Giardiasis, balantidiasis, isosporiasis, and microsporidiosis

Article about giardiasis, balantidiasis, isosporiasis, and microsporidiosis. 

giardia parasite

Topics covered:

  • Essentials
  • Introduction
  • Historical perspective
  • Giardiasis
  • Balantidiasis
  • Isosporiasis
  • Microsporidiosis
  • Areas of uncertainty or controversy
  • Likely future developments
  • Further reading


Giardiasis (popularly known in the US as beaver fever)

Infection with Giardia intestinalis, a flagellate protozoan that colonizes the lumen of the small intestine, is acquired by ingesting environmentally resistant cysts of the parasite, typically in water or food. Strains of the parasite that can infect humans are harboured by various mammals, including domestic dogs and cattle.

Clinical features—manifestations include watery diarrhoea, abdominal discomfort and distension, weight loss, and malabsorption, with the infection typically being persistent and severe in individuals with genetic impairment of antibody production.

Diagnosis and treatment—diagnosis is by faecal examination for evidence of Giardia intestinalis infection, including (1) cysts—by microscopy, including immunofluorescence microscopy with fluorescent antibodies; (2) antigen—by enzyme-linked immunoassay; or (3) DNA—by polymerase chain reaction (PCR) amplification. Aside from supportive care, treatment is with metronidazole (although the parasite is becoming increasingly resistant), tinidazole and nitazoxanide.

Prevention—cysts of Giardia intestinalis in water can be killed by boiling or removed by filtration.


Balantidium coli is a ciliate protozoan that invades the colonic mucosa. Infection—which may or may not be acquired from pigs or other animals—may be asymptomatic or cause diarrhoea that can be watery or contain blood and mucus. Perforation of the colon can occur, leading to peritonitis, and the parasite can also spread to the liver and lungs.

Diagnosis is by recognition of the parasite on microscopic examination of diarrhoeal stools, colonic mucus, or rectal biopsies. Aside from supportive care, treatment with metronidazole or tetracycline has reportedly eradicated infection in some instances.

Prevention is by filtration or boiling of drinking water, hand washing before handling food, and careful cleaning and cooking of food.


Cystoisospora belli is a coccidian protozoan that colonises epithelial cells of the small intestine. Infection is presumed to be acquired by ingestion of parasite oocysts in water or food, but vehicles for transmission to humans are unknown, although the organism has been found on cockroaches.

Clinical features include watery diarrhoea, dehydration, fever, and weight loss, with isosporiasis being an opportunistic infection associated with HIV infection.

Diagnosis is by microscopic examination of faecal specimens for oocysts of Cystoisospora belli, which show blue autofluorescence under ultraviolet light. Aside from supportive care, trimethoprim–sulphamethoxazole is partially effective.


Microsporidia are minute intracellular parasites genetically related to fungi, which infect various animals and birds. About a dozen species can cause human infection (some only rarely). In at least some cases this appears to be acquired by ingestion of spores of the causative organism(s) in water.

Clinical features—clinical manifestations are most frequently reported in HIV-infected patients, exemplified by colonisation of the small intestinal mucosa by Enterocytozoon bieneusi or Encephalitozoon intestinalis leading to watery diarrhoea. Other manifestations of microsporidial infection include acalculous cholecystitis, sinusitis, cough/dyspnoea, urethritis, and keratoconjunctivitis.

Diagnosis, treatment, and prevention—intestinal microsporidiosis is diagnosed by microscopic examination of faecal specimens (after appropriate staining) for microsporidian spores, or by detection of microsporidian DNA in faecal specimens. Aside from supportive care, albendazole is an effective drug for treating encephalitozoon infections, although Enterocytozoon bieneusi does not respond. In HIV-infected patients, remission of Enterocytozoon bieneusi infection can be achieved by anti-retroviral drug treatment that reduces the HIV load. Prevention can be achieved by killing spores in water by boiling or exposure to ultraviolet light.


The organisms that cause the diseases covered in this article are not closely related to each other.

Of these infections, the first three are caused by protozoa: giardiasis by a flagellate, balantidiasis by a ciliate, and isosporiasis by a coccidian. The term ‘microsporidiosis’ encompasses a group of infections caused by approximately a dozen species of minute parasites (microsporidia) that are genetically related to fungi and that may have (speculatively) evolved from a fungal ancestor.

Transmission of the organisms covered in this chapter mainly occurs by drinking or eating water or food containing environmentally resistant life-cycle stages of the parasites. Two of the diseases, isosporiasis and, particularly, microsporidiosis, have become much more widely recognized since the start of the HIV/AIDS pandemic in the early 1980s and are included among the opportunistic infections seen in patients with AIDS. The four diseases occur worldwide; although most published reports of balantidiasis and isosporiasis are from tropical countries, these two diseases also occur in nontropical locations.

Historical perspective 

Before the 1990s, literature on human giardiasis emphasized a relationship between drinking unfiltered water in wilderness areas and acquiring this infection, as well as occurrence of giardia species in beavers and muskrats (which were presumed to be sources of the human infection). Since then, it has become evident that morphologically indistinguishable giardia organisms colonize a wide variety of mammals, including cattle, horses, and domestic pets (dogs and cats), in addition to human hosts. Genotyping of Giardia intestinalis organisms has now enabled morphologically identical parasites to be subclassified into genetic assemblages of particular host preference (in this article, the terms ‘genetic assemblage’ and ‘genotype’, as applied to G. intestinalis, are used interchangeably). This genetic fingerprinting of giardia organisms has helped to clarify the risks of human subjects becoming infected by giardia parasites from particular species of nonhuman host.

Historically, balantidiasis and isosporiasis were recognized sufficiently rarely that they were the subjects of anecdotal case reports. This apparent rarity made it difficult to perform clinical trials to identify drugs useful for treating these diseases. In the 1980s, however, such a trial established the utility of co-trimoxazole in treating isosporiasis.

Before the HIV/AIDS pandemic, most of the literature on microsporidian infections dealt with such infections in nonhuman hosts (e.g. silk moths, honeybees, fish, and rabbits). The burgeoning literature on human microsporidiosis in HIV-infected individuals has been complemented by increased awareness of microsporidia that typically infect immunocompetent people, notably organisms that infect the human corneal stroma.

Because they lack mitochondria and some other features of higher eukaryotic (nucleated) cells, giardia and microsporidia were formerly considered to be extremely primitive. Following the discovery in these organisms of gene sequences homologous with mitochondrial DNA and of organelles (mitosomes) that appear to be derived from mitochondria, the organisms are now regarded as highly specialized rather than primitive. The apparently primitive features are almost certainly adaptations to the parasitic lifestyle, reflecting the colonization of an anaerobic niche (vertebrate intestinal lumen) by giardia species and of host intracellular environments by microsporidia.


Aetiology, pathogenesis, and pathology

Giardia intestinalis (synonyms Giardia lamblia and Giardia duodenalis) colonizes the lumen of the small intestine. The parasite’s life cycle comprises two stages: motile trophozoites and thick-walled ellipsoidal cysts that are excreted in the faeces. G. intestinalis trophozoites are dorsoventrally flattened organisms with eight flagella, two nuclei, and a ventral adhesive disc that enables them to become attached to the luminal surface of intestinal epithelial cells. Trophozoites absorb nutrients in the small intestinal lumen and multiply in this environment. New hosts become infected by ingesting Giardia intestinalis cysts; exposure of cysts to gastric acid leads to emergence of trophozoites from the cysts. Trophozoites encyst in the intestinal lumen and the resulting cysts are excreted from the host. The environmentally resistant cyst wall consists of protein and a polymer of N-acetylgalactosamine.

giardiasis parasite

Above: Giardiasis intestinalis

The mechanisms responsible for diarrhoea and malabsorption in giardiasis are partially understood. Shortening of microvilli on the luminal surface of intestinal epithelial cells has been observed in small intestinal biopsies from patients with giardiasis. Reduced activity of intestinal disaccharidases has been reported in giardia-infected human subjects and rodents. This functional enzyme deficiency might lead to osmotic diarrhoea (via the presence of undigested disaccharides in the intestinal lumen).

Study of immunity against giardia species has been more feasible in rodents than in human subjects. In mice, clearance of giardia infection appears to be dependent on CD4+ (helper) T lymphocytes and to follow the generation of an intestinal IgA response against the parasite. Genetically altered knock-out mice that are unable to produce intestinal IgA have an impaired ability to clear giardia infection. In human volunteers who were deliberately infected with G. intestinalis, an intestinal IgA response to the parasite occurred. IgA directed against trophozoites binds to these organisms and may, conceivably, inhibit their attachment to the intestinal epithelium, such that they are susceptible to peristaltic expulsion from the host. Giardia infection in mice and in human subjects leads to intestinal hypermotility, which may promote clearance of the parasite. 


