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Lab testing critical to identify cause, guide treatment for persistent diarrhea
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An accurate diagnosis via laboratory testing is critical for effectively treating persistent diarrhea lasting more than 2 weeks, as the often poorly recognized syndrome can be caused by different pathogens than acute diarrhea, according to a clinical review recently published in JAMA.
“I’d like to educate doctors about the importance of taking the history and assessing duration of illness,” Herbert L. DuPont, MD, director of the Center for Infectious Diseases at The University of Texas Health Science Center at Houston School of Public Health, said in a press release. “For acute diarrhea, the lab has a minimal role, restricted to patients passing bloody stools. If a patient has had diarrhea for 2 weeks or more, the doctor should focus on the cause of the disease through laboratory testing, with an emphasis on parasites.”
Herbert L. DuPont
DuPont performed a review of relevant literature published up to February 2016 to provide an overview of the epidemiology, etiology, diagnosis and management of persistent diarrhea in immunocompetent patients.
Common causes of persistent diarrhea
Although acute diarrhea is usually caused by viruses or toxins, persistent diarrhea is usually caused by bacteria or parasites, DuPont wrote.
Protozoa are the most common parasitic cause of persistent diarrhea, including Giardia, Cryptosporidium and Cyclospora, whereas Entamoeba histolytica, Cystoisospora belli, Dientamoeba fragilis, Strongyloides stercoralis and Microsporidia species are less common.
Bacterial species that may cause persistent diarrhea include enteroaggregative Escherichia coli, Shigella, Campylobacter, Salmonella, Vibrio parahaemolyticus, Arcobacter butzleri and Aeromonas species.
Clostridium difficile can cause recurrent diarrhea in patients receiving antibiotics in health care settings, and viral agents, such as norovirus, and helminths can also cause persistent diarrhea.
“Parasites are more common in the developing world. Consequently, persistent diarrhea is more common in these areas and in local populations or people traveling to these locations,” DuPont wrote. “Persistent diarrhea occurs in approximately 3% of international travelers to developing regions.” Parasitic infection is less common in industrialized regions, where foodborne and waterborne pathogens and C. difficile are more common causes, he added.
Persistent diarrhea can also have noninfectious causes, including lactase deficiency, ingested osmotic substances, postinfectious irritable bowel syndrome, functional bowel diseases, inflammatory bowel disease, celiac disease, ischemic or microscopic colitis, carbohydrate malabsorption, cancer and other idiopathic illnesses.
Complete evaluation, new diagnostic methods
Duration of illness should be determined by health care providers when developing an evaluation plan, and the clinical assessment of patients with persistent diarrhea lasting more than 14 days should include a complete history, physical examination and diagnostic testing for infectious or noninfectious etiologies.
“The longer the duration of illness, the more likely it is that parasitic pathogens or noninfectious causes will eventually be identified,” DuPont wrote.
Previously, bacterial pathogens were identified using stool culture-based methods, and parasites are often identified using commercial enzyme immunoassay tests or microscopy. However, the recent advent of multiplex polymerase chain reaction (PCR) platforms enable simultaneous testing for a number of bacterial, viral and parasitic enteropathogens by identifying their DNA sequences.
The xTAG Gastrointestinal Pathogen Panel (Luminex Corp) tests for 14 viruses, bacteria, and parasites and the FilmArray GI panel (Biofire Diagnostics) tests for 22 viruses, bacteria, and parasites.
“These new tests are easy to use, are capable of detecting a broad range of pathogens and represent a significant improvement over culture-based diagnostic approaches,” DuPont said in the press release. “The technology needs to be more widely available. Diagnosis is critical when treating persistent diarrhea.” However, false positive results are problematic, he wrote.
Treatment depends on diagnosis
After treating any dehydration with oral rehydration therapy, a laboratory test should be performed to determine the cause of persistent diarrhea to determine the appropriate treatment. However, a single 1,000 mg dose of empirical azithromycin is appropriate concurrent to the lab test for adults who have traveled to the developing world, as bacterial causes that lab tests cannot usually identify are common.
Although antimicrobial agents are recommended for a number of pathogens, the antibiotic choice should be optimized based on the pathogen’s susceptibility to prevent antimicrobial resistance.
For patients with recurrent C. difficile infection who do not respond to antibiotic therapy, fecal microbiota transplantation is an effective treatment that normalizes the gut microbiota.
Finally, Protozoal infections should be treated based on the organism identified in a stool sample. Nitazoxanide can treat a broad range of parasites, and can be used to treat patients who test negative for a pathogen.
“Patients with persistent diarrhea lacking an identified infectious etiology should undergo further evaluation because other conditions ... may be causing the diarrhea,” DuPont wrote.
Further research is required to identify new pathogens, improve diagnostic tools and develop new treatments, he concluded. – by Adam Leitenberger
Disclosures: DuPont reports he has received research support from Takeda, Rebiotix and Seres, has served as a consultant for Salix, Bio-K Plus and Seres, and has received honoraria from Salix, Bio-K Plus, Seres and Romark Laboratories.
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