Our Tests Gut Health Assessment
The Gastrointestinal (GI) Pathogen Test is a new multiplex molecular diagnostic assay to simultaneously detect and identify 22 bacterial, viral, and parasitic pathogens that are responsible for the vast majority of infectious gastroenteritis. The FilmArray® system from Biofire Diagnostics is the new standard for syndromic infectious disease molecular diagnostics, and is the most comprehensive GI test to be cleared by the FDA.1
Gastroenteritis, or inflammation of the stomach and intestines, affects more than 179 million people per year in the United States. 2 Most cases are caused by infectious pathogens, often foodborne, with symptoms usually including diarrhea, abdominal cramps and/or discomfort, nausea, vomiting, fever, and/or blood in the stool.3,4 Asymptomatic carriers can also spread infection. By using a molecular approach and a broad test menu, the FilmArray® can better detect and identify the infectious agent(s) with just one simple diagnostic test.
Rapid identification of the infectious agent is critical for the timely administration of appropriate antimicrobial therapy (and sometimes isolation measures).5 Organism-specific diagnosis can also help reduce the unnecessary (and even harmful) use of antibiotics and/or procedures.5,6 The Salveo Diagnostics GI Pathogens Test provides a comprehensive appraisal of the cause of diarrheal disease, for improved patient management.
Most clinical laboratories use conventional methods to identify pathogens (e.g., culture, microscopy, and immunoassay), each having limitations. For example, microscopic detection of parasites is reliant on technical skill, and immunoassay/culture sensitivity results can be inconsistent (leading to false negatives and requiring evaluation of multiple samples) due to intermittent shedding of the organisms.7 Culture methods have a long turnaround time and are susceptible to unequal species viability/growth during sample transport to the lab, which may lead to inaccurate diagnoses and treatment. Immunoassays often suffer from poor antibody specificity.8
New molecular methods exhibit improved detection of viruses, bacteria, and parasites in a single stool sample, providing more diagnostically actionable results.9-11 With the improved performance and efficiency provided by multiplex technology in the GI Pathogen Test, it is now possible to not only achieve faster, more accurate results, but to simultaneously test for 22 of the most common causes of infectious diarrhea.1 Importantly, the ability to identify unsuspected pathogens and the reliability of “true-negatives” is a real boon to clinical management.
Clinical Utility & Indications
- Cryptosporidium: Cryptosporidia are protozoans responsible for GI illness often associated with watery diarrhea, stomach cramps, nausea, and vomiting. They are usually ingested in contaminated water and, as they are not easily killed by chlorine, are the most common cause of recreational waterborne illness in the US.3,13,14 Specific antidiarrheal options (e.g., nitazoxanide) are available, though many people with healthy immune systems will recover without treatment within 1–4 weeks.
- Cyclospora cayetanensis: These parasitic protozoa disseminate unsporulated oocysts in feces. After a period of maturation (days to weeks), the oocysts become infectious and can cause illness if ingested through contaminated food or water. 14 In the US, infections are generally associated with “travelers’ diarrhea” in persons returning from endemic areas, or after consumption of contaminated food from other countries.14,15 Illness presents as nonbloody diarrhea that may be present for several months.
