Leishmaniasis

Clinical features

Patients with VL present with chronic fever, splenomegaly and pancytopenia (Box 1). Weight loss is common and patients may present with the sequelae of pancytopenia (bleeding, severe anaemia and intercurrent infections). Clinical examination may also reveal hepatomegaly and lymphadenopathy. Other abnormalities include hypoalbuminaemia and polyclonal hypergammaglobulinaemia (which may cause false-positive results with autoantibody tests).

Box 1.

Visceral leishmaniasis (VL) case history.

Diagnosis

Diagnosis of VL can be made by direct visualisation of parasites via microscopy or culture. The best tissue to examine is a bone marrow biopsy, although splenic aspirates are used at specialised institutions because they provide additional information about the load of infection. These should be performed only by those with experience because of the risk of bleeding. Specialised parasitology laboratories can also perform polymerase chain reaction (PCR) tests on these samples to detect leishmania DNA. Two serology tests to look for antileishmania antibodies are available:

• The direct agglutination test: a semiquantitative agglutination test using killed leishmania parasites and increasing dilutions of patients' blood or serum (sensitivity 92.7–96.4%).

• The RK39 dipstick: a qualitative test using recombinant leishmania antigen with patients' blood (sensitivity 87.7–97.1%).³

Experience is needed to interpret these tests. They remain positive despite adequate VL treatment, thus cannot be used to assess cure post-treatment or following relapse. In endemic areas the specificity can be low, as exposed populations without clinical disease may have an antibody response (up to 32% of the population in some areas). Nearly half of patients with HIV will have false negative serology.⁴

Treatment

The first-line drug for treating VL in the UK is liposomal amphotericin B. The current treatment regimen which gives a 95% cure rate is 20 mg/kg in five doses over 10 days (ie 4 mg/kg/day on days 1, 2, 3, 5 and 10).⁵ Trials from India have reported a 90% cure rate after a single dose of liposomal amphotericin B.⁶ Side effects include renal impairment, hypokalaemia, infusion reactions and anaemia.

Other treatments such as sodium stibogluconate (SSG) are still widely used in other parts of the world because they are cheap and easy to use.⁷ Combination treatments have been proposed to avoid parasite resistance to therapy which has been reported in patients from India.⁸

Drug treatments for VL, including those used in the UK when patients are intolerant of, or poorly responsive, to liposomal amphotericin B, are summarised in Table 1.⁹

Visceral leishmaniasis in immunosuppressed patients

The presentation and management of VL is different in immunosuppressed patients. Worldwide, HIV is the main immunosuppressive influence seen in conjunction with VL, but other immunosuppressive states seen in patients with VL in the UK are advanced age, immunosuppressive therapy and treatment with tumour necrosis factor antibody therapies.

The main clinical features of VL may be absent or atypical, and there may be evidence of leishmania parasites in unusual body sites (eg skin, gut, genitourinary tract). Establishing the diagnosis of VL therefore may be more difficult.¹⁰ Abnormal tissue from any body site should be examined for evidence of leishmania parasites if the patient has been in an endemic area and is immunosuppressed.

Patients who remain immunosuppressed may respond poorly to the standard treatment protocols, so an attempt to improve their immune status is a key strategy in their management. If this is not possible, long-term prophylactic treatment may be considered after the initial treatment course as there is a high risk of recurrence after apparently successful treatment. When patients fail first-line treatment courses, second-line therapy needs to be considered from the options listed in Table 1. There is little evidence to guide the choice of prophylactic and second-line treatment courses and management of these patients should be discussed with an expert.

Cutaneous leishmaniasis

Several species of Leishmania protozoa can cause localised cutaneous leishmaniasis (CL). A simple geographical classification (Fig 2) divides species into ‘old world’ species, from Africa, the Middle East and Central Asia (OWCL), and ‘new world’ species, from South and Central America (NWCL).

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Fig 2.

Geographical distribution of cutaneous leishmaniasis. Reproduced with permission from the World Health Organization.¹

Of the patients seen from 1998–2009 at the Hospital for Tropical Diseases, London, 40% (90) had OWCL and 60% (133) had NWCL. Of the OWCL patients, 71% were tourists to the Mediterranean, 36% migrants or visiting friends and relatives, and 17% were military personnel. Of the NWCL, 44% were backpackers and 39% soldiers (Wall EC unpublished data).

Presentation and diagnosis

CL typically presents with a nodule(s) at the sandfly bite(s) site that enlarges and ulcerates over several weeks. The incubation period can be months to years (usually <2 years) after the initial bite. The lesions are usually in exposed body areas such as the face and hands (Fig 3). The edge of the lesion is well demarcated and raised, and there may be satellite lesions in the same area. The ulcer base may be crusted, bloody or with pus. Occasionally there is a nodular lymphangitis that can be palpated in the surrounding area.

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Fig 3.

Early Cutaneous leishmaniasis lesion with a raised indurated edges around a central ulcer. Papules can be seen spreading from the lesion. Figure courtesy of Colonel Mark Bailey.

Spontaneous resolution can occur, so at the time of clinical presentation there may be signs of healing, particularly in the centre of the lesion (up to 50–75% cases have healed within 4–6 months in some OWCL species¹¹). The differential diagnosis for these lesions includes infected insect bites, mycobacterial skin infections and malignancy.

Diagnosis

Diagnosis of CL is by direct visualisation of the parasites via microscopy and culture of a biopsy from the ulcer edge. Typical histopathological features are granulomatous inflammation and leishmania amastigotes. Leishmania DNA can be detected by PCR, so confirming infection and identifying the leishmania species. This is important if viannia species is suspected and the patient is at risk of mucocutaneous disease.

PCR testing has also shortened the time to diagnosis. At the HTD parasitology laboratory, microscopy is 62–77% sensitive and culture takes on average 11.6 days to a definitive result, whereas PCR results take on average eight days to process (Wall EC; unpublished data). Lesions difficult to biopsy (eg facial, ear, finger) can be scraped or aspirated, although the diagnostic yield is lower.