Stefania Marocco

Randomized Clinical Trial on Ivermectin versus Thiabendazole for the Treatment of Strongyloidiasis

Background Strongyloidiasis may cause a life-threatening disease in immunosuppressed patients. This can only be prevented by effective cure of chronic infections. Direct parasitologic exams are not sensitive enough to prove cure if negative. We used an indirect immune fluorescent antibody test (IFAT) along with direct methods for patient inclusion and efficacy assessment. Methodology/Principal Findings Prospective, randomized, open label, phase III trial conducted at the Centre for Tropical Diseases (Verona, Italy) to compare efficacy and safety of ivermectin (single dose, 200 µg/kg) and thiabendazole (two daily doses of 25 mg/Kg for two days) to cure strongyloidiasis. The first patient was recruited on 6th December, 2004. Follow-up visit of the last patient was on 11th January, 2007. Consenting patients responding to inclusion criteria were randomly assigned to one of the treatment arms. Primary outcome was: negative direct and indirect (IFAT) tests at follow-up (4 to 6 months after treatment) or subjects with negative direct test and drop of two or more IFAT titers. Considering 198 patients who concluded follow-up, efficacy was 56.6% for ivermectin and 52.2% for thiabendazole (p = 0.53). If the analysis is restricted to 92 patients with IFAT titer 80 or more before treatment (virtually 100% specific), efficacy would be 68.1% for ivermectin and 68.9% for thiabendazole (p = 0.93). Considering direct parasitological diagnosis only, efficacy would be 85.7% for ivermectin and 94.6% for thiabendazole (p = 0.21). In ivermectin arm, mild to moderate side effects were observed in 24/115 patients (20.9%), versus 79/108 (73.1%) in thiabendazole arm (p = 0.00). Conclusion No significant difference in efficacy was observed, while side effects were far more frequent in thiabendazole arm. Ivermectin is the drug of choice, but efficacy of single dose is suboptimal. Different dose schedules should be assessed by future, larger studies. Trial Registration Portal of Clinical Research with Medicines in Italy 2004–004693–87

Transmission of HIV-Associated Tuberculosis to Healthcare Workers

OBJECTIVE A retrospective investigation was made to compare the occupational risk of tuberculosis in personnel assisting human immunodeficiency virus (HIV)-infected and uninfected subjects with active tuberculosis. DESIGN We retrospectively reviewed 6 years of hospital activity in 3 units where HIV-infected patients with tuberculosis are hospitalized and in 2 units where non-HIV-infected tuberculosis patients are hospitalized. The risk of occupational tuberculosis in healthcare workers who assisted HIV-infected and non-HIV-infected patients with tuberculosis was investigated. PARTICIPANTS The risk of occupational tuberculosis in healthcare workers was studied by considering the numbers of potential source cases (hospitalized patients with tuberculosis) in the two conditions investigated (HIV-positive and HIV-negative). Both potential source cases and cases of tuberculosis in healthcare workers had to be microbiologically proven in order to be considered. RESULTS Seven cases of tuberculosis occurred in persons who cared for 85 HIV-infected subjects with tuberculosis, while only 2 cases occurred in staff members who took care of 1,079 HIV-negative tuberculosis patients over the same period (relative risk = 44.4; 95% confidence interval = 8.5-438). CONCLUSIONS Tuberculosis seems no longer to be a neglectable risk in healthcare workers assisting patients with HIV infection. Further study is urgently needed to see whether such unexpectedly high dissemination of tuberculosis also is demonstrable in the community.

Imported Malaria in Adults and Children: Epidemiological and Clinical Characteristics of 380 Consecutive Cases Observed in Verona, Italy

BACKGROUND Since the year 2000, in Italy, there has been a constant decrease in the number of cases of imported malaria in immigrants. Nevertheless, immigrants still account for about 70% of reported cases. To our knowledge, no data are yet available on imported malaria in children. This paper describes the main characteristics of malaria cases observed in recent years in the three main hospitals in Verona (roughly representing 10% of all cases reported in Italy in the period), with a special focus on the poorly known problem of imported malaria in children. METHOD All malaria cases occurring from 2000 to 2004 were retrospectively examined. Semi-immune and nonimmune patients were analyzed for clinical, laboratory, and parasitological findings. A separate analysis was carried out for children who traveled to endemic areas to visit relatives and friends (VRF) and children born in endemic countries who came to Italy for immigration purposes. RESULTS A total of 380 cases of imported malaria occurred in Verona in the 5-year period, 43 being children. Semi-immune patients had a significantly lower parasitemia (p = 0.0032) and parasite clearance time and significantly shorter fever duration than nonimmune (p = 0.025 and p = 0.0026). VRF children presented significantly higher parasitemia and significantly lower platelet count (p = 0.016 and p = 0.042) than recent immigrants. Parasitemia clearance time and fever duration were longer in VRF children than in recent immigrants (p = 0.014 and p = 0.0085). We observed 23 cases of severe malaria, including 4 cases in immigrants. CONCLUSIONS Our data confirm a significant difference both in clinical and in parasitological findings between semi-immune and nonimmune patients. We identified two populations of immigrant children: semi-immune (recent immigrants) and nonimmune (VRF). The latter is a high-risk group for severe malaria. Educational actions should be specially designed for immigrants traveling to VRF, focusing on the risk of severe malaria for both adults and children.

