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Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3β, 6β, 16β-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention. [ABSTRACT FROM AUTHOR]

The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin‐ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104, 105 and 106) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL‐4, IL‐10 and arginase in the lymph node followed by expression of both pro‐and anti‐inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a disease that represents a serious global health problem with a potentially fatal outcome in some cases. Leishmania spp. is transmitted by the bite of a sandfly and the disease is endemic in 98 countries. Treatment is carried out with toxic drugs and not consistently effective, so there is a need for new treatments. Oxadiazoles are five-membered heterocyclic compounds, and their antileishmanial activity is well documented in the literature. Specifically, n-cyclohexyl-1,2,4-oxadiazole (2b) was designed to obtain the simplified molecular data line entry system (SMILES). The approach for predicting pharmacokinetic properties used was pkCSM—Pharmacokinetics and ADME/TOX parameters were achieved. SMILES of 2b and Amphotericin B (ANF B) were submitted to the server and the results were compared. The cytotoxic action of 2b on host cells (LLC-MK2) was also evaluated, using MTT salt and antileishmanial activity against Leishmania infantum promastigotes at different concentrations for 24 h. The molecule 2b studied here demonstrated low toxicity in LLC-MK2 cells even at the highest concentration (1000 µM) with cell viability of 69%. Furthermore, it demonstrated anti-L. infantum action with cell viability of 13% at the highest concentration (1000 μM), while (ANF B) (16 μg/mL) demonstrated cell viability of 7%, justifying the need for further studies with n-cyclohexyl-1.2,4-oxadiazole employing experimental models of leishmaniasis. [ABSTRACT FROM AUTHOR]

Leishmania braziliensis is the main causative agent of American tegumentary leishmaniasis in Brazil. Current treatment includes different drugs that have important side effects and identification of cases of parasite resistance to treatment support the search for new therapeutic strategies. Recent findings have indicated that CXCL10, a chemokine that recruits and activates Th1 cells, NK cells, macrophages, dendritic cells and B lymphocytes, is a potential alternative to treat Leishmania infection. Here, we tested CXCL10 immunotherapy against experimental infection caused by an antimony‐resistant isolate of Leishmania braziliensis. Following infection, mice were treated with CXCL10 for 7 days after onset of lesions. We demonstrate that mice treated with CXCL10 controlled lesion progression and parasite burden more efficiently comparing to controls. An increased IFN‐γ, IL‐10, TGF‐β and low IL‐4 production combined with a distinct inflammatory infiltrate composed by activated macrophages, lymphocytes and granulomas was observed in the CXCL10‐treated group comparing to controls. However, CXCL10 and Glucantime combined therapy did not improve CXCL10‐induced protective effect. Our findings reinforce the potential of CXCL10 immunotherapy as an alternative treatment against infection caused by L. braziliensis resistant to conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Chikungunya virus (CHIKV) has caused worldwide epidemics that impose a major burden on health systems. Approximately half of infected individuals develop chronic debilitating arthralgia, affecting their quality of life. Here, we identified the relevant clinical and demographic variables in the acute phase of CHIKV infection prospectively linked to chronic arthralgia to elaborate a prognostic scoring system. Methods: Acute CHIKV infection cases (n = 134) confirmed by serology or molecular test were examined <10 days of disease onset and followed for one year to evaluate for disease progression. Potential risk factors for chronic arthralgia were evaluated by multivariate analysis to develop a prognostic scoring system, which was subsequently tested in an independent validation cohort consisting of 42 individuals. Results: A total of 107 out of 134 (80%) acute CHIKV-confirmed cases from the derivation cohort were re-examined one year after enrollment. Chronic arthralgia post-CHIKV infection was diagnosed in 64 (60%). Five of the 12 parameters evaluated in the acute phase were statistically associated with persistent arthralgia and were further tested by Bayesian analysis. These variables were weighted to yield a prognosis score denominated SHERA (Sex, Hypertension, Edema, Retroocular pain, Age), which exhibited 81.3% accuracy in predicting long-term arthralgia post-CHIKV infection in the derivation cohort, and 76.5% accuracy in the validation cohort. Conclusions: The simplified and externally validated prognostic scoring system, SHERA, is a useful method to screen acutely CHIKV-infected patients at elevated risk of chronic arthralgia who will benefit from specific interventions. This tool could guide public health policies, particularly in resource-constrained settings. Author summary: Debilitating articular pain frequently occurs as a consequence of Chikungunya virus infection, affecting individuals' quality of life for a long time. Here we present a simple tool to predict people at risk to remain with long-term articular pain after Chikungunya infection. We evaluated 134 patients acutely affected by Chikungunya virus searching for characteristics previously described as related to persistent symptoms. We examined about 80% of those individuals after one year to identify those with persistent arthralgia. We detected five features that represent good predictors and developed a scoring system named SHERA (www.sheracalculator.com/shera), the acronyms of Sex (female), Hypertension, Edema, Retroocular pain and Age (>26y). SHERA can correctly predict 8 out of every 10 Chikungunya infected individuals that will persist with articular pain symptoms at least one year after disease onset. These results were confirmed in the second group of patients from another city affected by Chikungunya outbreak. The easy-to-use scoring system can be applied in areas with limited access to health support, helping to identify the ones who will need special care and benefit from early intervention. [ABSTRACT FROM AUTHOR]

