Insect Transmitted NematodesInsect Transmitted Nematodes

• Filarial worms Filarial worms

• Tissue dwelling parasitesTissue dwelling parasites

• Order SpiruridaOrder Spirurida

• Transmitted to definitive host through Transmitted to definitive host through insect biteinsect bite

Filarial Nematodes Filarial Nematodes

1. Tissue-dwelling nematodes (not in digestive tract)

2. Possess a unique life cycle stage – the microfilaria - between the egg and J1

• Egg microfilaria J1 J2 J3 J4 Adult

• these are present in the bloodstream or skin of the definitive host.

3. Filarial worms utilize arthropods as vectors.

Lymphatic FilariasisLymphatic Filariasis

• Wucheria bancroftiWucheria bancrofti

• Brugia malayiBrugia malayi

• Lymphatic filariasisLymphatic filariasis

– 119 million infected119 million infected

• ElephantiasisElephantiasis

– Manifestation of Manifestation of lymphatic filariasislymphatic filariasis

Distribution of Distribution of Wucheria bancroftiWucheria bancrofti

• Broad equatorial beltBroad equatorial belt

• Africa, Middle East, Southeast Asia, Indo-Pacific islands, Africa, Middle East, Southeast Asia, Indo-Pacific islands, Parts of Australia and South AmericaParts of Australia and South America

HabitatHabitat

• Adults live in lymphatic ducts. Adults live in lymphatic ducts.

• Usually near major lymph glands in lower Usually near major lymph glands in lower half of bodyhalf of body

• Release juveniles (microfilariae) into lymphRelease juveniles (microfilariae) into lymph

• Microfilariae carried to blood streamMicrofilariae carried to blood stream

Lymphatic SystemLymphatic System

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

• Redirects lymph back Redirects lymph back into the blood streaminto the blood stream

Adults of Adults of Wuchereria bancroftiWuchereria bancrofti

Adults occur in the lymphatic vessels

Wuchereria bancroftiWuchereria bancrofti

Wuchereria bancroftiWuchereria bancrofti

• Females release Females release juveniles into lymph juveniles into lymph (ovoviviparous)(ovoviviparous)

• microfilariae swept microfilariae swept into blood streaminto blood stream

• Mosquitoes ingest Mosquitoes ingest microfilariae with microfilariae with blood mealblood meal

Wuchereria bancroftiWuchereria bancrofti

• Penetrate Penetrate stomach of stomach of mosquitomosquito

• Develop in Develop in thoracic thoracic musclesmuscles

• Develop into Develop into filariform filariform juvenilesjuveniles

Wuchereria bancroftiWuchereria bancrofti

• Migrate to the Migrate to the proboscisproboscis

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

• Mature in Mature in lymphatic lymphatic ductsducts

PeriodicityPeriodicity

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

• Wucheria bancroftiWucheria bancrofti– In peripheral blood between 10:00pm-2:00amIn peripheral blood between 10:00pm-2:00am– 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

PathogenesisPathogenesis

• Depends on inflammatory and immune Depends on inflammatory and immune responseresponse

• Clinical manifestation variesClinical manifestation varies

Phases of PathogenesisPhases of Pathogenesis

1.1. Asymptomatic PhaseAsymptomatic PhaseHigh levels of microfilaremiaHigh levels of microfilaremiaImmune response down regulatedImmune response down regulated

Sometimes no symptoms and no Sometimes no symptoms and no microfilaremiamicrofilaremia

• People in endemic areasPeople in endemic areas

Sometimes lymphatic inflammation Sometimes lymphatic inflammation and no microfilaremia and no microfilaremia

• Travelers who get infectedTravelers who get infected

Phases of PathogenesisPhases of Pathogenesis

2. Inflammatory (Acute) Phase2. Inflammatory (Acute) PhaseCaused by antigens from adult wormsCaused by antigens from adult wormsInflammation due to bacterial infectionInflammation due to bacterial infectionAdults interfere with lymph flowAdults interfere with lymph flow

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

– ChillsChills– FeverFever– Swollen and painful lymph nodesSwollen and painful lymph nodes– Swelling of reproductive organsSwelling of reproductive organs

• Lasts 5-7 daysLasts 5-7 days

Phases of PathogenesisPhases of Pathogenesis

3. Obstructive (Chronic) Phase3. Obstructive (Chronic) Phase– Lymph ducts become blockedLymph ducts become blocked– Fibrosis of infected areasFibrosis of infected areas– SwellingSwelling

• 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 skin.skin.

