Osmotic diarrhea occurs when too much water is drawn into the bowels. If a person drinks solutions with excessive sugar or excessive salt, these can draw water from the body into the bowel and cause osmotic diarrhea. [ 20 ] [ 19 ]  Osmotic diarrhea can also result from maldigestion (e.g., pancreatic disease or  coeliac disease ) in which the nutrients are left in the  lumen  to pull in water. Or it can be caused by osmotic  laxatives  (which work to alleviate  constipation  by drawing water into the bowels). In healthy individuals, too much  magnesium ,  vitamin C  or undigested  lactose  can produce osmotic diarrhea and distention of the bowel. A person who has  lactose intolerance  can have difficulty absorbing lactose after an extraordinarily high intake of dairy products. In persons who have  fructose malabsorption , excess fructose intake can also cause diarrhea. High-fructose foods that also have a high glucose content are more absorbable and less likely to cause diarrhea.  Sugar alcohols  such as  sorbitol  (often found in sugar-free foods) are difficult for the body to absorb and, in large amounts, may lead to osmotic diarrhea. [ 18 ]  In most of these cases, osmotic diarrhea stops when the offending agent (e.g., milk or sorbitol) is stopped.


Exudative diarrhea occurs with the presence of blood and pus in the stool. This occurs with  inflammatory bowel diseases , such as  Crohn's disease  or  ulcerative colitis , and other severe infections such as  E. coli  or other forms of food poisoning. [ 19 ] [ 18 ]


Inflammatory diarrhea occurs when there is damage to the mucosal lining or brush border, which leads to a passive loss of protein-rich fluids and a decreased ability to absorb these lost fluids. Features of all three of the other types of diarrhea can be found in this type of diarrhea. [ 21 ]  It can be caused by bacterial infections, viral infections, parasitic infections, or autoimmune problems such as inflammatory bowel diseases. It can also be caused by tuberculosis, colon cancer, and enteritis. [ 19 ]


If there is blood visible in the stools, it is also known as  dysentery . The blood is a trace of an invasion of bowel tissue. Dysentery is a symptom of, among others,  Shigella ,  Entamoeba histolytica , and  Salmonella . [ 19 ]


Diarrheal disease may have a negative impact on both physical fitness and mental development. "Early childhood malnutrition resulting from any cause reduces physical fitness and work productivity in adults", [ 22 ]  and diarrhea is a primary cause of childhood malnutrition. [ 23 ]  Further, evidence suggests that diarrheal disease has significant impacts on mental development and health; it has been shown that, even when controlling for  helminth  infection and early breastfeeding, children who had experienced severe diarrhea had significantly lower scores on a series of tests of intelligence. [ 22 ] [ 24 ]


Diarrhea can cause  electrolyte imbalances ,  kidney impairment ,  dehydration , and defective  immune system  responses. When oral drugs are administered, the efficiency of the drug is to produce a  therapeutic effect  and the lack of this effect may be due to the medication travelling too quickly through the digestive system, limiting the time that it can be absorbed. Clinicians try to treat the diarrheas by reducing the dosage of medication, changing the dosing schedule, discontinuation of the drug, and rehydration. The interventions to control the diarrhea are not often effective. Diarrhea can have a profound effect on the quality of life because fecal incontinence is one of the leading factors for placing older adults in  long term care facilities  (nursing homes). [ 19 ]


In the latter stages of human digestion, ingested materials are inundated with water and digestive fluids such as  gastric acid ,  bile , and  digestive enzymes  in order to break them down into their nutrient components, which are then absorbed into the bloodstream via the  intestinal tract  in the small intestine. Prior to defecation, the large intestine reabsorbs the water and other digestive solvents in the waste product in order to maintain proper hydration and overall equilibrium. [ 25 ]  Diarrhea occurs when the large intestine is prevented, for any number of reasons, from sufficiently absorbing the water or other digestive fluids from fecal matter, resulting in a liquid, or "loose", bowel movement. [ 26 ]


Acute  diarrhea is most commonly due to viral  gastroenteritis  with  rotavirus , which accounts for 40% of cases in children under five. [ 1 ]  In  travelers , however,  bacterial infections  predominate. [ 27 ]  Various toxins such as  mushroom poisoning  and drugs can also cause acute diarrhea.


Chronic diarrhea can be the part of the presentations of a number of chronic medical conditions affecting the intestine. Common causes include  ulcerative colitis ,  Crohn's disease ,  microscopic colitis ,  celiac disease ,  irritable bowel syndrome , and  bile acid malabsorption . [ 28 ]


There are many causes of infectious diarrhea, which include  viruses ,  bacteria  and parasites. [ 29 ]  Infectious diarrhea is frequently referred to as  gastroenteritis . [ 30 ]   Norovirus  is the most common cause of viral diarrhea in adults, [ 31 ]  but  rotavirus  is the most common cause in children under five years old. [ 32 ]   Adenovirus  types 40 and 41, [ 33 ]  and  astroviruses  cause a significant number of infections. [ 34 ]   Shiga-toxin producing Escherichia coli , such as  E coli o157:h7 , are the most common cause of infectious bloody diarrhea in the United States. [ 35 ]


Campylobacter   spp.  are a common cause of bacterial diarrhea, but infections by  Salmonella  spp.,  Shigella  spp. and some strains of  Escherichia coli  are also a frequent cause. [ 36 ]


In the elderly, particularly those who have been treated with antibiotics for unrelated infections, a toxin produced by  Clostridioides difficile  often causes severe diarrhea. [ 37 ]


Parasites, particularly  protozoa  e.g.,  Cryptosporidium  spp.,  Giardia  spp.,  Entamoeba histolytica ,  Blastocystis  spp.,  Cyclospora cayetanensis , are frequently the cause of diarrhea that involves chronic infection. The broad-spectrum antiparasitic agent  nitazoxanide  has shown efficacy against many diarrhea-causing parasites. [ 38 ]


Other infectious agents, such as  parasites  or  bacterial  toxins, may exacerbate symptoms. [ 27 ]  In sanitary living conditions where there is ample food and a supply of clean water, an otherwise healthy person usually recovers from viral infections in a few days. However, for ill or  malnourished  individuals, diarrhea can lead to severe  dehydration  and can become life-threatening. [ 39 ]


Open defecation  is a leading cause of infectious diarrhea leading to death. [ 40 ]


Poverty is a good indicator of the rate of infectious diarrhea in a population. This association does not stem from poverty itself, but rather from the conditions under which impoverished people live. The absence of certain resources compromises the ability of the poor to defend themselves against infectious diarrhea. "Poverty is associated with poor housing, crowding, dirt floors, lack of access to clean water or to sanitary disposal of fecal waste ( sanitation ), cohabitation with domestic animals that may carry human pathogens, and a lack of refrigerated storage for food, all of which increase the frequency of diarrhea   ... Poverty also restricts the ability to provide age-appropriate, nutritionally balanced diets or to modify diets when diarrhea develops so as to mitigate and repair nutrient losses. The impact is exacerbated by the lack of adequate, available, and affordable medical care." [ 41 ]


One of the most common causes of infectious diarrhea is a lack of clean water. Often, improper fecal disposal leads to contamination of groundwater. This can lead to widespread infection among a population, especially in the absence of water filtration or purification. Human feces contains a variety of potentially harmful human  pathogens . [ 42 ]


Proper nutrition is important for health and functioning, including the prevention of infectious diarrhea. It is especially important to young children who do not have a fully developed immune system.  Zinc deficiency , a condition often found in children in  developing countries  can, even in mild cases, have a significant impact on the development and proper functioning of the human immune system. [ 43 ] [ 44 ]  Indeed, this relationship between zinc deficiency and reduced immune functioning corresponds with an increased severity of infectious diarrhea. Children who have lowered levels of zinc have a greater number of instances of diarrhea, severe diarrhea, and diarrhea associated with fever. [ 45 ]  Similarly,  vitamin A deficiency  can cause an increase in the severity of diarrheal episodes. However, there is some discrepancy when it comes to the impact of vitamin A deficiency on the rate of disease. While some argue that a relationship does not exist between the rate of disease and vitamin A status, [ 46 ]  others suggest an increase in the rate associated with deficiency. [ 47 ]  Given that estimates suggest 127 million preschool children worldwide are vitamin A deficient, this population has the potential for increased risk of disease contraction. [ 48 ]


Malabsorption  is the inability to absorb food fully, mostly from disorders in the small bowel, but also due to maldigestion from diseases of the  pancreas .


Causes include: [ citation needed ]


The two overlapping types here are of unknown origin:


Another possible cause of diarrhea is irritable bowel syndrome (IBS), which usually presents with abdominal discomfort relieved by  defecation  and unusual  stool  (diarrhea or  constipation ) for at least three days a week over the previous three months. [ 49 ]  Symptoms of diarrhea-predominant IBS can be managed through a combination of dietary changes, soluble fiber supplements and medications such as  loperamide  or  codeine . About 30% of patients with diarrhea-predominant IBS have  bile acid malabsorption  diagnosed with an abnormal  SeHCAT  test. [ 50 ]


Diarrhea can be caused by other diseases and conditions, namely:


Over 700 medications, such as  penicillin , are known to cause diarrhea. [ 53 ] [ 54 ]  The classes of medications that are known to cause diarrhea are laxatives, antacids, heartburn medications, antibiotics, anti-neoplastic drugs, anti-inflammatories as well as many dietary supplements. [ 19 ]


According to two researchers,  Nesse  and  Williams , diarrhea may function as an evolved expulsion defense mechanism. As a result, if it is stopped, there might be a delay in recovery. [ 56 ]  They cite in support of this argument research published in 1973 that found that treating  Shigella  with the anti-diarrhea drug (Co-phenotrope,  Lomotil ) caused people to stay  feverish  twice as long as those not so treated. The researchers indeed themselves observed that: "Lomotil may be contraindicated in shigellosis. Diarrhea may represent a defense mechanism". [ 57 ]


The following types of diarrhea may indicate further investigation is needed:


A severity score is used to aid diagnosis in children. [ 58 ]


When diarrhea lasts for more than four weeks a number of further tests may be recommended including: [ 59 ]


A 2019 guideline recommended that testing for ova and parasites was only needed in people who are at high risk though they recommend routine testing for  giardia . [ 60 ]   Erythrocyte sedimentation rate  (ESR) and  C-reactive protein  (CRP) were not recommended. [ 60 ]


Worldwide in 2004, approximately 2.5 billion cases of diarrhea occurred, which resulted in 1.5 million deaths among children under the age of five. [ 1 ]  Greater than half of these were in Africa and South Asia. [ 1 ]  This is down from a death rate of 4.5 million in 1980 for gastroenteritis. [ 62 ]  Diarrhea remains the second leading cause of  infant mortality  (16%) after  pneumonia  (17%) in this age group. [ 1 ]


The majority of such cases occur in the developing world, with over half of the recorded cases of childhood diarrhea occurring in  Africa  and  Asia , with 696 million and 1.2 billion cases, respectively, compared to only 480 million in the rest of the world. [ 63 ]


Infectious diarrhea resulted in about 0.7 million deaths in children under five years old in 2011 and 250 million lost school days. [ 64 ] [ 65 ]  In the Americas, diarrheal disease accounts for a total of 10% of deaths among children aged 1–59 months while in South East Asia, it accounts for 31.3% of deaths. [ 66 ]  It is estimated that around 21% of child mortalities in developing countries are due to diarrheal disease. [ 67 ]


The  World Health Organization  has reported that "deaths due to diarrhoeal diseases have dropped by 45%, from sixth leading cause of death in 2000 to thirteenth in 2021." [ 68 ]


Even though diarrhea is best known in humans, it affects many other species, notably among  primates . [ 69 ]  The  cecal appendix , when present, appears to afford some protection against diarrhea to young primates. [ 70 ]


Numerous studies have shown that improvements in drinking water and sanitation ( WASH ) lead to decreased risks of diarrhoea. [ 71 ]  Such improvements might include for example use of water filters, provision of high-quality  piped water  and  sewer  connections. [ 71 ]


In institutions, communities, and households, interventions that promote  hand washing  with soap lead to significant reductions in the incidence of diarrhea. [ 72 ]  The same applies to preventing  open defecation  at a community-wide level and providing access to  improved sanitation . [ 64 ] [ 73 ]  This includes use of  toilets  and implementation of the entire  sanitation  chain connected to the toilets (collection, transport, disposal or reuse of  human excreta ).


