Merck Manual: Intestinal Protozoa

[Guest guest]

http://www.merck.com/mrkshared/mmanual/section13/chapter161/161d.jsp

 

 

Merck Manual

 

Intestinal Protozoa

 

Multiple pathogenic parasites and nonpathogenic commensals often are

present in the bowel. The most important pathogens are Entamoeba

histolytica, Giardia lamblia, Cryptosporidium, Isospora, Cyclospora,

and Microsporidia.

 

Intestinal protozoa are passed by the fecal-oral route, and infections

are widespread in developing countries with inadequate sanitation.

They are also common within the USA where fecal incontinence and poor

hygiene prevail, such as in mental institutions and day care centers.

Some amebas and GI protozoa are spread as sexually transmitted

diseases, especially among promiscuous male homosexuals, and several

protozoan species cause major opportunistic infections in patients

with AIDS. Asymptomatic infected persons are a major source of

environmental and person-to-person spread and should be treated.

 

Clinical diagnosis is unreliable; microscopic examination of suitable

stool specimens is necessary. Diagnosis may require several samples,

concentration methods, special stains, or semi-invasive diagnostic

techniques such as endoscopic biopsy (see Table 161-1).

AMEBIASIS

(Entamebiasis)

 

Infection of the colon with Entamoeba histolytica, which is commonly

asymptomatic but may produce clinical manifestations ranging from mild

diarrhea to severe dysentery.

Etiology and Pathogenesis

 

Amebiasis is a protozoan infection of the lower GI tract. E.

histolytica exists in two forms: the trophozoite and the cyst. The

trophozoite is a motile stage that feeds on bacteria and tissue,

reproduces, colonizes the lumen and the mucosa of the large intestine,

and sometimes invades tissues and organs. Some trophozoites in the

colonic lumen become cysts that are excreted with feces. Trophozoites

predominate in liquid stools (no matter what causes the diarrhea) but

rapidly die outside the body. Cysts predominate in formed stools.

 

Cysts are resistant to the external environment. They may spread

either directly from person to person or indirectly via food or water.

Amebiasis is a sexually transmitted disease in male homosexuals.

 

Two species of Entamoeba are morphologically indistinguishable: E.

histolytica is pathogenic and E. dispar harmlessly colonizes the

colon. Amebas adhere to and kill colonic epithelial cells and cause

dysentery with blood and mucus in the stool. Amebas also secrete

proteases that degrade the extracellular matrix and permit invasion

into the bowel wall and beyond. Amebas can spread via the portal

circulation and cause necrotic liver abscesses. The infection may

spread further by direct extension from the liver or through the

bloodstream to the lungs, brain, and other organs.

Symptoms and Signs

 

Most infected persons are asymptomatic but chronically pass cysts in

stools. Symptoms that occur with tissue invasion include intermittent

diarrhea and constipation, flatulence, and cramping abdominal pain.

There may be tenderness over the liver and ascending colon, and the

stools may contain mucus and blood.

 

Amebic dysentery, common in the tropics but uncommon in temperate

climates, is characterized by episodes of frequent (semi)liquid stools

that often contain blood, mucus, and live trophozoites. Abdominal

findings range from mild tenderness to frank abdominal pain with high

fevers and systemic toxic symptoms. Tender hepatomegaly frequently

accompanies amebic colitis. Between relapses, symptoms diminish to

recurrent cramps and loose or very soft stools, but emaciation and

anemia continue. Symptoms of subacute appendicitis may occur. Surgery

in such cases may result in peritonitis.

 

Chronic infection commonly mimics inflammatory bowel disease and

presents as intermittent nondysenteric diarrhea with abdominal pain,

mucus, flatulence, and weight loss. Chronic infection may also present

as tender, palpable masses or annular lesions in the cecum and

ascending colon that resemble carcinomas (amebomas).

 

Metastatic disease originates in the colon and can involve any organ,

but a liver abscess, usually single and in the right lobe, is the most

common. It can present in patients without prior symptoms, is more

common in men than in women (ratio of 7:1 to 9:1), and may develop

insidiously. Symptoms include pain or discomfort over the liver, which

is aggravated by movement and occasionally referred to the right

shoulder; intermittent fever; sweats; chills; nausea; vomiting;

weakness; and weight loss. Jaundice is unusual and low-grade when

present. The abscess may perforate into the subphrenic space, right

pleural cavity, right lung, and other adjacent organs. Skin lesions

caused by direct implantation of trophozoites are occasionally

observed, especially around the perineum and buttocks and particularly

in traumatic and operative wounds.

