Visceral Leishmaniasis
A SYSTEMIC PROTOZOAL DISEASE
Annie Kleve
April 6, 2010
Leishmaniasis is caused by various species of
Trypanosome in one genus
Genus: Leishmania
Characterized by
William Boog Leishman
Two lifecycle forms:
a small, round amastigote
AND
a larger, flagellated
promastigote
Promastigote being
engulfed by macrophage
Image taken from biologyreference.com
Leishmaniasis is caused by various species of
Trypanosome in one genus: Leishmania
Leishmania donovani
amastigotes in a PBL in
bone marrow
CDC Dr. Francis Chandler
Macrophages in the
spleen infected with
many amastigotes
WHO/TDR El-Hassan
Visceral Leishmaniasis aka Kala-azar*
is Endemic World-wide
WRAMC
*Hindi for “Black fever”
Chappuis et al. Nature Rev Micro 5, 2007
Visceral Leishmaniasis aka Kala-azar*
results from infection by different species of
Leishmania with different reservoirs
L. infantum
L. chagasi
L. donovani
L. donovani
L. chagasi
*Hindi for “Black fever”
Chappuis et al. Nature Rev Micro 5, 2007
But 90% of cases occur in just 5 countries:
Brazil, India, Bangladesh, Nepal, & Sudan
Chappuis et al. Nature Rev Micro 5, 2007
More than 500,000 people are infected
10% of those infected die every year
Left untreated, 95% of people with active,
presenting symptoms will die
Peter Martell/ IRIN news
Médecins Sans Frontières (MSF)
More than 50,000 deaths per year
200,000 million people live in at-risk areas
Symptoms:
• Fever
• Anemia
• Weight Loss and Muscle Atrophy
• Enlarged Spleen and Liver
Images taken from WHO/TDR Kuzoe
VL Appears in Very Different Environments
Vector/Host systems are
united by the close proximity
of animal reservoirs
Nature Revs Micro 5, (2007)
VL Has aTwo Stage Life Cycle
Diagnosis: Finding a Gold Standard
Parasite detection requires serological tests or
invasive tissue analysis
DAT test
OR
WHO/TDR
Chappuis et al. Nature Rev Micro 5, 2007
Treatment: Few Options Until Recently
intravenous
SSG = Sodium Stibogluconate
(Pentavalent Antimonials)
Amphotericin B
Paromomycin Developed by OneWorld Health
Aminoglycoside from Streptomyces
Given by intramuscular injection
Miltefosine: The first oral treatment
•Mass produced in India
beginning in 2004
•Major Restriction:
Teratogenic
VL and the “War on Terror”
Images taken from USACHPPM
Elimination through Vaccine and Vector Control?
WHO/TDR
MSF Station in Umkara, Sudan
WHO/TDR
Ongoing Vaccine Trials in Bihar, India
WHO/TDR/Crump
A Disease of the “Poorest of the Poor”
Treatment averages $20-50 U.S
Risk factors for visceral
leishmaniasis have increased in
the last 20 years
References and Further Reading
Chappuis F., Sundar S., Hailu A., Ghalib H., Rijal S., Peeling R.W., Alvar J., Boelaert M. Visceral leishmaniasis:
what are the needs for diagnosis, treatment and control? Nat Rev Microbiol, 5:873-882 (2007).
Desjeux P. The increase in risk factors for leishmaniasis worldwide. Trans R Soc Trop Med Hyg, 95: 239-243
(2001).
Murray H.W., Berman J.D., Davies C.R., Saravia N.G. Advances in leishmaniasis. Lancet, 366(9496): 1561–1577
(2005).
Van Griensven J., Balasegaram M., Meheus F., Alvar J., Lynen L., Boelaert M. Combination therapy for
visceral leishmaniasis. Lancet Infect Dis, 10: 184-194 (2010).
Rodriguez-Cortes A., Ojeda A., Francino O., Lopez-Fuertes L., Timon M., Alberola J. Leishmania Infection:
Laboratory Diagnosing in the Absence of a "Gold Standard" Am J Trop Med Hyg , 82: 251-256
(2010).
Sundar S., and Olliaro P.L. Miltefosine in the treatment of leishmaniasis: clinical evidence for informed clinical
risk management. Ther Clin Risk Manag, 3:733-740 (2007).
Sundar S., Rai M., Chakravarty J., et al. New treatment approach in Indian visceral leishmaniasis: single-dose
liposomal amphotericin B followed by short-course oral miltefosine. Clin Infect Dis, 47: 10001006 (2008).
References and Further Reading
The Institute for OneWorld Health
The United States first Non-profit pharmaceutical company
http://www.oneworldhealth.org/
U.S. Army Center for Health Promotion and Preventative Medicine
http://phc.amedd.army.mil/default2.asp
UNDP/World Bank/WHO/TDR Special Programme for Research and
Training in Tropical Diseases
http://apps.who.int/tdr/
.