Mednotes

L19 I&I Infection and Diarrhoea

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tagsinfectionandimmunity, lecture
aliasesL19 I&I Infection and Diarrhoea

13 min read

Overview

This lecture covers the microorganisms that commonly cause infectious diarrhoea in Aotearoa/New Zealand and globally: the viruses Rotavirus and Norovirus, and the bacteria Campylobacter, Salmonella, Shigella, Yersinia and diarrhoeagenic E. coli. For each it covers transmission, incubation, disease course, pathogenesis (where known) and treatment, then closes by comparing them on clinical presentation, diagnosis and treatment principles.

Burden and classification of infectious diarrhoea

  • Major global cause of morbidity and mortality: WHO estimates 6-60 x 10^9 infections/yr (~50,000/min) and 1.2 x 10^6 deaths (2021); highest burden in low- and middle-income countries, where malnourished children are especially at risk (diarrhoea accounts for 9% of all deaths in children <5 yrs).
  • In NZ: commonly notified but under-reported; estimated 4.5 x 10^6 infections/yr; many gastrointestinal pathogens are zoonotic (of animal origin).
  • 2020 notification rates per 100,000: Campylobacteriosis 107.6, COVID-19 44.2, Yersiniosis 25.6, Giardiasis 23.2, EHEC 17.2, Cryptosporidiosis 14.9, Salmonella 14.4.
  • Aetiological categories in NZ:
    • Non-infectious (preformed toxin ingestion, “food poisoning”): S. aureus, B. cereus, C. perfringens
    • Bacterial: Campylobacter, Salmonella, Shigella, Yersinia, E. coli (EHEC), Listeria monocytogenes, Clostridioides difficile
    • Viral: Norovirus, Rotavirus
    • Protozoa (covered elsewhere): Cryptosporidium, Giardia
    • Other, non-GI infections that can present with diarrhoea/gastro symptoms: sepsis, meningitis, respiratory tract infection, legionellosis
  • All these categories converge on a shared symptom picture: nausea, abdominal pain/cramps, vomiting, diarrhoea, fever, headache/weakness.

Rotavirus

  • Most common cause of diarrhoea in children worldwide; >500,000 children <5 die/yr, with 30% mortality in malnourished children.
  • Highest rates in infants/young children: most NZ children infected by 2 yrs; 80% have antibodies by 3 yrs. The 2014 national vaccine schedule is 75-90% protective against severe disease. Adults typically have mild disease.
  • Faecal-oral transmission; as few as ~10 virions may be infectious. Outbreaks occur in susceptible settings (daycare, nurseries, preschools). The virus is stable in the environment, contaminating food, water and fomites.
  • Disease: 24-48 hr incubation, then abrupt onset of vomiting and profuse watery, non-bloody diarrhoea (10-20 episodes/day), lasting 4-8 days. Severe dehydration/electrolyte imbalance can occur in susceptible individuals.
  • Treatment: rehydration (oral, nasogastric, or IV) depending on severity/hospitalisation.

Norovirus

  • Most common cause of gastroenteritis globally; highly infectious and spreads rapidly — <10 virions may be infectious, and ~50% of people exposed to a single virion become infected.
  • Transmission: faecal-oral; contaminated water/food; can persist on surfaces/fomites (relatively resistant to disinfection, viable after heating to 60°C or freezing).
  • Outbreaks are associated with institutions: hospitals, nursing homes, restaurants, sporting events, cruise ships. Despite the “cruise virus” reputation, most outbreaks occur in healthcare facilities (~61%) and restaurants (~22%), versus ~0.18% on cruise ships; risk of infection on land is about 1 in 15 versus 1 in 5,500 for a lab-confirmed case in a shipboard outbreak.
  • Disease: 24-48 hr incubation, then acute onset of vomiting, watery non-bloody diarrhoea, abdominal cramps and nausea, usually lasting 2-3 days. ~30% of infections are asymptomatic while still excreting viable virus, raising the question of ongoing transmission.
  • Treatment: generally mild and self-limiting; rehydration, with hospitalisation/IV rehydration in severe cases (children, elderly, immunocompromised). Immunity is strain-specific and not long-lasting, so repeated infections occur throughout life. Vaccines are in clinical trials.

