Case 12Case 12

Andrea De MesaAndrea De Mesa

Case DescriptionCase Description

MG, a native from Leyte, was MG, a native from Leyte, was brought to Manila and admitted to brought to Manila and admitted to your hospital because of swelling of your hospital because of swelling of both lower extremities and scrotal both lower extremities and scrotal edema, noted for the past 2 weeks.edema, noted for the past 2 weeks.

FilariasisFilariasis

DiagnosisDiagnosis

FilariasisFilariasis Caused by very small wormCaused by very small worm

* Wuchereria bancrofti* Wuchereria bancrofti

* Brugia malayi* Brugia malayi Endemic in the southern part of the Endemic in the southern part of the

countrycountry MOT: skin penetrationMOT: skin penetration

ELEPHANTIASISELEPHANTIASIS Massive swelling, esp. of the genitalia and Massive swelling, esp. of the genitalia and

lower extremities, resulting from obstruction lower extremities, resulting from obstruction of lymphatic vessels, for example by filarial of lymphatic vessels, for example by filarial parasites, malignancies, neurofibromatosis, parasites, malignancies, neurofibromatosis, or a familial congenital disease (Milroy's or a familial congenital disease (Milroy's disease). Prolonged swelling can cause an disease). Prolonged swelling can cause an increase in interstitial fibrous tissue and skin increase in interstitial fibrous tissue and skin puckering or breakdown. In patients with puckering or breakdown. In patients with parasitic elephantiasis (i.e, the filarial parasitic elephantiasis (i.e, the filarial diseases, which are common in the tropics), diseases, which are common in the tropics), single-dose therapy with ivermectin or single-dose therapy with ivermectin or ivermectin plus albendazole destroys ivermectin plus albendazole destroys immature but not adult worms immature but not adult worms

Lymphatic filariasisLymphatic filariasis Lymphatic filarial wormsLymphatic filarial worms

Wuchereria bancroftiWuchereria bancrofti Brugia malayi & timoriBrugia malayi & timori

In tropical areas:In tropical areas:SE Asia, India, Indonesia,SE Asia, India, Indonesia,China, South Pacific, CentralChina, South Pacific, CentralAmerica, CaribbeanAmerica, Caribbean

120 million infected120 million infected Vectored by various mosquitoesVectored by various mosquitoes Show different periodicityShow different periodicity

Larval stages (microfilaria) Larval stages (microfilaria) circulate in blood atcirculate in blood at

different times, corresponding to different times, corresponding to times whentimes when

vector feedsvector feeds

Generalized life cycleGeneralized life cycle 11stst stage larvae stage larvae

(microfilaria=mf) (microfilaria=mf) circulating in blood of circulating in blood of human ingested as human ingested as mosquito takes blood mosquito takes blood mealmeal

Develop over 1-3wks in Develop over 1-3wks in mosquito to infective 3mosquito to infective 3rdrd stage larvae, deposited stage larvae, deposited onto skin and enter blood onto skin and enter blood streamstream

Mature in lymphatics, Mature in lymphatics, mate, produce mffmate, produce mff

MorphologyMorphology

AdultsAdults Females 80-100 mm long, males halfFemales 80-100 mm long, males half White, threadlike, in lymphaticsWhite, threadlike, in lymphatics Females bear live young (mff)Females bear live young (mff)

MicrofilariaMicrofilaria SheathedSheathed In bloodIn blood

Sheath

Lymphatic MicrofilariaLymphatic MicrofilariaWuchereria bancroftiWuchereria bancrofti Brugia Brugia sppspp

250-300 250-300 μμmm

Pointed tailPointed tail

Nuclei stop short of tipNuclei stop short of tip

Nuclei discrete, not Nuclei discrete, not smudgedsmudged

175-230 175-230 μμmm

Tapered tail w/nuclei to tipTapered tail w/nuclei to tip

A constriction separates last 2 A constriction separates last 2 nuclei (subterminal & terminal)nuclei (subterminal & terminal)

Sheath of Sheath of B. malayiB. malayi stains pink stains pink w/ Giemsaw/ Giemsa

Lymphatic FilariasisLymphatic Filariasis Initially asymptomatic until mechanical damage Initially asymptomatic until mechanical damage

caused by highly motile adult worms in lymphatic caused by highly motile adult worms in lymphatic channels induce an inflammatory responsechannels induce an inflammatory response

Inflammation leads to valve damage, flow Inflammation leads to valve damage, flow inhibition, fibrosis, collateral channel developmentinhibition, fibrosis, collateral channel development

Bancroftian filariasis usually in inguinal, Bancroftian filariasis usually in inguinal, epitrochlear, axillary, testicular areasepitrochlear, axillary, testicular areas

Brugian filariasis usually in inguinal or axillary Brugian filariasis usually in inguinal or axillary area, affecting distal extremitiesarea, affecting distal extremities

Early diseaseEarly disease Retrograde lymphangitis, fever, chills, malaise for 3-15 Retrograde lymphangitis, fever, chills, malaise for 3-15

days, occurring several times/yeardays, occurring several times/year Lymph node abscesses in brugian typeLymph node abscesses in brugian type Can get marked eosinophilia (1000->2500 cu mm)Can get marked eosinophilia (1000->2500 cu mm)

Tropical Pulmonary Tropical Pulmonary EosinophiliaEosinophilia

Sequestration of mff in lungs, no Sequestration of mff in lungs, no microfilaremiamicrofilaremia

Allergic responseAllergic response Recurring episodes of wheezing or Recurring episodes of wheezing or

nocturnal paroxysmal coughnocturnal paroxysmal cough Persistent hypereosinophilia (>3000/ cu Persistent hypereosinophilia (>3000/ cu

mm), high IgE levels, miliary lesions on mm), high IgE levels, miliary lesions on xrayxray

