Filarisis

Filariasis
Dr. Suprakash Das
Assist. Prof.

Lecture Objectives
1. Introduction of filariasis
2. Parasitological description –Morphology and Life cycle
3. History of filariasis in ancient and modern times.
4. Epidemiology of filariasis and the burden of the disease.
5. Pathogenesis
6. Clinical spectrum of filarial diseases.
7. Laboratory diagnosis- Conventional and newer methods
8. Treatment of filariasis in short.

Introduction
 Nematodes belonging to the superfamily Filarioidea are slender thread-like worms (Latin,
filum and thread), which are transmitted by the bite of blood-sucking insects.
 The filarial worms reside in the subcutaneous tissues, lymphatic system, or body cavities of
humans.
 The adult worm generally measures 80-100 mm in length and 0.25-0.30 mm in breadth; the
female worm being longer than the males.
 The tail of the male worm has perianal papillae and unequal spicules but no caudal bursa.
 The female worms are viviparous and give birth to larvae known as microfilariae. The
microfilariae released by the female worm, can be detected in the peripheral blood or cutaneous
tissues, depending on the species.
 In some species, the microfilariae retain their egg membranes which envelop them as sheath.
They are known as sheathed microfilariae.
 In some other species of filarial nematodes, the egg membrane is ruptured and is known as
unsheathed microfilariae.

Introduction
 Once the microfilariae are classified on the basis of sheath as "sheathed" or
"unsheathed", their further differentiation can be done on the characteristic
arrangement of nuclei.
 Periodicity Depending on when the largest number of microfilariae occur in blood,
filarial worms can exhibit nocturnal, diurnal periodicity or no periodicity at all.
 The basis of periodicity is unknown but it may be an adaptation to the biting habits of the
vector.
 The life cycle of filarial nematodes is passed in two hosts: (1) definitive host is man and
(2) intermediate host are the blood-sucking arthropods.
 The microfilariae complete their development in the arthropod host to produce the
infective larval stages.
 These are transmitted to humans by arthropod, which are their vectors also during the
next feed.
 Adult worms live for many years whereas microfilariae survive for 3-36 months.

Introduction
Eight species of filarial worms infect humans, of them six are pathogenic-
(1) Wuchereria bancrofti,
(2) Brugia malayi and
(3) B. timori cause lymphatic filariasis;
(4) Loa loa causes malabar swellings and allergic lesions;
(5) Onchocerca volvulus causes eye lesions and dermatitis;
(6) Mansonella streptocerca leads to skin diseases; and two of them,
(7) M. ozzardi and (8) M. perstans are virtually nonpathogenic.
 Infection with any of the filarial worms may be called filariasis, but
 Traditionally, the term filariasis refers to lymphatic filariasis caused by
Wuchereria or Brugia species.

LYMPHATIC FILARIASIS-
Introduction
 Lymphatic filariasis (LF) is the second most common mosquito-borne
disease globally.
 LF infection occurs by exposure to mosquito bites. There are three parasites,
which cause human LF
Wuchereria bancrofti,
Brugia malayi, and
Brugia timori all of them are transmitted by Anopheles, Aedes, and
Culex.
 W. bancrofti is responsible for more than 90% of infections globally,
 B. malayi is mostly contributed to the transmission of the remainder.

Introduction
 The third parasite, B. timori, is common in a few countries in
Southeast Asia.
 The most important filarial diseases for humans are lymphatic
filariases, in which the adult worms are found in the lymphatic system.
 The lymphatic form of filariasis will be the focus of the site.
Lymphatic is also referred to sometimes as “elephantiasis.”
 Elephantiasis is actually an extreme clinical feature of filariasis.

History
Ancient Time
 It is known that lymphatic filariasis occurred in the Nile region, and ancient artifacts
suggest that the disease may have been found as early as 2000BC.
 A statue of Pharaoh Mentuhotep depicts swollen limbs, a characteristic of elephantiasis.
 Artifacts from the Nok civilization in West Africa also show scrotal swelling, another
characteristic of elephantiasis.
 The first reliable documentation of lymphatic filariasis symptoms is from an exploration
of Goa between 1588 and 1592 ( by writings of Jan Huygen Linschoten)
Recent Times
 In 1863, French surgeon Jean-Nicolas Demarquay Microfilariae in fluid extracted
from a hydrocoele (another common symptom of lymphatic filariasis) firstly.
 Three years later, Otto Henry Wucherer Microfilariae in urine.