There is limited evidence that safe disposal of child or adult feces can prevent diarrheal disease. [ 74 ] [ 75 ]


Basic sanitation techniques can have a profound effect on the transmission of diarrheal disease. The implementation of hand washing using soap and water, for example, has been experimentally shown to reduce the incidence of disease by approximately 30–48%. [ 76 ] [ 77 ] [ 72 ]  Hand washing in developing countries, however, is compromised by poverty as acknowledged by the  CDC : "Handwashing is integral to disease prevention in all parts of the world; however, access to soap and water is limited in a number of less developed countries. This lack of access is one of many challenges to proper hygiene in less developed countries." Solutions to this barrier require the implementation of educational programs that encourage sanitary behaviours. [ 78 ]


Given that water contamination is a major means of transmitting diarrheal disease, efforts to provide clean  water supply  and  improved sanitation  have the potential to dramatically cut the rate of disease incidence. In fact, it has been proposed that we might expect an 88% reduction in child mortality resulting from diarrheal disease as a result of improved water sanitation and hygiene. [ 42 ] [ 79 ]  Similarly, a meta-analysis of numerous studies on improving water supply and sanitation shows a 22–27% reduction in disease incidence, and a 21–30% reduction in mortality rate associated with diarrheal disease. [ 80 ]


Chlorine treatment of water, for example, has been shown to reduce both the risk of diarrheal disease, and of contamination of stored water with diarrheal pathogens. [ 81 ]


Immunization against the pathogens that cause diarrheal disease is a viable prevention strategy, however it does require targeting certain pathogens for vaccination. In the case of Rotavirus, which was responsible for around 6% of diarrheal episodes and 20% of diarrheal disease deaths in the children of developing countries, use of a Rotavirus vaccine in trials in 1985 yielded a slight (2–3%) decrease in total diarrheal disease incidence, while reducing overall mortality by 6–10%. Similarly, a Cholera vaccine showed a strong reduction in morbidity and mortality, though the overall impact of vaccination was minimal as Cholera is not one of the major causative pathogens of diarrheal disease. [ 82 ]  Since this time, more effective vaccines have been developed that have the potential to save many thousands of lives in developing nations, while reducing the overall cost of treatment, and the costs to society. [ 83 ] [ 84 ]


Rotavirus vaccine  decreases the rates of diarrhea in a population. [ 1 ] [ 85 ]  New vaccines against rotavirus,  Shigella ,  Enterotoxigenic Escherichia coli (ETEC) , and cholera are under development, as well as other causes of infectious diarrhea. [ medical citation needed ]


Dietary deficiencies in developing countries can be combated by promoting better eating practices. Zinc supplementation proved successful showing a significant decrease in the incidence of diarrheal disease compared to a control group. [ 86 ] [ 87 ]  The majority of the literature suggests that vitamin A supplementation is advantageous in reducing disease incidence. [ 88 ]  Development of a supplementation strategy should take into consideration the fact that vitamin A supplementation was less effective in reducing diarrhea incidence when compared to vitamin A and zinc supplementation, and that the latter strategy was estimated to be significantly more cost effective. [ 89 ]


Breastfeeding practices have been shown to have a dramatic effect on the incidence of diarrheal disease in poor populations. Studies across a number of developing nations have shown that those who receive  exclusive breastfeeding  during their first 6 months of life are better protected against infection with diarrheal diseases. [ 90 ]  One study in Brazil found that non-breastfed infants were 14 times more likely to die from diarrhea than exclusively breastfed infants. [ 91 ]  Exclusive breastfeeding is currently recommended for the first six months of an infant's life by the  WHO , [ 92 ] [ 93 ]  with continued breastfeeding until at least two years of age. [ 93 ]


Probiotics  decrease the risk of diarrhea in those taking  antibiotics . [ 94 ]  Insecticide spraying may reduce fly numbers and the risk of diarrhea in children in a setting where there is seasonal variations in fly numbers throughout the year. [ 95 ]


In many cases of diarrhea, replacing lost fluid and salts is the only treatment needed. This is usually by mouth –  oral rehydration therapy  – or, in severe cases,  intravenously . [ 1 ]  Diet restrictions such as the  BRAT diet  are no longer recommended. [ 96 ]  Research does not support the limiting of milk to children as doing so has no effect on duration of diarrhea. [ 97 ]  To the contrary, WHO recommends that children with diarrhea continue to eat as sufficient nutrients are usually still absorbed to support continued growth and weight gain, and that continuing to eat also speeds up recovery of normal intestinal functioning. [ 20 ]  CDC recommends that children and adults with cholera also continue to eat. [ 98 ]  There is no evidence that early refeeding in children can cause an increase in inappropriate use of intravenous fluid, episodes of vomiting, and risk of having persistent diarrhea. [ 99 ]


Medications such as  loperamide  (Imodium) and  bismuth subsalicylate  may be beneficial; however they may be  contraindicated  in certain situations. [ 100 ]


Oral rehydration solution (ORS)  (a slightly sweetened and salty water) can be used to prevent dehydration. Standard home solutions such as salted rice water, salted yogurt drinks, vegetable and chicken soups with salt can be given. Home solutions such as water in which cereal has been cooked, unsalted soup, green coconut water, weak tea (unsweetened), and unsweetened fresh fruit juices can have from half a teaspoon to full teaspoon of salt (from one-and-a-half to three grams) added per liter. Clean plain water can also be one of several fluids given. [ 20 ]  There are commercial solutions such as  Pedialyte , and relief agencies such as  UNICEF  widely distribute packets of salts and sugar. A WHO publication for physicians recommends a homemade ORS consisting of one liter water with one teaspoon salt (3 grams) and two tablespoons sugar (18 grams) added [ 20 ]  (approximately the "taste of tears" [ 101 ] ). Rehydration Project recommends adding the same amount of sugar but only one-half a teaspoon of salt, stating that this more dilute approach is less risky with very little loss of effectiveness. [ 102 ]  Both agree that drinks with too much sugar or salt can make dehydration worse. [ 20 ] [ 102 ]


Appropriate amounts of supplemental zinc and potassium should be added if available. But the availability of these should not delay rehydration. As WHO points out, the most important thing is to begin preventing dehydration as early as possible. [ 20 ]  In another example of prompt ORS hopefully preventing dehydration, CDC recommends for the treatment of cholera continuing to give Oral Rehydration Solution during travel to medical treatment. [ 98 ]


Vomiting often occurs during the first hour or two of treatment with ORS, especially if a child drinks the solution too quickly, but this seldom prevents successful rehydration since most of the fluid is still absorbed. WHO recommends that if a child vomits, to wait five or ten minutes and then start to give the solution again more slowly. [ 20 ]


Drinks especially high in simple sugars, such as  soft drinks  and fruit juices, are not recommended in children under five as they may  increase  dehydration. A too rich solution in the gut draws water from the rest of the body, just as if the person were to drink sea water. [ 20 ] [ 103 ]  Plain water may be used if more specific and effective ORT preparations are unavailable or are not palatable. [ 103 ]  Additionally, a mix of both plain water and drinks perhaps too rich in sugar and salt can alternatively be given to the same person, with the goal of providing a medium amount of sodium overall. [ 20 ]  A  nasogastric tube  can be used in young children to administer fluids if warranted. [ 104 ]


The WHO recommends a child with diarrhea continue to be fed. Continued feeding speeds the recovery of normal intestinal function. In contrast, children whose food is restricted have diarrhea of longer duration and recover intestinal function more slowly. The WHO states "Food should  never  be withheld and the child's usual foods should  not  be diluted. Breastfeeding should  always  be continued." [ 20 ]  In the specific example of cholera, the CDC makes the same recommendation. [ 98 ]  Breast-fed infants with diarrhea often choose to breastfeed more, and should be encouraged to do so. [ 20 ]  In young children who are not breast-fed and live in the developed world, a lactose-free diet may be useful to speed recovery. [ 105 ]
Eating food containing  soluble fibre  may help, but insoluble fibre might make it worse. [ 106 ]


Antidiarrheal  agents  can  be  classified  into  four  different groups: antimotility, antisecretory, adsorbent, and anti-infectious. [ 107 ]  While  antibiotics  are beneficial in certain types of acute diarrhea, they are usually not used except in specific situations. [ 108 ] [ 109 ]  There are concerns that antibiotics may increase the risk of  hemolytic uremic syndrome  in people infected with  Escherichia coli O157:H7 . [ 110 ]  In resource-poor countries, treatment with antibiotics may be beneficial. [ 109 ]  However, some bacteria are developing  antibiotic resistance , particularly  Shigella . [ 111 ]  Antibiotics can also cause diarrhea, and  antibiotic-associated diarrhea  is the most common adverse effect of treatment with general antibiotics.


While bismuth compounds ( Pepto-Bismol ) decreased the number of bowel movements in those with travelers' diarrhea, they do not decrease the length of illness. [ 112 ]  Anti-motility agents like  loperamide  are also effective at reducing the number of stools but not the duration of disease. [ 8 ]  These agents should be used only if bloody diarrhea is not present. [ 113 ]


Diosmectite , a natural aluminomagnesium silicate clay, is effective in alleviating symptoms of acute diarrhea in children, [ 114 ]  and also has some effects in chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. [ 52 ]  Another absorbent agent used for the treatment of mild diarrhea is  kaopectate .


Racecadotril  an antisecretory medication may be used to treat diarrhea in children and  adults. [ 107 ]  It has better tolerability than  loperamide , as it causes less  constipation  and  flatulence . [ 115 ]  However, it has little benefit in improving acute diarrhea in children. [ 116 ]


Bile acid sequestrants  such as  cholestyramine  can be effective in chronic diarrhea due to  bile acid malabsorption . Therapeutic trials of these drugs are indicated in chronic diarrhea if bile acid malabsorption cannot be diagnosed with a specific test, such as  SeHCAT  retention. [ 117 ]


Zinc supplementation may benefit children over six months old with diarrhea in areas with high rates of malnourishment or zinc deficiency. [ 118 ]  This supports the World Health Organization guidelines for zinc, but not in the very young.