Diagnosis

 

Nondysenteric amebiasis is often misdiagnosed as irritable bowel

syndrome, regional enteritis, or diverticulitis. Amebic dysentery may

be confused with shigellosis, salmonellosis, schistosomiasis, or

ulcerative colitis. The stools in amebic dysentery are more fecal and

less frequent and watery than those in bacillary dysentery. They

characteristically contain tenacious mucus and flecks of both fresh

and altered blood. Unlike stools in shigellosis, salmonellosis, and

ulcerative colitis, amebic stools do not contain large numbers of WBCs.

 

Hepatic amebiasis and amebic abscess must be differentiated from other

hepatic infections, including bacterial abscesses and infected

echinococcus cysts.

 

Intestinal amebiasis is confirmed by finding E. histolytica in the

stool or tissues. Diagnosis may require examination of 3 to 6 stool

specimens and concentration methods (see Table 161-1). Antibiotics,

antacids, antidiarrheals, enemas, and intestinal radiocontrast agents

may interfere with recovery of the parasite and should not be given

until the stool has been examined. E. histolytica has to be

distinguished from nonpathogenic amebas and E. coli.

 

In symptomatic patients, proctoscopy often shows flask-shaped mucosal

lesions, which should be aspirated and the material examined for

trophozoites. Biopsy specimens from rectosigmoid lesions may also show

trophozoites.

 

Extraintestinal amebiasis is more difficult to diagnose. Stool

examination is usually negative, and recovery of trophozoites from

aspirated pus is uncommon. A therapeutic trial of amebicides may be

the most helpful diagnostic tool for an amebic liver abscess.

 

Serologic tests are positive in almost all patients with amebic liver

abscess and in > 80% of those with amebic dysentery. The tests are

positive in only about 10% of asymptomatic carriers. The indirect

hemagglutination and enzyme-linked immunosorbent assays (ELISA) are

the most sensitive tests available. Antibody titers may persist for

months or years.

 

When a liver abscess is present, x-rays may show elevation and

fixation or impaired excursion of the right diaphragm. Radioisotopic

liver scanning or CT may show the extent of the abscess, while

ultrasound scans may show it to be fluid-filled. The alkaline

phosphatase level may be elevated. Needle aspirations are usually

reserved for lesions > 10 cm, suspicion of imminent rupture, or poor

response to 5 days of drug therapy. The abscesses contain thick,

semifluid material ranging from yellow to chocolate-brown. A needle

biopsy may show necrotic tissue, but motile amebas are difficult to

find in the abscess material and cysts are not present.

Prevention

 

Contamination of food and water with human feces must be prevented, a

problem complicated by the high incidence of asymptomatic carriers.

Chlorine levels sufficient to kill bacteria will not affect the cysts

of E. histolytica, but boiling or treating water with tetraglycine

hydroperiodide tablets (1 to 2 tablets per quart or liter) kills cysts.

Treatment

 

General therapy relieves symptoms, replaces blood, and corrects fluid

and electrolyte losses. If symptoms of appendicitis are thought to be

of amebic origin, surgery may be delayed for 48 to 72 h to observe the

effects of chemotherapy.

 

Asymptomatic persons who pass cysts should be treated to prevent their

spreading the infection. One course of oral diloxanide furoate (500 mg

tid for 10 days in adults or 20 mg/kg/day in 3 divided doses for

children) is usually given. A suitable alternative is 20 days with

iodoquinol (650 mg po tid for adults or 30 to 40 mg/kg/day in 3

divided doses for children, with a maximum of 2 g to avoid causing

optic neuritis). Metronidazole has a high failure rate in asymptomatic

cyst passers unless used at high doses.

