Loa loa,Onchocerca, Dirofilaria, Mansonella

12.10.12

Contd.

Acanthocheilonemantinae

Genus Species Habitat of adult worm

Microfilaria

Wuchereria W.bancrofti Lymphatic system

Blood

Brugia B.malayi Lymphatic system

Blood

Oncocerca O.volvulus Connective tissue

Skin

Dipetalonema

Mansonella

D.PerstansD.Streptocerca

M.ozzardi

Connective tissue

Mesentery

BloodSkin

Blood

Contd.

Dirofilarinae

Genus Species Habitat of adult worm

Microfilaria

Dirofilaria D. repensD. tenuis

Connective tissues & eyelid

Dirofilaria D. immitis Heart of dog Blood

Loa L.loa Connective tissue & Conjunctiva

Blood

Differential characters of adult worms

Superfamily FILARIOIDEA

↓ ↓Cuticuta smooth Cuticula not smooth↓ ↓ ↓ ↓Head with Head without Provided with ProvidedCuticular Cuticular Appendages minute warts withAppendages W.bancrofti L.loa annular andD.Perstans B.malayi oblique

thickningsO.volvulus

Diffential characters of Microfilariae

Microfilaria↓ ↓Found in blood Found in skinMf.bancrofti, Mf.malayi, Mf.loa, Mf.perstans Unsheathed and non-

Mf.ozzardi periodicMf.volvulus,Mf.streptocerca

↓↓ ↓ ↓ ↓Sheathed and Unsheathed and non-periodic Nuclei up to tail tip Tail tip Periodic Mf.perstans, Mf.ozzardi ( tail end crook like) free from Mf.bancrofti, Mf.malayi, Mf.streptocerca nuclei Mf.loa ↓ ↓ ↓ ↓ Volvulus

Nucei upto tail tip Tail tip free Nuclei upto tail tip Free tail tipMf.malayi,Mf.loa Mf.bancrofti Mf.perstans Mf.ozzardi

Contd.• While examining a blood film the following microfilariae should be kept in

mind-

In Africa: Mf.bancrofti., Mf. Loa and Mf.perstans.

In South America:Mf.bancrofti, Mf. Perstans and Mf.ozzardi.

In India:Mf.bancrofti and Mf.malayi.

Loa-loa• Common name -The African eye worm

• Geographical distribution; 

• Central and West Africa

• Habitat:• Adult worms live in the subcutaneous tissues of man• often in the sub‐conjunctival tissue of the eye.

Contd.

• Morphology-• Adult worm- Microscopically, the cuticula is found to have

numerous rounded protuberances ( cuticular bosses) which vary in number and arrangement in the two sexes.

• Exists in three forms: Adult• Microfilarial• Larval• Adult male 30‐34mmx0.4mm• Adult female 50‐77mmx0.5mm

Contd.• Embroys- They are found in the peripheral blood by daytime.

• Mf. Loa is enveloped in a sheath and measures 300µm by 7µm.

• The column of nuclei extends to the tail tip.

• Life cycle- The worm passes its life cycle in two hosts:Man

Chrysops ( mango or deer flies)• Larval development follows the same course as in other microfilariae.

• Loa-loa is maintained in nature by interhuman transmission.

Day‐biting Chrysops flies

Contd.• The infection is transmitted by a day-biting female chrysops, C.silacea and

C.dimidiata.

• Only females suck blood.

• Pathogenicity- The worm produces the disease in man called loisis.

• Man is infected by the bites of chrysops.

• The incubation period is 3 to 4 years.

• On entering the human host, the worm migrates rapidly to the various parts of the body through the subdermal connective tissues.

Contd.• The worm shows itself a special prediclection for creeping in and around

the eyes.

• During migration, it causes oedema of subcutaneous tissues, known as Calabar swellings or fugitive swellings.

• They disappear in course of 2 to 3 days and are regarded as allergic reaction of tissues to filarial toxins.

• Microfilariae can seldom be found during the period of calabar swellings.

• The diagnosis is based on history of such fugitive swellings associated with intense eosinophilia ( 30-40%).

Lab diagnosis• Initial Diagnosis is based upon the history of fugitive swellings and intense

eosinophilia (30-40%)

• Demonstration of the microfilariae in the peripheral blood during the day.

• Microfilariae are shed by the females on a random schedule.

• Therefore, multiple samples should be collected during daytime, preferably between 10 a.m. and 2 p.m.

• Demonstration of the sheathed microfilariae with nuclei extending to the tip of the tail is sufficient for the diagnosis.

