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Medication

Medication Summary

The drugs of choice for each protozoon are listed in Table 3 and are followed by specific considerations for each drug.

Table 3. Specific Therapy for Intestinal Protozoal Infections (Open Table in a new window)

Organism	Drugs, Pediatric Dose, and Treatment Duration
E histolytica (Luminal disease or colonization)	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d
E histolytica (Luminal disease or colonization)	Paromomycin: 25-30 mg/kg/d PO divided tid for 7 d
E histolytica (Moderate colitis)	Metronidazole: 50 mg/kg/d PO divided tid for 10 d
E histolytica (Moderate colitis)	Tinidazole: 50 mg/kg/d PO for 3 d; not to exceed 2 g/d
E histolytica (Severe colitis or liver abscess)	Metronidazole: 50 mg/kg/d PO divided tid for 10 d
	Dehydroemetine*: 1-1.5 mg/kg/d divided bid PO for 5 d
	Tinidazole†: 50 mg/kg/d PO for 3-5 d; not to exceed 2 g/d
G lamblia	Tinidazole: 50 mg/kg/d PO once; not to exceed 2 g/dose
	Metronidazole: 15-20 mg/kg/d PO divided tid for 5
	Albendazole: 15 mg/k/d (not exceed 400 mg) PO q24 h, for 5-7 days
	Furazolidone: 6 mg/kg/d PO divided qid for 7-10 d
	Paromomycin: 40 mg/kg/d PO divided tid for 7 d
	Nitazoxanide: 200-400 mg/d PO divided bid for 3 d
D fragilis	Iodoquinol: 50 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d
	Paromomycin: 30 mg/kg/d PO divided tid for 7 d
	Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d
C parvum§	Paromomycin*: 30 mg/kg/d PO divided tid (duration unknown)
C parvum§	Nitazoxanide: 200-400 mg/d PO divided bid for 3 d
I belli	Trimethoprim/sulfamethoxazole (TMP/SMZ): 20/100 mg/kg/d PO divided bid for 10 d, followed by 10/50 mg/kg/d PO divided bid for 21 d
C cayetanensis	TMP/SMZ: 10/50 mg/kg/d PO divided bid for 3 d
Microsporidia S intestinalis	Albendazole* (adult dose): 800 mg/d PO divided bid
Microsporidia E bieneusi	No treatment recommended; albendazole may decrease the number of organisms
B coli	Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d
	Metronidazole: 35-50 mg/kg/d PO divided tid for 5 d
	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d
B hominis	Metronidazole: 35-50 mg/kg/d PO divided tid for 10 d
	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d
	Nitazoxanide\|\|: 500 mg/d PO divided bid for 3 d
*Efficacy is unknown. †Drug is available from the CDC Drug Service (phone: 404-639-3670; evenings, weekends, and holidays: 404-639-2888). ‡ Drug is not available in the United States. §Recommended regimens are indicated only in patients who are immunosuppressed. A recent meta-analysis has not shown evidence for a reduction in the duration or frequency of diarrhea by nitazoxanide or paromomycin when compared with placebo in immunosuppressed patients, nevertheless, oocyst clearance was significantly reduced.^[25] \|\|Recent studies have shown effective outcomes when compared to placebo, but no clinical trials have compared with other antiparasitic drugs.

Class Summary

Protozoal infections occur throughout the world and are a major cause of morbidity and mortality in some regions. Immunocompromised patients are especially at risk. Primary immune deficiency is rare, whereas secondary deficiency is more common. Immunosuppressive therapy, cancer and its treatment, HIV infection, and splenectomy can all increase vulnerability to infection. Infectious risk is proportional to neutropenia duration and severity. Protozoal infections are typically more severe in immunocompromised patients than in immunocompetent patients. In the case of cryptosporidiosis, nitazoxanide has been shown to be effective in immunocompetent and probably in immunocompromised patients, and the role of HAART has significantly reduced the incidence of all spore-forming protozoal infections.

Iodoquinol (Yodoxin)

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Used for infections caused by E histolytica, B coli, B hominis, and D fragilis. Iodoquinol, also known as diiodohydroxyquin, is a halogenated quinoline.

Metronidazole (Flagyl)

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Used for infections caused by E histolytica, B coli, B hominis, and G lamblia. Metronidazole is a nitroimidazole.

Paromomycin (Humatin)

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Used for infections caused by E histolytica, G lamblia, D fragilis, and C parvum. It is a nonabsorbable oral aminoglycoside.

Tetracycline (Sumycin)

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Used for infections caused by B coli and D fragilis. It is a broad-spectrum antibiotic.

Trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim, Septra)

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Used for infections caused by C cayetanensis and I belli. It is a broad-spectrum antibacterial and antiprotozoal antibiotic. Considered DOC for isosporiasis and cyclosporiasis.

