Leishmaniasis

Leishmaniasis is a protozoan disease whose clinical manifestations depend both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sandfly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis (CL), to the mucous membranes in mucosal leishmaniasis or spread internally in visceral leishmaniasis (VL). In the last 2 decades, leishmaniasis, especially VL, has been recognized as an opportunistic disease in immunocompromised patients, particularly those infected with HIV. Leishmaniasis is characterized by a spectrum of disease phenotypes that correspond to the strength of the host's cell-mediated immune response. Both susceptible and resistant phenotypes exist within human populations. Clinical cutaneous disease ranges from a few spontaneously-healing lesions, to diffuse external or internal disease, to severe mucous membrane involvement. Spontaneously-healing lesions are associated with positive antigen-specific T cell responsiveness, diffuse cutaneous and visceral disease with T cell non-responsiveness, and mucocutaneous disease with T cell hyperresponsiveness. Current research is focused on determining the extent to which this spectrum of host response is genetically determined. In endemic areas, diagnosis is often made on clinical grounds alone including: small number of lesions; on exposed areas; present for a number of months; resistant to all types of attempted treatments; and usually no pain or itching. Multiple diagnostic techniques are available. When evaluating treatment, the natural history of leishmaniasis must be considered. Lesions of CL heal spontaneously over 1 month to 3 years, while lesions of mucocutaneous and VL rarely, if ever, heal without treatment. Consequently, all the latter patients require treatment. Therapy is not always essential in localized CL, although the majority of such patients are treated. Patients with lesions on the face or other cosmetically important areas are treated to reduce the size of the resultant scar. In addition, the species of parasite should be identified so that infection with Leishmania braziliensis and Leishmania panamensis can be treated to reduce the risk of development of mucocutaneous disease. Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates. Proven treatments include: antimonials, pentamidine, amphotericin B, interferon with antimony. Treatments where current clinical experience is too limited include: allopurinol, ketoconazole, itraconazole, immunotherapy, rifampin, dapsone, localized heat, paromomycin ointment and cryotherapy. Investigational treatments include: WR6026, liposomal amphotericin and miltefosine. In addition, vaccines for leishmaniasis are being investigated in clinical trials.     

Clinical spectrum of cutaneous leishmaniasis: an overview from Pakistan

The clinical spectrum of leishmaniasis encompasses subclinical (inapparent), localized (skin lesions), and disseminated infection (cutaneous, mucosal, or visceral). The clinico-pathological picture of cutaneous leishmaniasis is variable and depends not only on the leishmania species but also on endemic region, host factors, and immuno-inflammatory responses. Symptomatic disease is subacute or chronic and diverse in presentation and outcome. Pakistan is one of the countries in which cutaneous leishmaniasis is becoming an epidemic disease and because of its morbidity and disfiguring scars, it is considered a serious public health problem. This is an attempt to review the clinical spectrum of old world cutaneous leishmaniasis, classical and unusual clinical presentations, occurring in Pakistan.     

Presence of Leishmania organisms in specific and non-specific skin lesions in HIV-infected individuals with visceral leishmaniasis

BACKGROUND: Leishmania coinfection is frequently seen in human immunodeficiency virus (HIV)-infected patients in endemic areas, and from time to time the protozoan is detected in cutaneous biopsies. OBJECTIVE: To establish the characteristics and possible ethiologic role of the presence of Leishmania in these lesions. METHODS: We studied 12 cutaneous biopsies with Leishmania organisms from nine HIV-infected patients (seven men and two women) with visceral leishmaniasis, diagnosed by bone marrow examination, seen over a period of 9 years. RESULTS: Based on clinical characteristics, evolution and response to anti-leishmanial treatment, cutaneous alterations were found to be related to the presence of the protozoan in six cases, whereas in the other six cases it was not considered responsible for the dermatological lesions (dermatofibroma, and lesions of psoriasis, Reiter's syndrome, bacillary angiomatosis, cryptococcosis and oral aphthae). Of note was the high prevalence of specific mucocutaneous manifestations, usually accompanied by intense pruritus, great variability, and a tendency to relapse after treatment stopped. On two occasions, detection of the protozoa in skin biopsies led to the diagnosis of a previously unsuspected visceral leishmaniasis. CONCLUSIONS: Cutaneous detection of Leishmania is frequent in HIV-infected individuals with visceral leishmaniasis. Sometimes Leishmania is associated with changes attributable to other dermatological processes, and its presence does not imply a causative role. A clear relationship between the systemic process and the therapeutic response is necessary to demonstrate an ethiologic role.     

