Merck Manual: Nematode (Roundworm) Infections

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Merck Manual

 

Nematode (Roundworm) Infections

 

Nematodes are nonsegmented cylindric worms ranging from 1 mm to almost

1 m in length. Nematodes have a body cavity, distinguishing them from

tapeworms and flukes. Depending on the species, different stages in

the nematode life cycle are infectious to humans.

ASCARIASIS

 

Infection with Ascaris lumbricoides, causing early pulmonary and later

intestinal manifestations.

Etiology and Pathogenesis

 

Ingesting eggs initiates infection. Eggs hatch in the duodenum, and

the resulting larvae penetrate the wall of the small intestine and

migrate via the circulation to the heart and lungs. They ascend the

bronchial tree into the oropharynx, are swallowed, then return to the

small intestine, where they develop into adult worms. The life cycle

is completed in about 2 mo; adult worms may live 6 to 12 mo.

 

The disease occurs worldwide but is concentrated in tropical and

subtropical areas with poor sanitation. Infection is common in rural

parts of the southeastern USA. Ascariasis is the most prevalent

intestinal helminth infection in the world; current estimates suggest

that more than 1 billion persons are infected, of whom about 20,000

will die each year.

Symptoms and Signs

 

Migrating larvae may produce " verminous pneumonia, " a typical

Löffler's syndrome. Adult worms usually produce no GI symptoms.

Passage of an adult worm by mouth or rectum may bring an otherwise

asymptomatic patient to medical attention. However, heavy infection,

especially in children, may produce abdominal cramps, and a mass of

tangled worms may cause intestinal obstruction. Aberrant migration of

individual adult worms occasionally leads to obstructions resulting in

cholangitis, cholecystitis, liver abscess, pancreatitis, appendicitis,

or peritonitis. Fever from other illnesses and certain drugs (such as

tetrachlorethylene) may provoke this aberrant migration.

 

Even moderate infections frequently lead to malnutrition in children.

The pathogenesis is unclear and may include competition for nutrients,

impairment of absorption, and depression of appetite.

Diagnosis

 

Diagnosis is made by microscopic detection of characteristic eggs in

stools. Occasionally, adult worms are passed in the stool or vomited,

and larvae are sometimes found in the sputum during the pulmonary

phase. Eosinophilia can be marked while larvae migrate though the

lungs but usually subsides when the adult worms settle in the small

intestine.

Prevention and Treatment

 

Prevention requires adequate sanitation. Uncooked or unwashed

vegetables should be avoided in areas where human feces is used as

fertilizer.

 

All infections should be treated. Mebendazole (100 mg po bid for 3

days), albendazole (400 mg po once), piperazine citrate (75 mg/kg po

once daily for 2 days; maximum 3.5 g/day), pyrantel (11 mg/kg, maximum

1 g in one oral dose) are the drugs of choice. Mebendazole should not

be used in pregnancy. If other intestinal helminths are present,

Ascaris must be treated first to prevent aberrant migration of adult

worms. Alleviation of obstructive complications may require surgical

or endoscopic intervention.

TRICHURIASIS

(Whipworm Infection; Trichocephaliasis)

 

Infection with Trichuris trichiura, causing abdominal pain and diarrhea.

Etiology and Pathogenesis

 

Infection is spread via the fecal-oral route. Ingesting eggs initiates

infection. Eggs hatch in the duodenum, where the larvae invade and

mature in the mucosa before migrating to the large intestine. Adult

whiplike worms embed their heads into the superficial mucosa of the

colon and caecum. The life cycle is completed in about 3 mo; adult

worms may live 7 to 10 yr.

 

The parasite is found principally in the tropics and subtropics. Mild

asymptomatic infections are common in rural parts of the southern USA.

Symptoms, Signs, and Diagnosis

 

Light infections are often asymptomatic. Heavy infections cause

abdominal pain, anorexia, and diarrhea and may retard growth. Very

heavy infections may cause weight loss, anemia, and rectal prolapse in

children and parturient women. The characteristic lemon-shaped eggs

are readily found in feces.

Prevention and Treatment

 

Prevention requires adequate sanitation and good personal hygiene. No

treatment is needed for asymptomatic or light infections. Mebendazole

(100 mg po bid for 3 days) is used for more severe infections. The

drug should not be used during pregnancy.

HOOKWORM INFECTION

(Ancylostomiasis)

 

Infection with Ancylostoma duodenale or Necator americanus causing

abdominal pain and iron-deficiency anemia.

