combinations, but composition and duration of regimens hugely varied. Surgical intervention was performed in 16 patients (53.3%). Only 11 patients obtained full recovery of articular mobility after treatment. CONCLUSION: This work highlights the difficulties in diagnosing and treating M. xenopi osteoarticular infections. Globally, evidence supporting the best practice for diagnosis and treatment of this infection is scanty.

Imported Infections with Mansonella perstans Nematodes, Italy.

We report 74 patients in Italy infected with Mansonella perstans nematodes, a poorly described filarial parasite. M. perstans nematodes should be included in the differential diagnosis for patients with eosinophilia from disease-endemic countries. Serologic analysis is useful for screening, and testing for microfilaremia in peripheral blood should be performed for parasite-positive patients.

The hidden epidemic of schistosomiasis in recent African immigrants and asylum seekers to Italy.

The prevalence of schistosomiasis among recent refugees from sub-Saharan Africa in Italy is unknown. This is a retrospective review of African immigrants screened at Centre for Tropical Diseases of Negrar from March 2014 to February 2016. Of the 373 immigrants tested, 34% were positive at least at one schistosomiasis test. The proportion of positive ELISA serology was 103/373 (27.6%). At microscopy, infected subjects were 65/373 (17.4%), (51% Schistosoma haematobium, 38% Schistosoma mansoni, 11% both). CCA antigen for S. mansoni was positive in 47/373 individuals (12.6%). We found a particularly high positivity rate in subjects from Mali (72.1%) and Ivory Coast (48%). This "hidden epidemic" of schistosomiasis cannot be longer neglected, considering the risk of severe complications, and the effective and inexpensive treatment available.

Chronic malaria and hyper-reactive malarial splenomegaly: a retrospective study on the largest series observed in a non-endemic country.

BACKGROUND: Chronic malaria is usually defined as a long-term malarial infection in semi-immune subjects, usually without fever or other acute symptoms. The untreated infection may evolve to hyper-reactive malarial splenomegaly (HMS), a life-threatening complication. This paper describes the largest series of HMS ever observed outside endemic countries, and the clinical outcome after a single anti-malarial treatment. Contrarily to most authors, still reporting the traditional, long-term treatment, regardless possible further exposure, the patients in this series did not receive any further prophylaxis if they were not re-exposed to malaria infection. METHODS: A retrospective, longitudinal study, describing all patients with HMS diagnosed at the Centre for Tropical Diseases of Negrar, Verona, took place over a 25-year period. HMS was defined by a longitudinal spleen diameter ≥16 cm, IgM ≥ 2.5 g/L, anti-malarial antibody titre ≥160, exclusion of other causes of splenomegaly. The short-term (≤6 months) clinical outcome after a single anti-malarial treatment was analysed and so was the long-term outcome of subjects re-exposed to malaria and submitted or not to anti-malarial prophylaxis or intermittent treatment. The association of the outcome with the main independent variables was first assessed with univariate analysis. Logistic regression was also performed. RESULTS: Forty-four subjects with HMS were retrieved. Of those with a short-term follow-up visit (<6 months, median 43 days) available before returning to endemic areas, 20/22 resulted improved/cured, two were unchanged. Of 22 expatriates seen at long-term follow-up after re-exposure, 18 were improved/cured, including eight out of nine who had followed an anti-malarial prophylaxis and 10/13 who had opted for the alternative of an intermittent treatment. CONCLUSION: HMS is the most severe form of chronic malaria. A single anti-malarial treatment is probably adequate to treat HMS in the absence of re-exposure, while an adequate prophylaxis is necessary for patients exposed again to malaria transmission. Intermittent treatment would probably be the only viable approach in endemic countries.

Recurrent seizures during acute acquired toxoplasmosis in an immunocompetent traveller returning from Africa.

INTRODUCTION: We report an unusual case of acute acquired toxoplasmosis (AAT) presenting as lymphadenopathy and recurrent seizures in an immunocompetent 15-year-old boy. MATERIALS AND METHODS: The patient reported an 18-day vacation to Africa (Ethiopia), 39 days prior to the first seizure. Electroencephalogram (EEG) showed sporadic single-spike or sharp-wave paroxysms and the magnetic resonance imaging (RMI) of the brain was negative. The serology for T. gondii was compatible with an acute infection defined as positive for both toxoplasma-specific IgG and IgM and a low avidity (6 %), confirmed by a reference laboratory. The patient reported other two episodes of seizures, occurring 7 days apart. He was treated with pyrimethamine plus sulfadiazine and leucovorin for 4 weeks, with an improvement of lymphadenitis and normalization of EEG. After 5 months, new seizures were reported and a diagnosis of epilepsy was done. Toxoplasma polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and blood were negative. A treatment with valproic acid was started, obtaining control of the neurological disease. CONCLUSION: Awareness of this neurologic manifestation by clinicians is required, also in immunocompetent patients. The relationship between toxoplasmosis and recurrent seizure needs to be investigated by new studies.

