Skin Lesions Of Cutaneous Leishmaniasis Research Articles

Identification of molecular mechanisms causing skin lesions of cutaneous leishmaniasis using weighted gene coexpression network analysis (WGCNA)

Leishmaniasis is an infectious disease, caused by a protozoan parasite. Its most common form is cutaneous leishmaniasis, which leaves scars on exposed body parts from bites by infected female phlebotomine sandflies. Approximately 50% of cases of cutaneous leishmaniasis fail to respond to standard treatments, creating slow-healing wounds which cause permanent scars on the skin. We performed a joint bioinformatics analysis to identify differentially expressed genes (DEGs) in healthy skin biopsies and Leishmania cutaneous wounds. DEGs and WGCNA modules were analyzed based on the Gene Ontology function, and the Cytoscape software. Among almost 16,600 genes that had significant expression changes on the skin surrounding Leishmania wounds, WGCNA determined that one of the modules, with 456 genes, has the strongest correlation with the size of the wounds. Functional enrichment analysis indicated that this module includes three gene groups with significant expression changes. These produce tissue-damaging cytokines or disrupt the production and activation of collagen, fibrin proteins, and the extracellular matrix, causing skin wounds or preventing them from healing. The hub genes of these groups are OAS1, SERPINH1, and FBLN1 respectively. This information can provide new ways to deal with unwanted and harmful effects of cutaneous leishmaniasis.

Transcriptomic landscape of skin lesions in cutaneous leishmaniasis reveals a strong CD8+ T cell immunosenescence signature linked to immunopathology.

The severity of lesions that develop in patients infected by Leishmania braziliensis is mainly associated with a highly cytotoxic and inflammatory cutaneous environment. Recently, we demonstrated that senescent T and NK cells play a role in the establishment and maintenance of this tissue inflammation. Here, we extended those findings using transcriptomic analyses that demonstrate a strong co-induction of senescence and pro-inflammatory gene signatures in cutaneous leishmaniasis (CL) lesions. The senescence-associated signature was characterized by marked expression of key genes such as ATM, Sestrin 2, p16, p21 and p38. The cell type identification from deconvolution of bulk sequencing data showed that the senescence signature was linked with CD8+ effector memory and TEMRA subsets and also senescent NK cells. A key observation was that the senescence markers in the skin lesions are age-independent of patients and were correlated with lesion size. Moreover, a striking expression of the senescence-associated secretory phenotype (SASP), pro-inflammatory cytokine and chemokines genes was found within lesions that were most strongly associated with the senescent CD8TEMRA subset. Collectively, our results confirm that there is a senescence transcriptomic signature in CL lesions and supports the hypothesis that lesional senescent cells have a major role in mediating immunopathology of the disease.

Role of Histopathology in the Diagnosis of Cutaneous Leishmaniasis: A Case-Control Study in Sri Lanka.

Cutaneous leishmaniasis (CL) displays a spectrum of manifestations clinically and histologically. Then, it becomes a diagnostic challenge and must discern from the other clinical and histological mimics, especially when the Leishman-Donovan bodies are inattentive. In this study, we compared the distinguishing histomorphological characteristics of CL against the other skin diseases with similar clinical and histological features. Skin biopsies of 181 patients, which suspect CL clinically, are evaluated histologically. Pertaining to the first case-control comparison, which performed between skin lesions of CL with or without discernible organisms and the other granulomatous dermatitis, highlighted that the ill-formed coalescent granulomata (OR = 14.83) and diffuse dense dermal plasma cell infiltrate (OR = 74.25) are significantly associated with the skin lesions of CL. The second case-control analysis was between CL without discernible organisms and the other granulomatous dermatitis, and identified a significant association in the presence of ill-formed coalescent granulomata (OR = 16.94) and diffuse dense (>50/HPF) dermal plasma cell infiltrate (OR = 74.5) in the skin lesions of CL. Pertaining to epidermal changes, acanthosis (OR = 2.38), spongiosis (OR = 9.13), and the presence of ulceration (OR = 20.26) are among the major concerns in CL. In conclusion, in the presence of clinical suspicion, dermal granulomata in ill-formed coalescent morphology with high plasma cell density in a diffuse arrangement are positive factors for the diagnosis of CL, especially when the discernible Leishmania amastigotes are absent. Resource utilization such as polymerase chain reaction and other ancillary techniques during the diagnosis of CL can be minimized by using a range of histopathological features and special attention should be focused on this in the future.