Etiology and Pathogenesis

 

Both hookworm species have similar life cycles. Eggs passed in the

stool hatch in 1 to 2 days (if they are deposited in a warm, moist

place on loose soil) and release rhabdoid larvae, which change into

slender filariform larvae in 5 to 8 days. Filariform larvae penetrate

human skin, reach the lungs via blood vessels, climb up the

respiratory tree to the epiglottis, and are swallowed. The larvae then

attach to the wall of the small intestine and mature into adults that

chronically suck blood. Adult worms may live 2 to 10 yr.

 

A. duodenale is widely distributed in the Mediterranean basin, India,

China, Japan, and the Pacific coastal areas of South America but is

rare in the USA and equatorial Africa. N. americanus is the

predominant hookworm of Central and South Africa, southern Asia,

Melanesia, and Polynesia. It is widely distributed in the southern

USA, on islands of the Caribbean, and on the Atlantic side of Central

and South America. About 25% of the world's population is infected

with hookworms.

 

Infection with A. caninum, the hookworm species that ordinarily

infects dogs, is a common cause of eosinophilic enteritis in

Queensland, Australia; several cases have been diagnosed in the USA.

Eggs are not usually found in stool. Infection may be asymptomatic or

cause acute abdominal pain and eosinophilia. Diagnosis and treatment

are by endoscopic removal of the worm.

Symptoms, Signs, and Diagnosis

 

Hookworm infection is asymptomatic in most cases. However, a pruritic

papulovesicular rash (ground itch) may develop at the site of larval

penetration. Migration of large numbers of larvae though the lungs

occasionally causes Löffler's syndrome. During the acute phase, adult

worms in the intestine may cause colicky epigastric pain, anorexia,

flatulence, diarrhea, and weight loss. Chronic infection may lead to

iron-deficiency anemia and hypoproteinemia, causing pallor, dyspnea,

weakness, tachycardia, lassitude, impotence, and edema. A low-grade

eosinophilia often persists. Severe chronic blood loss may lead to

growth retardation, cardiac failure, and anasarca.

 

A. duodenale and N. americanus produce thin-shelled oval eggs that are

readily detected in fresh stool. If the stool is not kept warm and

examined within several hours, the eggs may hatch and release larvae

that may be confused with those of Strongyloides. Nutritional status,

anemia, and iron stores should be evaluated.

Prevention and Treatment

 

Preventing unhygienic defecation and avoiding direct skin contact with

the soil are effective but impractical in most endemic areas. Periodic

mass deworming may be effective for high-risk populations.

 

General support and correction of anemia may be needed first if the

infection is heavy and the anemia is severe. Anemia usually responds

well to oral iron, but parenteral iron or blood transfusions may be

required in very severe cases.

 

An anthelmintic may be given as soon as the patient's condition is

stable. Mebendazole is the drug of choice in the USA. A cure rate of >

99% has been reported after a course of 100 mg po bid for 3 days.

Since the drug is also ovicidal, it is particularly valuable in the

control of infection in endemic areas. Mebendazole should not be used

in pregnancy. Single-dose albendazole (400 mg) and pyrantel (for N.

americanus, a single daily dose of 11 mg/kg [1 g maximum] is given po

for 3 days; for A. duodenale, 1 day of treatment usually suffices) are

also effective.

STRONGYLOIDIASIS

(Threadworm Infection)

 

Infection with Strongyloides stercoralis, causing skin rashes,

eosinophilia, and abdominal pain.

Etiology and Pathogenesis

 

Strongyloidiasis is endemic throughout the tropics and subtropics,

including rural areas of the southern USA. Adult worms live in the

mucosa and submucosa of the duodenum and jejunum. Released eggs hatch

immediately and liberate rhabdoid larvae that migrate to the lumen and

are passed in feces. After a few days on soil, the larvae metamorphose

into infectious filariform larvae. Like hookworms, Strongyloides

larvae penetrate the skin of humans, migrate through the lungs, and

reach the intestine, where they mature in about 2 wk.

 

In the soil, several generations of free-living worms may be produced

before the worms revert to being parasitic. Filariform larvae can

bypass the soil phase and directly penetrate the colon or the skin.

Transmission is often due to exposure of bare skin to larvae in

contaminated soil in unsanitary conditions. Person-to-person

transmission by the fecal-oral route accounts for most infections

reported in mental institutions and day care centers and among

promiscuous homosexual men.

 

Self-reinfection may occur. Reinfection can result in extremely high

worm burdens (hyperinfection syndrome) and probably explains why

infection can persist for many decades. The hyperinfection syndrome is

usually seen in persons with impaired cell-mediated immunity,

occasionally in persons with achlorhydria or prolonged intestinal

transit time, and rarely in otherwise healthy persons. Accelerated

autoinfection and hyperinfection occur frequently in persons infected

with the human T-cell lymphotropic virus type I or receiving

immunosuppressive drugs, but disseminated strongyloidiasis is uncommon

among AIDS patients, even those from African countries where

strongyloidiasis infects almost 50% of the population.

