CHOLERA Definition

Acute diarrheal disease caused by infection of the intestine with Vibrio cholerae Cholera gravis: severe form of cholera

Etiology
Vibrio cholerae is a highly motile, flagellated, curved, Gram-negative rod that colonises the human small intestine The natural habitat of V. cholerae is coastal salt water and brackish estuaries. V. cholerae exists in two bioty es, classical and !l tor, and each bioty e is further subdivided into two seroty es, "naba and #gawa "t survives for u to $ weeks in fresh water and % weeks in salt water.

Pathogenesis
Transmission occurs by the faecal-oral route usually through contaminated water and occationaly food contaminated by flies, or on the hands of carriers. Cholera is a toxin-mediated disease. "ts characteristic watery diarrhea is due to the action of cholera toxin, a otent rotein enterotoxin elaborated by the organism after it coloni&es the small intestine. Achlorhydria and hy ochlorhydria facilitate the assage of cholera bacilli into the small intestine. The has enterotoxin A and ' subunits. The ' subunit binds to the e ithelial cell wall. The A subunit then activates intracellular adenylate cyclase, which results in massive secretion of isotonic fluid. "n the villus cell sodium absor tion is inhibited. "n the cry t cell active secretion of chloride ion is stimulated. The net effect is accumulation of sodium chloride in the intestinal lumen. (ater moves assively to maintain osmolality, and when this volume exceeds the ca acity of the gut to reabsorb fluid, watery diarrhoea ensues.

Clinical features
Cholera is redominantly a disease of children with attack rates highest in the ) to * years age grou . Classically there are three disease hases. a. !vacuation hase- which occurs after an incubation eriod of $+-+% hours, is characterised by the abru t onset of ainless, rofuse, watery diarrhea associated with vomiting in severe cases. ,-ice water. stools, so called because of mucus flecksfloating in the watery stools, are characteristic of this stage. b. Colla se hase - "f a ro riate treatment is not given the atient asses on to the colla se hase. This is characterised by circulatory shock, with a cold, clammy skin,hy otension and dehydration ,washerwoman.s hands.,

and falling urine out ut. /uscle cram s may be severe. At this stage renal failure and metabolic acidosis may be the ma0or com lications. c. -ecovery hase - 1hould the atient survive this stage, the recovery phase sets in with a gradual return to normal of clinical and biochemical arameters in )-2 days. Cholera sicca refers to severe disease in which the massive out ouring of fluid and electrolytes stays in dilated intestinal loo s. 3iarrhoea and vomiting do not occur and the mortality is high. Diagnosis The clinical sus icion of cholera can be confirmed by the identification of V. cholerae in stool can be detected directly by dark-field microsco y on a wet mount of fresh stool The best selective medium is thiosulfate4citrate4bile salts4sucrose 5TC'16 agar, on which the organism grows as a flat yellow colony The yield of stool cultures for the diagnosis of V. cholerae infection declines late in the course of the illness or when effective antibacterial thera y is initiated.

Treatment
a) Restoration of fluid volume electrolytes and !ase" -e lacement of fluid by the oral rehydration solution 5#-16 is highly effective #-1 takes advantage of a co-trans ort mechanism not affected by cholera toxin wherein sodium 57a86 moves across the gut mucosa along with actively trans orted glucose "ntravenous fluids are necessary for the severely dehydrated and for those with acidosis 5 9 : ;.$6. -inger-<actate is the best fluid for intravenous re lacement The fluid re=uired is calculated every % hours from the urine volume, stool and vomit out ut, and estimated insensible loss Accurate records are greatly facilitated by the use of a >cholera cot> which has a reinforced hole under the atient>s buttocks beneath which a graded bucket is laced !) Anti!iotics A single dose of doxycycline 2?? mg or tetracycline 5$ g6 or ci rofloxacin ) g in adults all reduce the duration of excretion of Vibrio

Prevention
1trict ersonal hygiene is vital and drinking water should come from a clean i ed su ly or be boiled @accines- Aarenteral vaccination with a killed sus ension of V. cholerae and oral vaccines containing killed V. cholerae and the ' subunit of cholera toxin are available but are of limited efficacy

#OOD PO$%O&$&' A&D 'A%TROE&TER$T$%

Acute gastroenteritis is a ma0or cause of morbidity and mortality /a0ority of e isodes may be directly linked to infection or infectious agents s read by the faecal-oral route. Causes of acute diarrhea A) $nfectious To)in*mediated 'acillus cereus 1ta hylococcal enterotoxin $nfective food +oisoning -otavirus gastroenteritis 1almonella, 1higella !. coli e.g. travellers> diarrhoea Cholera Proto-oal Giardiasis Amoebic dysentery () &on $nfectious 'astrointestinal Acute diverticulitis Aelvic inflammatory disease ,eta!olic u+set Betosis 5e.g. diabetic ketoacidosis6 Craemia Carcinoid syndrome Drugs and to)ins Antibiotics Cytotoxic agents Ciguatera fish oisoning

