Lymphatic FilariasisLymphatic FilariasisLymphatic FilariasisLymphatic Filariasis

•• Wucheria bancroftiWucheria bancroftiWucheria bancroftiWucheria bancrofti•• Brugia malayiBrugia malayi•• Lymphatic filariasisLymphatic filariasis

–– 119119 million infectedmillion infected119 119 million infectedmillion infected•• ElephantiasisElephantiasis

–– Manifestation of Manifestation of lymphatic filariasislymphatic filariasislymphatic filariasislymphatic filariasis

Morphology IMorphology Ip gyp gy•• Adult: White and threadAdult: White and thread--like. Two rings like. Two rings

of small papillae on the head.of small papillae on the head.Female:Female:55~~1010cm in lengthcm in lengthFemale:Female:55~~1010cm in lengthcm in lengthMale: Male: 22..55~~44cm and a curved tail with cm and a curved tail with

two copulatory spicules.two copulatory spicules.

Wuchereria Wuchereria MorphologyMorphology

10 cm 250 :m10 cm 250 :m

Adults ofAdults of Wuchereria bancroftiWuchereria bancroftiAdults of Adults of Wuchereria bancroftiWuchereria bancrofti

Ad lt i th l h ti lAdults occur in the lymphatic vessels

Distribution ofDistribution of Wucheria bancroftiWucheria bancroftiDistribution of Distribution of Wucheria bancroftiWucheria bancrofti

•• Broad equatorial beltBroad equatorial belt•• Africa, Middle East, Southeast Asia, IndoAfrica, Middle East, Southeast Asia, Indo--Pacific islands, Pacific islands,

P t f A t li d S th A iP t f A t li d S th A iParts of Australia and South AmericaParts of Australia and South America

HabitatHabitatHabitatHabitat

•• Adults live in lymphatic ducts. Adults live in lymphatic ducts. •• Usually near major lymph glands in lowerUsually near major lymph glands in lowerUsually near major lymph glands in lower Usually near major lymph glands in lower

half of bodyhalf of bodyR l j il ( i fil i ) i l hR l j il ( i fil i ) i l h•• Release juveniles (microfilariae) into lymphRelease juveniles (microfilariae) into lymph

•• Microfilariae carried to blood streamMicrofilariae carried to blood streamc o e c ed o b ood s ec o e c ed o b ood s e

Wuchereria bancroftiWuchereria bancrofti

•• Females release Females release j il i tj il i tjuveniles into juveniles into lymph lymph (ovoviviparous)(ovoviviparous)(ovoviviparous)(ovoviviparous)

•• microfilariae microfilariae c o ec o eswept into blood swept into blood streamstream

•• Mosquitoes Mosquitoes ingestingestingest ingest microfilariae microfilariae with blood mealwith blood meal

Wuchereria bancroftiWuchereria bancrofti

•• Penetrate Penetrate ffstomach of stomach of

mosquitomosquito

•• Develop in Develop in ppthoracic thoracic musclesmuscles

•• Develop into Develop into ppfilariform filariform juvenilesjuveniles

Wuchereria bancroftiWuchereria bancrofti

•• Migrate to the Migrate to the iiproboscisproboscis

•• Injected into Injected into human with human with blood mealblood meal

•• Mature in Mature in lymphatic lymphatic y py pductsducts

PeriodicityPeriodicityPeriodicityPeriodicity

•• Microfilariae in peripheral blood at Microfilariae in peripheral blood at periodic intervalsperiodic intervalspp

•• Wucheria bancroftiWucheria bancroftiI i h l bl d b tI i h l bl d b t 1010 0000 22 0000–– In peripheral blood between In peripheral blood between 1010::0000pmpm--22::0000amam

–– In blood of deep tissues during the dayIn blood of deep tissues during the day–– Coincides with feeding time of intermediate Coincides with feeding time of intermediate

hostshosts

Microfilariae of Microfilariae of Wuchereria bancroftiWuchereria bancrofti

Nocturnal periodicity of microfilariae

Phases of PathogenesisPhases of PathogenesisPhases of PathogenesisPhases of Pathogenesis

22 I fl t (A t ) PhI fl t (A t ) Ph22. Inflammatory (Acute) Phase. Inflammatory (Acute) PhaseCaused by antigens from adult wormsCaused by antigens from adult wormsI fl ti d t b t i l i f tiI fl ti d t b t i l i f tiInflammation due to bacterial infectionInflammation due to bacterial infectionAdults interfere with lymph flowAdults interfere with lymph flow

•• LymphedemaLymphedema•• LymphedemaLymphedema•• Inflammation of lymph channelsInflammation of lymph channels•• Inflammation of lymph nodesInflammation of lymph nodes

S tS t•• Symptoms:Symptoms:–– ChillsChills–– FeverFever

S ll d i f l l h dS ll d i f l l h d–– Swollen and painful lymph nodesSwollen and painful lymph nodes–– Swelling of reproductive organsSwelling of reproductive organs

