Rogelio López-Vélez

Changes in the immune response after treatment with benznidazole versus no treatment in patients with chronic indeterminate Chagas disease

Symptomatic chronic Chagas disease affects up to 40% of patients infected with Trypanosoma cruzi. The lack of reliable early markers of cure after therapy hinders disease management and clinical trials with new drugs. We performed a study with 18 months of follow-up to compare changes in immune parameters and T. cruzi-specific immune responses as surrogate markers of response to therapy between patients treated with benznidazole and untreated patients. This was a pilot, open-label, randomised clinical trial of treatment with benznidazole versus no treatment in patients with indeterminate chronic T. cruzi infection. In both groups we investigated changes in T-cell activation, T-cell subpopulations, regulatory T-cell counts, IL6, and sCD14 levels, and T. cruzi-specific immune responses (Th1, Th2, and Th17 responses). Fourteen patients were included in the study (seven in each group). Median age was 35 years (P25-75 31-43), 57% were female, and 93% were Bolivian. Benznidazole was administered at 5mg/kg/day for 60days. Three patients discontinued benznidazole owing to adverse reactions and were not evaluated. At the end of the follow-up period, treated patients showed significantly less immune activation and lower regulatory T-cell counts, with an increased Th17 and Th1 response. This randomised pilot clinical trial administering benznidazole to patients with indeterminate chronic Chagas disease brings about changes in the adaptive immunity, leading to a general decrease in inflammatory status. This apparently beneficial response could act as the basis for monitoring new antiparasitic drugs.

Prevention of Tropical and Parasitic Infections: The Immunocompromised Traveler

The number of immunocompromised xadtravelers is increasing and persons with significant preexisting medical conditions may be exposed to infectious diseases at their destination of choice. The risks of developing severe disease are increased and advising these complex patients may be challenging for health care professionals. Recommendations for prevention of specific travel-related infections and vaccination in immunocompromised patients as well as general advice for the cancer patient wishing to travel are outlined.

Treatment of Visceral Leishmaniasis

All persons with symptomatic visceral leishmaniasis (VL) should be treated with antileishmanial drugs. The therapeutic options for VL are diverse and depend on different factors, such as geographical area of the infection; the Leishmania species involved, the development of failure to habitual treatment, the evidence of HIV co-infection or other infections and the presence of malnourishment. The traditional treatment of VL used to be pentavalent antimonials, but the development of resistance, as their potential toxicity, made necessary new treatment options such as amphotericin B deoxycholate or lipid formulations of amphotericin B which due to their efficacy and lower toxicity have become the first-choice treatment in different world areas. In countries of fewer resources, studies have been carried out demonstrating the efficacy of parenteral paromomycin. Within the range of oral treatments, miltefosine had demonstrated very good cure rates; however, currently, also a high rate of clinical failures has been reported. In this chapter we provide a review on the treatment of VL and give therapeutic options with the grade of recommendation according to the Leishmania implicated and the geographical location of the infection.