- Entamoeba histolytica: Entamoeba infection is common in the US (particularly in recent travelers to tropical areas or those living with poor sanitation), though only 10–20% of patients express overt symptoms.19 E. histolytica infection can present as diarrhea with or without dysentery (i.e. diarrhea with mucus and blood).16,17 Effective treatments include metronidazole or tinidazole immediately followed with paromomycin, diloxanide furoate or iodoquinol.3,4
- Giardia lamblia: The most common intestinal parasite in the US (overall prevalence 1–7%), Giardia can adhere to or invade the intestinal mucosa, causing diarrhea accompanied by abdominal cramps, vomiting, and general malaise.17,18 Usually acquired from infected water or daycare facilities, the infection can become chronic and cause a malabsorption syndrome.3 Effective treatments include nitroimidazole derivatives (e.g., metronidazole), and more recent alternatives such as paromomycin, quinacrine, and furazolidone.19 Infection with Giardia may triple the risk of irritable bowel syndrome and chronic fatigue, even years after infection.20
Bacteria and Bacterial Toxins
- Campylobacter spp. (C. jejuni, C. coli, C. lari): These gram-negative bacteria invade the intestinal mucosa and are the second most common bacterial infection in the US.3,21 Typically transmitted via intake of contaminated water or food (particularly undercooked poultry), Campylobacter species are responsible for ~15% of hospitalizations due to food contamination.22 Symptoms include fever, vomiting, and headaches, followed by 3–7 days of watery or bloody diarrhea with abdominal pain. Campylobacter infection has been linked to development of inflammatory bowel disease and Guillain Barré syndrome.23,24
- Clostridium difficile (Toxin A/B): C. difficile is a gram-positive anaerobic bacterium that produces diarrhea-inducing toxins (enterotoxin A and cytotoxin B). C. difficile is the most common cause of nosocomial (acquired in the hospital) infectious diarrhea and antibiotic-associated colitis.25,26 Symptoms of fever and diarrhea can range from mild to severe, or even toxic megacolon.27 In most cases, broad-spectrum antibiotics and antidiarrheal drugs should be avoided. Please see current guidelines for treatment.28
- Escherichia coli: Pathogenic E. coli are a significant cause of diarrheal illness worldwide and differ as to the clinical manifestations, progression, and severity of the diseases they cause. 29 Some of these differences are due to specific virulence factors (e.g., toxins), whose genes can be targeted by molecular assays to detect and differentiate these pathogens.30
- Enteroaggregative E. coli (EAEC): Defined by their aggregative adherence pattern on cultured cells, EAEC are generally transmitted by the fecal-oral route via contaminated food and water. 31 EAEC infections may be asymptomatic, but often cause an inflammatory diarrheal illness characterized by watery, sometimes bloody stool with low-grade fever, vomiting, and abdominal pain. EAEC are considered one of the most common causes of diarrheal illness in the US and the second most common cause of travelers’ diarrhea.32-34
- Enteropathogenic E. coli (EPEC): Globally, EPEC are estimated to have a prevalence of 8.8% in the community setting, 9.1% in the outpatient setting, and 15.6% in the inpatient setting.35 Illness caused by typical EPEC is associated with acute diarrhea whereas atypical EPEC cause a prolonged, nonbloody diarrhea and vomiting with fever.30 Carriers of EPEC may also be asymptomatic.
- Enterotoxigenic E. coli (ETEC): The leading cause of travelers’ diarrhea, these bacterial strains are typically transmitted by contaminated food or water. ETEC produce both heat-labile (lt) and heat-stable (st) toxins that bind to intestinal epithelial cells, triggering loss of electrolytes resulting in watery diarrhea. In most cases, symptoms will resolve within a few days without requiring specific treatment. 36
- Shiga-toxin-producing E. coli (STEC) stx 1/ stx2: There are two main types of Shiga-like toxins, Shiga-like toxin 1 (stx1) and 2 (stx2). STEC are important food- or waterborne pathogens and a major cause of bloody diarrhea, which can lead to a potentially fatal condition called hemolytic uremic syndrome (HUS; destruction of red blood cells that leads to renal failure), especially in the very young and very old.14,36,37
- Escherichia coli O157: A subset of STEC contain the O157 antigen. Of more than 170,000 STEC infections in the US each year, an estimated 73,000 illnesses and 60 deaths are attributable to E. coli O157.38,39 Transmitted via consumption of contaminated food or water, disease presentation ranges from mild, nonbloody diarrhea to hemorrhagic colitis and HUS. Symptoms typically resolve in 5–10 days.
