Isospora belli

Cystoisospora (formerly Isospora) belli is a coccidian intestinal protozoa. C. belli is found worldwide, but infects only humans and is almost always in individuals with an immuno-compromised status. Infection leads to diarrhea and malabsorption, and C. belli may be present along with other co-infecting parasites. Rare cases of disseminated disease have been described in severely immunocompromised hosts. Diagnosis is typically made by finding characteristic elliptical oocysts on stool microscopy using modified acid-fast or other special stains. Multiple stool collections may need to be examined. On intestinal tissue histopathology, C. belli may be found invading beyond the epithelium, and eosinophils may be seen. The drug of choice for treatment of cystoisosporiasis is trimethoprim-sulfamethoxazole. Ciprofloxacin and pyrimethamine are alternative therapies. In HIV-infected individuals, antiretroviral therapy may be administered without delay, and secondary prophylaxis should follow initial treatment. Even after an adequate initial response to therapy, relapse and chronic infection can develop despite immune reconstitution.

Места локализации

Помимо кишечника (тонкая, двенадцатиперстная кишка), изоспоры паразитируют в других органах человеческого тела. Средой для размножения ооцист могут стать ткани сердца, почек, печени, глазных яблок.

Реакция организма на жизнедеятельность паразитов зависит от того, в каком месте обитают простейшие:

• при наличии ооцист в тонкой кишке у человека наблюдается метеоризм;
• больной страдает от малокровия, если паразиты питаются кровью;
• отклонения в работе центральной нервной системы из-за ее интоксикации.

При поражении простейшими паразитами органов дыхания в легких нарушаются газообменные процессы. При заражении изоспорами человека мучает одышка и кашель, сопровождающийся отделением мокроты.

The coccidian parasite, Cystoisospora belli, infects the epithelial cells of the small intestine, and is the least common of the three intestinal coccidia that infect humans.

Life Cycle

At time of excretion, the immature oocyst contains usually one sporoblast (more rarely two) . In further maturation after excretion, the sporoblast divides in two (the oocyst now contains two sporoblasts); the sporoblasts secrete a cyst wall, thus becoming sporocysts; and the sporocysts divide twice to produce four sporozoites each . Infection occurs by ingestion of sporocysts-containing oocysts: the sporocysts excyst in the small intestine and release their sporozoites, which invade the epithelial cells and initiate schizogony . Upon rupture of the schizonts, the merozoites are released, invade new epithelial cells, and continue the cycle of asexual multiplication . Trophozoites develop into schizonts which contain multiple merozoites. After a minimum of one week, the sexual stage begins with the development of male and female gametocytes . Fertilization results in the development of oocysts that are excreted in the stool .

Geographic Distribution

Worldwide, especially in tropical and subtropical areas. Infection occurs in immunodepressed individuals, and outbreaks have been reported in institutionalized groups in the United States.

Clinical Presentation

Infection causes acute, nonbloody diarrhea with crampy abdominal pain, which can last for weeks and result in malabsorption and weight loss. In immunodepressed patients, and in infants and children, the diarrhea can be severe. Eosinophilia may be present (differently from other protozoan infections).

La cystoisosporose est due à Cystoisospora belli (ex-Isospora belli), protozoaire parasite spécifique de l’Homme. Il s’agit d’une coccidiose intestinale dont le cycle comporte une schizogonie au niveau des cellules épithéliales de l’intestin grêle et une gamogonie conduisant à la production d’oocystes (figure 3.5). Les oocystes sont émis dans la lumière intestinale sous forme non sporulée ; la sporulation peut s’effectuer en partie lors du transit intestinal et conduire à l’émission d’oocystes contenant deux sporocystes dans les selles. Les oocystes éliminés dans les selles peuvent contaminer l’eau ou les végétaux ; ils deviennent infectants après maturation dans le milieu extérieur.

La contamination humaine s’effectue par ingestion d’oocystes sporulés contenus dans l’eau ou des aliments contaminés, ou sur les mains. Il s’agit d’une parasitose largement répandue en zone tropicale. Sa fréquence est variable, mais peut atteindre plus de 10 % chez les patients infectés par le VIH dans des zones de faible niveau d’hygiène.

