Paralytic Shellfish Poisoning

By BW

Have you ever heard the culinary rule, “Never eat shellfish in a month which does not contain the letter ‘R’?” The origin of this phrase is contested, but many people believe that this is related to red tide algal blooms, which are most prevalent in the warm summer months (1). Red tide algal blooms are large oceanic populations of microorganisms. These blooms contain photosynthetic dinoflagellates, which are small, unicellular eukaryotic organisms. These organisms can inhabit shellfish, and produce a wide variety of toxins which can lead to severe illness in those who ingest the contaminated shellfish. There are four main kinds of shellfish poisoning: amnesic shellfish poisoning (ASP), diarrheic shellfish poisoning (DSP), neurotoxic shellfish poisoning (NSP), and paralytic shellfish poisoning (PSP) (2). PSP is the most lethal of these illnesses, as it has an estimated 8-9.5% mortality rate (3). It is caused by a dinoflagellate called Alexandrium tamarense, which produces a neurotoxin called saxitoxin (4). Due to the increasing global temperature and acidification of the ocean, a result of climate change, red tide may become a more relevant danger to the seafood industry, as these oceanic conditions favor the generation of red tide algal blooms.

Structure of a dinoflagellate. The transverse flagella wraps around the body of the organism,
while the longitudinal flagella extends behind the organism. Image obtained from here.

Dinoflagellates are unicellular eukaryotic organisms with a few unique characteristics. They have both a transverse and longitudinal flagella. The transverse flagella spans around the circumference of the organism, and allows for rotational and forward motion. The longitudinal flagella is located at the back end of the organism, and mainly acts as a rudder to help with control of movement, though it does provide some forward motion. Many dinoflagellates are photosynthetic and live in the water. They contain a wide range of photosynthetic pigments, ranging in color from green to a reddish brown. When certain species of these dinoflagellates appear in high concentration in the water, they cause the surface of the water to have a reddish brown appearance, leading to the classification of these algal blooms as ‘red tide’. As stated above, these dinoflagellates can cause people and animals alike to become ill if they ingest their toxins, which can accumulate in shellfish which live near the red tide (3). \

Alexandrium tamarense is one of these red tide dinoflagellates, and the etiology of the illness which it causes has to do with the toxin which it produces, saxitoxin. Saxitoxin is a neurotoxin, as it causes the malfunction of neurons in the human body by altering the function of sodium gated channels in the neuron which are vital to neuronal firing. This can cause feelings of numbness and tingling throughout the body, nerve dysfunction, nausea, vomiting, and in severe cases leads to death by respiratory failure, as the muscles which contribute to breathing are paralyzed (5). PSP can be diagnosed by examining the suspected infected tissues of a shellfish vector which was consumed by a patient experiencing PSP like symptoms, and subjecting this to an enzyme-linked immunosorbent assay (ELISA), which uses antibodies to detect the presence of the toxin (6). Treatment of PSP generally involves symptom management. If the patient is seen and diagnosed very early after ingestion of the contaminated food, then stomach pumping and administration of activated charcoal or a dilute bicarbonate solution can help to relieve the severity of the symptoms. If the patient is experiencing respiratory symptoms, then the patient is typically given respiratory support, which involves ventilatory support and administration of an anticurare agent, a class of drug which reverses neuromuscular paralysis (3).

Due to the relative isolation of PSP, as algal blooms typically form in small pockets along an oceanic coast, cases are very rare, but come in clusters. One of the largest outbreaks of PSP occurred in the summer of 1987 in Guatemala. A total of 187 cases of PSP with 26 associated deaths were reported at this time. It was found that the vector for this poisoning was Amphichaena kindermani, a species of clam which is commonly used to make clam soup. Children under the age of 6 had a much higher fatality rate than adults, at around 50 and 7% respectively. The lethal dose calculated for children was 140 µg/kg, which was much lower than previously reported lethal doses, and suggested that children may be more sensitive to PSP than adults. The contaminated clams were obtained by the victims of PSP through private fishing, meaning that they did not undergo commercial testing for the toxins produced by red tide dinoflagellates (7). This illustrates the dangers of private fishing, because most private citizens do not have the means to test their food for dangerous compounds prior to eating them, leaving them susceptible to shellfish poisoning.

