Geraldo Badona Monteiro

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

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.

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.

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.

Schistosomiasis in immigrants, refugees and travellers in an Italian referral centre for tropical diseases

BackgroundSchistosomiasis is one of the most important neglected tropical diseases. If unrecognised and untreated, the chronic infection can lead to irreversible complications.MethodsRetrospective observational study aimed at describing clinical history, laboratory findings and imaging presentation of imported schistosomiasis diagnosed at the Centre for Tropical Diseases, Sacro Cuore Don Calabria Hospital of Negrar, Verona, Italy from 2010 to 2014. The aim of our study was to assess differences in demographic characteristics, clinical presentation, laboratory data and ultrasound findings between immigrants/visiting friends and relatives (VFR) from endemic countries (endemic group) and expatriates/travellers (non-endemic group).ResultsA total of 272 patients were retrieved: 234 in the endemic and 38 in the non-endemic group. Most of the patients acquired schistosomiasis in Africa (97.4%). Symptoms were reported by 52.9% of the patients; abdominal pain (36%), macroscopic hematuria (11.3%), and genito-urinary symptoms (7.4%) being the most frequently reported. Increased IgE and blood eosinophilia were observed in 169 (63.8%) and 130 (47.8%) patients, respectively. The proportion of positive serology was 250/272 (91.9%).The Circulating Cathodic Antigen CCA for Schistosoma mansoni was positive in 14/61 individuals (23%). At microscopy, infected subjects were 103/272 (37.9%). The species of Schistosoma found were S. haematobium (47.6%), S. mansoni (46.6%) or both (5.8%). Schistosomiasis was classified as confirmed in 103 (37.9%), probable in 165 (60.6%) and suspected in 4 (1.5%) cases using clinical presentation, laboratory data and ultrasound findings. The infection was further classified based on organ involvement: intestinal (17.9%), hepatosplenic (5.1%), urogenital (48.9%), and indeterminate (43.8%).The comparative analysis of endemic and non-endemic patients highlighted differences in sex and age. Endemic patients had more frequent ova identification (41.9% vs. 13.2%, P < 0.001) and increased IgE (70% vs. 26.3%, P < 0.001) when compared with non-endemic. Multivariate analyses showed that younger age, abnormal ultrasound findings and blood eosinophilia were significantly associated with positive microscopy (OR = 0.94, OR = 2.12, OR = 1.98, respectively).ConclusionsSymptoms, eosinophilia and abnormal ultrasound findings were present in about half of patients, without differences between groups. Many patients had positive serology but negative microscopy, indicating that schistosomiasis might be misdiagnosed. A combination of diagnostic tools may facilitate the diagnosis.