Diseases of the digestive system

Learning objectives

Explain why staphylococcal food poisoning has such a rapid onset Explain why some pathogens have to be ingested in large numbers to cause infection Explain why antibiotic therapy is unnecessary with many bacterial infections Explain differences in the transmission of hepatitis A and hepatitis B and C viruses Explain how difference in life cycle determine if tapeworm infections can be transmitted from person to person

Case 1

This 18-year-old male presented to the outpatient medical clinic for evaluation of diarrhea and abdominal discomfort. The patient first noted mild abdominal discomfort and three loose bowel movements per day 1 week prior to evaluation. Two days prior to evaluation he noted intermittent, crampy periumbilical abdominal pain. He denied drinking well water, fever, blood in the stool, relation of the pain to meals, dysuria, or hematuria. On examination, the patient was afebrile and had normal vital signs. The abdominal examination was notable for mild lower abdominal tenderness. The fecal examination demonstrated a greenish, watery stool that was negative for occult blood. Laboratory evaluation included a normal white blood cell count, hematocrit, and platelet count. Examination of the feces microscopically was remarkable for the presence of white blood cells. The organism causing his illness is shown in Fig. 1 (Gram stain) and Fig. 2 (growth on special medium).

Case 1

Case 1

Etiology? White cells in feces?

Special laboratory conditions?

Invasive diarrhea, 50% bloody stool Cf Vibrio cholerae, non-invasive, white cells in stool rare Special selective media, microaerophilic, growth at 42 deg C. W. Salmonella most frequent cause of gastroenteritis Fecal/oral Poultry (98% chicken), non-pasteurized milk, water Warm weather months Infants, adolescent/young adult

Epidemiology

Case 1

Increasing incidence?

Drug resistance?

Factory farming Finishing in feedlots Automated processing

Bacteremia unusual?

Dramatic increase in fluoroquinolone resistance Low incidence with macrolides (GI side effects

Cannot survive within macrophages

Digestive system
Gastrointestinal tract mouth, pharynx, oesophagus, stomach, small and large intestine Accessory structures teeth, tongue, salivary glands, liver, gallbladder and pancreas

Bacterial diseases of mouth

300 species of oral bacteria Cariogenic, caries-forming Strep. mutans Attachment to tooth attach to pellicle of protein, bacteria produce dextran sucrose > glucose + fructose, glucose polymerized as dextran Fructose fermented to lactic acid

Dental caries

Dental plaque predominantly streptococci and actinomyces Plaque is impermeable to saliva so lactic acid is not diluted or neutralized so it attacks the enamel Different populations of bacteria cause decay in dentin

Periodontal disease

Gingivitis inflammation of the gums Porphyromonas spp. Gingival crevices contain large numbers of bacteria, 75% anaerobes,

Actinomyces viscous, Actinobacillus, Bacteroides

Periodontitis destruction of bone supporting the teeth Necrotizing ulcerative gingivitis Prevotella intermedia

Gastrointestinal disease
Infections: pathogen enters the GI and multiplies Penetration of the gastric mucosa, growth and/or passage to other systemic organs Fever

Intoxications: caused by response to toxin, very rapid onset

6-80,000,000 illnesses per year, 9000 deaths

Staphylococcal food poisoning

Typical scenario: food cooked, contaminated with S. aureus from hands, food held at room temperature, bacteria release toxins, toxins ingested, vomiting in 3-6 hours, recovery in 24 hours Five serologically distinct enterotoxins, all heat stable, protease resistant, superantigens Type A most often associated with food poisoning Type B associated with staphylococcal enterocolitis (rare)

Shigellosis
Bacillary dysentry

Shigella sonnei, S, dysentreriae, S. flexneri, S. boydii

S. sonnei most common in US, S. dysenteriae most

severe Release of shiga toxin, protein synthsis inhibitor Small dose infective

Not much affected by stomach acidity

Multiply in small intestine Damage large intestine, destroy tissue in intestinal mucosa, severe diarrhea with blood and mucus in stool Rarely invades bloodstream (except S. dysenteriae) 20,000 30,000 cases per year few deaths in US 20% mortality