Giardia is the most common pathogenic parasitic infection in humans worldwide; in 2013, there were about 280 million people worldwide with symptomatic giardiasis

Giardia intestinalis infection is acquired by drinking water that contains cysts. Other modes of spread include faecal–oral transmission of cysts, as in day-care centres for small children, and foodborne transmission of cysts. Waterborne giardiasis occurs as a result of drinking unfiltered, unboiled water from streams and lakes containing G. intestinalis cysts. Swimming in (and inadvertently drinking) water in lakes and rivers containing the cysts is also a risk factor for giardiasis. Outbreaks of this infection have resulted from the unintended presence of G. intestinalis cysts in public drinking water supplies and in swimming pools. Giardiasis is one of several parasitic and bacterial diseases that are potentially or actually transmitted by eating raw vegetables grown on fields irrigated or contaminated with untreated human sewage or animal manure. Aquatic molluscs, such as mussels grown commercially in estuarine water, concentrate particulate materials (including giardia cysts) from water by filter feeding, thus posing a potential infection hazard to human subjects who eat the molluscs raw.

Genotyping of G. intestinalis organisms has revealed genetic similarity between giardia isolates from people and from dogs occupying the same households in India, a finding consistent with transmission of G. intestinalis between dogs and people. Approximately 10% of giardia isolates from cattle belong to genotypes that can cause human infection. Flies that feed on garbage and sewage are able to carry giardia cysts on their exoskeletons and in their alimentary tracts and may therefore contaminate human food with viable cysts.

Immunodeficiency predisposes to the occurrence of severe and persistent giardiasis. Human immunodeficiency states that are associated with giardiasis include conditions that impair host antibody responses, notably ‘common variable’ hypogammaglobulinaemia and X-linked immunoglobulin deficiency. Impairment of intestinal IgA production is a feature of these particular immunodeficiency diseases and may explain how they predispose to chronic giardiasis (via impaired production of antitrophozoite IgA).

giardiasis life cycle

Above: Giardia Life cycle


Giardia intestinalis cysts can be removed from water by filtration, for example using membrane filters with a pore diameter of less than 5 μm. Cysts in water are killed by boiling. Exposure of water to ultraviolet light can inactivate giardia cysts and other organisms in the water. Water intended for human consumption can be screened for G. intestinalis cysts by exposure to magnetic beads coated with an antibody directed against cyst antigens (to capture cysts from suspension) followed by immunofluorescence microscopy using a fluorescent antibody to detect any cysts. Viable and dead cysts retrieved from water can be distinguished by staining with fluorescent dyes that selectively stain living or dead cysts, respectively.

Clinical features

Giardia infection can be asymptomatic (as shown by cyst excretion in the absence of symptoms) and also causes various clinical problems. These include abdominal discomfort, tenderness, and distension, a sensation of fullness, nausea, anorexia, and watery diarrhoea. Other clinical features include heartburn, flatulence, steatorrhoea, and weight loss. In immunologically normal persons, untreated giardiasis typically lasts for several weeks, with symptoms that fluctuate in severity. Clinical sequelae that have occasionally been reported include megaloblastic anaemia resulting from impaired absorption of vitamin B12 or folic acid.

Laboratory diagnosis

In a patient suspected of having parasitic infection of the gastrointestinal tract (with one or more species of parasite that might include G. intestinalis), faecal light microscopy may be informative. If the patient has giardiasis, Giardia intestinalis cysts may be seen during this examination. Diagnostic sensitivity can be increased by immunofluorescence microscopy of faecal specimens incubated with a fluorescent antibody that binds to G. intestinalis cysts. If there is a strong suspicion of infection with G. intestinalis (or if the aim is to check the effectiveness of treatment in clearing known giardiasis), immunoassay for G. intestinalis antigens is a recommended method. This approach, which involves enzyme-linked immunoassay (ELISA) of faecal specimens with one of several commercially available kits, is more objective and less labour intensive than immunofluorescence microscopy (which detects whole cysts).

Giardia duodenalis cyst in a wet mount stained with iodine.

Above: Giardia duodenalis cyst in a wet mount stained with iodine.

