Filarial Worms

7 November 2011

I. Filarial diseases A. Introduction 1. Superfamily Filaroidea a. Wuchereria bancrofti b. Brugia malayi c. Onchocerca volvulus d. Loa loa e. Mansonella perstans f. M. ozzardi g. M. streptocerca 2. blood and tissue habitats-live in blood of tissues 3. vector transmission 4. ovoviviparous- adult females. Eggs hatch in uterus, microfilariae(mf) released 5. microfilaria a. advanced embryos- not as developed as L1 in other species, they are instead called advanced embryo b. sheath- maybe sheathed- flexible egg shell- covering membrane-blood dwelling spp. c. long-lived- survive in blood for many years d. vector blood meal- ingested with blood meal by suitable vector e. identification nuclei- stain mf, location of nuclei f. periodicity- mf in peripheral blood only at certain times of day. Ex. W. bancrofti-maximum # of mf in peripheral blood during 10 PM to 2 AM. Vector=night-feeding mosquito. Day-mf in blood vessels of deep tissue- primary in lungs. Causes-physiology of host while sleeping. Decreases body time and H2O excretion by kidneys and increases body acidity. II. Wuchereria bancrofti. Elephantiasis, lymphatic filariasis A. Life cycle- adult worms live in major lymphatic ducts of humans- females- 8-10 cm, males-40mm.sheathed mf. 1. Periodicity 2. mosquito- Mf in lymphbloodingested by mosquito. Inside mosquitomoltL1L2L3-infective stage. L3 into proboscis, mosquito injected- lubricant, anticoagulant. L3 injected into host. L3 in skin of phlymphaticmolt to L4 molt to adult B. Pathology 1. incubation-asymptomatic, no detectable microfilaremia(mf in blood). ELISAdetect antigen. 2. acute(=inflammatory) response to antigen released from degenerating adults. a. episodic adenolymphangitis- (ADL)- inflammation of lymph nodes, inguinal, attacks of fever, chills + edema 3. chronic(=obstructive) 10-20 years after 1st exposure. Lymph tissue blockedworms, granulomas, fibrous connective tissue a. Grade I lymphedema- transient+soft, pressure- pit forms in skin. Treatment- rest and elevation of limb.

b. Grade II lymphedema-hard + permanent-does not pit on pressure. c. Grade III lymphedema-subcutaneous thickening outer skin layer. Hypertrophy-increase cell sizehyperkeratosis- nodules and fissures. d. Elephantiasis-repeated acute and chronic attaches legs, arms, scrotum. Chromic Lymph blockagefat fibrous tissue, psycholigcal+social impact. Rarely in people younger than 25 years old and mostly in people older than 40 yrs old. C. Diagnosis- mf in blood at times of peak periodicity 1. circulating filarial antigen test- (CFA)- any times and only blood droplets 2. ultrasonography- visualize worms in ducts. filarial dance D. Treatment 1. hygiene- wash-soap and water. Shoes and antibiotic creams. Raise limbs and exercise. 2. drugs a. diethylcarbamazine-(DEC)- may increase hosts immune responseaffects worm cuticle release of antigenic compounds b. albendazole- disrupts metabolic function c. ivermectin-increase GABA E. Costs associated with W. bancrofti infection 1. Costs of disease- permanent long-term disability, decrease in economic productivity and social loss 2. Costs of treatment- DEC- single annual dose- cost $0.02/person/year. DEC fortified salt- tasteless, survives cooking- cost- about $0.30/person/year. Albendazole- single annual dose- donated by smith-kline beecham- $0. Ivermectin- single annual dose- donated by Merck- $0. 3. Costs of diagnosis- CFA test- $1/test. Duagbisus +treatment=$1.32/person/yr. Ex. India- losses- $800 million-1 billion per year. F. Control of lymphatic filariasis- one of the 7 diseases targeted by WHO 1. elimination- reduction to 0 in a particular area 2. eradication- reduction to 0 worldwide. Bracunculus, T. solum, measles, mumps, rubella, polio. 3. characteristics-no amplification in vectors, no animal reservoirs, simple and accurate diagnostic tests, treatment- effective and inexpensive, variety of drugs, collateral health benefits, plans of actions, drug companies. III. Brugia malayi A. Adults- female- 55mm. males-25mm B. Mf- sheathed, do undergo periodicity-inperipheral blood at night, vector=mosquito C. South and southeast asia D. Same as w. bancrofti for life cycle, pathology, diagnosis, and treatment. IV. Onchocerca volvulus River blindness- Africa, central, South America by Slave trade.

A. Life cycle- female-50cm male-40cm. in nodules under skin- oncnocercoma- some subcutaneous. Others- deep tissue. 9-10 yras . remain in skin, no periodcity, positively phototactic ingested by blackfly. 1. microfilaria2. Simulian fly- ingested by this black fly-blood meal. Scarifies skin, blood of blood, fly laps up blood + mf. Insdie black fly-mfhemocoelL1L2L3migrates to mouth parts. L3 infect next host into skin. In skin, L4adult B. Pathology 1. adults onchocercoma 2. onchocerciasis-by mf, skin+eyes a. microfilaria alive-little pathology b. microfilaria dead/degenerating-response to bacterium present in mf c. Wolbachia intracellular, inherited, found in many insects + crystaceans. Found in many filarial worm i. endosymbiont ii. LPS- molbachia cell wall- lipopolysaccharide. Endotoxin, stimulates host inflammatory response. Antibiotics-tertracycline-effective. Penicillin and liprofloxiacin-ineffective. d. acute skin lesions- mf in skin, persistent, itchy rash.scratch open skinsecondary bacterial infection, skin thickens, enlargemtn of lymph node in area. e. chronic lesions of skin and enlarged lymph nodes- skin-thickens and discolored, loss of skin elasticity. Femeral+inguinal lymph nodes enlarged + hanging loose skin hanging groins. f. ocular lesions- mf enter eyes + die, inflammation blindness. C. Simulian 1. female blood meal- females lay eggs in water of fast flowing rivers. 2. fast-flowing rivers D. Diagnosis 1. skin snip-small bits of skin raised, sliced with razer, in saline on slide, look for mf in microscope, should be no blood in sample. E. Treatment 1. Ivermectin 2. Mectizan 3. surgery- remove nodules 4. antibiotics F. Control programs 1. drugs, insecticides, antibiotics 2. Onchocerciasis Program of West Africa- 1974- 11 west African countries. 20*10^6 cases. Ended in Dec 2002.

