Introduction ; Definition & Epidemiology
Causal Agents
The Worm
The vector
Signs & Symptoms
Risk Factors
Diagnosis
Treatment
Prevention & Control
Definition:Lymphatic filariasis, commonly known as
elephantiasis, is a neglected tropical disease
Filariasis (Philariasis) is a parasitic and
infectious It's caused by microscopic, threadlike parasitic worm (mosquito-borne parasitic
disease) that invades the body's lymphatic
system. It is a disease that is characterized by
the thickening of the skin and underlying
tissues, especially in the legs and male genitals.
Epidiomology
An estimated 1.3 billion people
around the world are at risk of LF
infection affects over 120 million
people in 73 countries. Countries
where LF is found are mostly in the
tropical and sub-tropical regions of
Asia, Africa, the Western Pacific,
and parts of the Caribbean and
South America. They also are
among the world’s poorest
countries, as LF is closely linked to
poor sanitation and poor housing
quality.
Geographic distribution
The areas in red indicate the geographic
distribution of lymphatic filariasis.
Classification
There are three types of these thread-like filarial worms:
Wuchereria bancrofti, which is responsible for 90% of the cases.
W. bancrofti is the most well-documented and widespread cause of
lymphatic filariasis. It is more common to find elephantiasis in patients
affected with W. bancrofti than those affected with the Brugian filariasis,
although it can occur. W. bancrofti is transmitted mainly by Anopheles. They
have no known animal reservoir.
Brugia malayi, which causes most of the remainder of the cases.
The distribution of B. malayi is very similar to that of W. bancrofti. However,
cases are concentrated in Asia, including South China, India, Indonesia,
Thailand, Vietnam, Malaysia, the Philippines, and South Korea. B. malayi is
mainly transmitted by Mansonia mosquitos. This type of worm has been
found in other mammals other than humans ; Macaques, leaf monkeys, cats
and civet cats. In Indonesia, human cases have been transmitted from
animals, which pose a particular challenge to the control of B. malayi.
Brugia timori, which also causes the diseases.
B. timori is the least common, and therefore least studied
species of filaria known to cause lymphatic filariasis. This
species was first reported on the island of Timor in 1964, and
has since been found in other islands in Indonesia. In regards
to vectors, and reservoirs, B. timori is more similar to W.
bancrofti than to B. malayi. Transmission of B. timori is by
the Anopheles barbirostris, also has no known animal
reservoir
Mode of transmission
The worms are spread by mosquitoes, which picks it up from an
infected person when they feed on the blood as they bite. The
tiny worms develop in the mosquito over the next seven to 21
days into a larval “Infective stage” stage which can be passed on
to another human when the mosquito bites them.
Life Cycle & Pathogenesis
Human filarial nematode worms have a complicated life cycle,
which primarily consists of five stages. After the male and
female worm mate(The female worms measure 80 to 100 mm in
length and 0.24 to 0.30 mm in diameter, while the males
measure about 40 mm by .1 mm.), the female gives birth to live
microfilariae by the thousands. The microfilariae are taken up by
the vector insect (intermediate host) during a blood meal. In the
intermediate host, the microfilariae molt and develop into 3rd
stage (infective) larvae. Upon taking another blood meal the
vector insect injects the infectious larvae into the dermis layer
of our skin.
After approximately one year the larvae molt through 2 more stages, maturing
into the adult worm. Infective larvae are transmitted by infected
biting mosquitoes during a blood meal. The larvae migrate to lymphatic vessels
and lymph nodes, where they develop into microfilariae-producing adults. The
adults dwell in lymphatic vessels and lymph nodes where they can live for
several years. The female worms produce microfilariae which circulate in the
blood. The microfilariae infect biting mosquitoes. Inside the mosquito, the
microfilariae develop in 1 to 2 weeks into infective filariform (third-stage)
larvae. During a subsequent blood meal by the mosquito, the larvae infect the
human host. They migrate to the lymphatic vessels and lymph nodes of the
human host, where they develop into adults.
Lymphatic filariasis is transmitted by different
types of mosquitoes.
Wuchereria bancrofti is transmitted mainly
by Anopheles mosquitoes.
Brugia malayi is transmitted by Mansonia mosquitoes.
Brugia timori is transmitted by Anopheles barbirostris
mosquito.
Lymphatic filariasis infection involves asymptomatic, acute, and
chronic conditions.
Asymptomatic:
Although the parasite damages the lymph system, majority of infected
people are asymptomatic and will never develop clinical symptoms. These
people do not know they have lymphatic filariasis unless tested. These
asymptomatic infections still cause damage to the lymphatic system and the
kidneys as well as alter the body's immune system.