Comparison of clinical characteristics of tuberculosis between two age groups at an Italian Tertiary Hospital.

Differences in clinical characteristics and outcome between elderly (>60 years) and younger (18-59 years) tuberculosis (TB) patients were retrospectively evaluated. Alcohol abuse, radiological evidence of cavitation, and cough at presentation were more frequent among younger patients. Older patients were more likely to have comorbidities, disseminated TB, longer duration of symptoms and higher TB-related mortality (19 vs 0%). Very old patients (≥80 years) showed increased liver toxicity and hospital acquired infections compared to patients aged 60-79 years.

Mortality in ICU Patients with COVID-19-Associated Pulmonary Aspergillosis.

A review of 38 studies involving 1437 COVID-19 patients admitted to intensive care units (ICUs) with pulmonary aspergillosis (CAPA) was conducted to investigate whether mortality has improved since the pandemic's onset. The study found that the median ICU mortality was 56.8%, ranging from 30% to 91.8%. These rates were higher for patients admitted during 2020-2021 (61.4%) compared to 2020 (52.3%), and prospective studies found higher ICU mortality (64.7%) than retrospective ones (56.4%). The studies were conducted in various countries and used different criteria to define CAPA. The percentage of patients who received antifungal therapy varied across studies. These results indicate that the mortality rate among CAPA patients is a growing concern, mainly since there has been an overall reduction in mortality among COVID-19 patients. Urgent action is needed to improve prevention and management strategies for CAPA, and additional research is needed to identify optimal treatment strategies to reduce mortality rates among these patients. This study serves as a call to action for healthcare professionals and policymakers to prioritize CAPA, a serious and potentially life-threatening complication of COVID-19.

Leprosy in an Adopted Woman Diagnosed by Molecular Tools: A Case Report from a Non-Endemic Area.

Coupled with its rarity in non-endemic areas, the clinical heterogeneity of leprosy makes diagnosis very challenging. We report a diagnosis of multibacillary leprosy in a 22-year-old Indian woman, adopted at the age of 10 and living in Italy. The patient presented with painful skin lesions on the face, trunk, and lower and upper extremities, associated with dysesthesia and a motor deficit in her left leg following corticosteroid therapy interruption. Histopathology results from the skin lesions suggested leprosy, but no acid-fast bacilli were identified. Molecular biology in a center specializing in tropical diseases confirmed the diagnosis, allowing prompt and adequate treatment. Genotype analysis allowed the identification of a genotype 1D of M. leprae, facilitating the epidemiological investigation of the plausible infection origin. No resistances to rifampicin, dapsone, or ofloxacin were detected. Leprosy will continue to exist in high-income nations, and the incidence may rise over time due to increasing migration and globalization. CARE guidelines were followed.

Touching Base with Some Mediterranean Diseases of Interest from Paradigmatic Cases at the "Magna Graecia" University Unit of Infectious Diseases: A Didascalic Review.

Among infectious diseases, zoonoses are increasing in importance worldwide, especially in the Mediterranean region. We report herein some clinical cases from a third-level hospital in Calabria region (Southern Italy) and provide a narrative review of the most relevant features of these diseases from epidemiological and clinical perspectives. Further, the pathogenic mechanisms involved in zoonotic diseases are reviewed, focusing on the mechanisms used by pathogens to elude the immune system of the host. These topics are of particular concern for individuals with primary or acquired immunodeficiency (e.g., people living with HIV, transplant recipients, patients taking immunosuppressive drugs). From the present review, it appears that diagnostic innovations and the availability of more accurate methods, together with better monitoring of the incidence and prevalence of these infections, are urgently needed to improve interventions for better preparedness and response.

Negative prognostic impact of electrolyte disorders in patients hospitalized for Covid-19 in a large multicenter study.

BACKGROUND: The prognostic impact of electrolyte disorders in hospitalized COVID-19 patients is unclear. METHODS: The study included all adult patients hospitalized for COVID-19 in four hospitals in Northern Italy between January 2020 and May 2021 with at least one serum potassium and sodium measurement performed within 3 days since admission. Primary outcome was in-hospital death; secondary outcome was Intensive Care Unit (ICU) admission. A cause-specific Cox proportional-hazards regression model was used for investigating the association between potassium and sodium (as either categorical or continuous variables) and mortality or admission to ICU. RESULTS: Analyses included 3,418 adult hospitalized COVID-19 patients. At multivariable analysis, both hyperkalemia (Hazard Ratio, [HR] 1.833, 95% Confidence Interval [CI] 1.371-2.450) and sK above the median (K 5.1 vs 4.1 mmol/L: HR 1.523, 95% CI 1.295-1.798), and hypernatremia (HR 2.313, 95%CI 1.772-3.018) and sNa above the median (Na 149 vs 139 mmol/L: HR 1.442, 95% CI 1.234-1.686), were associated with in-hospital death, whereas hypokalemia and hyponatremia were not. Hyponatremia was associated with increased hazard of ICU admission (HR 1.884, 95%CI 1.389-2.556). CONCLUSIONS: Electrolyte disorders detected at hospital admission may allow early identification of COVID-19 patients at increased risk of adverse outcomes.

