Case 12

1. Case 12 Andrea De Mesa

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

3. Filariasis

4. Diagnosis • Filariasis • Caused by very small worm * Wuchereria bancrofti * Brugia malayi • Endemic in the southern part of the country • MOT: skin penetration

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

6. Lymphatic filariasis • Lymphatic filarial worms • Wuchereria bancrofti • Brugia malayi & timori • In tropical areas: SE Asia, India, Indonesia, China, South Pacific, Central America, Caribbean • 120 million infected • Vectored by various mosquitoes • Show different periodicity • Larval stages (microfilaria) circulate in blood at different times, corresponding to times when vector feeds

7. Generalized life cycle • 1st stage larvae (microfilaria=mf) circulating in blood of human ingested as mosquito takes blood meal • Develop over 1-3wks in mosquito to infective 3rd stage larvae, deposited onto skin and enter blood stream • Mature in lymphatics, mate, produce mff

9. Morphology • Adults • Females 80-100 mm long, males half • White, threadlike, in lymphatics • Females bear live young (mff) • Microfilaria • Sheathed • In blood Sheath

10. Lymphatic Microfilaria

11. Lymphatic Filariasis • Initially asymptomatic until mechanical damage caused by highly motile adult worms in lymphatic channels induce an inflammatory response • Inflammation leads to valve damage, flow inhibition, fibrosis, collateral channel development • Bancroftian filariasis usually in inguinal, epitrochlear, axillary, testicular areas • Brugian filariasis usually in inguinal or axillary area, affecting distal extremities • Early disease • Retrograde lymphangitis, fever, chills, malaise for 3-15 days, occurring several times/year • Lymph node abscesses in brugian type • Can get marked eosinophilia (1000->2500 cu mm)

12. Tropical Pulmonary Eosinophilia • Sequestration of mff in lungs, no microfilaremia • Allergic response • Recurring episodes of wheezing or nocturnal paroxysmal cough • Persistent hypereosinophilia (>3000/ cu mm), high IgE levels, miliary lesions on xray • Lasts for weeks • Tx as for bancroftian filariasis

13. Chronic disease • Prolonged infection leads to obstructive disease • Chyluria w/ obstruction of renal lymphatics • Hydrocele most common complaint in genital area • Lymphadema & elephantiasis most common in extremities (full leg w/ bancroftian, lower leg w/ brugian)

14. Elephantiasis of Extremities

15. LABORATORYEXAMS

16. Thick blood Smear • Thick blood smear – most commonly used for detection of microfilaremia - taken 8pm-4am (filarial species have nocturnal periodicity) • In many chronic infections, microfilariae may not be demosntrable in the peripheral blood. Among the reasons include: a. low intensity infection b. dead worms c. obstructed lymphatics

17. For low infections, perform filtration using Nucleopore filter or Knott’s method • Ultrasonography – may be able to demonstate live worms in the lymphatics • Contrast lymphangiography and Lymphscintigraphy using radiolabelled albumin or dextran – may be able to demonstrate obstructed lymphatics

18. MANAGEMENT & PHARMACOKINETICS • The most useful nonspecific procedure in swelling of both lower limbs is pressure bandaging using 6-inch strips of bath toweling, covering with cotton elastic bandage and an outer muslin bandage to keep out dirt. • Exercise is required to prevent cyanosis and hasten reduction of the lymphedema

19. Diethylcarbamazine • DEC for treatment of infections with these parasites, given its high order of therapeutic efficacy and lack serious toxicity. • Synthetic piperazine derivative, given at dose of 6mg/kg/BW, orally for 12 days, given preferably in divided doses after meals. • Rapidly absorbed in GIT • Peak plasma level is reached within 1-2 hrs

20. Plasma half-life is 2-3 hrs in presence of acidic urine but about 10 hrs if urine is alkaline. • Drug rapidly equilibrates with all tissue except fat • It is excreted, principally in the urine unchanged • It immobilized microfilariae (which results in their displacement in tissues) and alters their surface structure, making them more susceptible to destruction by host defense mechanisms. • Mode of action against adult worm is unknowm

21. Ivermectin • Semisynthetic macrocyclic lactone • Derived from the soil actinomycete, Steptomyces avermitilis • Given orally at 200-400μg/kg for 12 days • The drug is rapidly absorbed, reaching maximum plasma concentration at 4 hrs • Has a wide tissue distribution • Half life is 11 hrs • Excretion is almost exclusively in the feces

22. Ivermectin • By opening glutamate-gated chloride channels (found only in invertebrates) and increasing chloride conductance • Thru binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an increase in transmission leading to motor paralysis. • Side effects include: skin rashes, fever, giddiness, headaches and pain in muscles, joints and lymph gland • In general, the drug is well tolerated

23. THANK YOU FORYOUR ATTENTION. Enjoy the rest of your day!