391 JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS

INFECTIOUS DISEASE

Infectious Diseases: Filariasis—Bancroftian filariasis, Malayan filariasis, Loiasis (loa loa), Onchocerciasis (river blindness)

Charles Kemp, FNP, CRNH

Amy Roberts, RN, MSN, FNP

Primary Distribution: Numerous areasof the world, with variants and locationsnoted below under vectors and agents.

Agents and Vectors: The filarial parasitesare tissue-dwelling nematodes (round-worms) whose microfilaria (MF) larvaeare transmitted by several species of mos-quitoes or flies as follows (Bell, 1995;Chin, 2000; King, & Freedman, 2000;Nutman, & Weller, 1998):• Bancroftian filariasis is caused by the

nematode Wuchereria bancrofti, trans-mitted by Anopheline mosquitoes, andoccurs in much of the tropical and sub-tropical world (except western SouthAmerica and Northern Australia)between the Tropics of Cancer andCapricorn, and primarily in cosmopoli-tan areas in India, China, andIndonesia.

• Malayan filariasis is caused by thenematode Brugia malayi, transmittedby Mansonia or Anopheline mosqui-toes, and occurs primarily in Malaysia,Indonesia, and some nearby PacificIslands, as well as scattered areas ofIndia, Bangladesh, Vietnam, andChina. Brugia timori infections are sim-ilar, are confined to Timor and nearby(Indonesian) islands, and transmittedby Anopheles barbinostris, which alsocarries malaria.

• Loiasis (loa loa) is caused by the nema-

tode Loa loa (African eye worm), istransmitted by Chrysops (red or deer)flies, and occurs in West and CentralAfrica.

• Onchocerciasis (river blindness) iscaused by the nematode Onchocercavolvulus, and is transmitted bySimulium blackflies. Onchocerciasisoccurs primarily in Africa, South andCentral America, and the Middle East.The vectors breed only in swiftly mov-ing water, hence endemic areas are con-fined to such locales.

The location of the invading MF inhumans is in the blood with the excep-tion of onchocerciasis, which is found insubcutaneous tissue. The adult loa loa isfound in subcutaneous tissue but the MFis found in the blood (King, &Freedman, 2000). Other filarial parasitesexist but are of less public health signifi-cance (Bell, 1995).

Incubation: Variable according tospecies. Symptoms may begin six monthsor longer after infection.

CLINICAL FINDINGS & TREATMENT:Bancroftian filariasis or Wuchereriabancrofti and Brugia malayi infection(Note: Wuchereria bancrofti and Brugiamalayi infections are similar, except thatB. malayi is less widely distributed [see

above] and the clinical features of B.malayi tend to be less severe.)

Signs and Symptoms: Adult worms livein lymph vessels and nodes, while the MFare found primarily in the blood.Symptoms begin 4-12 months (usuallymore than 6 months) after infection; notall infected persons are symptomatic.Symptoms usually begin with localizedinflammation in genitalia or extremities.Lymphadenitis and lymphangitis begin ata single site and spread regionally withinhours. Acute-onset, recurrent bouts offever, chills, headache, and malaise alsooccur. Lymphedema may begin accumu-lating in the first 24 hours. Acute symp-toms of mild attacks resolve within a fewdays, although the lymphedema takesseveral weeks to resolve. Hydrocele,orchitis, epididymitis, and/or funiculitis(inflammation of the spermatic cord) arecommon in males. Filarial abscesses areusually found in the groin or axillae;among patients from the Pacific Islands,the abscesses may also occur in deep fas-cial spaces of muscles. Chronic diseasemay lead to chronic obstruction of lymphand serous fluid resulting in chronic, per-manent, and disabling elephantiasis ofthe lower extremities or testes, and to alesser extent, arms, breasts, labia, andpenis. Chyluria (galacturia) results fromchyle (lymph and triglyceride in an emul-

This series is based on the Infectious Diseases section of the web site Refugee Health ~ Immigrant Health, avail-able on the World Wide Web at http://www.baylor.edu/~Charles_Kemp/Refugee_Health.htm. The site was devel-oped through a contract with the Texas Department of Health as part of an ongoing effort to improve the health ofrefugees and immigrants.

Authors: Amy Roberts,RN, MSN, FNP, is the coordinator of the International Family Nurse Practitioner Program atthe Louise Herrington School of Nursing, Baylor University. Charles Kemp, FNP, CRNH, is on the CommunityHealth Faculty at the Louise Herrington School of Nursing, Baylor University. Contact the author atamy_roberts@baylor.edu.