Immunosuppression may lead to overwhelming hyperinfection in persons

with previously asymptomatic infection.

Symptoms and Signs

 

More than half of infected persons are asymptomatic, even though >=

75% have eosinophilia; the eosinophilia may be suppressed by drugs

such as steroids or cytotoxic chemotherapeutic agents, which also

increase the risk of hyperinfection. Cutaneous symptoms are unusual in

acute but not chronic strongyloidiasis. Larva currens, a serpiginous,

migratory, urticarial lesion, usually on the buttocks, perineum, or

thighs, is pathognomonic, but other nonspecific maculopapular or

urticarial eruptions may occur. Pulmonary symptoms are absent in most

cases, although heavy infections may produce Löffler's syndrome.

Occasionally, larvae mature in the bronchial submucosa and produce

chronic bronchitis and asthma.

 

Intestinal infection in the duodenum and adjacent jejunum may damage

mucosa and submucosa. The resulting symptoms include epigastric pain

and tenderness, diarrhea, nausea, vomiting, constipation, and weight

loss. Chronic infection may lead to glucose malabsorption and

protein-losing enteropathy.

 

In hyperinfection, adult female worms accumulate in the upper small

bowel while filariform larvae invade the intestinal tract elsewhere.

Early GI symptoms include nausea, vomiting, diarrhea, and abdominal

pain. Untreated infection may cause ileus, obstruction, massive GI

bleeding, severe malabsorption, and peritonitis. Pulmonary symptoms

include cough, sputum, dyspnea, hemoptysis, bronchospasm, and

respiratory failure. Chest x-rays may show diffuse interstitial

infiltrates, consolidation, or abscess.

 

Migratory larvae can infect the CNS, leading to parasitic meningitis,

brain abscess, and diffuse invasion of brain. Liver infection may

cause cholestatic and granulomatous hepatitis. The high incidence of

secondary gram-negative meningitis, pneumonia, and bacteremia probably

reflects disruption of bowel mucosa or carriage of bacteria by

migrating larvae. Infection may be fatal in immunosuppressed patients.

The mortality of untreated hyperinfection syndrome approaches 100%;

mortality with treatment is 50 to 80%.

Diagnosis

 

Microscopic visualization of larvae in a single stool is successful

about 25% of the time. Repeated examination of concentrated stool or

zinc flotation, Baermann technique, or agar-plate method raises the

sensitivity to >= 85%. If the specimen stands at room temperature for

several hours, rhabdoid larvae may transform into longer filariform

larvae, leading to erroneous diagnosis of accelerated hyperinfection.

Sampling of proximal small intestine with string capsules (Enterotest

capsules) or by aspiration may be required in low-level infections.

The latter should be done endoscopically to permit biopsy of

suspicious duodenal and jejunal lesions. In the hyperinfection

syndrome, filariform larvae may be found in stool, duodenal contents,

sputum and bronchial washings and uncommonly in CSF, urine, and

pleural or ascitic fluid.

 

ELISA is 80 to 85% sensitive for diagnosis of uncomplicated

strongyloidiasis, but yields false-positive results in persons

infected with other intestinal nematodes. Other serodiagnostic assays

are not available commercially.

Prevention and Treatment

 

Prevention of primary infections is the same as for hookworms. To

prevent the highly fatal hyperinfection syndrome, patients with

possible exposure to Strongyloides (even in the distant past), those

with unexplained eosinophilia, and those with symptoms suggestive of

strongyloidiasis should undergo several stool examinations and, if

necessary, a string test or duodenal aspiration before receiving

corticosteroids or other immunosuppressive therapy. If infected,

treatment should be instituted and parasitologic cure documented

before immune suppression. Immunosuppressed persons who have recurrent

strongyloidiasis may require monthly courses of thiabendazole.

 

Thiabendazole is the drug of choice. In uncomplicated infection, 25

mg/kg bid po for 2 days (maximum 3 g/day) results in 80 to 90% cure;

repeated courses or direct instillation of drug into the upper

intestine may be required. Cure should be documented by repeated stool

examination and string tests. In the hyperinfection syndrome, 25 mg/kg

bid po or by nasogastric tube must be given for a minimum of 5 to 7

days, but therapy should be continued for at least several days after

parasites have disappeared from all sites. Long-term follow-up of

stool and upper intestinal samples is mandatory. Side effects of

thiabendazole are frequent and occasionally disabling: nausea,

vomiting, abdominal pain, dizziness, headache, paresthesia, malaise,

pruritus, flushing.