Diffuse (anergic) cutaneous leishmaniasis responding to amphotericin B

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen‐specific immunodeficiency that often presents with multiple disfiguring non‐ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.     

South American cutaneous leishmaniasis: report of ten cases in Israeli travelers

Background Cutaneous South American leishmaniasis is caused by several species of leishmaniasis. Lack of appropriate treatment may lead to mucocutaneous leishmaniasis, mainly with L. b. braziliensis and L. b. panamensis.
Objective To describe the clinical findings of Israeli travelers infected with cutaneous South American leishmaniasis and to draw attention to this problem.
Subjects Ten patients were interviewed, examined and treated.
Results Twenty-two lesions of cutaneous leishmaniasis were found, all in exposed areas. Patients were seen by an average three physicians (range 1–6) before the final diagnosis was confirmed by direct smear, after an average period of 125 days (range 88–270 days). Treatment with Pentostam was started after an average period of 134 days (range 94–275 days). All lesions healed completely, but with scarring.
Conclusion Travelers to endemic areas, as well as physicians, should be instructed about the potential risks and the clinical manifestations of cutaneous and mucocutaneous South American leishmaniasis. Such awareness will prevent undue delay in diagnosis and treatment.     

Leishmaniasis

Infections with Leishmania spp. rank among the top three most common travel‐associated dermatoses. Depending on the country where the infection was acquired and the patient's immune status, different disease manifestations may be observed. Ninety percent of cases present as cutaneous leishmaniasis, but the infection may also affect internal organs (visceral leishmaniasis). Without treatment, the latter is often fatal. Intermediate types include recurrent, diffuse, or mucocutaneous forms. Nodular lesions on exposed skin with a tendency to ulcerate over time in combination with a travel history should therefore prompt workup for leishmaniasis. The diagnosis is made through histology, parasite culture, and PCR using biopsy material. Therapeutic options range from local therapies in cases with singular lesions to systemic therapy in patients with more severe forms. The present review discusses the most important clinical features, details about diagnostic measures, and current therapeutic approaches.     

Unusual manifestations of tegumentary leishmaniasis in AIDS patients from the New World

Background  Comorbidity from tegumentary leishmaniasis and AIDS is poorly characterized.
Objectives  To describe a series of patients coinfected with Leishmania and human immunodeficiency virus (HIV).
Methods  Clinical records from patients were analysed by demographic data, clinical manifestations, diagnoses, treatments and outcomes.
Results  Fifteen cases of AIDS/tegumentary leishmaniasis were found. The diagnosis of leishmaniasis was confirmed by the detection of Leishmania amastigotes or antigens from the cutaneous or mucosal lesions. The mean CD4+ T-cell count was 84 cells mm⁻³ (range 8–258) and all patients were classified as having AIDS according to the Centers for Disease Control and Prevention. A wide range of manifestations was found, varying from a single ulcer to multiple and polymorphic lesions. Mucosal lesions were present in 80% and cutaneous lesions in 73% of patients (53% with mucocutaneous form), disseminated lesions in 60% and genital lesions in 27% of patients. All patients received anti- Leishmania therapy and 53% showed relapses. Sixty-seven per cent received highly active antiretroviral therapy but showed no difference in outcomes and relapses compared with those not using medication. Forty per cent died during the study period. In these patients, the anti- Leishmania antibody and Montenegro skin test were useful in the diagnosis of leishmaniasis, probably because leishmaniasis preceded immunosuppression due to HIV infection.
Conclusions  Clinical manifestations of tegumentary leishmaniasis in HIV-infected patients are diverse. Our data emphasize possible unusual manifestations of this disease in HIV-infected patients, particularly in severely immunosuppressed cases (< 200 CD4+ cells mm⁻³).     

Cutaneous leishmaniasis in a child treated with oral fluconazole

We report a case of cutaneous leishmaniasis in a 3‐year‐old West African girl with a 3‐month history of multiple disfiguring, infiltrated, ulcerating and variably necrotic granulomatous plaques on the limbs and face that occurred after swimming in a river approximately 6 weeks before arriving in Australia. A diagnosis of cutaneous leishmaniasis, a protozoal zoonosis usually transmitted by the Phlebotomus species of sandfly, was considered. The clinico‐pathological features were consistent with Leishmania major infection, known to be the major endemic species causing cutaneous leishmaniasis in the country of origin. Because of the presence of lesions on the face, active treatment was instituted. Continuing resolution of all lesions over 6 weeks was noted to occur with cribiform scarring with the use of oral fluconazole 150 mg daily. Oral fluconazole appears to be emerging as a therapy for uncomplicated cutaneous leishmaniasis, with advantages particularly important in paediatrics.     