History
 Timothy Lewis Microfilariae in both blood and urine.
 The adult worm was discovered by Joseph Bancroft.
 Patrick Manson in 1877 Pinpoint the microfilariae in mosquitoes.
 In 1900, George Carmichael Low discovered microfilariae in the
proboscis of mosquitoes, and finally pinpointed the true mechanism of
transmission, which is attributed to infective bite from a mosquito
vector.

Jean-Nicolas
Demarquay
Otto Henry Wucherer
Joseph Bancroft
Patrick Manson

Epidemiology
 One of the most important infectious diseases worldwide Lymphatic
filariasis most common.
 120M people in at least eighty countries are infected with the parasites
associated with lymphatic filariasis.
 90% of this infection W. bancrofti.
 1B people are estimated to be at risk for Infection.
 25M men have the genital disease (hydrocele) and almost 15M, mostly
women, have lymphoedema or elephantiasis of the leg.
 Many kinds of mosquitoes can transmit the parasite, depending on the
geographic area. For example, in AfricaAnopheles
 AmericasCulex,
 Aedes and Mansonia Pacific and Asia.

Life Cycle
 The extrinsic life cycle starts when the microfilariae are ingested with
the human blood by a bite of a mosquito.
 The microfilariae migrate through the gut wall of the mosquito to
thoracic muscles where they become shorter and thicker, later develop
into the first-stage larvae (L1).
 After 5–7 days, the L1 grow and develop to become the second stage
(L2), which is more active and finally by 10–11 days, they develop to
become the infective stage larvae (L3).
 After maturity, most of the infective larvae (L3) move to the
mosquito’s proboscis, where they become ready to infect another
human.

Life Cycle
 When the mosquito bites the host, L3 is put on the skin surface and
after pulling the proboscis; they get into the wound and travel to the
lymphatics.
 After about 9–10 days of entering, the L3 molt to become the fourth
stage larvae (L4).
 The L4 stage needs several days to few months before it develops and
becomes an adult. In the human body, adult worms (male and female)
live in lymph vessels and lymph nodes.
 After mating, the females produce numerous microfilariae, which
migrate into the lymphatic system and spread through the bloodstream

Parasite Morphology
Adult worm
 The adults are whitish, translucent, thread-like worms with smooth cuticle
and tapering ends.
 The female is larger (70-100 × 0.25 mm) than the male (25-40 x 0.1 mm).
 The posterior end of the female worm is straight, while that of the male is
curved vertically and contains two spicules of unequal length.
 Males and females remain coiled together usually in the abdominal and
inguinal lymphatics and in the testicular tissues.
 The female worm is viviparous and directly liberates sheathed microfilariae
into lymph.
 The adult worms live for many years, probably 10-15 years or more.

Parasite Morphology
Microfilariae:
 The microfilaria has a colorless, translucent body with a blunt head, and pointed
tail.
 It measures 250-300 µm in length and 6-10 µm in thickness.
 It can move forwards and backwards within the sheath which is much longer than
the embryo.
 It is covered by a hyaline sheath, within which it can actively move forwards and
backwards as sheath is much longer than the embryo.
 When stained with Leishman or other Romanowsky stains, structural details can
be made out.
 Along the central axis of the microfilaria, a column of granules can be seen, which
are called somatic cells or nuclei.

Parasite Morphology
 The granules are absent at certain specific locations- a feature which helps in the
identification of the species.
The specific locations are as following
 At the head end is a clear Space devoid of granules, called the cephalic space.
 In Microfilaria bancrofti, the cephalic space is as long as it is broad, while in
Microfilaria malayi, it is longer than its breadth.
 With vital a stains, a stylet can be demonstrated projecting from the cephalic
space.
 The anterior half of the microfilaria, is an oblique area devoid of granules called
the nerve ring.
 Approximately midway along the length of the microfilaria is the anterior V-spot,
which represents the rudimentary excretory system.
 The posterior V-spot (tail spot) represents the cloaca or anal pore.

