User:Gastro guy/emerg

Introduction

Gastrointestinal pathogens are organisms which can infect the digestive organs, causing illness. Several types of pathogens exist, such as Virus, bacteria, protozoa and helminthes (worms). They are usually transmitted through contaminated food or water. The association of gastrointestinal pathogens with disease can be a complex and controversial process, in some cases requiring decades or even centuries to achieve.

19th Century

Vibrio cholerae (1849-1884)

Cholera is a sometimes fatal disease caused by infection with the bacteria Vibrio cholerae This bacteria is carried in water. Once ingested, the bacteria colonizes the intestinal tract of the host and produces a toxin which causes body fluids to flow across the lining of the intestine. Death can result in 2-3 hours if no treatment is provided

Prior to the discovery of an infectious cause, the symptoms of Cholera were thought to be caused by an excess of bile in the patient . The disease Cholera gets its name from the Greek word choler meaning bile. This was consistent with medical thought at the time, which held that four humors controlled health, and lead to such medical practices as bloodletting as a method of curing illnesses. The bacteria was first reported in 1849 by Pouchet, who discovered it in stools from patients with Cholera. But he did not appreciate its significance. The first scientist to understand the significance of Vibrio cholerae was an Italian anatomist Filippo Pacini, who published detailed drawings of the organism in "Microscopical observations and pathological deductions on cholera" in 1854. He would go onto publish additional papers in 1866, 1871, 1876 and 1880, all of which were ignored by the scientific community. He correctly described how the bacteria caused diarrhea, and developed treatments that were found to be effective. But his findings did not influence medical opinion. In 1874, scientific representatives from 21 countries voted unanimously to resolve that Cholera was caused by environmental toxins from miasmatas, or clouds of unhealthy substances which float in the air. In 1884, Later, Robert Koch re-discovered Vibrio cholerae as a causal element in Cholera. Some scientists opposed the new theory, and even drank Cholera cultures to disprove it:

Koch announced his discovery of the cholera vibrio in 1884. His conclusions were based upon the constant finding of the peculiar "comma bacillus" in the stools of cholera patients, and the failure to demonstrate this organism in the feces of other persons. It was not possible to reproduce typical cholera in laboratory animals. At the time the "germ theory" of disease had not yet obtained general acceptance, and Koch's announcement was received with considerable skepticism, particularly after it was found that similar "comma bacilli" could be found at times in the feces of persons not suffering from cholera, and often in all sorts of other environments - well and river waters, cheese, etc. We now know that these were saprophytic species of Vibrio, which may be differentiated from the cholera vibrio by cultural and immunological methods. But the correctness of Koch's opinion was dramatically demonstrated by von Pettenkofer and Emmerich who, doubting the etiological relationship of Koch's organisms, deliberately drank cultures of it. Von Pettenkofer developed merely a transient diarrhea, but Emmerich suffered from a typical and severe attack of cholera.

— by A.T. Henrici, The Biology of Bacteria, DC Heath and Company, 1939. ASIN B00085GABK,

Von Pettenkofer considered his experience proof that Vibrio cholerae was harmless, as he did not develop Cholera from consuming the culture. Between 1849 when Pouchet discovered Vibrio cholerae and 1991, over a million people died in Cholera epidemics in Europe and Russia . In 1995, researchers published a study in Science Magazine explaining why some persons are able to be infected with Cholera] without symptoms, possibly explaining why Pettenkofer did not get sick. The study showed that a series of genetic mutations in some people provide resistance to Cholera toxin. However, these mutations come with a price. If too many of them occur in a person, they will develop Cystic Fibrosis, an incurable and often fatal genetic disorder. Persons who have some of the mutations are resistant to Cholera, but also carry a genetic code which could leave their children or grand-children with Cystic Fibrosis.

20th Century

Giardia lamblia (1681-1975)

Giardiasis is a disease caused by infection with the protozoan Giardia lamblia. Infection with Giardia can produce diarrhea, gas, and abdominal pain in some people. If untreated, infection can be chronic, lasting many years. In children, chronic Giardia infection can cause stunting (stunted growth) and lowered intelligence . Infection with Giardia is now universally recognized as a disease, and treated by physicians with anti-protozoal drugs. Since 2002, Giardia cases must be reported to the Center for Disease Control, according to the CDC’s Reportable Disease Spreadsheet. The United States National Institutes of Health Gastrointestinal Parasites Lab Giardia experienced an extraordinarily long term of emergence, from its discovery in 1681, until the 1970's when it was fully accepted that infection with Giardia was a treatable cause of chronic diarrhea.

