Gastrointestinal Infections & Enteric Pathogens – Key Vocabulary
Enteric Pathogens Implicated in Diarrhoeal Illness
Comprehensive list of causative agents divided by biological class:
Viruses
Rotaviruses
Noroviruses
Adenoviruses
Astroviruses
Bocaviruses
Toroviruses
Coronaviruses
Protozoa
Giardia lamblia (aka G. duodenalis)
Entamoeba histolytica
Cryptosporidium parvum
Cyclospora cayetanensis
Bacteria
Enteropathogenic E.\ coli (EPEC)
Enteroaggregative E.\ coli (EAEC)
Shigella dysenteriae
Salmonella typhi
Vibrio cholerae
Campylobacter jejuni
Staphylococcus aureus
Yersinia enterocolitica
Clostridium difficile
Helminths (Worms)
Ascaris lumbricoides (roundworm)
Enterobius vermicularis (pinworm)
Trichuris trichiura (whipworm)
Taenia saginata (beef tapeworm)
Hookworms: Ancylostoma duodenale & Necator americanus
Intended Learning Outcomes (ILOs)
Recognise diseases caused without bacterial colonisation (toxinoses)
Explain infections by variably invasive bacteria with emphasis on Escherichia\ coli
Fully invasive, partially invasive, non-invasive categories
Introduce viral causes of GI infection (rotavirus, norovirus, etc.)
Summarise eukaryotic gastrointestinal (GI) infections (protozoa & helminths)
Toxinoses – Disease in the Absence of Colonisation
Concept: Illness produced solely by pre-formed toxins; no need for live bacterial growth in host
Key examples
Staphylococcus aureus food-poisoning enterotoxins
Clostridium botulinum toxins → botulism
Botulism
Rare yet life-threatening; characterised by flaccid paralysis of peripheral nerves
Causative agent: Clostridium botulinum
Gram-positive, motile rod; obligate anaerobe
Forms sub-terminal spores that germinate & secrete botulinum neurotoxin (BoNT) under low O_2
Latin "botulus" = sausage (historical link to smoked/sausage meat)
Clinical variants & pathogenesis
Food-borne botulism: ingestion of pre-formed toxin in improperly processed foods
Infant botulism: spores ingested 1 intestinal colonisation ➔ in-situ toxin release (honey a notable risk)
Wound botulism: spores contaminate wounds; anaerobic pockets support toxin production
Disease course & symptoms
Early: blurred vision, ptosis (drooping eyelids), dysarthria
GI upset possible with BoNT types B & E
Progresses to symmetrical descending paralysis; respiratory muscle involvement necessitates prolonged mechanical ventilation
Recovery may require months; mortality 5\text{–}10\% in developed nations
Prevention & treatment
Heat foods >85\,^\circ\text C for >5 min to inactivate toxin
No honey for children <12 months
Administration of equine-derived antitoxin ASAP
Metronidazole or penicillin for wound form (kills vegetative cells)
Mechanism of action (molecular)
BoNT serotypes (A–G) are Zn-dependent endopeptidases
Each cleaves specific SNARE proteins (VAMP/synaptobrevin, SNAP-25, syntaxin) inside cholinergic nerve terminals ➔ blocks acetylcholine release at neuromuscular junction ➔ flaccid paralysis
Medical/biotechnological applications
Local BoNT injections produce controlled paralysis for: hemifacial spasm, blepharospasm, strabismus, axillary hyperhidrosis, over-active bladder, cosmetic wrinkle reduction (Botox)
Escherichia coli – Diversity & Pathotypes
Gram-negative, facultative anaerobe; commensal & pathogenic strains coexist
Genomic plasticity: only \approx20\% of genes shared among all strains
Beneficial roles: synthesises vitamin K_2, confers colonisation resistance
Acquisition of mobile genetic elements (plasmids, phages, pathogenicity islands) transforms commensals into pathogens
Six major pathovars
Enteropathogenic (EPEC) – traveller’s diarrhoea
Enterotoxigenic (ETEC) – traveller’s diarrhoea
Enterohemorrhagic (EHEC) – O157:H7; haemolytic uraemic syndrome (HUS)
Diffusely adherent (DAEC) – characteristic long fimbrial extensions
Enteroaggregative (EAEC) – biofilm formation