 

Ivermectin (200 µg/kg/day po for 1 to 2 days) may be highly effective

against Strongyloides and produce fewer side effects than

thiabendazole. Mebendazole and albendazole are less active than

thiabendazole and are not recommended.

TOXOCARIASIS

(Visceral or Ocular Larva Migrans)

 

Human infections with nematode larvae that ordinarily infect animals,

causing eosinophilic granulomatous tissue reactions to migrating

larvae or visual impairment.

Etiology and Pathogenesis

 

The eggs of Toxocara canis, T. cati, and Baylisascaris procyonis

mature in soil and usually infect dogs, cats, and raccoons,

respectively. Eggs passed by these animals may be ingested by humans

and hatch in the intestine. Larvae penetrate the intestinal wall and

migrate through liver, lungs, CNS, eyes, and almost all other tissues.

The larvae usually do not complete their development in the human

body, but they remain alive for many months. Ingestion of raw or

poorly cooked liver or meats of various animals may also cause infection.

Symptoms and Signs

 

The visceral larva migrans (VLM) syndrome consists of fever, anorexia,

hepatosplenomegaly, skin rashes, pneumonitis, and asthmatic attacks,

depending on the affected organs. Hyperglobulinemia, leukocytosis, and

marked eosinophilia are common. Tissue damage is caused by focal

eosinophilic granulomatous reactions to the migrating larvae. VLM

occurs mostly in 2- to 5-yr-old children with a history of geophagia.

The syndrome is self-limiting in 6 to 18 mo if egg intake ceases.

Deaths due to invasion of the brain or heart occur rarely.

 

Ocular larva migrans (OLM), also called ocular toxocariasis, usually

presents with no or very mild systemic manifestations. OLM lesions

consist mostly of granulomatous reactions in the retina that may cause

visual impairment. OLM occurs in older children and less commonly in

young adults.

Diagnosis

 

Diagnosis is based on clinical, epidemiologic, and serologic findings.

A highly specific ELISA test to detect antibodies to T. canis larvae

has been developed. Biopsies of the liver or other affected organs may

show eosinophilic granulomatous reactions. The larvae are difficult to

find in tissue sections, and biopsies are low yield. Stool

examinations are worthless. OLM should be distinguished from

retinoblastoma to prevent unnecessary surgical enucleation of the eye.

Prevention and Treatment

 

Infection in puppies exceeds 80% in the USA; infection in cats is much

less common, but both should be dewormed regularly. Contact between

animal feces and children should be minimized.

 

No proven treatment for VLM is available. The usefulness of

diethylcarbamazine (2 mg/kg po tid for 1 to 2 wk), mebendazole (100 to

200 mg po bid for 5 days), or albendazole (400 mg po bid for 3 to 5

days) remains uncertain. Antihistamines for mild symptoms may suffice;

treatment with corticosteroids (prednisone 20 to 40 mg/day po) for

severe symptoms may be lifesaving. Corticosteroids are also indicated

for acute OLM. Laser photocoagulation may be attempted to kill larvae

in the retina.

TRICHINOSIS

(Trichiniasis)

 

Infection with Trichinella spiralis, which may cause mild GI symptoms

followed by periorbital edema, muscle pains, fever, and eosinophilia.

Etiology and Pathogenesis

 

Trichinosis occurs worldwide. The life cycle is maintained by animals

that are fed (eg, pigs) or that hunt (eg, bears, boars) other animals

whose striated muscles contain encysted infective larvae (eg,

rodents). Humans become infected by eating undercooked or processed

meat from infected carnivores. Larvae undergo excystation in the small

intestine, penetrate the mucosa, and become adults in 6 to 8 days.

Mature females release living larvae for 4 to 6 wk and then die or are

expelled. Newborn larvae migrate but survive only within striated

skeletal muscle cells. Larvae fully encyst in 1 to 3 mo and remain

viable for many years as intracellular parasites. The cycle continues

only if encysted larvae are ingested by another carnivore.

Symptoms and Signs

 

GI symptoms are absent or mild in many infected persons. During the

1st wk, nausea, abdominal cramps, and diarrhea may occur; 1 to 2 wk

after infection, the characteristic pentad of signs and symptoms

begins: facial or periorbital edema or cheilosis, myalgia, persistent

fever, headache, and subconjunctival hemorrhages and petechiae. Eye

pain and photophobia often precede myalgia.

 

Muscle cells invaded by larvae cause symptoms that mimic polymyositis.

Soreness may affect the muscles of respiration, speech, mastication,

and swallowing. Severe dyspnea may occur in heavy infections.

 

Fever is generally remittent, rising to 39° C (102° F) or higher,

remaining elevated for several days, and then falling gradually.

