Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL)

Leishmaniasis is a neglected tropical disease that affects 12 million people worldwide. The disease has high morbidity and mortality rates and is prevalent in over 80 countries, leaving more than 300 million people at risk of infection. Of all of the manifestations of this disease, cutaneous leishmaniasis (CL) is the most common form and it presents as ulcerating skin lesions that can self-heal or become chronic, leading to disfiguring scars. This review focuses on the different pathologies and disease manifestations of CL, as well as their varying degrees of severity. In particular, this review will discuss self-healing localized cutaneous leishmaniasis (LCL), leishmaniasis recidivans (LR), mucocutaneous leishmaniasis (MCL), anergic diffuse cutaneous leishmaniasis (ADCL), disseminated leishmaniasis (DL), and Post Kala-azar Dermal Leishmaniasis (PKDL), which is a cutaneous manifestation observed in some visceral leishmaniasis (VL) patients after successful treatment. The different clinical manifestations of CL are determined by a variety of factors including the species of the parasites and the host’s immune response. Specifically, the balance between the pro and anti-inflammatory mediators plays a vital role in the clinical presentation and outcome of the disease. Depending upon the immune response, Leishmania infection can also transition from one form of the disease to another. In this review, different forms of cutaneous Leishmania infections and their immunology are described.

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766. Everything Old is New Again-A Case Series of New World Leishmaniasis in African Children in Portland, Maine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.956 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S428-S428

Author(s):

Jennifer Jubulis ◽

Amanda Goddard ◽

Elizabeth Seiverling ◽

Marc Kimball ◽

Carol A McCarthy

Keyword(s):

Latin America ◽

Cutaneous Leishmaniasis ◽

New World ◽

Pediatric Patients ◽

Data Extraction ◽

Clinical Manifestations ◽

Case Series ◽

Surgical Excision ◽

Skin Lesions ◽

Travel History

Abstract Background Leishmaniasis has many clinical manifestations and treatment regimens, dependent on species and host. Old world leishmaniasis is found primarily in Africa and Asia, and is associated with visceral disease, while new world disease, seen primarily in Latin America, is more commonly mucocutaneous. We present a case series of pediatric African patients with New World cutaneous leishmaniasis (NWCL). Methods Data extraction was performed via chart review, analyzing travel history, clinical presentation, diagnosis, and management in children with cutaneous leishmaniasis presenting to the pediatric infectious diseases clinic in Portland, ME. Biopsy specimens were sent to the federal CDC for identification by PCR and culture. Results Five cases of NWCL were diagnosed in pediatric patients in Maine from November 2018 through February 2020. Median age of patients was 10 years (range 1.5-15 years). Four cases (80%) occurred in children from Angola or Democratic Republic of Congo, arriving in Maine via Central/South America, with one case in a child from Rwanda who arrived in Maine via Texas. Three patients had multiple skin lesions and two had isolated facial lesions. Leishmaniasis was not initially suspected resulting in median time to diagnosis of 5 months (range 1-7 months). Four patients were initially treated with antibacterials for cellulitis and one was treated with griseofulvin. After no improvement, patients underwent biopsy with 2 patients diagnosed with L panamensis, 1 with L braziliensis, 1 with mixed infection (L panamensis and L mexicana), and 1 with Leishmania species only. One patient was managed with surgical excision, 3 with ketoconazole, and 1 was observed off therapy. Four patients were referred to otolaryngology. All continue to be followed in infectious disease clinic. Conclusion We present five cases of new world cutaneous leishmaniasis in African pediatric patients arriving to Maine through Latin America or Texas. Patients were diagnosed with cellulitis, tinea corporis or atopic dermatitis initially, underscoring importance of high index of suspicion in migrant patients. Detailed travel history and epidemiologic knowledge is essential to diagnosis, as patients may present with illness not congruent with country of origin. Optimal therapy remains unclear. Disclosures All Authors: No reported disclosures

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A transient increase in MHC-IIlow monocytes after experimental infection with Avibacterium paragallinarum (serovar B-1) in SPF chickens

Veterinary Research ◽

10.1186/s13567-020-00840-7 ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Karla Lucía F. Alvarez ◽

Astrid Poma-Acevedo ◽

Manolo Fernández-Díaz

Keyword(s):

Immune Response ◽

Large Body ◽

Clinical Signs ◽

Clinical Manifestations ◽

Nasal Discharge ◽

High Morbidity ◽

Upper Respiratory Tract ◽

Secondary Infections ◽

Avibacterium Paragallinarum ◽

Facial Swelling

Abstract Infectious coryza (IC), an upper respiratory tract disease affecting chickens, is caused by Avibacterium paragallinarum. The clinical manifestations of IC include nasal discharge, facial swelling, and lacrimation. This acute disease results in high morbidity and low mortality, while the course of the disease is prolonged and mortality rates are increased in cases with secondary infections. Studies regarding the immune response in infected chickens are scarce, and the local immune response is the focal point of investigation. However, a large body of work has demonstrated that severe infections can impact the systemic immune response. The objective of this study was to evaluate the systemic effects of Avibacterium paragallinarum (serovar B-1) infection on immune cells in specific pathogen-free (SPF) chickens. The current study revealed the presence of a transient circulating monocyte population endowed with high phagocytic ability and clear downregulation of major histocompatibility complex class II (MHC-II) surface expression. In human and mouse studies, this monocyte population (identified as tolerant monocytes) has been correlated with a dysfunctional immune response, increasing the risk of secondary infections and mortality. Consistent with this dysfunctional immune response, we demonstrate that B cells from infected chickens produced fewer antibodies than those from control chickens. Moreover, T cells isolated from the peripheral blood of infected chickens had a lower ability to proliferate in response to concanavalin A than those isolated from control chickens. These findings could be related to the severe clinical signs observed in complicated IC caused by the presence of secondary infections.

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Involvement of the Inflammasome and Th17 Cells in Skin Lesions of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia) panamensis

Mediators of Inflammation ◽

10.1155/2020/9278931 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

K. Gonzalez ◽

J. E. Calzada ◽

C. E. P. Corbett ◽

A. Saldaña ◽

M. D. Laurenti

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Th17 Cells ◽

Inverse Correlation ◽

Skin Lesions ◽

Leishmania Infection ◽

Caspase 1 ◽

Immunological Markers ◽

Th2 Immune Response ◽

Skin Biopsies

Localized cutaneous leishmaniasis (LCL) caused by Leishmania (Viannia) panamensis is an endemic disease in Panama. This condition causes ulcerated skin lesions characterized by a mixed Th1/Th2 immune response that is responsible for disease pathology. However, the maintenance of the in situ inflammatory process involves other elements, such as Th17 and inflammasome responses. Although these processes are associated with parasite elimination, their role in the increase in disease pathology cannot be discarded. Thus, the role in Leishmania infection is still unclear. In this sense, the present study aimed at characterizing the Th17 and inflammasome responses in the skin lesions of patients with LCL caused by L. (V.) panamensis to help elucidate the pathogenesis of this disease in Panama. Th17 and inflammasome responses were evaluated by immunohistochemistry (IHQ) in 46 skin biopsies from patients with LCL caused by L. (V.) panamensis. The Th17 immune response was assessed using CD3, CD4, RoRγt, IL-17, IL-6, IL-23, and TGF-β1 antibodies, and the inflammasome response was assessed by IL-1β, IL-18, and caspase-1 antibodies. The presence of the Th17 and inflammasome responses was evidenced by a positive reaction for all immunological markers in the skin lesions. An inverse correlation between the density of amastigotes and the density of RoRγt+, IL-17+, IL-1β+, and caspase-1+ cells was observed, but no correlation between Th17 and the inflammasome response with evolutionary disease pathology was reported. These data showed the participation of Th17 cells and the inflammasome in the inflammatory response of the skin lesions of LCL caused by L. (V.) panamensis infection. These results suggest a role in the control of tissue parasitism of IL-17 and the activation of the NLRP3 inflammasome dependent on IL-1β but cannot exclude their role in the development of disease pathology.