A Cochrane Review from 2020 concludes that  probiotics  make little or no difference to people who have diarrhea lasting 2 days or longer and that there is no proof that they reduce its duration. [ 119 ]  The  probiotic   lactobacillus  can help prevent  antibiotic-associated diarrhea  in adults but possibly not children. [ 120 ]  For those with  lactose intolerance , taking digestive  enzymes  containing  lactase  when consuming dairy products often improves symptoms.


Diverticulosis  is the condition of having multiple pouches ( diverticula ) in the  colon  that are not inflamed. These are outpockets of the colonic  mucosa  and submucosa through weaknesses of  muscle  layers in the colon wall. [ 1 ]  Diverticula do not cause symptoms in most people. [ 2 ]   Diverticular disease  occurs when diverticula become clinically inflamed, a condition known as  diverticulitis . [ 3 ]


Diverticula typically occur in the  sigmoid colon , which is commonplace for increased pressure. The left side of the colon is more commonly affected in the United States while the right side is more commonly affected in Asia. [ 4 ]  Diagnosis is often during routine  colonoscopy  or as an incidental finding during  CT scan . [ 2 ]


It is common in Western countries with about half of those over the age of 60 affected in Canada and the United States. [ 4 ]  Diverticula are uncommon before the age of 40, and increase in incidence beyond that age. [ 5 ]  Rates are lower in Africa; [ 4 ]  the reasons for this remain unclear but may involve the greater prevalence of a high  fiber  diet in contrast with the lower-fiber diet characteristic of many Western populations. [ 6 ]


Some people with diverticulosis complain of symptoms such as cramping, bloating, flatulence, and irregular defecation. However, it is unclear if these symptoms are attributable to the underlying diverticulosis or to coexistent  irritable bowel syndrome . [ 7 ]


Diverticular disease was found associated with a higher risk of left sided colon cancer. [ 8 ]


Diverticular disease can present with painless rectal bleeding as bright red blood per rectum. Diverticular bleeding is the most common cause of acute lower gastrointestinal bleeding. [ 9 ]  However, it is estimated that 80% of these cases are self-limiting and require no specific therapy. [ 10 ]


Infection of a diverticulum can result in  diverticulitis . A 2013 study [ 11 ]  found that it happens only about 4% of the time. That contradicts the prevailing thinking that 10% to 25% of people with diverticulosis go on to develop diverticulitis. Tears in the colon leading to bleeding or perforations may occur; intestinal obstruction may occur (constipation or diarrhea does not rule this possibility out); and  peritonitis ,  abscess  formation,  retroperitoneal   fibrosis ,  sepsis , and  fistula  formation are also possible occurrences.  Rarely, an  enterolith  may form. Infection of a diverticulum often occurs as a result of stool collecting in a diverticulum.


Diverticulitis is defined as diverticular disease with signs and symptoms of diverticular inflammation. Clinical features of acute diverticulitis include constant abdominal pain, localized abdominal tenderness in the left lower quadrant of the abdomen, nausea, vomiting, constipation or diarrhea, fever and  leukocytosis . [ 12 ]


Most people with colonic diverticulosis are unaware of this structural change. When symptoms do appear in a person over 40 years of age it is important to obtain medical advice and exclude more dangerous conditions such as cancer of the colon or rectum. [ 13 ] [ 14 ] [ 15 ] [ 16 ]


Segmental colitis associated with diverticulosis (SCAD) is a condition characterized by localized  inflammation  of the colon between diverticula (interdiverticular mucosa) while sparing the diverticular orifices. SCAD may lead to abdominal pain, especially in the left lower quadrant, intermittent rectal bleeding, and chronic diarrhea.


The U.S.  National Institutes of Health  notes that, although the low-fiber theory of the cause of diverticulosis is the leading theory, it has not yet been proven. [ 17 ]


The predisposition to diverticulosis for specific individuals is likely explained by a genetic component, a theory that is supported by studies examining the rates of diverticulosis among twins. [ 1 ]   The  heritability  of diverticulosis is estimated to be approximately 40%. [ 1 ]


Another theory suggests the degeneration of  glial   neurons  in the  myenteric plexus  and the  interstitial cells of Cajal  lead to slowed intestinal movement and consequently fecal content exerts increased pressure on the colon wall resulting in the formation of diverticula. [ 1 ]


The precise mechanisms by which diverticula are formed are unknown. [ 1 ]  Multiple theories have been proposed including genetic susceptibility, diet, intestinal motility, changes in the  microbiome , and  inflammation . One leading theory suggests that diverticula form in weakened areas of the colon wall that are subjected to increased pressure. [ 1 ]  The strength of the colon wall is known to decrease with age. [ 1 ]  Previous theories proposed that impacted fecal matter and certain foods would get stuck in diverticula (thereby causing trauma), which caused  poor blood flow ,  death of the affected intestinal wall cells , and  intestinal perforation . [ 1 ]  Newer theories have called this paradigm into question. [ 1 ]


Diverticulosis is defined by the presence of multiple pouches (diverticula) in the colon. [ 22 ]  In people without symptoms, these are usually found incidentally during other investigations. [ citation needed ]


While a good history is often sufficient to form a diagnosis of diverticulosis or diverticulitis, it is important to confirm the diagnosis and rule out other pathology (notably  colorectal cancer ) and complications.


It is important to note that both barium enema and colonoscopy are contraindicated during acute episodes of diverticulitis, as the barium may leak out into the abdominal cavity, and colonoscopy can cause perforations of the bowel wall.


Many people with diverticulosis have minimal to no symptoms and do not require any specific treatment. Colonic stimulants should be avoided. Treatments, like some colon cleansers, that cause hard stools, constipation, and straining, are not recommended. [ citation needed ]


A high-fiber diet and fiber supplements are advisable to prevent constipation. [ 23 ] [ 24 ]  The American Dietetic Association recommends 20–35 grams each day. Wheat bran has been shown to reduce intra colonic pressure. [ 25 ] [ 26 ]


The US  National Institute of Diabetes and Digestive and Kidney Diseases  (NIDDK) says foods such as nuts, popcorn hulls, sunflower seeds, pumpkin seeds, caraway seeds, and sesame seeds have traditionally been labeled as problem foods for people with this condition; however, no scientific data exists to prove this hypothesis. The seeds in tomatoes, zucchini, cucumbers, strawberries, raspberries, and poppy seeds, are not considered harmful by the NIDDK. [ 2 ]


One study found that nuts and popcorn do not contribute positively or negatively to patients with diverticulosis or diverticular complications. [ 27 ] [ 28 ]


Complicated diverticulosis requires treatment of the complication. These complications are often grouped under a single diagnosis of  diverticulitis  and require skilled medical care of the infection, bleeding and perforation which may include intensive antibiotic treatment, intravenous fluids, and surgery. Complications are more common in patients who are taking  NSAIDs  or aspirin. As diverticulosis occurs in an older population such complications are serious events. [ citation needed ]


The prevalence of diverticulosis progressively increases with age. Approximately 50% of people over the age of 60 and 70% of people over the age of 80 have diverticulosis. [ 1 ]  This disease is common in the U.S., Britain, Australia, Canada, and is uncommon in Asia and Africa. [ 5 ]  Large-mouth diverticula are associated with  scleroderma . Diverticular disease is more common in collagen disorders such as Ehlers–Danlos syndrome. [ 29 ]


The modern emphasis on the value of fiber in the diet began with  Thomas L. Cleave . [ 30 ]  A strong case was made by Neil Painter [ 31 ]  and Adam Smith [ 32 ]  that a deficiency of dietary fiber is the cause of diverticular disease. They argued that the colonic muscles needed to contract strongly in order to transmit and expel the small stool associated with a fiber deficient diet.  The increased pressure within the segmented section of the bowel over years gave rise to herniation at the vulnerable point where blood vessels enter the colonic wall.


"The complications of diverticulosis cause considerable morbidity in the United States; health care expenditures for this disorder are estimated to be $2.5 billion per year." [ 33 ]


Dysentery  ( UK :  / ˈ d ɪ s ən t ər i /   DISS -ən-tər-ee , [ 7 ]   US :  / ˈ d ɪ s ən t ɛr i /   DISS -ən-terr-ee ), [ 8 ]  historically known as the  bloody flux , [ 9 ]  is a type of  gastroenteritis  that results in  bloody   diarrhea . [ 1 ] [ 10 ]  Other symptoms may include  fever , abdominal pain, and a  feeling of incomplete defecation . [ 2 ] [ 6 ] [ 11 ]  Complications may include  dehydration . [ 3 ]


The cause of dysentery is usually the bacteria from genus  Shigella , in which case it is known as  shigellosis , or the amoeba  Entamoeba histolytica ; then it is called  amoebiasis . [ 1 ]  Other causes may include certain chemicals, other bacteria, other protozoa, or  parasitic worms . [ 2 ]  It may spread between people. [ 4 ]  Risk factors include contamination of food and water with  feces  due to poor  sanitation . [ 6 ]  The underlying mechanism involves  inflammation  of the  intestine , especially of the  colon . [ 2 ]


Efforts to prevent dysentery include  hand washing  and  food safety  measures while traveling in countries of high risk. [ 4 ]  While the condition generally resolves on its own within a week, drinking sufficient fluids such as  oral rehydration solution  is important. [ 4 ]  Antibiotics such as  azithromycin  may be used to treat cases associated with travelling in the  developing world . [ 11 ]  While medications used to decrease diarrhea such as  loperamide  are not recommended on their own, they may be used together with antibiotics. [ 11 ] [ 4 ]


Shigella  results in about 165 million cases of diarrhea and 1.1 million deaths a year with nearly all cases in the developing world. [ 5 ]  In areas with poor sanitation nearly half of cases of diarrhea are due to  Entamoeba histolytica . [ 6 ]   Entamoeba histolytica  affects millions of people and results in more than 55,000 deaths a year. [ 12 ]  It commonly occurs in less developed areas of Central and South America, Africa, and Asia. [ 12 ]  Dysentery has been described at least since the time of  Hippocrates . [ 13 ]


The most common form of dysentery is bacillary dysentery, which is typically a mild sickness, causing symptoms normally consisting of mild abdominal pains and frequent passage of loose stools or diarrhea. Symptoms normally present themselves after 1–3 days, and are usually no longer present after a week. The frequency of urges to defecate, the large volume of liquid feces ejected, and the presence of blood, mucus, or pus depends on the  pathogen  causing the disease. Temporary  lactose intolerance  can occur, as well. In some occasions, severe abdominal cramps,  fever ,  shock , and  delirium  can all be symptoms. [ 2 ] [ 14 ] [ 15 ] [ 16 ]


In extreme cases, people may pass more than one liter of fluid per hour. More often, individuals will complain of  diarrhea  with  blood , accompanied by extreme abdominal pain,  rectal pain  and a low-grade  fever . Rapid weight loss and  muscle aches  sometimes also accompany dysentery, while  nausea  and  vomiting  are rare.