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The aim of the present work was to evaluate antileishmanial activity of Astronium fraxinifolium and Plectranthus amboinicus. For the in vitro tests, essential oil of P. amboinicus (OEPA) and ethanolic extracts from A. fraxinifolium (EEAF) were incubated with 106 promastigotes of L. (Viannia) braziliensis. The OEPA was able to reduce the parasite growth after 48h; nonetheless, all the EEAFs could totally abolish the parasite growth. For the in vivo studies, BALB/c micewere infected subcutaneously (s.c.)with 107 L. braziliensis promastigotes. Treatment was done by administering OEPA intralesionally (i.l.) for 14 days. No difference was found in lesion thickness when those animals were compared with the untreated animals. Further, golden hamsters were infected s.c. with 106 L. braziliensis promastigotes. The first protocol of treatment consisted of ethanolic leaf extract from A. fraxinifolium (ELEAF) administered i.l. for 4 days and a booster dose at the 7th day. The animals showed a significant reduction of lesion thickness in the 6th week, but it was not comparable to the animals treated with Glucantime. The second protocol consisted of 15 daily intralesional injections. The profiles of lesion thickness were similar to the standard treatment. In conclusion, in vivo studies showed a high efficacy when the infected animals were intralesionally treated with leaf ethanolic extract from A. fraxinifolium. [ABSTRACT FROM AUTHOR]

Epidemiologic aspects of the relationship between infection with Leishmania chagasi and development of clinical visceralleishmaniasis (VL)werestudied in all children <11 years old in a defined, endemic, rural area of the state of Ceará in northeast Brazil. Antileishmanial antibodies were measured in the same subjects by ELISA on six occasions between May 1987 and August 1989, Seroconversion was documented during this period in 108 children, with a cumulative annual incidence of 4.6%. Twelve (11.1%) of these children developed VL. Age <4 years, hematocrit <33%, and living in the mountains predicted the development of clinically apparent VL after seroconversion. Despite a high percentage of dogs serologically positive in the region (38%), there was no increased risk of infection for children living in the same household with dogs. Since children in households with a prior case of VL had a threefold increased risk of infection, human-sandfly-human transmission might have been important. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented related to a case study on cysticercosis, a tapeworm infection in the tongue and states the importance of the study of parasitic infections of the oral cavity as essential to healthcare professionals who work with diagnosis and surgery.

Discusses the natural history of Leishmania chagasi infection, or Leishmaniasis, in a cohort of persons in Ceara in northeastern Brazil. Decrease in the incidence of visceral leishmaniasis; Effect of differences in rainfall, vector density and herd immunity; Possibility that L. chagasi infection is not likely to progress to visceral leishmaniasis if it has not done so within the first or second year after infection.