The health and welfare of any civilized population have always depended first and foremost on the detection, treatment, and prevention of contagion. The most common are enteric (gastrointestinal) pathogens, particularly those of a parasitic nature. Those who are infected experience chronic disability, fatigue, and malnutrition, and often present systemic-disease-like symptoms. They are the most likely source of transmission to others. A clear and current understanding of the true prevalence of endemic parasitosis in a patient population is essential to practice. So are the connections between enteropathogens and health conditions not commonly associated with infection, including and especially HPA/pineal dysfunction and celiac disease.
This article represents what was learned from a retrospective examination of 1336 medical records from a private practice centered in the Greater Los Angeles Metropolitan Area (GLAMA) from 2000 through 2013. Specimens of stool and saliva were collected cosynchronously and submitted by patients who presented with nonspecific gastrointestinal symptoms that would generally be characterized as colitis, irritable bowel syndrome, and so on.
Stool was examined by bacterial culture for enteric pathogens, C. difficile toxins, by microscopy for ova and parasites, and antigens for Cryptosporidium parvum and Giardia lamblia. Saliva was examined for detection of antibodies to antigens of pathogenic species of bacteria, protozoa, helminthes, and gliadin
Additional salivary specimens were collected in subjects every 4 hours over a 24-hour period and sent to Sabre Sciences (Carlsbad, California). Circadian panels of salivary cortisol and DHEA-S, and nocturnal measurement of salivary melatonin, were obtained in a cross section of those patients with enteropathogens and compared with normal controls. Patients with enteropathogens also commonly give a clinical history of sleep disorder, which suggests an abnormality of melatonin production by the pineal gland. Concurrent analysis of salivary cortisol, DHEA-S, and melatonin provides a noninvasive, easy, and accurate measure of circadian HPA and pineal function all at once.
(The full details of this study, including subject parameters, pathogens investigated, and methodology, are available in an abstract of the author's paper "Celiac Disease and Enteropathogens," American Journal of Gastroenterology; 2013. The abstract is available on the author's website: www.stuppymd.com/51.pdf.)
Among the 1336 patient tested, the three most common infections were T. gondii (633), E. histolytica/dispar (346), and H. pylori (265). Of significance is the fact that 45% of all patients tested positive for more than one enteropathogen, with 13% testing positive for four or more.
Table 1: Analysis of Infections
Number of infections 0 1 2 3 >4
Total Number of Patients 390 342 274 159 171
A total of 441/1336 (33%) patients were positive for gliadin antibodies; of these, 55% also tested positive for an enteropathogen, demonstrating a more than casual relationship.
One hundred and forty-two of the subjects (11%) were positive for Cryptosporidium parvum, and 23% of these were positive for gliadin Ab, SIgA. These patients were all treated with the antiparasitic drug nitazoxanide. After a 2-week course of treatment, symptom resolution and normalization of antigliadin secretory IgA was found in 30/33 (91%) of patients. The overall cure rate of cryptosporidiosis in nitazoxanide-treated patients was 45/49 (92%).
Enteropathogen Infection and Economic Status
Unexpectedly, the likelihood of infection was directly proportional to socioeconomic status; the areas of greatest wealth had the highest number and density of infection. This is illustrated in Figure 1, in which the zip codes of residence for all tested in GLAMA were mapped. and geographical density of infection was determined.
This was layered over a similar map of GLAMA's urban amenities (Figure 2), creating a sort of cultural and socioeconomic axis for the region. Major cities of the world have their own unique urban character.
Map courtesy of Trojan Family Magazine, University of Southern California. Source: Krueger SG. Delimiting the postmodern urban center: an analysis of urban amenity clusters in Los Angeles. Master's thesis, University of Southern California, 2012. Available at TinyURL.com/SamuelKrueger.
The presence of enteropathogens is generally misconceived as the consequence of poor sanitation; inadequate inspection, choice, and preparation of food and water; poor personal or public sanitary habits or services; low socioeconomic status; the inadequacies of development; and/or response to natural or civil disaster/turmoil. But note that the incidence and density of infection in GLAMA was high in affluent areas. The profession and public alike should be aware that higher economic status, even with the concomitant public and private health advantages, is associated with a high incidence of enteropathogens. (Ironically, it has been speculated that the high incidence for this demographic comes eating high amounts of organic raw food for health purposes.) Whatever the reasons for this, practitioners should be aware of an elevated risk of parasitosis in their more affluent patients.
The Greater Los Angeles Area is the quintessential 21st-century metropolis. As of the 2010 US Census, by population and area, it is the second largest metropolitan region of the country in one of the fastest-growing regions, and the most densely populated urbanized area in the US. It is one of the largest urban agglomerations in the world. These findings regarding enteropathogens from a retrospective analysis of practice are probably indicative of the current status of the health and welfare of the US in general now and into the future, as shown in Figure 3.
