Pathogens

• ALSO KNOWN AS: Germs, infectious agents

Definition

The term pathogen, introduced in 1880, is a combination of patho ("disease") and gen, which indicates a "producer." Hence, the term "pathogen" most commonly refers to any infectious organism that can inflict damage on its host. Pathogens include diverse groups of microorganisms, including bacteria, viruses, fungi, prions, and parasites. The term pathogen, however, is less commonly used in referring to noninfectious agents of disease, such as chemicals. Furthermore, some organisms classified as pathogens are not negative to their host. That is, they serve as natural or introduced controls to suppress arthropod populations.

Pathogens generally best exist in their human, animal, and plant hosts. Harmful microorganisms, however, can also be found in abundance in soil, water, air, and on various surfaces for a range of time. Each pathogen has a particular host range or specificity that it can affect. In other words, some pathogens can infect only a particular type (genus and species) of host, such as humans, whereas other pathogens can affect a large number and wide range of hosts. Research has shown, though, that pathogens can evolve because of their interactions with their hosts and other microorganisms in their environment, sometimes leading to a changed or expanded host range. For instance, various strains of the influenza virus can spontaneously arise, leading to the need for regularly altered flu vaccines to treat annual outbreaks of influenza. The avian influenza virus is an example of a pathogen originally found in one host (birds) but can cause infection in another host (humans).

Many pathogens grow and reproduce preferentially in certain environments and in the presence of certain resources, preferring warm, moist, neutral environments that are representative of the natural physiology of their biological hosts. Many other infectious agents, however, can adapt to and even beat difficult conditions. Most potential hosts have natural defenses against pathogens in the form of immune response, helpful normal flora (in mammals), and other mechanisms. Still, pathogens continue to successfully infect and kill millions of people worldwide annually.

Pathogens prey on persons with weakened immune defenses (caused by diseases such as human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), and by chemotherapy, malnutrition, and immunosuppression for surgery or pregnancy). Those infections acquired in hospital settings are referred to as nosocomial and can be quite difficult to prevent and control. Furthermore, other pathogens overcome human defense mechanisms by altering their own genetic code and employing other strategies to avoid the defense efforts of the human body. For instance, multi-drug-resistant Staphylococcus aureus has acquired resistance to many of the most commonly used and effective antibiotics (including methicillin and penicillin). These superbugs are of constant concern to researchers and clinicians.

Types of Pathogens

Pathogens can be divided into five broad classifications: bacterial, viral, fungal, prionic, and other.

Bacterial. A small percentage of bacteria are actually classified as pathogens. In contrast to commensal bacteria, which can be useful or helpful, pathogenic bacteria cause infection and serious disease in humans, nonhuman animals, and plants. The diseases and symptoms caused by pathogenic bacteria are almost as diverse as the biological organisms they infect.

Symptoms of bacterial infection can be minor, such as itchiness or sore throat, to significantly more serious, such as open wounds and sepsis (excessive bacteria in the blood). Certain bacteria have even been linked to certain types of cancer, although this has been shown to occur most commonly in immunocompromised persons.

Some bacterial infections or diseases are caused by a single species or genus, whereas others can result from multiple organismal sources that are either closely related or quite distant in terms of phylogeny. For instance, tetanus, a medical condition sometimes induced by an infected deep cut or wound, is caused only by Clostridium tetani. The most common human bacterial disease, tuberculosis, however, can be caused by many related strains of the Mycobacterium genus (M. tuberculosis, M. africanum, M. canettii, M. caprae, and M. microti). Moreover, pneumonia can be caused by an extremely wide range of bacterial genera, including Pseudomonas, Streptococcus, Mycoplasma, and Legionella, rather than by a single organism or closely related organisms. Also, food-borne illnesses and gastrointestinal disorders can be caused by several types of bacteria, including Salmonellae spp., Shigella spp., Campylobacter spp., Bacillus cereus, Clostridium spp., Yersinia enterocolitica, Cryptosporidium parvum, Escherichia coli, Listeria monocytogenes, and Vibrio spp.

Conversely, some bacterial species can cause a single ailment, whereas others can lead to several, quite different infections. For example, the microorganism Salmonella typhi is known to cause typhoid fever only, whereas the species Staphylococcus pyogenes can cause both the commonly diagnosed strep throat, which can be treated with prescription antibiotics, and scarlet fever or rheumatic fever, which can be chronic and even lead to heart failure.

