NEW YORK (Reuters Health) – Commercially available rapid immunological tests can exclude leishmaniasis only in the Indian subcontinent, not elsewhere, a new study shows.
The test sensitivity was significantly lower in Eastern Africa and Brazil, and the researchers advise against ruling out leishmaniasis in those regions based on a negative rapid test.
In email to Reuters Health, lead investigator Dr. Jane Cunningham from the World Health Organization’s Special Program for Research and Training in Tropical Diseases attributed the regional differences to “parasite diversity and/or differences in antibody concentrations which may in turn be linked to different age patterns, immune response, and nutritional status of patients.”
She offered a couple of options for health care providers in “regions where the rapid tests perform less well.” One approach, she said, is “to use the clinical case definition (at least two weeks of fever plus clinical splenomegaly) in combination with a more sensitive test such as the direct agglutination test (DAT) or parasitological confirmation by splenic puncture.”
Or, she added, providers can incorporate the rapid test into the algorithm implemented by Medecins Sans Frontiere (MSF) in Sudan: “If the patient meets the clinical case definition and the rapid diagnostic test is positive, they can treat for visceral leishmaniasis, but if the rapid test is negative the patient must have a second line (more sensitive test) such as DAT, before a diagnosis of visceral leishmaniasis can be excluded.”
Microscopic confirmation of the parasite from bone marrow or spleen is the gold standard for diagnosis of visceral leishmaniasis, However, Dr. Cunningham and her colleagues noted in a paper August 31 in Clinical Infectious Diseases, “The invasiveness and potentially fatal complications associated with splenic aspiration has motivated the development of noninvasive serological tests such as the direct agglutination test.”
In an international effort, the researchers analyzed the sensitivity and specificity of five commercial rapid diagnostic tests in disease endemic regions of the Indian subcontinent, Eastern Africa and Brazil. The five tests are the Crystal KA (Span Diagnostics Ltd.), DiaMed-IT LEISH (Bio-Rad Laboratories), Kalazar Detect (InBios International, Inc.), Signal (KA Span Diagnostics Ltd.), and Leishmania Ab Rapid Test (CTK Biotech Inc.).
The tests were chosen because they are easy to perform and interpret, give results within 15 minutes, and employ either direct agglutination or lateral flow immunochromatography, the authors said.
Four laboratories in India, Bangladesh and Nepal, two in Brazil, and three in Kenya and Sudan tested stored serum samples from a total of 250 patients with confirmed leishmaniasis in each region and an equal number of controls, using each of these tests.
The study did not include HIV coinfected patients.
Overall, the sensitivity of the rapid tests was highest in the Indian subcontinent, ranging there from 92.8% to 100%. Next best was Brazil, with sensitivity ranging from 61.5% to 79.2%, followed by East Africa at 36.8% to 73.2%.
Specificity was above 96% in all regions.
A negative result on a test of low sensitivity does not necessarily rule out disease, while a positive result on a highly specific test is highly suggestive of the disease, the authors note.
The authors also point out that maintaining the thermal stability of the tests during transport and storage in field conditions is important in routine use.
Dr. Cunningham concludes that “clinicians using (these tests) outside of the Indian subcontinent, should be particularly cautious using them to exclude a diagnosis of visceral leishmaniasis.”
Clin Infect Dis 2012.