Ports of entry for infectious pathogens in human disease

Statistics and Part Maintenance

L. Jones

Infectious Bacteria, Viruses, Eukaryotes:

When one considers the possibilities of human disease, be it originating from a virus, bacteria, or even eukarote, it is important to first consider possible ports of entry. Most disease causing organisms prefer specific entry points to gain access to their hosts. These entry points are known as "ports of entry" that are particularly vulnerable to the offending organism. This means that whereas a particular virus, bacteria or parasite may be relatively harmless if it comes in contact with the skin, for example, may be extremely infectious should it gain entry into the mouth.

Indeed, the specialized preferences of many organisms with regard to ports of entry are so consistent that it is often taken as a hallmark of a particular organism in the diagnosis phase. This is especially important when one notes that the symptoms of characteristic of a specific infection usually give clear clues as to the point of entry. Although it is important to consider the point of entry when diagnosing the cause of illness in a patient, it can also be important for many aspects of disease prevention, especially when a high risk for a particular organism is present in one's environment. For example, if one knows that he or she is working in an environment where there is a high incidence of an airborne pathogen, steps can be taken (the wearing of masks the use of patient isolation procedures for example) to minimize possible exposures to that pathogen.

Typical portals of entry include the mouth, ears, eyes, urethra, nose and skin. Non-typical portals might include wounds, broken skin, insect bites, or even animal bites or stings. For example, the herpes virus can be acquired through the eyes and mucus membranes, parasitic amoebas can be introduced through the nose, and rabies can be acquired through the bite of an infected animal. Additionally, even the way in which an organism can gain entry into a particular portal can vary. For example, the mouth can act as an entry point for a pathogen that survives on surfaces or food and water, as a skin entry point should the mouth tissues be injured, or even as an entry point for organisms that survive in the air or in aerosol form.

Although in today's bioterrorism age, much emphasis is placed on the perils of airborne pathogens (anthrax, for example), one of the most likely sources of illness are contact-based. This is especially true of some of the most interesting (and potentially damaging) diseases are acquired through the mouth, and, by extension, passed on to the gastrointestinal system. Three of these include Escherichia coli or "E. Coli" (a bacteria), Hepatitis a (a virus), and Guardia lamblia (a eukaryote).

The Mouth and Gastrointestinal Tract:

Defense Mechanisms

Although many infectious organisms can enter trough the mouth, there are actually several "defense mechanisms" designed to prevent disease. First among these are the various microbes that normally "set up house" in the mouth. These are usually "symbiotic" in that their existence in the mouth both benefits the microbe, as well as the host (the human) in that their presence there prevents other organisms (many potential pathogens), from moving in (Hulbert, 1999). Further, the presence of saliva serves to continually flush microbes into the stomach (which can either help or harm matters).

The stomach itself also has very effective defense mechanisms, foremost among them the presence of stomach acid which kills many infectious microbes. Beneath the stomach, the small intestine also contains substances (digestive enzymes and bile) which serve to destroy many microbes as well. Additionally, the anaerobic atmosphere of the small intestine also functions to "kill off" oxygen dependent microbes quickly (Hulbert).

Even the last leg on the gastrointestinal tract, the large intestine acts to prevent infection through its protective mucus layer, which protects the cells lining the walls of the large intestinal tract. This is particularly remarkable when one considers that the end product arising out the large intestine (feces) weighs in at about %40% bacteria (Hulbert). Additionally, it is also in this area that one of the most obvious defense mechanisms against infection occurs, namely diarrhea. However, like the defense mechanism of the upper GI tract (vomiting), it must also be noted that without proper fluid and electrolyte maintenance, these defenses can actually do more harm than good to the patient. In severe cases, they can even lead to due to dehydration or heart problems.

Taxonomy

Unlike illness resulting from E. coli bacteria, the illness arising from Hepatitis a infection results from a virus. Specifically, Hepatitis a is known as an enteric virus. It belongs to the genus Hepatovirus, and resides in the family Picornaviridae (ICTV, 2002). The morphological properties of the virion are non-enveloped, with isometric Necleocapsids 27 nm in diameter. The symmetry is icosahedral, with the Nucleocapsids round in shape. Further, there are 12 capsomers per neucleocapsid (ICTV). Additionally, the virions each hold one molecule of linear positive-sense single stranded RNA, with a total genome length of 7500 nt, and a hairpin structure (ICTV).