Other notable ailments caused by bacterial infection include diphtheria (Corynebacterium diphtheriae), chlamydia (Chlamydia trachomatis), syphilis (Treponema pallidum), gonorrhea (Neisseria gonorrhoeae), listeriosis (Listeria monocytogenes), and various issues affecting the skin, including purulent discharges, boils, blisters, and minor infections (Staphylococcus aureus). Bacterial infection also can lead to more serious "flesh-eating" and destructive diseases (Streptococcus spp.). Bacteria have also been linked to certain types of cancer. Studies have shown that the organism Helicobacter pylori, a bacterial species that can exist in abundance in the stomach, is linked to the formation of ulcers and possibly gastric cancer.

Bacteria also affect agriculture and food-based industries by leading to costly infections, such as fire blight (Erwinia amylovora), leaf spot (Cercopsora spp. and Pseudomonas cichorii), and wilts (Erwinia tracheiphila) in commercial crops, and to anthrax (Bacillus anthracis), Johne’s disease (M. avium subspecies paratuberculosis), and leptospirosis (Lectospora spp.) in livestock.

Viral. Viral pathogens make up the most abundant biological entity, and they can affect various species of animals, plants, and even bacteria through various mechanisms. Examples of common human diseases caused by viral pathogens include the common cold (rhinovirus, coronavirus, and picornavirus), influenza (Orthomyxoviridae), chickenpox (varicella-zoster virus), measles (morbillivirus), mumps (rubulavirus), rubella (rubivirus), cold sores (human papillomavirus types 1 and 2), and mononucleosis. Viral pathogens also cause many serious human diseases, including hepatitis (viruses A, B, C, and D), smallpox (Variola), Ebola virus infection (Ebola virus), HIV/AIDS (lentivirus), yellow fever (flavivirus), West Nile virus, SARS-associated coronavirus (SARS-CoV), and avian influenza.

Many viruses have also been linked to various cancers. Epstein-Barr virus, otherwise known as human herpesvirus-4 (HHV-4), causes not only cold sores and mononucleosis; it has also been linked to Burkitt’s lymphoma, nasopharyngeal carcinoma, and central nervous system lymphomas associated with HIV infection. Furthermore, HHV-8 has been linked to Kaposi’s sarcoma. HPV is also a causative agent in cervical cancer. Some studies also link viruses to neurological diseases such as multiple sclerosis and chronic fatigue syndrome.

Viruses can also affect animals and agriculture. The highly pathogenic avian influenza A (H5N1) and A (H7) viruses sometimes infect humans but are highly contagious among birds, including poultry. Some other commonly found viruses in food, water, and animals include hepatitis virus, rhabdovirus, picornavirus (foot-and-mouth disease), and paramyxovirus.

Fungal. Fungi are the most common cause of diseases in crops and other plants. Fungal infections also occur in humans, with the majority of advanced infections occurring in immunocompromised persons, particularly on their skin and nails and as yeast infections in body cavities. Some commonly occurring fungal infections include athlete’s foot, ringworm (Trichophyton and Microsporum), a form of meningitis (Cryptococcus neoformans), and candidiasis (Candida albicans).

Prionic. Prions are infectious particles composed primarily of protein that do not, unlike other pathogens, contain nucleic acids. Prions cause a number of diseases in a variety of mammals and have received significant media attention. These prion diseases include bovine spongiform encephalopathy (mad cow disease) in cattle and Creutzfeldt-Jakob disease in humans. All known prion diseases affect brain structure or neural tissue and are untreatable and universally fatal.

Other parasites. Some parasitic eukaryotic organisms, including protists and helminths, also cause disease in humans and animals. Protists in the genus Plasmodium are mosquito-borne and cause the highly infectious disease malaria. Other protozoa of the species Trypanosoma brucei are transmitted by the tsetse fly and cause African sleeping sickness (a form of trypanosomiasis). Leishmania is another genus of protozoa that is carried by sandflies and causes the disease leishmaniasis in many types of mammals. Each of these devastating diseases is endemic to several tropical and subtropical regions of the world, especially in the Americas, Asia, and Africa. Helminths are parasitic wormlike organisms that disrupt their host’s digestion and nutrient absorption, causing weakness and disease. These organisms are also more common in developing countries.

Transmission

In general, the transmission of pathogens largely involves three steps: exit from a primary host, travel or existence in an intermediate location, and infection of a new host. There are, however, several specific routes and mechanisms by which pathogens can reach and colonize their hosts. Collectively, pathogens can essentially affect all facets of anatomy, in mammals and plants alike. The specific pathology and epidemiology of an infection, however, are largely dependent on the pathogen involved.