3. Carter Center River Blindness Program- 1996- 11 countires in Africa + Americas. MDP- Mectizan distribution Program. 1988- Merch. Elimination- in colombia- 2007. In Ecuador- 2010, V. Loa loa- eye worm- in Africa. A. Life cycle- females- 50mm and females- 30 mm. subcultaneous tissue- migrate freely. Mf-sheathed. 1. periodicity-peripheral- day. Lungs- night 2. Chrysops- vectors- deerfly- mfL1L2L3. L3 enters skin with next meal. B. Pathology- mold- adults migrate stimulates inflammatory reaction 1. Calabar swelling- if adult remains in one location host reaction- localized, painful, swelling. Adults can migrate through conjectiva and cornea. C. Diagnosis- mf in blood D. Treatment and control- ivermectin+ DEC- kill mf, surgery. Control- deerfliesswampy areas of forests. VI. Mansonella spp.-minor A. Adult worms in body cavites+tissues B. Mf-unsheathed, no periodicity C. Vector- midges D. Pathology- localized tissue reaction VII. Dirofilaria immitis- heartworm A. Life cycle- similar to human filarial spp. Adults live in heart + pulmonary ateries. Mfin blood. Vector- mosquito B. Pathology- heart function impaired, fatigued, gernal loss of condition, cough+ respiratory problems C. Diagnosis- mf in blood. D. Treatment 1. Immiticide- arsenic- containing compound kill adult worms. Problemsa.arsenic toxicity- low margin of safety. B. dead worms- blockage. 2. Surgery- caval syndrome- heavy infection of heart worm in venae cava + right atrium. Immiticide contraindicated potential of obstruction. Surgery- risky and expensive. 3. Heartgard- ivermectin+pyrantel. Targets L3s.

Study Questions Nematodes Filarial worms

1. What are the seven species in the superfamily Filaroidea which are of significant human health importance? Where do filarial worms live in the definitive host? How are filarial worms transmitted to the definitive host? 2. What are microfilaria? What is the sheath? Do all species have a sheath? How long do mf survive in the host? How can they be identified? What is periodicity? Give an example of periodicity using Wuchereria bancrofti. 3. What disease is caused by Wuchereria bancrofti? Trace its life cycle. How big are the adult worms and where do they live? Are the mf sheathed? What is the vector? 4. What are the 3 phases of pathology? Describe the incubation phase. What is microfilaremia? 5. What is episodic adenolymphangitis and in which phase of pathology does it occur? 6. When does chronic pathology develop? What is lymphoedema? Compare the three grades of lymphoedema. What is elephantiasis? 7. What are the advantages of the CFA test for diagnosis of W. bancrofti infection? What can be observed using ultrasonography? 8. How is infection treated? What drugs are effective? Why is hygiene important? 9. What are the costs of infection with lymphatic filariasis? Compare the costs of disease and treatment. How do these costs and other factors contribute to the control of lymphatic filariasis? 10. What is the size of Brugia malayi adults? Is there periodicity in this species? Are the mf sheathed? This species is very similar to which other species?

11. Trace the life cycle of Onchocerca volvulus. What are onchocercomas and where are they found? How long do the adults live? What is the vector in the life cycle? What stage is infective to the vector? How does the vector become infected? What is the development of the parasite inside the vector? 12. What is Wolbachia? What is lipopolysaccharide and how is it related to pathology in Onchocerca infections? Compare acute, chronic, and ocular lesions in onchocerciasis. 13. Why do Simulian flies live near rivers? How is onchocerciasis diagnosed? Why is it important not to draw blood during the skin snip? 14. What is the treatment? How do Ivermectin and Mectizan function? Briefly describe the Onchocerciasis Program of West Africa and the Carter Center River Blindness Program. 15. In what part of body do Loa loa adults live? What is the vector? What is the pathology? How is infected diagnosed? How can infection be treated? 16. Where do Mansonella spp. adults live in the DH? What is the vector? Is pathology usually severe in these infections? 17. What is the common name of Dirofilaria immitis? What is the vector? What pathology results? How is infection diagnosed? How is infection treated? What stage is killed by Immiticide? Why should a drug such as Heartgard be used? 18. Figure Assignment Fig. 17-1. Life cycle of filarial worms (p. 364)

Sample questions 1. Which of the following is a characteristic of Grade II lymphoedema? A. Transient and soft B. Pressure causes pit to form in skin C. Skin does not pit on pressure D. Thickening of subcutaneous tissue E. Fissures, nodules, and warty appearance 2. Periodicity in Wuchereria bancrofti is triggered by changes that occur in the host during A. puberty B. eating C. sleeping D. exercise E. sickness 3. One characteristic of Onchocerca volvulus is that A. it is transmitted by blackflies B. the vector can survive only in slow-moving streams C. onchocercomas form primarily in the lungs and brain D. the microfilariae are the infective stage to humans E. the infective stage is transmitted to humans by copepods

1. C; 2. C; 3. A