Treatment and Prevention:

The impact of the Hepatitis a can vary from mild to serious illness. It is normally transmitted by the ingestion of contaminated food or water which has come in contact with the feces of a carrying person (again, usually through bad hand washing, or poor sewage systems). The symptoms vary, but usually result in liver involvement causing weakness, loss of appetite, nausea, fever and jaundice. Severe reactions can lead to liver damage, failure, and even death. Unfortunately, there is no specific (or effective) treatment for Hepatitis a Instead, physicians are relegated to supportive care, including bed rest, nutritional care, and prohibition of alcohol (which affects the liver). Even in severe cases when serious hepatic complications occur (including liver failure), the patient is mainly supported to maintain liver function as much as possible. This may mean limiting protein as well as sodium. As indicated previously, even a liver transplant may be necessary.

Although the virus is typically acquired through oral contact (it can be transmitted via blood, but such transmission is very rare (Deodhare, 2000). Instead, the majority of patients become infected through the fecal/oral route, with the severity of the illness seemingly dependant on the strength of the immune system, the overall health of the liver, as well as unknown factors.

Finally, there are no significant defense mechanisms found in the mouth or GI tract against the virus. However, one of the best ways to prevent infection with the virus is trough a very effective Hepatitis a vaccine, available virtually worldwide. After one recovers from hepatitis a, though, the immune defense system ensures protection from further attacks in the future. This is because, like many viruses, individuals who do become infected become immune following recovery through the development of antibodies. Additionally, the disease may be prevented in many people by an injection if immune globulin, which contains "ready made" antibodies against the virus. However the protection afforded by IG is short-term (Carmel, 2004), and does not produce the antibodies in the body that would occur during an infection or during a reaction to the vaccine.

Guardia lamblia

Guardia is extremely common in incidence worldwide, and is the most oft-cited cause of non-bacterial diarrhea within the U.S. (USDA, 2004). Like the organisms found in Hepatitis a, the Guardia lamblia organism is most often acquired by consuming contaminated water as well as food that has been contaminated by infected food handlers. Once ingested, the typical disease process includes diarrhea within one week, and lasts for approximately one to two weeks. However, there have been reports of chronic cases -- especially in individuals who have immune deficiency issues (USDA).

Taxonomy

Guardia lamblia is a eukaryote. Unlike viruses or even bacteria, Guardia is regarded as an animal. Although it is extremely small and simple, this protozoa actually moves by using five "flagella," much as other animals might use arms or legs to move. It belongs in the genus Giardiavirus found within the family Totivirdae. Further, its virions are not enveloped, its Nucleocapsids are isometric and 36 nm in diameter, and it contains one molecule of double stranded RNA (ICTB, 2002 (b)). Interestingly, much is still unknown about the actual disease mechanism caused by the Guardia organism. Some theories include the idea that the organism produces a toxin (which has yet to be confirmed), and that it could function as a "mechanical obstruction of the surface of the intestine (USDA).

Although there are several strains of Guardia, none seem to cause more severe reactions than the others. However, like E. Coli and Hepatitis a, the severity of the disease can vary according to individual based both on unknown factors, as well as on known factors such as age, overall health, and immune suppression. Further, unlike many diseases, a very small infectious dose is required to produce illness (one is enough).

Guardia frequently occurs more in children than adults. This is perhaps due to the fact that, like Hepatitis a, suffers usually demonstrate immunity after the initial infection. In addition to day care centers (due to diapering and possible fecal transmission and contamination), the homosexual male population is also at high risk for the disease, indicating that there is a high possibility of sexual transmission (USDA). The most common effects of Guardia on the human are disaccharide intolerance, lactose intolerance, chronic infections of the GI tract, and in some cases, a malabsorption syndrome resulting in difficulty maintaining weight.

Because the Guardia organism normally resides in the intestines of animals and people, therefore the reservoir of the disease is considered to be in humans as well as wild (including beavers and bears) and domesticated animals such as cats and dogs (PPHB, 2001). It is transmitted person to person or even animal to person (through poor hand washing), especially be infected food handlers. Additionally, as previously stated, fecally contaminated water is also a method of transmission. Further, the organism can also survive on surfaces and soil.

