INTESTINAL INFECTIONS MUDr. RNDr. František Stejskal, Ph.D. November 19, 2007 Department of Tropical Medicine 1st Faculty of Medicine Charles University and Hospital Bulovka Studničkova 7, 128 00 Praha 2

DIARRHEA - DEFINITION DIARRHEA ACUTE DIARRHEA Increase in fluidity, volume or frequency of bowel movement Normal bowel habit varies greatly from person to person Above 12 mo age, more than 3 loose stools per day are abnormal ACUTE DIARRHEA Subside spontaneously within a few days PERSISTENT AND CHRONIC DIARRHEA Persist for more than 2 – 3 weeks

TERMINOLOGY OF DIARRHEAL DISEASES Symptoms/signs Example/etiology Gastritis Vomiting, nausea, no fever Food poisoning, preformed toxins (Staphylococcus aureus, Bacillus cereus) Gastroenteritis Vomiting, nausea, diarrhea usually watery without blood, abdominal pain/cramps, fever may be present Food poisoning, preformed toxins Cholera Salmonellosis, giardiasis Enteritis No vomiting Salmonellosis, giardiasis, cryptosporidiosis Enterocolitis No vomiting, diarrhea often with blood, abdominal pain/cramps Campylobacter, Yersinia enterocolitica Colitis - ulcerative - pseudomembranose Diarrhea with blood and pus, abdominal cramps, tenesm, fever may be present Bacillary, amoebic dysentery Intestinal schistosomiasis Ulcerative colitis Bloody diarrhea, abdominal cramps, usually without fever Clostridium perfringens C (pigbel), Cl. difficile

INFECTIVE DIARRHEA VIRUSES Rotaviruses Norwalk virus (Noroviruses) Caliciviruses Astroviruses Enteric adenoviruses

INFECTIVE DIARRHEA - BACTERIA Enterotoxicoses (preformed toxin) Bacillus cereus Staphylococcus aureus Clostridium perfringens C Cholera and other Vibria Enterotoxigenic E. coli (ETEC) Salmonellosis Campylobacter jejuni Yersinia enterocolitica Shigellosis Enteroinvasive (EIEC) and enteroadherent E. coli Aeromonas hydrophila Plesiomonas shigelloides

INFECTIVE DIARRHEA - PARASITES Protozoa Giardiasis Amebiasis Cryptosporidium Cyclospora Isospora Helminths Ascariasis Trichuriasis Ancylostomosis Strongyloidosis Taeniasis

PATHOGENESIS OF INFECTIVE DIARRHEA Toxin production Staphylococcus pyogenes, St. aureus (preformed toxin) Vibrio cholerae, ETEC toxin (↑cAMP – inhibition of Na+ absorption) Enterocytes adhesion and colonisation E.coli Giardia intestinalis Destruction of intestinal mucous membrane at the bacterial or parasite attachment place Enteropathogenic E. coli, viruses Cryptosporidium Mucous membrane and submucose invasion Salmonella, Campylobacter jejuni, Yersinia enterocolitica Isospora, Cyclospora Colonic wall invasion and ulcers formation Shigella, enteroinvasive E.coli (EIEC) Entamoeba histolytica

PATHOGENESIS OF DIARRHEA II Host defense mechanism: Increased risc: - Treatment with anacides, proton pump inhibitors, H2 inhibitors - Immunity defects – IgA deficiency Infective dose: Low (less than 103 bacteria cells) - shigellosis, Campylobacter (contagious infections) High (more than 103 bacteria cells) - salmonellosis

SOURCE OF INFECTION EPIDEMIOLOGY Contaminated water Undercoched or roh meat, fish or seafood Fruits and vegetabele Milk products

ACUTE DIARRHEA – DIFFERENTIAL DIAGNOSIS With fever and with blood Shigellosis, Campylobacter, EIEC, Cl. perfringens C – enteritis necroticans, (salmonellosis - 50%, typhoid) With fever and without blood Rotaviruses, Norwalk, salmonellosis (50 %); any localized infection at small children (otitis, tonsillitis, pneumonia), malaria Without fever and with blood Amoebiasis, intestinal schistosomiasis, balantidiosis, trichuriasis Without fever and without blood cholera, ETEC, enterotoxicosis (stafylococcal, B. cereus), cryptosporidiosis, isosporiasis, cyclosporiasis

CHRONIC DIARRHEA With fever Without fever and with blood Intestinal tuberculosis, visceral leishmaniasis, yersiniosis, HIV infection, CMV Without fever and with blood Amoebiasis, intestinal schistosomiasis, balantidiosis, trichuriasis, Crohn disease, idiopatic proctocolitis Without fever and without blood Giardiasis, tropical sprue, coeliacal sprue, lactase deficiency, strongyloidosis, cryptosporidiosis, Whipple disease, intestinal malignant lymphoma, mucoviscidosis

INVESTIGATION IN DIARRHEA Fecal smear: fecal leucocytes Stool culture Parasitic stool investigation (persistant diarrhea, for more than 2-3 weeks)

DIRECT FAECAL SMEAR Place a drop of sterile saline on the left hand site of the slide; place a drop of iodine on the right hand site of the slide and add a small portion of stool to each drop and mix to form suspension Cover with a coverslip and examine with the x10 objective first Mr. Brown X 10/12/04