Leishmaniasis as an emerging infection

Leishmaniasis is a protozoan disease whose diverse clinical manifestations are dependent both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sand fly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis, limited to the mucous membranes in mucosal leishmaniasis, or spread internally in visceral leishmaniasis or kala azar. The overall prevalence of leishmaniasis is 12 million cases worldwide, and the global yearly incidence of all clinical forms approaches 2 million new cases (World Health Organization WHO/ LEISH/200.42, Leishmania/HIV Co-Infection in Southwestern Europe 1990-98: Retrospective Analysis of 965 Cases, 2000). In the last two decades, leishmaniasis, especially visceral leishmaniasis, has been recognized as an opportunistic disease in the immunocompromised, particularly in patients infected with human immunodeficiency virus.     

Cutaneous leishmaniasis: successful treatment with itraconazole

BACKGROUND: Leishmaniasis is a disease produced by several species of protozoa of the Leishmania genus. These protozoa are injected into the human bloodstream by sandflies. The symptomathology, either cutaneous, mucocutaneous or visceral, depends on the infective species and the immune status of the patient. Antimonial drugs are the mainstay treatment for all the clinical forms of the disease. Amphotericin B is the second-choice drug. METHODS: We report two clinical cases of cutaneous leishmaniasis treated with itraconazole. One case was a relapsing form unresponsive to conventional therapy. RESULTS: Both patients achieved fast resolution of their lesions with no secondary effects. CONCLUSIONS: Itraconazole may be a valid option for the treatment of cutaneous leishmaniasis, mainly in those cases unresponsive to conventional drugs.     

Clinical features of cutaneous and disseminated cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis in Paraty, Rio de Janeiro

Background  American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) braziliensis is endemic in Rio de Janeiro State (RJ), where the disease shows epidemiologic and clinical characteristics distinct from those of ATL in other Brazilian regions. Paraty is the second most important endemic area in RJ; however, reports on leishmaniasis in this region refer to the occurrence of the disease without describing its characteristics.
Methods  The clinical features of 71 cases of ATL reported between 1991 and 1997 in Paraty are presented. Thirty patients were re-evaluated 10 years later.
Results  Males and females were affected in similar proportions, and the disease was more prevalent in patients aged between 10 and 49 years (63.4%). Cutaneous leishmaniasis was the most prevalent clinical form observed. Unique lesions were present in 69% of cases, 91.6% of which displayed an ulcerated aspect. Although mucosal leishmaniasis was not observed, severe clinical manifestations, such as disseminated cutaneous lesions caused by L. braziliensis , were diagnosed in two patients. These patients presented skin lesions with different clinical aspects spread throughout the body, as well as low cellular immune responses. Montenegro skin test (92% positivity) and serology (8% IgM and 56% IgG anti- Leishmania positive results) were the most utilized tests for supporting the diagnosis of leishmaniasis. Parasites, detected in 27 of the 33 cases analyzed, were characterized as L. braziliensis .
Conclusion  ATL in Paraty shares the clinical and laboratory characteristics reported for ATL in other regions of RJ, probably because of the similar epidemiologic context related to the Atlantic rainforest region.     

Cutaneous leishmaniasis as travelers' disease. Clinical presentation, diagnostics and therapy

Leishmaniasis is a disease with worldwide increasing incidence, which in Germany is almost exclusively observed in patients who have travelled to classical endemic regions such as the Mediterranean basin. Cause of the disease is an infection with protozoan parasites of the genus Leishmania, which are transmitted by sand flies and replicate intracellularly within mammalian hosts. Depending on the inoculated parasite (sub-) species and the immune status of the host, a local cutaneous, diffuse cutaneous, mucocutaneous or visceral form of leishmaniasis will develop. Cutaneous leishmaniasis, which frequently appears only weeks after the bite of a sand fly, starts with the formation of a papule, which subsequently can turn into a skin ulcer. The latter may heal spontaneously after months leaving behind a scar or persist as chronic, non-healing cutaneous leishmaniasis. If cutaneous leishmaniasis is suspected, a sterile skin biopsy followed by appropriate diagnostic measures in a specialized laboratory to identify the pathogen should be performed. For the decision on the type of therapy, several clinical parameters (e.g. number and localization of lesions, immune status) and, most importantly, the underlying parasite (sub-) species need to be considered. Therapy can consist of a variety of topical measures or systemic drug treatment. A modern and safe vaccine does not yet exist.     

