Lymphatic Filariasis

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Lymphatic Filariasis

• Dan Imler
• Morning Report

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EPIDEMIOLOGY

• W. bancrofti occurs in the following regions
  sub-Saharan Africa, Southeast Asia, the Indian
  subcontinent, many of the Pacific islands, and
  focal areas in Latin America.
• B. malayi occurs mainly in China, India,
  Malaysia, the Philippines, Indonesia, and various
  Pacific islands.
• B. timori is limited to the Timor Island of
  Indonesia.
• Within endemic regions, the infection has a focal
  distribution that coincides with areas conducive
  to breeding sites for the mosquito vector.

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EPIDEMIOLOGY

• It is estimated that more than 120 million people
  worldwide are infected with one of these three
  microfilariae.
• More than 90 percent of these infections are due
  to W. bancrofti, and the remainder are mostly due
  to B. malayi.
• Estimates suggest that more than 40 million
  infected individuals are seriously incapacitated
  and disfigured by the disease.
• A study from India, which accounts for 40 percent
  of the global prevalence of infection, estimated
  that a minimum of 842 million is lost each year
  there, secondary to treatment costs and working
  days lost from filariasis.

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• 85 of Haitis population lives in areas at risk
  of LF transmission.
• According to a 2001 antigen survey, 117 of 133
  communes are endemic for LF.
• In 2002, an estimated 2,130,000 people (30 of
  the total population) were thought to be
  infected.
• The parasite responsible for LF in Haiti is
  Wuchereria bancrofti spread mainly by Culex
  mosquitoes. 

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EPIDEMIOLOGY

• Adult worms are gradually acquired over years,
  slowly accumulating and producing microfilariae
  in infected individuals.
• Thus, the prevalence of microfilaremia in endemic
  communities increases with age.
• After the third or fourth decade of life, most
  people have been exposed and the proportion of
  infected individuals remains relatively constant.

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EPIDEMIOLOGY

• New sensitive diagnostic tests reveal that
  lymphatic filariasis is first acquired in
  childhood, often with as many as one-third of
  children asymptomatically infected before age
  five
• The risk of infection in childhood may be related
  to the maternal immune response during pregnancy.
  In one study of mother-newborn pairs, there was a
  13-fold increased risk of developing childhood
  Wuchereria infection, compared to uninfected
  controls, if the mother had active infection and
  there were absent filarial-specific T cell
  responses in cord blood at birth.
• However, the risk of childhood filariasis was
  only five-fold higher if there was evidence of
  T-cell specific immunity in cord blood
  lymphocytes.

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EPIDEMIOLOGY

• As with most helminth infections, the adult
  parasite does not replicate within the human
  host. Thus, the adult worm burden (as opposed to
  the microfilarial burden) cannot increase once an
  individual is no longer exposed to infective
  larvae, such as after leaving an endemic region.
• Since the mosquito vectors are not efficient
  transmitters of filariasis, a relatively
  prolonged stay in an endemic area is usually
  required for the acquisition of infection.

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EPIDEMIOLOGY

• Unlike most other mosquito-borne infections,
  several different mosquito species, including
  Anopheles, Culex, Aedes, and Mansonia species can
  serve as vectors for transmitting filariasis.
• The geographic distribution of these mosquitoes
  varies, and both urban and rural transmission of
  disease occurs.
• In many tropical and subtropical areas, the
  prevalence of infection is increasing due to
  progressive urbanization and increased breeding
  sites for the mosquito vectors.

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LIFE CYCLE

• W. bancrofti, B. malayi, and B. timori are all
  acquired via the bite of mosquitoes.
• When mosquitoes bite humans, they deposit
  third-stage infective larvae into the skin.
• These larvae travel through the dermis and enter
  local lymphatic vessels. Over a period of
  approximately nine months, these larvae undergo a
  series of molts and develop into mature adult
  worms, which range from 20 to 100 mm in length.
• These adults reside in the lymphatics, generally
  several centimeters from lymph nodes. They
  survive for approximately five years
  (occasionally up to 12 to 15 years), during which
  time male and females worms mate and produce
  microfilariae.
• Female parasites can release more than 10,000
  microfilariae per day into the bloodstream. These
  microfilariae are also known as embryonic or
  first-stage larvae, and measure approximately 200
  to 300 µm by 10 µm.

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LIFE CYCLE

• Mosquitoes, which bite infected individuals, can
  take up these circulating microfilariae. Within
  the mosquito, these embryonic larvae develop into
  second then third stage larvae over a period of
  10 to 14 days. The mosquito is then ready to bite
  and infect a new human host, thereby completing
  the life cycle.
• The interval between acquisition of infective
  larvae from a mosquito bite and detection of
  microfilariae in the blood is known as the
  prepatent period. This interval is usually
  approximately 12 months in duration.

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CLINICAL FEATURES

• Most people infected with Brugian or Bancroftian
  filariasis in endemic areas are asymptomatic,
  since the development of symptoms relates to the
  cumulative acquisition of increasing numbers of
  worms.
• Estimates suggest that at most one-third of
  infected individuals have clinical
  manifestations.
• In endemic communities, clinical symptoms are not
  usually evident until adolescence or adulthood.
  The clinical course of lymphatic filariasis
  includes three distinct phases asymptomatic
  microfilaremia, acute episodes of
  adenolymphangitis (ADL), and chronic disease
  (irreversible lymphedema), which is often
  superimposed upon repeated episodes of ADL.