Eosinophilia usually begins when newborn larvae invade tissues, peaks

2 to 4 wk after infection, and gradually declines as the larvae encyst.

 

In heavy infections, the inflammation may cause cardiac (myocarditis,

heart failure, arrhythmia), neurologic (encephalitis, meningitis,

visual or auditory disorders, seizures), or pulmonary (pneumonitis,

pleurisy) complications. Deaths usually result from myocarditis.

 

Signs and symptoms gradually improve, and most disappear by about the

3rd mo, when the larvae have become fully encysted in muscle cells and

eliminated from other organs and tissues. Vague muscular pains and

fatigue may persist for months.

Diagnosis

 

No specific tests to diagnose the intestinal stage of trichinosis are

available. After the 2nd wk of infection, a muscle biopsy may disclose

larvae and cysts. Diffuse inflammation in muscle tissue indicates

recent infection; dead larvae eventually are resorbed or calcify.

 

Serologic tests include an ELISA and bentonite flocculation; each can

give false-negative results, especially if testing is done within 2 to

3 wk of infection. Since antibodies may persist for years, serologic

tests are of most value if they are initially negative and then turn

positive. Serology and muscle biopsy are complementary tests: either

one can be negative in a given patient. Skin testing with larval

antigens is unreliable.

 

Muscle enzymes (creatine phosphokinase and LDH) are elevated in 50% of

patients and correlate with abnormal electromyograms.

 

Trichinosis must be differentiated from acute rheumatic fever, acute

arthritis, angioedema, and myositis; febrile states from TB, typhoid

fever, sepsis, and undulant fever; pulmonary manifestations from

pneumonitis; neurologic manifestations from meningitis, encephalitis,

and poliomyelitis; and eosinophilia from Hodgkin's disease,

eosinophilic leukemia, polyarteritis nodosa, and disease caused by

other migrating nematodes.

Prevention and Treatment

 

Trichinosis is prevented by cooking meat thoroughly (55° C [140° F]

throughout). Larvae can usually be killed by freezing the meat at -15°

C (5° F) for 3 wk or -18° C (0° F) for 1 day. Smoking or salting meat

may not kill larvae.

 

The infection is self-limited, often requiring only symptomatic and

supportive therapy commensurate with disease severity. Analgesics (eg,

aspirin or narcotics) may be required for muscle pains. For patients

with severe allergic manifestations or myocardial or CNS involvement,

prednisone 20 to 60 mg/day po in divided doses is given for 3 or 4

days; dosage is gradually reduced and the drug is discontinued in 10

to 14 days.

 

Anthelmintic drugs are seldom indicated. Mebendazole (200 to 400 mg po

tid for 3 days, then 400 to 500 mg tid for 10 days), thiabendazole (25

mg/kg po bid for 5 to 10 days), or pyrantel (11 mg/kg po for 5 days)

eliminates adult worms from the GI tract, but these drugs have no

effect on encysted larvae.

DRACUNCULOSIS

(Guinea Worm Disease; Dracontiasis; " Fiery Serpent " )

 

Infection with Dracunculus medinensis, which may cause a painful skin

ulcer and debilitating arthritis.

Etiology and Pathogenesis

 

Dracunculosis is endemic in much of tropical Africa, India, Pakistan,

the Near East, parts of South America, and the West Indies. Ten to 40

million people are infected annually worldwide.

 

Humans become infected by drinking water containing infected

microcrustaceans. The larvae penetrate the intestinal wall, mature

into adult worms, and migrate to connective tissues. When the gravid

female migrates to subcutaneous tissues, the cephalic end of the worm

produces an indurated papule that vesiculates and eventually

ulcerates. On contact with water, a loop of the uterus prolapses

through the anterior end of the worm and discharges motile larvae in

water. If there are no complications, expulsion of the worm through

the blister takes 1 to 3 wk of repeated immersion in water. Worms that

fail to reach the skin disintegrate and are resorbed or become

calcified. In most areas, one infectious episode lasts about 1 yr, and

transmission occurs each year during the same season.

Symptoms and Signs

 

Infection is generally asymptomatic during the 1st yr. Symptom onset

coincides with eruption of the worm. Local symptoms include intense

itching and a burning pain at the small blister. Urticaria, erythema,

dyspnea, vomiting, and pruritus are thought to reflect allergic

reactions to toxic worm products that produce the blister. If the worm

is broken during expulsion or extraction and larvae escape in tissues,

a severe inflammatory reaction ensues with disabling pain. Symptoms

subside, and the ulcer heals once the adult worm is expelled. In about

50% of cases, secondary bacterial infections occur along the track of

the emerging worm. Chronic sequelae include fibrous ankylosis of

joints and contraction of tendons.