Giardia lamblia was first discovered by Leeuwenhoeck (1681) who found the parasite in his own {diarrheal} stools. It was long considered to be a harmless commensal organism, but in recent years has been recognized as a cause of intestinal disease often acquired by travelers to foreign countries, persons drinking contaminated water in this country, children in day care nurseries and homosexual males. It is the most common pathogenic intestinal parasite in the United States, being found in 4% of stool specimens submitted to state public health laboratories for parasite examination. Attesting to its increasing importance in the United States, a symposium on Giardiasis, sponsored by the Environmental Protection Agency, was held in the Fall of 1978..

— by JW Smith, Giardiasis, 1980

Some of the first evidence in modern times of Giardia's pathogenicity came during World War II (1940-1945), soldiers were treated for malaria with the antiprotozoal Quinacrine, and their diarrhea disappeared, as did the Giardia from their stool samples. In 1954, Dr. R.C. Rendtorff performed experiments on prisoner volunteers, infecting them with Giardia to demonstrate pathogenicity. In the experiment, the prisoners became ill, and Giardia cysts were recovered from their stools, fulfilling the requirements for Koch's Postulates. His experiments were described in the EPA Symposium on Waterborne Transmission of Giardiasis in 1979:

We also included Giardia lamblia, which at that time was not generally believed to be an invasive pathogenic parasite of man. Giardia was thought in the 1950s to cause occasional problems of diarrhea in children but its appearance was so common and, in adults so lacking in clinical symptomatology, that most considered it a non-pathogen. As a result we felt safe in exposing prisoners to Giardia...

— by Dr. RC Rettndorf in an EPA Symposium on the Waterborne Transmission of Giardiasis - in 1979

In 1954-55, an outbreak of Giardia infection occurred in Oregon (US), sickening 50,000 people. This was documented in a paper by Lyle Veazie, which was published in The Lancet in 1969. It was also published in the EPA Symposium on Waterborne Transmission of Giardiasis in 1979, and it includes the following quote from the Director of the Oregon State Board of Health, showing that diarrhea from Giardia was still being attributed to other causes:

While an unidentified virus seems the most likely etiologic agent, the unusual prevalence of Giardia lamblia cysts in stools of patients seems worthy of record.

— by Oregon State Board of Health, as quoted in Veazie, 1969.

Helicobacter pylori (1892-1982)

Infection with the bacteria Helicobacter pylori is the cause of most stomach ulcers. The discovery that a bacteria was the true cause of stomach ulcers is generally credited to Australian gastroenterologists Dr. Barry Marshall and Dr. J Robin Warren, who published their findings in 1983. The pair received the Nobel Prize in 2005 for their work. Before this, nobody really knew what caused stomach ulcers, though a popular belief was that the "stress of modern life" played a role. Some people even believed that ulcers were a psychosomatic illness

In H Pylori Pioneers, Dr. Marshall noted that other physicians had produced evidence of H. pylori infection as early as 1892. Marshall writes that earlier reports were disregarded because they conflicted with existing belief. The first description of H. Pylori came in 1892 from Giulio Bizzozero, who identified acid-tolerant bacteria living in a dog’s stomach. Later, a theory would be developed that no bacteria could live in the stomach. Although the theory has no scientific basis, it would become a stumbling block for scientists, discouraging them for searching for infective causes of stomach ulcers. In 1940, two physicians, Dr. A. Stone Freeberg and Dr. Louis E. Barron published a paper describing a spiral bacteria found in about half of their gastroenterology patients who had stomach ulcers. Dr. John Lykoudis, a Greek physician, was one of the first physicians to treat stomach ulcers as an infectious disease. Between 1960 and 1970, he treated over 10,000 ulcer patients in Athens with antibiotics. Lykoudis tried to publish a paper on his findings, but they conflicted with traditional theory, and his work was never published. Lykoudis' experience was was followed in 1975 by a further publication in Gut magazine that included spiral bacteria living on the borders of duodonal ulcers. The medical significance of Steer’s findings was disregarded, but he “continued to publish papers on H. Pylori, mostly as a hobby."

H. pylori can infect the stomach of some people without causing stomach ulcers. In investigating asymptomatic carriers of H. pylori, researchers identified a genetic mutation called Interleuik-1 beta-31 which some patients to produce more stomach acid, and develop stomach ulcers when they become infected with H. pylori. Patients who produce less stomach acid did not develop ulcers, but were found to be at increased risk for stomach cancer when infected with H. pylori. Investigation into other gastrointestinal infections has also shown that the symptoms are the result of interaction between the infection and specific genetic mutations in the host.