- Shigella/Enteroinvasive E. coli (EIEC): Shigella bacterial infections (S. boydii, S. sonnei, S. flexneri, S. dysenteriae) account for 5–20% of all diarrheal episodes and can occur at any age, although most often in children less than 5 years old. Shigella is typically transferred through person-to-person contact or ingestion of contaminated food or water. Shigellosis often begins with fever, watery diarrhea, and abdominal cramps, and blood may appear in the stool. It is self-limiting but can become life-threatening in immunocompromised patients.3,26 Zinc supplementation may reduce the duration of diarrhea and improve weight gain during recovery.40 Although rare in the US, EIEC strains produce virulence factors that allow the bacteria to invade the colon and produce a watery diarrhea syndrome identical to that caused by Shigella.14
- Plesiomonas shigelloides: These gram-negative bacteria are isolated from a wide range of environmental sources including freshwater and many animals, both wild and domestic. P. shigelloides gastroenteritis often follows consumption of seafood, as well as contaminated water used for drinking or preparing uncooked foods.14 Symptoms generally include watery diarrhea and infections may be prolonged (more than 2 weeks duration) but are generally self-limiting.41 Most cases reported in the US are from individuals with pre-existing health problems leading to a more severe disease outcome.42
- Salmonella: Salmonellae are gram-negative anaerobic bacteria responsible for more foodborne infections in the US than any other pathogen.21 This infection is often contracted from ingesting undercooked poultry or eggs.3
- Vibrio spp. (V. parahaemolyticus/V. vulnificus/V. cholerae): Vibrio are gram-negative bacteria typically found in marine environments. Several species are capable of causing illness in humans, both extraintestinal (soft tissue infection, septicemia, eye and ear infections) and intestinal. Gastrointestinal illness is commonly associated with eating contaminated food.21 V. cholerae is the only Vibrio species that causes cholera, with severe disease mediated by the cholera toxin (CTX). In the US, cholera may occur in travelers returning from overseas.
- Vibrio cholerae cholera toxin gene (ctx): Vibrio cholera is a common cause of diarrhea in many parts of the world but is only found sporadically in the US.26 When detected, it is often associated with consumption of raw or undercooked shellfish.43
- Yersinia enterocolitica: These gram-negative bacilli are transmitted via ingestion of contaminated food or water, often raw undercooked meats (especially pork) and are estimated to cause ~100,000 foodborne illnesses annually in the US.39 The severity of the illness ranges from self-limiting gastroenteritis to terminal ileitis and mesenteric lymphadenitis. Symptoms of illness mimic appendicitis and may lead to unnecessary surgery, highlighting the importance of properly identifying this organism when it is present in stool specimens.
Viruses are the most common cause of gastroenteritis in the US. By infecting enterocytes in the lining of the small bowel, they draw fluid and salts into the gut lumen to create watery diarrhea.
- Adenovirus F40/41: Adenovirus (especially type 40 and 41) is a common cause of acute gastroenteritis, with an estimated infection prevalence of 1–8% in industrialized countries.44,45 Symptoms typically include watery diarrhea that lasts for 1–2 weeks, sometimes with vomiting and fever. Adenoviral infections can occur year-round and are particularly prevalent in the elderly and children under 2 years of age.45,46
- Astrovirus: Named for their characteristic star-like structure, astroviruses are associated with gastroenteritis in both children and adults.14 The infection route is fecal-oral and at-risk populations include children, immuno- compromised adults, caregivers of sick children, and those in nursing homes. Symptoms are reported to be milder than other enteric viruses and include diarrhea, vomiting, abdominal pain, and fever lasting 72 hours.47
- Norovirus GI/GII: Norovirus is the leading cause of acute gastroenteritis across all age groups but most commonly affects older children and adults.48 It is highly contagious and occurs year-round, but 80% from November to April.3 It is usually self-limiting and rarely causes severe symptoms.
- Rotovirus A: Rotavirus is the most common cause of severe, life-threatening diarrheal infections in young children around the world (peak incidence, 3–15 mo).3 It is highly contagious, although in adults the symptoms are often mild. Most prevalent in winter, its morbidity in the US has been reduced by vaccination programs.49
- Sapovirus (Genogroups I, II, IV, and V): Sapovirus is similar to Norovirus in disease presentation, causing disease mostly in children.50,51 Like Norovirus, Sapovirus is spread via the fecal-oral route and infections are highest during the winter months. Symptoms primarily include vomiting and diarrhea with nausea and fever lasting 5–10 days.52,53 In general, illness is self-limiting with treatment consisting of supportive care.
