Cutaneous Leishmaniasis (CL)

1) Cutaneous Leishmaniasis (CL) 1) Cutaneous Leishmaniasis (CL)  Skin leishmaniasis  Oriental sore  Salak 1) Cutaneous Leishmaniasis (CL) or Salak a) Localized or simple CL Most common form, relatively benign self-healing skin lesions b) Diffuse Cutaneous Leishmaniasis (DCL) Rare cutaneous infection with non-ulcerating nodules resembling lepromatous leprosy c) Leishmaniasis Recidiva Rare hypersensitive relapsing dermal response 1) Cutaneous Leishmaniasis (CL) or Salak Causative agents: In the Old World (such as Iran): In the New World: Leishmania tropica complex: Leishmania mexicana complex L. tropica (Iran) L. mexicana L. major (Iran) L. amazonensis L. aethiopica L. garnhami L. pifanoi L. venezuelensis Epidemiology Life cycle The bite of the during dusk active female sandflies starts the infection 1. Phlebotomus 2. Lutzomyia 3. Sergentomyia  In these cases so-called promastigote stages (their flagellum protrudes at the apical pole) are transmitted Inside the skin they enter cells of the endothelium, histiocytes and macrophages There they are transformed to very tiny amastigotes (2–4 μm) containing a central nucleus and a kinetoplast with typical strands of DNA. Their flagellum cannot be observed by light microscopy, because it is too short and does not protrude the cell surface Host cells in the area around the bite site are mostly damaged due to the repeated divisions of the parasite. Therefore these zoonotic pathogens will spread concentrically around the bite sites. The stages of the salivary leishmaniasis (promastigotes) are only rarely found in the blood or inside local lymph nodes Thus spreading of these parasites can be seen only locally around the area of the bite site. Therefore these parasites can most easily be demonstrated with the help of biopsies and smear preparations taken from borders of infected skins When the sandfly bites again, it ingests further amastigotes, which then are transformed to large amounts of infectious promastigotes in the intestine of this fly; the life cycle is closed When the sandfly bites again, it ingests further amastigotes, which then are transformed to large amounts of infectious promastigotes in the intestine of this fly; the life cycle is closed Symptoms of the disease (CL) 1- L. tropica (Old World) Dry cutaneous leishmaniasis Urban cutaneous leishmaniasis Anthroponotic cutaneous leishmaniasis (ACL) Vector or intermediate host: Phlebotomus serjenti Reservoir host: Human (Dogs) • The dog may be a natural host, but is not thought to be an effective reservoir for humans L. tropica produces chronic disease that, if not treated, lasts for a year or longer It is characterized by the production of dry lesions that ulcerate only after several months, are usually single, and occur primarily on the face It is found in urban areas, widely distributed around the Mediterranean littoral, in Armenia, Azerbaijan, Turkmenistan, and Uzbekistan; it is seen also in Afghanistan, India, and Kenya Iran 2- L. major (Old World) – Humid (wet or moist) cutaneous leishmaniasis (Oriental and Aleppo sore) – Rural cutaneous leishmaniasis – Zoonotic cutaneous leishmaniasis (ZCL) –Vector or intermediate host: Phlebotomus papatasi – Reservoir host: Rodents (gerbils) – Leishmania major produces an acute infection with a duration of 3 to 6 months The lesions occur primarily on the lower limbs  The lesions are moist and tend to ulcerate very early; there may be secondary or satellite lesions  L. major occurs in: Asia: Kara Kum and Kyzyl Kum deserts of Turkmenistan, Uzbekistan, Kazakhstan, Iran, Syria, Jordan Africa: Algeria, Egypt, Tunisia, the Sahara, Sudan, Chad, Nigeria, Niger, Burkina Faso, Mali, Senegal, and Kenya It is primarily a disease of rural areas Reservoir hosts: gerbils and other rodents are important sources of human infection 3- L. aethiopica (Old World) – CL and also Diffuse cutaneous/mucosa leishmaniasis (CL, DCL, MCL) – A chronic disease (CL), seen in the highlands of Ethiopia, in Kenya, and possibly in south Yemen – Reservoir host: rock hyrax CL in New World In the New World, cutaneous leishmaniasis is caused by species of the Leishmania mexicana complex, of which L. mexicana and L. pifanoi are the most important (L. mexicana, L. amazonensis, L. garnhami, L. pifanoi, L. venezuelensis) The Chiclero ulcer or Bay sore is caused by L. mexicana • Chiclero ulcer Guatemala is found in Belize, the Yucatan peninsula, and • Amastigotes of the L. mexicana complex have been isolated from dermal lesions of humans and from woodrats and a cat in the same area of Texas • Lesions are usually single, and 40% affect the ear, where they can be quite destructive of cartilage • Rarely the diffuse cutaneous (DCL) form is seen, with extensive proliferative lesions more or less all over the body • Reservoir hosts: forest rodents • Vector or intermediate host: sandfly of the genus Lutzomyia L. pifanoi occurs in the Amazon basin, in Mato Grosso State in Brazil, and in Venezuela • It has been isolated only from patients with the diffuse cutaneous (DCL) form of the disease • The initial lesion is a single one, and often a period of months or years passes (during which it may ulcerate or even disappear) before the disease spreads both locally and to distant skin areas • The irregularly shaped papules, which bear a resemblance to the lepromatous lesions of leprosy, spread slowly and do not ulcerate or heal • The organisms do not invade the viscera, and the patient remains in general good health L. amazonensis is found in the Amazon basin of Brazil and is the cause of cutaneous and diffuse cutaneous forms of leishmaniasis (CL and DCL) Reservoir hosts for this species of the L. mexicana complex are: • Forest mammals including rodents: marsupials, and foxes Principal vector (intermediate host): Lutzomyia sandfly L. garnhami causes Venezuelan Andean cutaneous leishmaniasis (CL) (Venezuela) L. venezuelensis