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WHO/C. Black
NEGLECTED TROPICAL DISEASES
Leishmaniasis is a neglected tropical disease caused by
protozoan parasites belonging to the genus Leishmania
that are transmitted through the bites of sandflies. It
comprises a group of infections with important clinical
and epidemiological diversity spread across 98
countries in Africa, Asia, Europe and the Americas. The
global burden of these infections combined is estimated
to be millions of disability-adjusted life years.
Approximately 200,000 to 400,000 cases of visceral
leishmaniasis (VL) and 700,000 to 1.2 million cases of
cutaneous leishmaniasis (CL) are reported each year.
The most serious form is VL, which is 90% fatal if left
untreated. Treated patients of VL sometimes develop a
condition known as post-kala-azar dermal leishmaniasis
(PKDL), which presents as dermal lesions that can
harbour parasites for years and can act as a reservoir of
VL.
FIND has been scaling up the fight against leishmaniasis
(VL in particular) and is addressing critical diagnostic
gaps for the disease by:
 reducing the burden of leishmaniasis through
improved and innovative diagnostic solutions
 improving detection and understanding of the role of
asymptomatic infections and cases of PKDL in
regions targeted for elimination.
FIND and partners are developing tests for early and accurate diagnosis of leishmaniasis, detection of
infection in asymptomatic patients and monitoring treatment. These include tests to detect parasite
antigens in the urine of VL patients (antigen detection test) and to detect parasite DNA in various
biological samples (molecular detection test).
The clinical signs of VL are not specific enough for
accurate diagnosis of the disease, as other infections
have similar clinical manifestations. Patients with
suggestive clinical signs are usually tested serologically,
followed by confirmation of the presence of parasites
through microscopic examination of bone marrow or
splenic aspirates. Due to the complexity associated with
sampling, treatment of symptomatic patients is
sometimes based solely on positive serological tests.
Detection of parasite components such as antigens or
DNA would be a better indicator of infection than
detecting host antibodies, which remain in the blood for
long periods after curative treatment. Most VL patients
excrete Leishmania antigens in their urine, but current
tests for detecting them are difficult to implement. An
easy-to-use test is vital for monitoring treatment.
FIND and Kalon Biological have developed a prototype
ELISA assay that detects parasite antigens in the urine of
VL patients without the need for boiling samples.
Promising results were obtained from test samples
collected in Bangladesh and East Africa in collaboration
with Drugs for Neglected Diseases initiative (DNDi),
International Centre for Diarrheal Disease Research,
Bangladesh (icddr,b) and Kenya Medical Research
Institute (KEMRI).
The ELISA assay is being used to test urine samples
obtained from patients before, during and after treatment
in a study carried out by DNDi in Sudan. In addition, the
feasibility of using the ELISA reagents to develop a rapid
test is being explored in partnership with Standard
Diagnostics, Inc. (SD). FIND is also working with the
Royal Tropical Institute (KIT) and the Infectious Disease
Research Institute (IDRI) to validate the performance of
the ELISA assay using stored samples. Prototype rapid
diagnostic tests for VL are being evaluated in clinical
trials in Kenya, Sudan and Bangladesh.
FIND is committed to establishing strong partnerships
to fight leishmaniasis with ministries of health and
national programmes in endemic countries, NGOs and
Detection of Leishmania DNA in body fluids of
patients would be a significant improvement to
parasitological examination. In 2011, FIND initiated a
partnership with Eiken Chemical Co. Ltd. to develop a
test for detecting Leishmania DNA using the loopmediated isothermal amplification (LAMP) technology.
LAMP detects pathogen DNA with very high sensitivity
and specificity. The reagents for LAMP are dried on
the inside of the cap of the reaction tube and, unlike
most other molecular tests, target DNA is amplified at
a constant temperature. The results are read visually
using LED light, meaning the test can be performed
with much less laboratory equipment than other DNA
detection tests and by technicians with limited training
in molecular biology.
Development of the LAMP test is being undertaken in
collaboration with KIT, the Sanger Institute, TiPharma
and Eiken.
Eiken has developed prototype LAMP tests using a
combination of two sets of primers. One primer set
amplifies all species of Leishmania, while the other
only amplifies species belonging to the L. donovani
complex (which causes VL). The prototype LAMP
assay has been evaluated at KIT using purified
parasite DNA, and subsequently on a number of
clinical samples, including ulcer swabs from CL
patients in Colombia, blood from VL patients in
Sudan, Ethiopia and endemic controls.
Clinical trials to determine the performance of the
LAMP kit are being initiated in Kenya, Sudan and
Bangladesh. The feasibility of using LAMP to monitor
treatment and to identify asymptomatic individuals will
also be determined.
the WHO. FIND will also work with groups that are
discovering novel biomarkers and support validation of
reagents that show promise for use in a sensitive test.
Leishmaniasis: FIND 2015 – 2020 Priorities and Interventions
Development / Policy priorities for new tools:
 Point-of-care test for diagnosis of VL in eastern Africa that will also diagnose VL in immunocompromised
patients (antigen detection)
 Test of cure for VL and PKDL (antigen detection and/or molecular)
Enabling interventions:
 Facilitate access to specimens for product development
 Support operational research to improve understanding and management of asymptomatic carriers
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