Explore the vast range of titles available.

Leishmaniasis is a poverty-related disease with two main clinical forms: visceral leishmaniasis and cutaneous leishmaniasis. An estimated 0·7–1 million new cases of leishmaniasis per year are reported from nearly 100 endemic countries. The number of reported visceral leishmaniasis cases has decreased substantially in the past decade as a result of better access to diagnosis and treatment and more intense vector control within an elimination initiative in Asia, although natural cycles in transmission intensity might play a role. In east Africa however, the case numbers of this fatal disease continue to be sustained. Increased conflict in endemic areas of cutaneous leishmaniasis and forced displacement has resulted in a surge in these endemic areas as well as clinics across the world. WHO lists leishmaniasis as one of the neglected tropical diseases for which the development of new treatments is a priority. Major evidence gaps remain, and new tools are needed before leishmaniasis can be definitively controlled.

The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes. This review discusses the distinct cutaneous syndromes described in humans, and current knowledge of the inflammatory responses associated with divergent cutaneous pathologic responses to different Leishmania species. The contribution of key hematopoietic cells in experimental cutaneous leishmaniasis in mouse models are also reviewed and compared with those observed during human infection. We hypothesize that local skin events influence the ensuing adaptive immune response to Leishmania spp. infections, and that the balance between inflammatory and regulatory factors induced by infection are critical for determining cutaneous pathology and outcome of infection.

The clinical manifestation of leishmaniasis has historically been determined by the Leishmania species involved. However, recent emergence of novel Leishmania lineages has caused atypical pathologies. We isolated and characterized 2 new Leishmania donovani parasites causing cutaneous leishmaniasis in Himachal Pradesh, India.

Cutaneous leishmaniasis (CL) is endemic to Israel. Previously, CL caused by Leishmania infantum had been reported in Israel only once (in 2016). We report 8 L. infantum CL cases; 7 occurred during 2020-2021. None of the patients had systemic disease. L. infantum CL may be an emerging infection in Israel.

This review is aimed at providing a comprehensive outline of the immune response displayed against cutaneous leishmaniasis (CL), the more common zoonotic infection caused by protozoan parasites of the genus Leishmania. Although of polymorphic clinical presentation, classically CL is characterized by leishmaniotic lesions on the face and extremities of the patients, which can be ulcerative, and even after healing can lead to permanent injuries and disfigurement, affecting significantly their psychological, social, and economic well-being. According a report released by the World Health Organization, the disability-adjusted life years (DALYs) lost due to leishmaniasis are close to 2.4 million, annually there are 1.0–1.5 million new cases of CL, and a numerous population is at risk in the endemic areas. Despite its increasing worldwide incidence, it is one of the so-called neglected tropical diseases. Furthermore, this review provides an overview of the existing knowledge of the host innate and acquired immune response to cutaneous species of Leishmania. The use of animal models and of in vitro studies has improved the understanding of parasite-host interplay and the complexity of immune mechanisms involved. The importance of diagnosis accuracy associated with effective patient management in CL reduction is highlighted. However, the multiple factors involved in CL epizoology associated with the unavailability of vaccines or drugs to prevent infection make difficult to formulate an effective strategy for CL control.