Treatment and Prevention:

Thankfully, the organism is highly sensitive to medications, including quinacrine hydrochloride, metronidazole, tinidazole, albendazole and furazolidone (PPHB). Further, the organism can be killed before infection with a one percent solution of sodium hypoclorite, or two percent glutaraldehyde. However, it is important to note that the chlorine contained in drinking water is not strong enough to kill the organism. Instead, the approved method of disinfecting drinking water is by boiling for a minimum of one minute. Unfortunately, unlike Hepatitis a, there is no vaccine against Guardia. Therefore, much emphasis is placed on prevention of infection.

Because Guardia lamblia is an animal, it is important to note that it has a predictable life cycle. This life cycle also hallmarks the different stages of the infection in the host. To describe this life cycle, it is helpful to begin with the cyst stage, or the stage in which the organism is actually transmitted or acquired by the host. Within this stage, the organism is extremely resilient. This is because it is characterized by a thin, yet amazingly protective wall that allows it to survive in fecal material for weeks or in cold water for literally months. When this cyst is ingested via contaminated food or water, the cysts pass through the stomach (where they are unfazed by acid or enzymes), and enter the small intestine (Mitchell, Faaborg, Seyfert, and Wallin, 2001).

Once the cyst enters the environment of the small intestine, the alkaline environment acts as a trigger for a process known as excystment, in which the cyst's wall ruptures and the flagella emerge. This is known as the trophozoite stage in which the organism is not only motile, but begins to cause the symptomatic characteristics in the host. It does this (in part) by blocking and absorbing nutrients that normally transport across the epithelial lining of the intestine, including fats, carbohydrates, vitamin a, B12, and folic acid (Mitchell, Faaborg, Seyfert, and Wallin). After this stage, the organism again begins to form into a cyst again, preparing itself to exit the body and infect another host.

Conclusions:

Although E. Coli, Hepatitis a and Guardia lamblia are very different organisms in form as well as action, they all share common characteristics. Not only do all three organisms share similar typical portals of entry through the mouth and into the gastrointestinal tract, but they also can cause symptoms ranging from virtually none to severe illness -- sometimes resulting in lingering illness, the need for organ transplant or blood transfusion, or even (in severe cases) death.

Unfortunately, many questions remain concerning the eradication or control of all three pathogens. For example, E. Coli remains a significant public health threat despite health department food handling guidelines as well as public information campaigns. Further, the effect of the bacteria upon the very young as well as the elderly and immune suppressed can be so severe that death or organ failure often results. This is all the more frustrating when one notes that the care available to infected individuals is regulated to supportive care in that no antidote or effective treatment is currently available.

Hepatitis a shares many of the same issues with E. Coli. Again, despite widespread dissemination of good food handling procedures, Hepatitis a continues to be spread mainly via food and water contamination. Further, due to the relatively good drinking water sanitation procedures within the United States, the majority of cases there result from fecal/oral contamination -- especially in restaurants. Also like E. coli, Hepatitis a has no effective treatment once contracted, and doctors are relegated to offering supportive care. Although this may seem sufficient in mild cases, the frustration many encounter as a result of this reality becomes all to apparent in the severest cases causing complete hepatic failure.

Of course, the good news concerning Hepatitis a is that there is a vaccine against the illness, as well as IG treatments for those who are likely to have been exposed or are likely to be exposed before the vaccine can take effect. Unfortunately, however, the vaccine is not yet required within the United States, nor is it readily available for those living in poor or underdeveloped countries.

Finally, Guardia lamblia is much like E. coli and Hepatitis a in that it too can present with symptoms from mild to severe. Further, like E. coli, and Hepatitis a, poor sanitary procedures can result in infection. Unfortunately, there seems to be even less known about the actual disease mechanism caused by Guardia than the other two diseases. Not only does this cause significant problems with treatment and prevention, but it also may have something to do with the reason that some are drastically sickened by the organism while others are not.

In short, much is known about E. coli, Hepatitis a and Guardia. However, there remains significant work to be done both in the scientific, medical, as well as public health education realms. Although much work has been done already, future microbiologists as well as research physicians certainly have their work cut out for them. Considering that these three are but a tiny sample of the pathogenic organisms in existence, one can only hope that significant advances can be made in the fight against E. coli, Hepatitis a and Guardia as well as the countless others both known and yet to be discovered.

Comparison Chart: