Intralesional infiltration versus parenteral use of meglumine antimoniate for treatment of cutaneous leishmaniasis: A cost-effectiveness analysis.

Cutaneous leishmaniasis (LC) is a complex and variable disease in terms of epidemiology, aetiology, pathology and clinical characteristics. The mainstay of treatment is still pentavalent antimony (Sbv) compounds administered systemically, despite their recognized toxicity. The advantages of antimony intralesional (IL) infiltration are the use of lower doses of Sbv and, therefore, less toxic effects. The objective of this study was to estimate the cost-effectiveness ratio of intralesional meglumine antimoniate therapy (IL-MA) compared with endovenous meglumine antimoniate therapy (EV-MA) for the treatment of CL in the context of the Brazilian National Health System (SUS). An analytical decision model (decision tree) was developed using TreeAge Pro 2018 software. Data from the open-label, uncontrolled phase II clinical trial evaluating IL-MA were used as a reference for posology, efficacy, and adverse event rates (AE). The same premises for the intravenous approach (EV-MA) were extracted from systematic literature reviews. Macro and micro calculations of spending were included in the analysis. The IL-MA and EV-MA strategies had a total cost per patient cured of US$330.81 and US$494.16, respectively. The intralesional approach was dominant, meaning it was more economic and effective than was endovenous therapy. The incremental cost-effectiveness ratio showed that IL-MA could result in savings of US$864.37 for each additional patient cured, confirming that the IL-MA strategy is cost effective in the context of the Brazilian public health scenario.

Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients.

The maintenance of chronic immune activation due to leishmaniasis or even due to microbial translocation is associated with immunosenescence and may contribute to frequent relapses. Our aim was to investigate whether patients with HIV-associated visceral leishmaniasis (VL/HIV) who experience a single episode of VL have different immunological behaviors in comparison to those who experience frequent relapses. VL/HIV patients were allocated to non-relapsing (NR, n = 6) and relapsing (R, n = 11) groups and were followed from the active phase of VL up to 12 months post-treatment (mpt). The patients were receiving highly active antiretroviral therapy (HAART) and secondary prophylaxis after VL therapy. During active VL, the two groups were similar in all immunological parameters, including the parasite load. At 6 and 12 mpt, the NR group showed a significant gain of CD4+ T cells, a reduction of lymphocyte activation, and lower soluble CD14 and anti-Leishmania IgG3 levels compared to the R group. The viral load remained low, without correlation with the activation. The two groups showed elevated but similar percentages of senescent T cells. These findings suggest a decreased ability of the R group to downmodulate immune activation compared to the NR group. Such functional impairment of the effector response may be a useful indicator for predicting clinical prognosis and recommending starting or stopping secondary prophylaxis.

Cost-effectiveness analysis of diagnostic tests for human visceral leishmaniasis in Brazil.

BACKGROUND: The objective of study was to estimate the incremental cost-effectiveness ratio (ICER) of diagnostic options for visceral leishmaniasis (VL) in Brazil. METHODS: Six diagnostic tests were considered: IT LEISH, Kalazar Detect, DAT-LPC (DAT made in the Laboratório de Pesquisas Clínicas), IFAT, PCR and direct examination of bone marrow aspirate performed in either an ambulatory or a hospital setting. A database was built using the cost and effectiveness. The perspective of this study was the Brazilian public healthcare system and the results were expressed in costs per correctly diagnosed cases. RESULTS: In a favorable hypothetical scenario, DAT-LPC presented the lowest cost (US$4.92) and highest effectiveness (99%). Paired analyses showed that IT LEISH was dominant compared to IFAT, microscopy and Kalazar Detect and that Kalazar Detect was dominant over IFAT and microscopy. PCR was dominant over the bone marrow aspirate in the hospital and showed an ICER of 57.76 compared with aspirate in an ambulatory setting. CONCLUSIONS: These results highlight the need for the revision of algorithm for VL diagnostic in Brazil. Replacements of IFAT with DAT-LPC, Kalazar Detect with IT LEISH and bone marrow aspirate performed in a hospital setting with PCR are cost-effective public health measures.

Predictive models for the diagnostic of human visceral leishmaniasis in Brazil.

BACKGROUND AND OBJECTIVES: In Brazil, as in many other affected countries, a large proportion of visceral leishmaniasis (VL) occurs in remote locations and treatment is often performed on basis of clinical suspicion. This study aimed at developing predictive models to help with the clinical management of VL in patients with suggestive clinical of disease. METHODS: Cases of VL (n = 213) had the diagnosis confirmed by parasitological method, non-cases (n = 119) presented suggestive clinical presentation of VL but a negative parasitological diagnosis and a firm diagnosis of another disease. The original data set was divided into two samples for generation and validation of the prediction models. Prediction models based on clinical signs and symptoms, results of laboratory exams and results of five different serological tests, were developed by means of logistic regression and classification and regression trees (CART). From these models, clinical-laboratory and diagnostic prediction scores were generated. The area under the receiver operator characteristic curve, sensitivity, specificity, and positive predictive value were used to evaluate the models' performance. RESULTS: Based on the variables splenomegaly, presence of cough and leukopenia and on the results of five serological tests it was possible to generate six predictive models using logistic regression, showing sensitivity ranging from 90.1 to 99.0% and specificity ranging from 53.0 to 97.2%. Based on the variables splenomegaly, leukopenia, cough, age and weight loss and on the results of five serological tests six predictive models were generated using CART with sensitivity ranging from 90.1 to 97.2% and specificity ranging from 68.4 to 97.4%. The models composed of clinical-laboratory variables and the rk39 rapid test showed the best performance. CONCLUSION: The predictive models showed to be a potential useful tool to assist healthcare systems and control programs in their strategical choices, contributing to more efficient and more rational allocation of healthcare resources.