• The infection can also be diagnosed by detection or removal of adults from the eye or Calabar swellings.

• Increased levels of anti- filarial antibodies.

Treatment• Treatment- Hetrazan is an effective remedy for loiasis, causing a quick

disappearance of microfilariae from the peripheral blood and death of adult worms.

• Allergic reactions during the course of hetrazan therapy may occur.

• With large number of Mf. Loa ( in excess of about 30 per mm3 ) there is great risk of development of meningoencephalitis and nephrotic syndrome.

• These cases are treated with diethylcarbamazine.

• DOC is diethylcarbamazine.

Contd.• Prophylaxis- Loisis can be prevented by:

• Protection from Chrysops bites in endemic areas by application of repellents to exposed skin.

• Destructive campaigns against Chrysops.

• Detection and treatment of infected individuals with diethylcarbamazine.

ONCHOCERCA VOLVULUS

THE CONVOLUTED FILARIA

Onchocerca volvulus• Common name is convoluted filaria.

• The generic name Onchocerca means “hooked tail”.

• Geographical Distribution-In various parts of Africa and Central America also reported from south Arabia.

• Habitat-Adult worm in the subcutaneous connective tissues of man.

• Morphology-• Adult worm-Microscopically the cuticula is seen to be raised in well

marked annular and oblique thickenings.

Contd.• These are more prominent in females than in males.

• The male measures 3 cm in length by about 0.13 mm in breadth, it has a coiled tail.

• The female is very long, measuring up to 50 cm in length by 0.4 mm in its greatest diameter.

• The gravid females may live as long as 15 years.

Contd• Microfilariae:• These are found in the skin.

• They are unsheathed and non-periodic.

• The column of nuclei does not extend to the tail tip.

• They measures 300µm in length by 6 to 8 µm in breadth.

Mf of Onchocerca volvulus

The microfilariae are sheathless with sharply pointed, curved 

tails. 

Life cycle• O.volvulus completes its life cycle in two hosts.

• Man is the definitive host.

• Day biting female black fly of the genus Simulium is the intermediate host.

• Humans become infected by the bite of black fly, which possesses in its mouth parts the infective third stage larvae.

• The larvae enter the skin through the puntured wound and migrate to the subcutaneous tissue in which they moult twice and develop into male and female adult worms.

Simulium flies breed in fast flowing rivers i.e well oxygenated water, because their larvae have an obligatory aquatic stage during which they require high oxygen tension (see picture below).

'.  Thus Onchocerciasis  is often referred to as 'river blindness

Contd.• The adult worms live singly, in pairs, or in coiled entangled masses in the

deep fascia or in the subcutaneous tissue.

• The females release actively motile, unsheathed microfilariae which migrate to the skin and eyes of infected subjects.

• They can survive in the body for 1-2 years.

• When a black fly again bites a diseased human at one of the infected sites, the microfilariae are taken up with the blood meal.

• They migrate from the gut of the vector into the thoracic muscles.

Contd.• They moult twice here and develop into infective larvae over a period of 6-

8 days.

• These larvae then migrate to the mouth parts of the black fly where they may be transmitted to humans at the next blood meal.

• The cycle is thus repeated.

Pathogenicity• The infection is transmitted by the bite of an infected female Simulium.

• The infective larvae remain localised in the skin and grow into adult worms.

• The pathological changes in the skin and eyes result from a hypersensitivity reaction to the dead or dying microfilaria.

• The incubation period in man is about one year.

• O.volvulus causes the disease Onchocerciasis in man.

• The adult worms live in the subcutaneous connective tissues.

Contd.• They do not invade the muscle or viscera.

• The pathological lesions in Onchocerciasis may be divided into two groups as follows:

1. Formation of subcutaneous fibrous nodules (Onchocercomas) caused by the adult worms.

2. Ocular lesions caused by microfilariae

3. Metabolites of adult worms may also be responsible for ocular lesions.

Contd.• The nodules are raised above the skin surface.

• They are painless and nonsuppurative.

• On section, they appear as a concentric mass of fibrous tissue with a honeycombed central area containing the adult worms of both sexes.

• Dead worms become calcified and initiate foreign body giant cell reaction.

• Actively motile microfilariae are found in subepithelial and deeper connective tissue in many areas of the body without any tissue reaction.

Contd.• Skin lesions such as dermatities associated with pruritus may be caused

by a “toxin” from larva or adult worm.

• A high eosinophilia is observed in such cases.

