Artesunate monotherapy versus artesunate plus quinine combination therapy for treatment of imported severe malaria: a TropNet retrospective cohort study.

BACKGROUND: The addition of intravenous quinine (IVQ) to intravenous artesunate (IVA) has been recently suggested by World Health Organization  in areas where artemisinin resistance is highly prevalent. Since IVA is not yet widely available as "Good Manufacturing Practices" product, for several years combination treatment with IVA and IVQ was used in some Italian centers to mitigate the legal risks in using an unlicensed drug. METHODS: A retrospective cohort study was designed to compare IVA + IVQ and IVA treatment for imported severe malaria. We collected data from three Italian centers. Adult and pediatric cohorts were analyzed separately. RESULTS: Forty-nine patients treated with IVA and 44 with IVA + IVQ were enrolled, 45 were adults and 48 children. All acquired malaria in Sub-Saharan Africa. In the adult cohort, median of fever clearance time (FCT) was similar in both groups (48 h vs 48 h, p = 0.19) but number of patients who reached apyrexia within 48 h (FCT48) was higher in IVA group (20/24, 83.3% vs 8/17, 47%, p = 0.002). The parasite clearance time (PCT) measure did not differ (median 48 h vs 48 h, p = 0.669). In the pediatric cohort, FCT did not differ in the two groups (median 30 vs 48 h, p = 0.50) while PCT was longer in IVA + IVQ group (median 72 vs 48 h, p = 0.002). Adverse events (AEs) in adults were more common in the combination treatment group (6/19, 31.58% vs 2/26, 7.69%, p = 0.055). CONCLUSION: IVA + IVQ treatment did not show better outcome with respect to IVA monotherapy. AEs were more frequent in the IVA + IVQ group compared to the monotherapy. Further studies are necessary to investigate whether IVA + IVQ could be an efficient strategy to treat severe malaria cases in areas at high risk of artemisinin resistance.

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort).

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Case Report: Intravenous Pentamidine Rescue Treatment for Active Chronic Visceral Leishmaniasis in an HIV-1 Infected Patient.

The management of visceral leishmaniasis (VL) in HIV-infected patients is complex because of high mortality rates, toxic drug-related side effects, and a high risk of treatment failure and relapse. We report a case of active chronic VL in an HIV-1-infected woman presenting multiple secondary VL episodes over 7 years leading to massive splenomegaly and blood transfusion-dependent anemia despite several treatment courses and secondary prophylaxis. The patient was finally successfully treated with rescue treatment based on intravenous pentamidine. Twenty months after discontinuation of pentamidine the patient presented complete clinical and parasitological response. In patients with active chronic VL, treatment with intravenous pentamidine can be effective and should be considered as rescue treatment.