Diagnosis

 

Diagnosis is obvious once the head of the adult worm appears at the

ulcer. Discharge of larvae may be stimulated by cooling the ulcerated

area. Calcified worms can be localized with x-ray examination (they

have been found in Egyptian mummies). Skin testing with crude worm

extract produces a wheal and flare reaction but is often negative

before the female worm emerges. Serodiagnostic tests are not specific.

Prevention and Treatment

 

Although chemoprophylaxis with diethylcarbamazine appears to be

effective, the simplest method to prevent infection is to filter

drinking water through a piece of cheesecloth.

 

Treatment consists of slow removal of the adult worm over days to

weeks by rolling it on a stick. Surgical removal, which can reduce

disability, is possible but seldom available in endemic areas. The

beneficial effect of thiabendazole (50 to 75 mg/kg po in 2 divided

doses for 3 days) or metronidazole (250 mg po tid for 6 days) has been

ascribed to the drugs' anti-inflammatory and antibacterial properties

rather than to their anthelmintic effects.

 

Prevention of secondary infection and reduction of the local

inflammatory response with topical antibiotics and hydrocortisone (or

with systemic antibiotics if needed) may speed worm expulsion and

extraction.

FILARIAL NEMATODE INFECTIONS

 

Threadlike adult filarial worms reside in tissues. Gravid females

produce live offspring (microfilariae) that circulate in blood or

migrate through tissues. When ingested by a suitable insect

(mosquitoes or flies), microfilariae develop into infective larvae

that are inoculated or deposited on the skin during the insect bite.

Only a few worm species regularly infect humans. In addition, filarial

parasites of animals occasionally infect, but do not fully develop, in

the human host.

Lymphatic Filariasis

 

Infections with 3 species of Filarioidea, which may lead to acute

adenolymphangitis and chronic lymphedema, hydroceles, or chyluria.

Etiology and Pathogenesis

 

Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi,

or B. timori, which is spread by mosquitoes. Infective larvae escape

from the proboscis as the mosquito bites, enter the puncture wound,

and migrate to the lymphatics, where they develop into adult worms

within 6 to 12 mo. Gravid females produce microfilariae that circulate

in blood.

 

Bancroftian filariasis is present in tropical and subtropical areas of

Africa, Asia, the Pacific, and the Americas, including parts of the

Caribbean. Brugian filariasis is limited to South and Southeast Asia.

Current estimates suggest that about 90 million people are infected.

Symptoms and Signs

 

Infection often leads to microfilaremia without clinical

manifestations. However, acute inflammatory filariasis consists of

episodes (often recurrent) lasting 4 to 7 days of fever, acute

adenitis with typical retrograde lymphangitis (ADL), or acute

funiculitis and epididymitis. Transient lymphedema of an affected limb

may result in an abscess that drains externally and leaves a scar. ADL

in areas draining the legs is often caused or aggravated by secondary

bacterial infections.

 

Chronic filarial disease often develops insidiously after many years.

In most patients, asymptomatic lymphatic dilatation occurs, but

chronic inflammatory responses to adult worms may lead to chronic

lymphedema of the affected body area or to scrotal hydroceles.

Hyperkeratosis and increased local susceptibility to bacterial and

fungal infections then lead to elephantiasis. Other forms of chronic

filarial disease are caused by disruption of lymphatic vessels or

aberrant drainage of lymph fluid, leading to chyluria and chyloceles.

 

Tropical pulmonary eosinophilia (TPE) is uncommon. It is manifested by

recurrent asthmatic attacks, transitory lung field mottlings,

low-grade fever, and marked leukocytosis and eosinophilia.

Microfilariae usually are not found in blood but are present in

eosinophilic abscesses in the lungs or lymph nodes. TPE is most likely

due to allergic reactions to microfilariae. Chronic TPE can lead to

pulmonary fibrosis. Other extralymphatic signs include chronic

microscopic hematuria and proteinuria and mild polyarthritis, all

presumed to result from immune complex deposition.

 

ADL episodes usually precede onset of chronic disease by >= 2 decades.

Acute filariasis is more severe and progression to chronic disease is

faster in previously unexposed immigrants to endemic areas than in

native residents. Microfilaremia and symptoms gradually disappear

after leaving the endemic area.

Diagnosis

 

Microscopic detection of microfilariae in blood establishes the

diagnosis. Filtered or centrifuged concentrates of blood are much more

sensitive than thick blood films. Blood samples must be obtained when

peak microfilaremia occurs, ie, at night in most endemic areas but

during the day in many Pacific islands. Viable adult worms can be

visualized in dilated lymphatics by ultrasonography; their movement

has been called the filarial dance.

 

Serologic tests cannot differentiate past exposure from current active

infection. A highly sensitive and specific test to detect worm antigen

in sera from patients with bancroftian filariasis is available.

