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.
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
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.
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.
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
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
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.
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
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