Infection

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Infectious disease
Malaria.jpg
A false-colored electron micrograph shows a malaria sporozoite migrating through the midgut epithelium of a rat.
Specialty Infectious disease

Infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to the infectious agents and the toxins they produce. [1] [2] Infectious disease, also known as transmissible disease or communicable disease, is illness resulting from an infection.

Tissue (biology) An ensemble of similar cells and their matrix with similar origin and function

In biology, tissue is a cellular organizational level between cells and a complete organ. A tissue is an ensemble of similar cells and their extracellular matrix from the same origin that together carry out a specific function. Organs are then formed by the functional grouping together of multiple tissues.

Disease abnormal condition negatively affecting organisms

A disease is a particular abnormal condition that negatively affects the structure or function of part or all of an organism, and that is not due to any external injury. Diseases are often construed as medical conditions that are associated with specific symptoms and signs. A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders.

Host (biology) organism that harbours another organism

In biology and medicine, a host is an organism that harbours a parasitic, a mutualistic, or a commensalist guest (symbiont), the guest typically being provided with nourishment and shelter. Examples include animals playing host to parasitic worms, cells harbouring pathogenic (disease-causing) viruses, a bean plant hosting mutualistic (helpful) nitrogen-fixing bacteria. More specifically in botany, a host plant supplies food resources to micropredators, which have an evolutionarily stable relationship with their hosts similar to ectoparasitism. The host range is the collection of hosts that an organism can use as a partner.

Contents

Infections are caused by infectious agents (pathogens) including:

In biology, a pathogen, in the oldest and broadest sense, is anything that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Virus Type of non-cellular infectious agent

A virus is a small infectious agent that replicates only inside the living cells of an organism. Viruses can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

Viroids are the smallest infectious pathogens known. They are composed solely of a short strand of circular, single-stranded RNA that has no protein coating. All known viroids are inhabitants of higher plants, in which most cause diseases, some of which are of slight to catastrophic economic importance.

Prion pathogenic type of misfolded protein

Prions are misfolded proteins which characterize several fatal neurodegenerative diseases in humans and many other animals. It is not known what causes the normal protein to misfold; the abnormal three-dimensional structure is suspected of conferring infectious properties. The word prion derives from "proteinaceous infectious particle". Prions composed of the prion protein (PrP) are hypothesized as the cause of transmissible spongiform encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in deer, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans.

Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involving inflammation, followed by an adaptive response. [3]

Immune system A biological system that protects an organism against disease

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system, or humoral immunity versus cell-mediated immunity. In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain.

Mammal class of tetrapods

Mammals are vertebrate animals constituting the class Mammalia, and characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex, fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles and birds, from which they diverged in the late Triassic, 201–227 million years ago. There are around 5,450 species of mammals. The largest orders are the rodents, bats and Soricomorpha. The next three are the Primates, the Cetartiodactyla, and the Carnivora.

Innate immune system

The innate immune system is one of the two main immunity strategies found in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and it is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.

Specific medications used to treat infections include antibiotics, antivirals, antifungals, antiprotozoals, and antihelminthics. Infectious diseases resulted in 9.2 million deaths in 2013 (about 17% of all deaths). [4] The branch of medicine that focuses on infections is referred to as infectious disease. [5]

Classification

Subclinical versus clinical (latent versus apparent)

Symptomatic infections are apparent and clinical, whereas an infection that is active but does not produce noticeable symptoms may be called inapparent,silent, subclinical , or occult. An infection that is inactive or dormant is called a latent infection . [6] An example of a latent bacterial infection is latent tuberculosis. Some viral infections can also be latent, examples of latent viral infections are any of those from the Herpesviridae family.

The word infection can denote any presence of a particular pathogen at all (no matter how little) but also is often used in a sense implying a clinically apparent infection (in other words, a case of infectious disease). [7] This fact occasionally creates some ambiguity or prompts some usage discussion. To get around the usage annoyance, it is common for health professionals to speak of colonization (rather than infection) when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present.

A short-term infection is an acute infection. A long-term infection is a chronic infection. Infections can be further classified by causative agent (bacterial, viral, fungal, parasitic), and by the presence or absence of systemic symptoms (sepsis).