Molecular diagnosis of cutaneous leishmaniasis in an endemic area of Acre State in the Amazonian Region of Brazil.

This study proposes to identify the Leishmania species found in the skin lesions of cutaneous leishmaniasis (CL) patients from Brasiléia municipality (Acre). Skin biopsy imprints or biopsy fragments were assayed via kDNA-PCR/RFLP and FRET-real-time PCR. Of individuals with suspected CL, 18 were positive for Leishmania kDNA. Leishmania (Viannia) braziliensis (61.1%) and Leishmania (Viannia) guyanensis (5.5%) were identified in the positive samples. These results are congruent with the previous reports in Acre and Bolivia, revealing L. braziliensis as the most prevalent species. L. guyanensis identification also corroborates with the epidemiology of the disease in the Amazon Basin.

Direct diagnosis of Leishmania species on serosity materials punctured from cutaneous leishmaniasis patients using PCR-RFLP

This study was aimed at identifying the Leishmania species using serosity materials punctured from skin lesions of cutaneous leishmaniasis (CL) patients by using internal transcribed spacer1 (ITS1) polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). We used the PCR-RFLP on 60 parasitological confirmed CL patients who referred to leishmaniasis laboratory from the School of Public Health, Tehran University of Medical Sciences. The PCR-RFLP could correctly detect 51 Leishmania species of the 60 confirmed positive specimens, where all the other 10 parasitological (microscopy and culture) negative samples that were prepared from other bacterial- and fungal-infected lesions had negative results. The results also revealed that Leishmania major was the dominant species (53.3%). This study suggests that the PCR-RFLP assay with serosity materials punctured from CL patients using Hae III enzyme is useful for the rapid identification of Leishmania species.

Lymph node involvement in leishmaniasis

Two U.S. Army soldiers acquired skin lesions of cutaneous leishmaniasis and enlarged lymph nodes while stationed in Panama. In the first case, parasites were histologically identified and cultured from the skin lesion and a contralateral lymph node. In the second case, parasites were cultured from an enlarged lymph node in a nodal group draining the lesion. These findings suggest that metastasis of cutaneous leishmanial infection may be more common than is generally appreciated.

Experimental cutaneous leishmaniasis with Leishmania tropica in albino hairless mice, Mus musculus

Cutaneous leishmaniasis was produced in 90 hairless mice, Mus musculus, with cultures of two strains of Leishmania tropica (one isolated from an exogenous human case in Texas, and the other a gerbil strain from the USSR). The mice were inoculated intradermally in five areas of the dorsal side of the body. Most of the inoculated mice developed visible cutaneous leishmaniasis. The early lesions at the sites of inoculation were small red papules appearing within one to two months following inoculation; some of these papules disappeared after a few weeks, others became nodular or pustular. These lesions gradually enlarged and became ulcerated, measuring about 5 to 10 mm in diameter, and some persisted as long as 386 days. The edges of the lesions were usually raised, indurated, and pink; the adjacent skin showed no visible reaction. The centre of the ulcer was either moist or covered with a dry brownish-grey crust. In a few cases the lesions were very extensive and merged with each other, covering nearly two thirds of the dorsal body surface. Smears from the edges of the lesions were positive for the amastigote (aflagellar) form of L. tropica, which produced infections when inoculated into other hairless mice and grew readily in promastigote (flagellar) form on NNP-2 medium ( Packchanian, 1959 ) with suitable antibiotics ( Packchanian, 1957 ). Although mice were inoculated intradermally with L. tropica, several animals with extensive skin lesions of cutaneous leishmaniasis also developed generalized leishmaniasis. This was proved by positive blood culture tests for promastigotes (from 15 mice) and by demonstration of the amastigote form of L. tropica in various organs such as the spleen, liver, kidney, heart and lymph nodes. On the other hand, heart blood from 18 mice with small skin lesions when tested during 62 to 269 days following infection, yielded negative results for promastigotes. The mice were kept under observation (60 to 478 days) before they were killed or died. The results of this study have demonstrated that the hairless mouse, Mus musculus, is a suitable laboratory animal for studying experimental cutaneous leishmaniasis.