Enteropathic infection is common in patients seen for chronic nonspecific signs and symptoms of gastrointestinal dysfunction/disease in immune competent patients who reside in the US – it would not be an overstatement to describe it as endemic. Cosynchronous infection with more than one parasite is evident in the majority, which may indicate multiple sources of exposure (food, water, environment, intimate physical and/or familial contacts). It may also indicate a compromised immune systems, including dysregulation of gut flora, creating a vulnerable terrain for opportunistic bugs. In roughly one-third of intimate physical relationships, the same parasitic infection(s) were shared by the partners. It is not surprising that intimate contact is a very reliable way to transmit IGPs. Addressing the infection in one partner, only to have that person reinfected by the untreated partner – passing a bug back and forth – was the number one cause of treatment failure. It would be wise to also encourage testing of those in intimate contact with those infected regardless of symptoms or lack thereof.
HPA and Pineal Dysfunction
Patients with enteropathogens commonly demonstrate HPA and pineal dysfunction and dysregulation on the basis of elevated salivary cortisol and decreased DHEA-S and melatonin levels and patterns. Circadian salivary hormone panels clearly show that this happens especially between midnight and morning. This systemic neuroendocrine extraintestinal disorder in patients with a chronic enteropathogen infection has broad clinical significance in respect to prognosis and therapy. Patients with enteropathogens should be presumed to have HPA and pineal dysfunction and dysregulation. Those with the same neuroendocrine symptoms should again be thoroughly examined for enteropathogen infection using all methods available.
Celiac disease is currently considered an autoimmune disorder with increasing attention to the pathogenic role of food, gluten in particular. However, as long ago as the 1940s, the connection between giardia and celiac disease (or sprue) was known but seems to have been largely forgotten. The patient database was analyzed for a correlation of salivary antigliadin secretory antibody IgA2, indicative of celiac disease, to the presence of enteropathogenic infection.
More often than not, patients with infection by enteropathogens demonstrate evidence of celiac disease; for example, elevated levels of salivary antibody IgA to gliadins, gliadin Ab and SIgA. A search for parasitosis as a cause must be made before relegation by exclusion to the diagnoses of gluten enteropathy, sensitivity, or celiac disease with "no evidence of infection." The effect on nutritional assessment and dietary habits is enormous. With eradication of infection, cause and effect are obvious and of demonstrable benefit. Patients with the diagnosis of celiac disease should be thoroughly tested for enteropathogens using all methods available.
As with many of the patients with enteropathogens, those detected with cryptosporidiosis (the most common water-borne infection in the nation) often demonstrate concurrent evidence of celiac disease with abnormally elevated (positive) levels of salivary antigliadin secretory IgA. In these patients, eradication of infection is followed by return of elevated antibody levels to normal, along with resolution of symptoms and possibly the ability to resume dietary freedom from further restrictions. It is unsure what causes this association: it may be secondary to immune activation in the gastrointestinal tract. What is clear is a convincing case of cause, effect, and enduring relief without adverse effect of therapy. The presence and treatment of enteric pathogens should be the first step in the work-up of suspected celiac disease patients.
Buzoni-Gatel D, Buzoni-Gatel D, Schulthess J, Menard LC, Kasper LH. Mucosal defenses against orally acquired protozoan parasites; emphasis on Toxoplasma gondii infections. Cell Microbiol. 2006;8:535–544.
Fasano A, Catassi C. Celiac disease. N Engl J Med. 2012;367(25):2419–2426.
Hilavsa MC, Roberts VA, Anderson AR, et al. Surveillance for waterborne disease outbreaks and other health events associated with recreational water–United States 2007–8. MMWR Surveill Summ. 2011;60:1–37.
Khashan AS et al. Increased risk of miscarriage and ectopic pregnancy among women with irritable bowel syndrome. Clin Gastroenterol Hepatol. 2012;10:902–909.
Ross GP et al. Enteropathogens and chronic illness in returning travelers. N Engl J Med. 2013 368;19:1817–1825.
Rujner J et al. Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for celiac disease. Acta Paediatrica. 1996;85(7):814–817.
Stuppy WP, Borkin, IM. Chronic infectious enteritis and dysregulation of the hypothalamic pituitary adrenal axis. Am J Gastroenterol. October 2009;104(S3):S115. Abst. #306.
———. Disturbances in melatonin output in chronic infectious enteritis. Am J Gastroenterol. October 2009;04(S3):S116. Abst. #308.
Stuppy WP, Garcia TT. Enteropathogens and chronic disease in the twenty-first century: Los Angeles, California. Am J Gastroenterol. 2013;108(suppl 1):S313. Abst. #1048.
———. Celiac disease and enteropathogens. Am J Gastroenterol. 2013;108(suppl 1):S105. Abst. #354.
———. Nitazoxanide, cryptospridium, and celiac disease – a case of cure, cause, and effect. Am J Gastroenterol. 2013;108(suppl 1):S104. Abst. #351.
William P. Stuppy, MD, is board certified in gastroenterology, pathology, internal medicine, and hyperbaric medicine. He has been in private practice in the Los Angeles area for over 30 years, with staff privileges at Good Samaritan and other hospitals. He is the owner of the Hyperbaric Oxygen Clinic of Santa Monica. He has had more than 50 papers published in peer-reviewed journals on a variety of medical topics.