The pathology of cutaneous leishmaniasis due to Leishmania major in Sudan.

The pathology of cutaneous leishmaniasis in Sudan, where the disease is caused by Leishmania major, was studied by light and electron microscopy. Lesions were classified into four distinct groups based on the ratio of different cell types, especially lymphocytes, macrophages, and plasma cells in the inflammatory infiltrate, and the formation of compact epithelioid granulomas or the presence of necrosis. In the lesions, there was a positive correlation between the number of lymphocytes and the number of activated macrophages and epithelioid cells. We suggest that the parasites are eliminated from the lesion by two processes: 1) a lytic mechanism in which parasites are lysed within activated macrophages and 2) necrosis of parasitized macrophages. Morphologic evidence for these two mechanisms of parasite elimination was detected by both light and electron microscopy. The evolution of the pathology of the lesions was followed by rebiopsy when the lesion had regressed in size under antileishmanial therapy.

Sporotrichoid cutaneous leishmaniasis due to Leishmania major of different zymodemes in the Sudan and Saudi Arabia: a comparative study.

Sporotrichoid cutaneous leishmaniasis is due to dissemination of amastigotes via the lymphatics to the subcutaneous tissues. A comparison was made between the potential to disseminate by this route of 2 parasites of different zymodemes in Sudan and Saudi Arabia. In Sudan cutaneous leishmaniasis is caused by Leishmania major zymodeme LON-1, and in Saudi Arabia by L. major LON-4. Sporotrichoid leishmaniasis was significantly more common in Sudan, occurring in 23% of patients compared with 10% in Saudi Arabia. Lymph node involvement was slightly more prevalent in the Sudan. Clinical and pathological differences between subcutaneous nodules, particularly when they ulcerate, and multiple primary cutaneous lesions are described and treatment of localized and sporotrichoid leishmaniasis is discussed. The pathological features of the primary lesions in the Sudan and Saudi Arabia were similar.

Necrotizing and suppurative lymphadenitis in Leishmania major infections.

The pathology of lymph nodes and subcutaneous nodules in 6 patients with cutaneous leishmaniasis (Oriental sore) due to Leishmania major is described in this paper. In 3 patients enlarged epitrochlear lymph nodes were found to be associated with primary skin lesions in the forearm. The lymph node in one patient showed a necrotizing granulomatous reaction that simulated tuberculous lymphadenitis. Leishmania parasites were, however, found in sections of the node, and staining for mycobacteria was negative. The second patient presented with an abscess and a discharging sinus in the epitrochlear region. Parasites were found in smears of the pus and cultures for bacteria were negative. The lesion healed with antimonial therapy. In the third patient the lesion resembled cat-scratch disease and showed stellate abscesses and granulomas. Leishmania parasites were also identified in the sections. Sections of a subcutaneous nodule from the fourth patient showed a necrotizing granuloma. The lesion healed spontaneously and the patient became leishmanin-positive. In two other patients fine needle aspiration of the subcutaneous nodules showed parasites, granuloma and necrosis. We concluded that L. major disseminates from the primary cutaneous lesion via the lymphatics to the subcutaneous tissues and the regional lymph nodes. The subcutaneous nodules and lymphadenopathy may persist long after the primary lesion had healed. The primary lesion is sometimes inconspicuous. Necrotizing and suppurative lymphadenitis due to L. major have to be distinguished from other causes of necrosis and suppuration such as tuberculosis and cat-scratch disease.

Dichotomy of the T cell response to Leishmania antigens in patients suffering from cutaneous leishmaniasis; absence or scarcity of Th1 activity is associated with severe infections.

The T cell response was studied in 25 patients suffering from cutaneous leishmaniasis caused by Leishmania major with severe (n = 10) and mild (n = 15) disease manifestations. Peripheral blood mononuclear cells (PBMC) from the patients were activated by sonicates of Leishmania promastigotes (LMP) and amastigotes (LDA), and the surface protease gp63. The proliferative responses to Leishmania antigens were lower in patients with severe disease than in patients with mild disease (P = 0.01-0.05), and such a difference was not observed in the response to purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). LMP-induced interferon-gamma (IFN-gamma) production was lower in patients with severe than in patients with mild disease (P < 0.05). When the IL-4 and IFN-gamma responses of each patient were considered, two response patterns were observed in the cultures activated by the Leishmania sonicates. One response pattern was characterized by high production of IFN-gamma without production of IL-4 (a Th1-like pattern), the other was characterized by low IFN-gamma levels which in most cases were associated with IL-4 production (not a Th1-like pattern). These patterns could not be distinguished when the cells from the same donors were stimulated by TT and PPD. The percentages of patients with a Th1-like response pattern after stimulation by LMP in patients with severe and mild disease manifestations were 30% and 80%, respectively. This difference was statistically significant (P = 0.034).