Though not widely available in diagnostic laboratories, the ability to detect Giardia intestinalis DNA in faecal specimens by polymerase chain reaction (PCR) is a sensitive and specific method.


Table 1 summarizes various drug regimens for treating giardiasis. Metronidazole resistance of G. intestinalis is an increasingly recognized problem, which has prompted a continuing search for alternative therapeutic agents. In recent years, nitazoxanide has been introduced for treating giardiasis.

Table 1 Various drug regimens for treating giardiasis
Drug Dose Treatment duration
Metronidazole 250 mg, three times daily (adult) 5 days
15 mg/kg body wt per day, in 3 doses (paediatric) 5 days
Albendazole 400 mg daily 5 days
Tinidazole 2 g (adult) Single dose
50 mg/kg (paediatric) Single dose (2 g maximum)
Ornidazole 2 g (adult) Single dose
Furazolidone 100 mg, four times daily (adult) 7–10 days
6 mg/kg per day, in 4 doses (paediatric) 7–10 days
Quinacrine 100 mg, three times daily 5 days
Nitazoxanide 500 mg, twice daily (adult) 3 days
100 mg, twice daily (age 1–3 years) 3 days
200 mg, twice daily (age 4–11 years) 3 days


Aetiology, pathogenesis, and pathology

Balantidium coli, the cause of balantidiasis, is the largest protozoan parasite of man. Balantidium coli has a two-stage life cycle comprising motile trophozoites that invade the colonic mucosa and nonmotile cysts. Spread of the infection to new hosts occurs by ingestion of the parasite. Balantidium coli trophozoites invade and cause ulceration of the colonic mucosa. The mechanisms responsible for tissue invasion by these organisms are not known.

Balantidium coli as seen in a wet mount of a stool specimen

Above: Balantidium coli as seen in a wet mount of a stool specimen. The organism is surrounded by cilia


There is circumstantial evidence that humans can acquire Balantidium coli infection from animals. This infection has been described in pigs and in many species of nonhuman primates. A high prevalence of the infection has been seen in human communities that live in close proximity to B. coli-infected pigs (e.g. in New Guinea). Consequently, there has been speculation that pigs are a reservoir for spread of B. coli to humans. Balantidiasis has also occurred in human subjects who had no known contact with pigs or other animals. Clusters of cases of balantidiasis have been seen in long-stay psychiatric hospitals. In India, Balantidium coli cysts have been found in water available for either drinking or use in cooking, and cysts of the organism have been found on cockroaches in Nigeria.

balantidium life cycle

Above: Balantidium Life cycle

Clinical features

Human subjects with Balantidium coli infection can be asymptomatic or can develop diarrhoea with stools that are either watery or that consist of blood and mucus. In severe B. coli infection, patients can develop colonic perforation, peritonitis, gangrene of the appendix (resulting from the presence of Balantidium coli in the appendiceal wall), and spread of the parasite to the liver or lungs. Balantidiasis is a rare cause of liver abscess. As is evident from the clinical features outlined above, balantidiasis may be clinically indistinguishable from amoebiasis, bacillary dysentery, ulcerative colitis, and Crohn’s disease, and can be fatal. B. coli infection in the lungs has been described in occasional patients with concurrent malignant disease (including chronic lymphocytic leukaemia).

Laboratory diagnosis

Balantidiasis can be diagnosed by microscopic examination of diarrhoeal stools or colonic mucus obtained at sigmoidoscopy. Examination may show motile trophozoites or, less frequently, cysts of B. coli. Histological examination of rectal biopsies may reveal B. coli trophozoites. Pulmonary balantidiasis can be diagnosed by bronchoalveolar lavage and finding the parasite in the lavage fluid.

Left: Balantidium coli cyst. Right: B. coli trophozoite in a wet mount at 1000x magnification.

Above: Left: Balantidium coli cyst. Right: B. coli trophozoite in a wet mount at 1000x magnification. 

Prevention and treatment

Prevention of balantidiasis involves avoidance of B. coli cyst ingestion, via filtration or boiling of drinking water, hand washing before handling food, and careful cleaning and cooking of food. Patients with balantidiasis have been treated empirically with various antimicrobial drugs. There is, however, little interpretable information about the effectiveness of such treatment, although eradication of Balantidium coli has been reported in some individuals treated with metronidazole or tetracycline. Surgical intervention may be necessary in patients with liver abscess or clinical evidence of appendicitis or colonic perforation.