Primary versus opportunistic

Among the many varieties of microorganisms, relatively few cause disease in otherwise healthy individuals. [8] Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen, depends upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. However a host's immune system can also cause damage to the host itself in an attempt to control the infection. Clinicians therefore classify infectious microorganisms or microbes according to the status of host defenses - either as primary pathogens or as opportunistic pathogens :

Primary pathogens
Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts.
Opportunistic pathogens
Opportunistic pathogens can cause an infectious disease in a host with depressed resistance (immunodeficiency) or if they have unusual access to the inside of the body (for example, via trauma). Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as pathogenic bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridium difficile colitis) or from the environment as a result of traumatic introduction (as in surgical wound infections or compound fractures). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as Chronic granulomatous disease), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy), exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with measles, malaria or HIV disease). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host. [9]
Primary infection versus secondary infection
A primary infection is infection that is, or can practically be viewed as, the root cause of the current health problem. In contrast, a secondary infection is a sequela or complication of a root cause. For example, pulmonary tuberculosis is often a primary infection, but an infection that happened only because a burn or penetrating trauma (the root cause) allowed unusual access to deep tissues is a secondary infection. Primary pathogens often cause primary infection and also often cause secondary infection. Usually opportunistic infections are viewed as secondary infections (because immunodeficiency or injury was the predisposing factor).

Infectious or not

One way of proving that a given disease is "infectious", is to satisfy Koch's postulates (first proposed by Robert Koch), which demands that the infectious agent be identified only in patients and not in healthy controls, and that patients who contract the agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis. Koch's postulates cannot be applied ethically for many human diseases because they require experimental infection of a healthy individual with a pathogen produced as a pure culture. Often, even clearly infectious diseases do not meet the infectious criteria. For example, Treponema pallidum , the causative spirochete of syphilis, cannot be cultured in vitro – however the organism can be cultured in rabbit testes. It is less clear that a pure culture comes from an animal source serving as host than it is when derived from microbes derived from plate culture. Epidemiology is another important tool used to study disease in a population. For infectious diseases it helps to determine if a disease outbreak is sporadic (occasional occurrence), endemic (regular cases often occurring in a region), epidemic (an unusually high number of cases in a region), or pandemic (a global epidemic).

Contagiousness

Infectious diseases are sometimes called contagious disease when they are easily transmitted by contact with an ill person or their secretions (e.g., influenza). Thus, a contagious disease is a subset of infectious disease that is especially infective or easily transmitted. Other types of infectious/transmissible/communicable diseases with more specialized routes of infection, such as vector transmission or sexual transmission, are usually not regarded as "contagious", and often do not require medical isolation (sometimes loosely called quarantine) of victims. However, this specialized connotation of the word "contagious" and "contagious disease" (easy transmissibility) is not always respected in popular use. Infectious diseases are commonly transmitted from person to person through direct contact. The types of contact are through person to person and droplet spread. Indirect contact such as airborne transmission, contaminated objects, food and drinking water, animal person contact, animal reservoirs, insect bites, and environmental reservoirs are another way infectious diseases are transmitted, [10]

By anatomic location

Infections can be classified by the anatomic location or organ system infected, including:

In addition, locations of inflammation where infection is the most common cause include pneumonia, meningitis and salpingitis.

Signs and symptoms

The symptoms of an infection depends on the type of disease. Some signs of infection affect the whole body generally, such as fatigue, loss of appetite, weight loss, fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes, coughing, or a runny nose.

In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host. [9]

Bacterial or viral

Bacterial and viral infections can both cause the same kinds of symptoms. It can be difficult to distinguish which is the cause of a specific infection. [11] It's important to distinguish, because viral infections cannot be cured by antibiotics. [12]

Comparison of viral and bacterial infection
Characteristic Viral infection Bacterial infection
Typical symptomsIn general, viral infections are systemic. This means they involve many different parts of the body or more than one body system at the same time; i.e. a runny nose, sinus congestion, cough, body aches etc. They can be local at times as in viral conjunctivitis or "pink eye" and herpes. Only a few viral infections are painful, like herpes. The pain of viral infections is often described as itchy or burning. [11] The classic symptoms of a bacterial infection are localized redness, heat, swelling and pain. One of the hallmarks of a bacterial infection is local pain, pain that is in a specific part of the body. For example, if a cut occurs and is infected with bacteria, pain occurs at the site of the infection. Bacterial throat pain is often characterized by more pain on one side of the throat. An ear infection is more likely to be diagnosed as bacterial if the pain occurs in only one ear. [11] A cut that produces pus and milky-colored liquid is most likely infected.[ clarification needed ] [13]
Cause Pathogenic viruses Pathogenic bacteria

Pathophysiology

There is a general chain of events that applies to infections. [14] The chain of events involves several steps—which include the infectious agent, reservoir, entering a susceptible host, exit and transmission to new hosts. Each of the links must be present in a chronological order for an infection to develop. Understanding these steps helps health care workers target the infection and prevent it from occurring in the first place. [15]

Colonization

Infection of an ingrown toenail; there is pus (yellow) and resultant inflammation (redness and swelling around the nail). Dit del peu gros infectat.jpg
Infection of an ingrown toenail; there is pus (yellow) and resultant inflammation (redness and swelling around the nail).