 

For those with mild GI symptoms, 5 to 10 days of treatment with oral

metronidazole is recommended (750 mg tid for adults, 35 to 50

mg/kg/day in 3 divided doses for children). Metronidazole should not

be given to pregnant women. For those with moderate GI symptoms, a

course of metronidazole may have to be followed by a second oral drug

such as iodoquinol or diloxanide furoate at the doses listed above or

with paromomycin (25 to 30 mg/kg/day in 3 divided doses for 7 days) to

prevent relapses. If symptoms are severe, oral drugs may be followed

by emetine 1 mg/kg/day (maximum 60 mg) or dehydroemetine 1 to 1.5

mg/kg/day (maximum 90 mg) given IM until symptoms are controlled

(maximum 5 days). Emetine and dehydroemetine are toxic, and patients

receiving them should be confined to bed and monitored by ECG. Therapy

should be stopped promptly if signs of toxicity appear, such as

tachycardia, hypotension, muscular weakness, marked GI effects, or

dermatoses. Contraindications include pregnancy and renal or cardiac

disease.

 

For extraintestinal amebiasis, metronidazole is the drug of choice and

is given as above. Alternatively, emetine or dehydroemetine can be

given for 5 days as described for severe amebic dysentery. Emetine or

dehydroemetine used to treat hepatic disease should be combined with

chloroquine (1 g/day po for 2 days, then 500 mg/day for 3 wk in

adults; 10 mg/kg/day in children, with a maximum of 300 mg chloroquine

base/day). If E. histolytica is present in stool, iodoquinol may also

be given, as described above.

 

Stools should be reexamined for relapse 1, 3, and 6 mo after

treatment, if feasible.

GIARDIASIS

 

Infection of the small intestine with the flagellated protozoan

Giardia lamblia, which can be asymptomatic or cause clinical

manifestations ranging from intermittent flatulence to chronic

malabsorption.

Etiology and Pathogenesis

 

Giardia trophozoites firmly attach to the duodenal and proximal

jejunal mucosa and multiply by binary fission. Released organisms

rapidly transform into environmentally resistant cysts that are passed

in stool and spread by the fecal-oral route. Waterborne transmission

is the major source of giardiasis. Transmission can also occur by

direct person-to-person contact, especially in mental institutions, in

day care centers, or between sexual partners. Filtration of water

through soil removes Giardia cysts, but these remain viable in surface

water and are resistant to routine levels of chlorination. In addition

to humans, wild animals may serve as reservoirs. Thus, mountain

streams as well as chlorinated but poorly filtered urban water supply

systems have been implicated in waterborne epidemics.

 

The infection occurs worldwide, especially among children and where

sanitation is poor. In the USA, giardiasis is one of the most common

intestinal infections. Infection rates are high among travelers to

many countries, in promiscuous male homosexuals, and in patients who

are postgastrectomy, have chronic pancreatitis, or have

hypogammaglobulinemia.

Symptoms and Signs

 

Most cases are asymptomatic. However, these persons pass infective

cysts and need to be treated. Symptoms of acute giardiasis generally

appear 1 to 3 wk after infection. Symptoms are usually mild and

include watery malodorous diarrhea, abdominal cramps and distention,

flatulence and eructation, intermittent nausea, and epigastric pain.

Low-grade fever, chills, malaise, and headaches may be present.

Malabsorption of fat and sugars can lead to significant weight loss in

severe cases. Blood and mucus usually are not found in stool.

 

The chronic phase may evolve from, or occur without, an acute illness.

Periodic loose foul stools, abdominal distention, and malodorous

flatus predominate. Chronic giardiasis occasionally is a cause of

failure to thrive in children.

Diagnosis

 

Characteristic trophozoites or cysts in stool are diagnostic. These

are readily seen in acute infections, but parasite excretion is

intermittent and at low levels in chronic infections. Thus, diagnosis

may require repeated stool examinations or sampling of the upper

intestinal contents obtained with a nylon string or by endoscopic

aspiration. Immunofluorescent assays and ELISAs to detect parasites or

parasite antigens in stool are available. Specific DNA probes are

under evaluation.

Prevention

 

Scrupulous personal hygiene may prevent person-to-person transmission.

Treatment of asymptomatic cyst passers reduces the spread of

infection, but whether treatment of asymptomatic infected children in

day care centers is cost-effective remains unclear. Water can be

decontaminated by boiling or heating to at least 70° C (158° F) for 10

min. Giardia cysts resist routine levels of chlorination; iodine-based

disinfection must be carried out for at least 8 h to be effective.

Some filtration devices can remove Giardia cysts from contaminated water.