Acute:
Acute episodes of local inflammation involving
Skin
Lymph nodes
Lymphatic vessels
Some of these episodes are caused by the body's immune response
to the parasite. However most are the result of bacterial skin
infection where normal defenses have been partially lost due to
underlying lymphatic damage.
Chronic:
When lymphatic filariasis develops into chronic conditions, in a
small percentage of people, it leads to lymphoedema (tissue
swelling). This is caused by fluid accumulation due to
inadequate functioning of the lymph system resulting in
swelling. This mostly affects the legs, but can also occur in the
arms, breasts, and genitalia.
The swelling and the decreased function of the lymph system makes it
difficult for the body to get rid of bacteria and unwanted pathogenes. This
will result in high number of bacterial infections in the skin and lymph system
causing hardening and thickening of the skin, which is called elephantiasis.
Men can develop hydrocele or swelling of the scrotum due to infection with
one of the parasites that causes LF specifically W. bancrofti.
Filarial infection can also cause tropical pulmonary
eosinophilia syndrome. This syndrome is typically found in
infected persons in Asia. Clinical manifestations of tropical
pulmonary eosinophilia syndrome include cough, shortness of
breath, and wheezing. The eosinophilia is often accompanied
by high levels of IgE (Immunoglobulin E) and antifilarial
antibodies
Patient with
elephantiasis
Patient with
lymphedema.
Since lymphatic filariasis does not always result in clinical symptoms, it is very
critical to perform diagnostic test to determine the diagnosis.
Microscopic Examination of blood smear: identification of microfilariae in a
blood smear by microscopic examination it is the standard method for
diagnosing an active infection.
Serologic techniques: provide an alternative to microscopic detection of
microfilariae Patients with active filarial infection typically have elevated
levels of antifilarial (IgG4) in the blood and these can be detected using
routine assays.
Immuno chromatographic test ( ICT ): antigen detection assay it can be done
by card test or through ELISA. Circulating Fitarial Antigen detection is the “
Gold Standard “ for diagnosing Wuchereria bancrofti .
The left ICT card
displays negative
results for LF infection,
while the right card
displays positive
results
Non pharmacological treatment:
1) Wearing shoes that can help prevent further exposure to the irritants.
2) Compression bandage and elastic stocking can also help manage the swelling
and inflammation caused by this condition.
3) Physicians often suggest cleaning the affected area with soap and water, as
well as soaking the area in a mixture of water and antiseptic, for the
management of non-filarial elephantiasis.
Medications
The most commonly used drugs for the treatment of lymphatic
filariasis are:
✦ Albendazole
✦ Diethylcarbamazine
✦ Ivermectin
» Albendazole and diethylcarbamazine have been found to be
effective in killing the microfilariae, and also the adult worms.
However, in the sub-Saharan Africa, albendazole is usually used
along with ivermectin. Ivermectin can kill the microfilariae,
though its effects on the adult worms are not very clear.
» Diethylcarbamazine is often regarded as a better option than
ivermectin for killing adult worms. This medicine is also effective
in reducing the size of enlarged lymph nodes considerably.
However, this medicine can sometimes produce an allergic
reaction, which can necessitate the use of antihistamines and
steroids. This side effect is generally attributed to the
destruction of the parasites. As the parasitic worms die, they
release certain chemicals that can produce the allergic reaction.
» Antibiotics such as doxycycline has also shown some promising results
in treating lymphatic filariasis. The parasitic worms that cause
elephantiasis have a population of symbiotic bacteria, known
as Wolbachia, without which they cannot survive. Antibiotics help
destroy these symbiotic bacteria, and thus wipe out the parasitic worms
as well.
» Along with medications, regular cleaning of the affected area can also
help control the symptoms of elephantiasis to a great extent. This is
probably due to the fact that, many times secondary skin infections play
a very important role in aggravating the symptoms of elephantiasis.
Daily cleaning can help prevent secondary infections.
Surgery
When elephantiasis causes gross enlargement of the scrotum, then surgery
may be required to address this condition. However, surgery is usually
ineffective in resolving the swelling of the limbs or trunk.
Class: benzimidazole drug
Indication: is an orally
administered broad-spectrum
anthelmintic e.g.
Neurocysticercosis, Hydatid
Disease
Mechanism of action
Albendazole causes degenerative alterations in the intestinal cells of the worm by
binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization
or assembly into microtubules. The loss of the cytoplasmic microtubules leads to
impaired uptake of glucose by the larval and adult stages of the susceptible
parasites, and depletes their glycogen stores. Also, degenerative changes in the
endoplasmic reticulum, the mitochondria of the germinal layer, and the
subsequent release of lysosomes result in decreased production of adenosine
triphosphate (ATP), which is the energy required for the survival of the helminth.