W. Bancfrofi microfilariae in Thick blood smear

Pathogenesis
• Infection caused by W. bancrofti is termed as wuchereriasis or bancroftian filariasis.
• The disease can present as:
Classical filariasis
Occult filariasis.
Classical filariasis:
 It occurs due to blockage of lymph vessels and lymph nodes by the adult worms.
 The blockage could be due to mechanical factors or allergic inflammatory reaction to
worm antigens and secretions.
 The affected lymph nodes and vessels are infiltrated with macrophages, eosinophils,
lymphocytes and plasma cells.
 The vessel walls get thickened and the lumen narrowed or occluded, leading to lymph
stasis and dilatation of lymph vessels.

Pathogenesis
 The worms inside lymph nodes and vessels may cause granuloma formation, with subsequent
scarring and even calcification.
 Inflammatory changes damage the valves in lymph vessels, further aggravating lymph stasis.
 Increased permeability of lymph vessel walls lead to leakage of protein-rich lymph into the
tissues.
 This produces the typical hard pitting or brawny edema of filariasis.
 Fibroblasts invade the edematous tissues, laying down fibrous tissue, producing the nonpitting
gross edema of elephantiasis.
 Recurrent secondary bacterial infections cause further damage.
Occult fllariasis:
 It occurs as a result of hypersensitivity reaction to microfilarial antigens, not directly due to
lymphatic involvement.
 Microfilariae are not found in blood, as they are destroyed by the allergic inflammation in the
tissues.

Clinical Manifestations
 The most common presentations of lymphatic filariasis are
Symptomatic (subclinical) microfilaremia,
Acute adenolymphangitis (ADL) and
Chronic lymphatic disease.
 Most of the patients appear clinically asymptomatic but virtually all of them have
subclinical disease including
Microscopic hematuria or proteinuria,
Dilated lymphatics (visualized by imaging) and in men with W. bancrofti
infection,
Scrotal lymphangiectasia [Lymphangiectases represent superficial lymphatic
dilatation caused by a wide range of scarring processes. Lymphangiectasia occurs
as a consequence of lymphatic damage by an external cause, leading to obstruction
of local lymphatic drainage.] (detected by ultrasound).

Acute adenolymphangitis is characterized by
High fever,
Lymphatic inflammation (lymphangitis and lymphadenitis) and
Transient local edema.
Fever is of high grade, sudden in onset, associated with rigors and last for 2 or 3
days.
Lymphangitis is inflamed lymph vessels seen as red streaks underneath the skin.
Lymphatics of the testes and spermatic cord are frequently involved, with
epididymo-orchitis and funiculitis.
Acute lymphangitis is usually caused by allergic or inflammatory reaction to
filarial infection, but may often be associated with streptococcal infection also.

Lymphadenitis
 Inflammation of lymph nodes.
 Most common affected lymph nodes being inguinal nodes followed by
axillary nodes.
 The lymph nodes become enlarged, painful and tender.
Lymphedema
 This follows successive attacks of lymphangitis and usually starts as
swelling around the ankle, spreading to the back of the foot and leg.
 It may also affect the arms, breast, scrotum, vulva, or any other part of body.
 Initially, the edema is pitting in nature, but in course of time, becomes
hard and nonpitting.

Lymphangiovarix
 Dilatation of lymph vessels commonly occurs in the inguinal, scrotal, testicular and abdominal
sites.
 The lymphangitis and lymphadenitis can involve both the upper and lower extremities but
involvement of genital lymphatic occurs exclusively with W. bancrofti infection.
 The genital involvement Funiculitis, Epididymitis and Hydrocele formation.
Hydrocele:very common manifestation of filariasis.
 Accumulation of fluid occurs due to obstruction of lymph vessels of the spermatic cord and also
by exudation from the inflamed testes and epididymis.
 The fluid is usually clear and straw colored but may sometimes be cloudy, milky, or hemorrhagic.
 The hydrocele may be unilateral or bilateral and is generally small in size in the early stage, but
may occasionally assume enormous proportions in association with elephantiasis of the scrotum.
 The largest reported hydrocele weighed over 100 kilograms.

Lymphorrhagia
 Rupture of lymph varices leading to release of lymph or chyle and resulting in
 Chyluria,
 Chylous diarrhea,
 Chylous ascites and
 Chylothorax, depending on the involved site.
Elephantiasis
 Repeated leakage of lymph into tissues first results in lymphedema, then to elephantiasis, in which there is
 Nonpitting brawny edema
 Growth of new adventitious tissue
 Thickened skin, cracks, and fissures
 Secondary bacterial and fungal infections, commonly seen in leg but may also involve other parts of body.