New world leishmaniasis. Serologic aids to diagnosis.

The increase in travel to endemic areas of South and Central America has led to an increase in the number of cases of cutaneous leishmaniasis diagnosed in the United States. Traditional methods of diagnosis for this disease include microscopical examination of infected tissue, culture of Leishmania on special media, and the leishmanin skin test. The present communication describes a case of cutaneous leishmaniasis and the difficulties that were encountered in diagnosis. New methods of serologic testing allow more prompt and accurate diagnosis.     

Unusual clinical variants of cutaneous leishmaniasis in Sicily

Background  The term "leishmaniasis" defines a group of vector-borne diseases caused by species of the genus Leishmania and characterized by a spectrum of clinical manifestations. Parasite properties (infectivity, pathogenicity, virulence), host factors, and host responses regulate heterogeneous disease expression. Sicily is one of the major islands of the Mediterranean Basin and is considered to be a hypo-endemic area for cutaneous leishmaniasis. Leishmania infantum is the most common species on the island.
Methods  Fifty patients (both sexes and different ages) with lesions clinically suggestive of cutaneous leishmaniasis were recorded over a 1-year period. The diagnosis was based on positive slit-skin smear and histopathologic studies when needed. Polymerase chain reaction (PCR) was performed as test confirmation.
Results  Twenty-five patients had typical solitary lesions of cutaneous leishmaniasis. Multiple lesions were present in five patients. In 20 patients, the lesions were very unusual, including erysipeloid, zosteriform, and lupoid leishmaniasis. The results of Leishmania isoenzyme characterization identified Leishmania infantum as the species responsible for the 20 atypical cases.
Conclusion  The global number of cases of cutaneous leishmaniasis in Sicily has increased in recent years, and such increases can be explained, in part, by the fact that, in this region, sandflies are present during a large part of the year. This is a result of the climatic variation in recent years (increasing temperature and humidity). There has also been an increase in the number of new and rare variants of cutaneous leishmaniasis. A knowledge of the unusual clinical variants of cutaneous leishmaniasis, as well as classical forms, allows early detection.     

Old world cutaneous leishmaniasis in Los Angeles: a case report,overview of the current literature,and guide for the treating dermatopathologist

We describe a case of cutaneous leishmaniasis in a Spanish patient visiting Los Angeles. Leishmania species cause both cutaneous and visceral disease; the majority of infections with Leishmania are of the cutaneous form. Although leishmaniasis is a relatively rare occurrence in the United States, travel by United States' citizens to endemic regions and increased United States military operations in the Middle East raise the chances of encountering cutaneous leishmaniasis. The following case report and overview of the current literature outlines the major morphologic findings and current diagnostic modalities available to diagnose cutaneous leishmaniasis.     

Comparative study of cutaneous leishmaniasis in human immunodeficiency virus (HIV)-infected patients and non-HIV-infected patients in French Guiana

BACKGROUND: Few data are available on cutaneous leishmaniasis caused by dermotropic species in human immunodeficiency virus (HIV)-infected patients. OBJECTIVES: To describe nine cases of cutaneous leishmaniasis in HIV+ patients and to compare their clinical features and their response to treatment with those of HIV- patients with the forms of leishmaniasis commonly found in French Guiana. METHODS: A case-control study was carried out between July 1994 and December 2000 in French Guiana. We compared the following variables in nine HIV-infected patients with leishmaniasis and 27 matched controls: clinical type of leishmaniasis, number of lesions, presence of lymphangitis and adenopathy, the rate of recovery after treatment, and recurrence or reinfection. RESULTS: Eight of the HIV-infected patients had localized cutaneous leishmaniasis and one had mucocutaneous leishmaniasis. All of the controls had localized cutaneous leishmaniasis. Leishmania guyanensis was the only species isolated from HIV-infected subjects. HIV-Leishmania coinfected patients had a higher rate of recurrence or reinfection (P < 0.02) and a lower rate of recovery after one treatment cycle with pentamidine (P < 0.02) than did HIV- subjects. The CD4+ lymphocyte counts exceeded 200 mm(-3) in all HIV+ patients at the time of the diagnosis with leishmaniasis. CONCLUSIONS: In French Guiana, cutaneous leishmaniasis in moderately immunosuppressed HIV-infected subjects (> 200 CD4+ T cells mm(-3)) is characterized by a higher rate of recurrence or reinfection and is more difficult to treat than that in HIV- subjects.     