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Acute adenolymphangitis

• Acute adenolymphangitis (ADL) characteristically
  presents with the sudden onset of fever and
  painful lymphadenopathy.
• Often there is retrograde lymphangitis, meaning
  that the inflammation spreads distally away from
  the lymph node group, which distinguishes it from
  the pattern typically associated with
  streptococcal lymphangitis.
• ADL is thought to occur because of
  immune-mediated responses to dying adult worms.
  It can manifest in a variety of locations, but
  the inguinal nodes and lower limbs are commonly
  involved.
• The inflammation tends to resolve spontaneously
  after four to seven days, but recurrences are
  frequent.
• Recurrences are typically seen one to four times
  per year, but the number of attacks increases
  with increasing severity of lymphedema.
• In addition, secondary bacterial infections can
  occur related to the breakdown of skin barriers
  in edematous or elephantatic skin or overlying
  intensely inflamed lymph nodes.

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Worms within Lymph Vessel
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Filarial fever

• Another clinical syndrome is known as filarial
  fever. This is characterized by acute,
  self-limiting episodes of fever, often in the
  absence of any obvious lymphangitis or
  lymphadenopathy.
• Because of the lack of associated features, this
  syndrome is frequently confused with other causes
  of fever in the tropics, such as malaria.

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Tropical pulmonary eosinophilia

• Tropical pulmonary eosinophilia is characterized
  by nocturnal wheezing.
• It is caused by an immune hyperresponsiveness to
  microfilariae trapped in the lungs and is
  typically seen in young males.

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Chronic Lymphedema

• Lymphedema, or swelling of a limb related to
  chronic inflammation of the lymphatic vessels, is
  a common late sequela of filarial infection.
• When the lymph vessels in the inguinal region are
  involved, swelling of the lower limb(s) ensues.
• When axillary lymph nodes are involved, swelling
  of the upper limb(s) results.
• Involvement of the breast can also occur in
  women.
• Pitting edema is present early, but with more
  chronic inflammation, brawny edema and hardening
  of the tissues develops, eventually resulting in
  hyperpigmentation and hyperkeratosis.
• When lymphedema is severe, it is often referred
  to as elephantiasis.

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Chronic Lymphedema

• The World Health Organization (WHO) has developed
  a system to grade the severity of lymphedema.
• Grade I Pitting edema that is reversible by
  elevating the leg
• Grade II Nonpitting edema that does not reverse
  with elevation of the extremity
• Grade III Severe swelling with sclerosis and
  skin changes

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Chronic Lymphedema

• Chronic lymphatic disease can also involve the
  genitalia, resulting in the development of
  unilateral or bilateral hydroceles.
• Hydroceles can be larger than 30 cm in diameter
  but are usually painless unless complicated by
  bacterial infection.
• Localization of adult worms in the lymphatics of
  the spermatic cord can also lead to palpable
  thickening of the cord.
• Lymphatic filariasis of the ovary and mesosalpinx
  has also been reported.

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DIAGNOSIS

• Nonspecific test abnormalities Eosinophilia up
  to 3000/microL
• Blood examination for detection of microfilariae
  should be performed in all individuals in whom
  the diagnosis of filariasis is suspected.
  Bancroftian and Brugian filariasis tend to show
  nocturnal periodicity. Blood should be drawn
  between 10 p.m. and 2 a.m. because the greatest
  number of microfilariae can be found in blood
  during this peak biting time of the mosquito
  vectors. The pattern of periodicity can be
  reversed by changing the patient's sleep-wake
  cycle.
• Antibody tests  Serologic tests for filarial
  antibodies which detect elevated levels of IgG
  and IgE are available
• Antigen tests  Different methods for detection
  of antigen in the blood have been attempted using
  various monoclonal antibodies.

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TREATMENT

• Diethylcarbamazine  DEC is not distributed for
  use in the United States but can be obtained from
  the Centers for Disease Control and Prevention
  (CDC) under an Investigational New Drug (IND)
  protocol
• Ivermectin  Studies have established that
  ivermectin given as a single dose in Bancroftian
  filariasis reduces microfilaremia by
  approximately 90 percent even one year after
  treatment
• Albendazole  has also been used in filarial
  infections. Prolonged courses of high dose
  albendazole have a significant macrofilaricidal
  effect and result in a gradual decrease in
  microfilarial levels.
• Doxycycline  Initial studies suggested that
  coxycycline, which has good activity against
  Wolbachia, leads to sterility of adult worms

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Workers in Port-au-Prince clean sea salt before
spraying it with a deworming drug and bagging it.
The treated salt is then sold at a loss to
Haitians.
Mass drug administration  This approach reduces
both the transmission of infection and disease
morbidity. The hypothesis is that once
populations have been treated long enough, levels
of microfilaremia will remain below that required
to sustain transmission. This period has been
estimated to be four to six years, corresponding
to the usual reproductive lifespan of the adult
parasite. Ideally, programs should focus on
treating both adults and children.
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• Uptodate.com
• Diagnosis, treatment, and prevention of
  lymphatic filariasis
• Epidemiology, pathogenesis, and clinical
  features of lymphatic filariasis
• NYtimes.com
• Beyond Swollen Limbs, a Disease's Hidden Agony
• http//www.nytimes.com/2006/04/09/world/americas/
  09lymph.html