Epidemiology and Management of Diarrheal Diseases Amal Mitra, MD, MPH, DrPH Professor University of Southern Mississippi Readings: Diarrhoeal Diseases

DEFINITION Watery Diarrhea: 3 or more liquid or watery stools in 24 h Dysentery: Presence of blood and/or mucus in stools Persistent Diarrhea: Diarrhea lasting for 14 days or more The World Health Organization defines diarrhea as the passing of liquid or watery stools at least 3 times in a 24-hour period. However, it is the consistency rather than the number of stools that is important. Frequent passing of formed stools is not diarrhea. Breastfed babies normally passes loose or pasty stools. The mother can tell if her baby has an abnormal stool. If stools contain blood or mucus, it is called dysentery. If diarrhea persists for 14 days or longer, it is called persistent diarrhea.

TYPES OF DIARRHEA This chart shows common diarrheal pathogens. There are a number of other pathogens and agents that cause diarrhea. Some of them are as follows: Campylobacter (or Helicobacter pylori) Salmonella Vibrio parahemolyticus Giardia lamblia More recently, a newer strain of Vibrio, known as “Bengal strain” (Vibrio cholera O139) caused a big epidemic in India, Bangladesh, and some other areas.

COMMON CAUSES OF DIARRHEA- BACTERIA Vibrio cholera Shigella Escherichia coli Salmonella Campylobacter jejuni Yersinia enterocolitica Staphylococcus Vibrio parahemolyticus Clostridium difficile

COMMON CAUSES OF DIARRHEA- VIRUS Rotavirus Adenoviruses Caliciviruses Astroviruses Norwalk agents and Norwalk-like viruses

COMMON CAUSES OF DIARRHEA- PARASITE Entameba histolytica Giardia lamblia Cryptosporidium Isospora

COMMON CAUSES OF DIARRHEA-OTHERS Metabolic disease Hyperthyroidism Diabetes mellitus Pancreatic insufficiency Food allergy Lactose intolerance Antibiotics Irritable bowel syndrome

TRANSMISSION Most of the diarrheal agents are transmitted by the fecal-oral route Some viruses (such as rotavirus) can be transmitted through air Nosocommial transmission is possible Shigella (the bacteria causing dysentery) is mainly transmitted person-to-person Food and water contaminated directly or indirectly with feces or vomitus of infected persons are the principal mode of transmission. Ingestion of raw or inadequately cooked seafood or eating shelfish from coastal and estuarine waters can cause outbreaks of diarrhea. Person-to-person transmission occurs by hand-to-mouth transfer of the agent from feces of an infected individual. Respiratory spread is possible for rotavirus.

SEASONALITY Although diarrhea occurs in any time of the year, outbreak of diarrhea usually follows a seasonal pattern in most developing countries.

PERSON-AT-RISK Cholera: 2 years and above, uncommon in very young infants Shigellosis: more common in young children aged below 5 years Rotavirus diarrhea: more common in young infants and children aged 1-2 years E. coli diarrhea: can occur at any age Amebiasis: more common among adults

TYPES OF VIBRIO CHOLERA Two major biotypes of Vibrio cholera that cause diarrhea are: Classical ElTor Two common serotypes of Vibrio cholera that cause diarrhea are: Inaba Ogawa

Vibrio cholerae O139 Vibrio cholerae in O-group 139 was first isolated in 1992 and by 1993 had been found throughout the Indian subcontinent. This epidemic expansion probably resulted from a single source after a lateral gene transfer (LGT) event that changed the serotype of an epidemic V. cholerae O1 El Tor strain to O139. More information: http://www.cdc.gov/ncidod/EID/vol9no7/02-0760.htm

Vibrio vulnificus The organism Vibrio vulnificus causes wound infections, gastroenteritis or a serious syndrome known as "primary septicema."  V. vulnificus infections are either transmitted to humans through open wounds in contact with seawater or through consumption of certain improperly cooked or raw shellfish. This bacterium has been isolated from water, sediment, plankton and shellfish (oysters, clams and crabs) located in the Gulf of Mexico, the Atlantic Coast as far north as Cape Cod and the entire U.S. West Coast.  Cases of illness have also been associated with brackish lakes in New Mexico and Oklahoma. For more information: http://hgic.clemson.edu/factsheets/HGIC3663.htm

TYPES OF SHIGELLA The major serotypes of Shigella that cause diarrhea are: Dysenteriae type 1 or Shigella shiga Shigella flexneri Shigella sonnei Shigella boydii

TYPES OF E. COLI Six major types of Escherichia coli cause diarrhea: Enterotoxigenic E. coli (ETEC) Enteroinvasive E. coli (EIEC) Enteropathogenic E. coli (EPEC) Enterohemorrhagic E. coli (E. coli O157:H7) Enteroaggregative E. coli (EAggEC) Diffuse adherent E. coli (DAEC)

CLINICAL FEATURE: CHOLERA Rice-watery stool Marked dehydration Projectile vomiting No fever or abdominal pain Muscle cramps Hypovolemic shock Scanty urine Cholera has an acute onset. Death can occur as early as 4-8 hours of onset if the disease is severe. In a day, an adult passes several liters of watery stools of typical fishy smell and rice-water color. Dehydration is often moderate to severe. Some patients are brought unconscious or semiconscious because of hypovolemia. Sings of shock including a low blood pressure, poor or imperceptible pulse, poor skin elasticity, and poor urine output are common.