Infection begins when an organism successfully enters the body, grows and multiplies. This is referred to as colonization. Most humans are not easily infected. Those who are weak, sick, malnourished, have cancer or are diabetic have increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections. Entrance to the host at host-pathogen interface, generally occurs through the mucosa in orifices like the oral cavity, nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids.

Wound colonization refers to nonreplicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon, and an example of the latter are the various species of staphylococcus that exist on human skin. Neither of these colonizations are considered infections. The difference between an infection and a colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and viridans streptococci , prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with the host, preventing infection and speeding wound healing.

This image depicts the steps of pathogenic infection. Pathogenic Infection.png
This image depicts the steps of pathogenic infection.

The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include:

As an example, several staphylococcal species remain harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum, multiply without resistance and cause harm.

An interesting fact that gas chromatography–mass spectrometry, 16S ribosomal RNA analysis, omics, and other advanced technologies have made more apparent to humans in recent decades is that microbial colonization is very common even in environments that humans think of as being nearly sterile. Because it is normal to have bacterial colonization, it is difficult to know which chronic wounds can be classified as infected and how much risk of progression exists. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in the Journal of the American Medical Association's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection. [19] The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11–20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64–0.88) does not rule out infection (summary LR 0.64–0.88).

Disease

Disease can arise if the host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis. Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected with polio develop disease. [20] On the other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease invariably kills all animals and people that are infected.

Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain a persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise.

Persistent infections cause millions of deaths globally each year. [21] Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries.

Transmission

A southern house mosquito (Culex quinquefasciatus) is a vector that transmits the pathogens that cause West Nile fever and avian malaria among others. CulexNil.jpg
A southern house mosquito ( Culex quinquefasciatus ) is a vector that transmits the pathogens that cause West Nile fever and avian malaria among others.

For infecting organisms to survive and repeat the infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Infection transmission can take place via many potential routes:

The relationship between virulence versus transmissibility is complex; if a disease is rapidly fatal, the host may die before the microbe can be passed along to another host.

Diagnosis

Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts, cutaneous abscesses, respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is benign.

Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion.

Symptomatic diagnostics

The diagnosis is aided by the presenting symptoms in any individual with an infectious disease, yet it usually needs additional diagnostic techniques to confirm the suspicion. Some signs are specifically characteristic and indicative of a disease and are called pathognomonic signs; but these are rare. Not all infections are symptomatic. [25]

In children the presence of cyanosis, rapid breathing, poor peripheral perfusion, or a petechial rash increases the risk of a serious infection by greater than 5 fold. [26] Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C. [26]

Microbial culture

Four nutrient agar plates growing colonies of common Gram negative bacteria. K pneumoniae M morganii providencia styphimuriuma.JPG
Four nutrient agar plates growing colonies of common Gram negative bacteria.

Microbiological culture is a principal tool used to diagnose infectious disease. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Most pathogenic bacteria are easily grown on nutrient agar, a form of solid medium that supplies carbohydrates and proteins necessary for growth of a bacterium, along with copious amounts of water. A single bacterium will grow into a visible mound on the surface of the plate called a colony, which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit the growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of viruses: the medium in this case being cells grown in culture that the virus can infect, and then alter or kill. In the case of viral identification, a region of dead cells results from viral growth, and is called a "plaque". Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent.

In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as Mycobacterium leprae and Treponema pallidum can be grown in animals, although serological and microscopic techniques make the use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent. Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of the causative agent, Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case, xenodiagnosis involves the use of the vector of the Chagas agent T. cruzi, an uninfected triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of T. cruzi within its gut.

Microscopy

Another principal tool in the diagnosis of infectious disease is microscopy. Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound light microscope, or with instruments as complex as an electron microscope. Samples obtained from patients may be viewed directly under the light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with biochemical staining techniques, and can be made exquisitely specific when used in combination with antibody based techniques. For example, the use of antibodies made artificially fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific antigens present on a pathogen. A fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly.

Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basic dyes due to the electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as Giemsa stain or crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures is used in the taxonomic classification of microbes as well. Two methods, the Gram stain and the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Firmicutes and Actinobacteria, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinobacterial genera Mycobacterium and Nocardia .

Biochemical tests

Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids, alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.

The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to bind red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an enzyme and has no metabolic function.

Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent, S. pyogenes , that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive. [9]

Complex serological techniques have been developed into what are known as Immunoassays. Immunoassays can use the basic antibody – antigen binding as the basis to produce an electro-magnetic or particle radiation signal, which can be detected by some form of instrumentation. Signal of unknowns can be compared to that of standards allowing quantitation of the target antigen. To aid in the diagnosis of infectious diseases, immunoassays can detect or measure antigens from either infectious agents or proteins generated by an infected organism in response to a foreign agent. For example, immunoassay A may detect the presence of a surface protein from a virus particle. Immunoassay B on the other hand may detect or measure antibodies produced by an organism's immune system that are made to neutralize and allow the destruction of the virus.

Instrumentation can be used to read extremely small signals created by secondary reactions linked to the antibody – antigen binding. Instrumentation can control sampling, reagent use, reaction times, signal detection, calculation of results, and data management to yield a cost effective automated process for diagnosis of infectious disease.

PCR-based diagnostics

Technologies based upon the polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids in order to cause a disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers, are derived from the genomes of infectious agents, and with time those genomes will be known, if they are not already.

Thus, the technological ability to detect any infectious agent rapidly and specifically are currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases (tetanus and botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.

Metagenomic sequencing

Given the wide range of bacteria, viruses, and other pathogens that cause debilitating and life-threatening illness, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases of encephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using state-of-the-art clinical laboratory methods. Metagenomics is currently being researched for clinical use, and shows promise as a sensitive and rapid way to diagnose infection using a single all-encompassing test. This test is similar to current PCR tests; however, amplification of genetic material is unbiased rather than using primers for a specific infectious agent. This amplification step is followed by next-generation sequencing and alignment comparisons using large databases of thousands of organismic and viral genomes.

Metagenomic sequencing could prove especially useful for diagnosis when the patient is immunocompromised. An ever-wider array of infectious agents can cause serious harm to individuals with immunosuppression, so clinical screening must often be broader. Additionally, the expression of symptoms is often atypical, making clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A broad, sensitive test for pathogens that detects the presence of infectious material rather than antibodies is therefore highly desirable.

Indication of tests

There is usually an indication for a specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of AZT for the treatment of AIDS, the course of the disease was closely followed by monitoring the composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of HIV in specific communities permitted the advancement of hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing the number of new infections. The specific serological diagnostic identification, and later genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the temporal and geographical origins of the virus, as well as a myriad of other hypothesis. [9] The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment with anti-retroviral drugs. Molecular diagnostics are now commonly used to identify HIV in healthy people long before the onset of illness and have been used to demonstrate the existence of people who are genetically resistant to HIV infection. Thus, while there still is no cure for AIDS, there is great therapeutic and predictive benefit to identifying the virus and monitoring the virus levels within the blood of infected individuals, both for the patient and for the community at large.

Prevention

Washing one's hands, a form of hygiene, is an effective way to prevent the spread of infectious disease. OCD handwash.jpg
Washing one's hands, a form of hygiene, is an effective way to prevent the spread of infectious disease.

Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed from one person to another. Aseptic technique was introduced in medicine and surgery in the late 19th century and greatly reduced the incidence of infections caused by surgery. Frequent hand washing remains the most important defense against the spread of unwanted organisms. [28] There are other forms of prevention such as avoiding the use of illicit drugs, using a condom, wearing gloves, and having a healthy lifestyle with a balanced diet and regular exercise. Cooking foods well and avoiding foods that have been left outside for a long time is also important.