Therapy of uncomplicated falciparum malaria in Europe: MALTHER - a prospective observational multicentre study.

BACKGROUND: Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe. METHODS: A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine. RESULTS: Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group. CONCLUSIONS: This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

Toxoplasma gondii Serotypes in Italian and Foreign Populations: A Cross-Sectional Study Using a Homemade ELISA Test.

Toxoplasma gondii is a protozoan parasite responsible for human toxoplasmosis. The three major clonal lineages and different recombinant strains of T. gondii have a varied global distribution. This study aimed at evaluating the epidemiological distribution of types II and I-III and recombinant or mixed T. gondii in Italians and foreigners residing in Italy, establishing an association between serotypes and demographic characteristics. We collected the sera of 188 subjects who had tested positive for specific T. gondii antibodies. The population was differentiated into groups based on sex, nationality, and place of birth (Italy, Africa, South America, Asia, or Europe (except Italy)). We then performed a homemade ELISA test that detected both the antibodies against the amino acid sequences of the three main genotype antigens (I-III) in human sera and discerned the T. gondii strains. Serotype II of T. gondii was the most prevalent in the Italian population, whereas type I-III was the most prevalent in the foreign group. Surprisingly, we observed a notable amount of recombinant or mixed serotypes in European and Italian subjects. Moreover, we showed a significant difference in the prevalence of T. gondii serotypes between men and women, Italians, and foreigners. This descriptive study is the first to investigate the epidemiological distribution of T. gondii serotypes in humans in Italy using a homemade ELISA. We considered this technique suitable for discriminating between serotypes II and I-III and, consequently, for an epidemiological study focusing on the observation of circulating T. gondii strains and clinical correlations.

Tropheryma whipplei, Helicobacter pylori, and Intestinal Protozoal Co-Infections in Italian and Immigrant Populations: A Cross-Sectional Study.

Tropheryma whipplei (TW), Helicobacter pylori (HP), and intestinal protozoa (IP) are widespread pathogens with similar routes of transmission and epidemiological risk factors. Epidemiological data on co-infection between TW, HP, and IP are scarce. We aim to more deeply investigate the co-infection rate for these pathogens, evaluating the risk factors and symptoms. Methods: This is a cross-sectional study conducted at the IRCCS Sacro Cuore Don Calabria Hospital in Northern Italy, a referral center for tropical and Whipple's disease (WD). Stored stool samples from 143 subjects previously tested for TW DNA by real-time PCR were explored for HP and IP DNA detection. The virulence factor cagA was investigated in HP-positive patients. Results: A history of migration was reported significantly more in TW-positive than in negative subjects (34.1% vs. 9.1%, p = 0.001) and in HP-infected than in those non-infected (59.1% vs. 9.1%, p < 0.001). The HP infection rate differed significantly between TW-infected and uninfected groups (31.8% vs. 8.1%, p = 0.001), while no difference was observed for IP infection. Significantly higher TW intestinal colonization was found in HP-infected patients than in non-infected (63.6% vs. 24.8%, p < 0.001). In addition, the proportion of Blastocysts positive finding was also significantly higher in HP-infected than in non-infected (40.9% vs. 17.4%, p = 0.018). Conclusions: The present study is the first to report a high TW and HP co-infection rate. To reduce the risk of morbidity from a chronic infection of either pathogen, clinicians may consider TW-HP molecular screening on the same stool sample for patients with suspected HP disease or WD, particularly in case of travel history.

ELISA Test Based on the Phenolic Glycolipid-I (PGL-I) of Mycobacterium leprae: A Reality of a Laboratory from a Non-Endemic Country.

BACKGROUND: Leprosy is a neglected tropical disease caused by Mycobacterium leprae, leading to disabilities if untreated. The ELISA based on phenolic glycolipid I (PGL-I), or its synthetic version ND-O-BSA, is almost universally positive in multibacillary leprosy and thus extensively used in endemic countries. Household contacts with a positive antibody titer have ~6-fold higher probability to develop the disease than those with a negative titer. Thus, the aim of the study was to evaluate the performance of this ELISA in the setting of a non-endemic country. METHODS: We calculate the cut-off using optimized O.D. thresholds, generated by receiver operating characteristics (ROC) curve analysis, testing 39 well-characterized sera obtained from lepromatous leprosy patients with strongly positive ND-O-BSAELISA titer and 39 sera from healthy non-endemic patients never exposed to M. leprae or M. tuberculosis. Indeed, we tested a second set of sera from suspected or confirmed leprosy or household contacts (SLALT group, n=50), and patients with tuberculosis (control group, n=40). RESULTS: We detected 56.4% of SLALT and 22.5% of tuberculosis as positive, consistent with the literature. CONCLUSION: The ELISA based on ND-O-BSA may thus be considered a good option to be used in a non-endemic area as a screening tool in at risk population usually coming to our center.

