Lymphatic Filariasis Elephantiasis

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Lymphatic Filariasis / Elephantiasis
Onchocerciasis (river blindness)
Loiasis
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What is it ?

• Wuchereria bancrofti and Brugia malayi are
  filarial nematodes
• Spread by several species of night - feeding
  mosquitoes
• Causes lymphatic filariasis, also known as
  Elephantiasis
• Commonly and incorrectly referred to as
  Elephantitis

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Definitive Host

• Humans are the definitive host for the worms that
  cause lymphatic filariasis
• There are no known reservoirs for W.bancrofti.
• B.malayi has been found in macaques, leaf
  monkeys, cats and civet cats

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Anopheles
Intermediate Host
Aedes

• W.bancrofti is transmitted by Culex, Aedes, and
  Anopheles species
• B.malayi is transmitted by Anopheles and Mansonia
  species.

Culex
Mansonia
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Lymphatic Filariasis by the numbers

• Endemic in 83 countries
• 1.2 billion at risk
• More than 120 million people infected
• More than 25 million men suffer from genital
  symptoms
• More than 15 million people suffer from
  lymphoedema or elephantiasis of the leg

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Morphology I

• Adult White and thread-like. Two rings of small
  papillae on the head.
• Female510cm in length
• Male 2.54cm and a curved tail with two
  copulatory spicules.

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Morphology II

• Microfilaria 177296 µm in length, a sheath
  with free endings. Bluntly rounded anteriorly and
  tapers to a point posteriorly. A nerve ring with
  no nuclei at anterior 1/5 of the body.

Wuchereria bancrofti
Brugia malayi
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Morphology - B.malayi

• B.malayi microfilariae are slightly smaller than
  those of W.bancrofti.
• Microfilariae are sheathed, and about 200 to 275
  µm.
• Not much is known about the adult worms, as they
  are not often recovered
• One distinctive feature of B.malayi is that the
  microfilarial nuclei extends to the tip of the
  tail

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The morphological differences between two
microfilaria

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  W.bancrofti B. malayi
• Size 244296 µm
  177230 µm
• Cephalic space Shorter
  Longer
• Nuclei Equal sized
  Unequal sized
• clearly
  coalescing
• countable
  uncountable
• Terminal nucleus No
  Two

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Characteristic of life cycle

• Host Mosqutoes (intermediate host)
• Human (final host)
• Location Lymphatics and lymph nodes
• Infective stage Infective larvae
• Transmission stage Microfilariae
• Diagnostic stage Microfilariae

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Life cycle
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Wuchereria Life Cycle
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Nocturnal periodicity

• Phenomen which the number of microfilariae in
  peripherial blood is very low density during
  daytime, but increase from evening to midnight
  and reach the greatest density at 10p.m to 2
  a.m.May be related to cerebral activity and
  vasoactivity of pulmonary vessels.

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• Larva deposited by mosquito bite
• Travel through dermis to lymphatic vessels
• Growth (approx 9 months) to mature worms(20-100mm
  long)
• Worms live 5-7 years (occasionally up to15 years)
• Mate-gtMicrofilariae (1st stage larva)
• Females-gtrelease up to 10,000 microfilariae/day
  into bloodstream
• Microfilarie taken up by mosquito bite
• Develop into 2nd and 3rd stage larva over 10-14
  days inside mosquito vector

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Lymphatic System

• Network of vessels that collect fluid that leaks
  out of the blood into tissues (lymph)
• Redirects lymph back into the blood stream

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Clinical Course

• Initially asymptomatic
• Symptoms develop with increasing numbers of worms
• Less than 1/3 of infected individuals have acute
  symptoms
• Clinical Course is 3 phases
• Asymptomatic Microfilaremia
• Acute Adenolymphangitis (ADL)
• Chronic/Irreversible lymphedema
• Superimposed upon repeated episodes of ADL

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Acute ADL

• Presents with sudden onset of fever and painful
  lymphadenopathy
• Retrograde Lymphangitis
• Inflammation spreads distally away from lymph
  node group
• Immune mediated response to dying worms
• Most common areas Inguinal nodes and Lower
  extremities

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• Inflammation spontaneously resolve after 4-7 days
  but can recur frequently
• Recurrences usually 1-4 times/year with
  increasing severity of lymphedema
• Secondary bacterial infections in
  edematous(elephantatic) areas
• Filarial fever (fever w/o lymphangitis)
• Tropical Pulmonary Eosinophilia
• Hyperresponsiveness to microfilariae trapped in
  lungs
• Nocturnal Wheezing

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Chronic Manifestations

• Lymphedema
• Mostly LE and inguinal, but can affect UE and
  breast
• Initially pitting edema, with gradual hardening
  of tissues ? hyperpigmentation hyperkeratosis
• Genitalia?Hydroceles

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Chronic Manifestations

• Renal involvement
• Chyluria?lymph discharge into urine
• Loss of fat and protein? hypoproteinemia anemia
• Hematuria, proteinuria from ?immune complex
  nephritis
• Secondary bacterial/fungal infections

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• Elephantiasis accumulation of lymph in
  extremeties, fibrosis, and thickening of skin.

