Drug | Recommendation |
Ciprofloxacin | 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 | |
Trimethoprim/sulfamethoxazole | First-line agent. Highly effective. The preferred choice for secondary prophylaxis. |
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.
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.
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.
Immature oocysts. Unstained wet mount. Source: CDC
Immature oocyst w/ stain. Oocysts, safranin stain. Source: CDC
Cystoisoporiasis Life Cycle. Source: CDC