Aetiology, pathogenesis, and pathology

The organism that causes isosporiasis was formerly known as Isospora belli. Organisms formerly included in the genus Isospora that are parasitic to mammals have now been assigned to the genus Cystoisospora (the generic name Isospora has been retained for avian parasites). Cystoisospora belli is a parasite of the human small intestine. There is limited evidence that Cystoisospora belli infects nonhuman hosts: oocysts of Cystoisospora belli have been isolated from dog faeces in India and the parasite has been transmitted experimentally to gibbons.

Cystoisospora belli oocysts are ellipsoidal structures that are excreted in the faeces of infected individuals. Studies of cystoisospora species that parasitize nonhuman hosts indicate that infection occurs via ingestion of oocysts and that sporozoites (which emerge from oocysts) penetrate epithelial cells of the small intestine. Subsequent development of cystoisospora species comprises: 

  1. an asexual pathway, with production of merozoites, which can infect additional epithelial cells; and 
  2. a sexual pathway, in which fusion of gametes produces oocysts that are excreted from the host.

Mechanisms responsible for the watery diarrhoea that occurs in isosporiasis are unknown. Presumably, the parasitization of epithelial cells in the small intestine contributes to the diarrhoea.


Cystoisospora belli infection has been documented in immunosuppressed and, rarely, in immunocompetent individuals. Among 397 HIV-infected patients in Venezuela, 56 (14%) were found to have C. belli infection (as judged by the presence of oocysts in faecal specimens). Of these 56 patients with Cystoisospora belli infection, 98% had diarrhoea. Vehicles for transmission of Cystoisospora belli oocysts to human subjects have not been identified, but presumably include water and food. Oocysts of this parasite are among the human pathogens found on cockroaches in Nigeria.

Clinical features

In patients infected with HIV, Cystoisospora belli infection is associated with chronic watery diarrhoea, abdominal cramps, nausea, fever, and weight loss. Severe dehydration can result from diarrhoea attributable to Cystoisospora belli infection in HIV-infected patients. In immunocompetent individuals, symptoms ascribed to isosporiasis are similar to those that occur in AIDS-associated C. belli infection. Isosporiasis has been described in a few patients with haematological malignancy (including Hodgkin’s disease, non-Hodgkin’s lymphoma, and adult T-cell leukaemia), in whom immunosuppression was presumably a risk factor for Cystoisospora belli infection.

Rarely, extraintestinal Cystoisospora belli infection has been described in patients with AIDS; in the relevant patients, tissues parasitized by Cystoisospora belli have included gallbladder epithelium, liver, spleen, and mesenteric lymph nodes.

Laboratory diagnosis

Isosporiasis can be diagnosed by microscopic examination of faecal specimens for Cystoisospora belli oocysts. Although these structures are relatively large (c.20 to 30 μm in length), they are translucent and may be difficult to see in unstained samples. Their visibility is increased by incubation with carbol fuchsin, which stains oocyst internal structures red, or by incubation with lactophenol cotton blue. An alternative approach is to examine faecal smears under ultraviolet light; with this type of illumination, Cystoisospora belli oocysts show blue autofluorescence.

Treatment and prognosis

The efficacy of oral co-trimoxazole in treating Cystoisospora belli-induced diarrhoea was demonstrated in a study of patients with AIDS and isosporiasis in Haiti. Recognition of adverse drug reactions to co-trimoxazole, and less than 100% efficacy of this drug combination in treating isosporiasis, have prompted alternative therapeutic approaches. Diclazuril, albendazole–ornidazole, and pyrimethamine–sulphadiazine are three such alternatives that have shown anecdotal promise in treating isosporiasis associated with HIV infection. In immunocompetent patients without HIV infection, isosporiasis can persist for weeks or months if untreated. The overall prognosis in patients with isosporiasis and HIV infection is determined by the HIV infection.


Aetiology, genetics, pathogenesis, and pathology

Microsporidia are obligate intracellular parasites, whose lifecycle comprises an extracellular stage (spore) and stages that occur in the cytoplasm of host cells. Spores are shed into the environment by infected hosts and infect other members of the host species. The spores induce infection by high velocity extrusion of a hollow tube that penetrates a host cell and forms a channel for delivering sporoplasm (spore contents) into this cell. Replication of the parasite and subsequent production of spores occur in host cells. Some species of microsporidia invade and survive in macrophages and can become anatomically disseminated within the host in these mobile cells. Microsporidia have a small genome (e.g. 2.9 × 106 bp in the case of Encephalitozoon cuniculi).