- Huang RSP, et al. Diag Microbiol Infect Dis 2016; doi:10.1016/j.diagmicrobio.2016.09.013.
- Wikswo ME, et al. MMWR Surveill Summ 2015;64(12):1–16.
- Boyce TG. Overview of gastroenteritis. Merck Manual [database online]. Kenilworth, NJ; Merck Sharp & Dohme Corp 2016. Accessed June 16, 2016.
- Guerrant RL, et al. Clin Infect Dis 2001;32(3):331–351.
- Cartwright CP. J Clin Microbiol 1999;37:2408–2411.
- Guarino A, Giannattasio A. Curr Opin Gastroenterol 2010;27:24–29.
- Whiley H, Taylor M. Crit Rev Microbiol 2014;42(1):65–74.
- Johnston SP, et al. J Clin Microbiol 2003;41:623–626.
- Amar CFL, et al. Eur J Clin Microbiol Infect Dis 2004;23:529–534.
- De Boer RF, et al. J Clin Microbiol 2010;48:4140–4146.
- Verweij JJ, et al. J Clin Microbiol 2004;42:1220–1223.
- Chako CZ, et al. J Vet Intern Med 24(1):37–43.
- Yoder JS, et al. MMWR Surveill Summ 2010;59(6):1–14.
- Versalovic J & American Society for Microbiology. Manual of clinical microbiology. (ASM Press, 2011).
- Legua P, Seas C. Curr. Opin. Infect. Dis. 2013;26:479–483.
- Stauffer W, Ravdin JI. Curr Opin Infect Dis 2003;16(5):479–485.
- Kappagoda S, et al. Mayo Clin Proc 2011;86(6):561–583.
- Yoder, JS, et al. Surveill Summ 2010;59(6):15–25.
- Escobedo AA, Cimerman S. Expert Opinion Pharmacother 2007;8:1885–1902.
- Hanevik K, et al. Clin Infect Dis 2014;59(10):1394–1400.
- Centers for Disease Control and Prevention (CDC). Foodborne Diseases Active Surveillance Network (FoodNet): FoodNet Surveillance Report for 2014 (Final Report). Atlanta, Georgia: U.S. Department of Health and Human Services, CDC. 2014.
- Man SM. Nat Rev Gastroenterol Hepatol 2011;8(12):669685.
- Dasti JI, et al. Int J Med Microbiol 2010;300(4):205–211.
- Moore JE, et al. Vet Res 2005;36(3):351–382.
- Yoo J, Lightner AL. Perm J 2010;14(2):35–40.
- Navaneethan U, Giannella RA. Nat Clin Pract Gastroenterol Hepatol 2008;5(11):637–647.
- Bobo LD, et al. Chest 2011;140(6):1643–1653.
- Surawicz CM, et al. Am J Gastroenterol 2013;108:478–498.
- Nataro JP, Kaper JB. Clin Microbiol Rev 1998;11(1):142–201
- Croxen MA, et al. Clin Microbiol Rev 2013;26:822–880.
- Kaur, P. et al Interdiscip Perspec Infect Dis 2010:2010:254159.
- DuPont HL. Bacterial diarrhea. New Engl J Med 2009;361:1560–1569.
- Nataro JP, et al. Clin Infect Dis 2006;43:402.
- Huang DB. J Med Microbiol 2006;55:1303–1311.
- Lanata CF, et al. Geneva, Switzerland: World Health Organization (2002). Available at adolescent/documents/pdfs/improving_diarrhoea _estimates.pdf>
- Page AV, Liles WC. Med Clin N Am 2013;97:681–695.
- Center for Food Safety and Applied Nutrition. Bacteriological Analytical Manual (BAM). At /LaboratoryMethods/BacteriologicalAnalytical ManualBAM/default.htm
- Mead PS, et al. Emerg Infect Dis 1999;5:607.
