ACUTE INFECTIOUS DIARRHEA

Normal bowel movement frequency ranges from three times a day to three times a week in the normal population. Diarrhea is defined as more frequent passage of stool, with consistency less solid than normal [or even watery]. Acute diarrhea is defined as a greater number of stools of decreased form from the normal lasting for less than 14 days. If the illness persists for more than 14 days, it is called persistent. If the duration of symptoms is longer than 1 month, it is considered chronic diarrhea. Most cases of acute diarrhea are self-limited, caused by infectious agents (e.g. viruses, bacteria, parasites), and do not require medication unless the patient has a decreased immune system. The incidence of acute infectious diarrhea is higher in children and infants. Diarrhea is associated with problems in the small and large intestine; pathology further up in the stomach is more usually associated with nausea and vomiting.

Worldwide, acute diarrhea constitutes a major cause of illness and even death, especially among the very young, very old, and infirm. It is estimated that each year, U.S. adults experience almost 100 million episodes of acute diarrhea, resulting in about 8 million physician visits and more than 250,000 hospital admissions (1.5% of adult hospitalizations). Most cases of acute diarrhea are caused by infections of the small and/or large intestine. In developed countries, including the United States, diarrhea outbreaks are more often linked to contaminated water supplies, person-to-person contact in places such as child-care centers, or "food poisoning" (when people get sick from improperly processed or preserved foods contaminated with bacteria). Diarrhea is more prevalent among adults who are exposed to children and non-toilet-trained infants, particularly in a daycare setting. It is also more prevalent in travelers to tropical regions; homosexual males, persons with a compromised immune system, and those living in unhygienic environments (who have exposure to contaminated water or foods).

Infection with rotavirus is the most common cause of acute diarrhea in children and usually occurs during the winter months. Enteroviral infections are common in children during the summertime. Infections outside of the gastrointestinal tract, such as middle ear infections, can be

associated with diarrhea in children. Bacterial and parasitic gastrointestinal infections of children are more common in underdeveloped countries.

Approximately 8 L of fluid enter the intestines daily—1 to 2 L represents food and liquid intake, and the rest is from internal sources such as salivary, gastric, pancreatic, biliary, and intestinal secretions. Most of the fluid, about 6 to 7 L, is absorbed in the small intestine, and only about 1 to 2 L is presented to the colon. Most of this is absorbed as it passes through the colon, leaving a stool output of about 100 to 200 g/day. Although many organisms simply impair the normal absorptive processes in the small intestine and colon, others, such as Vibrio cholerae, secrete a toxin that causes the cells lining the intestine to secrete, rather than absorb, fluid and electrolytes. Voluminous diarrhea may result.

Diarrhea-causing pathogens are usually transmitted through the fecal-oral route. Risk factors for this type of transmission include improper disposal of feces and lack of proper hand washing following defecation and feces contact before handling food. Other risk factors include improper food hygiene, inadequate food refrigeration, food exposure to flies, and consumption of contaminated water. Multiple host factors that determine the level of illness once exposure to infectious agents has occurred include age, personal hygiene, gastric acidity and other barriers, intestinal motility, immunity, and intestinal receptors.

Viruses (e.g., adenovirus, enterovirus, rotavirus, Norwalk virus) are the most common cause of diarrhea in the United States. Escherichia coli, Clostridium difficile, and Campylobacter, Salmonella, and Shigella spp. are common bacterial causes. Bacillus cereus, Clostridium perfringens, Staphylococcus aureus, Salmonella species, and others cause food poisoning. Entamoeba histolytica and Giardia, Cryptosporidium, and Cyclospora species are parasitic agents that cause diarrhea.

Acute watery diarrhea is most commonly seen with traveler's diarrhea caused by enterotoxigenic E. coli (ETEC), parasite-induced diarrhea from Giardia and Cryptosporidium species and, in cases of food poisoning (ingestion of preformed toxins), from B. cereus and S. aureus.

Some infectious agents cause inflammation of the intestinal walls, which may be mild or severe. Bacteria such as enteroadherent or enteropathogenic E. coli and viruses such as rotavirus, Norwalk agent, and HIV can cause minimal to moderate inflammation. Bacteria that destroy cells lining the intestinal wall such as Shigella, enteroinvasive E. coli, the parasite E. histolytica, and bacteria that penetrate the mucosa such as Salmonella, Campylobacter jejuni, and Yersinia enterocolitica result in moderate to severe inflammation with or without ulceration.