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Clinical Manifestations and Distribution of Cutaneous Leishmaniasis in Pakistan

Journal of Tropical Medicine ◽

10.1155/2011/359145 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Abaseen Khan Afghan ◽

Masoom Kassi ◽

Pashtoon Murtaza Kasi ◽

Adil Ayub ◽

Niamatullah Kakar ◽

...

Keyword(s):

Primary Care ◽

Health Care ◽

Cutaneous Leishmaniasis ◽

Primary Care Physicians ◽

Health Workers ◽

Clinical Manifestations ◽

Public Health Problem ◽

Skin Lesions ◽

Major Public Health Problem ◽

Local Health

Cutaneous leishmaniasis (CL) is a rising epidemic in Pakistan. It is a major public health problem in the country especially alongside regions bordering the neighboring Afghanistan and cities that have had the maximum influx of refugees. The purpose of our paper is to highlight the diverse clinical manifestations of the disease seen along with the geographic areas affected, where the hosts are particularly susceptible. This would also be helpful in presenting the broad spectrum of the disease for training of health care workers and help in surveillance of CL in the region. The increased clinical diversity and the spectrum of phenotypic manifestations noted underscore the fact that the diagnosis of CL should be not only considered when dealing with common skin lesions, but also highly suspected by dermatologists and even primary care physicians even when encountering uncommon pathologies. Hence, we would strongly advocate that since most of these patients present to local health care centers and hospitals, primary care practitioners and even lady health workers (LHWs) should be trained in identification of at least the common presentations of CL.

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Evaluation of Regulatory Immune Response in Skin Lesions of Patients Affected by Nonulcerated or Atypical Cutaneous Leishmaniasis in Honduras, Central America

Mediators of Inflammation ◽

10.1155/2018/3487591 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Gabriela Venicia Araujo Flores ◽

Carmen Maria Sandoval Pacheco ◽

Thaise Yumie Tomokane ◽

Wilfredo Sosa Ochoa ◽

Concepción Zúniga Valeriano ◽

...

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Central America ◽

Normal Skin ◽

Skin Lesions ◽

Moderate Correlation ◽

Inflammatory Infiltration ◽

Histological Techniques ◽

Cellular Immune

In Honduras, Leishmania (L.) infantum chagasi causes both visceral leishmaniasis (LV) and nonulcerated or atypical cutaneous leishmaniasis (NUCL). NUCL is characterized by mononuclear inflammatory infiltration of the dermis, composed mainly of lymphocytes followed by macrophages with discrete parasitism. Considering that little is known about the pathogenesis of NUCL, the aim of this study was to evaluate the regulatory response in situ in skin lesions of patients affected by NUCL. Biopsies (n=20) from human cutaneous nonulcerative lesions were collected and processed by usual histological techniques. The in situ regulatory immune response was evaluated by immunohistochemistry using antihuman CD4, FoxP3, IL-10, and TGF-β antibodies. CD4+, FoxP3+, TGF-β+, and IL-10+ cells were observed in the dermis with inflammatory infiltration in all studied cases and at higher densities compared to the normal skin controls. A positive and strong correlation was observed between CD4+ and FoxP3+ cells, and a positive and moderate correlation was observed between FoxP3+ and TGF-β+ but not with IL-10+ cells. The data suggest that T regulatory FoxP3+ cells and the regulatory cytokines, especially TGF-β, play an important role in the immunopathogenesis of NUCL, modulating a cellular immune response in the skin, avoiding tissue damage, and leading to low tissue parasitic persistence.

