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Global Health Landscape
Lymphatic filariasis (LF)
Background information
• What isLymphatic filariasis (LF)?
Lymphatic filariasis (LF), also known as elephantiasis, is caused by parasitic worms and leads to severedisfigurement
of the extremities. While not directly life-threatening, LF is among the world’s leading causes of permanent and
long-term disability. Those infected are disabled in their most productive stage of life, resulting in an economic and
psychosocial burden on afflicted individuals, families, and communities.
• Global burden
More than 120 million people are infected with LF; over 40 million are seriously disfigured by the disease. It is
estimated that 1.3 billion people are at risk for the disease.
• Geographic distribution
LF is endemic in 83 countries. One-third of the people infected with LF live in India, and one-third live in Africa. Most of
the remaining cases are distributed throughout South Asia, the Pacific, and the Americas.
• Causative agent/transmission
The thread-like, parasitic worms Wuchereria bancrofti and Brugia malayi cause lymphatic filariasis. Adult worms lodge
in the lymphatic system, where they live for four to six years and produce millions of immature microfilariae (minute
larvae) that circulate in the blood. The parasites are transmitted to a mosquito vector when its blood meal includes
microfilariae. Inside the mosquito, over the course of one to thee weeks, the larvae mature blood meal.
Presentation
The worst symptoms of the chronic disease generally appear in adults. Elephantiasis of an entire leg, arm, the vulva, or the
breast—swelling up to several times normal size—is common. In endemic communities, some 10 to 50 percent of men suffer
from genital damage, especially formation of hydrocoeles (fluid-filled balloon-like enlargements of the sacs around the testes)
and elephantiasis of the
penis and scrotum. Once hydrocoele formation has begun, the most effective way to deal with it is generally surgery, but this
solution is tooexpensive for the majority of people affected by the disease.
Trends
The Global Programme to Eliminate Lymphatic Filariasis has targeted elimination of LF by 2020. Results from the program’s
first eight years (2000-2007) are encouraging. Yearly, single-dose mass drug adminstration has reached 570 million
individuals in 48 LF-endemic countries, protecting an estimated 9.5 million people with subclinical disease from progressing to
clinical disease and preventing disease in 6.6 million newborns.
Existing Products
Drugs
Combination Treatment —
Albendazole with Diethylcarbamazine
(DEC) or Ivermectin
Vaccines
Diagnostics
None
Microscopy
• Difficult because the parasites
often have a “nocturnal
periodicity” that restricts their
appearance in the blood to the
hours between 10 p.m. and 2
a.m.
• Use of single doses of two
drugs administered
concurrently is 99 percent
effective in removing
microfilariae from the blood
for a full year after treatment
• Does not kill adult worms
• Current standard of care is to
treat children annually for five
years to prevent disease and
break the chain of infection
• Treatment with DEC can
cause serious side effects if
onchocerciasis is also
present, as occurs in certain
African countries; ivermectin
is used as an alternative in
these regions
BinaxnOW® Filariasis Test
• Antigen detection test
• Rapid; requires 10 minutes
• Detects antigens of W.
bancrofti in whole blood,
serum, or plasma
• Simple, very sensitive, and
specific
• Expensive to use; generally
used to identify populations at
risk rather than individual
diagnosis
New Product Needs
Drugs
• Kills adult worms
(macrofilaricidal) and reduces
swelling
• Decreases necessity of
repeated, annual treatment;
inhibits microfilariae
production
Vaccines
Diagnostics
• Prevents establishment of
infection by microfilariae
• Further development of
diagnostics for B. malayi
• Adapt existing serologic
assays to work with oral fluids
or urine
Pipeline
Drugs
Discovery
Pre-Clinical
Clinical
Phase I
Clinical
Phase II
Clinical
Phase III
Anti-Wolbachia Consortium: Liverpool School of Tropical
Medicine/CombinatoRx/New England Biolabs, and others
(anti-Wolbachia treatments)
Market Opportunities
• The critical issues for LF are delivery into remote, endemic areas and maintenance of treatment over many years to
reduce adult disease and break the chain of transmission. Currently, all drugs used to treat LF are donated.
• Many current LF treatments are also effective against other diseases common in the developing world; new drugs
might likewise have multiple markets.
Development Issues
Drugs
• Recent evidence (June 2007)
suggests that ivermectin
resistance is emerging in
onchocerciasis (a filarial worm
disease); this observation
reinforces the need for new
drugs in the event resistance
appears in LF
Vaccines
• Lack of an in vitro culture
system for filariae
• Absence of tools for easy
genetic manipulation
• Need for improved animal
models
Diagnostics
• The major challenge is to
reduce cost of each diagnostic
to below $1
Additional Information
General Disease Links
• World Health Organization (WHO)
• Centers for Disease Control and Prevention (CDC)
Key Organizations
•
•
•
•
Anti-Wolbachia Consortium
The Carter Center
The Global Alliance to Eliminate Lymphatic Filariasis
Special Programme for Research and Training in Tropical Diseases (TDR)
Important Papers
• Galvez Tan, JZ. The elimination of lymphatic filariasis: A strategy for poverty alleviation and sustainable
development—perspectives from the Philippines. Filaria Journal 2:12 (2003)
• Johnston, KL, and Taylor, MJ. Wolbachia in filarial parasites: Targets for filarial infection and disease control. Curr
Infect Dis Rep 9:55-9 (2007)
• Molyneux, D. Lymphatic filariasis (elephantiasis) elimination: A public health success and development opportunity.
Filaria Journal 2:13 (2003)
• Ottesen, EA, et al. The global program to eliminate lymphatic filariasis: Health impact after 8 years. PLoS NTD 2:e317
(2008)
• Perera, M, et al. Neglected patients with a neglected disease? A qualitative study of lymphatic filariasis. PLoS NTD
1:e128 (2007)
• Towards a strategic plan for research to support the global program to eliminate lymphatic filariasis: Summary of
immediate needs and opportunities for research on lymphatic filariasis. Supplement 5 to AJTMH 71 (2004)
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