Campylobacter

  • C. jejuni (>80% of infections): a motile, gram-negative spiral rod.
  • Most notified disease in NZ (33% of all notifications in 2019); 6089 notified cases in 2023 (117/10^5), down from a 2006 peak of 384/10^5; higher than Australia’s 2019 rate of 145/10^5. Notified cases understate true incidence by an estimated 10-30x.
  • Routes of infection: ingestion of contaminated food (undercooked poultry accounts for 85% of NZ cases; also red meat, unpasteurised milk); direct contact with poultry, livestock, pets, or person-to-person (faecal-oral); waterborne (contaminated drinking or recreational water).
  • Epidemiology: infections peak in summer; bimodal age distribution peaking at 0-4 yrs and 15-29 yrs; asymptomatic infection is common (25%), particularly in children 5-14 yrs, who may act as a reservoir.
  • Disease: incubation 2-7 days; prodromal flu-like symptoms (malaise, headache, fever, myalgia, arthralgia); then acute onset of severe cramping abdominal pain, nausea/vomiting, and watery diarrhoea +/- blood (10+ episodes/day). Two distinct diarrhoea patterns suggest different pathogenic mechanisms:
    • Secretory: profuse, watery stools (jejunum/ileum)
    • Dysentery-like: blood, mucus, white blood cells (colon)
  • Pathogenesis (stepwise): motility allows penetration of the mucus layer; adhesion via LPS, pili and fimbriae; invasion of epithelial cells (mechanisms not well understood, but important for disease). Bacteria translocate across tight junctions, partially resist neutrophil phagocytosis, release IL-8 and pro-inflammatory cytokines, and interact with macrophages (inducing apoptosis). Proposed toxins (both hypothesised):
    • Cholera-like enterotoxin: activates adenylate cyclase → increased cAMP → efflux of Cl-/Na+ → water loss → watery diarrhoea
    • Cytolethal distending toxin: DNase activity → apoptosis and cell death → bloody diarrhoea
  • Treatment: self-limiting, lasting 2-21 days; severe dehydration treated with fluids/electrolytes. Antimicrobial treatment is controversial (reduces symptoms by only ~1 day): erythromycin, or ciprofloxacin (resistance common). Treat only if infection is persistent, diarrhoea is bloody, or the patient is at risk (elderly, children, immunocompromised).
  • Complications: reactive arthritis, bacteraemia, and (rarely) Guillain-Barré syndrome — an acute autoinflammatory demyelinating condition affecting the peripheral nervous system.

Salmonella

  • Two clinically distinct patterns depending on serotype:
    • Typhi/Paratyphi: causes systemic illness (enteric/typhoid/paratyphoid fever). Bacteria cross the gut mucosa (via Peyer’s patches) into mesenteric lymph nodes, then disseminate via the bloodstream (bacteraemia) to secondary sites (liver, spleen, gallbladder, bone marrow). Humans are the only reservoir; transmitted via food/water contaminated with human faeces. Incubation 1 week to 1 month. Features: high fever, anorexia, fatigue, headache, abdominal pain, vomiting, rose-spot rash, dry cough, hepatosplenomegaly, chills, convulsions, delirium; constipation is more common than diarrhoea. Mortality 10-20% if untreated. Asymptomatic carriage occurs in 5%, with a gallbladder reservoir. A vaccine is available for travel to endemic regions (SE Asia, India/Pakistan/Bangladesh, Central & South America, Africa, PNG).
    • Typhimurium: causes gastroenteritis without systemic infection — invades but does not cross the gut mucosa. Associated with contaminated chicken, eggs, milk, meat, water, and pet contact. Incubation 12-36 hrs: abdominal pain, watery diarrhoea, vomiting, fever; mild, self-limiting, confined to the small bowel. Can produce typhoid-like disease in immunocompromised patients (elderly, children).

Shigella

  • S. sonnei: mild, self-limiting infection confined to the small bowel; spread person-to-person and via fomites; causes outbreaks in childcare centres and kindergartens.
  • S. dysenteriae: causes more serious disease (dysentery); uncommon in NZ. Shiga toxin (Stx) disrupts protein synthesis → apoptosis and cell death → ulceration of the large bowel → blood and mucus in stools.

Yersinia

  • Yersinia enterocolitica: zoonotic, carried by domestic animals (pigs, pets); transmitted via pork, untreated water, unpasteurised milk.
  • Clinical presentation is age-related:
    • Children (1-5 yrs): mild, self-limiting — fever, diarrhoea, abdominal pain
    • Adolescents/adults: fever, abdominal pain, colitis with ulceration; can mimic acute appendicitis
  • Higher incidence in those with cirrhosis, diabetes, or HIV/AIDS.
  • NZ notifications have risen substantially, from ~400-600/yr (2004-2013) to ~1300-1400/yr by 2022-2023 — a distinct long-term upward trend compared with other notifiable diarrhoeal pathogens.

Diarrhoeagenic E. coli

  • E. coli causes disease by acquiring specific virulence factors; several pathotypes exist, only some endemic to NZ:
    • Enteropathogenic (EPEC) — endemic to NZ
    • Shigatoxin/Verotoxin-producing (STEC/VTEC/EHEC) — endemic to NZ
    • Enteroinvasive (EIEC) — not endemic
    • Enteroadherent (EAEC) — not endemic
    • Enteroaggregative (EAgEC) — not endemic
    • Enterotoxigenic (ETEC) — not endemic
  • EPEC: causes an attachment/effacement lesion on epithelial cells, altering Cl-/HCO3- ion secretion, damaging tight junctions and reducing absorptive surface, and recruiting neutrophils, together increasing epithelial permeability and causing diarrhoea (exact pathogenesis not fully certain). Causes traveller’s diarrhoea and infantile diarrhoea.
  • EHEC: produces Shiga-like toxin (Stx) (also called STEC/VTEC). Bacteria and released Stx cross the epithelium (via M cells and dendritic/macrophage uptake in Peyer’s patches into the lamina propria), enter the bloodstream, cause macrophage apoptosis, and have downstream effects on kidneys, GI tract and brain.
  • EHEC disease: mild to severe non-bloody diarrhoea that may progress to haemorrhagic colitis (blood, mucus), with vomiting, nausea, and abdominal distension.
  • EHEC complications — Stx damages small blood vessels, causing:
    • Haemolytic uraemic syndrome (HUS): predominantly children <5 yrs; acute renal injury, haemolytic anaemia, thrombocytopenia. Mechanism: toxin damages capillary lining → platelets clump and form a mesh in capillaries → damages red blood cells and obstructs blood flow → organ dysfunction/failure.
    • Thrombotic thrombocytopenic purpura (TTP): platelet clots form in blood vessels (including brain and kidney) → clots rupture red blood cells → ischaemia of CNS/kidney and other organs supplied by affected small vessels.