Largest red tide algal bloom ever observed, near the western coast of the United States in 2015.
This photo was taken off the coast of La Jolla San Diego, California. Image from here.

Due to the rising global temperature, many experts believe that marine biotoxins may increasingly become a problem for the seafood industry in the coming years. Last year, in 2015, scientists discovered a toxic algal bloom off the coast of Washington, which they believe may be the largest ever encountered. Traveling from California to British Columbia, the bloom posed a threat to the numerous shellfish beds in that stretch of coast, which are harvested commercially for eating. The outbreak was thought to be due to the abnormally warm weather in that area last year, as well as the increasing acidity of the ocean, a problem which marine biologists believe is likely a consequence of climate change. The main biotoxic components of the bloom were domoic acid, DSP toxins, and PSP toxins, which was the first time these toxins were all observed off the coast of the state of Washington at one time. The coastal shellfish manager for the Washington Department of Fish and Wildlife, Dan Ayers, has been working with scientists and others in his field to attempt to develop a means to predict these toxic algal outbreaks, much like the tools which are used to predict hurricanes, which are based on characteristic weather patterns which have produced hurricanes in the past. Aside from acidity and water temperature, many other factors influence the growth of red tide algal blooms, including ocean current and wind speed and direction. However, Ayers notes that they are still significantly far away from an effective, predictive model (8). More information about the environment which produces toxic algal blooms is needed, so that we can predict and prepare for these algal blooms before it is too late.

While paralytic shellfish poisoning is a rare ailment, it may become increasingly relevant as climate change effects the marine ecosystem. For this reason, it is important that we know the warning signs of an Alexandrium tamarense outbreak, and that we understand what to do if someone ingests shellfish containing saxitoxin. It is also important to be mindful of the risks associated with ingesting shellfish which is not commercially tested for marine biotoxins, as the consequences could be lethal.

References

1. O’Connor, A. “The Claim: Never Eat Shellfish in a Month Without an R.” The New York Times. 22 July 2008. Web.
2. FAO Corporate Document Repo. Marine biotoxins. Food and Agriculture Organization. Web.
3. Fleming, L. E. Paralytic Shellfish Poisoning. NIEHS Marine and Freshwater Biomedical Sciences Center.
4. Hansen, P. J. (1989). The red tide dinoflagellate Alexandrium tamarense: effects on behaviour and growth of a tintinnid ciliate. Mar. Ecol. Prog. Ser. 53, 105-116.
5. Strichartz, G., Rando, T., Hall, S., Gitschier, J., Hall, L., Magnani, B., Hansen Bay, C. (1986) On the Mechanism by Which Saxitoxin Binds to and Blocks Sodium Channels. Ann. NY Acad. Sci. 479, 96-112.  
6. Garet, E., Gonzalez-Fernandez, A., Lago, J., Vieites, J. M., Cabado, A. G. (2010) Comparative Evaluation of Enzyme-Linked Immunoassay and Reference Methods for the Detection of Shellfish Hydrophilic Toxins in Several Presentations of Seafood. J Ag. Food Chem. 58, 1410-1415.
7. Rodrigue, D. C., Etzel, R. A., Hall, S., De Porras, E., Velasquez, O. H., Tauxe, R. V., Kilbourne, E. M., Blake, P. A. (1990) Lethal paralytic shellfish poisoning in Guatemala. The American Journal of Tropical Medicine and Hygiene. 42, 267-271.  
8. Doughton, S. “Toxic algae bloom might be largest ever.” The Seattle Times. 15 June 2015. Web.