Treatment

 

Oral metronidazole (250 mg tid for 5 days in adults; 15 mg/kg/day in 3

divided doses for 5 days in children) is effective, but it is not

currently licensed in the USA for use in giardiasis. Side effects

include nausea, headaches, and, less commonly, black urine,

paresthesia, and dizziness. Oral quinacrine (100 mg tid for 5 days in

adults; 2 mg/kg tid [maximum 300 mg/day] for 5 days in children) is

highly effective but may produce GI disturbances, dizziness, and

headaches and, rarely, exfoliative dermatitis and toxic psychosis. It

is no longer available in the USA. Oral furazolidone (100 mg qid for 7

to 10 days in adults; 6 mg/kg/day in 4 divided doses for 7 to 10 days

in children) is less effective than quinacrine and metronidazole but

is available as a suspension, making it useful in children.

 

Household and sexual contacts should be examined and treated if

infected. Treatment during pregnancy should be avoided if possible;

metronidazole should not be given to pregnant women. If therapy cannot

be delayed because of severe symptoms, a nonabsorbable aminoglycoside

such as paromomycin (25 to 35 mg/kg/day po in 3 divided doses for 7

days) can be used.

CRYPTOSPORIDIOSIS

 

Infection with protozoa of the genus Cryptosporidium, causing

diarrheal disease.

Etiology and Pathogenesis

 

Cryptosporidia are coccidian protozoa that replicate intracellularly

in the brush border of the small intestine. Infective oocysts are shed

into the lumen and passed in the feces. After its ingestion by another

vertebrate, the oocyst releases sporozoites that transform into

trophozoites in the brush border, replicate, and then produce oocysts

after about 12 days.

 

C. parvum causes most cases. Infections result from zoonotic spread,

direct person-to-person contact, or waterborne transmission. The

disease occurs worldwide; children, travelers to foreign countries,

immunocompromised patients, and medical personnel caring for patients

with cryptosporidiosis are at high risk. Cryptosporidiosis is

responsible for up to 5% of all gastroenteritis in both industrialized

and developing countries. Outbreaks have occurred in day care centers;

nosocomial transmission has caused large waterborne outbreaks in

several U.S. cities.

Symptoms and Signs

 

The incubation period is about 1 wk, and clinical illness occurs in >

80% of infected persons. The onset is acute, with profuse watery

diarrhea, abdominal cramping, and, less commonly, nausea, anorexia,

fever, and malaise. Symptoms generally persist 1 to 2 wk, rarely >= 1

mo, and then abate. Fecal excretion of oocysts may continue for

several weeks after clinical symptoms have subsided. Asymptomatic

shedding of oocysts is common among older children in developing

countries.

 

In the immunocompromised host, the onset of disease may be more

gradual, but diarrhea can be more severe. Unless the underlying immune

defect is corrected, infection is not cleared. Thus, profuse

intractable diarrhea may continue persistently or intermittently for

life, with fluid losses > 5 to 10 L/day.

Diagnosis

 

Identifying the acid-fast oocysts in stool confirms the diagnosis;

conventional methods of stool examination are unreliable. Using the

formalin-ethyl acetate sedimentation or the sugar flotation stool

concentration procedures enhances diagnosis. Cryptosporidium oocysts

can be identified by phase-contrast microscopy or by staining with the

Kinyoun modified acid-fast reagent. Fluorescein-labeled monoclonal

antibody and ELISA kits provide excellent detection of oocysts.

Intestinal biopsy is a last resort.

Prevention and Treatment

 

Stools of patients with cryptosporidiosis are highly infectious;

strict stool precautions should be observed. Boiling water is the most

reliable decontamination method; only filters with pore sizes <= 1 µm

remove Cryptosporidia.

 

In immunocompetent persons, cryptosporidiosis is self-limiting,

requiring only supportive treatment. No completely effective drug is

available, but paromomycin (500 to 750 mg po qid) has the highest

success rate; relapses are common. In some AIDS patients, symptoms of

cryptosporidiosis have abated after antiretroviral therapy. Supportive

measures, oral and parenteral rehydration, and hyperalimentation are

often vital in immunocompromised persons.

ISOSPORIASIS AND CYCLOSPORIASIS

 

Infections with the coccidian protozoa Isospora belli or Cyclospora

cayetanensis, causing diarrhea.

Etiology and Pathogenesis

 

The life cycles of I. belli and C. cayetanensis are similar to that of

Cryptosporidium, except that oocysts must sporulate before becoming

infective. Human isosporiasis is most common in tropical and

subtropical climates. Transmission is by the fecal-oral route via

contaminated food or drink. Dogs and other mammals are believed to

harbor I. belli.