•• Lasts Lasts 55--7 7 daysdays

Phases of PathogenesisPhases of PathogenesisPhases of PathogenesisPhases of Pathogenesis

33 Ob i (Ch i ) PhOb i (Ch i ) Ph33. Obstructive (Chronic) Phase. Obstructive (Chronic) Phase–– Lymph ducts become blockedLymph ducts become blocked

Fib i f i f dFib i f i f d–– Fibrosis of infected areasFibrosis of infected areas–– SwellingSwelling

•• Accumulation of lymphAccumulation of lymph•• Accumulation of lymph Accumulation of lymph •• Elephantiasis: accumulation of lymph in Elephantiasis: accumulation of lymph in

extremeties, fibrosis, and thickening of extremeties, fibrosis, and thickening of skinskinskin.skin.

–– Chyluria (lymph in the urine)Chyluria (lymph in the urine)

Affected AreasAffected AreasAffected AreasAffected Areas

•• LegsLegs•• ScrotumScrotum•• ArmsArms•• BrestBrest•• BrestBrest

Pathology of Pathology of Wuchereria bancroftiWuchereria bancrofti

Ob t ti h h tObstructive phase photos

ImpactsImpactsImpactsImpacts

•• Rarely fatalRarely fatal•• DisfiguringDisfiguringg gg g

–– 40 40 million peoplemillion people

•• DisabilityDisabilityDisabilityDisability–– Daily functionsDaily functions–– Sexual disabilitySexual disabilitySexual disabilitySexual disability

•• WHO: second leading cause of permanent and WHO: second leading cause of permanent and longlong term disability in the world (after leprosy)term disability in the world (after leprosy)longlong--term disability in the world (after leprosy)term disability in the world (after leprosy)

•• Social impactsSocial impacts

Wuchereria Wuchereria DiagnosisDiagnosis

HistoryHistorySymptomsSymptomsSymptomsSymptomsMicrofilariMicrofilari

i bl di bl da in blooda in blood

Demonstration of microfilariae in bloodDemonstration of microfilariae in bloodPCR diagnosisPCR diagnosis

Microfilariae of Microfilariae of Wuchereria bancroftiWuchereria bancrofti

Microfilariae are seen in blood smears and are DIAGNOSTIC

bl d i fil iblood microfilaria

1 – direct examination (thick or thin smear)1 – direct examination (thick or thin smear)

2 – Knotts concentration techniqueq

3 – millipore filtration

4 – antigen capture

Treatment and PreventionTreatment and PreventionTreatment and PreventionTreatment and Prevention

•• DiethylDiethyl--carbamazine and Ivermectincarbamazine and Ivermectin–– Kills adults and microfilariaeKills adults and microfilariae

•• Edematous limbsEdematous limbsP b dP b d–– Pressure bandagesPressure bandages

–– Surgical removal of elephantoid tissueSurgical removal of elephantoid tissueElimination of mosquitoes.Protection of people from mosquitoes bitibiting.

Brugia malayiBrugia malayi

Causes Malayan filariasis

Distribution - Orient, South Pacific, and Southern Asia to India overlaps with Wuchereria bancroftiAsia to India – overlaps with Wuchereria bancrofti - but does not occur in Africa or South America

Brugia malayiBrugia malayiBrugia malayiBrugia malayiMorphology and life cycle is similar to that of Wuchereria bancroftibancrofti

Brugia malayiBrugia malayig yg yPathology - Adults live in lymphatic vessels of the arms and legs and cause elephantiasis in these regionslegs and cause elephantiasis in these regions

Brugia malayi microfilaria thick film (hematoxylin stain) microBrugia malayi microfilaria, thick film (hematoxylin stain) micro

Onchocerca volvulusOnchocerca volvulusCausative agent of Onchocerciasis or River Blindness

DISTRIBUTION – Areas of Africa, Arabia, Guatemala, Mexico, Venezuela and Colombia

DISTRUBUTION MAPDISTRUBUTION MAPDISTRUBUTION MAPDISTRUBUTION MAP

Onchocerca volvulus Onchocerca volvulus MorphologyMorphology

10 cm

Adults of Adults of Onchocerca volvulusOnchocerca volvulus

Skin nodule cut open to reveal adults coiled together

Microscopic section showing adults and scar tissue reaction around them forming the nodule

Microfilariae of Microfilariae of Onchocerca volvulusOnchocerca volvulus

Unsheathed microfilariae occur in the skin, never the bloodsteam

Life Cycle ofLife Cycle of Onchocerca volvulusOnchocerca volvulus1. Adults live in coiled masses encapsulated punder the skin.

Life Cycle of Life Cycle of Onchocerca volvulusOnchocerca volvulus2. Females produce microfilariae

- Microfilariae of Onchocerca NEVEROnchocerca NEVER invade the bloodstream.