Enteroinvasive (EIEC) – dysentery-like bloody diarrhoea
Serotyping criteria
O antigen (LPS), H antigen (flagellin), K antigen (capsule); e.g. O157:H7
>190 serotypes recorded; serotype ≠ phylogeny, so pathotyping (EPEC, etc.) preferred in clinical practice
Sources & transmission
Reservoirs: GI tracts of humans, cattle, pigs, amphibians, fish
Infections via under-cooked meat, unpasteurised dairy, contaminated produce, faecally polluted water
Non-Invasive Pathotypes (EPEC, EHEC, ETEC)
Remain on mucosal surface; no traversal of epithelium
Common molecular themes
Adherence to small intestinal mucosa (pili, fimbriae, adhesins)
Attaching & effacing (A/E) lesion formation (EPEC/EHEC) – pedestal actin rearrangements, microvilli effacement
Exotoxin release; in some cases toxin alone drives watery diarrhoea
Enterotoxigenic E. coli (ETEC)
Colonisation factors: pili, flagellar tip adhesin EtpA; tighter binding via Tia & TibA
Toxins: heat-labile (HLT) & heat-stable (HST)
HLT ➔ activates \text{adenylate cyclase} \Rightarrow \uparrow cAMP
HST ➔ activates \text{guanylate cyclase} \Rightarrow \uparrow cGMP
Both signal via CFTR to secrete Cl^-; water follows osmotically
EPEC & EHEC
Type III secretion injects effectors altering ion channels ( Cl^-, OH^-, Na^+ / H^+ exchangers ), mislocalises aquaporins, inhibits SGLT1
EHEC harbours Shiga-like toxin (SLT) encoded by lysogenic phage; tototoxic for intestinal & renal endothelial cells ➔ HUS (microvascular damage in kidneys)
EPEC may produce cytolethal distending toxin (CLDT) → host cell cycle arrest
Partially Invasive Pathotype – EIEC
Similar to Shigella spp.; invades colonic epithelium but usually confined to mucosa
Virulence traits
Entry via M-cells ➔ phagosome lysis ➔ cytosolic replication
Actin-based motility allows lateral cell-to-cell spread
Induces inflammatory dysentery with limited systemic invasion
Evolutionary intermediacy between classical E.\ coli & Shigella noted
Viral Gastroenteritis
Third leading global cause of child mortality
Dominant viral agents
Infants/children: Rotavirus (most severe)
Adults: Norovirus (most prevalent); adenovirus, astrovirus, sapovirus also contribute
Transmission routes
Faecal–oral: direct contact, aerosols from vomitus, contaminated food, water, surfaces, shellfish
Mortality trend improvements
1976!:\ 5 million deaths ➔ 2015!:\ 1.3 million (vaccines, ORT, sanitation)
Rotavirus Biology
Family Reoviridae; 11 dsRNA genome segments
10 species (A–J); group A infects children predominantly
Capsid: triple-layered, highly stable; >60 spike proteins enabling attachment & protease activation
Key proteins
VP7 (G-type) & VP4 (P-type) define serotype/host range
Non-structural: NSP1 (innate immunity modulator), NSP4 (enterotoxin & viroporin), others for replication
Infectious dose (ID_{50}) ≈ 10 viral particles; massive shedding in faeces
Rotavirus Pathogenesis
Targets mature enterocytes on small-intestinal villi
Consequences of infection
↓ brush-border disaccharidases (sucrase, maltase, lactase) → osmotic diarrhoea
NSP4 triggers Ca^{2+} release → cytoskeleton disruption, autophagy, tight-junction loosening, inhibition of SGLT1 glucose-sodium co-transport
Activation of enteric nervous system → secretion of fluid & electrolytes
Clinical spectrum
Incubation 24\text{–}72\,h; illness ranges from asymptomatic to severe dehydration
Nearly every child infected ≥ once by age 5; immunity increases with repeat exposures, adults rarely symptomatic
Rotavirus Vaccines & Control
First licensed vaccine 2006 (USA)
WHO-prequalified oral formulations: Rotarix, RotaTeq, RotaSiil, Rotavac
2006\text{–}2019: 139\,000 under-5 deaths averted; 2019 alone: 15\% fewer deaths
Universal 100\% coverage could prevent additional 83\,200 deaths
Oral rehydration therapy (ORT) remains life-saving, low-tech adjunct
Eukaryotic Gastrointestinal Pathogens
Giardia duodenalis (Giardiasis)