- Scallan E. Emerg Infect Dis 2011;17(1):7–15.
- Rahman MJ, et al. Am J Clin Nutr 2005;81(2):495–502.
- Wong TY, et al. Kong Med J 2000;6:375–380.
- Center for Food Safety and Applied Nutrition (U.S.). The bad bug book: foodborne pathogenic microorganisms and natural toxins handbook. (International Medical Pub., 2004).
- Barr W, Smith A. Am Fam Physician 2014;89:180–189.
- Wilhelmi I, et al. Clin Microbiol Infect 2003;9(4):247–262.
- Dennehy PH. Pediatr Infect Dis J 2011;30(1):63–64.
- Blutt SE, Conner ME. Front Immunol 2013;4:402.
- Utagawa ET, et al. J. Clin. Microbiol. 1994;32:1841–1845.
- Hall AJ, et al. Emerg Infect Dis 2013;19(8):1198–1205.
- Dennehy PH. Adv Pediatr 2012;59(1):47–74.
- Lee LE, et al. Emerging Infect. Dis. 2012;18:873–876.
- Svraka, S. et al. J Clin Microbiol 2010;48:2191–2198.
- Rockx B, et al. Clin Infect Dis 2002;35:246–253.
- Johansson PJH, et al. Scand J Infect Dis 2005;37:200–204.
- Vandenplas Y. Best Pract Res Clin Gastroenterol 2016;30(1):49-53
Helicobacter pylori, or H. pylori as it is more commonly known, is a ubiquitous bacterium which is estimated to be present in 40–50% of the world’s population.1Prevalence and incidence of H. pylori infection differs by geography and race. In the United States, H. pylori prevalence is 60% in Hispanics, 54% in African Americans, and 20% in Caucasians.2
In general, patients infected with H. pylori are asymptomatic; however, when symptoms are present they may include abdominal pain and bloating, heartburn, nausea, vomiting, diarrhea, and halitosis. In addition, several studies have demonstrated a potential association between iron deficiency anemia and H. pylori.3 The explanation for this has may be related to decreased iron absorption due to chronic atrophic gastritis or occult blood loss from erosive gastritis.
H. pylori is indicated in up to 90% of stomach ulcer cases and the organism is classified as a carcinogen because of its causal association with gastric adenoma, one of the world’s deadliest cancers.4
Testing for H. pylori
Testing for H. pylori should be performed in symptomatic patients to diagnose the presence of the bacteria and to evaluate the effectiveness of treatment. Recommended and most commonly used tests to detect the presence of H. pylori include a stool/fecal antigen test and the urea breath test. The detection of H. pylori antigen in feces has evolved into a reliable, sensitive, and specific method in recent years.5,6 H. pylori antibody testing is not recommended for routine diagnosis or evaluation of treatment effectiveness.
Clinical Utility & Indications
Although there is no staging system for H. pylori infection, well-described steps in the disease process include chronic gastritis, atrophic gastritis, intestinal metaplasia that may develop into dysplasia, and gastric adenocarcinoma.
Thus, in patients with symptoms suggestive of H. pylori infection, laboratory testing to aid in the confirmation of the presence of H. pylori is important. Only patients with a positive test result for H. pylori should be treated.
Testing at Salveo Diagnostics involves a fecal antigen test for the presence of H. pylori in a stool sample from the patient. The test result will be reported as either positive for the presence of H. pylori, or H. pylori not detected.
1. The EUROGAST Study Group. Gut 1993;34:1672–1676.
2. Everhart JE, et al. J Infect Dis 2000;181(4):1359–1363.
3. Chey WD, et al. Am J Gastroenterol 2007;102:1808–1825.
4. Peter S, Beglinger C. Digestion 2007;75:25–35.
5. Blanco S, et al. Diag Microbiol Infect Dis 2008;61:150–155.
6. Wu DC, et al. Diag Microbiol Infect Dis 2006;56:373–378.
Blastocystis spp. Antigens
Blastocystis is a group of single-celled organisms with 17+ subtypes belonging to the protist (protozoa) family.1 It is one of the most common intestinal parasites of animals, including humans (in which 9+ subtypes have thus far been identified), and the most prevalent infection by a single organism in symptomatic American patients.1-3
Despite evidence suggestive of a role for Blastocystis in gastrointestinal and other diseases, a causal link has not yet been shown in all cases.