Prevention and Treatment

 

Protection requires reducing contact with infected mosquitoes. The

effectiveness of chemoprophylaxis with diethylcarbamazine (DEC) is

unproven.

 

Treatment of lymphatic filariasis is problematic. DEC kills

microfilariae but only a variable proportion of adult worms. A single

oral dose of 6 mg/kg is recommended. Ivermectin rapidly reduces

microfilaremia levels and may inhibit larval development in

mosquitoes, but the drug does not kill adult worms and is not very

effective against brugian filariasis.

 

Acute attacks generally resolve spontaneously, although antibiotics

may be required to control secondary infections. TPE often responds to

DEC, but relapses are common and may require multiple courses. Whether

DEC prevents or lessens chronic lymphedema remains controversial.

 

Treatment of chronic lymphedema can be remarkably effective. Surgical

creation of nodal-venous shunts to improve lymphatic drainage offers

long-term benefit even in advanced cases of elephantiasis, and

conservative measures such as elastic bandaging of the affected limb

help to reduce swelling. Meticulous skin care, including the use of

antibiotic ointments and systemic antibiotic prophylaxis, may reverse

lymphedema and prevent its progression to elephantiasis.

Onchocerciasis

(River Blindness)

 

Infection with the filarial nematode Onchocerca volvulus, causing

chronic skin disease and eye lesions that may lead to blindness.

Etiology and Pathogenesis

 

Onchocerciasis is spread by blackflies (Simulium sp) that breed in

swiftly flowing streams (hence the term river blindness). Infective

larvae inoculated into the skin during the bite of a blackfly develop

into adult worms in about 1 yr. Adult female worms may live up to 15

yr in subcutaneous deeper fibrous nodules. Adult male worms migrate

between nodules and periodically inseminate the females. Mature worms

produce live microfilariae that migrate mainly through the skin and

invade the eyes. About 18 million people are infected, of whom about

270,000 are blind and a further 500,000 are visually impaired.

Infection and disease are most common in tropical and Sahel regions of

Africa; smaller foci exist in Yemen, southern Mexico, Guatemala,

Ecuador, Colombia, Venezuela, and the Brazilian Amazon.

Symptoms and Signs

 

The subcutaneous (or deeper) nodules (onchocercoma) that contain adult

worms are visible or palpable but otherwise asymptomatic. They are

composed of inflammatory cells and fibrotic tissue in various

proportions; old nodules may caseate and calcify.

 

Onchocercal dermatitis is caused by the microfilarial stage of the

parasite. Intense pruritus may be the only symptom in lightly infected

persons. Skin lesions usually consist of a nondescript maculopapular

rash with secondary excoriations, scaling ulcerations and

lichenification, and mild to moderate lymphadenopathy. Premature

wrinkling, skin atrophy, massive enlargement of inguinal or femoral

nodes, lymphatic obstruction, patchy hypopigmentation, and transitory

localized areas of edema and erythema can occur. Onchocercal

dermatitis is generalized in most patients, but a localized and

sharply delineated form of eczematous dermatitis with hyperkeratosis,

scaling, and pigment changes (Sowdah) is common in Yemen and Saudi Arabia.

 

Eye disease ranges from mild visual impairment to complete blindness.

Lesions of the anterior eye include punctate (snowflake) keratitis, an

acute inflammatory infiltrate surrounding dying microfilariae that

resolves without causing permanent damage; sclerosing keratitis, an

ingrowth of fibrovascular scar tissue that may cause luxation of the

lens and blindness; and anterior uveitis or iridocyclitis that may

deform the pupil. Chorioretinitis, optic neuritis, and optic atrophy

may also occur.

 

Onchocerciasis is the second leading cause of blindness worldwide

(after trachoma). Blindness is common in Savannah regions of Africa,

where it is due mostly to sclerosing keratitis; is much less common in

rain forest areas, where it is caused by chorioretinal lesions; and is

fairly rare in the Americas, where it is caused mostly by lesions of

the posterior eye segment.

Diagnosis

 

Demonstration of microfilariae in skin snips is the traditional method

of determining the presence and severity of infection (see Table

161-1). Microfilariae may also be seen in the cornea and anterior

chamber of the eye. PCR-based methods to detect parasite DNA in skin

snips with species-specific DNA probes may be more sensitive than

standard techniques. Evaluation of a serodiagnostic test that uses

Onchocerca-specific recombinant antigens is in progress.

 

Palpable nodules (or deep nodules detected by ultrasonography or MRI

scanning) can be excised and examined for adult worms by routine

histology or after digestion with collagenase. Blinding and

nonblinding forms of African O. volvulus can be distinguished from

each other with specific DNA probes.