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Spontaneous regional heading of extensive skin lesions in diffuse cutaneous leishmaniasis (DCL)

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821995000100008 ◽

1995 ◽

Vol 28 (1) ◽

pp. 45-47 ◽

Cited By ~ 6

Author(s):

Jackson M.L. Costa ◽

Ana Cristina R. Saldanha ◽

Conceição de Maria P. e Silva ◽

Maria dos Remédios F.C. Branco ◽

Aldina Barrai ◽

...

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Cellular Immune Response ◽

Skin Lesions ◽

In Situ Characterization ◽

Spontaneous Healing ◽

Specific Therapy ◽

Mucosal Involvement ◽

Cellular Immune

The authors report a case of diffuse cutaneous leishmaniasis, with longstanding evolution and presenting with diffuse infiltrated lesions rich in amastigotes in the absence of mucosal involvement. In situ characterization with monoclonal antibodies revealed Leishmania amazonensis. Large regional lesions have presented spontaneous healing without specific therapy. Considering that DCL presents with a defect in the cellular immune response, thisfact demonstrate that this patient may develop a regional cellular immune response enough to destroy the parasites and to produce clearing of some lesions.

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Congenital syphilis in Argentina: experience in a pediatric hospital

10.1101/2020.06.16.20132795 ◽

2020 ◽

Author(s):

Luciana Noemí Garcia ◽

Alejandra Destito Solján ◽

Nicolas Falk ◽

Nicolás Leonel Gonzalez ◽

Griselda Ballering ◽

...

Keyword(s):

Medical Records ◽

Congenital Syphilis ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Skin Lesions ◽

Penicillin G ◽

High Morbidity ◽

Laboratory Findings ◽

Therapeutic Decisions

AbstractAlthough congenital syphilis (CS) is preventable, it is still an important health problem worldwide. Recently, an increase in the number of primary and congenital syphilis cases has been observed. Fetal infection can be particularly aggressive, but newborns can be asymptomatic at birth and run the risk of developing systemic compromise with a poor prognosis.We conducted a study (1987-2019) analyzing the medical records of CS diagnosis cases assisted at the Buenos Aires Children’ Hospital. Sixty-one patients were included. Information about demographics, clinical and laboratory findings, T. pallidum serology and treatment was collected. Median age at diagnosis was 2 months (IQ 1-6 months). The distribution of cases showed a bimodal curve, with a peak in 1993 and in 2017. The main clinical findings were: bone alterations in 36/61 (59%); hepatosplenomegaly in 33/61 (54.1%); anemia in 32/51 (62.8%); skin lesions 26/61 (42.6%) and renal compromise in 15/45 (33.3%). Cerebrospinal fluid was studied in 50/61 (81.9%); 5 (10%) were abnormal (reactive VDRL and/or cell alteration count). Only 23 (60.5%) patients had nontreponemal titers fourfold higher than their mothers did. Intravenous penicillin G for an average of 10-14 days was prescribed in 60/61 subjects and one patient received ceftriaxone. Remarkably, only 28 (46%) mothers were tested for syphilis during pregnancy.During follow-up, a decrease in RPR titers was observed reaching seroconversion in 31/34 (91%) subjects at a median of 19.2 months after treatment. Treponemal titers (TPHA) remained reactive.Our results highlighted that an increase in the number of cases of CS is occurring in our population with high morbidity related to delayed diagnosis. A good therapeutic response was observed.CS requires a greater effort from obstetricians to adequately screen for the disease during pregnancy and pediatricians should be alert in order to detect cases earlier, to provide an adequate diagnosis and treatment of CS.Author SummaryCS is caused by mother-to child transmission. Although screening of pregnant women and treatments are available, new cases are increasing worldwide. We reviewed the medical records of CS-patients assisted in our hospital over the past 30 years. Our results showed that there was an increase in the number of CS cases. At birth, most children were asymptomatic and later developed CS clinical manifestations. Penicillin treatment, and in one case ceftriaxone, was prescribed with a good clinical response. Nevertheless, one infant died, four had persistent kidney disorders and one showed bone sequelae damage. Spinal lumbar puncture did not modify therapeutic decisions. In the follow-up, a decrease in nontreponemal antibodies was observed as a marker of treatment response. We concluded that the detection and treatment of CS remains a great challenge for clinical practice in our region.It is crucial that pediatricians and obstetricians give greater attention and make a greater effort to detect this neglected disease in an attempt to reverse its upwards trend.