On rare occasions, the  amoebic parasite  will invade the body through the bloodstream and  spread beyond the intestines . In such cases, it may more seriously infect other organs such as the  brain ,  lungs , and most commonly the  liver . [ 17 ]


Dysentery results from  bacterial  or  parasitic  infections. Viruses do not generally cause the disease. [ 10 ]  These pathogens typically reach the  large intestine  after entering orally, through ingestion of contaminated food or water, oral contact with contaminated objects or hands, and so on. Each specific pathogen has its own mechanism or pathogenesis, but in general, the result is damage to the intestinal linings, leading to the  inflammatory immune responses . This can cause  elevated physical temperature , painful spasms of the intestinal muscles ( cramping ), swelling due to fluid leaking from capillaries of the intestine ( edema ) and further tissue damage by the body's immune cells and the chemicals, called  cytokines , which are released to fight the infection. The result can be impaired nutrient absorption, excessive water and mineral loss through the stools due to breakdown of the control mechanisms in the intestinal tissue that normally remove water from the stools, and in severe cases, the entry of pathogenic organisms into the bloodstream.  Anemia  may also arise due to the blood loss through diarrhea. [ citation needed ]


Bacterial infections that cause bloody diarrhea are typically classified as being either invasive or toxogenic. Invasive species cause damage directly by invading into the mucosa. The toxogenic species do not invade, but cause cellular damage by secreting toxins, resulting in bloody diarrhea. This is also in contrast to toxins that cause watery diarrhea, which usually do not cause cellular damage, but rather they take over cellular machinery for a portion of life of the cell. [ 18 ]


Definitions of dysentery can vary by region and by medical specialty. The U. S. Centers for Disease Control and Prevention (CDC) limits its definition to "diarrhea with visible blood". [ 19 ]  Others define the term more broadly. [ 20 ]  These differences in definition must be taken into account when defining mechanisms. For example, using the CDC definition requires that intestinal tissue be so severely damaged that blood vessels have ruptured, allowing visible quantities of blood to be lost with defecation. Other definitions require less specific damage. [ citation needed ]


Amoebiasis , also known as amoebic dysentery, is caused by an infection from the  amoeba   Entamoeba histolytica , [ 21 ]  which is found mainly in tropical areas. [ 22 ]  Proper treatment of the underlying infection of amoebic dysentery is important; insufficiently treated amoebiasis can lie dormant for years and subsequently lead to  severe, potentially fatal, complications . [ citation needed ]


When amoebae inside the bowel of an infected person are ready to leave the body, they group together and form a shell that surrounds and protects them. This group of amoebae is known as a cyst, which is then passed out of the person's body in the feces and can survive outside the body. If hygiene standards are poor – for example, if the person does not dispose of the feces hygienically – then it can contaminate the surroundings, such as nearby food and water.
If another person then eats or drinks food or water that has been contaminated with feces containing the cyst, that person will also become infected with the amoebae. Amoebic dysentery is particularly common in parts of the world where human feces are used as fertilizer.
After entering the person's body through the mouth, the cyst travels down into the stomach. The amoebae inside the cyst are protected from the stomach's digestive acid. From the stomach, the cyst travels to the intestines, where it breaks open and releases the amoebae, causing the infection. The amoebae can burrow into the walls of the intestines and cause small abscesses and ulcers to form. The cycle then begins again. [ citation needed ]


Dysentery may also be caused by  shigellosis , an infection by  bacteria  of the genus  Shigella , and is then known as bacillary dysentery (or Marlow syndrome). The term  bacillary dysentery  etymologically might seem to refer to any dysentery caused by any  bacilliform  bacteria, but its meaning is restricted by convention to  Shigella  dysentery. [ citation needed ]


Some strains of  Escherichia coli  cause bloody diarrhea. The typical culprits are  enterohemorrhagic  Escherichia coli , of which  O157:H7  is the best known. These types of  E. coli  also make Shiga toxin. [ 23 ]


A diagnosis may be made by taking a history and doing a brief examination. Dysentery should not be confused with  hematochezia , which is the passage of fresh blood through the anus, usually in or with stools. [ 24 ]


The mouth, skin, and lips may appear dry due to dehydration. Lower abdominal tenderness may also be present. [ 17 ]


Cultures  of  stool samples  are examined to identify the organism causing dysentery. Usually, several samples must be obtained due to the number of amoebae, which changes daily. [ 17 ]   Blood tests  can be used to measure abnormalities in the levels of essential  minerals and salts . [ 17 ]


Efforts to prevent dysentery include  hand washing  and  food safety  measures while traveling in areas of high risk. [ 4 ]


Although there is currently no vaccine that protects against  Shigella  infection, several are in development. [ 25 ] [ 26 ]  Vaccination may eventually become a part of the strategy to reduce the incidence and severity of diarrhea, particularly among children in low-resource settings. For example,  Shigella  is a longstanding World Health Organization (WHO) target for vaccine development, and sharp declines in age-specific diarrhea/dysentery attack rates for this pathogen indicate that natural immunity does develop following exposure; thus, vaccination to prevent this disease should be feasible. The development of vaccines against these types of infection has been hampered by technical constraints, insufficient support for coordination, and a lack of market forces for research and development. Most vaccine development efforts are taking place in the public sector or as research programs within biotechnology companies. [ citation needed ]


Dysentery is managed by maintaining fluids using  oral rehydration therapy . [ 4 ]  If this treatment cannot be adequately maintained due to vomiting or the profuseness of diarrhea, hospital admission may be required for  intravenous  fluid replacement. In ideal situations, no antimicrobial therapy should be administered until microbiological microscopy and culture studies have established the specific infection involved. When laboratory services are not available, it may be necessary to administer a combination of drugs, including an  amoebicidal  drug to kill the  parasite , and an  antibiotic  to treat any associated bacterial infection. [ citation needed ]   Laudanum  (Deodorized Tincture of Opium)] may be used for severe pain and to combat severe diarrhea.


If shigellosis is suspected and it is not too severe, letting it run its course may be reasonable – usually less than a week. If the case is severe, antibiotics such as  ciprofloxacin  or  TMP-SMX  may be useful. However, many strains of  Shigella  are becoming resistant to common antibiotics, and effective medications are often in short supply in developing countries. If necessary, a doctor may have to reserve antibiotics for those at highest risk for death, including young children, people over 50, and anyone suffering from dehydration or malnutrition. [ citation needed ]


Amoebic dysentery is often treated with two antimicrobial drugs such as  metronidazole  and  paromomycin  or  iodoquinol . [ 27 ]


With correct treatment, most cases of amoebic and bacterial dysentery subside within 10 days, and most individuals achieve a full recovery within two to four weeks after beginning proper treatment. If the disease is left untreated, the prognosis varies with the immune status of the individual patient and the severity of disease. Extreme dehydration can delay recovery and significantly raises the risk for serious complications including death. [ 28 ]


Insufficient data exists, but  Shigella  is estimated to have caused the death of 34,000 children under the age of five in 2013, and 40,000 deaths in people over five years of age. [ 25 ]  Amoebiasis infects over 50 million people each year, of whom 50,000 die (one per thousand). [ 29 ]


Shigella evolved with the human expansion out of Africa 50,000 to 200,000 years ago. [ 30 ]


The seed, leaves, and bark of the  kapok  tree have been used in traditional medicines by indigenous peoples of the rainforest regions in the Americas, west-central Africa, and Southeast Asia in the treatment of this disease. [ 31 ] [ 32 ] [ 33 ]


In 1915, Australian  bacteriologist   Fannie Eleanor Williams  was serving as a medic in Greece with the  Australian Imperial Force , receiving casualties directly from  Gallipoli . In Gallipoli, dysentery was severely affecting soldiers and causing significant loss of manpower. Williams carried out  serological  investigations into dysentery, co-authoring several groundbreaking papers with Sir  Charles Martin , director of the  Lister Institute . [ 34 ]  The result of their work into dysentery was increased demand for specific  diagnostics  and curative sera. [ 35 ]


Bacillus subtilis  was marketed throughout America and Europe from 1946 as an immunostimulatory aid in the treatment of gut and urinary tract diseases such as rotavirus and  Shigella , [ 36 ]  but declined in popularity after the introduction of consumer antibiotics.


Gastritis  is the  inflammation  of the  lining of the stomach . [ 1 ]  It may occur as a  short episode  or may be of a  long duration . [ 1 ]  There may be no symptoms but, when symptoms are present, the most common is upper  abdominal pain  (see  dyspepsia ). [ 1 ]  Other possible symptoms include  nausea  and  vomiting , bloating, loss of appetite and  heartburn . [ 1 ] [ 2 ]  Complications may include  stomach bleeding ,  stomach ulcers , and  stomach tumors . [ 1 ]  When due to  autoimmune problems ,  low red blood cells  due to not enough  vitamin B12  may occur, a condition known as  pernicious anemia . [ 3 ]


Common causes include infection with  Helicobacter pylori  and use of nonsteroidal anti-inflammatory drugs ( NSAIDs ). [ 1 ]  When caused by  H. pylori  this is now termed  Helicobacter pylori  induced gastritis, and included as a listed disease in  ICD11 . [ 6 ] [ 7 ]  Less common causes include  alcohol ,  smoking ,  cocaine , severe illness,  autoimmune  problems,  radiation therapy  and  Crohn's disease . [ 1 ] [ 8 ]   Endoscopy , a type of  X-ray  known as an  upper gastrointestinal series , blood tests, and stool tests may help with diagnosis. [ 1 ]  Other conditions with similar symptoms include  inflammation of the pancreas ,  gallbladder problems , and  peptic ulcer disease . [ 2 ]


Prevention is by avoiding things that cause the disease. [ 4 ] [ examples needed ]  Treatment includes medications such as  antacids ,  H2 blockers , or  proton pump inhibitors . [ 1 ]  During an acute attack drinking  viscous lidocaine  may help. [ 9 ]  If gastritis is due to NSAIDs these may be stopped. [ 1 ]  If  H. pylori  is present it may be treated with a combination of  antibiotics  such as  amoxicillin  and  clarithromycin . [ 1 ]  For those with pernicious anemia, vitamin B12 supplements are recommended either by mouth or by injection. [ 3 ]  People are usually advised to avoid foods that bother them. [ 10 ]


Gastritis is believed to affect about half of people worldwide. [ 4 ]  In 2013 there were approximately 90 million new cases of the condition. [ 11 ]  As people get older the disease becomes more common. [ 4 ]  It, along with a similar condition in the first part of the  intestines  known as  duodenitis , resulted in 50,000 deaths in 2015. [ 5 ]   H. pylori  was first discovered in 1981 by  Barry Marshall  and  Robin Warren . [ 12 ]


Many people with gastritis experience no symptoms at all. However,  upper central   abdominal pain  is the most common symptom; the pain may be dull, vague, burning, aching, gnawing, sore, or sharp. [ 13 ]  Pain is usually located in the upper central portion of the  abdomen , [ 14 ]  but it may occur anywhere from the upper left portion of the abdomen around to the back.