In HIV-infected patients, diarrhoea is the clinical feature that has been most frequently associated with microsporidiosis. In particular, this symptom has been linked to infection with Enterocytozoon bieneusi and with Encephalitozoon intestinalis. The diarrhoea in these microsporidian infections presumably results from the presence of microsporidia in the small intestinal mucosa. Microsporidian parasitization of the intestinal mucosa can be seen on microscopic examination of biopsy specimens.

Microsporidia that infect humans are listed in Table 2. Authenticated human infections with microsporidia other than Enterocytozoon bieneusiEncephalitozoon (Septata) intestinalis, and Encephalitozoon hellem, are rare and some of the microsporidian species have been found in one or two patients only. ‘Microsporidium’ is a nontaxonomic genus created for microsporidia of unclear identity.

In mice at least, interferon-γ contributes to protective immunity against Encephalitozoon intestinalis and Encephalitozoon cuniculi infections.


Most of the documented clinical experience with microsporidiosis has occurred in patients with HIV infection. Among 91 HIV-infected children with diarrhoea in Uganda, 70 were infected with Enterocytozoon bieneusi. After its initial description as an intestinal parasite in the HIV-infected population during the 1980s, Enterocytozoon bieneusi was reported in several HIV-negative, purportedly immunocompetent persons with diarrhoea. Similarly, human encephalitozoon infections have been reported most frequently in HIV-infected patients, but also occur in immunocompetent individuals. Microsporidian infections, sometimes fatal, have been described in immunosuppressed recipients of solid organ or bone marrow transplants. 

Experimental work with animals suggests that human infection with some species of microsporidia occurs via ingestion of spores. Environmental sources of microsporidian spores that can infect human subjects include water and, possibly, nonhuman hosts. Encephalitozoon intestinalis DNA has been found in drinking water in Guatemala, by PCR amplification. 

Risk factors for Enterocytozoon bieneusi infection, in a population of HIV-infected patients surveyed in France, included swimming in a pool in the 12 months before the survey. In rural Mexican households, faecal excretion of Encephalitozoon spores was associated with the use of unboiled water for drinking and for preparing food. Heavy parasitization of respiratory tract epithelial cells with Encephalitozoon hellem, in at least one HIV-infected patient examined at autopsy, raises the possibility that some microsporidian infections can be acquired by inhaling spores. 

Some species of microsporidia listed in Table 2 are known to infect nonhuman hosts: e.g. DNA of three microsporidian species (Enterocytozoon bieneusiEncephalitozoon intestinalis, and Encephalitozoon hellem) has been identified in faecal specimens from urban pigeons in Spain. Spores of Encephalitozoon intestinalis have been identified in faecal specimens from nonhuman mammals (dogs, pigs, goats, cows, and donkeys). Enterocytozoon bieneusi can infect dogs, cats, pigs, goats, and cows.

Table 2 Species of microsporidia that infect humans
Species Reported sites of infection
Enterocytozoon bieneusi Small intestinal epithelium, gallbladder epithelium, rarely in respiratory tract and maxillary sinus
Encephalitozoon (formerly Septata) intestinalis Intestinal epithelium, gallbladder epithelium, paranasal sinuses, respiratory tract, liver, kidney, pituitary, conjunctiva. Colonizes macrophages
Encephalitozoon hellem Corneal epithelium, respiratory tract, kidney, paranasal sinuses
Encephalitozoon cuniculi Kidney, urinary bladder, duodenal mucosa, conjunctiva, respiratory tract, adrenal glands, brain, heart, spleen, lymph nodes, cerebrospinal fluid
Vittaforma corneae (formerly Nosema corneum) Corneal stroma, urinary tract
Trachipleistophora hominis Skeletal muscle, conjunctiva, corneal stroma, nasopharynx (washings)
Trachipleistophora anthropophthera Brain, kidney, heart, pancreas, thyroid, parathyroid glands, liver, spleen, lymph nodes, bone marrow, cornea
Pleistophora ronneafiei Skeletal muscle
Anncaliia algeraea Skeletal muscle, skin, corneal stroma
Anncaliia vesicularuma Skeletal muscle
Anncaliia connoria Generalized
Nosema ocularum Corneal stroma
‘Microsporidium ceylonensis’ Corneal stroma
‘Microsporidium africanum’ Corneal stroma

a Organisms in the genus Anncaliia were formerly designated by the generic names Brachiola and Nosema.


Water can be screened for microsporidian spores by immunocapture of spores on magnetic beads coated with antispore antibody, followed by PCR to detect microsporidian DNA. Microsporidian spores in water can be killed by boiling or by exposure of water to ultraviolet light.

A gene chip method has been developed for detecting and discriminating between DNA of Enterocytozoon bieneusi and of all three encephalitozoon species simultaneously. This method is potentially applicable to environmental screening of drinking water samples and to diagnostic testing of clinical material, such as human faecal specimens, to look for evidence of microsporidian infection in a patient.

Clinical features

Clinical features of microsporidian infections reflect the anatomical site colonized by the microsporidia (Table 2). Besides watery diarrhoea, weight loss and fat malabsorption have been reported in HIV-infected patients with intestinal microsporidiosis. Microsporidian infection of the gallbladder has been described in occasional HIV-infected patients who had acalculous cholecystitis (characterized by right upper abdominal pain, nausea, and vomiting) and who were treated by cholecystectomy. Symptoms of sinusitis, cough, and dyspnoea have been reported in patients with microsporidian infection of the paranasal sinuses and respiratory tract. Symptomatic urethritis has been ascribed to microsporidian infection in occasional HIV-infected patients. Pulmonary Enterocytozoon bieneusi infection, though rarely reported, has occurred in patients with HIV infection.

Microsporidian infection of the conjunctiva and corneal epithelium causes symptoms of keratoconjunctivitis (foreign body sensation in the eye, ocular discomfort and redness, photophobia, blurred vision, and sometimes reduced visual acuity). Microsporidian infections of the corneal stroma lead to reduced visual acuity, with or without corneal ulceration. Clinical features in patients with actual or presumed cerebral microsporidiosis have included headache, cognitive impairment, nausea, vomiting, and epileptic seizures. Symptoms of myositis (muscle pain, tenderness, weakness, and wasting) have been described in patients with microsporidian infection of skeletal muscles.

Laboratory diagnosis

Intestinal infection with Enterocytozoon bieneusi or Encephalitozoon intestinalis can be diagnosed by finding microsporidian spores in faecal samples, for example by microscopic examination after exposure to various stains. The spores (which are ovoid) can be detected by microscopy after incubation with crystal violet plus iodine and chromotrope 2R (leading to violet staining of the spores), with optical brighteners such as Uvitex 2B and Calcofluor White M2R (which bind to chitin in the spores, resulting in fluorescence), or with fluorescent antibodies directed against the spores. Spores of Enterocytozoon bieneusi are smaller (c.1.5 μm × 0.9 μm) than those of Encephalitozoon intestinalis (c.2.5 μm × 1.5 μm). Microsporidian infection of the nasal mucosa and paranasal sinuses can be diagnosed by microscopic examination of nasal secretions for spores after staining. Similarly, microsporidian spores can be found in urine and bile from patients with urinary tract and biliary tract microsporidiosis, respectively. 

Detection of microsporidian DNA in clinical specimens (e.g. via the gene chip technique mentioned above) is a more sensitive ex vivo method than microscopy for diagnosing microsporidiosis.

Approaches to diagnosis of microsporidian keratoconjunctivitis include examining conjunctival/corneal scrapings or biopsies for spores and (noninvasively) in vivo examination of the cornea with a scanning confocal microscope to look for spore-filled epithelial cells.

Treatment and prognosis

Encephalitozoon infections can be treated effectively with albendazole. In a small controlled trial, HIV-infected patients with Encephalitozoon intestinalis infection were treated with albendazole (400 mg orally twice daily) or with placebo. Albendazole treatment led to clearance of gastrointestinal Enceph. intestinalis infection in this study. Uncontrolled trials and anecdotal case reports describe partial or complete resolution of symptoms (diarrhoea, sinusitis, and keratoconjunctivitis) in patients with Encephalitozoon intestinalis, Encephalitozoon hellem, or Encephalitozoon cuniculi infection following albendazole treatment. Pregnancy is a contraindication to albendazole treatment. 