Symptoms and Signs

 

The main complaint is watery diarrhea; the onset may be sudden with

fever, malaise, and abdominal pain. The illness usually resolves

spontaneously in a few days or weeks, but it may persist for months or

years. Prolonged disease is associated with malabsorption and weight loss.

 

In the immunocompromised host, isosporiasis and cyclosporiasis may

cause intractable, voluminous diarrhea similar to that observed in

cryptosporidiosis. Extraintestinal disease has been reported,

including cholangitis and disseminated infections.

Diagnosis

 

Detection of characteristic oocysts by microscopic examination of the

stool establishes the diagnosis. Multiple stool specimens may be

needed; detection of oocysts is facilitated by staining stool samples

with the modified acid-fast stain. Diagnosis is sometimes made only

when intracellular parasite stages are detected in biopsies of

intestinal tissue. The stool of persons with I. belli infection often

contains Charcot-Leyden crystals derived from eosinophils; peripheral

blood eosinophilia is often present. Biopsies from patients infected

with these parasites show shortened villi and infiltrates of

lymphocytes, plasma cells, and eosinophils in the lamina propria.

Prevention and Treatment

 

Prevention is as for cryptosporidiosis. Treatment of choice for both

isosporiasis and cyclosporiasis is double-strength oral

trimethoprim-sulfamethoxazole (TMP-SMX) 160 mg TMP and 800 mg SMX qid

for 10 days, then bid for 3 wk. In AIDS patients, this should be

followed by lifelong suppressive treatment with 1 double-strength

tablet of TMP-SMX 3 times/wk. Alternative treatments for isosporiasis

include pyrimethamine (25 mg/day po) plus sulfadiazine (500 mg/day po)

with leucovorin rescue; sulfonamide-sensitive patients may benefit

from high-dose pyrimethamine alone (50 to 75 mg/day with leucovorin

rescue) or roxithromycin.

MICROSPORIDIOSIS

 

Infection with Microsporidia, causing a spectrum of manifestations

that range from asymptomatic infection in immunocompetent persons to

chronic diarrhea, corneal disease, and myositis in patients with AIDS.

Etiology and Pathogenesis

 

Microsporidia are obligate intracellular spore-forming protozoan

parasites. In the lumen of the GI tract, they uncoil, harpoon a host

cell, and inoculate it with nucleated sporoplasm. Intracellular

division then produces sporoblasts that mature into spores, which

disseminate to other cells or pass into the environment via feces,

urine, or skin.

 

Little is known about routes of transmission or possible animal

reservoirs. Microsporidia probably are a common cause of subclinical

or mild self-limited illness in otherwise healthy persons. Serologic

surveys have shown that up to 50% of healthy populations, especially

those in tropical environments, have antibodies to the microsporidium

Enterocytozoon cuniculi, but only a few cases of human infection had

been reported in the pre-AIDS era. The organisms are important

opportunistic pathogens in persons with AIDS. Up to 30% of AIDS

patients with otherwise unexplained chronic diarrhea have intestinal

microsporidiosis. Others develop infections involving sites other than

the GI tract.

Symptoms and Signs

 

Clinical disease caused by microsporidia varies with the infecting

parasite species and the immune status of the host. In AIDS patients,

various species cause chronic diarrhea, cholangitis, punctate

keratoconjunctivitis, peritonitis, hepatitis, myositis, or sinusitis.

Infections of kidneys, gallbladder, and sinuses have been described.

Enterocytozoon bieneusi is present in AIDS patients both with and

without diarrhea and thus may not be the cause of diarrhea. Nosema

corneum can cause severe, vision-threatening stromal keratitis in

immunocompetent persons as well as in patients with AIDS.

Diagnosis and Treatment

 

Organisms must be demonstrated in specimens of affected tissue

obtained by biopsy, or in corneal scrapings. Microsporidia are best

seen after staining with Giemsa, PAS, Gram, or acid-fast stains. The

small spores may be detectable in feces, urine, or other secretions.

 

Albendazole (400 mg po bid) may be effective for controlling

intestinal infection with Septata intestinalis. The drug also reduces

the number of E. bieneusi in small-bowel biopsies but does not

eliminate this infection. No established treatment exists for ocular

or disseminated microsporidiasis, but some success with fumagillin

eyedrops and imidazole compounds (fluconazole, itraconazole) has been

reported.