Occult filariasis:
Massive eosinophilia (30-80%)
Hepatosplenomegaly
Pulmonary symptoms like dry nocturnal cough, dyspnea and asthmatic
wheezing.
Arthritis,
Glomerulonephritis,
Thrombophlebitis,
Tenosynovitis, etc.
Classical features of lymphatic filariasis are absent.
Meyers Kouwenaar syndrome is a synonym for occult filariasis.

Tropical pulmonary eosinophilia
 This is a manifestation of occult filariasis which Presents with
Low-grade fever,
Loss of weight, and
Pulmonary symptoms such as dry nocturnal cough, dyspnea and asthmatic wheezing.
 Children and Young adults are more commonly affected in areas of endemic filariasis including
the Indian subcontinent.
 There is a marked increase in eosinophil count (>3000 µm - ≥ 50,000 µm).
 Chest X-ray shows mottled shadows similar to miliary tuberculosis.
 It is associated with a high level of serum immunoglobulin E (IgE) and filaria antibodies.
 Serological tests with filarial antigen are usually strongly positive.
 The condition responds to treatment with diethylcarbamazine (DEC), which acts on
microfilariae.

Laboratory Diagnosis
 The diagnosis of filariasis depends on
Clinical features,
History of exposure in endemic areas and
Laboratory findings.
Demonstration of microfilaria
 Microfilaria can be demonstrated in blood, chylous urine, exudate of
lymph varix and hydrocele fluid.
 Peripheral blood is the specimen of choice.
 The method has the advantage that the species of the infecting filaria can be
identified from the morphology of the microfilaria seen.
 It is also the method used for carrier surveys.

 In India and other areas, where the prevalent filarial species is nocturnally
periodic, it is best to collect "night blood" samples between 10 pm and 4
am.
 Microfilaria can be demonstrated in unstained as well as stained
preparations and in thick as well as thin smears.
Unstained film
 Examination under the low power microscope shows the actively motile
microfilariae lashing the blood cells around.
 The timing of blood collection is critical and should be based on the
periodicity of the microfilariae.
 The examination may be conveniently made the next morning as
microfilariae retain their viability and motility a for a day or 2 at room
temperature.

Microfilaria in unstained
Blood film

Stained film
 A "thick and thin" blood smear is prepared on a clean glass slide and dried.
 The thick part of the smear is dehemoglobinized by applying distilled water.
 The smear is fixed in methanol and stained with Giemsa, Leishman, or
polychrome methylene blue stains.
 Microfilariae may be seen under the low power microscope in the thick film.
 The morphology of microfilariae can be studied in thin film.
 The microfilaria of W. bancrofti are sheathed and appear smooth curves in stained
smear and are 298 µm long and 7.5-10 µm in diameter.
 By using a micropipette for taking a known quantity of blood (20-60 mm") for
preparing the smear and counting the number of microfilariae in the entire stained
smear, microfilaria counts can be obtained.

Concentration techniques
Knot's concentration technique:
 Anticoagulated blood (1 mL) is placed in 9 mL of 2% formalin and centrifuged 500 x g
for 1 minute.
 The sediment is spread on a slide to dry thoroughly.
 The slide is stained with Wright or Giemsa stain and examined microscopically for
microfilariae.
Nucleopore filtration:
 In the filtration methods used at present, larger volumes of blood, up to 5 mL, can be
filtered through millipore or nucleopore membranes (3 µm diameter).
 The membranes may be examined as such or after staining, for microfilariae.
 The filter membrane technique is much more sensitive, so that blood can be collected
even during day time for screening.

 The disadvantages of the technique are the cost and the need for venipuncture.
Diethylcarbamazine provocation test
 A small dose of DEC (2 mg per kg body weight) induces microfilariae to appear in
peripheral blood even during day time.
 For surveys, blood samples can be collected 20-50 minutes after the administration of one
100 mg tablet of DEC to adults.
 Other specimens: Microfilaria may be demonstrated in centrifuged deposits of
Lymph,
Hydrocele fluid,
Chylous urine or
Other appropriate specimens.
 Usually 10-20 mL of the first early morning urine is collected for examination and
demonstration.