Pathogenic variants of Escherichia coli (1947-1983)

Enterotoxigenic Escherichia coli (ETEC) is a type of bacteria that causes illness in humans. There are different types of E. Coli, some of which are found in humans and are harmless. ETEC is a special kind of E. Coli which has a gene that allows it to manufacture a substance toxic to humans. Cattle are immune to the effects of ETEC, but when people eat food contaminated with cattle feces, the organism can cause disease. But physicians and microbiologists had published reports of pathogenic E. Coli as early as 1947 . Publications regarding variants of E. Coli which cause disease appeared in medical journals regularly in the 1950's, 1960's, and 1970's. In the 1970's, reports began surfacing that animals and infants were beginning to die from E. Coli Despite the earlier reports, pathogenic E. Coli did not rise to public prominence until 1983, when Dr. Joyce Riley of the Center for Disease Control published a paper identifying ETEC as the cause of a series of outbreaks of unexplained hemmoragic gastrointestinal illness. The New York Times account of the discovery mentions the opposition Dr. Riley encountered in 1983 in establishing ETEC as a pathogen, despite the earlier publication of pathogenic variants of E. Coli. Since then, another type of pathogenic E. Coli has been identified in developing countries called Entero-Aggregative E. Coli (EAEC).

Cyclospora (1995)

Cyclospora is a gastrointestinal pathogen that causes fever, diarrhea, vomiting, and severe weight loss. Outbreaks of the disease occurred in Chicago in 1989 and other areas in the United States . The disease puzzled officials at the Center for Disease Control. The discovery of the cause was made by Mr. Ramachandran Rajah, the head of a a medical clinic's laboratory in Katmandu, India. Mr. Rajah was trying to discover why local residents and visitors were becoming ill every summer. He identified an unusual looking organism in stool samples from patients who were sick. But when the clinic sent slides of the organism to the Center for Disease Control, it was identified as Blue-Green algae, which is harmless. Many pathologists had seen the same thing before, but dismissed it as irrelevant to the patient's disease. . Later, the organism would be identified as a special kind of parasite, and treatment would be developed to help patients with the infection. In the United States, Cyclospora infection must be reported to the Center for Disease Control according to the | CDC's Reportable Disease Chart

21st Century

In the 21st Century, Irritable Bowel Syndrome has become the target of researchers looking for unrecognized infectious diseases, just as Cholera and stomach ulcers were of interest in earlier times. Figure 1 shows the prevalence of gastrointestinal protozoal infection in studies from the United States and Canada. In the 1970's, Giardia was the most prevalent protozoal infection, and its significance was debated among physicians. Figure 1 suggests shows Blastocystis and Dientamoeba fragilis as being the most prevalent in these studies. Varying opinons exist as to thir significance, with physicians in some areas of the world treating them, while researchers from other areas report that infection with these protozoa is considered incidental. The majority of research into these protozoa comes from South East Asia, the Middle East, and to a lesser extent, Europe. To date, this research has suggested a relationship between these protozoa and Irritable Bowel Syndrome. Additionally, researchers have suggested that existing clinical diagnostics may fail to detect infection. In the case of Giardia and other protozoal infections, the use of an immunoassay has been found to be necessary to reliably detect the infection in patients. .

Dientamoeba fragilis

Dientamoeba fragilis is a single-celled parasite which infects the large intestine causing diarrhea, gas, and abdominal pain. An Australian study identified patients with symptoms of IBS who were actually infected with Dientamoeba fragilis . Their symptoms resolved following treatment. A study in Denmark identified a high incidence Dientamoeba fragilis infection in a group of patients suspected of having gastrointestinal illness of an infetious cause.. The study also noted that the ability to identify the infection was dependent on the type of diagnostic stain used.

Blastocystis

Blastocysits is a single-celled protozoan which infects the large intestine. Physicians report that patients with infection show symptoms of abdominal pain, constipation, and diarrhea.. It's ability to cause symptoms has been the subject of debate. In the United States, one study of symptomatic patients found that Blastocystis was the only infective organism found in the majority of symptomatic patients

A relationship between Blastocystis infection and Irritable Bowel Syndrome has been proposed because researchers note that it occurs more frequently in IBS patients, and case reports suggest it produces symptoms that match IBS symptoms closely. Researchers at Agha Khan University in Pakistan found that Blastocystis infection was present in 46% of IBS patients vs 7% of controls by stool culture. . Another study examined immune response to Blastocystis, a technique used to detect the presence of some difficult-to-identify infections. This study found that IBS patients exhibited a heightened immune response to a Blastocystis antigen not present in controls. The immune response was present even in patients from whom Blastocystis could not be found with culture. A recent study using molecular diagnostics suggested that Blastocystis infection can be present in patients with diarrhea, but undetectable even with stool culture. In one study, 40% of the Blastocystis isolates from IBS patients were found to be resistant to common anti-protozoal drugs with in-vitro testing. Case reports also suggest the infection may be difficult to treat in some patients.