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Development of Cutaneous Leishmaniasis after Leishmania Skin Test

Case Reports in Medicine ◽

10.1155/2011/631079 ◽

2011 ◽

Vol 2011 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Paulo R. Machado ◽

Augusto M. Carvalho ◽

Gustavo U. Machado ◽

Marina L. Dantas ◽

Sérgio Arruda

Keyword(s):

Immune Response ◽

Cutaneous Leishmaniasis ◽

Skin Test ◽

Mononuclear Cells ◽

Previous History ◽

Self Healing ◽

Necrosis Factor Alpha ◽

Cutaneous Ulcer ◽

The Right

Thirty-year-old female with a previous history of a cutaneous ulcer suspicious of leishmaniasis 20 years ago presented with a new complaint of a depressed papular lesion8×7 mm in the right lower extremity. The lesion was of 10-day duration. Because early cutaneous leishmaniasis (CL) lesions may have a non-ulcerated appearance, a Leishmania skin test (LST) was performed on the forearm with a strong positive result (38×32 mm). After 8 days, the lesion in the leg, which was diagnosed as folliculitis, completely healed. However, a typical CL ulcer (26×24 mm) developed at the LST site. Histopathology of the new lesion did not identifiy parasites, but the findings were consistent with a diagnosis of CL. Further analysis identified amastigotes by immunohistochemical stain. Mononuclear cells harvested from the patient were stimulated with Leishmania antigen and showed high levels of production of both tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ): 2,943 pg/mL and 2,313 pg/mL, respectively. After 40 days of treatment with antimony and pentoxifylline, the ulcer resolved. The development of CL at the LST site suggests a strong Th1 immune response, and it is anin vivodocumentation of the role of the host immune response in the pathology of CL. It teaches us that LST should be cautiously, if at all, used in patients with self-healing CL ulcers.

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Disseminated Cutaneous Leishmaniasis in Colombia: Report of 27 Cases

Case Reports in Dermatology ◽

10.1159/000441120 ◽

2015 ◽

Vol 7 (3) ◽

pp. 275-286 ◽

Cited By ~ 10

Author(s):

Iván D. Vélez ◽

Alejandra Jiménez ◽

Daniel Vásquez ◽

Sara M. Robledo

Keyword(s):

Cutaneous Leishmaniasis ◽

Causative Agent ◽

Clinical Manifestations ◽

Mixed Race ◽

Upper Extremities ◽

Response To Treatment ◽

Kala Azar ◽

Clinical Presentations

Disseminated leishmaniasis (DL) is a poorly described disease that is frequently misdiagnosed as other clinical manifestations of cutaneous leishmaniasis (CL) such as diffuse CL or post-kala-azar dermal leishmaniasis. Twenty-seven cases of DL diagnosed between 1997 and 2015 are described. A higher prevalence was observed in men (mean age 32 years). The number of lesions per patient ranged from 12 to 294, distributed mainly in the upper extremities, face and trunk. The lesions were mostly plaques or nodules. Seven patients had nasal mucous damage, 74% of the patients were of mixed race, 92% lived in northwestern Colombia, and Leishmania (Viannia) panamensis was identified as the causative agent in 58% of cases. Eighteen patients recovered with pentavalent antimonial. The importance of distinguishing DL from those other clinical presentations is based on the fact that disseminated, diffuse and post-kala-azar CL are very different in etiology, clinical manifestations and response to treatment and prognosis.

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