Other signs and symptoms may include the following: [ 13 ]


There are two categories of gastritis depending on the cause of the disease. There is erosive gastritis, for which the common causes are  stress ,  alcohol , some  drugs , such as  aspirin  and other nonsteroidal anti-inflammatory drugs  (NSAIDs) , and Crohn's disease.  And, there is non-erosive gastritis, for which the most common cause is a  Helicobacter pylori  infection.  [ 15 ] [ 1 ]


Helicobacter pylori  colonizes the stomachs of more than half of the world's population, and the infection continues to play a key role in the pathogenesis of a number of gastroduodenal diseases. Colonization of the gastric mucosa with  Helicobacter pylori  results in the development of chronic gastritis in infected individuals and, in a subset of patients, chronic gastritis progresses to complications (e.g., ulcer disease,  stomach cancers , and some distinct extragastric disorders). [ 16 ]  Gastritis caused by  H. pylori  infection is termed  Helicobacter pylori  induced gastritis, and listed as a disease in  ICD11 . [ 6 ] [ 7 ]  More than 80% of individuals infected with the bacterium are  asymptomatic  and it has been postulated that it may play an important role in the natural stomach ecology. [ 17 ]


Gastritis may also develop after major surgery or traumatic injury (" Cushing ulcer "), burns (" Curling ulcer "), or severe infections. Gastritis may also occur in those who have had weight loss surgery resulting in the  banding  or reconstruction of the digestive tract. [ citation needed ]


Evidence does not support a role for specific foods, including spicy foods and coffee, in the development of  peptic ulcers . [ 18 ]  People are usually advised to avoid foods that bother them. [ 10 ]  There is little specific advice on diet published by authoritative sources. The  National Health Service  of the  United Kingdom  advises avoiding spicy, acidic or fried foods which may irritate the stomach. [ 19 ]


Acute erosive gastritis typically involves discrete foci of surface necrosis due to damage to mucosal defenses. [ 20 ]  NSAIDs inhibit  cyclooxygenase-1 , or COX-1, an enzyme responsible for the biosynthesis of  eicosanoids  in the stomach, which increases the possibility of  peptic ulcers  forming. [ 21 ] [ 22 ] [ 23 ]   Also, NSAIDs, such as aspirin, reduce a substance that protects the stomach called  prostaglandin . These drugs used in a short period are not typically dangerous. However, regular use can lead to gastritis. [ 24 ]  Additionally, severe physiologic stress from sepsis, hypoxia, trauma, or surgery is also a common etiology for acute erosive gastritis, resulting in " stress ulcers ". This form of gastritis can occur in more than 5% of hospitalized patients. [ citation needed ]


Also, alcohol consumption does not cause chronic gastritis.  It does, however, erode the mucosal lining of the stomach; low doses of alcohol stimulate  hydrochloric acid  secretion. High doses of alcohol do not stimulate secretion of acid. [ 25 ]


Chronic gastritis refers to a wide range of problems of the gastric issues. [ 20 ]   The immune system makes proteins and antibodies that fight infections in the body to maintain a  homeostatic  condition.  In some disorders the body targets the stomach as if it were a foreign protein or pathogen; it makes antibodies against, severely damages, and may even destroy the stomach or its lining. [ 24 ]   In some cases bile, normally used to aid digestion in the small intestine, will enter through the  pyloric valve  of the stomach if it has been removed during surgery or does not work properly, also leading to gastritis.  Gastritis may also be caused by other medical conditions, including  HIV/AIDS ,  Crohn's disease , certain  connective tissue disorders , and  liver  or  kidney failure . Since 1992, chronic gastritis lesions are classified according to the Sydney system. [ 26 ]


Mucous gland  metaplasia , the reversible replacement of differentiated cells, occurs in the setting of severe damage of the gastric glands, which then waste away ( atrophic gastritis ) and are progressively replaced by mucous glands. Gastric ulcers may develop; it is unclear if they are the causes or the consequences.  Intestinal metaplasia typically begins in response to chronic mucosal injury in the antrum and may extend to the body. Gastric mucosa cells change to resemble intestinal mucosa and may even assume absorptive characteristics.  Intestinal metaplasia  is classified histologically as complete or incomplete. With complete metaplasia, gastric mucosa is completely transformed into small-bowel mucosa, both histologically and functionally, with the ability to absorb nutrients and secrete peptides. In incomplete metaplasia, the epithelium assumes a histologic appearance closer to that of the large intestine and frequently exhibits  dysplasia . [ 20 ]


Often, a diagnosis can be made based on  patients' description of their symptoms. Other methods which may be used to verify gastritis include:


The OLGA staging frame of chronic gastritis on histopathology. Atrophy is scored as the percentage of atrophic glands and scored on a four-tiered scale. No atrophy (0%) = score 0; mild atrophy (1–30%) = score 1; moderate atrophy (31–60%) = score 2; severe atrophy (>60%) = score 3. These scores (0–3) are used in the OLGA staging assessment in each 10 compartment: [ 28 ]


Antacids  are a common treatment for mild to medium gastritis. [ 29 ]  When antacids do not provide enough relief, medications such as  H 2  blockers  and  proton-pump inhibitors  that help reduce the amount of acid are often prescribed. [ 29 ] [ 30 ]


Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. [ 31 ]  They include the medications  sucralfate  and  misoprostol . If  NSAIDs  are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is  bismuth subsalicylate . [ 32 ]


Several regimens are used to treat  H. pylori  infection. Most use a combination of two  antibiotics  and a proton pump inhibitor. Sometimes bismuth is added to the regimen.


In 1,000 A.D,  Avicenna  first gave the description of stomach cancer. In 1728, German physician  Georg Ernst Stahl  first coined the term "gastritis". Italian anatomical pathologist  Giovanni Battista Morgagni  further described the characteristics of gastric inflammation. He described the characteristics of erosive or ulcerative gastritis and erosive gastritis. Between 1808 and 1831, French physician  François-Joseph-Victor Broussais  gathered information from the autopsies of dead French soldiers. He described chronic gastritis as "Gastritide" and erroneously believed that gastritis was the cause of  ascites ,  typhoid fever , and  meningitis . In 1854,  Charles Handfield Jones  and  Wilson Fox  described the microscopic changes of stomach inner lining in gastritis which existed in diffuse and segmental forms. In 1855,  Baron Carl von Rokitansky  first described  hypertrophic  gastritis. In 1859, British physician,  William Brinton  first described about  acute ,  subacute , and  chronic  gastritis. In 1870, Samuel Fenwick noted that  pernicious anemia  causes glandular  atrophy  in gastritis. German surgeon Georg Ernst Konjetzny noticed that both gastric ulcer and gastric cancer are the results of gastric inflammation.  Shields Warren  and Willam A. Meissner described the  intestinal metaplasia  of the stomach as a feature of chronic gastritis. [ 33 ]


Gastroenteritis , also known as  infectious diarrhea , is an  inflammation  of the  gastrointestinal tract  including the  stomach  and  intestine . [ 8 ]  Symptoms may include  diarrhea ,  vomiting , and  abdominal pain . [ 1 ]   Fever , lack of energy, and  dehydration  may also occur. [ 2 ] [ 3 ]  This typically lasts less than two weeks. [ 8 ]  Although it is not related to  influenza , in the U.S. and U.K., it is sometimes called the " stomach flu ". [ 9 ]


Gastroenteritis is usually caused by  viruses ; [ 4 ]  however, gut  bacteria ,  parasites , and  fungi  can also cause gastroenteritis. [ 2 ] [ 4 ]  In children,  rotavirus  is the most common cause of severe disease. [ 10 ]  In adults,  norovirus  and  Campylobacter  are common causes. [ 11 ] [ 12 ]  Eating improperly prepared food, drinking contaminated water or close contact with a person who is infected can  spread the disease . [ 2 ]  Treatment is generally the same with or without a definitive diagnosis, so testing to confirm is usually not needed. [ 2 ]


For young children in impoverished countries, prevention includes  hand washing  with soap, drinking  clean water ,  breastfeeding  babies instead of using  formula , [ 2 ]  and proper disposal of  human waste . The  rotavirus vaccine  is recommended as a prevention for children. [ 2 ] [ 10 ]  Treatment involves getting enough fluids. [ 2 ]  For mild or moderate cases, this can typically be achieved by drinking  oral rehydration solution  (a combination of water, salts and sugar). [ 2 ]  In those who are breastfed, continued breastfeeding is recommended. [ 2 ]  For more severe cases,  intravenous fluids  may be needed. [ 2 ]  Fluids may also be given by a  nasogastric tube . [ 13 ]   Zinc  supplementation is recommended in children. [ 2 ]   Antibiotics  are generally not needed. [ 14 ]  However, antibiotics are recommended for young children with a fever and bloody diarrhea. [ 1 ]


In 2015, there were two billion cases of gastroenteritis, resulting in 1.3 million deaths globally. [ 6 ] [ 7 ]  Children and those in the  developing world  are affected the most. [ 15 ]  In 2011, there were about 1.7 billion cases, resulting in about 700,000 deaths of children under the age of five. [ 16 ]  In the developing world, children less than two years of age frequently get six or more infections a year. [ 17 ]  It is less common in adults, partly due to the development of  immunity . [ 18 ]


Gastroenteritis usually involves both  diarrhea  and  vomiting . [ 18 ]  Sometimes, only one or the other is present. [ 1 ]  This may be accompanied by abdominal cramps. [ 1 ]  Signs and symptoms usually begin 12–72 hours after contracting the infectious agent. [ 15 ]  If due to a virus, the condition usually resolves within one week. [ 18 ]  Some viral infections also involve  fever , fatigue,  headache  and  muscle pain . [ 18 ]  If the  stool is bloody , the cause is less likely to be viral [ 18 ]  and more likely to be bacterial. [ 19 ]  Some bacterial infections cause severe abdominal pain and may persist for several weeks. [ 19 ]


Children infected with rotavirus usually make a full recovery within three to eight days. [ 20 ]  However, in poor countries treatment for severe infections is often out of reach and persistent diarrhea is common. [ 21 ]   Dehydration  is a common complication of  diarrhea . [ 22 ]  Severe dehydration in children may be recognized if the skin color and position returns slowly when pressed. [ 23 ]  This is called "prolonged  capillary refill " and "poor  skin turgor ". [ 23 ]  Abnormal breathing is another sign of severe dehydration. [ 23 ]  Repeat infections are typically seen in areas with poor sanitation, and  malnutrition . [ 15 ]   Stunted growth  and long-term cognitive delays can result. [ 17 ]


Reactive arthritis  occurs in 1% of people following infections with  Campylobacter  species. [ 19 ]   Guillain–Barré syndrome  occurs in 0.1%. [ 19 ]   Hemolytic uremic syndrome  (HUS) may occur due to infection with  Shiga toxin -producing  Escherichia coli  or  Shigella  species. [ 24 ]  HUS causes  low platelet counts ,  poor kidney function , and  low red blood cell count (due to their breakdown) . [ 24 ]  Children are more predisposed to getting HUS than adults. [ 17 ]  Some viral infections may produce  benign infantile seizures . [ 1 ]


Viruses  (particularly  rotavirus  (in children) and  norovirus  (in adults)) and the bacteria  Escherichia coli  and  Campylobacter  species are the primary causes of gastroenteritis. [ 15 ] [ 25 ]  There are, however, many other infectious agents that can cause this syndrome including  parasites  and  fungi . [ 17 ] [ 4 ]  Non-infectious causes are seen on occasion, but they are less likely than a viral or bacterial cause. [ 1 ]  Risk of infection is higher in children due to their lack of  immunity . [ 1 ]  Children are also at higher risk because they are less likely to practice good  hygiene  habits. [ 1 ]  Children living in areas without easy  access to water and soap  are especially vulnerable. [ 1 ]