Photodynamic treatment of cutaneous leishmaniasis

Leishmaniasis is a widespread arthropod‐borne protozoan zoonosis caused by more than 21 Leishmania species. Vectors are sandflies of different genera. The disease is classified into ?Old World” versus ?New World” leishmaniasis and further subclassified in cutaneous, mucocutaneous and visceral forms. Most therapeutic approaches are not evidence‐based. We report a patient with facial cuta‐neous Leishmania tropica infection which proved to be resistant to various therapeutic regimes. Excellent results were achieved with photody‐namic therapy.     

Disseminated mucocutaneous leishmaniasis resulting from chronic use of corticosteroid

Mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin and mucosal lesions whose clinical manifestations can regress spontaneously, but with possible long subclinical evolution. The course of the disease is often related to the host immune response. The purpose of this article is to describe the clinical and microscopic findings of cutaneous and mucosal lesions of mucocutaneous leishmaniasis in a patient who presented an unusual form of the disease associated with an immunosuppressive state.     

American tegumentary leishmaniasis (ATL) in Rio de Janeiro State, Brazil: main clinical and epidemiologic characteristics

BACKGROUND: Rio de Janeiro State in Brazil is an endemic area of American tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis. Objective Our purpose was to describe the main clinical and epidemiologic characteristics of the disease in Rio de Janeiro State. METHODS: Patients from endemic areas of Rio de Janeiro State attending the Evandro Chagas Hospital were included in the study. A general physical, dermatologic, and otorhinolaryngologic examination was performed in all patients, as well as a Leishmanin skin test. Skin biopsy specimens were obtained and utilized for touch preparations (stained with Leishman dye), culture in special media (Nicolle, Nevy and McNeal; NNN), and histopathologic examination after hematoxylin and eosin stain. Positive cultures were identified with regard to species by the isoenzyme technique. Therapy with pentavalent antimonial compounds was employed in all cases. Eco-epidemiologic characteristics were studied through regular field visits to endemic foci. RESULTS: Cutaneous disease was present in 87.2% of patients, and mucosal disease in only 12.7%. A single ulcerative cutaneous lesion was the most common clinical presentation. Demonstration of the parasite was always difficult and culture in special media gave the best results for diagnosis. The species involved in transmission was Leishmania (Viannia) braziliensis. Vectors included phlebotomine sand flies (Diptera: Psychodidae) of the genus Lutzomyia, and the most common species was Lutzomyia intermedia, captured mainly on the external walls of houses. CONCLUSIONS: ATL in Rio de Janeiro is mostly a cutaneous disease. In general, the cases showed great sensitivity to antimony. A pattern of peridomestic transmission seems to be the rule.     

Reactivation of dormant cutaneous Leishmania infection in a kidney transplant patient

BACKGROUND: Leishmaniasis is an infection caused by a protozoan parasite belonging to genus Leishmania and transmitted by the Phlebotomus sandfly. Clinical presentations of infection include visceral, cutaneous, and mucocutaneous forms. Leishmaniasis is endemic in Africa, Asia, Europe, South America, and southern part of North America. This infection is extremely rare in the US and is mostly found among travelers coming from endemic areas. Cases of cutaneous and visceral leishmaniasis have been reported in organ transplant recipients in endemic areas. CASE REPORT: We describe a case of cutaneous leishmaniasis in a kidney transplant patient, originally from Bolivia, who resides in the area known to be non-endemic for leishmaniasis and who is known not to travel within or outside of the US after the transplantation. RESULTS: Histologic examination of cutaneous lesion revealed extensive subcutaneous lymphohistiocytic inflammation with clusters of amastigote within histiocytes. CONCLUSION: To our knowledge, this is the first case of cutaneous leishmaniasis in a kidney transplant patient residing in the US in an area known to be non-endemic for leishmaniasis, probably after reactivation of a previously dormant infection acquired outside of the US at least 9 months prior to developing clinical symptoms.