Ingestion of preformed toxin produced by bacteria such as B. cereus, S. aureus, and Clostridium perfringens can result in acute intestinal inflammation. Aeromonas, Shigella, and Vibrio species (e.g., V. parahaemolyticus) produce enterotoxins and also invade the intestinal mucosa. Patients therefore often present with watery diarrhea, followed within hours or days by bloody diarrhea. Bacteria that produce inflammation from cytotoxins include Clostridium difficile and hemorrhagic E. coli O157:H7.

Exudative (or mucous-filled) diarrhea results from extensive injury of the small bowel or colon mucosa as a result of inflammation or ulceration, leading to a loss of mucous, serum proteins, and blood into the bowel lumen. Increased fecal water and electrolyte excretion results from impaired water and electrolyte absorption by the inflamed intestine rather than from secretion of water and electrolytes into the exudates.

Noninfectious causes of diarrhea include inflammatory bowel disease, irritable bowel syndrome, ischemic bowel disease, partial small bowel obstruction, pelvic abscess in the rectosigmoid area, fecal impaction, and the ingestion of poorly absorbable sugars, such as lactulose and acute alcohol ingestion. Diarrhea is one of the most frequent adverse effects of prescription medications; it is important to note that drug-related diarrhea usually occurs after a new drug is initiated or the dosage increased.

The most common symptoms of acute infectious diarrhea are: frequent stools, watery stools, fever, chills, anorexia, nausea and vomiting, malaise, headache, muscle pains and abdominal pain. The passage of red or black stools may be a sign of bleeding and a more severe infection. Dehydration is the principal complication of infectious diarrhea and can be life-threatening if severe, particularly in young children and the elderly. Symptoms include dry mouth and thirst, dizziness or lightheadedness especially upon standing, decreased or absent sweating, muscle cramps, racing heart and/or palpitations and confusion or passing out in severe cases.

In most cases of acute diarrhea, fluid and electrolyte replacement are the most important forms of therapy. If patients are otherwise healthy and are not dehydrated, adequate oral intake can be achieved with soft drinks, fruit juice, broth, soup, and salted crackers. In those with excessive fluid losses and dehydration, more aggressive measures such as IV fluids or oral rehydration therapy with isotonic electrolyte solutions containing glucose or starch should be instituted. Oral rehydration therapy is less expensive, often just as effective, and more practical than intravenous fluids. A number of oral rehydration solutions are available, including Pedialyte, Rehydralyte, Ricelyte (Infalyte), Resol, the World Health Organization formula, and the newer reduced osmolarity formula for children. An equally effective homemade mixture is 1/2 tsp salt (3.5 g), 1 tsp baking soda (2.5 g NaHCO₃), 8 tsp sugar (40 g), and 8 oz orange juice (1.5 g KCl), diluted to 1 L with water. Fluids should be given at rates of 50 to 200 mL/kg/24 hr, depending on the patient's hydration status. IV fluids (e.g., lactated Ringer's solution) are preferred acutely for patients with severe dehydration and for those who cannot tolerate oral fluids.

Total food abstinence is unnecessary and not recommended. Foods providing calories are necessary to facilitate renewal of cells lining the intestines. Patients should be encouraged to take frequent feedings of fruit drinks, tea, flat carbonated beverages, and soft, easily digested foods such as bananas, applesauce, rice, potatoes, noodles, crackers, toast, and soups. Dairy products should be avoided, because transient lactase deficiency can be caused by enteric, viral, and bacterial infections. Caffeinated beverages and alcohol, which can enhance intestinal motility and secretions, should be avoided.

Antidiarrheal agents can be useful for the amelioration of symptoms. The most effective agents are the opioid derivatives loperamide, diphenoxylate-atropine, and tincture of opium. These agents inhibit intestinal peristalsis, facilitating intestinal absorption, and have antisecretory properties. Loperamide may reduce the duration of diarrhea in those with traveler's diarrhea and bacillary dysentery. These agents should be avoided in patients with fever, bloody diarrhea, and possible inflammatory diarrhea because they may be associated with prolonged fever in patients with shigellosis, toxic megacolon in patients with C. difficile infection, and the hemolytic-uremic syndrome in children with Shiga toxin–producing E. coli.

Bismuth subsalicylate, somewhat less effective than loperamide, is effective in relieving symptoms of diarrhea, nausea, and abdominal pain in patients with traveler's diarrhea. Bismuth subsalicylate is contraindicated in HIV-infected patients because it may cause bismuth encephalopathy.