Rotaviruses ,  noroviruses ,  adenoviruses , and  astroviruses  are known to cause viral gastroenteritis. [ 26 ]  Rotavirus is the most common cause of gastroenteritis in children, [ 25 ]  and produces similar rates in both the  developed  and  developing world . [ 20 ]  Viruses cause about 70% of episodes of infectious diarrhea in the pediatric age group. [ 13 ]  Rotavirus is a less common cause in adults due to acquired immunity. [ 27 ]  Norovirus is the cause in about 18% of all cases. [ 28 ]  Generally speaking, viral gastroenteritis accounts for 21–40% of the cases of infectious diarrhea in developed countries. [ 29 ]


Norovirus is the leading cause of gastroenteritis among adults in America accounting for about 90% of viral gastroenteritis outbreaks. [ 18 ]  These localized  epidemics  typically occur when groups of people spend time proximate to each other, such as on  cruise ships , [ 18 ]  in hospitals, or in restaurants. [ 1 ]  People may remain infectious even after their diarrhea has ended. [ 18 ]  Norovirus is the cause of about 10% of cases in children. [ 1 ]


In some countries,  Campylobacter jejuni  is the primary cause of bacterial gastroenteritis, with half of these cases associated with exposure to  poultry . [ 19 ]  In children, bacteria are the cause in about 15% of cases, with the most common types being  Escherichia coli ,  Salmonella ,  Shigella , and  Campylobacter  species. [ 13 ]  If food becomes contaminated with bacteria and remains at room temperature for several hours, the bacteria multiply and increase the risk of infection in those who consume the food. [ 17 ]  Some foods commonly associated with illness include raw or undercooked meat, poultry, seafood, and eggs; raw sprouts; unpasteurized milk and soft cheeses; and fruit and vegetable juices. [ 30 ]  In the developing world, especially sub-Saharan Africa and Asia,  cholera  is a common cause of gastroenteritis. This infection is usually transmitted by contaminated water or food. [ 31 ]


Toxigenic  Clostridioides difficile  is an important cause of diarrhea that occurs more often in the elderly. [ 17 ]  Infants can carry these bacteria without developing symptoms. [ 17 ]  It is a common cause of diarrhea in those who are hospitalized and is frequently associated with antibiotic use. [ 32 ]   Staphylococcus aureus  infectious diarrhea may also occur in those who have used antibiotics. [ 33 ]  Acute " traveler's diarrhea " is usually a type of bacterial gastroenteritis, while the persistent form is usually parasitic. [ 34 ]  Acid-suppressing medication appears to increase the risk of significant infection after exposure to several organisms, including  Clostridioides difficile ,  Salmonella , and  Campylobacter  species. [ 35 ]  The risk is greater in those taking  proton pump inhibitors  than with  H 2  antagonists . [ 35 ]


A number of  parasites  can cause gastroenteritis. [ 13 ]   Giardia lamblia  is most common, but  Entamoeba histolytica ,  Cryptosporidium  spp., and other species have also been implicated. [ 13 ] [ 34 ]  As a group, these agents comprise about 10% of cases in children. [ 24 ] [ 34 ]   Giardia  occurs more commonly in the developing world, but this type of illness can occur nearly everywhere. [ 36 ]  It occurs more commonly in persons who have traveled to areas with high prevalence, children who attend  day care ,  men who have sex with men , and following  disasters . [ 36 ]


Transmission may occur from drinking contaminated water or when people share personal objects. [ 15 ]  Water quality typically worsens during the rainy season and outbreaks are more common at this time. [ 15 ]  In  areas with four seasons , infections are more common in the winter. [ 17 ]  Worldwide,  bottle-feeding  of babies with improperly sanitized bottles is a significant cause. [ 15 ]  Transmission rates are also related to poor hygiene, (especially among children), [ 18 ]  in crowded households, [ 37 ]  and in those with poor nutritional status. [ 17 ]  Adults who have developed immunities might still carry certain organisms without exhibiting symptoms. [ 17 ]  Thus, adults can become  natural reservoirs  of certain diseases. [ 17 ]  While some agents (such as  Shigella ) only occur in  primates , others (such as  Giardia ) may occur in a wide variety of animals. [ 17 ]


There are a number of non-infectious causes of inflammation of the gastrointestinal tract. [ 1 ]  Some of the more common include medications (like  NSAIDs ), certain foods such as  lactose  (in those who are intolerant), and  gluten  (in those with  celiac disease ).  Crohn's disease  is also a non-infectious cause of (often severe) gastroenteritis. [ 1 ]  Disease secondary to  toxins  may also occur. Some food-related conditions associated with nausea, vomiting, and diarrhea include:  ciguatera poisoning  due to consumption of contaminated predatory fish,  scombroid  associated with the consumption of certain types of spoiled fish,  tetrodotoxin poisoning  from the consumption of  puffer fish  among others, and  botulism  typically due to improperly preserved food. [ 38 ]


In the United States, rates of emergency department use for noninfectious gastroenteritis dropped 30% from 2006 until 2011. Of the twenty most common conditions seen in the emergency department, rates of noninfectious gastroenteritis had the largest decrease in visits in that time period. [ 39 ]


Gastroenteritis is defined as  vomiting  or  diarrhea  due to inflammation of the  small  or  large bowel , often due to infection. [ 17 ]  The changes in the small bowel are typically noninflammatory, while the ones in the large bowel are inflammatory. [ 17 ]  The number of pathogens required to cause an infection varies from as few as one (for  Cryptosporidium ) to as many as 10 8  (for  Vibrio cholerae ). [ 17 ]


Gastroenteritis is typically diagnosed clinically, based on a person's signs and symptoms. [ 18 ]  Determining the exact cause is usually not needed as it does not alter the management of the condition. [ 15 ]


However,  stool cultures  should be performed in those with blood in the stool, those who might have been exposed to  food poisoning , and those who have recently traveled to the developing world. [ 13 ]  It may also be appropriate in children younger than 5, old people, and those with poor immune function. [ 40 ]  Diagnostic testing may also be done for surveillance. [ 18 ]  As  hypoglycemia  occurs in approximately 10% of infants and young children, measuring serum  glucose  in this population is recommended. [ 23 ]   Electrolytes  and  kidney function  should also be checked when there is a concern about severe dehydration. [ 13 ]


A determination of whether or not the person has  dehydration  is an important part of the assessment, with dehydration typically divided into mild (3–5%), moderate (6–9%), and severe (≥10%) cases. [ 1 ]  In children, the most accurate signs of moderate or severe dehydration are a prolonged  capillary refill , poor  skin turgor , and abnormal breathing. [ 23 ] [ 41 ]  Other useful findings (when used in combination) include sunken eyes, decreased activity, a lack of tears, and a dry mouth. [ 1 ]  A normal urinary output and oral fluid intake is reassuring. [ 23 ]  Laboratory testing is of little clinical benefit in determining the degree of dehydration. [ 1 ]  Thus the use of urine testing or ultrasounds is generally not needed. [ 42 ]


Other potential causes of signs and symptoms that mimic those seen in gastroenteritis that need to be ruled out include  appendicitis ,  volvulus ,  inflammatory bowel disease ,  urinary tract infections , and  diabetes mellitus . [ 13 ]   Pancreatic insufficiency ,  short bowel syndrome ,  Whipple's disease ,  coeliac disease , and  laxative  abuse should also be considered. [ 43 ]  The differential diagnosis can be complicated somewhat if the person exhibits  only  vomiting or diarrhea (rather than both). [ 1 ]


Appendicitis may present with vomiting, abdominal pain, and a small amount of diarrhea in up to 33% of cases. [ 1 ]  This is in contrast to the large amount of diarrhea that is typical of gastroenteritis. [ 1 ]   Infections of the lungs  or urinary tract in children may also cause vomiting or diarrhea. [ 1 ]  Classical  diabetic ketoacidosis  (DKA) presents with abdominal pain, nausea, and vomiting, but without diarrhea. [ 1 ]  One study found that 17% of children with DKA were initially diagnosed as having gastroenteritis. [ 1 ]


A supply of easily accessible uncontaminated water and good  sanitation  practices are important for reducing rates of infection and clinically significant gastroenteritis. [ 17 ]  Personal  hygiene  measures (such as  hand washing  with soap) have been found to decrease rates of gastroenteritis in both the developing and developed world by as much as 30%. [ 23 ]  Alcohol-based gels may also be effective. [ 23 ]  Food or drink that is thought to be contaminated should be avoided. [ 44 ]
 Breastfeeding  is important, especially in places with poor hygiene, as is improvement of hygiene generally. [ 15 ]  Breast milk reduces both the frequency of infections and their duration. [ 1 ]


Due to both its effectiveness and safety, in 2009 the World Health Organization recommended that the  rotavirus vaccine  be offered to all children globally. [ 25 ] [ 45 ]  Two commercial rotavirus vaccines exist and several more are in development. [ 45 ]  In Africa and Asia these vaccines reduced severe disease among infants [ 45 ]  and countries that have put in place national immunization programs have seen a decline in the rates and severity of disease. [ 46 ] [ 47 ]  This vaccine may also prevent illness in non-vaccinated children by reducing the number of circulating infections. [ 48 ]  Since 2000, the implementation of a rotavirus vaccination program in the United States has substantially decreased the number of cases of diarrhea by as much as 80 percent. [ 49 ] [ 50 ] [ 51 ]  The first dose of vaccine should be given to infants between 6 and 15 weeks of age. [ 25 ]  The  oral cholera vaccine  has been found to be 50–60% effective over two years. [ 52 ]


There are a number of vaccines against gastroenteritis in development. For example, vaccines against  Shigella  and enterotoxigenic  Escherichia coli  (ETEC), which are two of the leading bacterial causes of gastroenteritis worldwide. [ 53 ] [ 54 ]


Gastroenteritis is usually an acute and self-limiting disease that does not require medication. [ 22 ]  The preferred treatment in those with mild to moderate  dehydration  is  oral rehydration therapy  (ORT). [ 24 ]  For children at risk of dehydration from vomiting, taking a single dose of the  anti vomiting  medication  metoclopramide  or  ondansetron , may be helpful, [ 55 ]  and  butylscopolamine  is useful in treating  abdominal pain . [ 56 ]


The primary treatment of gastroenteritis in both children and adults is  rehydration . This is preferably achieved by drinking rehydration solution, although  intravenous  delivery may be required if there is a  decreased level of consciousness  or if dehydration is severe. [ 57 ] [ 58 ]  Drinking replacement therapy products made with complex carbohydrates (i.e. those made from wheat or rice) may be superior to those based on simple sugars. [ 59 ]  Drinks especially high in simple sugars, such as  soft drinks  and fruit juices, are not recommended in children under five years of age as they may  increase  diarrhea. [ 22 ]  Plain water may be used if more specific ORT preparations are unavailable or the person is not willing to drink them. [ 22 ]  A  nasogastric tube  can be used in young children to administer fluids if warranted. [ 13 ]  In those who require intravenous fluids, one to four hours' worth is often sufficient. [ 60 ]