Association Between Sex Hormone Levels and Clinical Outcomes in Patients With COVID-19 Admitted to Hospital: An Observational, Retrospective, Cohort Study.

Understanding the cause of sex disparities in COVID-19 outcomes is a major challenge. We investigate sex hormone levels and their association with outcomes in COVID-19 patients, stratified by sex and age. This observational, retrospective, cohort study included 138 patients aged 18 years or older with COVID-19, hospitalized in Italy between February 1 and May 30, 2020. The association between sex hormones (testosterone, estradiol, progesterone, dehydroepiandrosterone) and outcomes (ARDS, severe COVID-19, in-hospital mortality) was explored in 120 patients aged 50 years and over. STROBE checklist was followed. The median age was 73.5 years [IQR 61, 82]; 55.8% were male. In older males, testosterone was lower if ARDS and severe COVID-19 were reported than if not (3.6 vs. 5.3 nmol/L, p =0.0378 and 3.7 vs. 8.5 nmol/L, p =0.0011, respectively). Deceased males had lower testosterone (2.4 vs. 4.8 nmol/L, p =0.0536) and higher estradiol than survivors (40 vs. 24 pg/mL, p = 0.0006). Testosterone was negatively associated with ARDS (OR 0.849 [95% CI 0.734, 0.982]), severe COVID-19 (OR 0.691 [95% CI 0.546, 0.874]), and in-hospital mortality (OR 0.742 [95% CI 0.566, 0.972]), regardless of potential confounders, though confirmed only in the regression model on males. Higher estradiol was associated with a higher probability of death (OR 1.051 [95% CI 1.018, 1.084]), confirmed in both sex models. In males, higher testosterone seems to be protective against any considered outcome. Higher estradiol was associated with a higher probability of death in both sexes.

Incident Atrial Fibrillation and In-Hospital Mortality in SARS-CoV-2 Patients.

(1) Background: Among the different cardiovascular (CV) manifestations of the coronavirus disease 2019 (COVID-19), arrhythmia and atrial fibrillation (AF) in particular have recently received special attention. The aims of our study were to estimate the incidence of AF in patients hospitalized for COVID-19, and to evaluate its role as a possible predictor of in-hospital all-cause mortality. (2) Methods: We enrolled 3435 people with SARS-CoV2 infection admitted to three hospitals in Northern Italy from February 2020 to May 2021. We collected data on their clinical history, laboratory tests, pharmacological treatment and intensive care unit (ICU) admission. Incident AF and all-cause in-hospital mortality were considered as outcomes. (3) Results: 145 (4.2%) patients developed AF during hospitalization, with a median time since admission of 3 days (I-III quartile: 0, 12). Patients with incident AF were admitted more frequently to the ICU (39.3 vs. 12.4%, p < 0.001), and more frequently died (37.2 vs. 16.9%, p < 0.001). In the Cox regression model, the significant determinants of incident AF were age (HR: 1.041; 95% CI: 1.022, 1.060 per year), a history of AF (HR: 2.720; 95% CI: 1.508, 4.907), lymphocyte count (HR: 0.584; 95% CI: 0.384, 0.888 per 103/µL), estimated glomerular filtration rate (eGFR, HR: 0.988; 95% CI: 0.980, 0.996 per mL/min) and ICU admission (HR: 5.311; 95% CI: 3.397, 8.302). Incident AF was a predictor of all-cause mortality (HR: 1.405; 95% CI: 1.027, 1.992) along with age (HR: 1.057; 95% CI: 1.047, 1.067), male gender (HR: 1.315; 95% CI: 1.064; 1.626), dementia (HR: 1.373; 95% CI: 1.045, 1.803), lower platelet (HR: 0.997; 95% CI: 0.996, 0.998 per 103/µL) and lymphocyte counts (HR: 0.843; 95% CI: 0.725, 0.982 per 103/µL), C-Reactive protein values (HR: 1.004; 95% CI: 1.003, 1.005 per mg/L), eGFR (HR: 0.990; 95% CI: 0.986, 0.994 per mL/min), and ICU admission (HR: 1.759; 95% CI: 1.292, 2.395). (4) Conclusions: Incident AF is a common complication in COVID-19 patients during hospitalization, and its occurrence strongly predicts in-hospital mortality.