Because most patients have mild, self-limited disease caused by viruses or noninvasive bacteria, routine antibiotic treatment is usually not warranted. Empirical treatment is indicated for those patients with suspected invasive bacterial infection, traveler's diarrhea, or a suppressed immune system. Empirical antibiotic treatment is also appropriate specifically for early Campylobacter infections and C. difficile–associated diarrhea as well as for the febrile patient with fecal white blood cells and blood-positive stools. Empirical treatment for Giardia can be prescribed for those with a 2-week or longer history of diarrhea. Empirical parasitic treatment should be considered for those in the following situations: history of diarrhea following travel to Russia, Nepal, or other endemic areas; exposure to infants in daycare centers; homosexual exposure or exposure to patients with AIDS; community waterborne outbreak and history of bloody diarrhea with a history of few or no white blood cells (WBCs), suggesting amoebiasis.

Immune mechanisms appear to be important in limiting acute infectious diarrhea. To this end, EnercelÒ has been proven to improve immune system function as per the following published study:

Either 5% ethanol placebo or the homeopathic medication was administered to groups of adolescents CD-1 mice at a dose of 0.35 cc daily for 28 days.  None of the mice manifested any evidence of gross or microscopic toxicity (brains, kidneys, livers, pancreases, or hearts).  Splenic NK function versus YAC-1 targets was significantly greater in mice treated with homeopathic agent (mean 103 +/- 10.9 lytic units [LU]; p<.05) compared to placebo (mean 81 +/- 7.4 LU).  Groups of mice were treated with 21-, 14-, 7-, or 0-day courses of the homeopathic tincture or placebo.  They were then challenged with 1 x 104 plaque-forming units (PFU) of a diabetogenic strain of coxsackie virus B4 (E2).  Treatment was continued for an additional three days; then the mice were sacrificed.  Titers of virus in the pancreas were significantly reduced in the homeopathic group that was treated for 21 days prior to viral challenge (mean [log 10] 3.14 +/- 0.79pfu/mg; p<.05) compared to placebo (4.29+/-0.90pfu/mg). The homeopathic mixture did not exhibit any antiviral effect in vitro. Thus, a homeopathic medication increased NK function both in vitro and in vivo and was non-toxic to mice.  In vivo antiviral activity was demonstrated, presumably through immune enhancement. 

EnercelÒ has been proven in a clinical study to improve the outcome of acute infectious diarrhea in children. The following manuscript abstract has been submitted for publication:

BACKGROUND: Infectious diarrhea in children still results in significant morbidity and mortality in developing countries. Inexpensive, safe, easy-to-administer treatment modalities are needed.

PRIMARY STUDY OBJECTIVE: The homeopathic medicine Enercel^® was tested in acute cases of presumed or documented infectious diarrhea in children less than 5 years of age.

METHODS/DESIGN:  A total of 123 cases were evaluated-- 59 in the control (observation) group and 64 in the test (Enercel^®) group. Test subjects received 3 ml intramuscular doses at baseline and 12 hours. Patients with parasitic and non-infectious causes of diarrhea were excluded. A clinical score to determine improvement or deterioration was created and applied to both groups.

SETTING: Subjects were sequentially enrolled from the emergency ward of B. Bloom Hospital in San Salvador, El Salvador

PARTICIPANTS: Eligible subjects were children less than 5 years of age with acute, presumed infectious diarrhea.

INTERVENTION: Enercel^® is a complex homeopathic medicine with documented imunomodulatory and antibiotic properties through enhancement of energy pathways in the body.

PRIMARY OUTCOME MEASURES: Clinical status score and fecal output measures were applied to determine outcomes. Statistical analysis was worked through EPI-INFO and SPSS programs. Clinical changes were measured every 6 hours for the first 24 hours, then again at 72 post-enrollment.

RESULTS: Both groups were comparable statistically in terms of clinical presentation, demographics and laboratory findings on enrollment. Differences in clinical status score became become significant at 18 and 24 hours (p < 0.05) and more so at 72 hours after enrollment (p < 0.01). The Enercel^®-treated group had significant improvement in fecal output at 12 ® 18 hours and 18 ® 24 hours (p < .01 for both). Seventeen subjects in the control and 15 in the test group had rotavirus infection. There was a borderline significant difference in clinical status at 18 hours (p = 0.08) and 24 hours (p = 0.06) after enrollment. At 72 hours, however, the difference was significant (p < 0.01).

Enercel^® has significant immune-inducing, indirect antimicrobial and energy-improving qualities. Based upon its mechanisms of action, the above studies and extensive clinical experience, Enercel^® may be considered in cases of acute infectious diarrhea in both adults and children.