Anna Beltrame

Efficacy and Tolerability of Topical 1% Cidofovir Cream for the Treatment of External Anogenital Warts in Hiv-infected Persons

Background Treatment options for anogenital warts in patients with HIV-1 are unsatisfactory because they fail to eradicate latent human papillomavirus. Goal To determine tolerability and efficacy of topical 1% cidofovir cream for the treatment of external anogenital warts in HIV-infected patients. Study Design A randomized, placebo-controlled, single-blind, crossover pilot study of either 1% cidofovir cream or placebo applied once daily 5 days a week for 2 weeks followed by 2 weeks of observation was performed. Results Six patients were randomized to 1% cidofovir cream and six to placebo. The latter patients eventually received 1% cidofovir cream. Thus, 12 treatment rounds of cidofovir were compared with six rounds of placebo. A reduction of more than 50% in the total wart area achieved by seven cidofovir treatments (58%), as compared with no placebo regimen (P = 0.02). Local reactions occurred in 10 of the 12 patients treated with cidofovir, as compared with 0 of the 6 subjects in the placebo group (P < 0.001). Conclusions For the initial clearance of anogenital warts in HIV-infected patients, 1% cidofovir cream is significantly more effective than vehicle cream. Local mucosal erosion is a common side effect.

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

BackgroundMalaria 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.MethodsA 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.ResultsBetween 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.ConclusionsThis 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.

Schistosomiasis Screening of Travelers from Italy with Possible Exposure in Corsica, France

To the Editor: Since 2014, many cases of urogenital schistosomiasis acquired in Corsica, France, have been described (1–4). The infections, which all occurred in persons who had bathed in the Cavu River in 2011 or 2013, represent the first cases of autochthonous Schistosoma haematobium infection acquired in Europe since the last reported case in Portugal in 1965 (5). In June 2014, France established a screening program for persons reporting exposure to the Cavu River during 2011–2013. By March 2015, a national surveillance journal had reported 110 autochthonous urogenital schistosomiasis cases in residents of France (6). We describe the diagnostic work-up for and clinical management of persons from Italy who reported bathing in the Cavu River at least once during 2011–2014. All of the patients had requested screening after learning of the risk for acquiring schistosomiasis after freshwater exposure in Corsica. Exclusion criteria for the study included residence in or travel to a country where schistosomiasis is endemic. At least 3 months after their last exposure to the Cavu River, each participant had a filtered terminal urine sample and a serum sample tested for schistosomiasis. Different commercial tests were used, depending on local availability: 3 different ELISAs and an indirect immunofluorescent antibody test (IIFAT). All serum samples were tested in parallel in a laboratory in Florence, Italy, by using 2 Western blots (WBs): a Schistosoma WB IgG kit containing antigens from adult S. mansoni worms and a second kit containing S. mansoni and S. haematobium antigens from a crude adult extract (LDBio Diagnostics, Lyon, France). Confirmed urogenital schistosomiasis was defined by confirmation of S. haematobium eggs in urine by microscopy, positive WB result, or both. Probable urogenital schistosomiasis was defined by positive serologic test results. Possible urogenital schistosomiasis was defined by signs or symptoms suggestive of schistosomiasis (i.e., urogenital symptoms), eosinophilia (>0.4 × 109 cells/L of blood), or both (7). All participants who met the case definition received 1 oral dose of praziquantel (40 mg/kg). Forty-three persons were consecutively enrolled during January 2014–January 2015; of these, 15 (34%) had confirmed (6 patients), probable (2 patients), or possible (7 patients) urogenital schistosomiasis (Table). Of these 15 patients, 7 (47%) reported repeat visits to Cavu River over a period of at least 2 years. The mean eosinophil count was 295 (range 40–1,540) cells/μL of blood; 6 (40%) patients had eosinophilia. Genitourinary symptoms were reported by 7 (47%) patients, and blood was detected by dipstick in the urine of 1 patient. Schistosoma eggs were not found in any urine samples. Table Demographic, epidemiologic, clinical, and laboratory data for 15 patients with urogenital schistosomiasis acquired after bathing in the Cavu River, Corsica, France* Schistosomiasis screening has been suggested for persons with exposure to the Cavu River (6); however, clinical history and clinical evaluation alone and eosinophilia, have low sensitivity for the diagnosis of urogenital schistosomiasis (7,8). Asymptomatic infection has been reported in 25%–36% of persons with travel-associated schistosomiasis, and eosinophilia was present in 50% of the patients (7,8). In screenings in France, only 27% of schistosomiasis-positive patients reported genitourinary symptoms (6). For the diagnosis of urogenital schistosomiasis, serologic testing is more sensitive than detection of eggs in urine, particularly in mild infections (7–9). Many asymptomatic family members of the index case-patients who acquired infection in Corsica tested positive only by serologic testing (1–4). However, commercial serologic tests for schistosomiasis have low sensitivity (9). Kinkel et al. (9) showed that sensitivity of an IIFAT and 3 ELISAs for S. haematobium ranged from 21.4% to 71.4%. In the Corsica outbreak, serologic testing may be even less sensitive because of the hybrid nature of the schistosoma (S. haematobium/S. bovis) (6). In our study, only 2 patients had positive ELISA results. Combinations of >2 serologic tests can markedly increase testing sensitivity to almost 78.6% (9). Sulahian et al. (10) found that a WB containing S. mansoni antigens had 89.5% sensitivity and 100% specificity for S. mansoni. In our study, no patients with urogenital schistosomiasis tested positive by WB containing S. mansoni antigens, but 6 patients tested positive by WB containing S. haematobium antigens. In mild infections, the absence of schistosoma antibodies cannot exclude a diagnosis of urogenital schistosomiasis (7). Therefore, we provided treatment to patients with possible urogenital schistosomiasis; our decision to treat these patients considered the tolerability of praziquantel and the possible severe genitourinary complications of untreated infections (e.g., bladder carcinoma, infertility). Our findings suggest that a sensitive screening strategy for urogenital schistosomiasis consists of a patient’s travel history (exposure in multiple years), clinical history (any new genitourinary complaints after freshwater exposure), eosinophil count, and serologic testing. Because of the failure of commercial ELISA and IIFAT methods, we emphasize that a WB containing S. haematobium antigen should also be used for screening. Of note, a confirmed urogenital schistosomiasis case acquired after a single exposure in 2014 was never reported (1–4,6). The risk for delayed diagnosis of this insidious, neglected disease, which has recently reappeared in Europe, must be reduced. To accomplish this, information regarding the risk for schistosomiasis after freshwater exposure in Corsica must be disseminated to physicians worldwide.