Clinical features The clinical features of food-borne disease all involve gastrointestinal u set The attern of sym tomatology is de endent on the athogenic mechanisms involved and are two ty es A) To)in mediated 1ome organisms 5Bacillus cereus, Staph. aureus and Vibrio cholerae6 elute exotoxins which exert their ma0or effects on the stomach and small bowel, where they cause mucosal inflammation They fre=uently roduce vomiting andDor a so-called >secretory> diarrhoea. This is watery without blood and faecal leucocytosis "n general, the >incubation eriod> of these intoxications, i.e. the time from ingestion to the onset of sym toms, is short and, other than dehydration, little systemic u set occurs () Direct $nvasion #rganisms, such as Shigella, Salmonellaand enterohaemorrhagic E. coli, may directly invade the mucosa of the small bowel or roduce cytotoxins that damage and ulcerate the mucosa with inflammation, ty ically affecting the terminal small bowel and colon

 9ere the incubation eriod is longer and more systemic u set occurs with rolonged diarrhoea. "f the colon is inflamed, blood and leucocytes may be resent in the stool. Assessment of the +atient with acute diarrhea History This includes history of sus ect foods, the duration and fre=uency of diarrhoea, the resence of blood, abdominal ain and tenesmus, and whether family or community members have been affected. "ncubation eriods of less than )% hours suggest toxin-mediated food oisoning A eriod longer than * days suggests diarrhoea caused by roto&oa or helminths. Examination The degree of dehydration can be assessed by skin turgor and blood ressure measurement. The urine out ut and ongoing stool losses should be measured carefully. Investigations These should include stool ins ection for blood and microsco y for leucocytes -enal functions and electrolytes ,anagement of acute diarrhea "solation to minimise erson-to- erson s read of infection There are three elements to the management of acute diarrhoea in individual cases: Eluid re lacement AntibioticsDantimicrobial thera y Ad0unctive antidiarrhoeal thera y. Fluid replacement 'y far the most im ortant as ect of the management of acute gastroenteritis is re lacement of fluid losses. The fluid lost in diarrhoea is isotonic, so a source of electrolytes, in either continued food intake or re lacement fluid, is re=uired. 3uring gastroenteritis a source of carbohydrate, either starch or sugar, is re=uiredF otherwise fluids, even with electrolyte content, will not be absorbed. This is the basis of oral rehydration solution 5#-16 There are three elements to the calculation of a ro riate volumes: -e lacement of established losses -e lacement of ongoing losses -e lacement of normal daily re=uirement. Antimicrobial agents Antibiotics should therefore not be used routinely in diarrhoea Antibiotics in non-s ecific gastroenteritis have been shown to shorten sym toms 3ysentery roduced by Sh. dysenteriae is a clear indication for antibiotic thera y and cholera e idemics Antidiarrhoeal, antimotility and antisecretory agents

 "n general these agents are not recommended and their use may even be contraindicated in the management of infective or otentially infective gastroenteritis. Antisecretory agents such as bismuth and chlor roma&ine may be effective but can cause significant sedation.

Escherichia coli
!scherichia coli organisms are gram-negative bacteria of the family !nterobacteriaceae. /ulti le distinct strains cause a. Gastroenteritis 5intestinal athogenic !. coli6 )6 1higa toxin4 roducing !. coli 51T!C6Denterohemorrhagic !. coli 5!9!C6- #)*; strains $6 !nterotoxigenic !. coli 5!T!C6 26 !ntero athogenic !. coli 5!A!C6 +6 !nteroinvasive !. coli 5!"!C6 *6 !nteroaggregative !. coli 5!A!C6 ' !xtraintestinal infections 5extraintestinal athogenic !. coli G!xA!CH6 )6 Crinary tract $6 'loodstream 26 Cerebros inal fluid Pathogenesis $ntestinal Aathogenic !. coli are ac=uired via the fecal-oral route. !T!C is a ma0or cause of endemic and traveler.s diarrhea. Aathogenicity caused by enterotoxins E)tra intestinal /a0or ortion are normal facultative intestinal flora in most humans The rate-limiting ste is entry from a site of coloni&ation 5e.g., the colon, vagina, or oro harynx6 into a normally sterile extraintestinal site. Clinical features A6 "ntestinal 1 ectrum from mild illness to life-threatening cholera-like illness 9emorrhagic colitis '6 !xtra intestinal Crinary tract infection Abdominal and elvic infections 'acteremia $nvestigations 1tool examination for leukocytes and blood 1tool cultures or Culture of infected site 5e.g., urine, blood, wound, 6 Testing for 1higa toxins or toxin genes Treatment

A6 3iarrhea The mainstay is re lacement of water and electrolytes !arly atient-initiated =uinolone use decreases the duration of illness. '6 !xtraintestinal Trimetho rim4sulfamethoxa&ole, ce halos orins 5third-, and fourth-generation6, =uinolones, monobactams can be used for treatment 3rainage of abscesses and removal of infected foreign bodies are often needed for cure.