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sion) in the urine caused by obstructionbetween the intestinal lymphatics and thethoracic duct leading to rupture of renallymphatics into renal tubules. Chyluria isoften associated with back pain.Recurrent episodes of dyspnea and bron-chospasms are common (Alonso, 2001;Chin, 2000; King, & Freedman, 2000).

Complications: Chronic lymphedemaleads to elephantiasis, which includeshyperplasia of skin and subcutaneous tis-sue, and predisposes the patient to ulcer-ation and secondary infection. This ele-phantiasis is a nonpitting edema that canaffect an entire limb, with the size andweight of the affected part leading to dis-ability. Some hydroceles may becomegrapefruit size and surgical drainage isnecessary (Alonso, 2001; King, &Freedman, 2000).

Laboratory Findings: Moderateeosinophilia, elevation of serum concen-trations of IgE, and antifilarial antibodiesare commonly found.

Diagnosis: Note that the life cycle of theMF varies according to species and areain which the disease is contracted.Microfilarial concentrations vary accord-ing to the time of day (diurnal periodici-ty), and, depending on these factors,peripheral blood of infected persons mayor may not have MF. Microfilariae aredetectable primarily in blood and hydro-cele fluid and are at their highest num-bers in the late afternoon and betweenmidnight and 2 a.m.

Giemsa-stained thick blood film is acommonly used test. Polymerase chainreaction-based assays are available for thepresence of W. bancrofti and B. malayi inblood and sputum. Ultrasound of thescrotum detects adult worms, nodules, orlymphatic dilatation in 80% of affectedmen. Enzyme-linked immunosorbantassay (ELISA), and indirect flourescentantibody (IFAT) tests for serum are alsoavailable and are highly accurate, but theIFAT is often unable to distinguishbetween various forms of filariasis. Animmunoassay for circulating filaria anti-gen (CFA) can be done for those patientswith detectable microfiliaria. Eosinophiliais predominant only during acute lym-

phangitis or lymphadenitis (Abbasi et al.,1999; Alonso, 2001; King, & Freeman,2000).

Differential Diagnosis: Differentialsinclude acute bacterial lymphangitis,lymphogranuloma inguinale and otherlymphatic infections; other causes ofrecurrent fever, such as tuberculosis orurinary tract infection; other causes oforchitis and related disorders such as gon-orrhea, tubercular epididymitis, hernia,or trauma; Milroy’s disease; post opera-tive scarring; and malignancy. Individualsfrom Ethiopian highlands may presentwith African “bigfoot” disease that doesnot include hydrocele.

Treatment: Unfortunately, no drug iseffective in killing all adult worms, whichare the cause for the pathological changesassociated with the disease. The WorldHealth Organization (WHO) notes thatall three recommended regimens, diethyl-carbazine (DEC) alone, ivermectin alone,and DEC + ivermectin will reduce MFbut not eliminate it. Recent research byboth the WHO and others show thatperhaps the combination therapy ofDEC and ivermectin will have the bestresults as it produces 84%-99% reduc-tion in transmission of MF. This combi-nation regimen includes combining DECand ivermectin as follows: DEC 6mg/kg/day split in two daily doses for 10-14 days for a total cumulative dose of 72mg/kg. Initially a lower dose of 1-3mg/kgcan be given for three days before advanc-ing to the 6 mg/kg/day to minimize sideeffects. Ivermectin augments the DEC ina single oral dose of 200-400 mcg/kg.(WHO, 2001; King, & Freedman 2000;Alonso, 2001; Grove, 2000). This regi-men is effective because DEC kills adultworms while ivermectin only kills theMF, dosing is simple, and there isincreased compliance. The problem withDEC alone is that in patients with aheavy parasitic load, the medication mayprecipitate acute inflammation that cul-minates in a severe granulomatousprocess and progressive fibrosis. Otherside effects of DEC include asthma, fever,headache, myalgia, vomiting, and weak-ness resulting from rapid destruction ofthe adult worms (Goldsmith, 2001;

Grove, 2000; King, & Freedman, 2000).Some researchers combined single oral

doses of ivermectin 400 mcg/kg andalbendazole 400 mg and found this moreeffective than ivermectin alone (King, &Freedman, 2000). This combination hasthree major advantages: (a) albendazolealso treats intestinal worms and iver-mectin also treats scabies, (b) the singledose regimen increases compliance, and(c) the manufacturers have donated thedrugs for control purposes. This singledose regimen of ivermectin and albenda-zole is repeated annually to control trans-mission of filariasis in endemic areas.