Human granulocytic anaplasmosis in northeastern Italy

Abstract:  Sporadic cases of human granulocytic anaplasmosis (HGA) have been reported in areas with a high prevalence of tick‐borne diseases (TBDs) in Europe. We aimed at estimating the sero‐prevalance of A. phagocytophilum and other TBDs in northeastern Italy in outpatients with a history of recent tick bite or suspected TBD. In the 1‐year study, 79 patients were enrolled and 30 (38%) received a diagnosis of TBD: 24 (30%) with Lyme desease and 5 (6%) with HGE. Our findings indicate the presence of HGA in northernsterm Italy; so, since co‐infection with Lyme disease appeared to be frequent, physicians assessing patients after a tick bite should consider HGA in the diagnosis.

Tick-borne encephalitis in Friuli Venezia Giulia, northeastern Italy.

Tick-borne encephalitis (TBE) is an infectious zoonotic disease occurring in so-called natural foci present in many European countries, rarely encountered in Italy [1, 2]. Ixodes ricinus is the dominant hard tick vector of the European subtype of TBE virus. In Italy, it represents the main vector of the infection that may be sub-clinical in 70–95% of cases [3]. We report the first confirmed autochtonous case of TBE in Friuli Venezia Giulia (FVG). On July 28, 2003, a 36-year-old female was admitted to the Department of Neurology at the Hospital of Udine complaining of fever (39 °C), headache, vomiting, pain in the shoulders, and neck stiffness, which had begun 24 h before. On physical examination, neck stiffness, paralysis of upper limbs more prominent on the left side and shoulder girdle, and weakness on the left leg were detected. The computerized tomography scan of the brain was normal. Lumbar puncture (LP) was performed and disclosed a clear fluid, WBC count of 343 cells/mm3 (300 polymorphonuclear cells), a glucose level of 48 mg/dl and a protein level of 900 mg/dl. She had never been vaccinated against yellow fever or Japanese encephalitis and she had not traveled outside Italy over the last 12 months. On July 5–6, 2003, she spent the weekend in a rural area of the northeastern Alps in FVG (near Moggio – Chiusaforte) and she reported a tick bite during a walk through dense vegetation. About 2 weeks later, she had fever (37.5 °C) and flu-like symptoms of 3day duration. She was otherwise well until July 26, 2 days before the first hospital admission. An electromyography revealed critical illness neuropathy with severe damage to the bilateral brachial plexus, more relevant on the left side with a distal gradient. The MRI of the cervical spine showed an increased signal on T2-weighted images of the spinal cord anterior horns of the vertebrae cervicales C4-C6. Another LP was performed on August 18, and serological tests for viruses that cause neurological diseases were performed on paired serum and CSF samples. The result of enzyme immunoassay for the quantitative detection of specific IgG and IgM antibodies to the TBE virus in serum and CSF showed the presence of specific IgM (6.8 and 4.8 index, respectively; normal value < 1) and IgG (49 and 48 U/ml, respectively; normal value < 5). The result was later confirmed with hemagglutination inhibition antibody test and neutralization assay by a reference center [2]. The patient was discharged home with a diagnosis of meningoencephalomyelitis form of TBE complicated by diplegia of the upper limbs, more evident on the left side. The emergence and recognition of an increasing number of new TBE cases in Europe in recent years highlights the significance of this zoonosis as a public health problem of growing importance [4, 5]. The clinical features of our case were typical, but the area in which it occurred was not considered endemic; this in turn entailed low clinical suspicion index and delays in diagnosis. Presently this region is only reported as an area of endemicity for Lyme borreliosis, and not for TBE [6]. In Italy, the first clinical case of TBE was documented in 1975 in Tuscany [7]. Since then, sporadic cases have been reported particularly in the northeast provinces (TrentinoAlto Adige and Veneto) [8]. During the years 1995–2001, the number of cases of TBE increased, with a total of 102 indigenous TBE cases recorded. By comparing the median number of TBE cases per year recorded in the period 1975– 1991 and in the period 1992–2001, a 10-fold increase in the incidence of the TBE can be calculated [1]. Infection Correspondence