It is recommended that breast-fed infants continue to be nursed in the usual fashion,  and that formula-fed infants continue their formula immediately after rehydration with ORT. [ 61 ]  Lactose-free or lactose-reduced formulas usually are not necessary. [ 61 ]  Children should continue their usual diet during episodes of diarrhea with the exception that foods high in  simple sugars  should be avoided. [ 61 ]  The  BRAT diet  (bananas, rice, applesauce, toast and tea) is no longer recommended, as it contains insufficient nutrients and has no benefit over normal feeding. [ 61 ]


A Cochrane Review from 2020 concludes that  probiotics  make little or no difference to people who have diarrhea lasting 2 days or longer and that there is no proof that they reduce its duration. [ 62 ]  They may be useful in preventing and treating  antibiotic associated diarrhea . [ 63 ]  Fermented milk products (such as  yogurt ) are similarly beneficial. [ 64 ]   Zinc  supplementation appears to be effective in both treating and preventing diarrhea among children in the developing world. [ 65 ]


Antiemetic  medications may be helpful for treating vomiting in children.  Ondansetron  has some utility, with a single dose being associated with less need for intravenous fluids, fewer hospitalizations, and decreased vomiting. [ 55 ] [ 66 ] [ 67 ] [ 68 ]   Metoclopramide  might also be helpful. [ 68 ]  However, the use of ondansetron might possibly be linked to an increased rate of return to hospital in children. [ 69 ]  The intravenous preparation of ondansetron may be given orally if clinical judgment warrants. [ 70 ]   Dimenhydrinate , while reducing vomiting, does not appear to have a significant clinical benefit. [ 1 ]


Antibiotics are not usually used for gastroenteritis, although they are sometimes recommended if symptoms are particularly severe [ 71 ]  or if a susceptible bacterial cause is isolated or suspected. [ 72 ]  If antibiotics are to be employed, a  macrolide  (such as  azithromycin ) is preferred over a  fluoroquinolone  due to higher rates of resistance to the latter. [ 19 ]   Pseudomembranous colitis , usually caused by antibiotic use, is managed by discontinuing the causative agent and treating it with either  metronidazole  or  vancomycin . [ 73 ]  Bacteria and protozoans that are amenable to treatment include  Shigella [ 74 ]   Salmonella typhi , [ 75 ]  and  Giardia  species. [ 36 ]  In those with  Giardia  species or  Entamoeba histolytica ,  tinidazole  treatment is recommended and superior to metronidazole. [ 36 ] [ 76 ]  The  World Health Organization  (WHO) recommends the use of antibiotics in young children who have both bloody diarrhea and fever. [ 1 ]


Antimotility medication has a theoretical risk of causing complications, and although clinical experience has shown this to be unlikely, [ 43 ]  these drugs are discouraged in people with bloody diarrhea or diarrhea that is complicated by fever. [ 77 ]   Loperamide , an  opioid  analogue, is commonly used for the symptomatic treatment of diarrhea. [ 78 ]  Loperamide is not recommended in children, however, as it may cross the immature blood–brain barrier and cause toxicity.  Bismuth subsalicylate , an insoluble complex of trivalent  bismuth  and salicylate, can be used in mild to moderate cases, [ 43 ]  but  salicylate toxicity  is theoretically possible. [ 1 ]


It is estimated that there were two billion cases of gastroenteritis that resulted in 1.3 million deaths globally in 2015. [ 6 ] [ 7 ]  Children and those in the  developing world  are most commonly affected. [ 15 ]  As of 2011, in those younger than five, there were about 1.7 billion cases resulting in 0.7 million deaths, [ 16 ]  with most of these occurring in the world's poorest nations. [ 17 ]  More than 450,000 of these fatalities are due to rotavirus in children under five years of age. [ 10 ] [ 79 ]   Cholera  causes about three to five million cases of disease and kills approximately 100,000 people yearly. [ 31 ]  In the developing world, children less than two years of age frequently get six or more infections a year that result in significant gastroenteritis. [ 17 ]  It is less common in adults, partly due to the development of acquired  immunity . [ 18 ]


In 1980, gastroenteritis from all causes caused 4.6 million deaths in children, with the majority occurring in the developing world. [ 73 ]  Death rates were reduced significantly (to approximately 1.5 million deaths annually) by 2000, largely due to the introduction and widespread use of  oral rehydration therapy . [ 80 ]  In the US, infections causing gastroenteritis are the second most common infection (after the  common cold ), and they result in between 200 and 375 million cases of acute diarrhea [ 17 ] [ 18 ]  and approximately ten thousand deaths annually, [ 17 ]  with 150 to 300 of these deaths in children less than five years of age. [ 1 ]


Gastroenteritis is associated with many colloquial names, including " Montezuma's revenge ", "Delhi belly", "la turista", and "back door sprint", among others. [ 17 ]  It has played a role in many military campaigns and is believed to be the origin of the term "no guts no glory". [ 17 ]


Gastroenteritis is the main reason for 3.7 million visits to physicians a year in the United States [ 1 ]  and 3 million visits in France. [ 81 ]  In the United States gastroenteritis as a whole is believed to result in costs of US$23 billion per year, [ 82 ]  with rotavirus alone resulting in estimated costs of US$1 billion a year. [ 1 ]


The first usage of "gastroenteritis" was in 1825. [ 83 ]  Before this time it was commonly known as  typhoid fever  or "cholera morbus", among others, or less specifically as "griping of the guts", "surfeit", "flux", "colic", "bowel complaint", or any one of several other archaic names for acute diarrhea. [ 84 ]  Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically  cholera . [ 85 ]


Many of the same agents cause gastroenteritis in cats and dogs as in humans. The most common organisms are  Campylobacter ,  Clostridioides difficile ,  Clostridium perfringens , and  Salmonella . [ 86 ]  A large number of toxic plants may also cause symptoms. [ 87 ]


Some agents are more specific to a certain species.  Transmissible gastroenteritis coronavirus  (TGEV) occurs in pigs resulting in vomiting, diarrhea, and dehydration. [ 88 ]  It is believed to be introduced to pigs by wild birds and there is no specific treatment available. [ 89 ]  It is not transmissible to humans. [ 90 ]


Giardia duodenalis , also known as  Giardia intestinalis  and  Giardia lamblia , is a  flagellated   parasitic   protozoan  microorganism of the genus  Giardia  that colonizes the  small intestine , causing a diarrheal condition known as  giardiasis . [ 1 ] [ 2 ] [ 3 ]  The parasite attaches to the  intestinal epithelium  by a ventral disc ( syn .  adhesive disc or sucker ), and  reproduces  via  binary fission . [ 4 ] [ 5 ]   G. duodenalis  is a non-invasive parasite, that does not spread to other parts of the  gastrointestinal tract , but remains confined to the  lumen  of the small intestine. [ 6 ] [ 7 ]  The parasite exists in two forms;  trophozoites  and  cysts . The microorganism can undergo encystation, transforming into a dormant  cyst  that enables it to survive outside of its  host . [ 8 ]   Giardia   trophozoites  are  anaerobic , and absorb their nutrients from the intestinal lumen. If the organism is  stained , its characteristic pattern resembles the familiar " smiley face " symbol. [ 9 ]


Chief pathways of human infection include ingestion of  untreated  drinking water (which is the most common method of transmission for this parasite), [ 3 ]  food, soil contaminated with human feces, and  sewage , a phenomenon particularly common in many  developing countries . [ 10 ] [ 3 ]  Contamination of natural waters also occurs in  watersheds  where intensive  grazing  occurs.


Giardia  infections occur worldwide. It is the most commonly identified intestinal parasite among children in day-care centers, hikers and  immunocompromised  patients. About 20,000 cases per year in the United States are reported. [ 11 ]


Almost half of those infected with giardiasis remain asymptomatic. For those who do experience symptoms, they usually appear 1 to 2 weeks after infection. Common symptoms include abdominal pain, nausea, and bloating, along with large, watery, foul-smelling, and greasy stools. Due to frequent loose stools, individuals with giardiasis often experience dehydration. [ 12 ]  It has also been shown that  G. intestinalis  damages the intestinal epithelium, which directly affects nutrient absorption. [ 5 ]  In severe cases, giardiasis can lead to chronic diarrhea, chronic fatigue syndrome and cognitive impairment in children. [ 13 ]


G. duodenalis  takes on two morphologically distinct forms during its lifecycle.  Trophozoites  are the replicative stage of the parasite, characterized by a pear-shaped,  motile ,  flagellated  cell that survives only in the small intestine of the host. [ 14 ]  The trophozoites do not penetrate host cells, but rather attaches to the intestinal epithelium cells to establish an infection. A cyst is the environmentally stable stage of the parasite, that facilitates transmission between hosts. [ 8 ]


The infection process in the host begins with the ingestion of cysts, which pass through the stomach into the first part of small intestine, or the  duodenum . Exposure to  digestive enzymes  and an acidic  pH  triggers excystation, where the cysts release trophozoites. [ 8 ]  Trophozoites swim through the intestinal mucus until they eventually adhere to the  intestinal epithelium  using their  ventral disc . [ 15 ] [ 14 ]  Adhered trophozoites can then feed, divide by  binary fission  and cause the disease. Trophozoites cause structural and functional damage to the host epithelial cells, impairing the intestine's ability to absorb nutrients effectively. [ 16 ]  Some trophozoites differentiate back into cysts under specific conditions, such as high organism density. [ 8 ]  As the trophozoites travel through the intestinal lumen to the  large intestine , the alkaline environment and the presence of  pancreatic proteases  trigger the encystation. Trophozoites develop into cysts through encystation, which involves specialized vesicles (ESVs) that facilitate the formation of the cyst wall. [ 16 ]


Cysts and trophozoites pass through the host's  large intestine  and are shed in the feces. [ 14 ]  Trophozoites cannot survive outside of the host, whereas cysts can remain viable in the external environment for several months. [ 17 ]  The cysts remain  dormant  until ingested by a host animal. When a new potential host ingests water or food contaminated with this feces, the cysts gain entry to the gastrointestinal tract of the new host, repeating the cycle. [ 18 ]


The trophozoite has an elaborate structure with two nuclei and four pairs of  flagella  which allow it to swim within the intestinal lumen of the host. It also has an adhesive disk on its  ventral  surface that is associated with the parasite's attachment to the intestinal epithelium. The adhesive disk is composed of  microtubules , and is found only in  Giardia . The parasite lacks  Golgi apparatus  and  mitochondria  but has  mitosomes , which probably evolved from mitochondria. [ 19 ]  The mitosome is a double-membraned organelle, that lacks the enzymatic components required for classic mitochondrial functions, such as ATP synthesis and lipid metabolism. However, they do contain certain mitochondrial genes associated with iron-sulfur complex biosynthesis, which suggests that this organism likely lost its mitochondria during evolution. [ 16 ]


The cyst contains four nuclei,  axonemes , median bodies as well as the rigid cyst wall. Additionally, the cysts contain fragments of the adhesive disc within the cytoplasm. [ 8 ] [ 16 ]  The two-layered cyst wall protects the parasite against different environmental conditions such as chemical treatments. The metabolic activity of the cyst is significantly lower compared to that of the trophozoites, which allows the parasite to survive for longer periods in harsh conditions, such as in cold environments. [ 8 ]


G. duodenalis  is the most widespread intestinal parasite affecting humans. The parasite  Giardia duodenalis  can be found all over the world, in both developing and industrialized nations. However, it is most commonly found in tropical and temperate climates. [ 20 ]   Giardia duodenalis  is common around the world because the parasite resides in bodies of water; typically rivers, lakes, and recreational swimming pools. [ 21 ]  Giardiasis is more prevalent in  developing countries , where the sanitation and overall hygiene is poorer compared to  developed countries . [ 22 ]  In developed nations, giardiasis has a prevalence of 2%-5%, whereas in developing nations it is significantly higher, ranging from 20% to 30%. [ 23 ]  In the United States, it has been discovered that a majority of whom are infected by the  Giardia duodenalis  parasite tend to reside in more urban areas, and, patients who are infected are more likely to live in the Southern United States. [ 24 ]


G. duodenalis  causes an infection called giardiasis. This disease is the cause of both endemic and epidemic disease worldwide and is the most frequently identified intestinal parasite in the United States and Canada. An infected individual can excrete between 1 million and 1 billion cysts daily, and the  infectious dose  can be as low as 10 cysts. This makes Giardia extremely infectious.