Global burden: \approx 200\,\text{million} infections, 500\,000 deaths annually
Higher prevalence (20\text{–}30\%) in developing vs 2\text{–}5\% in developed nations; children most affected
Transmission: ingestion of hardy cysts via water, food, faecal-oral hands/fomites; cysts survive months in cool water & warm climates
Life-cycle in host
Excystation in small intestine → each cyst releases 2 trophozoites
Trophozoites (2 nuclei, 8 flagella) replicate by longitudinal binary fission, adhere via ventral sucking disk → malabsorption, dysentery
Encyst during transit to colon; cysts + trophozoites excreted → diagnostic microscopy
Cryptosporidium spp. (Cryptosporidiosis)
Watery diarrhoea; severe in immunocompromised individuals
Main human species: C. parvum, C. hominis; broad zoonotic reservoir
Transmission chiefly via contaminated drinking/recreational water, occasionally food (e.g. chicken salad)
Soil-Transmitted Helminths (STHs)
Transmission: embryonated eggs/larvae in faecally contaminated soil where sanitation poor
General statistics: >1.5 billion people (≈24\% global population) harbour STHs
Light infections: asymptomatic; heavy loads → diarrhoea, abdominal pain, malnutrition, impaired development
Diagnosis: Kato-Katz thick smear; egg counts quantify burden
Treatment: benzimidazoles (albendazole, mebendazole) 1\text{–}3-day regimens
Hookworms (Ancylostoma duodenale, Necator americanus)
Infected population: 576\text{–}740\,million
Life-cycle
Eggs hatch in soil (moist, shaded) → L3 filariform larvae in 5\text{–}10 days; survive 3\text{–}5 weeks
Penetrate skin (usually feet) → bloodstream → lungs → trachea → swallowed → mature in distal jejunum
Adults live 1\text{–}2 years; size 8\text{–}15\,\text{mm}
Clinical
Entry itch & rash, iron-deficiency anaemia, stunted growth in children & pregnant women
Ascaris lumbricoides (Ascariasis)
Most prevalent helminth: 807\text{–}1.2 billion infections
Biology
Adults: females 20\text{–}35\,\text{cm}, males 15\text{–}30\,\text{cm}
Pre-patent period ≈ 2\text{–}3 months; each female sheds 200\,000 eggs/day; lifespan 1\text{–}2 years
Larval pulmonary migration causes cough; adults may obstruct biliary tract, appendix, intestine
Trichuris trichiura (Trichuriasis)
Global load: \approx 800\,million
Adult worm fixed in cecum/ascending colon; anterior thread-like portion embedded in mucosa
Life-cycle details
Eggs embryonate in soil 15\text{–}30 days
Females begin oviposition 60\text{–}70 days post infection; shed 3,000\text{–}20,000 eggs/day; adult lifespan ≈ 1 year
Heavy paediatric infections → Trichuris dysentery syndrome (pain, diarrhoea), possible rectal prolapse
Summary Points
Intestinal microbiota provide colonisation resistance yet diverse pathogens (bacteria, viruses, protozoa, helminths) circumvent defences causing diarrhoea/vomiting
Toxinosis (e.g. botulism) illustrates pathology without colonisation; management hinges on toxin inactivation/neutralisation
E.\ coli demonstrates spectrum of invasiveness & molecular virulence strategies; Shiga toxin of EHEC exemplifies phage-encoded extraintestinal danger (HUS)
Viral gastroenteritis remains major paediatric killer; rotavirus vaccines + ORT markedly reduce mortality
Eukaryotic GI pathogens contribute heavy global burden; control via sanitation, anthelmintics, water safety crucial
Further Reading
Croxen MA & Finlay BB (2010) Molecular mechanisms of E.\ coli pathogenicity. Nat Rev Microbiol 8:26–38
Ramig RF (2004) Rotavirus pathogenesis. J Virol 78:10213–10220
Our World in Data – Diarrhoeal diseases statistics
Else KJ et al. (2020) Whipworm & roundworm infections. Nat Rev Dis Primers 6:44
Example Exam Question
"Compare and contrast gastrointestinal diseases caused by bacterial infection and by bacterial toxins alone (toxinoses). Discuss risk factors, treatment options & patient outcomes."