Gee Wiz

Less wizzing and more of number 2, but still. I also couldn't say Gi Wiz cause a Gi is an actual thing and it would be pronounced gee for it to make sense. Would you like to hear me ramble on for a while longer? I can you know. Why Gee? Because giardia that's why. I could also have made a joke about smiling, but nah. Why you ask again? Because giardia is also known as the "smiling parasite" since it is always in a good mood probably. 

Giardia is an anaerobic, flagellated parasite that lives in the small intestines of many animals around the world. Dare I say, it is almost cute looking. While there are many species of giardia, giardia lambila most commonly infects you humans. I mean we humans.....The parasite thrives in the lumen of our small intestine but is hardy enough to live outside of the body. It is adept at surviving in the environment in a cyst stage, not at all like the cysts on Dr. Pimple Popper, but rather a dormant form of the parasite. During the encystment (going into cyst form, I think giardia needs a leaf stone) the metabolic processes slow or stop to allow the cell to survive in hostile environments. Kinda like a bear in hibernation or me in the winter. Once the cyst comes back to a hospitable place, it explodes out like the Kool-Aid man through a brick wall. Maybe not but it does break down the cyst wall so I imaging the red pitcher doing his thing. 

While in this protective cyst stage, not only is the giardia able to survive outside the host, but it is also able to survive common cleaning agents like chlorine. The best is bleach or boiling to kill the buggers but given that they are larger than most bacteria (the cysts that is) filtration can work as well. If those don't seem exotic enough for you, UV light and ozone can also be used, as if those were actually exotic. These cysts are what start the process of infection as they are ingested and take a ride to the intestines through the stomach acid. Once in the intestines, see the Kool-Aid man reference above, the cyst experience excystation and out come the trophozoite. These are the form that reproduce and start colonization. Where do they come from so as to get into the intestines? Everywhere. Uncooked contaminated foods and contaminated water are the two major sources. 

When in the walls of the intestine, the Giardia starts to cause chaos. First, the brush border of the intestine gets degraded, its enzymes are broken down and become much less effective. The brush border is what you'd imagine, the microscopic surface of the intestine looks like a brush from all the microvilli that increase the surface area and help break down and absorb nutrients from the food we eat. Or lack of nutrients depending on your diet. Next the Giardia causes damage to the epithelial cells of the intestine and this brings T lymphocytes to the area to take out the damaged cells. This leaves holes in the wall or more appropriately, intestinal permeability. All of this is compounded by some science stuff about programmed cell death, nitric oxide, and the protein Bax. Non of which I know enough about but just believe me, it's sciencey and truthy. 

All this damage means less absorption of nutrients leading to malnutrition in serious cases, and diarrhea in most. When nutrients are not absorbed, weird stuff happens to the stool so as if diarrhea wasn't bad enough, it tends to be greasy and floats due to undigested fats and proteins. Otherwise just think of all the abdominal symptoms that come to mind, gas, cramps, nausea, vomiting, these are all common with Giardiasis (infection with Giardia). You can get other symptoms, fever, pruritus, and hives but these are not as common. While this is bad enough, chronic infections can lead to much more chronic, yes I did, effects, some of which may be lifelong. 

Malnutrition will have to be a post on its own, but for those of us in hospital settings, we know how harmful even moderate hypo/hyper electrolyte levels can be. With the outflow of water, this is a major risk as if lack of water was not bad enough. Now start to take away other nutrients. Say hello to anemia from lack of B vitamin absorption, inflammation and slow healing times from vitamin A deficiency, and a host of hormonal imbalances, inflammation, and subsequent vitamin deficits from a lack of fat absorption. These are hard enough for a healthy adult to deal with, now apply something like hormonal issues to a kid entering puberty or just growing, not a pediatric nurse but that ain't good y'all. Slower wound healing? Do older adults need help not healing faster? Aside from older adults, if a kid doesn't heal correctly there can be long term issues, think about fractures that don't heal up right. Cuts and the like may not heal leading to increased risk of other infections from the environment. 

Over in more affluent nations we have less to worry about as you can now get antibiotics/antiparasitics cheaply and quickly, sometimes online, so treatment can be swift. Other areas, this is not the case. Cost is a big factor, but in some places where antibiotics are OTC, you may not be getting the real deal or the advertised dose leading to inadequate "treatment" or treatment failure. Not only does this lead to chronic infections, but can drive resistance to Giardia and many other bugs. Let's say the unlucky soul who use the fake/underpowered antibiotics finally goes to a doctor due to intractable diarrhea, the infection might be resistant leading to the need for more expensive and/or toxic drugs. 

Generally the drugs used are metronidazole, tinidazole, albendazole, medendazole, and nitazoxanide to name a few. Other options include paromomycin and quinacrine to name a few. These drugs are often given as a single large dose or a short course to treat symptomatic Giardiasis, unless resistance is present. The current guidance is to use second and subsequent lines of therapy with the drugs not used, possibly in combination of the resistance characteristics warrants it. Speaking of resistance, I've talked about resistance by bacteria and cancer cells but parasites introduce new methods of resistance into the mix. 

There is not a vast array of work going into the study of Giardia resistance given the course of diseases is generally benign, unless you don't have a good toilet read in your bathroom. However, this realm of study is important for those of us whose immune systems cannot take care of the infections on our own. If I understood the science of Giardia resistance better it would be cooler, but the short version is that most of the anti-Giardial drugs used need to be activated by the parasite. Where as some bacteria modify the binding sites of antibiotic targets, Giardia looses or reduces the enzymes produced that would activate different medications. Like baking soda and vinegar, together you get your grade school volcano or natural drain-o, take away the soda and you just get vinegar smell every where and no reaction. In the same way, Giardia ferredoxin activated metronidazole, which kills the Giardia, so Mr. G-man might just loose the ferredoxin. 

I hope everyone has a fantastic week and no one gets Giardia, though if you do you can read all my blog posts while you sit on the toilet. Just saying, might as well put the time to good use. Bye. 

References

Assessment of prevalence of Giardia lamblia infection and its associated factors among government elementary school children from Sidama zone, SNNPR, Ethiopia by Hajare et al., in PLoS One March 2022

Burden and Epidemiology of Human Intestinal Giardia duodenalis Infection in Colombia: A Systematic Review by Fusaro et al., in MDPI the Journal of Tropical Medicine and Infectious Diseases September 2022

The Secretion and Action of Brush Border Enzymes in the Mammalian Small Intestine by Hooton et al., in the Reviews of Physiology, Biochemistry, and Pharmacology 2015

Treatment-refractory giardiasis: challenges and solutions by Lalle & Hanevik. in Infection and Drug Resistance October 2018

Treatment of Giardiasis by Gardner & Hill in the 13th edition of the Manual of Clinical Microbiology 2001

Giardia and giardiasis from the WHO, NIH, StatPearls, CDC, and ASM website pages

Giardia duodenalis: Biology and Pathogenesis from the ASM mSphere by R. Adams in 2021

Giardiasis by Desai in JAMA April 2021

Giardiasis-why do the symptoms sometimes never stop? by Robertson et al., in Trends in Parasitology January 2010

Image of Giardia trophozoites 100x magnification by Nohynkova in PLoS Neglected Tropical Diseases May 2014

Removing Giardia Cysts from Drinking Water by Swistock at PennState University August 2022

Shaping the intestinal brush border by Crawley et al., in the Journal of Cell Biology November 2014

Substandard and falsified antibiotics: neglected drivers of antimicrobial resistance? by Zabala et al., in BNJ Global Health 2022