La cystoisosporose est observée chez des sujets immunocompétents mais elle est plus fréquente et plus sévère chez les malades immunodéprimés.

Sintomas de Isosporíase

Normalmente a Isosporíase não causa sintomas e a infecção regride espontaneamente, no entanto em algumas situações, principalmente quando a pessoa possui o sistema imunológico comprometido, é possível haver:

• Diarreia;
• Cólicas;
• Dor abdominal;
• Febre;
• Náuseas e vômitos;
• Perda de peso;
• Fraqueza.

Em pessoas que possuem qualquer alteração no sistema imunológico, a isosporíase pode favorecer a ocorrência de outras infecções crônicas, além de aumentar o risco de desidratação, já que a diarreia é aquosa e prolongada, sendo necessária hospitalização da pessoa.

O diagnóstico é feito por meio da identificação da presença de oocistos nas fezes, mas também pode ser indicado pelo médico a realização de endoscopia, em que pode ser observada alteração na mucosa do intestino e atrofia das vilosidades intestinais, sendo indicativo de infecção por Isospora belli.

Less effective than TMP/SMX; appropriate when the sulfa drug (TMP/SMX) cannot be used. Considered a second-line alternative by the CDC.

Use only if the patient is allergic or intolerant to TMP/SMX.nd Considered a better alternative than some to ciprofloxacin. Add folinic acid (leucovorin) to stymie effects on normal cells. Has been used in the past for secondary prophylaxis, e.g., AIDS patients with CD4

First-line agent. Highly effective. The preferred choice for secondary prophylaxis.

• Shedding may persist even after adequate therapy; follow patients symptomatically.
• Continued prophylaxis the norm for patients with AIDS unless ART provides immune reconstitution.
  • No known cases of IRIS have been described in the treatment of C. belli.
  • For AIDS, discontinue secondary prophylaxis when CD4 >200cell/ul x 6mos post ART initiation.
  • Other agents with case report level data reporting successes/failures include nitazoxanide, albendazole, spiramycin, doxycycline, roxithromycin, diclazuril (veterinary compound).
  • No cases of IRIS have been reported with the institution of ART in HIV-infected patients with cytoisosporiasis.
  Shane AL, Mody RK, Crump JA, et al. 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the Diagnosis and Management of Infectious Diarrhea. Clin Infect Dis. 2017. [PMID:29053792]

  Comment: Parasitic causes of diarrhea may be considered in diarrhea lasting > 14 days. TMP/SMX is the drug of choice fo rCytoisospora belli.

  Comment: Guidance for treatment, but also prevention as stated in this module.

  page last updated 5/21/20; accessed 8/30/20,

  Comment:
  CDC resource page includes suggested treatments. Lists ciprofloxacin as the second line, with pyrimethamine listed as the first alternative if cannot use TMP/SMX.

  Dubey JP, Almeria S. Cystoisospora belli infections in humans: the past 100 years. Parasitology. 2019;146(12):1490-1527. [PMID:31303182]

  Comment: The rirst comprehensive review in

  20 years since earlier in the HIV/AIDS epidemic.

  Comment: Surprising report finding that nearly 10% of gallbladder removed for acalculous cholecystitis had C. belli organisms. Other reports have described such findings. Limitations included that this retrospective study had the organisms identified by H&E stain—unclear if identified at initial pathology read.

  Comment: One of a number of reports that counter the high incidence of C. belli seen in gallbladder usually diagnosed my H&E stain with microscopy.

  Comment: Review describes the pooled prevalence to be 14.0% (3283/43,218; 95% CI: 13.0-15.0%) for Cryptosporidium, 11.8% (1090/18,006; 95% CI: 10.1-13.4%) for microsporidia, and 2.5% (788/105,922; 95% CI: 2.1-2.9%) for Isospora. A low prevalence of microsporidia and Isospora infection was found in high-income countries, and a high prevalence of Cryptosporidium and Isospora infection was found in sub-Saharan Africa.

  Comment: Reported disseminated infection in pt with AIDS where microscopy of blood detected parasites also identified through DNA analysis.