Scientists typically group transmission into two general categories, direct and indirect contact, which are further divided into several subcategories. Direct transmission refers to those instances when an infected host transmits a pathogen directly to another host. For example, pathogens that cause many sexually transmitted diseases, including gonorrhea, syphilis, and HIV/AIDS, are most commonly passed directly from person to person and cannot survive in environments external to their hosts for any extended time.

In contrast, indirect transmission involves transference of a pathogen from one host to another by way of an intermediate agent, which can be either animate or inanimate. Animate objects include both disease vehicles (including food, water, and air) and disease vectors (including insects, fleas, and rodents). Inanimate objects (or fomites) are those items on which pathogens are deposited and remain; fomites include clothes, bedding, and clinical apparatuses. Many gastrointestinal, respiratory, and blood-borne infections are passed through indirect transmission.

Prevention and Outcomes

Because the range of pathogens is great, the ranges of prevention and treatment for infections are similarly broad. Researchers and clinicians have developed many effective strategies for the prevention and treatment of pathogens. It should be noted, however, that many pathogens remain to be understood, preventable, or clinically treatable. Those in the field of epidemiology, the study the health and illness of populations, use their knowledge of current trends to predict future behavior and to formulate logical interventions in the interest of public health and preventive medicine. Pathogens are a cornerstone interest to researchers and policymakers alike because they are drivers of disease and death worldwide.

The control of pathogens and related infectious diseases is largely the result of advancements in the comprehensive understanding of disease processes, in improved sanitary and living conditions, and in the discovery of antimicrobial agents and other biotechnological strategies for prevention and treatment. Persons can reduce the incidence of many pathogenic infections by being educated about potential threats, by adopting certain behaviors, and by avoiding other behaviors. In particular, because many pathogens spread indirectly by oral, fecal, genital, and blood-borne routes, good hygiene (such as properly storing and preparing foodstuffs, regularly washing hands and bathing, avoiding intravenous drugs, and avoiding direct sexual contact with infected persons) can prevent many types of infections. At the community level, infectious disease can be prevented by providing uncontaminated water for drinking and agriculture, by educating the public about infectious disease, and by ensuring adequate healthcare for all.

One effective way of preventing viral infection is vaccination, which has led to a dramatic decline in morbidity (illness) and mortality (death) associated with infection. Many viral infections have been essentially eradicated (including smallpox, measles, mumps, and rubella) since the introduction of their respective vaccinations. However, vaccines do not exist for all viruses, and they can be difficult and expensive to develop and administer.

Treatment

The treatment of pathogens includes using a wide range of compounds and substances collectively known as antimicrobials. Infections caused by bacteria are most commonly treated with prescription antibiotics, which either slow the growth of (bacteriostatic) or kill (bactericidal) certain bacteria. Antibiotics can be naturally derived, synthetic, or semi-synthetic, and can target either a few or a broad spectrum of organisms.

Some of the most commonly prescribed antibiotics include beta-lactams, sulfonamides, quinolones, and oxazolidinones. Similarly, antifungals are used to treat various fungal infections. Several of these drugs can be purchased without a prescription; others require one. The most commonly prescribed antifungals include those of the azole group. Antiviral drugs are used for treating viral infections. Unlike most antibiotics, antivirals do not destroy their target pathogen; instead, they inhibit their development. In contrast, another group of agents, viricides, destroy virus particles outside the body. Drugs are available for the management of influenza A and B viruses, HIV, herpesviruses, and hepatitis B and C. Protozoa and other parasites are typically treated with antimicrobial drugs.

Impact

Pathogens make up a very small fraction of all microorganisms, yet they play a particularly powerful role in human life, and in human illness. Several agencies monitor and regulate the control of infectious diseases worldwide, including the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), the US Food and Drug Administration (FDA), and the US Environmental Protection Agency (EPA).

Despite advancements in the prevention and containment of pathogenic diseases, especially smallpox, mumps, and plague, some pathogenic diseases, especially HIV, tuberculosis, and influenza, continue to persist in large numbers and threaten human life. Because the effectiveness of epidemiology directly influences the spread, treatment, and outcome of pathogenic diseases, the developing world, which has limited epidemiological resources, remains unequally affected by diseases that are rarely reported in modern Western nations. There are many reasons for the discrepancy, including a lack of access to infrastructure, education, and funding resources.

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