CLINICAL FEATURE: E. COLI DIARRHEA Watery stools Vomiting is common Dehydration moderate to severe Fever– often of moderate grade Mild abdominal pain E. coli is a less severe watery diarrhea than cholera. However, the clinical presentations may mimic cholera. Usually, patients present with moderate grade fever which is absent in cholera. Also, there may be mild abdominal pain. Features of shock are often less prominent in E. coli diarrhea than cholera.

CLINICAL FEATURE: ROTAVIRUS DIARRHEA Insidious onset Prodromal symptoms, including fever, cough, and vomiting precede diarrhea Stools are watery or semi-liquid; the color is greenish or yellowish– typically looks like yoghurt mixed in water Mild to moderate dehydration Fever– moderate grade The most differentiating points of rotavirus diarrhea include: (1) diarrhea in very young kids; (2) flu-like symptoms before diarrhea; (3) stools typically look like yoghurt mixed in water.

CLINICAL FEATURE: SHIGELLOSIS Frequent passage of scanty amount of stools, mostly mixed with blood and mucus Moderate to high grade fever Severe abdominal cramps Tenesmus– pain around anus during defecation Usually no dehydration Typically, presence of altered blood in stools and frequent motions (20 or more times a day) accompanied by high fever and abdominal pain in older children or adults are characteristic features of shigellosis. This disease is often confused with amebiasis, which present with less or no blood, but more mucus, and less frequent motions. In malnourished patients, fever may be less prominent.

CLINICAL FEATURE: AMEBIASIS Offensive and bulky stools containing mostly mucus and sometimes blood Lower abdominal cramp Mild grade fever No dehydration The distinguishing features of amebiasis from shigellosis are: (1) usually affect the elderly people; (2) chronic in nature; (3) more mucus and less blood in stools; (4) stools are very offensive; (5) stools are bulky

LABORATORY DIAGNOSIS Stool microscopy Dark field microscopy of stool for cholera Stool cultures ELISA for rotavirus Immunoassays, bioassays or DNA probe tests to identify E. coli strains Presence of fecal leukocytes 20 or more and RBC per high power field of stool microscopy suggests invasive diarrhea (possibly shigellosis). Stool microscopy also reveals parasitic and helminthic infections. Dark field microscopy is a rapid diagnostic test for Vibrio. Stool cultures are available for detecting bacteria including Vibrio cholera, Salmonella, Shigella, and others. Enzyme linked immunosorbent assay (ELISA) is done to detect rotavirus. Antigen tests are done for different serotypes of E. coli.

ASSESSMENT OF DEHYDRATION Anterior fontanelle: This is the bony junction of the frontal and two parietal bones of the skull. This sign may be found only in infants aged <18 months.

ASSESSMENT OF DEHYDRATION (contd.)

ASSESSMENT OF DEHYDRATION (contd.)

TREATMENT Rehydration– replace the loss of fluid and electrolytes Antibiotics– according to the type of pathogens Start food as soon as possible Rehydration is the correction of dehydration. Salts and water are lost during diarrhea. These can be replaced by oral rehydration salt (ORS) or intravenous fluids, based on the type of dehydration. Mild and moderate dehydration can be managed by ORS. Severe dehydration should be treated with IV solution. Mutiple antibiotic resistance is a growing problem in many countries. Therefore, antibiotics should be chosen according to the sensitivity pattern of the organism. Food should be started as soon as the patient can eat. Complete withdrawal of food during diarrhea is not recommended. Breastfeeding should be continued throughout the course of diarrhea. Extra protein intake is needed during and after some diarrheal diseases, for example shigellosis.

COMPOSITION OF ORS Home-made ORS: Sugar or molasses (40 g) can be used as a substitute for glucose to prepare home-made ORS. Common salt (5 g) will be added to it and dissolved in one liter of clean water. Rice-ORS: Rice powder (50 g) can replace the sugar or glucose. The amount of the other salts will remain the same. These will be dissolved in one liter of clean water to prepare rice-based ORS. Studies showed that rice-based ORS can reduce vomiting and diarrhea more in some cases compared to the conventional ORS prepared with glucose.

AMOUNT OF SALT LOSS DURING DIARRHEA The amount of salt and water loss resulting in dehydration is higher in patients with cholera than other types of diarrhea (Molla et al. 1981). However, loss of potassium is higher and loss of other salts is lower in rotavirus diarrhea compared to other diarrheal diseases. Therefore, kids who commonly suffer from rotavirus diarrhea should be given extra plain water and/or breast-milk in between ORS to prevent hypernatremia (a salt overload).

ANTIMICROBIAL AGENTS Sensitivity pattern of the microbial agents should be checked to select an appropriate antibiotic.

COMPLICATIONS: WATERY DIARRHEA Dehydration Electrolyte imbalances Tetany Convulsions Hypoglycemia Renal failure

COMPLICATIONS: DYSENTERY Electrolyte imbalances Convulsions Hemolytic uremic syndrome (HUS) Leukemoid reaction Toxic megacolon Protein losing enteropathy Arthritis Perforation

VACCINES An oral cholera vaccine is available, which gives immunity to 50-60% of those who take the vaccine, and this immunity lasts only a few months. No vaccines are available against shigellosis A vaccine against rotavirus diarrhea has been withdrawn recently from the market.

PREVENTION Safe drinking water and food “Boil it, cook it, peel it, or forget it. " Hand washing Proper sanitation