Evaluation of an indirect immunofluorescence assay for strongyloidiasis as a tool for diagnosis and follow-up.

ABSTRACT The diagnostic accuracy of an indirect immunofluorescence antibody test (IFAT) for Strongyloides stercoralis at different serum antibody titers was evaluated. To assess diagnostic sensitivity, sera from 156 patients with known strongyloidiasis were collected. Negative control sera were obtained from a composite group of 427 subjects (blood donors and hospitalized patients). With an area under the receiver-operating characteristic plot of 0.98, the IFAT showed a high level of diagnostic accuracy for strongyloidiasis. An antibody titer of ≥1:20, with 97% sensitivity and 98% specificity, was identified as the diagnostic threshold with the best overall performance. Cross-reactions were evaluated with 41 additional samples from patients with other known helminth infections, and the IFAT detected low-titer positivity in only one subject with filariasis. A positive IFAT result at an antibody dilution of ≥1:80 was virtually 100% specific, with 71% sensitivity. To test the usefulness of the IFAT as a monitoring tool, the changes in specific-antibody titers after treatment in a group of 155 patients were evaluated. Seroreversion or a decrease in antibody titer of twofold or more was observed in 60% of the patients. Response to treatment was directly correlated to the initial antibody titer, and a baseline titer of ≥1:80 was identified as the best predictor of response. In conclusion, a positive IFAT result at an antibody dilution of ≥1:20 is the optimal cutoff for screening. A titer of ≥1:80, with virtually no false-positive result, is a reliable cutoff for a serological assessment of treatment efficacy and for inclusion in clinical trials.

Imported Malaria in Immigrants to Italy: A Changing Pattern Observed in North Eastern Italy

BACKGROUND Seventy percent of imported malaria cases in Italy occur in immigrants, generally with milder clinical presentation due to premunition acquired through repeated infections. Nevertheless, premunition could be progressively lost after a long period of nonexposure. We investigated the changing pattern of malaria in immigrants in two definite 5-year periods one decade apart. METHODS We retrospectively examined the main laboratory findings of all malaria cases observed in immigrants from 1990 to 1994 and from 2000 to 2004. We stratified patients by reason for traveling: subjects in Italy who traveled to visit friends and relatives (VFR) or new immigrants (NI). RESULTS Forty-eight cases of malaria in immigrants occurred from 1990 to 1994, while 161 were observed from 2000 to 2004. Patients admitted in the latter period had a significantly higher parasitemia (median 6,298 vs 3,360 trophozoites/microL, p= 0.028) and lower platelet count (median 96.5 vs 132 x 10(9)/L, p= 0.012) and hemoglobin (median 12.6 vs 13.4 g/dL, p= 0.049). While NI did not show any significant difference in the two study periods, in the VFR subgroup a higher parasitemia (median 8,845 vs 2,690 trophozoites/microL, p= 0.003) and lower platelet count (median 96 vs 131 x 10(9)/L, p= 0.034) were observed during the second period, during which three cases of severe malaria occurred in VFR. A longer stay in Italy was reported in VFR admitted during the second study period (median 8.3 vs 5.7 years). CONCLUSIONS We found a changing pattern of malaria presentation in immigrants over a decade. The most likely explanation is the longer average stay outside endemic countries and subsequent loss of premunition observed in the second cohort. Immigrants living in Italy for some time and traveling to VFR should no more be considered a low-risk group for severe malaria. Pretravel advice should be particularly targeted to this group.

Autochthonous cases of mycetoma in Europe: report of two cases and review of literature.

Background Mycetoma is a chronic granulomatous infection involving cutaneous and subcutaneous tissues. It is endemic in tropical and subtropical areas, but sporadic cases have been reported also in countries of temperate climate. The purpose of this paper is to review the cases of mycetoma in European subjects (and presumably acquired in Europe), to give an insight in the main factors associated with this condition, and to describe two previously unpublished cases observed at our Centre. Methods and Findings PubMed was systematically searched for case reports and case series of mycetoma in Europeans reported between 1980 and 2014, using specific search strategies. Two further cases diagnosed by the authors are described. Forty-two cases were collected. Eleven cases were caused by Scedosporium apiospermium, mainly in immunosuppressed patients from Bulgaria, Germany, the Netherlands, Portugal, Slovenia, Spain and the United Kingdom. Excluding all patients with immunosuppression, 29 cases remain. Most of them were reported from Bulgaria and in Albanian patients (all diagnosed outside Albania). In the Bulgarian case series many different micro-organisms, both bacteria and fungi, were isolated, while all the 5 cases from Albania were caused by Actinomadura spp. Other countries reporting cases were Greece, Italy and Turkey. In general, Actinomadura spp is the most frequent causative agent isolated, followed by Nocardia spp and Madurella mycetomatis. The foot was the most reported site involved. Most patients were medically treated, but unfortunately a long-term follow up (at least one year) was available only in a few cases. Conclusions Our review and our own cases suggest that Europeans without travel history can be affected by Madura foot. The lack of a surveillance system is likely to cause an underreporting of cases. Moreover, the unfamiliarity of Western doctors with this peculiar infection may cause a mismanagement, including unnecessary amputations.