Children with filariasis are more likelyto have sleep disturbances, fewer tenderspots, and a better prognosis than adults(Alonso, 2001). Symptomatic treatmentincludes elevation of the affected limb,use of elastic stockings, scrotal support,wearing non-constricting footwear, andgood foot hygiene.

Prevention: Individuals traveling to orliving in endemic areas should use mos-quito netting and insect repellent, espe-cially at night.

CLINICAL FINDINGS ANDTREATMENT: LOIASIS (LOA LOA)Signs and Symptoms: Loiasis is oftenasymptomatic among indigenous peopleliving in endemic areas, but more prob-lematic among non-indigenous peoplewho are infected. The worms live in sub-cutaneous tissues and cause intermittentdevelopment of localized areas of erythe-ma and angioedema (Calabar swellings),usually on the extremities. Calabarswellings are usually only in one area at atime and are preceded by pain and itch-ing at the site. Swellings are non-erythe-matous, 10-20 cm in length, and last sev-eral days to weeks. The wrist and knee arecommon sites for Calabar swellings,which may recur at the same or differentsites. Patients sometimes also complain ofurticaria and pruritus. Moving worms aresometimes visible in the eye between thebulbar conjunctiva and sclera for 30-60minutes, followed by several days of acuteconjunctivitis. Worms have also beenseen in the penis and around the nipple(Chin, 2000; King, & Freedman, 2000;Nutman, & Weller, 1998).

393 JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS

Complications: Rarely seen complica-tions are nephropathy, encephalopathy,and cardiomyopathy. Other complica-tions include retinopathy, peripheral neu-ropathy, arthritis, pleural effusion, andbreast calcification (King, & Freedman,2000).

Laboratory Findings: Common find-ings include eosinophilia, increasedantifilarial antibodies, hypergammaglob-ulinemia, increased IgE, and increasedleukocyte and eosinophil counts.

Diagnosis: Diagnosis is usually made onclinical symptoms and/or the presence ofMF in the daytime blood (as described inthe section on Wuchereria bancrofti andBrugia malayi infections). The presenceof a worm in the eye is diagnostic.

Treatment: Diethylcarbamazine (DEC)is the drug of choice and is given in grad-uated doses as follows: Day 1 give 50 mgpo; Day 2 give 50 mg po tid; Day 3 give100 mg po tid; Days 4-21 give 9mg/kg/day in 3 divided doses.Unfortunately, DEC may precipitateencephalitis, especially when MF loadsare high (> 25 /mcL). A single oral doseof ivermectin 200-400 mcg/kg willdecrease the density of MF in the bloodand thus lower the risk of encephalitiswith DEC; however, it is not an option ifthe patient also has onchocerciasisbecause neurologic reactions may result.One course of DEC cures about 50% ofpatients and a treatment of three coursescures about 90%. Albendazole 200 mgbid for 3 weeks is being tested as an alter-native treatment to lower the density ofMF in the blood, thereby allowing DECto be given with a reduction in risk ofserious side effects. (King, & Freeman,2000; Goldsmith, 2001).

Prevention: Avoiding places where bitingflies live is the best prevention. Daytimeuse of insect repellent and light coloredprotective clothing helps somewhat.Mass treatment of DEC at 5mg/kg/dayfor 3 days each month or ivermectin 200-400 mcg given every three months hasreduced disease rates. For travelers toendemic areas, a weekly dose of DEC300 mg is an effective preventive treat-

ment. This is not indicated for casualtravelers or those that might have previ-ously acquired a filarial infection. Mostinfections run a benign course and recov-ery is excellent with treatment (Chin,2000; Goldsmith, 2001).

CLINICAL FINDINGS ANDTREATMENT: ONCHOCERCIASIS(RIVER BLINDNESS)Signs and Symptoms: Unlike other filar-ial infections, the problems of onchocer-ciasis are caused by MF rather than adultworms. Very severe pruritus, with orwithout papular rash, is caused by MF insubcutaneous tissue. Subcutaneous nod-ules (onchocercomata) contain adultworms. The skin may eventually lose itselasticity and become atrophied andfibrous, and in some cases, hypo- orhyper-pigmented. Eczema and secondaryinfections may result from scratching.Skin involvement among patients inAfrica tends to be greatest on the lowerextremities, while in Central America,the head is more commonly involved.Involvement of the eyes is usually mani-fested first by conjunctivitis and photo-phobia. Neovascularization, keratitis, andcorneal scarring occur in a small percent-age of patients and lead to blindness.Uveitis, chorioretinitis, and optic atrophymay also occur, as well as secondary glau-coma. Lymphadenopathy in the femoraland inguinal areas may lead to chronicenlargement of the scrotum (King, &Freedman, 2000; Nutman, & Weller,1998).