Antimicrobial substances used to prevent transmission of infections include:

One of the ways to prevent or slow down the transmission of infectious diseases is to recognize the different characteristics of various diseases. [29] Some critical disease characteristics that should be evaluated include virulence, distance traveled by victims, and level of contagiousness. The human strains of Ebola virus, for example, incapacitate their victims extremely quickly and kill them soon after. As a result, the victims of this disease do not have the opportunity to travel very far from the initial infection zone. [30] Also, this virus must spread through skin lesions or permeable membranes such as the eye. Thus, the initial stage of Ebola is not very contagious since its victims experience only internal hemorrhaging. As a result of the above features, the spread of Ebola is very rapid and usually stays within a relatively confined geographical area. In contrast, the Human Immunodeficiency Virus (HIV) kills its victims very slowly by attacking their immune system. [9] As a result, many of its victims transmit the virus to other individuals before even realizing that they are carrying the disease. Also, the relatively low virulence allows its victims to travel long distances, increasing the likelihood of an epidemic.

Another effective way to decrease the transmission rate of infectious diseases is to recognize the effects of small-world networks. [29] In epidemics, there are often extensive interactions within hubs or groups of infected individuals and other interactions within discrete hubs of susceptible individuals. Despite the low interaction between discrete hubs, the disease can jump to and spread in a susceptible hub via a single or few interactions with an infected hub. Thus, infection rates in small-world networks can be reduced somewhat if interactions between individuals within infected hubs are eliminated (Figure 1). However, infection rates can be drastically reduced if the main focus is on the prevention of transmission jumps between hubs. The use of needle exchange programs in areas with a high density of drug users with HIV is an example of the successful implementation of this treatment method. [6] Another example is the use of ring culling or vaccination of potentially susceptible livestock in adjacent farms to prevent the spread of the foot-and-mouth virus in 2001. [31]

A general method to prevent transmission of vector-borne pathogens is pest control.

Immunity

Mary Mallon (a.k.a. Typhoid Mary) was an asymptomatic carrier of typhoid fever. Over the course of her career as a cook, she infected 53 people, three of whom died. Mallon-Mary 01.jpg
Mary Mallon (a.k.a. Typhoid Mary) was an asymptomatic carrier of typhoid fever. Over the course of her career as a cook, she infected 53 people, three of whom died.

Infection with most pathogens does not result in death of the host and the offending organism is ultimately cleared after the symptoms of the disease have waned. [8] This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquired immunity against infectious diseases may be mediated by antibodies and/or T lymphocytes. Immunity mediated by these two factors may be manifested by:

The immune system response to a microorganism often causes symptoms such as a high fever and inflammation, and has the potential to be more devastating than direct damage caused by a microbe. [9]

Resistance to infection (immunity) may be acquired following a disease, by asymptomatic carriage of the pathogen, by harboring an organism with a similar structure (crossreacting), or by vaccination. Knowledge of the protective antigens and specific acquired host immune factors is more complete for primary pathogens than for opportunistic pathogens. There is also the phenomenon of herd immunity which offers a measure of protection to those otherwise vulnerable people when a large enough proportion of the population has acquired immunity from certain infections.

Immune resistance to an infectious disease requires a critical level of either antigen-specific antibodies and/or T cells when the host encounters the pathogen. Some individuals develop natural serum antibodies to the surface polysaccharides of some agents although they have had little or no contact with the agent, these natural antibodies confer specific protection to adults and are passively transmitted to newborns.

Host genetic factors

The organism that is the target of an infecting action of a specific infectious agent is called the host. The host harbouring an agent that is in a mature or sexually active stage phase is called the definitive host. The intermediate host comes in contact during the larvae stage. A host can be anything living and can attain to asexual and sexual reproduction. [32] The clearance of the pathogens, either treatment-induced or spontaneous, it can be influenced by the genetic variants carried by the individual patients. For instance, for genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in the treatment-induced clearance of the virus. This finding, originally reported in Nature, [33] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more possibly to achieve sustained virological response after the treatment than others. Later report from Nature [34] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

Treatments

When infection attacks the body, anti-infective drugs can suppress the infection. Several broad types of anti-infective drugs exist, depending on the type of organism targeted; they include antibacterial (antibiotic; including antitubercular), antiviral, antifungal and antiparasitic (including antiprotozoal and antihelminthic) agents. Depending on the severity and the type of infection, the antibiotic may be given by mouth or by injection, or may be applied topically. Severe infections of the brain are usually treated with intravenous antibiotics. Sometimes, multiple antibiotics are used in case there is resistance to one antibiotic. Antibiotics only work for bacteria and do not affect viruses. Antibiotics work by slowing down the multiplication of bacteria or killing the bacteria. The most common classes of antibiotics used in medicine include penicillin, cephalosporins, aminoglycosides, macrolides, quinolones and tetracyclines.[ citation needed ]