  Comment: Authors suggest that Cystoisospora infection of the gallbladder may be more common than suspected due to subtle findings. Infection was not suspected in any of 11 cases done for biliary dyskinesia (n=7), abdominal pain (n=7), suspected cholelithiasis (n=5), and cholecystitis (n=3). In 2 cases, Cystoisospora was found in donor gallbladders resected at the time of liver transplantation. All cases were followed for 15 months, without findings suggestive of active biliary disease that suggests immunocompetent individuals don’t have ongoing problems with infection.

  Comment: In US sporadic cases seen as well as travel-acquired.

  Comment: Case series of 8 patients from S. Africa reporting that despite ART and rise in CD4, there remained persistent parasitic infection despite therapy. The authors postulate that host factors or TMP/SMX resistance may be at play.

  Comment: A study performed in Haiti included patients with I. belli diarrhea. Mortality was 10% in the group starting ART as opposed to 5% (p = 0.009) without diarrhea, suggesting that diarrhea is indeed linked to mortality risks when initiating antivirals.

  Comment: A real-time polymerase chain reaction assay targeting the internal transcribed spacer 2 region of the ribosomal RNA gene was developed for the detection of Isospora belli DNA in fecal samples.

  Comment: Authors demonstrate that cockroaches represent an important reservoir for infectious pathogens, including Isospora; they suggest that control of roach populations might decrease disease transmission.

  Comment: Examination by autofluorescence of 192 stool samples (95.7%; 95% CI, 85.2-99.5) significantly more sensitive than iodine staining (48.4%; 95% CI, 37.7-59.1). Authors suggest that autofluorescence is simple, highly sensitive, inexpensive, and easily applicable method to detect Isospora oocysts in feces.

  Comment: Though a broad-spectrum antiparasitic, there is little published experience using this drug for Isospora infection.

  Comment: This is the only randomized trial regarding this infection in HIV-infected individuals. This small study looked at 22 pts with chronic diarrhea due to I. belli randomly assigned to receive PO TMP-SMX DS1 tab twice-daily or ciprofloxacin (500 mg) twice-daily x7d. Pts who responded received prophylaxis for 10 wks (1 tab 3x/wk). Diarrhea resolved more rapidly with TMP-SMX than with ciprofloxacin. All pts receiving secondary prophylaxis with TMP-SMX remained disease-free, and 15 of 16 receiving secondary prophylaxis with ciprofloxacin remained disease-free.
  Rating: Important

  Comment: An early study suggested activity against I. belli with nitazoxanide. Note failure with this drug also cited in the literature.

  Comment: The authors focus on the extraintestinal stages of I. belli in a pt with HIV infection. These stages are important because relapse of diarrhea is common in humans infected with I. belli and is believed to be associated with the presence of extraintestinal stages.

  Comment: Wet-mounts examined by phase-contrast and bright-field microscopy; smears stained with modified acid-fast stain compared to fluorescent stain with Uvitex 2B. Using a fluorescent stain, the oocysts of I. belli stained bright white/blue fluorescent and showed a structure similar to that of oocysts in acid-fast stains.

  Comment: I. belli, microsporidiosis and cryptosporidiosis were among the causes of HIV cholangiopathies, seen more frequently in the pre-ART era.

  Comment: Authors investigate their experience in Haiti in a small cohort of 32 patients with AIDS and chronic diarrhea. In a subgroup, long-term prophylaxis for 16 months prevented relapse or reinfection.

  Comment: Two patients with AIDS, sulfonamide allergy, and I. belli infection are reported. They were treated successfully with pyrimethamine 75 mg/d alone; recurrence prevented with pyrimethamine 25 mg/d.
  Rating: Important

  Comment: Study of 20 of 131 HIV+ pts in Haiti with diarrhea Dx’d with I. belli. Sx included chronic watery diarrhea & weight loss. In all pts with isosporiasis, diarrhea stopped within2 days of beginning oral TMP-SMX. Recurrent symptomatic isosporiasis developed in 47% but responded promptly to the re-initiation of therapy.
  Rating: Important

  Comment: Brazilian cohort of patients with IDS who had coccidial diarrheal infections. Of the 389 patients seen between 1993-2003, 19.7% were positive by modified Ziehl-Neelsen staining for coccidian (8.6% with Cryptosporidium sp, 10.3% with Cystoisospora belli and 0.8% with both coccidia. Only 8.5% of this group received ART. Of note, there was no seasonality to C. belli infection.