Cutaneous Leishmaniasis PDF

Cutaneous Leishmaniasis Leishmania tropica and L. major. Leishmania tropica and L. major produce cutaneous ulcers variously known as oriental sore, cutaneous leishmaniasis, Jericho boil, Aleppo boil, and Delhi boil. They are found in west central Africa, the Middle East, and Asia Minor into...

Cutaneous Leishmaniasis Leishmania tropica and L. major. Leishmania tropica and L. major produce cutaneous ulcers variously known as oriental sore, cutaneous leishmaniasis, Jericho boil, Aleppo boil, and Delhi boil. They are found in west central Africa, the Middle East, and Asia Minor into India. These two species have similar life cycles; however, L. tropica and L. major are found in different localities and have different reservoir and intermediate hosts. The lesions they cause also are somewhat different, although in humansthe lesions may vary in severity according to age and other factors. The two species can be differentiated biochemically. Morphology and Life Cycle. Amastigotes of L. tropica and L. major are similar to those of the other leishmanias.Sand flies of genus Phlebotomus are the intermediate hosts and vectors. When a fly takes a blood meal containing amastigotes, parasites multiplyin the midgut and then move to the pharynx; they are then inoculated into the next mammalian victim. There they multiply in the reticuloendothelial system and lymphoid cells of the skin. Few amastigotes are found except in the immediate vicinity of the site of infection, so the sand flies must feed there to become infected. Sand fly saliva contains low molecular weight compounds, as well as a peptide, that serve as vasodilators and facilitate infection. Pathogenesis.  The incubation period lasts from a few days to several months. The first symptom of infection is a small, red papule at the site of the bite. This may disappear in a few weeks, but usually it develops a thin crust that hides a spreading ulcer underneath. Two or more ulcers may coalesce to form a large sore.In uncomplicated cases the ulcer will heal within two months to a year, leaving a depressed, unpigmented scar. It is common, however, for secondary infection to occur, including, for example, yaws (a disfiguring disease caused by a spirochete) and myiasis (infection with fly maggots,). Leishmania tropica is found in more densely populated areas. Its lesion is dry, persists for months before ulcerating, and has numerous amastigotes within it. By contrast, L. major is found in sparsely inhabited regions. Its papule ulceratesquickly, is of short duration, and contains few amastigotes. Diagnosis. Diagnosis of infection is greatly facilitated by finding amastigotes. Scrapings from the side or edge of an ulcer smeared on a slide and stained with Wright‘s or Giemsa‘s stain will show the parasites in endothelial cells and monocytes, even though they cannot be found in the circulating blood. Cultures should be made in case amastigotes go undetected. Leishmania braziliensis Leishmania braziliensis produces a disease in humans variously known as espundia, uta, or mucocutaneous leishmaniasis. It is found throughout the vast area between central Mexico and northern Argentina, although its range does not extend into the high mountains, except for the south slope of the Andes. Clinically similar cases have been reported in northwest Africa, due to L. donovani. The clinical manifestations of the disease vary along its range, which has led to confusion regarding identity of the organisms responsible. Several species names have been proposed for different clinical and serological types. Life Cycle and Pathogenesis. The life cycle and methods of reproduction of L. braziliensis are identical to those of L. donovani and L. tropica except that the promastigotes reproduce in the hindgut of the sand fly, with several species of Lutzomyia serving as vectors. Inoculation of promastigotes by a sand fly‘s bite causes a small, red papule on the skin. This becomes an itchy, ulcerated vesicle in one to four weeks and is similar at this stage to oriental sore. This primary lesion heals within 6 to 15 months. The parasite never causes a visceral disease but often develops a secondary lesion on some region of the body. The secondary lesion often involves the nasal system and buccal mucosa, causing degeneration of the cartilaginous and soft tissues. Necrosis and secondary bacterial infection are common. Espundia and uta are the names applied to these conditions. The ulceration may involve the lips, palate, and pharynx, leading to great deformity. Invasion of the larynx and trachea destroys the voice. Rarely genitalia may become infected. The condition may last for many years, and death may result from secondary infection or respiratory complications. A similar condition is known to occur in the Old World due to L. major or L. infantum. Diagnosis and Treatment. Diagnosis is established by finding L-D bodies in affected