It is estimated to infect over 280 million people world every year [ 23 ] resulting over 500,000 deaths. The most affected demographic is children 0 to 4 years of age. Globally G.  duodenalis  is the most commonly identified protozoal intestinal parasite. [ 22 ]  Giardia has common seasonal patterns in the distribution of infection rates with highest peaks in the late summer to early fall. [ 25 ]


The cyst can survive for weeks to months in cold water, [ 17 ]  so the parasite can be present in contaminated wells and water systems, especially in stagnant water sources, such as naturally occurring ponds, storm-water storage systems, and even clean-looking mountain streams. Cysts can also be found on contaminated surfaces, soil and food. [ 26 ]  They may also occur in city reservoirs and persist after water treatment, as the cysts are resistant to conventional water-treatment methods, such as  chlorination  and  ozonolysis . [ 17 ]   Zoonotic  transmission is also possible, but is less frequent.  Giardia  infection is a concern for people camping in the wilderness or swimming in contaminated streams or lakes, especially the artificial lakes formed by  beaver  dams (hence the popular name for giardiasis, "beaver fever"). [ citation needed ]


In addition to waterborne sources, Giardia infections are more commonly found in children compared to adults, this is believed to be due to  fecal-oral  transmission of the cysts. For example, in developed countries it affects approximately 2% of adults and 8% of children. In developing countries the prevalence rates reach 15% to 20% in children under 10 years old. [ 12 ]  Thus, there is a significant variation in infection rates based on geographical area. [ 22 ]


Those who work with children are also at risk of being infected, as are family members of infected individuals. 7% of children aged 1 to 3 years and 11% of infants and toddlers tested for admission to day-care centers were found to be infected. [ 22 ]  Not all  Giardia  infections are symptomatic, and many people can unknowingly serve as carriers of the parasite. Re- infection and chronic infections of the parasite can occur.  [ 23 ] [ citation needed ]


Giardia  infects humans, but is also one of the most common parasites infecting cats, dogs, and birds. Mammalian hosts also include dozens of species, [ 27 ]  including  cattle ,  sheep , [ 28 ]  and  goats . [ 28 ]


Cats can be cured easily, and lambs usually simply lose weight, but in calves, the parasites can be fatal and often are not responsive to antibiotics or electrolytes. Carriers among calves can also be asymptomatic. This parasite is deadly for  chinchillas , so extra care must be taken by providing them with safe water. Dogs have a high infection rate, as 30% of the population under one year old are known to be infected in  kennels . The infection is more prevalent in puppies than in adult dogs. Infected dogs can be isolated and treated, or the entire pack at a kennel can be presumptively treated together. Kennels and areas used for exercise should be considered contaminated for at least one month after dogs show signs of infection, as cysts can survive in the environment for long periods of time. Prevention can be achieved by  quarantine  of infected dogs for at least 20 days and careful management and maintenance of a clean water supply. [ citation needed ]


G. duodenalis  trophozoites are pear-shaped cells, 10 to 20  μm  long, 7 to 10 μm across, and 2 to 4 μm thick. [ 14 ] [ 15 ]  They are motile by way of four pairs of  flagella , which propel the trophozoites through the intestine. [ 15 ]  Notably, each  G. duodenalis  cell has two  nuclei , both of which actively  transcribe  genes. [ 14 ]  Adjacent to the nucleus,  G. duodenalis  cells have an  endoplasmic reticulum  that extends through much of the cell. [ 29 ]  Trophozoites about to differentiate into cysts also contain prominent vesicles termed  encystation-specific vesicles  that disappear once cyst wall construction begins. [ 29 ]  Unlike most other eukaryotes,  G. duodenalis  cells contain no visible  mitochondria , but instead contains a substantially reduced metabolic organelle known as a  mitosome . [ 15 ]  Additionally, cells appear to contain no  Golgi bodies , and instead the  secretory system  consists entirely of the endoplasmic reticulum and numerous vesicles dispersed throughout the cell, termed  peripheral vesicles . [ 29 ]  Peripheral vesicles are responsible both for taking up extracellular nutrients, and expelling waste outside the cell. [ 30 ]  Each cell also contains a pair of rigid structures called  median bodies  which make up part of the  G. lamblia   cytoskeleton . [ 14 ]  Trophozoites adhere to host epithelial cells via a specialized disk-shaped organelle called the  ventral disk . [ 14 ]


Cysts are oval-shaped cells slightly smaller than trophozoites. [ 15 ]  They lack flagella, and are covered by a smooth, clear cyst wall. [ 15 ]  Each cyst contains four nuclei and fragments of the ventral disc. [ 15 ]


G. duodenalis  primarily generates its energy by breaking down  glucose  via  glycolysis , as well as the  arginine deiminase  pathway. It is unable to synthesize  nucleotides  on its own, instead salvaging them from its host. Synthesis of  iron–sulfur clusters  is done in a double-membrane-bound compartment called the mitosome, which is likely a remnant of mitochondria. [ 19 ]  Each cell contains 25 to 100 mitosomes divided into two categories - peripheral mitosomes, which are scattered throughout the cell, and central mitosomes, which gather at the center of the cell for unknown reasons. [ 31 ]  As in mitochondria, proteins with a certain peptide signal sequence are trafficked to and imported into the mitosome. Unlike mitochondria, mitosomes have no genome of their own. All mitosomal genes are encoded by the  Giardia  nuclear genome. [ 19 ]


Giardia  and the other  diplomonads  are unique in their possession of two  cell nuclei  that are similar in appearance, DNA content,  transcription , and time of replication.  Giardia  is a  polyploid  organism, with at least four, and perhaps eight or more, copies of each of five chromosomes per organism. [ 32 ]  The genome has been sequenced and was published in 2007, although the sequence contains several gaps. The sequence is about 12 million base pairs and contains about 5000 protein-coding genes. [ 33 ]  The  GC-content  is 46%. Trophozoites have a  ploidy  of four and the ploidy of cysts is eight, which in turn raises the question of how  Giardia  maintains homogeneity between the chromosomes of the same and opposite nuclei. Modern sequencing technologies have been used to resequence different strains. [ 34 ]


Infections with  Giardia  are self-limited in immunocompetent individuals, while people with immunodeficiency disorders may develop chronic giardiasis. [ citation needed ]  During the infection different mechanisms from the  innate  and  adaptive  immune system are activated. The first physical barrier is the mucus layer where the organism interacts with epithelial, immune cells, and some antimicrobial peptides released by those cells as well as  nitric oxide  and  inflammatory cytokines  like  interleukin 6 .  TLR2  and  TLR4  also can be activated by  Giardia . [ 35 ]  The T-cell response in giardiasis includes  T helper cells  and  cytotoxic T cells , and the production of  IgA  by  B cells  also helps to eliminate the infection. [ 36 ]


Giardia  had been assumed to be primitively asexual and with no means of transferring DNA between nuclei. These assumptions made  explaining the remarkably low level of allelic heterozygosity (< 0.01%) in the genome isolate, WB, very difficult, but all those assumptions of asexuality are now in doubt, with population genetics providing evidence for recombination [ 37 ]  and the identification of meiotic genes, evidence for recombination among isolates and the evidence for exchange of genetic material between nuclei during the process of encystation. [ 38 ]


These findings on sexuality in  Giardia , above, have important implications for understanding the origin of sexual reproduction in eukaryotes.  Though sexual reproduction is widespread among extant eukaryotes,  until recently, sex seemed unlikely to be a primordial and fundamental feature of eukaryotes.  A probable reason for the view that sex may not be fundamental to eukaryotes was that sexual reproduction previously appeared to be lacking in certain human pathogenic single-celled eukaryotes (e.g.  Giardia ) that diverged from early ancestors in the eukaryotic lineage. [ citation needed ]


In addition to the evidence cited above for recombination in  Giardia , Malik et al. [ 39 ]  reported that many meiosis specific genes occur in the  Giardia  genome, and further that homologs of these genes also occur in another unicellular eukaryote,  Trichomonas vaginalis .  Because these two species are descendants of lineages that are highly divergent among eukaryotes, Malik et al. [ 39 ]  suggested that these meiotic genes were present in a common ancestor of all eukaryotes.  Thus, on this view, the earliest ancestor of eukaryotes was likely capable of sexual reproduction.  Furthermore, Dacks and Roger [ 40 ]  proposed, based on phylogenetic analysis, that facultative sex was present in the common ancestor of all eukaryotes.  Bernstein et al. also reviewed evidence in support of this view. [ 41 ]


Eight genotype assemblages of  G. duodenalis  have been recognized to date (A-H). [ 27 ]  Genotyping of  G. duodenalis  isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main (or possibly only)  G. duodenalis  assemblages that undeniably infect human subjects. [ 27 ]


Frances Gillin of the  University of California, San Diego , and her colleagues cultivated the entire lifecycle of this  parasite  in the laboratory, and identified biochemical cues in the host's digestive system that trigger  Giardia' s lifecycle transformations. [ 42 ] [ 43 ]  They also uncovered several ways in which the parasite evades the defenses of the infected organism. One of these is by altering the proteins on its surface, which confounds the ability of the infected animal's  immune system  to detect and combat the parasite (called  antigenic variation ). Gillin's work reveals why  Giardia  infections are extremely persistent and prone to recur. In addition, these insights into its biology and survival techniques may enable scientists to develop better strategies to understand, prevent, and treat  Giardia  infections. [ citation needed ]


In December 2008,  Nature  published an article showing the discovery of an  RNA interference  mechanism that allows  Giardia  to switch variant-specific surface proteins to avoid host immune response. [ 44 ]  The discovery was made by the team working at the Biochemistry and Molecular Biology Laboratory, School of Medicine, Catholic University of Cordoba, Argentina, led by Dr. Hugo Lujan. [ citation needed ]


The main congress about  Giardia  is the International Giardia and Cryptosporidium Conference. A summary of results presented at the most recent edition (2019, in  Rouen , France) is available. [ 45 ]