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

Affected AreasAffected Areas

• LegsLegs• ScrotumScrotum• ArmsArms• BrestBrest

Pathology of Pathology of Wuchereria bancroftiWuchereria bancrofti

Obstructive phase photos

ImpactsImpacts

• Rarely fatalRarely fatal• DisfiguringDisfiguring

– 40 million people40 million people

• DisabilityDisability– Daily functionsDaily functions

– Sexual disabilitySexual disability

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

• Social impactsSocial impacts

DiagnosisDiagnosis

• Demonstration of microfilariae in bloodDemonstration of microfilariae in blood

• PCR diagnosisPCR diagnosis

Microfilariae of Microfilariae of Wuchereria bancroftiWuchereria bancrofti

Microfilariae are seen in blood smears and are DIAGNOSTIC

• worms are 230-320 µm long

TreatmentTreatment

• Diethyl-carbamazine and IvermectinDiethyl-carbamazine and Ivermectin– Kills adults and microfilariaeKills adults and microfilariae

• Edematous limbsEdematous limbs– Pressure bandagesPressure bandages– Surgical removal of elephantoid tissueSurgical removal of elephantoid tissue

EpidemiologyEpidemiology

• TimingTiming

• Takes 6-12 months for females to release Takes 6-12 months for females to release microfilariaemicrofilariae

• Produce microfilariae for 5-10 yearsProduce microfilariae for 5-10 years

• How do you get infected?How do you get infected?– Bite from infected mosquitoBite from infected mosquito

Brugia malayiBrugia malayi

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

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

Brugia malayiBrugia malayiPathology - Adults live in lymphatic vessels of the arms and legs and cause elephantiasis in these regions Difference from Wuchereria?  

Heartworms (Dirofilaria immitis):

Heartworms (Dirofilaria immitis):

Stages ofStages of Dirofilaria immitis Dirofilaria immitis

Unsheathed microfilaria in dog blood - DIAGNOSTIC

Adult male: 6-12 inches long

Adult female: 12-16 inches long

Adults coiled in right side of dog heart

Distribution Distribution

Pathology ofPathology of Dirofilaria immitis Dirofilaria immitis

PATHOLOGY caused by adult worms.

First signs of infection involve exercise intolerance

• due to inadequate blood supply to lungs

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

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

 

Dirofilaria immitisDirofilaria immitisPREVENTION - chemoprophylaxis

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

- How taken?

- How does it work?

- How long to treat?

Human Cases ofHuman Cases of Dirofilaria immitis Dirofilaria immitis

HUMAN INFECTIONS of Dirofilaria immitis are rare (~70 cases).

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 human heart. These were found incidentally at autopsy and were not related to the death of the patient.

Onchocerca volvulusOnchocerca volvulus

Causative agent of Onchocerciasis or River Blindness

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

Life Cycle ofLife Cycle of Onchocerca volvulus Onchocerca 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 ofLife Cycle of Onchocerca volvulus Onchocerca volvulus1. Adults live in coiled masses encapsulated under the skin.

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

- Microfilariae of Onchocerca NEVER invade the bloodstream.

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

Simulium

Life Cycle of Life Cycle of Onchocerca volvulusOnchocerca volvulus 4. Parasites develop to J3’s in the musculature of the black fly and migrate to the mouthparts.

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

Adults mature in a year within subcutaneous nodules.

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

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus

ADULTS cause onchocercomas

Nodules are about ½ -1 inch in diameter.

Nodules are relatively benign and cause only some disfigurement.

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus MICROFILARIAE cause 3 severe problems. This is the only filarial

worm in which microfilariae are pathogenic!

1. Microfilariae in the skin cause severe dermatitis

- skin becomes thickening, discoloration, and cracking.  -leading to secondary bacterial infections - itching is so severe some people have committed suicide

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus 2. Microfilariae in skin cont:

- in parts of Africa, the skin of the scrotum and inguinal area loses its elasticity causing hanging groin!

Pathology of Pathology of Onchocerca volvulusOnchocerca volvulus 3. Microfilariae invade the eye   -blindness occur as microfilariae die in the eye  - fibrosis causes clouding of cornea and aqueous and vitreous 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 responsible for leading the older blind adults.

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

- snip must be bloodless so as to not to confuse with microfilariae that may be circulating in the bloodstream.

(2) Adult worms in excised skin nodule.

 

Onchocerca volvulusOnchocerca volvulus  TREATMENT

Ivermectin!

Onchocerca volvulusOnchocerca volvulus PREVENTION – control of

intermediate host black flies!

- Larval black flies live in fast moving rivers

- After development in water, adults emerge and are blood feeders

Guinea Worm (Guinea Worm (Dracunculus Dracunculus medinensismedinensis))

Guinea worm (Dracunculus medinensis):• transmitted by infected copepods in drinking water • larvae move into the body cavity• female adult migrates to the subcutaneous tissue, causes an ulcer/blister, and releases eggs through hole when host comes in contact with water

Guinea worm (Dracunculus medinensis):• traditionally removed by winding the worm around a matchstick over the course of several days• this may be the basis for the Caduceus symbol used in the medical field

Guinea Worm (Guinea Worm (Dracunculus Dracunculus medinensismedinensis))