Clinical patterns, diagnosis and treatment

  • General clinical clues:
    • Watery diarrhoea suggests small bowel involvement; frequent stools with blood/mucus suggest large bowel involvement.
    • Most infections resolve spontaneously in 2-7 days and rarely require hospitalisation or treatment; children are at particular risk of severe dehydration.
    • Bacteraemia occurs in a minority, mainly the immunocompromised/elderly, and in typhoid/paratyphoid fever.
    • Serious complications are rare but include reactive arthritis, Guillain-Barré syndrome, HUS, and sepsis.

  • The lecture's comparative table of incubation period, duration and symptoms by pathogen (Salmonella, Campylobacter, Shigella, Vibrio cholerae, Clostridium perfringens, Bacillus cereus diarrhoeal/emetic forms, Yersinia, EPEC, ETEC, EHEC, EIEC) had some cells that were small and partially difficult to resolve at the rendered scale; values should be checked against the original slide if needed for fine-grained recall. Its overall point: clinical presentation alone often cannot distinguish between these pathogens.

  • Diagnosis: usually not required, since most infections in healthy people are mild and self-limiting. Differential diagnosis is difficult owing to overlapping symptoms:
    • Severe abdominal pain/dysentery → suggests Campylobacter or EHEC
    • Presentation mimicking appendicitis (right iliac fossa pain) → suggests Yersinia or Campylobacter
    • Typhoid/paratyphoid may not present with diarrhoea at all — travel history is important
    • Testing is indicated if infection is prolonged, severe, requires hospitalisation, or the patient is immunodeficient (very young/old).
    • Laboratory methods: PCR (detects multiple bacterial, viral and parasitic pathogens in the same sample), culture (selective media to isolate pathogens from normal microbiota), toxin detection, serology (antigen detection in faeces).
  • Treatment: most infections in healthy people are self-limiting and antimicrobials have minimal effect on duration. Treatment is indicated for typhoid/paratyphoid, neonates/elderly, severe disease (blood in stool), immunocompromised patients, or bacteraemia.
    • Supportive care: rehydration and electrolytes, especially for infants/elderly/immunocompromised. Antimotility agents are not typically recommended, as they prolong contact with toxins.
    • Specific antimicrobials: Salmonella, Yersinia and Shigella → fluoroquinolone; Campylobacter → erythromycin.
    • EHEC: antimicrobials are contraindicated, since Stx released from dying/dead E. coli may increase the risk of HUS.
    • No effective antivirals exist for Rotavirus or Norovirus.

Self-test

  1. Compare Rotavirus and Norovirus in terms of typical incubation period, duration of illness, and who is most severely affected.
  2. Describe the routes by which Campylobacter is transmitted, and explain why undercooked poultry is particularly significant in NZ.
  3. Distinguish the secretory and dysentery-like forms of Campylobacter-associated diarrhoea, including where in the gut each arises.
  4. Describe the stepwise pathogenesis of Campylobacter infection, from initial contact with the mucus layer through to toxin-mediated effects.
  5. Distinguish the disease caused by Salmonella Typhi/Paratyphi from that caused by Salmonella Typhimurium, including whether the gut mucosa is crossed.
  6. Explain why constipation, rather than diarrhoea, can be a feature of typhoid fever.
  7. Distinguish the disease caused by Shigella sonnei from that caused by Shigella dysenteriae, and describe the mechanism of Shiga toxin.
  8. Describe how the clinical presentation of Yersinia enterocolitica infection differs between young children and adolescents/adults.
  9. List the diarrhoeagenic E. coli pathotypes endemic to NZ, and describe the pathogenic mechanism of EHEC from initial toxin release to systemic effects.
  10. A 4-year-old presents with bloody diarrhoea, and several days later develops acute renal injury, haemolytic anaemia and thrombocytopenia. Name this complication, the toxin responsible, and the organism most likely to cause it.
  11. Explain why antimicrobial treatment is generally not recommended for most diarrhoeal infections, and why it is specifically contraindicated in EHEC infection.
  12. A patient presents with right iliac fossa pain resembling appendicitis. Which two organisms discussed in this lecture should be considered, and why is diagnosis of diarrhoeal disease generally difficult based on presentation alone?

Answers

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