Due to diminished energy production, the parasite is immobilized and eventually
dies
Side Effects:
Serious S.E
easy bruising or bleeding, unusual weakness
fever with chills, body aches, or flu-like symptoms
leukopenia ; aplastic anemia, bone marrow suppression and agranulocytosis
Less Serious S.E.
stomach pain
nausea, vomiting
headache, dizziness
temporary hair loss
PRECAUTIONS:
This medication may cause liver problems. Patients with liver
disease, appear to be more at risk of bone marrow suppression
Albendazole should not be used in pregnant women except in
clinical circumstances where no alternative management is
appropriate. Patients should not become pregnant for at least 1
month following cessation of albendazole therapy. If a patient
becomes pregnant while taking this drug, albendazole should be
discontinued immediately.
Pharmacokinetics
Absorption
Albendazole is poorly absorbed from the GI tract; however, it
is rapidly converted to its primary active metabolite,
albendazole sulfoxide, prior to reaching systemic circulation.
Fatty meals enhance bioavailability, as indicated by up to a 5fold increase in plasma concentration in albendazole sulfoxide
Disturbution
Albendazole sulfoxide is 70% protein bound and widely
distributed throughout the body.
Metabolisim
Hepatic metabolsim
Class: Diethylcarbamazine
citrate is derived from the
anthelminthic agent
piperazine.
Indication: Used for the
treatment of individual
patients with certain filarial
diseases including tropical
pulmonary eosinophilia,
loiasis, and lymphatic
filariasis caused by infection
with Wuchereria
bancrofti, Brugia malayi,
or Brugia timori.
Mechanism of Action:
Proposed mechanisms of action include platelet-mediated
triggering of the release of excretory antigen from
microfilariae, with killing involving free radicals, druginduced alteration of prostaglandin metabolism in
microfilariae and/or in host endothelial cells, leading to
immobilization of microfilariae on endothelial surfaces and
adherence and killing by host platelets and granulocytes and
inhibition of microtubule polymerization.
1)
2)
3)
4)
Side Effects:
More common
Itching and swelling of the face, especially the eyes
Headache
Joint pain
Unusual tiredness or weakness
Less common
1. Fever
2. Painful and tender glands in the neck, armpits, or groin
3. Skin rash
4. Dizziness
5. Nausea or vomiting
Pharmacokinetics:
Absorption: readily absorbed following oral administration.
Distribution: widely distributed throughout all body
compartments, except adipose tissue, Half-life: 8 hr
Metabolites: diethylcarbamazine N-oxide, -Excretion: urine &
feces
Pregnancy:No data exist regarding the safety or dose
modification of the drug in pregnancy.
Indication: Used as an
Anthelmintic, Antiprotozoal
Agent, and Antinematodal
Agent
Mechanism of action
Ivermectin binds selectively and with high affinity to glutamate-gated
chloride ion channels in invertebrate muscle and nerve cells of the
microfilaria. This binding causes an increase in the permeability of the cell
membrane to chloride ions and results in hyperpolarization of the cell,
leading to paralysis and death of the parasite. Ivermectin also is believed
to act as an agonist of the neurotransmitter gamma-aminobutyric acid
(GABA), thereby disrupting GABA-mediated central nervous system (CNS)
neurosynaptic transmission
1)
2)
3)
4)
Side Effects : Headache, dizziness, muscle pain, nausea, or diarrhea may
occur.
Precautions :
allergic reactions.
liver problems, Limit alcoholic beverages
During pregnancy, this medication should be used only when clearly needed.
Ivermectin passes into breast milk. Though there have been no reports of
harm to nursing infants.
Pharmacokinetics:
Absorption:
Readily absorbed.
Distribution:
Due to the high lipid solubility of ivermectin, this compound is widely
distributed within the body. However it does not cross the blood brain
barriers in humans and most mammalians
Ivermectin binds strongly to plasma proteins in healthy subjects (93.2%)
Elimination:
This drug is extensively metabolized by human liver microsomes by
cytochrome P450. Half life: 22 to 28 hours.
The best way to prevent lymphatic filariasis is to avoid
mosquito bites. The mosquitoes that carry the
microscopic worms usually bite between the hours of
dusk and dawn. If you live in an area with lymphatic
filariasis:
at night
sleep in an air-conditioned room
sleep under a mosquito net
between dusk and dawn
wear long sleeves and trousers and
use mosquito repellent on exposed skin.