Investigations

1st investigations to order

FBC

Test
Result
Test

Should be ordered in patients with visceral leishmaniasis.

Anaemia is the most common finding, followed by leukopenia and thrombocytopenia.

Pancytopenia was found in only 16% of patients in Nepal, but specificity was high (98%).[85] Pancytopenia is more frequent in HIV-co-infected patients.[86]

Result

anaemia, leukopenia, thrombocytopenia

liver function tests and urea/creatinine

Test
Result
Test

Treatment with paromomycin, pentavalent antimonial compounds, amphotericin-B, or miltefosine requires monitoring of liver and renal function; therefore, baseline liver function tests and urea/creatinine should be ordered.

Result

variable; may be elevated in visceral leishmaniasis, particularly alkaline phosphatase

serum human chorionic gonadotrophin (hCG)

Test
Result
Test

Pregnancy status determines treatment choices and later in pregnancy the immunological response, so all women of child-bearing age should be tested prior to treatment.

Result

may be positive or negative

Investigations to consider

microscopic examination of relevant specimen

Test
Result
Test

Recommended to confirm diagnosis of suspected cutaneous leishmaniasis (CL) or visceral leishmaniasis (VL). Probably the most common confirmatory test used in CL-endemic countries.[1]

CL: biopsy aspirates, smears, scrapings, and skin slit smears are used.[77] Sensitivity is variable and depends on sampling technique, duration of lesions, presence/absence of ulceration, and presence of super-infection. Sensitivity is poor (<50%) in mucosal leishmaniasis.[1][87]

VL: specimen can be obtained by aspiration of splenic tissue (discouraged due to risk of fatal haemorrhage), bone marrow, liver, or lymph nodes. Microscopic examination of splenic aspirates is the most sensitive technique (>95%), but carries a 1:1000 risk of major bleeding; considerable technical expertise is required.[88] Examination of bone marrow aspirate or lymph node fluid is safer, but is of lower sensitivity (70% to 90% and 58%, respectively). The sensitivity of a bone marrow examination is increased to 85% in patients with immunosuppression.[89][90] In people with HIV infection who are immunocompromised, tissue biopsy of gastrointestinal mucosa or buffy coat smears may be diagnostic.

May also be used to confirm diagnosis of post-kala-azar dermal leishmaniasis (PKDL). Sensitivity is improved if large or nodular skin lesions are sampled in PKDL.[6][Figure caption and citation for the preceding image starts]: Skin touch preparation showing Leishmania tropica amastigotes. Intact macrophage is practically filled with amastigotes, several of which have a clearly visible nucleus and kinetoplast (arrows)Image courtesy of CDC; NCID; DPDx [Citation ends].com.bmj.content.model.Caption@5ebcf013

Result

amastigote form of the Leishmania species in macrophages or monocytes

blood (buffy coat) or tissue culture

Test
Result
Test

Recommended to confirm diagnosis of suspected cutaneous or visceral leishmaniasis, and is especially useful when the goal is to characterise infecting parasite species.

Novy-Nicolle-McNeal medium or other biphasic-type media are often used, although modified Schneider’s medium is often sufficient.[91]

While 100% specific, sensitivity is variable (typically <50%), and depends on sampling technique and quality of culture media, sample processing and laboratory infrastructure, duration of lesions, and presence of super-infection. Culture with isoenzyme characterisation permits species identification.

May also be used to confirm diagnosis of post-kala-azar dermal leishmaniasis (PKDL). Sensitivity is improved if large or nodular skin lesions are sampled in PKDL.[6]

Result

promastigote forms of the Leishmania species in culture media

polymerase chain reaction (PCR)

Test
Result
Test

Recommended to confirm diagnosis of suspected cutaneous leishmaniasis (CL) or visceral leishmaniasis (VL), if available. More sensitive than microscopic examination or parasite culture for the diagnosis of suspected CL and VL.[8]

Sensitivity estimates range from 70% to 100% when using tissue biopsies for CL diagnosis and when using peripheral blood for VL diagnosis.[78][82][92][93]

Particularly useful in cases with a low parasite load (e.g., mucosal leishmaniasis [ML]).[78]

May also be used to confirm diagnosis of post-kala-azar dermal leishmaniasis. Sensitivity is improved if large or nodular lesions are sampled.[6]

Recommended when species characterisation is needed (e.g., to determine whether a patient may be at risk of ML in the future because of Leishmania [Viannia] species infection). There is no clinically available PCR on offer at a species level of determination; many are genus only.

The diagnostic value of PCR in patients with relapsed VL is uncertain, as PCR can remain positive in patients with clinical cure; however, quantitative PCR may show rising levels of DNA in relapse.[82]

Result

Leishmania DNA

serology

Test
Result
Test

Recommended to support diagnosis of suspected visceral leishmaniasis (VL).[8]

A useful test in immunocompetent patients with suspected VL, but less sensitive in patients who are immunosuppressed. However, it may be used in patients who are immunosuppressed if parasitological diagnosis is not feasible.[19][81]

Various highly sensitive and specific tests are available, and the choice depends mainly on availability and laboratory expertise.[2]

Direct agglutination test: one meta-analysis of 30 studies showed 94.8% sensitivity and 97.1% specificity.[94]

rK39 dipstick: rapid diagnostic test that takes 10 to 20 minutes. One meta-analysis of 18 studies showed 91.9% sensitivity and 92.4% specificity.[95] Less sensitive in East Africa than on the Indian subcontinent and in Latin America.[65][95][96][97]

Indirect fluorescent antibody test: moderate to high sensitivity (>85%) and high specificity (>90%) have been reported.[98][99]

Enzyme-linked immunosorbent assay (ELISA): highly sensitive and specific. Crude soluble Leishmania antigen or various recombinant proteins (including rK39) can be used; use of recombinant antigen may increase sensitivity.[2]

Western blot: promising test but experience is restricted to a few laboratories.[100]

Diagnosis of relapse cannot be based on serological tests, as antibodies against Leishmania donovani or Leishmania infantum (synonym: Leishmania chagasi) usually remain detectable for years after initial diagnosis.[83][84]

Result

positive for Leishmania antibodies, or antibody titre above locally validated threshold

leishmanin skin test (Montenegro skin test)

Test
Result
Test

A test to support the diagnosis of cutaneous leishmaniasis when healing lesions are primarily present.

Killed Leishmania parasites are inoculated intradermally, with the response to the inoculation read 48 hours after inoculation.[77]

May be useful to rule out leishmaniasis in a patient with consistent skin lesions and travel to an endemic region who resides in a non-endemic area.

Past and present infection cannot be discerned.

This test is not recommended or available in the US or South America.

Result

≥5 mm induration 48 hours after inoculation

serum HIV testing

Test
Result
Test

Visceral leishmaniasis is an opportunistic infection in patients with HIV/AIDS. Newly diagnosed patients should be assessed for HIV/AIDS.

Result

may be positive or negative

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