• Other complications which may be observed are:1. Development of hydrocele or even lymph scrotum.2. Elephantiasis of scrotum and legs.3. “Hanging groin” (seen in Africa).The atrophied, inelastic skin of the

groin hangs down in a fold containing enlarged, sclerosed femoral or inguinal lymph nodes.

• The skin shows lichenification and a mottled depigmentation(leopard skin).

Contd.• Ocular lesions-These are particularly seen in persons with nodules on head

or face.

• They result from the presence of microfilaria which may be found moving about in the substantia propria of the cornea and also in the anterior chamber.

• They can lead ultimately blindness.

• Because of the association of the vector with rivers, the condition is known as river blindness.

Clinical featuresocular

• Ocular involvement provides the common name associated with onchocerciasis, river blindness. The microfilariae migrate to the surface of the cornea. 

• Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides

• However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. 

• Over time the entire cornea may become opaque, thus leading to blindness. 

Laboratory diagnosis• The diagnosis of Onchocerciasis can be made by:

1. Demonstration of adult worms-These can be demonstrated inside the excised nodules.

2. Demonstration of microfilariae-These can be demonstrated in skin snips.

• Two to six skin snips are taken from iliac crests, buttocks, calves and shoulders.

• The skin is cleaned with spirit and allowed to dry before a piece of skin 2-3 mm in diameter and 0.5-1mm deep is taken.

• Biopsy specimens are placed in normal saline or distilled water on a slide or in the well of a microtitre plate for 30 minutes or longer.

Contd.• Then examined for microfilariae that migrate from the tissue.

• If no microfilariae are seen, the preparation should be left overnight and re-examined for the microfilariae.

• Live microfilariae can be seen moving vigorously in the medium by direct microscopy.

• In patients with ocular manifestations, small biopsied specimens of the corneal conjunctiva may yield the microfilariae.

• Live microfilariae may be demonstrated in the substantia propria of the cornea and in the anterior chamber of the eye by slit lamp examination.

Contd.• Rarely, the microfilariae may be found in the peripheral blood.

• A provocative test (Mazzotti test)-The appearance of a pruritic papular rash within 24 hours after an oral dose of 50 or 100 mg of diethylcarbamazine suggests the presence of cutaneous microfilaria.

• The reaction is caused by dead microfilaria of O.volvulus killed by the drug.

• Serological test-Cross reactivity of the antigens of O.volvulus with those of other nematodes, limit the usefulness of various serological tests.

• Recently, more specific enzyme immunoassays using recombinant O.volvulus antigens may help in diagnosing patients with suspected onchocerciasis.

Contd.• Polymerase chain reaction-Microfilarial antigens in skin samples may be

detected by polymerase chain reaction.

• Treatment-Treatment consists of surgical removal of detectable nodules (nodulectomy).

• It is simple, easy to perform and produces immediate results.

• Suramin was the first successful drug for the treatment of Onchocerciasis.

• It has lethal effect on adult worms.

• It is too toxic and significant side effects occur in 10-30 % of the patients.

Treatment contd.• Diethylcarbamazine is an effective microfilaricidal drug and produces

cutaneous and systemic side effects from death of the microfilariae.

• Ivermectin is as effective as diethylcarbamazine but has significantly fewer side effects.

• It does not kill adult worms but inhibits microfilarial release from female worms.

Prophylaxis• Onchocerciasis can be prevented by the application of insecticides to the

streams where the vector Simulium is breeding.

• Mass chemotherapy as a control measure is not recommended because the available drugs produce severe side effects.

Mansonella

Mansonella streptocerca• Mansonella streptocerca occurs in West and Central Africa.

• The adult worms live in the dermis, usually less than 1mm below the skin surface.

• The adult male measures 17-18 mm x 0.4 mm .

• The adult female measures 25-27mm x 0.6-0.8 mm.

• The microfilariae measure 180-240µm x 5 µm and are unsheathed.

• The tail end is bent in a crook like curve and the column of nuclei extends to the tail-tip.

Contd.• They are non-periodic.

• The microfilariae are found in the skin ingested by Culicoides spp. (midges) , the insect vectors.

• Microfilariae of M.streptocerca cause streptocerciasis.

• It is characterized by odema and thickning of the skin, hypopigmented macules, pruritus and papules.

• Diagnosis is made by demonstration and identification of characteristic microfilariae in the skin snips.

• Doc is Diethylcarbamazine.

Culicoides

Mf of Mansonella streptocerca

Mf of Mansonella streptocerca

Mansonella ozzardi• Mansonella ozzardi occurs in West Indies , and Central and South America.

• The common name is Ozzard’s filaria.

• Humans are the only known natural definitive hosts.

