Leishmaniasis is a parasitic infection spread by sandflies, which feed on humans and then inject parasites called mastigotes into the bloodstream or skin. These parasites then reproduce, causing the symptoms. Leishmaniasis occurs in three forms:

• Visceral: a chronic wasting illness also known as kala azar.

• Cutaneous: a skin disorder which results in ulceration.

• Mucocutaneous: lesions of the mucous membranes in the nose, mouth and throat.

The three forms are spread by separate types of sandflies.

All types occur in parts of India, China, Russia, Africa and South America, and also in Spain, Italy and southern France. Visceral leishmaniasis can be contracted in southern Europe, and can also be transmitted from one person to another. The countries most severely affected by visceral leishmaniasis are Brazil, Bangladesh, India, Nepal and Sudan, which account for 90% of reported cases each year.

Cutaneous leishmaniasis occurs most frequently in Brazil, Peru, Iran, Saudi Arabia, Afghanistan and Syria. Mucocutaneous leishmaniasis occurs most frequently in Bolivia, Brazil and Peru.

HIV and leishmaniasis co-infection has been reported most frequently in southern Europe and in Brazil, but the World Health Organization has suggested that if surveillance were better, it is likely that high levels of co-infection would also be detected in east Africa.

Leishmaniasis may be acquired during the first few decades of life and either be controlled but not cleared, or may lie dormant until HIV infection occurs. The suppression of the immune system can allow leishmaniasis to develop.

Symptoms

Cutaneous leishmaniasis results in raised sores on the skin which are painless but persistent, even in people with strong immune systems. Mucocutaneous leishmaniasis causes lesions of the mucous membranes in the nose, mouth and throat. Some forms of leishmaniasis result in tissue destruction, especially at sites such as the lips and genitals.

Visceral leishmaniasis causes wasting, malnutrition and lowered immune responses. The first symptoms include a fever which peaks twice a day, sweating, fatigue and enlargement of the liver and spleen. Leishmaniasis may also affect the lungs, the pleural membrane surrounding the lungs, the stomach, bone marrow and blood. Although not an AIDS-defining condition, visceral leishmaniasis presents in patients with CD4 cell counts below 200 cells/mm³ in 92% of cases (Desjeux 2002).

In HIV-positive individuals, enlargement of the spleen may not always be evident, but skin lesions at the same time as visceral disease is much more likely. This is because the infection disseminates much more widely in people with HIV infection. The symptoms seen in people with HIV infection may appear similar to other opportunistic infections.

Diagnosis

In HIV infection, the diagnosis of leishmaniasis is not always straightforward. In people with advanced immune suppression, antibodies to leishmaniasis may not appear. Consequently, false negative antibody tests for leishmaniasis have been reported in 40 to 50% of individuals with HIV (Montalban 1990). The skin test traditionally used to diagnose leishmaniasis is the Montenegro test. However, this test is also subject to similar false negative rates to the antibody test in HIV-positive people.

The preferred method of diagnosis is isolation of the parasite from a tissue sample from the affected organ or tissue in the case of visceral or mucocutaneous leishmaniasis.

A polymerase chain reaction (PCR) test has been developed for diagnosis of leishmaniasis and is the most sensitive method for diagnosing visceral leishmaniasis (Lachaud 2000; Pizzuto 2001).

Treatment

Meglumine antimoniate is the standard first-line treatment for leishmaniasis, but pentamidine (Pentacarinat) or liposomal amphotericin (Abelcet / AmBisome / Amphocil) may also be recommended if the disease becomes disseminated throughout the body. Meglumine antimoniate is listed as an anti-protozoal on the World Health Organization Essential Drugs List.

Meglumine antimoniate is administered by injection. There is evidence that if the full course of treatment is not taken, the Leishmania parasite can develop resistance to this drug and others in the antimonial class. These drugs are less effective in people with HIV than in the rest of the population. Relapse rates of up to 90% within one year have been reported. However, the use of highly active antiretroviral therapy (HAART) has reduced the incidence of leishmaniasis and lowered the risk of relapse (Tortajada 2002; de La Rose 2002; Pintado 2001).

Nevertheless, an immune response to HAART and HIV viral suppression does not necessarily protect a person from leishmaniasis relapse. Three cases of visceral leishmaniasis have been reported among people with viral loads below 500 copies/ml. One study found that seven of ten patients with leishmaniasis had an average of three relapses over 31 months of follow-up (Casado 2001). Relapse of leishmaniasis has also been reported in a person with a strong CD4 T-cell response to antiretroviral therapy (Petter 2001).

Imiquimod (Aldara), and a related compound called S-28463, have shown activity against Leishmania protozoa in test tube and animal studies. In addition, a recent case report has demonstrated that lipid formulations of amphotericin alone were a safe and effective treatment for cutaneous leishmaniasis in two immunocompromised patients (Amato 2004).

Key research

Duarte (2003) found leishmaniasis in 29 HIV-infected men attending a Portuguese hospital. Features were fever, pancytopenia and enlarged liver and spleen. 93% had CD4 counts below 200. Despite treatment with pentavalent antimony (n=21) or liposomal amphotericin B (n=9), only 5 people survived for more than 12 months, all of whom were on combination antiretroviral therapy.

de La Rose (2002) studied 479 HIV-infected people taking antiretrovirals from April 1989 to June 2000. Median follow-up time was 1380 days. 21 cases of visceral leishmaniasis occurred. Since the introduction of highly active antiretroviral therapy (HAART) in 1997, incidence fell by 65%. HAART was independently associated with reduced risk of leishmaniasis while a CD4 count below 300 was associated with increased risk.