PCP Outbreak and News Report (a dramatization)

by Matt Jorgensen

This last weekend an outbreak of Pneumocystis pneumonia was reported at St. Matthew’s Hospital in St. John’s, Minnesota. The disease has been found in the intensive care unit (ICU) and oncology floors of the hospital. The first case was documented around late Saturday night, with seven more cases popping up in the same department early Sunday morning. As of right now, there have not been any reported deaths caused by this outbreak, and all of us here at the station are hoping that continues. Based off studies on the disease, I advise all of you at home not to panic, however, you should understand the seriousness of this disease in a hospital setting. In order to lessen your worries and give you a better understanding of what is occurring, I am giving you all the information you will need to know about Pneumocystis pneumonia and help explain how the outbreak occurred.

To begin, I would like to make you familiar with the causative agent of Pneumocystis pneumonia (or PJP), Pneumocystis jiroveci, and why it’s important. P. jiroveci, although once thought to be a protozoan until 1988, was found to be a fungus that resides in the environment (1). Infection of P. jiroveci leads to PJP due to the colonization, or accumulation, of the fungus in the lower respiratory tract of the host (1). This is a very serious process and can lead to death. In fact, PJP is one of the leading causes of both morbidity and mortality in HIV patients, and is also the most common opportunistic infection in AIDs patients in the US (1, 2). The fungus is an opportunistic pathogen for humans, especially those who are diagnosed with HIV/AIDS (1). To be clear, an opportunistic pathogen is only able to infect human hosts who are immunocompromised, or when their immune system is weakened. Due to this, I suggest you not to worry at home and I will address this idea later in this article.

This may leave you asking “How does a deadly fungus like P. jiroveci get into a sanitized hospital?” It’s a fair question. You may not have known it at the time, but as children a majority of you were exposed to P. jiroveci while simply spending time outdoors, whether it be hiking, swimming, or playing sports. Also, P. jiroveci is commonly found in the environment, specifically in soil and water, and has the ability to infect human hosts/relocate itself through airborne fungal spores (2, 3). Therefore, the likely reasoning behind P. jiroveci accessing the patients in St. Matthew’s Hospital is through infection of an immunocompromised host through inhalation of airborne spores (which explains the outbreaks occurring in the ICU and oncology floors for those patients are all immunocompromised). The terrifying thing about P. jiroveci human to human transmission is it can infect another immunocompromised host up to 8 meters in distance away in hospitals (3). This leads to serious outbreaks in hospitals, like the one seen last weekend.

The severity of PJP is associated with the symptoms seen in infected human hosts, which everyone should be aware of and look for if need be. These symptoms can be mistaken for an average cold, and include weight loss, coughing, fever, dyspnea (or difficulty breathing), night sweats, and wheezing (4, 5). In terms of what happens inside the infected individual, the P. jiroveci goes through a cycle of trophozoites, precysts, and cysts stages (4). These cysts adhere to the epithelium, or outer layer, of the lung of the host, and can be seen by CT scans colonizing the lung (5). For those who are interested, I have attached CT scans from Kanne et al. depicting cyst formation along with ground-glass opacity below. These hazy, ground-glass opacities are nonspecific formations that show infection of the lung (6). (Left= cyst colonization, Right = ground-glass opacity) Theses cysts, especially when in high densities, lead to a triggered immune response by those who are infected, thus causing inflammation, irritation, and damage to the lungs. This is why the main symptoms associated with P. jiroveci infection are coughing and dyspnea, and therefore are what should be looked for when diagnosing infection.

There is good news, however, for there are medicines that can be used to fight PJP. Antimicrobials, like tri-methoprim-sulfamethoxazole (TMP-SMX), are the main treatment of choice when fighting a PJP infection (2). Also, corticosteroids, like glucocorticoids, have been shown to be effective in decreasing the inflammatory response of the host, and therefore lessening the likelihood of mortality (2). Luckily, the staff at St. Matthew’s recently received a shipment of both drug types, and therefore have been promptly administering the needed dosages.