Dehydroemetine (Mebadin)

Not FDA-approved in the United States. Used for infections caused by E histolytica. It is a main alkaloid of ipecac, less toxic than emetine; used only in combination with other drugs against severe forms of invasive amebiasis. Available in US only from the Parasitic Disease Drug Service, CDC (Atlanta, GA 30333; telephone: 404-639-3670). For more information, see CDC Drug Service.

Furazolidone (Furoxone)

Used for infections caused by G lamblia; it is an oxazolidine and belongs to the group of the nitrofurans.

Quinacrine (Atabrine)

Used for infections caused by G lamblia. It is an acridine derivative.

Albendazole (Albenza)

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Used for infections caused by E bieneusi. It is an imidazole derivative, mostly used for helminths. Its efficacy against microsporidia is still unknown.

Tinidazole (Fasigyn, Tindamax)

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Nitroimidazole, similar to metronidazole. It is used for infections caused by E histolytica and G lamblia.

Nitazoxanide (Alinia)

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Inhibits growth of C parvum sporozoites and oocysts and G lamblia trophozoites. Elicits antiprotozoal activity by interfering with pyruvate-ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction, which is essential to anaerobic energy metabolism. Available as a 20-mg/mL oral susp.

Follow-up

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Media Gallery

This micrograph stained with chlorazol black, revealed an Entamoeba histolytica cyst.
This is a scanning electron micrograph (SEM) of an in vitro Giardia lamblia culture. This photograph contains both trophozoites and a cluster of maturing cysts (bottom right). At far left, the 2 trophozoite-staged organisms are positionally situated opposite to one another, with the farthest left G lamblia displaying its dorsal, or upper surface, and the protozoan to its immediate right, its ventral, or bottom surface.
This photomicrograph revealed the morphologic details of Cryptosporidium parvum oocysts.
This is an illustration of the life cycle of Isospora belli, the causal agent of isosporiasis.
This photomicrograph of a fresh stool sample, which had been prepared using a 10% formalin solution, and stained with safranin, revealed the presence of 3 uniformly stained Cyclospora cayetanensis oocysts in the field of view.

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Table 1. Protozoa Associated with Intestinal Illness in Humans

Name	Mode of Transmission	Symptoms
Flagellates
G lamblia	Contaminated water, fecal-oral	Nausea, bloating, gas, diarrhea, anorexia
Dientamoeba fragilis	Fecal-oral, associated with Enterobius	Previously thought commensal; may cause diarrhea, abdominal, pain, nausea
Amebas
Entamoeba histolytica	Contaminated water, fecal-oral, contaminated food	Colitis, dysentery, diarrhea, liver abscess, other extraintestinal disease
Spore-forming (Coccidia)
Cryptosporidium parvum	Contaminated water, swimming pools, fecal-oral	Immunocompetent patients: Self-limited diarrhea Immunosuppressed patients: Severe and interminable diarrhea
Isospora belli	Fecal-oral	Same as in Cryptosporidium
Cyclospora cayetanensis	Fecal-oral, contaminated water and food	Same as in Cryptosporidium
Microsporidia (Septata intestinalis, Enterocytozoon bieneusi)	Fecal-oral, contaminated water	Same as in Cryptosporidium
Ciliates
Balantidium coli	Fecal-oral (frequently associated with pigs)	Colitis, diarrhea
Other
Blastocystis hominis	Fecal-oral	May cause mild diarrhea

Table.

Organism	Size (mm)	Stain Used	Other Tests
E histolytica	Trophozoite: 10-60 Cyst: 10-20	Wet mount,* trichrome, periodic Schiff	Enzyme-linked immunosorbent assay (ELISA)
G lamblia	Trophozoite: 9-21 Cyst: 7-12	Wet mount,* trichrome, hematoxylin, Lugol	ELISA*
C parvum	2-5	Modified acid-fast,* auramine-rhodamine, Sheafer method	ELISA*
I belli	30x12	Wet mount,* modified acid-fast*	None
C cayetanensis	8-10	Modified acid-fast,* wet mount	Electron microscopy
Microsporidia	1-2	Modified trichrome*	Electron microscopy, fluorescence methods, small intestine biopsy
D fragilis	7-12	Iron hematoxylin,* trichrome*	None
B. coli	50-200	Wet mount,* concentration techniques	None
B hominis	5-30	Trichrome,* iron hematoxylin*	None
*Preferred screening test in clinical settings.