Background American cutaneous leishmaniasis (ACL) is a protozoan parasitic disease caused by different Leishmania spp. from L. ( Leishmania ) and L. ( Viannia ) subgenera. In Brazil, seven Leishmania spp. act as ACL agents. Infection with L. ( L. ) amazonensis presents a wide clinical–immunopathological spectrum, ranging from localized cutaneous leishmaniasis (LCL), which usually responds well to antimony therapy, to borderline disseminated cutaneous leishmaniasis (BDCL), which may require twice as much LCL-antimony therapy to cure, and, finally, to anergic diffuse cutaneous leishmaniasis (ADCL), which is highly resistant to any chemotherapy. This clinical variability is driven by different degrees of T-cell immunosuppression, which negatively impact delayed-type hypersensitivity (DTH), as assessed by the Montenegro skin test (MST). Methods Given MST’s role as a T-cell-mediated resistance marker, we used it for diagnosing and monitoring patients with LCL ( n  = 8) and BDCL ( n  = 3) due to L. ( L. ) amazonensis to assess T-cell immunosuppression in these patients. MST was assessed at diagnosis and after treatment, although one patient with LCL refused treatment. The study took place at the Evandro Chagas Institute (Pará, Brazil), with diagnosis confirmed through parasitological assays, MST using L. ( V. ) braziliensis antigen, indirect fluorescent antibody test (IFAT)-immunoglobulin (Ig)G serology, histopathology, and PCR. Phenotypic and genotypic analyses were used to identify the primary agent. Results MST was negative in all patients, both before and after successful treatment. Notably, one patient with LCL who declined treatment also showed no MST reactivity both before and after spontaneous healing. The absence of MST reactivity persisted for up to 1 year postcure in LCL and up to 2 years in BDCL, indicating a sustained lack of MST reactivity regardless of treatment outcome or spontaneous healing. Conclusions The lack of MST reactivity pre- and post-treatment in LCL and BDCL challenges the role of DTH as a marker for T-cell-mediated resistance to L. ( L. ) amazonensis infection. Moreover, the first case of spontaneous LCL cure by L. ( L. ) amazonensis showed no MST reactivity pre- or post-resolution, raising doubts about the role of DTH in this process. Graphical Abstract

Although there are several areas in southern Ethiopia environmentally favourable for cutaneous leishmaniasis (CL), studies on the existence and risk factors of CL are lacking beyond a few well-known hotspots. This study aimed to assess the prevalence and risk factors of CL in Bilala Shaye, a village in the southern Ethiopian highlands at an altitude of 2,250 meters. A cross-sectional house-to-house survey was done between July-August 2021. Those with skin lesions were clinically assessed and data on individual risk behaviour and environmental and household features were collected using questionnaires. Univariate and multivariable logistic regression models were used to identify independent risk factors of CL at a 5% significance level with two-sided P-values <0.05 considered statistically significant. A total of 1012 individuals were interviewed; the median age was 23 years (interquartile range 12-50), with 7% below the age of five; 51% were female. All households had domestic animals, and for 143 (57%) households goats/sheep lived inside or around the house. Animal dung was found in the compounds of 194 (77%) households. The overall prevalence of active CL was 2.5% (95% confidence interval (CI) 1.6-3.6), reaching 6.7% (95% CI 3.6-11.2) in children between 5-12 years old. The prevalence of CL scars was 38.5% (95% CI 35.5-41.6). In multivariate analysis, the presence of animal dung in the compound (adjusted odds ratio (OR) 2.1; 95% CI: 1.3-3.5, P = 0.003) and time spent outside in the late evening in areas where hyraxes live (adjusted OR 2.4; 95% CI: 1.7-3.3, P <0.001) were identified as independent risk factors. This is the first report on the existence of CL in this village, with the high prevalence of CL scars indicating long-term endemicity. Further studies are needed to understand the role of animals and their dung in (peri)-domestic CL transmission.

Context.—Localized cutaneous leishmaniasis (CL) typically presents as papules, crusted nodules, plaques, or noduloulcerative lesions. Atypical CL does not show these features or mimic malignant lesion. In atypical forms, CL may be overlooked because of its similarity to other dermal diseases. Objective.—To compare conventional, molecular, and immunohistochemical methods in the diagnosis of typical and atypical CL. Design.—The kinetoplast DNA, nested, polymerase chain reaction assay and immunohistochemical methods were compared and validated against conventional methods, including cytology and pathology, using 100 specimens of typical and atypical lesions of suspected CL. Results.—Compared with other methods, polymerase chain reaction of the kinetoplast DNA showed the highest sensitivity (typical positive, 100%, 67 of 67; atypical positive, 94%, 31 of 33) and specificity (100%), followed by immunohistochemistry (typical positive, 97%, 65 of 67, with 100% specificity; atypical positives, 94%, 31 of 33, with 100% specificity), and cytology (typical positive, 79%, 53 of 67, with 100% specificity; atypical positive, 58%, 19 of 33, with 100% specificity), followed by pathology (typical positive, 70%, 47 of 67, with 100% specificity; atypical positive, 42%, 14 of 33, with 100% specificity). In addition, polymerase chain reaction enabled identification of 98% (98 of 100) of the positive samples that included strains of Leishmania major (99% [99 of 100] cases) and Leishmania tropica (1% [1 of 100] cases). Conclusions.—Because cytology is cheap and easy to perform with high sensitivity, it is the preferred, primary approach for typical CL, but cytology and pathology do not have sufficient sensitivity for diagnosis of atypical CL cases. Nested polymerase chain reaction and immunohistochemistry are sensitive tests for diagnosis of both typical and atypical CL and are recommended as complementary tests in suspected CL with negative conventional microscopy results.