BiopsyAdult filarial worms can be seen in sections of biopsied lymph nodes,
but this is not employed in routine diagnosis.
Skin testIntradermal injection of filarial antigens (extracts of microfilariae,
adult worms and third-stage larvae of B. malayi or of the dog filaria Dirofilaria
immitis) induce an immediate hypersensitivity reaction.
 But, the diagnostic value of the skin test is very limited due to the high rate of
false-positive and negative reactions.
Imaging techniques
Ultrasonography High frequency ultrasonography (USG) of scrotum and
female breast coupled with Doppler imaging may result in identification of motile
adult worm (filaria dance sign) within the dilated lymphatics.
 Adult worm may be visualized in the lymphatics of the spermatic cord in up to
80% of the infected men with microfilaria associated with W. bancrofti.

Radiology Dead and calcified worms can be detected occasionally by X-ray.
 In tropical pulmonary eosinophilia (TPE), chest X-ray shows mottled appearance resembling
military tuberculosis.
 Intravenous urography, retrograde pyelography, lymphangiography and lymphoscintigraphy may
be used to demonstrate abnormal lymphatic urinary fistula.
Serodiagnosis (Demonstration of antibody)
Complement fixation,
Indirect hemagglutination (IHA),
Indirect fluorescent antibody (IFA),
Immunodiffusion and
Immunoenzyme tests have been described.
 Indirect immunofluorescence an ELISA detect antibodies in over 95% of active cases and 70% of
established elephantiasis.

Demonstration of circulating antigen
 Highly sensitive and specific test for detection of specific circulating filarial antigen (CFA) have
been developed for detection of recent bancroftian filariasis.
Trop-bio test semiquantitative sandwich ELISA for detection of CFA in serum or plasma
specimen.
Immunochromatographic test (ICT) is a new and rapid filarial antigen test that detects soluble
W. bancrofti antigens using monoclonal antibody (ADI2) in the serum of infected humans.
 Both assay have sensitivities of 93-100% and specificities approaching 100%.
Specific IgG4 antibody against W. bancrofti antigen WbSXP-1 have been used to develop
ELISA for detecting circulating filarial antigen in sera of patients with filariasis.
 There is however, extensive cross-reactivity between filarial antigens and antigens of other
helminths, including intestinal roundworm, thus interpretation of serological findings can be
difficult.
 Advantages: Antigen detection tests are more sensitive than microscopy and can differentiate
between current and past infections.

Molecular diagnostic technique
 Polymerase chain reaction (PCR) can detect filarial deoxyribonucleic acid
(DNA) from patient's blood,
 only when circulating microfilaria are present in peripheral blood but not in
chronic carrier state.
 Usually the test provides sensitivities that are up to tenfold greater than
parasitic detection by direct examination and is 100% specific.
 Recently LAMP technique has also been used.
Indirect evidences
 Eosinophilia (5-15%) is a common finding in filariasis. Elevated serum IgE
levels can also be seen.

Treatment
 Diethylcarbamazine is the drug of choice.
 It is given orally in a dose of 6 mg/kg body weight daily for a period of 12 days amounting to a
total of 72 mg of DEC per kg of body weight.
 Following treatment with DEC severe allergic reaction (Mazzotti reaction) may occur due to death
of microfilariae.
 It kills both microfilaria and adult worm.
 Antihistamines or corticosteroids may require to control the allergic phenomenon.
 The administration of DEC can be carried out in three ways:
l. Mass therapy
 In this approach, DEC is given to almost everyone in community irrespective of whether they have
microfilaremia disease manifestation or no signs of infection except those under 2 years of age,
pregnant women and seriously-ill patients.

Treatment
 The dose recommended is 6 mg/kg body weight.
 In some countries it is used alone and in some, with albendazole or ivermectin.
 Mass therapy is indicated in highly endemic areas.
2. Selective treatment
 Diethylcarbamazine is given only to those who are microfilaria-positive.
 In India, the current strategy is based on detection and treatment of human carriers and filarial
cases.
 The recommended dose in the Indian program is DEC 6 mg/kg of body weight daily for 12 doses,
to be completed in 2 Weeks.
 In endemic areas, treatment must be repeated every 2 years.
3. Diethylcarbamazine medicated salts
 Common salt medicated with 1-4 gram of DEC per kg has been used for filariasis control in
 Lakshadweep island, after an initial reduction in prevalence had been achieved by mass or
selective treatment of microfilaria carriers.

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