• The adult female measures 65-81mm x 0.21 –o.25 mm.

• Microfilariae are found in blood.

• They are small 150-200µm x 4.5 µm, unsheathed and non-periodic.

Mf of Mansonella ozzardi

Contd.• The tail end is sharply pointed and the column of nuclei does not extend to the

tail tip.

• Adult male and female worms live in the subcutaneous and connective tissues.

• The microfilariae are found in the blood, where they can be ingested by Culicoides spp. Or Simulium spp. ( Black flies), the insect vectors.

• M.ozzardi infections have been associated with cutaneous itching, pruritus, articular pains, subcutaneous inflammation, enlarged inguinal lymph nodes and vague abdominal symptoms accompanied by high eosinophilia.

• Diagnosis is made by demonstration of characteristic microfilariae in the blood and also in skin snips.

Mansonella perstans• Geographical Distribution- Africa and South America.

• Habitat- Adults worms are found in the mesenteric tissues , also in the pleural and pericardial cavities.

• Morphology – Adult worms. The male measures 4 cm in length by 0.06 mm in breadth.

• The female measures 7 cm in length by 0.12 mm in breadth .

Contd.• The distinguish features are:

1. Microscopically, cuticula appears.

2. The anterior end is provided with short cuticular shields, called epaulettes.

3. The tail end is split and presents a cuticular thickning forming two triangular appendages.

• Embroys- Mf. perstans are found in the peripheral blood by day as well as by night (non-periodic).

• The distinguish features are : I smaller in size, ii without any sheath, iii the tail end is blunt and , iv the nuclei extend to the tail-tip.

Mf of Mansonella perstans

Contd.• Life cycle- The worm passes its life cycle in two hosts:

1. In man , Also in chimpanzee and gorilla.

2. In insects, culicoides austeni and C.grahami.

• Like other microfilariae, Mf. Perstans follows the same developmental changes in culicoides.

• Pathogenicity- Generally non- pathogenic.

• Diagnosis- By finding the characteristic unsheathed microfilariae in blood.

Contd.• Treatment- No specific chemotherapy. Hetrazan has no effect on Mf.

perstans.

• Prophylaxis- Protection from insect bite.

Dirofilaria

Dirofilaria• Genus Dirofilaria includes D.immitis , D.repens, D.tenuis and D.ursi.

• These are common parasites of dog, cat and raccon.

• They can cause occasional Zoonotic infections in man.

Dirofilaria immitis• Common name is dog heart worm.

• D. immitis is a common parasite of dogs in the tropical , subtropical and warm temperate regions of the world.

• Human cases have been reported from the USA , Japan , Australia , Brazil and New Zealand.

• The adult worms inhabit the right heart and large blood vessels joining it, in dog.

• The female measures 25-30 cm in length and about 1mm in width.

Contd.• The male is smaller and measures 12-18 cm in length.

• Microfilariae are unsheathed, 300-325 µm in width.

• They are found in the blood, where they are ingested by mosquitoes.

• Dog is the definitive host and the mosquitoes are the intermediate hosts.

• The infective larval forms, from the proboscis of the mosquito , are injected into the subcutaneous tissue of the dog by the bite of the mosquito.

• The larvae enter into the circulation and ultimately find their way to the heart, where they develop into adults.

Contd.• The diagnosis in dogs may be made by observing circulating microfilariae in

the peripheral blood.

• When humans, are bitten by infected mosquitoes the larvae are incapable of completing their life cycle because they are in the wrong host.

• They lodge and obstruct pulmonary arteriole and develop into local granulomatous nodules.

• Microfilariae do not circulate in human blood.

• The diagnosis is made by histologic observation of larvae of D. immitis within the pulmonary granulomatous

• Blood examination reveals eosinophilia.

Other Dirofilaria species• Occasional human infections by other species of Dirofilaria have been

reported.

• D.repens , D. tenuis and D.ursi are the subcutaneous parasites of dog and cat, raccoon and bear respectively.

• However, these may also cause subcutaneous dirofilariasis in man.

Zoonotic Filariasis• Zoonotic filariasis occurs when humans are accidentally infected by filariae

normally found in animals.

• Dirofilaria spp. being one among them.

• Transmission occurs through mosquito bite.

• In human infection, parasite development is impaired and microfilariae are not produced.

• Dirofilariasis is a common zoonotic infection in Sri Lanka.

• Subconjunctival dirofilariasis caused by D. repens and subcutaneous dirofilariasis of the medial aspect of the left upper lid caused by D.repens has been reported from Karnataka.