Life Cycle of Life Cycle of Onchocerca volvulusOnchocerca volvulus3. Microfilariae in the skin are ingested by the g yblack fly intermediate host, Simulium damnosum, when a blood meal is taken.

Life Cycle ofLife Cycle of Onchocerca volvulusOnchocerca volvulus

- Nodules are most common below the waist in region of Africa.

- Nodules are on the head and above the waist in Central & South America.

Life Cycle of Life Cycle of Onchocerca volvulusOnchocerca volvulus4. Parasites develop to J3’s in the musculature 3of the black fly and migrate to the mouthparts.

5. J3’s are inoculated into the skin when black fly bites.

Adults mature in a yearAdults mature in a year within subcutaneous nodules.

Onchocerca volvulus Onchocerca volvulus Life CycleLife Cycle

Black flySimulium damnosum

SimuliumSimulium

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus

ADULTS hADULTS cause onchocercomas

Nodules are about ½ -1 inch inNodules are about ½ 1 inch in diameter.

Nodules are relatively benign and cause only some disfigurementdisfigurement.

Onchocerca volvulus Onchocerca volvulus Skin NodulesSkin Nodules

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulusMICROFILARIAE cause 3 severe problems. This is the only filarial worm in which microfilariae are pathogenic!worm in which microfilariae are pathogenic!

1 Microfilariae in the skin cause1. Microfilariae in the skin cause severe dermatitis

- skin becomes thickening, discoloration, and cracking.

-leading to secondary bacterial infectionsinfections

- itching is so severe some people g p phave committed suicide

This woman has leopard skin and onchocercal skinskin and onchocercal skin lesions on both legs

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus3. Microfilariae invade the eyeeye

-blindness occur asblindness occur as microfilariae die in the eye

- fibrosis causes clouding of cornea and aqueous and vitreous humors resulting invitreous humors resulting in blindness

- fibrosis of the eye is a slow development and most affected persons are adults over 40 years old!

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus

In many parts of Africa, the sighted young are ibl f l di h ld bli d d lresponsible for leading the older blind adults.

Diagnosis of Diagnosis of Onchocerca volvulusOnchocerca volvulus(1)Microfilaria in skin

snips!snips!

- snip must be bloodless so as to not to confuse with

i fil i th tmicrofilariae that may be circulating i th bl d tin the bloodstream.

(2) Adult worms in i d ki d lexcised skin nodule.

Onchocerca volvulus Onchocerca volvulus DiagnosisDiagnosis

HistoryHistorySymptomsSymptomsMicrofilariMicrofilaria in a in nodulesnodules

Onchocerca volvulusOnchocerca volvulus

TREATMENT

Ivermectin!

SimuliumSimulium spp. spp. The vector of onchocerciasis inThe vector of onchocerciasis inThe vector of onchocerciasis in The vector of onchocerciasis in the old and New Worlds.the old and New Worlds.the old and New Worlds.the old and New Worlds.

An infected female blackfly takes a blood meal from a host. The hosts skin is stretched by the fly’s apical teeth and cut bythe fly s apical teeth and cut by

its mandible.

Onchocerciasis is linked with fast flowing rivers where

Simulium blackflies breed.

Loa loaLoa loaGeographic DistributionGeographic Distribution

Loa loaLoa loaProgressive KeratitisProgressive Keratitis

Loa loa (the “eye worm”)

Loa loa adult in Calabar swelling x section

Calabar swelling

Heartworms (Dirofilaria immitis):

Stages ofStages of Dirofilaria immitisDirofilaria immitisAdult male: 20-12cm longg

Adult female: 30-35 cm long

UnsheathedUnsheathed microfilaria in dog blood -DIAGNOSTIC

Adults coiled in right side of dog heartof dog heart

Heartworms (Dirofilaria immitis):

Pathology ofPathology of Dirofilaria immitisDirofilaria immitis

PATHOLOGY caused by adult wormsworms.

First signs of infection involve exercise intoleranceexercise intolerance

• due to inadequate blood supply to lungssupply to lungs

• infected dogs cough, have shortness of breath, andshortness of breath, and tire rapidly.

2. Eventually the dog suffers2. Eventually the dog suffers congestive heart failure-usually after a period of

iexercise.

Dirofilaria immitisDirofilaria immitisPREVENTION - chemoprophylaxis

2 drugs are used: ivermectin (in Heartgard) and milbemycin2 drugs are used: ivermectin (in Heartgard) and milbemycin oxime (in Sentinel and Interceptor)

Human Cases ofHuman Cases of Dirofilaria immitisDirofilaria immitis

HUMAN INFECTIONS of Dirofilaria immitis are rare.

Larvae are killed by the host reaction and scar tissue nodules form in lungs around worms

• Symptoms are coughing and chest pain.

In only 4 cases were adult worms recovered from the humanIn only 4 cases were adult worms recovered from the human heart. These were found incidentally at autopsy and were not related to the death of the patient.p