Table 3. Specific Therapy for Intestinal Protozoal Infections

Organism	Drugs, Pediatric Dose, and Treatment Duration
E histolytica (Luminal disease or colonization)	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d
E histolytica (Luminal disease or colonization)	Paromomycin: 25-30 mg/kg/d PO divided tid for 7 d
E histolytica (Moderate colitis)	Metronidazole: 50 mg/kg/d PO divided tid for 10 d
E histolytica (Moderate colitis)	Tinidazole: 50 mg/kg/d PO for 3 d; not to exceed 2 g/d
E histolytica (Severe colitis or liver abscess)	Metronidazole: 50 mg/kg/d PO divided tid for 10 d
	Dehydroemetine*: 1-1.5 mg/kg/d divided bid PO for 5 d
	Tinidazole†: 50 mg/kg/d PO for 3-5 d; not to exceed 2 g/d
G lamblia	Tinidazole: 50 mg/kg/d PO once; not to exceed 2 g/dose
	Metronidazole: 15-20 mg/kg/d PO divided tid for 5
	Albendazole: 15 mg/k/d (not exceed 400 mg) PO q24 h, for 5-7 days
	Furazolidone: 6 mg/kg/d PO divided qid for 7-10 d
	Paromomycin: 40 mg/kg/d PO divided tid for 7 d
	Nitazoxanide: 200-400 mg/d PO divided bid for 3 d
D fragilis	Iodoquinol: 50 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d
	Paromomycin: 30 mg/kg/d PO divided tid for 7 d
	Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d
C parvum§	Paromomycin*: 30 mg/kg/d PO divided tid (duration unknown)
C parvum§	Nitazoxanide: 200-400 mg/d PO divided bid for 3 d
I belli	Trimethoprim/sulfamethoxazole (TMP/SMZ): 20/100 mg/kg/d PO divided bid for 10 d, followed by 10/50 mg/kg/d PO divided bid for 21 d
C cayetanensis	TMP/SMZ: 10/50 mg/kg/d PO divided bid for 3 d
Microsporidia S intestinalis	Albendazole* (adult dose): 800 mg/d PO divided bid
Microsporidia E bieneusi	No treatment recommended; albendazole may decrease the number of organisms
B coli	Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d
	Metronidazole: 35-50 mg/kg/d PO divided tid for 5 d
	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d
B hominis	Metronidazole: 35-50 mg/kg/d PO divided tid for 10 d
	Iodoquinol: 40 mg/kg/d PO divided tid for 20 d
	Nitazoxanide\|\|: 500 mg/d PO divided bid for 3 d
*Efficacy is unknown. †Drug is available from the CDC Drug Service (phone: 404-639-3670; evenings, weekends, and holidays: 404-639-2888). ‡ Drug is not available in the United States. §Recommended regimens are indicated only in patients who are immunosuppressed. A recent meta-analysis has not shown evidence for a reduction in the duration or frequency of diarrhea by nitazoxanide or paromomycin when compared with placebo in immunosuppressed patients, nevertheless, oocyst clearance was significantly reduced.^[25] \|\|Recent studies have shown effective outcomes when compared to placebo, but no clinical trials have compared with other antiparasitic drugs.

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Author

Enrique Chacon-Cruz, MD, MSc Roster Member, Strategic Advisory Group of Experts in Immunization for the World Health Organization (SAGE-WHO); Member, Scientific Committee for the Ministry of Health, Baja-California, Mexico; Independent Advisor for Clinical Research and Academic Lectures, Houston, Texas (USA)

Enrique Chacon-Cruz, MD, MSc is a member of the following medical societies: Pediatric Infectious Diseases Society, Royal Society of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Martin Weisse, MD Program Director, Associate Professor, Department of Pediatrics, West Virginia University

Martin Weisse, MD is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Ashir Kumar, MD, MBBS FAAP, Professor Emeritus, Department of Pediatrics and Human Development, Michigan State University College of Human Medicine

Ashir Kumar, MD, MBBS is a member of the following medical societies: Infectious Diseases Society of America, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Acknowledgements

Douglas K Mitchell, MD Associate Professor, Department of Pediatrics, Eastern Virginia Medical School; Chair, Bronchiolitis Clinical Pathway Committee, Children's Hospital of the King's Daughters

Douglas K Mitchell, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Virology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Society for Healthcare Epidemiology of America, Society for Pediatric Research, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Intestinal Protozoal Diseases Medication

Medication Summary

Antiprotozoal agents

Class Summary

Iodoquinol (Yodoxin)

Iodoquinol (Yodoxin)

Metronidazole (Flagyl)

Metronidazole (Flagyl)

Paromomycin (Humatin)

Paromomycin (Humatin)

Tetracycline (Sumycin)

Tetracycline (Sumycin)

Trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim, Septra)

Trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim, Septra)

Dehydroemetine (Mebadin)

Furazolidone (Furoxone)

Quinacrine (Atabrine)

Albendazole (Albenza)

Albendazole (Albenza)

Tinidazole (Fasigyn, Tindamax)

Tinidazole (Fasigyn, Tindamax)

Nitazoxanide (Alinia)

Nitazoxanide (Alinia)

Intestinal Protozoal Diseases Medication

Medication Summary

Antiprotozoal agents

Class Summary

Iodoquinol (Yodoxin)

Metronidazole (Flagyl)

Paromomycin (Humatin)

Tetracycline (Sumycin)

Trimethoprim/sulfamethoxazole (TMP/SMZ, Bactrim, Septra)

Dehydroemetine (Mebadin)

Furazolidone (Furoxone)

Quinacrine (Atabrine)

Albendazole (Albenza)

Tinidazole (Fasigyn, Tindamax)

Nitazoxanide (Alinia)

References

Tables

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