Although non-fatal and mostly self-healing in the case of Leishmania (L . ) major , cutaneous leishmaniasis (CL) is mainly treated to reduce lesion healing time. Less attention is paid to the improvement of scars, especially in aesthetically relevant areas of the body, which can dramatically affect patients’ wellbeing. We explored patients’ perspectives about treatment options and the social and psychological burden of disease (lesion and scar). Individual in-depth interviews were conducted with ten confirmed CL patients at two L . major endemic sites in Southern Tunisia (Sidi Bouzid and Gafsa). Participants were selected using a sampling approach along a spectrum covering e.g. age, sex, and clinical presentation. Patients’ experiences, opinions and preferences were explored, and their detailed accounts gave an insight on the impact of CL on their everyday lives. The impact of CL was found to be considerable. Most patients were not satisfied with treatment performance and case management. They expected a shorter healing time and better accessibility of the health system. Tolerance of the burden of disease was variable and ranged from acceptance of hidden scars to suicidal thoughts resulting from the fear to become handicapped, and the stress caused by close relatives. Some believed CL to be a form of skin cancer. Unexpectedly, this finding shows the big gap between the perspectives of patients and assumptions of health professionals regarding this disease. This study provided valuable information for better case management emphasizing the importance of improving communication with patients, and accessibility to treatment. It generated context-specific knowledge to policy makers in Tunisia to implement effective case management in a country where access to treatment remains a challenge due to socio-economic and geographic barriers despite a long tradition in CL control.

American tegumentary leishmaniasis (ATL) diagnosis is an open question, and the search for a solution is urgent. The available tests that detect the etiological agent of the infection are specific for ATL diagnosis. However, they present disadvantages, such as low sensitivity and the need for invasive procedures to obtain the samples. Immunological methods (leishmanin skin test and search for anti- Leishmania antibodies) are good alternatives to the etiological diagnosis of ATL. Presently, we face problems with disease confirmation due to the discontinuity in the production of leishmanin skin test antigen, particularly in resource-poor settings. Aiming to diagnose ATL, we validated rLb6H-ELISA for IgG antibodies using 1,091 samples from leishmaniasis patients and healthy controls, divided into four panels, living in 19 Brazilian endemic and non-endemic states. The rLb6H-ELISA showed a sensitivity of 98.6% and a specificity of 100.0%, with the reference panel comprising 70 ATL patient samples and 70 healthy controls. The reproducibility evaluation showed a coefficient of variation of positive samples ≤ 8.20% for repeatability, ≤ 17,97% for reproducibility, and ≤ 8.12% for homogeneity. The plates sensitized with rLb6H were stable at 4°C and -20°C for 180 days and 37°C for seven days, indicating 12 months of validity. In samples of ATL patients from five research and healthcare centers in endemic and non-endemic areas, rLb6H-ELISA showed a sensitivity of 84.0%; no significant statistical difference was observed among the five centers (chi-square test, p = 0.13). In samples of healthy controls from four areas with different endemicity, a specificity of 92.4% was obtained; lower specificity was obtained in a visceral leishmaniasis high endemicity locality (chi-square test, p<0.001). Cross-reactivity was assessed in 166 other disease samples with a positivity of 13.9%. Based on the good diagnostic performance and the reproducibility and stability of the antigen, we suggest using ELISA-rLb6H to diagnose ATL.