Acute Strongyloidiasis in Italian Tourists Returning From Southeast Asia

Strongyloidiasis is a soil-transmitted helmithiasis with worldwide distribution. Contrary to chronic form, hyperinfestation and life-threatening dissemination, first (invasive) stages of the disease are not well characterized. This paper describes two cases of acute strongyloidiasis in travelers returning from Southeast Asia and highlights the need to take strongyloidiasis into account also among acute travel-related illnesses.

Mefloquine versus Quinine plus Sulphalene-Pyrimethamine (Metakelfin) for Treatment of Uncomplicated Imported Falciparum Malaria Acquired in Africa

ABSTRACT We conducted a multicenter, randomized, open-label trial to compare mefloquine with a 3-day quinine plus sulphalene-pyrimethamine (SP) regimen for the treatment of imported uncomplicated malaria acquired in Africa. The end points of the study were efficacy, tolerability, and length of hospital stay. From July 1999 to February 2003, 187 patients were enrolled in five centers in Italy, of whom 93 were randomized to receive mefloquine (the M group) and 94 were randomized to receive quinine plus SP (the QSP group). Immigrants and visiting relatives and friends represented 90% of the cases and were mainly from western African countries. A slightly increased proportion of cases in the QSP group had abnormal alanine aminotransferase levels at the baseline. The early cure rate was similar in the two groups: 98.9% (confidence interval [CI] = 97 to 100%) in the M group and 96.8% (CI = 93 to 100%) in the QSP group. The extended follow-up was completed by 135 subjects (72.2%), and no case of recrudescence was detected. There were no differences in the parasite clearance time, but patients in the M group had shorter mean fever clearance time (35.9 h versus 44.4 h for the QSP group; P = 0.05) and a shorter mean hospital stay (3.9 days versus 4.6 days for the QSP group; P = 0.007). The overall proportions of reported side effects were similar in the two groups, but patients in the M group had a significantly higher rate of central nervous system disturbances (29.0% versus 9.6% for the QSP group; P < 0.001).

Profile of Trypanosoma cruzi Infection in a Tropical Medicine Reference Center, Northern Italy

Background Chagas disease (CD) is endemic in Central and South America, Mexico and even in some areas of the United States. However, cases have been increasingly recorded also in non-endemic countries. The estimated number of infected people in Europe is in a wide range of 14000 to 181000 subjects, mostly resident in Spain, Italy and the United Kingdom. Methodology/Principal Findings Retrospective, observational study describing the characteristics of patients with CD who attended the Centre for Tropical Diseases (Negrar, Verona, Italy) between 2005 and 2013. All the patients affected by CD underwent chest X-ray, ECG, echocardiography, barium X-ray of the oesophagus and colonic enema. They were classified in the indeterminate, cardiac, digestive or mixed category according to the results of the screening tests. Treatment with benznidazole (or nifurtimox in case of intolerance to the first line therapy) was offered to all patients, excluding the ones with advanced cardiomiopathy, pregnant and lactating women. Patients included were 332 (73.9% women). We classified 68.1% of patients as having Indeterminate Chagas, 11.1% Cardiac Chagas, 18.7% as Digestive Chagas and 2.1% as Mixed Form. Three hundred and twenty-one patients (96.7%) were treated with benznidazole, and most of them (83.2%) completed the treatment. At least one adverse effect was reported by 27.7% of patients, but they were mostly mild. Only a couple of patients received nifurtimox as second line treatment. Conclusions/Significance Our case series represents the largest cohort of T. cruzi infected patients diagnosed and treated in Italy. An improvement of the access to diagnosis and cure is still needed, considering that about 9200 infected people are estimated to live in Italy. In general, there is an urgent need of common guidelines to better classify and manage patients with CD in non-endemic countries.

Pulmonary nodules in African migrants caused by chronic schistosomiasis

Schistosomiasis is a neglected tropical disease that can cause mainly hepatic and genitourinary damage, depending on the species. Involvement of the lungs has been commonly described in acute infection (Katayama syndrome) and chronic infection (pulmonary hypertension). Although rarely reported in the scientific literature, cases of lung nodules due to chronic schistosome infection are also possible and are probably more frequent than commonly thought. Here we report seven cases of African migrants who were diagnosed with chronic schistosomiasis and pulmonary nodules due to deposition of schistosome eggs, and we compare our findings to the case reports found in the scientific literature. We discuss the management of these patients in a non-endemic setting, beginning with a first fundamental step that is to include parasitic infections, namely schistosomiasis, in the differential diagnosis of pulmonary nodules in African immigrants. All patients responded to antiparasitic treatment with praziquantel after a relatively short time. We therefore conclude that lung biopsies and other invasive procedures (performed in the first cases to rule out other potential causes, such as tuberculosis or malignant nodules) can be avoided or postponed.