Tuesday, August 15, 2017

Infections of the Gastrointestinal System

Back to more content-heavy Microbiology posts! Just like in previous posts, pathogens found on Microbe Invader will be shown in red.

Different types of gastrointestinal diseases

There are many different terms used to describe gastrointestinal diseases. Some are somewhat similar, so here's a list of definitions just to be clear.
  • Food poisoning/Food-borne illness: GI disease caused by the consumption of food containing pathogenic microbes, microbial toxins, or non-microbial toxins.
  • Food intoxication: Similar to food poisoning, but only refers to illness caused by consumption of toxins (not the microbes themselves).
  • Gastro infection: Disease of the gastrointestinal tract caused by the establishment and multiplication of microorganisms.
  • Gastroenteritis: Inflammation of the gastrointestinal tract.
  • Diarrhoea: I think you know what this one is...
  • Dysentery: Severe diarrhoea with blood and pus in the stool. Usually indicates an invasive pathogen. (Diarrhoea without blood and pus is usually from enterotoxin production.)
Most GI tract diseases cause fun symptoms like diarrhoea, nausea, vomiting, and abdominal discomfort. Pathogens can remain confined to the GI tract or infect other parts of the body. GI tract diseases can be spread from person-to-person via the faecal-oral route, or via water or food.

Mechanisms of bacterial diarrhoea

The main mechanisms of contracting bacterial diarrhoea are eating the toxins produced by the bacteria, or by simply eating the bacteria. Bacterial infections of the GI tract are more common during warmer months.

Bacterial toxins can be present in food even if the bacteria are dead. This is partly because many of them are heat-stable. Toxins can cause vomiting and other fun symptoms (like diarrhoea) within 1-6 hours. Some common toxin-secreting bacteria include S. aureus, B. cereus and C. perfringens. S. aureus secretes more than 20 enterotoxins that are most likely to be found in uncooked ready-to-eat foods, like sandwiches. B. cereus secretes an emetic (vomit-inducing) toxin most likely to be found in cooked rice that hasn't been stored properly. C. perfringens secretes an enterotoxin that is most likely to be found in meat and poultry that hasn't been stored properly. Store yo' food properly, kids!

The bacteria themselves can also cause damage to our GI tract. Usually, our stomach acid is strong enough to kill most things, but when our acid barrier is impaired for some reason (e.g. antacids, surgery, certain drugs), we may become more vulnerable. Some bacteria can invade the mucosa, causing death of the mature cells lining the gut. When this occurs, red blood cells and/or white blood cells may be excreted in the stool. Our immune system will often respond via an inflammatory response, confining the infection and mediating the release of prostaglandins. Prostaglandins activate cAMP and fluid secretion, contributing to diarrhoea.

Several bacteria commonly causing GI tract infections (eg. E. coli, C. difficile, Salmonella)

E. coli

There are many different pathogenic forms of E. coli:

  • Enteropathogenic (EPEC): Does not make toxins (that we know of). Attaches to epithelial cells, disrupting microvilli and causing diarrhoea.
  • Enterotoxigenic (ETEC): Produces heat-labile and heat-stable toxins.
  • Enteroinvasive (EIEC): Has a plasmid coding for invasiveness.
  • Verotoxigenic (VTEC): Produces a verotoxin which can cause diarrhoea and haemolytic uraemic syndrome (severe kidney damage- a medical emergency!).
  • Cell-detaching (CDEC): Causes cell-associated cytotoxicity.
Also, according to Microbe Invader, there's also EHEC (enterohaemorrhagic E. coli).

S. typhi and S. paratyphi 

S. typhi and S. paratyphi cause typhoid and paratyphoid, respectively. These are also known as enteric fevers, as they can hide in macrophages, circulate through the body, and cause systemic infection. It's also possible to be a healthy carrier of one of these microorganisms (e.g. Typhoid Mary).

Listeria

L. monocytogenes, which is a food-borne pathogen, causes listeriosis. It invades and replicates inside host cells and causes systemic infection. It often presents as meningitis. Pregnant women, the immunosuppressed and the elderly are more at risk of listeriosis.

Several viruses commonly causing GI tract infections (eg. Rotaviruses, adenoviruses, norovirus)

Viruses are the most common cause of gastroenteritis in young children. They are more likely to strike during cooler months. Virus replication in the gut causes death and sloughing of mature cells, exposing more immature cells underneath. These immature cells have poor absorptive capacity, resulting in everything coming out the other end (diarrhoea!). Most viral gastro is due to rotavirus or norovirus, so let's start with them!

Rotavirus

Rotavirus is the most common cause of viral gastro, though that may change given that a vaccine has been developed. After an incubation period of 1-2 days, the patient suffers fever, vomiting, and diarrhoea for 4-7 days. The death rate from rotavirus is very low because rehydration therapy is fairly effective at keeping people alive. Rotavirus has a low infectious dose (i.e. very few viral particles are needed to cause infection), and it is shed in large numbers in the faeces.

Norovirus

Norovirus is one of the most common causes of gastro in adults, but it tends to mainly crop up during outbreaks. Like rotavirus, it has an incubation period of 1-2 days, followed by nausea, cramps, diarrhoea, vomiting, and sometimes fever or headache. Also like rotavirus, it has a low infectious dose and can shed, even after recovery. It is treated with oral rehydration therapy (again, like rotavirus). Unlike rotavirus, however, norovirus does not have a vaccine. This is because norovirus has around 30 genotypes, making it difficult to develop a vaccine.

Astrovirus

Astrovirus causes relatively mild, self-limited infections, mostly in children. Fever and vomiting are less common in this illness as compared to rotavirus and norovirus.

Adenovirus

Adenovirus, like astrovirus, causes mild, self-limited infections, mainly in children. The main serotypes that cause infection are serotypes 40 and 41. Adenovirus has a longer incubation period and a longer duration of diarrhoea compared to the other viruses affecting the GI tract.

Types of specimens examined and diagnostic tests performed 

It's almost impossible to diagnose someone's gastro based on clinical presentation, as all gastro looks pretty similar. That's where lab tests come in! Common specimens used are stool, duodenal aspirates, blood, and rectal swabs. Rectal swabs are not the best, however, as we have so many commensal bacteria there that it's a bit difficult to "sort the wheat from the chaff," if you will. Macroscopic and microscopic examination of faeces can be done to look for blood, pus, or Charcot Leyden crystals (crystals that are indicative of a parasitic infection). Multiplex PCRs can be used to look for multiple pathogens at a time. (Note, however, that it is unrealistic to look for every pathogen that could cause a GI disease, as there are a lot. Risk factors are generally taken into account when deciding which tests to do.)

Here are some tests that can be done if certain species are suspected:

Salmonella or Shigella

Salmonella and Shigella can be distinguished by using certain selective media (XLD- Xylose Lysine Deoxycholate, HE- Hektoen Enteric, or DCA- Deoxycholate Citrate). An enrichment culture is required to grow Salmonella, but not Shigella. I'm not sure if we need to know all of the details of the enrichment culture required, but here they are: strontium chloride, and a sub-culture onto DCA and BSA (bismuth sulphite agar). S. typhi also requires selenite.

Campylobacter 

Campylobacter doesn't require enrichment, but it does need to be grown in a micro-aerophilic (3-4% oxygen) atmosphere on either Skirrow's or Butzler's media.

C. difficile

C. difficile diagnosis has three components: NAAT (nucleic acid amplification test), culture, and toxin detection. In NAAT, a PCR for toxin genes is performed. C. difficile is cultured on CCFA (cycloserine cefoxitin fructose agar) or ChromAgar under anaerobic conditions. Toxins are detected via tissue culture (to detect cytotoxins) or by ELISA (to detect enterotoxins).

Vibrio spp.

Primary culture can be done in TCBS (thiosulphate citrate bile sucrose). Depending on whether the species can ferment sucrose or not, the colonies will appear yellow or green. V. cholerae ferments sucrose, so it is yellow, whereas V. parahaemolyticus does not ferment sucrose, so it appears green.

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