- Some people with Blastocystis infection have severe symptoms, while others have no symptoms at all
- Its high prevalence in asymptomatic individuals suggests that not all infected people are susceptible to disease and/or that not all Blastocystis subtypes are pathogenic4
- It may be a more serious issue in children or immunocompromised patients1
- However, a systematic survey conducted by infectious disease specialists from nine countries found that >95% of research studies published in the preceding 10 years reported causal links to illness in immunocompetent individuals1
Blastocystis infection is thought to result from accidentally swallowing the parasite picked up from surfaces, soil, uncooked food, or water contaminated with feces from an infected person or animal. Infection is more common in people living close to farm animals or pets.
Testing for Blastocystis
Testing for Blastocystis should only be performed in symptomatic patients to diagnose the presence of the parasite and to evaluate the effectiveness of treatment.
Although the “gold standard” tests for Blastocystis are believed to be microscopy, culture, and formyl acetate concentration (FECT), these methods can be unreliable and are time-consuming.5
- Microscopy is difficult as Blastocystis exists in several morphological subtypes (vacuolar, cyst, amoeboid, granular, multivacuolar, and avacuolar)
- FECT destroys the multivacuolar, vacuolar, and granular forms during processing
- Culture requires 2-3 days for diagnosis and can give misleading results if multiple subtypes are present that grow at different rates
Salveo assesses the presence of Blastocystis in a stool sample by detecting antigens to the parasite using a highly sensitive (83%) and specific (94%) enzyme-linked immunosorbent assay (ELISA).5
Clinical Utility & Indications
The Salveo test for Blastocystis antigens may aid in treatment of patients with unexplained gastrointestinal (or other) symptoms.1
- Presence of symptoms depends on parasite genotype (e.g., genes encoding toxins), host genotype (e.g., response to Blastocystis virulence factors), host immunity, and age1
- Between 50-80% of individuals who harbor Blastocystis but no other parasites will show symptoms characteristic of irritable bowel syndrome: diarrhea, constipation, nausea, abdominal cramps, bloating, excessive gas, and anal itching
- Some patients also report fatigue, skin rashes, headaches, and joint pain
If Blastocystis presents as an acute infection, with severe symptoms, the symptoms last for a relatively short time (a few weeks). A chronic infection can last indeterminately or until treated.
Debate continues as to the universal pathogenicity of Blastocystis and the infection is often self-limiting and some symptomatic patients recover without treatment. Therapy should be limited to patients with persistent symptoms after a complete workup for alternative etiologies.
Although there is no known efficient eradication strategy, potential medications for treating Blastocystis infection in symptomatic patients include the following:1,6,7
- Antibiotics, e.g., metronidazole, tinidazole, or rifamaxin
- Combination medications, e.g., cotrimoxazole (trimethoprim/ sulfamethoxazole or TMP/SMX)
- Antiprotozoal medications, such as paromomycin or nitazoxanide
- The probiotic yeast Saccharomyces boulardii
- Boorom KF, et al. Parasit Vectors 2008;1(1):40.
- Amin OM. Am J Trop Med Hyg 2002;66(6):799-803.
- Scanlan PD, Stensvold CR.Trends Parasitol 2013;29(11):523-529.
- Scanlan PD, et al. FEMS Microbiol Ecol 2014;90(1):326-30.
- CoproELISATM Blastocystis Enzyme-Linked Immunosorbent Assay (ELISA) for the detection of Blastocystis spp. antigens in human feces [package insert]. Ashdod, Israel: Savyon® Diagnostics Ltd., Israel; 2018.
- Stensvold CR, et al. J Clin Gastroenterol 2010;44:85-90.
- Sekar U, Shanthi M.Trop Parasitol 2013;3(1):35-39.