Salmonellosis
2000 species based on O (cell wall) and H (flagella) antigens

Most likely only a single species or at most three, thus S. enterica serovar typhimurium
Incubation time of 12-36 hours Invasion of intestinal mucosa and multiplication Can enter lymphatic system Multiplication stimulates an inflammatory response with release of prostoglandins Activation of cAMP and fluid secretion Apparently no involvement of enterotoxins

40000 50000 cases reported per year from estimated 2,000,000

500 2000 deaths

Typhoid fever
Caused by S. typhi, and S. paratyphi types A, B, and C Penetration trhough the gut mucosa Bacteremia Spleen bone marrow liver Reinvade blood and enter the intestine for a second time producing a strong inflammatory response Incubation period of 12-14 days Complications:

Hemorrhage and intestinal perforation

Toxemia myocarditis and liver and bone marrow damage Systemic spread meningitis, osteomylitis, endocarditis

Cholera
Endemic in Asia Occasional outbreaks in western countries Latin American epidemic 9seafood contaminated with ballast water 1,000,000 cases 9600 deaths Vibrio cholerae free living inhabitant of brackish water Serogroup O1 divided into classical and El Tor biotypes (serosubgroups and phage types Enterotoxin causes hormone dependent activation of adenylate cyclase resulting in secretion of salt and fluids 1l per hour causing shock resulting in cardiac failure Bacteria are not invasive Untreated mortality 50%, fluid replacement 1%

Gram-negative gastritis
Vibrio parahaemolytica: halophilic vibrio,
contaminates seafood, diarrheal disease, Hemolytic, invasive, heat stable cytotoxin

Yersinia enterocolitica, Y. pseudotuberculosis:

Diarrhea, fever headache, abdominal pain

Superficial necrosis of mucosa and ulceration

Sometimes misdiagnosed as appendicitis Growth at refrigerator temperatures

E. coli gastritis
Pathogenic group Enterotoxigenic ETEC Epidemiology Diarrhea in children Travelers diarrhea Contaminated water Usually foodborne Properties Noninvasive, enterotoxins (heat labile, heat stable) Mimics cholera Invade cells by endocytosis, tissue destruction, inflammation Colitis, hemolytic-uremic syndrome (kidney involvement

Enteroinvasive EIEC

Enterohemorrhagi Serotype O157:H7 c EHEC Food and unpast. Milk Verotoxinproducing Enteropathogenic EPEC Babies and young children

Destruction of microvilli

Case 2

The patient was an 8-year-old male with a 2-day history of diarrhea. He presented with worsening diarrhea (14 movements that day) which had become bloody. He also complained of pain on defecation. He had vomited once. He had attended a cookout 6 days previously. He claimed that his mother made him eat a hamburger that was "pink inside" even though "he did not like it." His physical examination was benign except for obvious dehydration. His laboratory findings were significant for a white blood cell count of 13,100/1 with 9,700 neutrophils/l, a methylene blue stain of feces that showed abundant polymorphonuclear cells, and a positive stool guaiac. He was treated with trimethoprim-sulfamethoxazole and intravenous fluid therapy for dehydration. He quickly improved and was discharged within 24 hours. Culture of his stool specimen on MacConkey-sorbitol agar is shown in Fig. 1.

Case 2

Case 2

Etiologic agent?

EHEC Bloody diarrhea, undercooked meat, abdominal pain Intimin Shiga toxin, target endothelial cells, damage blood vessels Already abundant E. coli. Inability to ferment sorbitol Toxin production Cytotoxicity assay on Vero cells EIA PCR

Virulence factors?

Detection in feces?

Detection?

Case 2

Spread? Prevention?

Reservoir cattle Cook your hamburger

Antibiotic therapy?

No-associated with hemolytic uremic syndrome

Sequelae?