Lasts for weeksLasts for weeks Tx as for bancroftian filariasisTx as for bancroftian filariasis

Chronic diseaseChronic disease

Prolonged infection leads to Prolonged infection leads to obstructive diseaseobstructive disease

Chyluria w/ obstruction of renal Chyluria w/ obstruction of renal lymphaticslymphatics

Hydrocele most common complaint in Hydrocele most common complaint in genital areagenital area

Lymphadema & elephantiasis most Lymphadema & elephantiasis most common in extremities (full leg w/ common in extremities (full leg w/ bancroftian, lower leg w/ brugian)bancroftian, lower leg w/ brugian)

Elephantiasis of Elephantiasis of ExtremitiesExtremities

LABORATORYLABORATORYEXAMSEXAMS

Thick blood SmearThick blood Smear Thick blood smear – most commonly used Thick blood smear – most commonly used

for detection of microfilaremiafor detection of microfilaremia - taken 8pm-4am (filarial species have - taken 8pm-4am (filarial species have

nocturnal periodicity)nocturnal periodicity) In many chronic infections, microfilariae In many chronic infections, microfilariae

may not be demosntrable in the peripheral may not be demosntrable in the peripheral blood. Among the reasons include:blood. Among the reasons include:

a. low intensity infectiona. low intensity infection b. dead wormsb. dead worms c. obstructed lymphaticsc. obstructed lymphatics

For low infections, perform filtration For low infections, perform filtration using using Nucleopore filterNucleopore filter or or Knott’s Knott’s methodmethod

UltrasonographyUltrasonography – may be able to – may be able to demonstate live worms in the demonstate live worms in the lymphaticslymphatics

Contrast lymphangiographyContrast lymphangiography and and LymphscintigraphyLymphscintigraphy using using radiolabelled albumin or dextran – may radiolabelled albumin or dextran – may be able to demonstrate obstructed be able to demonstrate obstructed lymphaticslymphatics

MANAGEMENT & MANAGEMENT & PHARMACOKINETICSPHARMACOKINETICS

The most useful nonspecific The most useful nonspecific procedure in swelling of both lower procedure in swelling of both lower limbs is pressure bandaging using 6-limbs is pressure bandaging using 6-inch strips of bath toweling, covering inch strips of bath toweling, covering with cotton elastic bandage and an with cotton elastic bandage and an outer muslin bandage to keep out dirt.outer muslin bandage to keep out dirt.

Exercise is required to prevent Exercise is required to prevent cyanosis and hasten reduction of the cyanosis and hasten reduction of the lymphedemalymphedema

DiethylcarbamazineDiethylcarbamazine

DEC for treatment of infections with these DEC for treatment of infections with these parasites, given its high order of parasites, given its high order of therapeutic efficacy and lack serious therapeutic efficacy and lack serious toxicity.toxicity.

Synthetic piperazine derivative, given at Synthetic piperazine derivative, given at dose of 6mg/kg/BW, orally for 12 days, dose of 6mg/kg/BW, orally for 12 days, given preferably in divided doses after given preferably in divided doses after meals.meals.

Rapidly absorbed in GITRapidly absorbed in GIT Peak plasma level is reached within 1-2 hrsPeak plasma level is reached within 1-2 hrs

Plasma half-life is 2-3 hrs in presence of Plasma half-life is 2-3 hrs in presence of acidic urine but about 10 hrs if urine is acidic urine but about 10 hrs if urine is alkaline.alkaline.

Drug rapidly equilibrates with all tissue Drug rapidly equilibrates with all tissue except fatexcept fat

It is excreted, principally in the urine It is excreted, principally in the urine unchangedunchanged

It immobilized microfilariae (which results in It immobilized microfilariae (which results in their displacement in tissues) and alters their their displacement in tissues) and alters their surface structure, making them more surface structure, making them more susceptible to destruction by host defense susceptible to destruction by host defense mechanisms. mechanisms.

Mode of action against adult worm is Mode of action against adult worm is unknowmunknowm

IvermectinIvermectin

Semisynthetic macrocyclic lactoneSemisynthetic macrocyclic lactone Derived from the soil actinomycete, Derived from the soil actinomycete,

Steptomyces avermitilisSteptomyces avermitilis Given orally at 200-400Given orally at 200-400μμg/kg for 12 daysg/kg for 12 days The drug is rapidly absorbed, reaching The drug is rapidly absorbed, reaching

maximum plasma concentration at 4 hrsmaximum plasma concentration at 4 hrs Has a wide tissue distributionHas a wide tissue distribution Half life is 11 hrsHalf life is 11 hrs Excretion is almost exclusively in the fecesExcretion is almost exclusively in the feces

IvermectinIvermectin

By opening glutamate-gated chloride channels By opening glutamate-gated chloride channels (found only in invertebrates) and increasing (found only in invertebrates) and increasing chloride conductancechloride conductance

Thru binding to a novel allosteric site on the Thru binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an acetylcholine nicotinic receptor to cause an increase in transmission leading to motor increase in transmission leading to motor paralysis.paralysis.

Side effects include: skin rashes, fever, Side effects include: skin rashes, fever, giddiness, headaches and pain in muscles, giddiness, headaches and pain in muscles, joints and lymph glandjoints and lymph gland

In general, the drug is well toleratedIn general, the drug is well tolerated

THANK YOU FORTHANK YOU FORYOUR YOUR

ATTENTION.ATTENTION.Enjoy the rest of your day!Enjoy the rest of your day!