Complications: Cachexia may occurwith heavy infestation. Impaired visualacuity is the most serious complication.Some researchers have found an increasein epilepsy with onchocerciasis.

Laboratory Findings: The primary labo-ratory finding is eosinophilia. Reliableimmunodiagnostic tests are not availablebut are under development.

Diagnosis: Bloodless skin biopsy (snips)are taken from over the scapula, buttocks,thighs, and iliac crests and are incubatedin tissue culture medium or saline.Within 30 minutes MF can be visualizedin a low power microscope. Slit-light

examination of the eye will show MF inthe anterior chamber. Adult worms arefound in nodule biopsy specimens. Ifonchocerciasis is strongly suspected, asingle oral dose of 50 mg of DEC can begiven. If a rash (Mazzotti reaction) occurswithin a few hours, the likelihood ofonchocerciasis is high (King, &Freedman, 2000).

Differential Diagnoses: Common dif-ferentials are other causes of pruritus,eczema, nodules, conjunctivitis, and eyeinfection.

Treatment: A single oral dose of iver-mectin 150 mcg/kg is the drug of choice.This should be given with water and onan empty stomach and the patient shouldnot eat for 2 hours after taking the med-ication. The treatment might need to berepeated at three-month intervals for 2-3years if symptoms continue or there isevidence of eye infection. Because ofproximity to the eyes, nodules on thehead are sometimes removed. Ivermectinshould not be used in pregnancy andused with caution with concurrent loa loainfections. (Grove, 2000; Goldsmith,2001).

Prevention: Avoidance of breedinggrounds for flies and use of protectiveclothing are recommended. Larvicidesare being applied to breeding places inthe effort to eradicate onchocerciasis(Grove, 2000).

REFERENCES Abbasi, I., Githure, J., Ochola, J.J., Agure, R.,

Koech, D.K., Ramzy, R.M., Williams, S.A., &Hamburger, J. (1999). Diagnosis of Wuchereriabancrofti infection by the polymerase chainreaction employing patient’s sputum.Parasitology Research, 85, 844-849.

Alonso, G. (2001). Filariasis. In F. Ferri (Ed.), Clinicaladvisor: Instant diagnosis and treatment(pp.272-273). St. Louis: Mosby.

Bell, D. (1995). Tropical medicine (4th ed.). Oxford:Blackwell Scientific.

Chin, J. (Ed.) (2000). Control of communicable dis-eases manual (17th ed.). Washington,DC:American Public Health Association.

Goldsmith, R. (2001). Infectious disease: Protozoaland helminthic. In L. Tierney, S. McPhee, & M.Papadakis (Eds.), Current medical diagnosis

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and treatment (40th ed.) (pp.1412-1480). New York: Lange Medical Books.Grove, D. (2000). Tissue nematodes (trichininosis, dracunculiasis, and filariasis).

In G. Mandell, J. Bennett, & R. Dolin (Eds.), Principles and practices of infec-tious diseases (5th Ed.; pp. 2943- 2949). New York: Churchill Livingston.

King, C., & Freedman, D. (2000). Filarial infections. In G. Strickland (Ed.),Hunter’s tropical medicine and emerging infectious diseases (8th ed.; pp.740-758). Philadelphia: W.B. Saunders.

Nutman, T.B., & Weller, P.F. (1998). Filariasis and related infections (loiasis,onchocerciasis, and dracunculiasis). In A.S. Fauci, E. Braunwald, K.J.Isselbacher, J.D. Wilson, J.B. Martin, D.L. Kasper, S.L. Hauser, & D.L. Longo(Eds.). Harrison’s principles of internal medicine (14th ed.; pp. 1212-1216).New York: McGraw-Hill.

World Health Organization (WHO) (2001). Research results: Filariasis/AFR.Retrieved July 10, 2001, from http://www.who.int/tdr/research/progress/fil_afr/filtreat.htm

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