HUS Kidney Renal failure

Campylobacter
Campylobacter jejuni: gram- microaerophilic
Leading of foodborne illness in US Virtually all retail chicken is contaminated Enterotoxin

Invasion and bacteremia not uncommon

1/1000 cases Guillian-Barre syndrome temporary paralysis autoimmune attack

Helicobacter

Helicobacter pylori: associated with 90% duodenal ulcers, 70-80% gastric ulcers

Clostridium perfringens and Bacillus cereus

Gram+ spore forming anaerobic bacteria
Food contaminated at slaughter Spores survive cooking

Produce enterotoxins
toxin producing strains produce necrotizing colitis

Case 3

The patient was a 1-year-old male admitted to the hospital in December because of fever and dehydration. His parents reported that he had a 1-day history of fever, diarrhea, emesis, and decreased urine output. On admission, his vital signs revealed a temperature of 39.5C, slight tachycardia with a pulse rate of 126/min, and a respiratory rate of 32/min. He was very somnolent. His general physical examination was remarkable only for hyperactive bowel sounds. Laboratory tests showed a leukocytosis with a white blood cell (WBC) count of 14,200/l with 80% polymorphonuclear leukocytes (PMNs). Urinalysis was significant for a high specific gravity and ketones (consistent with the patient's dehydration). Stool, blood, and urine samples were sent for culture. A stool sample was also checked for ova and parasites. There were no fecal leukocytes. The patient was given intravenous normal saline and had nothing by mouth. Over the next 48 hours his emesis abated. Once he was rehydrated and was tolerating oral feedings, he was discharged home. All cultures for bacterial pathogens gave negative results, but a rapid viral diagnostic test was positive (Fig. 1).

Case 3

Case 3

Differential diagnosis

Bacterial, viral, parasitic No fecal leukocytes Rotavirus, coronavirus, calicivirus, astrovirus Vomiting suggests virus Rotavirus EIA Symptoms prolonged and more severe Viral protein acts as toxin activating fluid secretion Fecal/oral Day care Winter months

Pediatric gastroenteritis

Epidemiology

Case 3

Rapid diagnosis

EIA, latex agglutination

Treatment?

Rehydration Can remain infectious for long periods Handwashing, gloves Vaccine produced, Withdrawn - intussusception

Infection control?

Vaccine?

Mumps
Paramyxovirus: ss strand RNA env
Entry via respiratory tract Multiplication in respiratory tract and lymph nodes of neck, viremia

Infection of parotid glands

Complications: orchitis, meningitis pacreatitis, inflammation of ovaries

Cytomegalovirus inclusion disease

Cytomegalovirus (CMV) HHV-5 Nuclear inclusions of host cells

Shed in saliva saliva virus

Normally sub-clinical unless CMI responses are affected or in pregnancy (8000 cases)

Interstitial pneumonia, retinitis

Congenital abnormalities

Hepatitis
Inflammation of liver:

6 different viruses
Hepatitis A enterovirus ss + strand RNA Hepatitis B hepadnavirus ds DNA env Hepatitis C flavivirus ss + strand RNA env. Hepatitis D deltavirus ss strand RNA

Hepatitis E calicivirus ss + strand RNA

Yellow fever flavivirus Bacterial spp. e.g Leptospira spp.

Hepatitis A
Infection by fecal oral route Multiplies in epithelial lining of intestine 50% cases subclinical Anorexia, malaise, nausea, diarrhea, abdominal discomfort Jaundice, enlargement of liver more common in adults

Hepatitis B

DS DNA > ss + RNA, translated, encapsulated w. DNA polymerase, -DNA strand sythesised, RNA primes 2/3 +strand DNA, replication completed in nucleus after infection

Hepatitis B
Transmission by body fluids and blood Incubation 4-26 weeks ~130,000 infections per year (10,000 reported) 5000 deaths ~50% cases asymptomatic

Loss of appetite, low grade fever

Jaundice Complications: Cirrhosis, hepatocellular carcinoma (20-30 years post infection)

10% of patients become chronic carriers:

Immunodificient people suffer less severe disease Younger patients more likely males