White blood cells (WBC) FECAL LEUCOCYTES Mucus (pus) from stool is stained with 2 drops of Lőffler’s methylen blue Infection/disease White blood cells (WBC) Viral gastroenteritis NO Cholera, ETEC, enterotoxicosis Giardia, Cryptosporidium Salmonella typhi Monocytes Salmonellosis (S. enteritidis) PMN Shigellosis, EIEC Campylobacter, Yersinia enterocolitica Entamoeba histolytica, Balantidium coli Ulcerative colitis, Crohn disease

DIRECT FAECAL SMEAR - RESULTS Cysts (Giardia, amoebas, etc.) Trophozoites (amoebas, Giardia, trichomonads, other flagellates, etc) Oocysts (Isospora, Cyclospora) of parasitic protists Blastocystis hominis Yeasts (Candida, Saccharomyces) Ova of parasitic helmints Vibrio cholerae Negative in cryptosporidiosis, special staining

STOOL CULTURE Routine: Salmonella sp., Shigella, Citrobacter, Proteus sp., Morganella sp. and other enterobacteria Special: Campylobacter, Vibrio cholerae, Yersinia enterocolitica Yeasts Virus isolation (enteroviruses) Parasites – special culture media: Amoebas, trichomonads, other flagellates

THERAPY OF DIARRHEA

ORAL REHYDRATATION SOLUTION NaCl 3,5 g KCl 1,5 g Na-bicarbonate 2,5 g or Na-citrate 2,9 g glucose 20 g or saccharose 40 g in 1 L of boiled water Add 1 tsp of salt and 2-3 tsp of sugar or honey and 1 lemon to 1 liter of water.

ORS WITH REDUCED OSMOLARITY ORS solution does not reduce stool output or duration of diarrhoea This solution, which is slightly hyperosmolar when compared with plasma, may cause hypernatraemia or an osmotically driven increase in stool output, especially in infants and young children For this reason paediatricians in some developed countries recommended the ORS with reduced osmalarity containing about 60 mEq/l sodium and having a total osmolarity of 250 mOsm/l

COMPARISON OF ORS and Valík solution Original ORS g/L Valík solution g/L NaCl 3,5 2,36 KCl 1,5 1,12 Na-bicarbonate 2,5 1,68 Glucose 20 27,0

ORS WITH REDUCED OSMOLARITY Na+: 60-75 mEq/l (original ORS 90 mEq/l) Glucose: 75-90 mmol/l Total osmolarity: 215 - 260 mOsm/l (original ORS 311 mOsm/l)

USE OF ANTIMICROBIAL DRUGS Bloody diarrhea with fever (dysentery) which does not improve after 2-3 days or rehydratation Cholera with severe dehydratation Bacterial diarrhea at immunocompromised patients Diarrhea with high fever in small children Parasitic diarrhea

CHOLERA

Seventh pandemic of cholera, 1961-1971 (CDC) CHOLERA PANDEMIC Seventh pandemic of cholera, 1961-1971 (CDC)

CHOLERA Humans are the only known natural host Large infective dose – contaminated food or water Incubation period: a few hours to 5 days Severe watery diarrhea (up to 30 L per day), painless, without fever Electrolyte imbalances, metabolic acidosis, prostration, dehydration Management: ORS, doxycyclin 300 mg in single dose in the severe cases

DIAGNOSIS OF CHOLERA In epidemics based on clinical grounds alone In non-epidemic periods, acute watery diarrhea resulting in severe dehydration: Dark-field microscopy of faecal material Transportation of samples in alkaline peptone water and kept cool Culture in selective media such as TCBS agar Bio- and serotyping in the reference laboratory Notify the infection!

CHOLERA PANDEMIC IN SOUTH AMERICA

CHOLERA OUTBREAK IN 2005                                                                

Shigella – species and serogroups SEROTYPE S. dysenteriae A 1 – 15 S. flexneri B 1 – 6 (15 subtypes) S. boydii C 1 - 18 S. sonnei D 1

EPIDEMIOLOGY OF SHIGELLOSIS Shigella is causing 80 mil. of symptomatic infections and 700 000 deaths each year 99% of infections are in developing countries 70% of cases and 60% of deaths at children under 5 years The recent epidemics: 1969 – 73: Central America – 0,5 mil. of cases, 20 000 of deaths 1993 – 95: countries of central and south Africa 1994: Rwandian refugies to DR of Congo (20 000 of deaths during the first month) 1999 – 03: Sierra Leone, Liberien, Guinea, Senagal, … 2000: India a Banglades – resistance to FQ

EPIDEMIOLOGY OF SHIGELLOSIS S. sonnei and S. boydii are causind ussually mild disease with watery or bloody diarrhea, they are more common in developed countries of temperate climate S. flexneri is the main cause of endemic shigellosis in developing countries S. dysenteriae typ 1 (Sd1, Shiga bacillus) is causing the most serious disease, it is causing epidemies in developing countries

Shigella dysenteriae serotype 1 It deffer from other species: It produces a potent cytotoxin (Shiga toxin) It is causing more severe, long-lasting, potentially deadly diarrhea The resistance to antibiotics is more common It may cause large, often regional epidemics: „high attack rates“ „high case fatality rates“

DYSENTERY SYNDROME Diarrhea with blood and pus Abdominal pain and cramps Tenesms

DIFFERENTIAL DIAGNOSTICS Entamoeba histolytica Campylobacter jejuni Entheroinvasive E. coli Enthero-hemorrhagic E. coli Salmonella sp. Intentestinal schistosomosis (Schistosoma mansoni, S. japonicum)