Prevention

 

No drug has been shown to protect against infection with O. volvulus.

However, annual or semiannual administration of ivermectin effectively

controls disease and may decrease transmission of the parasite.

Surgical removal of all accessible onchocercoma reduces skin

microfilaria counts and may decrease the prevalence of blindness.

 

In theory it is possible to minimize Simulium bites by avoiding

fly-infested areas, wearing protective clothing, and liberally using

insect repellents. Killing blackfly larvae is the mainstay of a

multinational onchocerciasis control program in West Africa.

Treatment

 

The drug of choice is ivermectin given as a single oral dose of 150

µg/kg once or twice a year. It should not be given to children <= 5 yr

old or weighing <= 15 kg, to pregnant women, to mothers nursing

infants during the 1st wk of life, and to severely ill persons.

Ivermectin rapidly reduces microfilariae in the skin and eyes. It does

not appear to kill adult worms but blocks the release of microfilariae

from the uterus for several months. Side effects are qualitatively

similar to those of diethylcarbamazine (DEC) but are much less common

and less severe. DEC is no longer recommended for onchocerciasis

because it causes nephrotoxicity and the Mazzotti reaction, which can

further damage skin and eyes, lead to cardiovascular collapse, and

precipitate blindness in heavily infected patients. Suramin is

effective but must be given IV over several weeks. Elimination of

adult worms may also be attempted by surgically removing onchocercoma.

Loiasis

 

Infection with Loa loa, which may cause localized angioedema of the

skin and a syndrome of allergic hypereosinophilia.

Etiology and Pathogenesis

 

Loa loa is transmitted by tabanid flies (Chrysops, the deerfly or

horsefly). Adults migrate in subcutaneous tissues and the eye, and

microfilariae circulate in blood. Loiasis is confined to the rain

forest belt of western and central Africa and equatorial Sudan.

Loiasis readily develops in visitors who live a few months in an

endemic area, such as missionaries or Peace Corps volunteers.

Symptoms, Signs, and Diagnosis

 

Infection in native residents produces mostly areas of angioedema

(Calabar swellings) that develop anywhere on the body but

predominantly on the extremities, usually last for 1 to 3 days, and

are presumed to reflect hypersensitivity reactions to allergens

released by migrating adult worms. Worms also migrate

subconjunctivally across the eyes; this may be unsettling, but

residual eye lesions are uncommon. Less common pathologic changes

include nephropathy, encephalopathy, and cardiomyopathy. Nephropathy

generally presents as proteinuria with or without mild hematuria and

is believed to be due to immune complexes. Proteinuria is transiently

exacerbated by treatment with diethylcarbamazine (DEC). Encephalopathy

is mild and usually associated with vague CNS symptoms. DEC

exacerbates CNS symptoms and can result in coma and death.

 

In visitors, unlike in native Africans, allergic hyperreactive

symptoms predominate. Calabar swellings tend to be more frequent and

severe in visitors, who may also develop a systemic hypereosinophilic

syndrome that may lead to endomyocardial fibrosis.

 

Microscopic detection of microfilariae in peripheral blood establishes

the diagnosis. Blood samples should be drawn around noontime, when

microfilaremia levels are the highest. Temporary residents of endemic

areas often remain amicrofilaremic. Serodiagnostic tests cannot yet

differentiate Loa loa from other filarial nematodes.

Prevention and Treatment

 

Insect repellents may reduce personal exposure to infected flies.

However, oral DEC (300 mg once weekly) is the only proven method to

prevent infection.

 

DEC is the only drug that kills microfilariae and adult worms. The

recommended course of 8 to 10 mg/kg/day po for 2 to 3 wk may have to

be repeated to cure some patients. In heavily infected patients,

treatment may trigger encephalopathy leading to coma and death. Such

patients may benefit from initial treatment with low doses of DEC

(such as 1 mg/kg/day) and simultaneous corticosteroids. Ivermectin in

doses used for treatment of onchocerciasis may be a safe and effective

alternative to DEC.

Dirofilariasis

(Dog Heartworm Infection)

 

Infection with Dirofilaria immitis, a common filarial parasite of dogs.

 

Transmission of D. immitis to humans by an infected mosquito is very

rare. The larvae become encapsulated in infarcted lung tissue and

produce well-defined pulmonary nodules. The patient may have chest

pain, cough, and occasionally hemoptysis. Many patients remain

asymptomatic, and a pulmonary nodule is discovered on routine chest

x-ray. The diagnosis is made by histologic examination of a surgical

specimen. Serodiagnostic tests are positive in only about 35% of cases

but may prevent unnecessary surgery. No treatment is indicated; the

infection is self-limited.