CT scan showing P. jiroveci cyst colonization (white arrows) of infected patient.

http://www.ajronline.org/doi/full/10.2214/AJR.11.7329    

CT scan showing ground-glass opacity (black arrows) in lung of infected patient.

http://www.ajronline.org/doi/full/10.2214/AJR.11.7329

Many concerned family members and friends have called in asking about the status of their loved ones. I want to reiterate that the P. jiroveci fungus is an opportunistic pathogen, and therefore you should not be concerned if your loved one does not have a weakened immune response. To be more precise, previous studies have shown that the immunocompromised, especially those with HIV, have a much higher risk of PJP (7). The study showed that for patients with HIV, 100% of them were male and in their late 30s, while patients that were immunocompromised without HIV were equally male and female and in their 50s (7). This information is shown in Table 1. from the article Li et al, which I attached below.

These experimental characteristics are similar to the observed characteristics reported by the head administrator of clinical practice at St. Matthew’s, John Adams, of those impacted in the current outbreak. Of those with HIV in the ICU, almost 100% of them are male, and those who are immunocompromised on the oncology floor. The names of the patients impacted are private information, but family members have been contacted by St. Matthew’s officials.

Now that you are experts in P. jiroveci and PJP, I hope that you understand that although it is a very serious outbreak, there is no need to panic. Remember that P. jiroveci is an opportunistic pathogen, and therefore can only infect those who are already immunocompromised. Also, remember that all of us have already encountered P. jiroveci as children, and that the fungus is most likely all around us while we are outside in the environment. Now, that does not mean as readers you must ignore P. jiroveci, and its seriousness. There are more ways to be immunocompromised other than having HIV or receiving chemotherapy, like in the unfortunate case at St. Matthew’s, that lead to a weakened immune response and susceptibility to P. jiroveci infection. I have attached another table from Morris et al. that outlines certain risk factors that may lead to P. jiroveci infection due to a weakened immune response below. (PCP = the former name of PJP; COPD = Chronic Obstructive Pulmonary Disease)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346301/ 

I ask you to please take the time to look over these risk factors, to think about those being affected at St. Matthew’s currently, and to hold onto what you have learned today about the very serious and important fungus P. jiroveci. As a community, having knowledge about P. jiroveci may potentially save many lives. However, there is no current need to panic, for you are most likely not in any situation or state to be infected by P. jiroveci.

There will be updates concerning the outbreak throughout the week, here at Eukaryotic Microbiology News. I want to thank you as readers for taking the time to learn more about the significant microbe P. jiroveci, and I hope you won’t forget it.

Article References:

1.     Vanspauwen et al. Molecular epidemiology of Pneumocystis jiroveci in human immunodeficiency virus-positive and –negative immunocompromised patients in The Netherlands. Journal of Medical Microbiology. Pgs. 1294-1302, 2014.

2.     Morris et al. Colonization by Pneumocystis jiroveci and Its Role in Disease. Clinical Microbiology Reviews. Pgs. 297-317, 2012.

3.     Coyle et al. Rising incidence of Pneumocystis jiroveci pneumonia suggests iatrogenic exposure of immune-compromised patients may be becoming a significant problem. Journal of Medical Microbiology. Pgs. 1009-1015, 2012.

4.     Kaur et al. Pneumocystis pneumonia in HIV patients: a diagnostic challenge till date. Medical Mycology. Pgs. 587-592, 2015.

5.     Kanne et al. Pneumocystis jiroveci Pneumonia: High-Resolution CT Findings in Patients With and Without HIV Infection. Cardiopulmonary Imaging. 2011.

6.     Knipe et al. Ground-glass opacification. Radiopaedia.org, online website. Accessed 2 December, 2016. Pgs 1-2.

7.     Li et al. Pneumocystis jiroveci pneumonia in immunocompromised patients: Delayed diagnosis and poor outcomes in non-HIV-infected individuals. Journal of Microbiology, Immunology, and Infection. Pgs. 42-47, 2014.