Hepatitis C
Identified as source of transfusion associated non A non B hepatitis
Present in blood. Spreads same way as hepatitis B 50% of patients develop chronic active hepatitis 20% proceed to cirrhosis or liver cancer

Hepatitis D
Can only multiply in cells infected with hepatitis B, defective virus needs HBs Ag to coat the protein core, allowing attachment to cells

Spread in similar manner to Hepatitis B and C

Occurs in ~5% of HBV carriers, increasing severity of disease

Hepatitis E

Fecal oral transmission Endemic in much of the world

Does not cause chronic liver disease

High mortality in pregnant women

Reoviral gastroenteritis
Rotavirus ds RNA 3,000,000 case per year >100 deaths Low grade fever, diarrhea, vomiting Norwalk agent (outbreak in Norwalk, Ohio) Possibly 2/3 of foodborne illness caused by Norwalk-like viruses

Fungal mycotoxins
Egort cereal contaminated with Claviceps purpurea
Restricted blood flow, gangrene, hallucinations

Aflatoxin contamination with Aspergillus flavus

cirrhosis

Giardia lamblia
Prolonged diarrheal disease 2-stage life cycle flagellate trophozoite and chlorination-resistant cyst ~7% of population are carriers Can be present in water supply Shed by wild animals

Case 4

The patient was a 3-year-old female. Her mother was an elementary school teacher, and on school days the patient attended a day care center. The patient presented with a 3-day history of increasingly severe diarrhea with three episodes of vomiting. In the previous 24 hours, she had 12 bowel movements. On physical examination, the child was lethargic and appeared dehydrated. She had a temperature of 38.3C, blood pressure of 90/60 mm Hg, and a heart rate of 100 beats/min. The child was weighed and found to weigh 1lb (ca. 0.4 kg) less than she had at a well-child visit 6 months previously. She had grown approximately 1.5 inches (4 cm) during that time. A stool specimen was obtained during her clinic visit. The stool specimen was reported as being watery, and no white or red blood cells were seen on microscopic examination. Cultures for enteric pathogens were negative. A modified acid-fast stain of a fecal specimen is shown in Fig. 1. The child's diarrhea persisted for approximately 1 more week before resolving.

Case 4

Case 4

Organism? Similar?

Cryptosporidium parvum
EIA DFA

Detection?

Disease course, management?

Typical for immunocompetent Cholera-like illness Crampy abdominal pain? Rehydration Day care Humans, cattle

Source of infection?

Case 4

Large outbreaks?

Widespread Resistant to chlorination Low infectious dose

Return to day care?

Once diarrhea has resolved Continued shedding

Reduced morbidity and mortality in HIV?

HAART

Cryptosporidiosis
Cryptosporidium parvum:
Complex life cycle, chlorination resistant oocyst which release sprozoites that invade epithelial tissue
Moderate to profuse diarrhea Chronic in immunocompromised individuals, may become lifethreatening

Amoebic dysentery
Entamoeba histolytica:
Trophozoites live in large intestine
Severe invasion of epthelial cells produces dysentery

Complications include perforation of the intestine and extraintestinal invasion spread by blood to the liver and lungs

Tapeworms
Taenia saginata; beef tapeworm
Eggs ingested and form larval stage (cysticercus) in muscle, ingested by human, develops into tapeworm in gut

Taenia solium: pork tapeworm

Eggs can produce larval stage in human Cysterci can develop in many organs including eye and brain (neurocysticercosis)

Hydatid disease
Echinococcus granulosus:
Eggs migrate to various sites, formhydatid cyst, ~1cm in a few months Can be enormous, danger of anaphylactic shock if cyst ruptures

Nematode worms
Ascariasis Ascaris lumbricoides

Eggs ingested, larvae pass from intestine into blood stream, to the lungs, then are swallowed and develop into adults in intestine Hookworm Necator americanus, duodenale Feeds on blood and tissue, heavy load will cause anemia

Trichinosis
Trichinella spiralis
Severity proportional to number of larvae ingested, can be fatal

Fever, gastrointestinal upset, small hemorrhages under fingernails