tissues. Espundialike conditions are also caused by tuberculosis, leprosy, syphilis, and various fungal and viral diseases, and these must be differentiated in diagnosis. Skin tests are available for diagnosis of occult infections. Culturing the parasite in vitro is also a valuable technique when L-D bodies cannot be demonstrated in routine microscope preparation. Treatment is similar to that for kala-azar and tropical sore: antimonial compounds applied on lesions or injected intravenously or intramuscularly. Secondary bacterial infections should be treated with antibiotics. Mucocutaneous lesions are particularly refractory to treatment and require extensive chemotherapy. Relapse is common, but, once cured, a person usually has lifelong immunity. However, if the infection is not cured but merely becomes occult, there may be a relapse with onsetof espundia many years later. Because this is primarily a sylvatic disease, there is little opportunity for its control. Visceral Leishmaniasis Leishmania donovani In 1900 Sir William Leishman discovered L. donovani in spleen smears of a soldier who died of a fever at Dum-Dum, India. The disease was known locally as Dum-Dum fever or kala-azar. Leishman published his observations in 1903, the year that Charles Donovan found the same parasite in a spleen biopsy. The scientific name honors these men, as does the common name of the amastigote forms, Leishman Donovan (L-D) bodies. The Indian Kala-Azar Commission (1931 to 1934) demonstrated the transmission of L. donovani by Phlebotomus spp. Morphology and Life Cycle. Leishmania donovani amastigotes cannot be differentiated from other Leishmania species on the basis of morphology as seen in a light microscope; the rounded or ovoid bodies measure 2 μm to 3 μm, with a large nucleus and kinetoplast. They live within cells of the reticuloendothelial (RE) system, including spleen, liver, mesenteric lymph nodes, intestine, and bone marrow. Amastigotes have been found in nearly every tissue and fluid of the body. The life cycle is similar to that of L. tropica except that L. donovani is primarily a visceral infection. When a sand fly of genus Phlebotomus ingests amastigotes along with a blood meal, the parasites lodge in the midgut and begin to multiply. They transform into slender promastigotes and quickly block theinsect‘s gut. Soon they can be seen in the esophagus, pharynx, and buccal cavity, from where they are injected into a new host with the fly‘s bite. Not all strains of L. donovani are adapted to all species and strains of Phlebotomus.Once in a mammalian host, parasites are immediately engulfed by macrophages, inwhich they divide by binary fission, eventually killing the host cell. Escaping the dead macrophage, parasites are engulfed by other macrophages, which they also kill; by this means they eventually severely damage the RE system, a system that plays a critical role in host defense. Interestingly, amastigotes engulfed by neutrophils and eosinophils are killed, but in untreated cases these polymorphonuclear leucocytes have little or no effect on the eventual outcome of the disease. Pathogenesis. Clinically, L. donovani infections may range from asymptomatic to progressive, fully developed kala-azar. The incubation period in humans may be asshort as 10 days or as long as a year but usually is two to four months. The disease typically begins slowly with low-grade fever and malaise and is followed by progressive wasting and anemia, protrusion of the abdomen from enlarged liver and spleen, and finally death (in untreated cases) in two to three years. In some cases symptoms may be more acute in onset, with chills, fever up to 40°C (104°F), and vomiting; death may occur within 6 to 12 months. Accompanying symptoms are edema, especially of the face, bleeding of mucous membranes, breathing difficulty, and diarrhea. The immediate cause of death often is invasion of secondary pathogens that the body is unable to combat. A certain proportion of cases, especially in India, recover spontaneously. Diagnosis and Treatment.  As in L. tropica, diagnosis of L. donovani depends on finding L-D bodies in tissues or secretions. Spleen punctures, blood or nasal smears, bone marrow, and other tissues should be examined for parasites, and cultures from these and other organs should be attempted. Immunodiagnostic tests are sensitive but cannot differentiate between species of Leishmania or between current and cured cases. The tests most frequently used are the enzyme-linked immunosorbent assay (ELISA) and the indirect fluorescent antibody test (IFA).Other diseases that might have symptoms similar to kalaazar are typhoid and paratyphoid fevers, malaria, syphilis, tuberculosis, dysentery, and relapsing fevers. Each must be eliminated in the diagnosis of kala-azar. Treatment consists of injections of various antimony compounds, as previously described for L. tropica, and good nursing care. 81