African Trypanosomiasis Gambiense, Italy

African trypanosomiasis caused by Trypanosoma brucei gambiense has not been reported in Italy. We report 2 cases diagnosed in the summer of 2004. Theses cases suggest an increased risk for expatriates working in trypanosomiasis-endemic countries. Travel medicine clinics should be increasingly aware of this potentially fatal disease.

Acute Renal Failure Due to Visceral Leishmaniasis by Leishmania infantum Successfully Treated With a Single High Dose of Liposomal Amphotericin B

We report a visceral leishmaniasis case in an immunocompetent immigrant with acute renal failure. Parasites were demonstrated in bone marrow, peripheral blood, and kidney samples. A collapsing focal segmental glomerulosclerosis was documented, which was successfully treated with a single infusion of 10 mg/kg liposomal amphotericin B.

Neurological manifestation of tick-borne encephalitis in North-Eastern Italy

Tick-borne encephalitis (TBE) is an infectious zoonotic disease, moving from Central Europe to other countries and still rare in Italy. The disease, produced by the European subtype virus, typically takes a biphasic course with neurological disorders of different severity during its second phase. We report the first three TBE cases in Friuli Venezia Giulia (FVG), characterised by extremely variable clinical features. Knowledge of these different presentations will assist physicians in increasing their level of attention to TBE also in this region, where no cases of TBE had been reported in the past, despite the fact that it borders countries with high prevalence of the infection.

Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis

Background Schistosomiasis is a neglected infection affecting millions of people, mostly living in sub-Saharan Africa. Morbidity and mortality due to chronic infection are relevant, although schistosomiasis is often clinically silent. Different diagnostic tests have been implemented in order to improve screening and diagnosis, that traditionally rely on parasitological tests with low sensitivity. Aim of this study was to evaluate the accuracy of different tests for the screening of schistosomiasis in African migrants, in a non endemic setting. Methodology/Principal findings A retrospective study was conducted on 373 patients screened at the Centre for Tropical Diseases (CTD) in Negrar, Verona, Italy. Biological samples were tested with: stool/urine microscopy, Circulating Cathodic Antigen (CCA) dipstick test, ELISA, Western blot, immune-chromatographic test (ICT). Test accuracy and predictive values of the immunological tests were assessed primarily on the basis of the results of microscopy (primary reference standard): ICT and WB resulted the test with highest sensitivity (94% and 92%, respectively), with a high NPV (98%). CCA showed the highest specificity (93%), but low sensitivity (48%). The analysis was conducted also using a composite reference standard, CRS (patients classified as infected in case of positive microscopy and/or at least 2 concordant positive immunological tests) and Latent Class Analysis (LCA). The latter two models demonstrated excellent agreement (Cohen’s kappa: 0.92) for the classification of the results. In fact, they both confirmed ICT as the test with the highest sensitivity (96%) and NPV (97%), moreover PPV was reasonably good (78% and 72% according to CRS and LCA, respectively). ELISA resulted the most specific immunological test (over 99%). The ICT appears to be a suitable screening test, even when used alone. Conclusions The rapid test ICT was the most sensitive test, with the potential of being used as a single screening test for African migrants.

Schistosomiasis in european travelers and migrants: Analysis of 14 years tropnet surveillance data

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.