Albendazole is not an effective treatment for Enterocytozoon bieneusi infection. In HIV-infected patients with Enterocytozoon bieneusi infection, remission of this microsporidian infection can be achieved by treatment of the HIV disease with highly active antiretroviral therapy (HAART). This treatment involves simultaneous administration of several drugs directed against HIV, including HIV protease inhibitors. When effective in HIV-positive Enterocytozoon bieneusi-infected patients, HAART leads to reduction of HIV load, elevation of the circulating CD4+ T-lymphocyte count, clearance of Enterocytozoon bieneusi infection, and cessation of diarrhoea. Fumagillin is active against Enterocytozoon bieneusi and Encephalitozoon species, although its clinical attractiveness for systemic administration is limited by toxicity to human subjects (manifested by thrombocytopenia and neutropenia). 

Microsporidial keratoconjunctivitis has been treated successfully with fumagillin eye drops in HIV-infected patients. HIV-negative patients with microsporidian infection of the corneal stroma have been treated by corneal transplantation, with results that have ranged from failure (opacification of the transplant) to apparent success, as judged by transparency of the graft 6 months after transplantation. Individual patients infected with Trachipleistophora hominis or Anncaliia vesicularum reportedly showed some clinical improvement after treatment with albendazole–sulphadiazine–pyrimethamine, or albendazole–itraconazole, respectively.

In HIV-infected patients with microsporidiosis, the overall prognosis is determined by the HIV infection.

Areas of uncertainty or controversy  

The importance, if any, of domestic drinking-water supplies in transmitting microsporidian spores is not known. Likewise, it is uncertain whether routine introduction of methods to screen domestic water supplies for microsporidian spores, and to remove/inactivate the spores if present would, be warranted.

Likely future developments 

It is likely that the mechanisms by which anti-giardia antibodies protect against Giardia intestinalis infection will be understood during the next 10 years. Such understanding would include the molecular characterization of giardia target antigens that are recognized by protective antibody. Further clarification of the importance of domestic pets and agricultural livestock as sources for human giardiasis and microsporidiosis is likely by genotyping of morphologically identical parasites from human and nonhuman hosts. Selective survival and geographical spread of metronidazole-resistant Giardia intestinalis strains are predictable challenges to the effective treatment of giardiasis.

At least two species of human pathogenic microsporidia, Anncaliia algerae and Trachipleistophora hominis, can infect mosquitoes and it is not known whether mosquitoes or other insects transmit microsporidia to human subjects. Future work may answer this question.

Further reading


Anonymous (2004). Drugs for parasitic infections. Med Lett Drugs Ther, 46, e1–e12. [Survey of treatment options for parasitic diseases, including the infections discussed in this article.]

Didier ES (2005). Microsporidiosis: an emerging and opportunistic infection in humans and animals. Acta Tropica, 94, 61–76. [Review of microsporidian infections, with emphasis on human microsporidiosis.]

Didier ES, et al. (2005). Therapeutic strategies for human microsporidia infections. Expert Rev Anti Infect Ther, 3, 419–34. [Review of drug treatment of microsporidiosis.]

Eckmann L (2003). Mucosal defences against Giardia. Parasite Immunol, 25, 259–70. [Review of Giardia infections, with emphasis on host protective mechanisms against Giardia organisms.]

Field AS (2002). Light microscopic and electron microscopic diagnosis of gastrointestinal opportunistic infections in HIV-positive patients. Pathology, 34, 21–35. [Review that includes photomicrographs of Cystoiospora (Isospora) belli and of microsporidia in human intestinal mucosa.]

Gajadhar AA, Allen JR (2004). Factors contributing to the public health and economic importance of waterborne zoonotic parasites. Vet Parasitol, 126, 3–14. [Review of waterborne transmission of parasitic diseases.]

Garcia LS (1999). Flagellates and ciliates. Clin Lab Med, 19, 621–38. [Review of human giardiasis and balantidiasis.] 

Lindsay DS, Dubey JP, Blagburn BL (1997). Biology of Isospora spp. from humans, nonhuman primates, and domestic animals. Clin Microbial Med, 10, 19–34. [Review of Cystoisospora (Isospora) species, including the human parasite Cystoisospora (Isospora) belli.]

Mathis A, Weber R, Deplazes P (2005). Zoonotic potential of the microsporidia. Clin Microbial Med, 18, 423–45. [Comprehensive review of microsporidian infections in human and nonhuman hosts.]