causes cutaneous leishmaniasis (CL) in a forested area along the River Turbio, state of Lara, Venezuela CL in New World due to Viannia subgenus: Leishmania braziliensis complex L. (Viannia) braziliensis, L. (V.) colombiensis, L. (V.) panamensis, L. (V.) guyanensis, L. (V.) peruviana, L. (V.) naiffi, L. (V.) equatorensis, L. (V.) lainsoni, L. braziliensis/L. guyanensis hybrid L. peruviana is confined to the western Peruvian Andes and causes a disease in humans known locally as Uta (CL in Peru) • Uta (CL in Peru): There may be one or a small number of skin lesions that are self-healing and similar to those of L. tropica; it has, in fact, been suggested that this species is actually imported L. tropica  Reservoir hosts: Domestic dog and probably a wild rodent  Vector (intermediate host): sandflies of the genus Lutzomyia L. guyanensis (which occurs in the Guyanas and northern Brazil) L. panamensis (which occurs in Panama, Costa Rica, and Colombia) • Produce single skin ulcers, but with both organisms lymphatic spread may occur, resulting in widespread ulceration • Mucocutaneous (MCL) involvement may occur, but it is rare. • The disease caused by L. guyanensis is known locally as pian bois Reservoir hosts of L. guyanensis : Arboreal sloths and anteaters Vector (intermediate host): Lutzomyia Reservoir hosts of L. panamensis : Arboreal sloths and anteaters Vector (intermediate host): Lutzomyia and Psychodopygus sandflies L. lainsoni:  Cause of cutaneous lesions (CL) in Brazil and Peru Reservoir hosts of L. panamensis : agouti Vector (intermediate host): Lutzomyia L. braziliensis:  The disease is alled Espundia (CL) Symptoms: The incubation period may be a couple of months or as long as 3 years in L. tropica and L. aethiopica infections; in L. major it is much shorter, as little as 2 weeks The first sign of infection is a small red papule and nodules at the injection site, which may itch intensely and grows to 2 cm or more in diameter. In L. major infections, the papule is covered with a serous exudate and ulcerates early; papules are dry and ulcerate only after several months in L. tropica and L. aethiopica infections Diffuse cutaneous leishmaniasis (DCL) in the anergic patient o L. aethiopica and L. pifanoi o The anergic patient is incapable of mounting a response to infection The hypersensitive patient is capable of excellent antibody and cellular responses but cannot completely eliminate the parasites, so as the central lesion heals, active peripheral ones continue to form. This type of response, known as leishmaniasis recidiva, may be seen with any of the cutaneous leishmaniasis (L. tropica). Diagnosis:  Diagnosis of cutaneous leishmaniasis is usually made in endemic areas on clinical grounds, but this requires much familiarity with the disease  In the case of cutaneous or mucocutaneous leishmaniasis, the parasites can be detected in probes or smear preparations taken from the lesions of skin or mucosa • Material of fresh lesions especially at the edge areas is used for tipping preparations to become coloured by Giemsa stain • It is usually possible to demonstrate the rounded or oval organisms, approximately 3-5 µm in diameter and having a typical amastigote structure, within large monocytic cells obtained by aspiration of fluid from beneath the ulcer bed, especially its active border. Scrapings taken from the ulcer surface do not reveal the organisms, which are destroyed in areas secondarily infected with bacteria.  Culture on NNN medium of material obtained by aspiration or biopsy may demonstrate promastigote forms. Schneider’s Drosophila medium supplemented with 30% fetal bovine serum has been useful in isolating organisms from humans with cutaneous leishmaniasis.  Aspirate or biopsy material may be inoculated subcutaneously into the nose of a hamster or BALB/c mice  The result of the Montenegro test (Skin test), involving the intradermal injection of a suspension of killed promastigotes, is positive in a high percentage of L. tropica infections and in more than 95% of L. brazillensis infections  Serology (IFT, ELISA) is mostly positive in the case of mucocutaneous infections • Recidives and diffuse cutaneous leishmaniasis are mostly seronegative  The PCR is today a very common technique as it is a very sensitive method to detect and to differentiate species from each other Skin Test (Montenegro test) • induration Prophylaxis: Application of repellents (e.g. Viticks®) on skin and clothes helps to protect against bites of the vectors. A vaccination with living pathogens (Leishmanization) was tested in endemic regions in order to establish an immunity; however, the success remained low. Treatment: A systemic therapy is not justified in cases of simple cutaneous leishmaniasis because of the tendency of self-healing and the potential toxicity of the drugs.  If necessary, only repeated perilesional injections with 1–3 ml (100–300 mg) sodium stibogluconate (antimony sodium gluconate; Pentostam) as well as treatment of secondary bacterial infections should be done. • Pentavalent antimony inhibits glycolytic enzymes and fatty acid oxidation in leishmanial amastigotes A systematic therapy, however, is strongly recommended in cases of mucocutaneous leishmaniasis (MCL); diffuse cutaneous, disseminated or deforming cutaneous leishmaniasis; and visceral leishmaniasis In areas where sodium stibogluconate is not readily available (such as Latin America), meglumine antimoniate (Glucantime) may be substituted. The recommended dose is 20 mg/kg per day intravenously or intramuscularly for 20 days  Drug of choice: Meglumine antimoniate (Glucantime) Amphotericin B has been used in patients unresponsive to pentavalent antimonials, administered by slow intravenous infusion, gradually increasing the dose to 1 mg/kg weight, at which level it should be continued on alternate days until a total of 2 to 3 g has been given A less toxic alternative is ketoconazole