Tortajada (2002) followed an HIV-infected cohort of 3589 patients from 1985 to 2000. 45 cases of visceral leishmaniasis were diagnosed at a mean CD4 count of 97. 78% had previously had an AIDS-defining illness. HAART was protective against leishmaniasis. Six deaths were associated with leishmaniasis among patients without access to HAART. The probability of HAART patients remaining free of relapse was 66% compared to 10% for those not treated with HAART. The trend towards fewer relapses is attributed to immune restoration due to HAART.

Casado (2001) identified 10 people with leishmaniasis with an average CD4 count of 70. One person took prophylaxis after the episode. Prior to the introduction of protease inhibitors, 6 individuals had an average of 2.6 relapses. After the introduction of PI-regimens, immunological and virological improvement occurred. However, after 31 months of follow-up 7 individuals had experienced an average of 3 relapses, including relapses which occurred at CD4 counts above 250 with undetectable viral load for over 26 months.

Petter (2001) reported a case of cutaneous relapse of visceral leishmaniasis in an AIDS patient with good virological and immunological response to antiretroviral therapy.

Pintado (2001) compared visceral leishmaniasis in 80 HIV-infected people and 40 HIV-negative people. HIV-infected patients had an average CD4 count of 90 at presentation and were less sensitive to blood serum tests than the HIV-negative patients. The HIV-positive group had greater frequency and severity of leukopenia, lymphocytopenia and thrombocytopenia compared to the HIV-negative group. Response rates to initial treatment was 55% vs 90% favouring the HIV-negative group. Secondary prophylaxis with antimonial compounds or amphotericin B reduced relapse among HIV-positive patients.

Torrus (1996) treated three patients with 200mg fluconazole intravenously and 300mg oral allopurinol per day with minimal toxicity for three weeks. No evidence of leishmaniasis infection was found after this period.

Laguna (1999) conducted an open, randomised study of 89 HIV-infected people with visceral leishmaniasis treated with either meglumine antimoniate or amphotericin B. After 28 days treatment, 29 of 44 (66%) of the meglumine group and 28 of 45 (62%) in the amphotericin B group were cured. Moderate to severe side-effects affected the heart and the pancreas in the meglumine group and the kidney in the amphotericin group.

References

Amato VS et al. Successful treatment of cutaneous leishmaniasis with lipid formulations of amphotericin B in two immunocompromised patients. Acta Trop 92: 127-132, 2004.

Asboe D et al. Failure to control visceral leishmaniasis despite effective introduction of HAART. Fifth Annual Meeting of the British HIV Association, abstract P45, 1999.

Casado JL et al. Relapsing visceral leishmaniasis in HIV-infected patients undergoing successful protease inhibitor therapy. European Journal of Clinical Microbiology and Infectious Diseases 20(3): 202-205, 2001.

Desjeux P et al. Leishmania/HIV co-infections: epidemiology in Europe. Ann Trop Med Parasitol 97: S3-S15, 2002.

de La Rosa R et al. Incidence of and risk factors for symptomatic visceral leishmaniasis among human immunodeficiency virus type 1-infected patients from Spain in the era of highly active antiretroviral therapy. Journal of Clinical Microbiology 40(3): 762-767, 2002.

Duarte C et al. Visceral leishmaniasis and HIV infection: report of 30 cases. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris (Antiviral Therapy 8:1), abstract 900, 2003.

Lachaud L et al. Optimized PCR using patient blood samples for diagnosis and follow-up of visceral leishmaniasis, with special reference to AIDS patients. J Clin Microbiol 38: 236-240, 2000.

Laguna F et al. Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing neglumine antimoniate with amphotericin B. AIDS 13(9): 1063-1070, 1999.

Montalban C et al. Visceral leishmaniasis in patients infected with the human immunodeficiency virus. Journal of Infectious Diseases 21: 261-270, 1990.

Paredes R et al. Leishmaniasis in HIV-infected persons: a review. Journal of International Association of Physicians in AIDS Care, June 1997.

Petter A et al. Visceral leishmaniasis in an AIDS patient on successful antiretroviral therapy: failure of parasite eradication despite increase in CD4+ T-cell count but low CD8+ T-cell count. Scandanavian Journal of Infectious Diseases 33(3): 236-238, 2001.

Pintado V et al. Visceral leishmaniasis in human immunodeficiency virus (HIV)-infected and non-HIV-infected patients. A comparative study. Medicine (Baltimore) 80(1): 54-73, 2001.

Pizzuto M et al. Role of PCR in diagnosis and prognosis of visceral leishmaniasis in patients coinfected with humman immunodeficiency virus type 1. J Clin Microbiol 39: 357-361, 2001.

Torrus D et al. Fluconazole plus allopurinol in treatment of visceral leishmaniasis. Journal of Antimicrobial Chemotherapy37(5): 1042-1043, 1996.

Tortajada C et al. Highly active antiretroviral therapy (HAART) modifies the incidence and outcome of visceral leishmaniasis in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes 30(3): 364-366, 2002.