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Onchocerciasis (river blindness)

• Debilitates millions of humans by scarring eyes
  causing permanent blindness
• Affects people along rivers in West Central
  Africa (native) South America (introduced via
  slavery)
• Caused by Onchocerca volvulus
• Adult females are up to 500mm long males up to
  40mm long
• Adults live up to 14 years
• Restricted to humans (no known animal reservoirs)
• Transmitted by black flies (Simuliidae)
• Larvae live in fast-flowing water

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Onchocerciasis (river blindness)

• Black flies ingest microfilariae from blood
• Move from gut to flight muscles mature into
  infective larvae (L3)
• L3 larvae migrate to head enter humans via bite
  wound mature into adults (2-4 months)
• Adults accumulate in subcutaneous nodules (1cm
  diameter) which dont cause much damage
• Mating in nodules produces microfilariae
• Live under skin causing rashes wrinkles
• Cause blindness when invade eyes tissues die
  there

Nodules
Damaged eye tissues
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Onchocerciasis (river blindness)

• Early stages of eye damage can be reversed by
  drug treatment
• Parasiticide ivermectin is most popular
• Transfer of worms affected by feeding behaviour
  of flies
• Waggle mouth parts during biting to increase
  wound size create pool of blood (pool
  feeders)
• Main vector Simulium damnosum
• Complex of gt40 sibling species in West East
  Africa
• Not all sibling species transmit worms
• Insecticide applications used to control larvae
  in rivers

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Loiasis
Microfilariae in human blood

• Caused by infection with Loa loa
• Adult worms move under human skin
• Observed beneath skin or passing through
  conjunctiva of eyes (eye worms)
• Worms 2 races (attack humans or arboreal
  primates)
• Transmitted by horse flies (Tabanidae) in genus
  Chrysops
• Day-feeding forest-dwelling
• Rare case of Tabanidae biological vectors
• Disease endemic to rain forest regions of West
  Central Africa
• Generally mild painless (chronic) with 10-15
  year incubation period
• May cause swellings of skin (Calabar swelling)

Adult in human eye
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Diagnosis

• The standard method for diagnosing active
  infection is the identification of microfilariae
  by microscopic examination
• However, microfilariae circulate nocturnally,
  making blood collection an issue

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Diagnosis

• A card test for parasite antigens requring only
  a small amount of blood has been developed
• Does not require laboratory equipment
• Blood drawn by finger stick
• Urinalysis, CBC and Comprehensive Chemistries
• Foot Biopsy Normal Skin with areas of chronic
  inflammation

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Microfilariae are seen in blood smears and are
DIAGNOSTIC
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Blood Smear - Microfilaria

• Note wavy microfilarial worm in the thick part of
  blood film.
• Dark blue structures are nuclei
• Tail end tapering (no nuclei)
• Sheath covering worm.

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Blood Smear - Microfilaria

• Note wavy microfilarial worm in the thick part of
  blood film.
• Head end of the worm rounded (no nuclei)
• (Sheath is not clearly seen)

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Blood Smear - Microfilaria

• Note wavy microfilarial worm in the thick part of
  blood film.
• Dark blue structures are nuclei
• Tail end - tapering sheath (no nuclei)

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Hydrocele fluid cell block.

• Note wavy microfilarial worms.
• Inflammatory cells lymphocytes.
• Hemorrhagic fluid sediment

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Hydrocele fluid cell block.

• Note wavy microfilarial worms.
• Inflammatory cells lymphocytes.
• RBC

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Hydrocele fluid cell block.

• Note wavy microfilarial worms.
• Inflammatory cells lymphocytes.
• RBC

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Hydrocele fluid cell block.

• Inflammatory cells lymphocytes.
• RBC

• Microfilaria.

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Control

• As with malaria, the most effective method of
  controlling the spread of W.bancrofti and
  B.malayi is to avoid mosquito bites
• The CDC recommends that anyone in at-risk areas
• Sleep under a bed net
• Wear long sleeves and trousers
• Wear insect repellent on exposed skin, especially
  at night

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Vector control

• Covering water-storage containers and improving
  waste-water and solid-waste treatment systems can
  help by reducing the amount of standing water in
  which mosquitoes can lay eggs.
• Killing eggs (oviciding) and killing or
  disrupting larva (larviciding) in bodies of
  stagnant water can further reduce mosquito
  populations.

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Treatment

• Treatment of filariasis involves two components
• Getting rid of the microfilariae in people's
  blood
• Maintaining careful hygiene in infected persons
  to reduce the incidence and severity of secondary
  (e.g., bacterial) infections.

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Drugs, Drugs, Drugs!

• Anti-filariasis medicines commonly used include
• Diethylcarbamazine (DEC)
• reduces microfilariae concentrations
• kills adult worms
• Albendazole
• kills adult worms
• Ivermectin
• kills the microfilariae produced by adult worms

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And more drugs!

• The disease is usually treated with single-dose
  regimens of a combination of two drugs, one
  targeting microfilariae and one targeting adult
  worms (i.e.,either diethylcarbamazine and
  albenadazole, or ivermectin and albendazole
• In some areas, DEC laced table salt is used as a
  prophylactic

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thank you for your attention