Not all infections require treatment, and for many self-limiting infections the treatment may cause more side-effects than benefits. Antimicrobial stewardship is the concept that healthcare providers should treat an infection with an antimicrobial that specifically works well for the target pathogen for the shortest amount of time and to only treat when there is a known or highly suspected pathogen that will respond to the medication. [35]

Epidemiology

Deaths due to infectious and parasitic diseases per million persons in 2012
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28-81
82-114
115-171
172-212
213-283
284-516
517-1,193
1,194-2,476
2,477-3,954
3,955-6812 Infectious and parasitic diseases world map-Deaths per million persons-WHO2012.svg
Deaths due to infectious and parasitic diseases per million persons in 2012
  28-81
  82-114
  115-171
  172-212
  213-283
  284-516
  517-1,193
  1,194-2,476
  2,477-3,954
  3,955-6812
Disability-adjusted life year for infectious and parasitic diseases per 100,000 inhabitants in 2004.
no data
<=250
250-500
500-1000
1000-2000
2000-3000
3000-4000
4000-5000
5000-6250
6250-12,500
12,500-25,000
25,000-50,000
>=50,000 Infectious and parasitic diseases world map - DALY - WHO2004.svg
Disability-adjusted life year for infectious and parasitic diseases per 100,000 inhabitants in 2004.
  no data
  ≤250
  250–500
  500–1000
  1000–2000
  2000–3000
  3000–4000
  4000–5000
  5000–6250
  6250–12,500
  12,500–25,000
  25,000–50,000
  ≥50,000

In 2010, about 10 million people died of infectious diseases. [37]

The World Health Organization collects information on global deaths by International Classification of Disease (ICD) code categories. The following table lists the top infectious disease by number of deaths in 2002. 1993 data is included for comparison.

Worldwide mortality due to infectious diseases [38] [39]
RankCause of deathDeaths 2002
(in millions)
Percentage of
all deaths
Deaths 1993
(in millions)
1993 Rank
N/AAll infectious diseases14.725.9%16.432.2%
1 Lower respiratory infections [40] 3.96.9%4.11
2 HIV/AIDS 2.84.9%0.77
3 Diarrheal diseases [41] 1.83.2%3.02
4 Tuberculosis (TB)1.62.7%2.73
5 Malaria 1.32.2%2.04
6 Measles 0.61.1%1.15
7 Pertussis 0.290.5%0.367
8 Tetanus 0.210.4%0.1512
9 Meningitis 0.170.3%0.258
10 Syphilis 0.160.3%0.1911
11 Hepatitis B 0.100.2%0.936
12-17 Tropical diseases (6) [42] 0.130.2%0.539, 10, 16–18
Note: Other causes of death include maternal and perinatal conditions (5.2%), nutritional deficiencies (0.9%),
noncommunicable conditions (58.8%), and injuries (9.1%).

The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases include pertussis, poliomyelitis, diphtheria, measles and tetanus. Children also make up a large percentage of lower respiratory and diarrheal deaths. In 2012, approximately 3.1 million people have died due to lower respiratory infections, making it the number 4 leading cause of death in the world. [43]

Historic pandemics

Great Plague of Marseille in 1720 killed 100,000 people in the city and the surrounding provinces Marseille-peste-Serre.jpg
Great Plague of Marseille in 1720 killed 100,000 people in the city and the surrounding provinces

A pandemic (or global epidemic) is a disease that affects people over an extensive geographical area.

Emerging diseases

In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host.

  1. Coevolution between parasite and host can lead to hosts becoming resistant to the parasites or the parasites may evolve greater virulence, leading to immunopathological disease.
  2. Human activity is involved with many emerging infectious diseases, such as environmental change enabling a parasite to occupy new niches. When that happens, a pathogen that had been confined to a remote habitat has a wider distribution and possibly a new host organism. Parasites jumping from nonhuman to human hosts are known as zoonoses. Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host. [51]

Several human activities have led to the emergence of zoonotic human pathogens, including viruses, bacteria, protozoa, and rickettsia, [52] and spread of vector-borne diseases, [51] see also globalization and disease and wildlife disease:

History

East German postage stamps depicting four antique microscopes. Advancements in microscopy were essential to the early study of infectious diseases. Stamps of Germany (DDR) 1980, MiNr Zusammendruck 2534-2537.jpg
East German postage stamps depicting four antique microscopes. Advancements in microscopy were essential to the early study of infectious diseases.

Ideas of contagion became more popular in Europe during the Renaissance, particularly through the writing of the Italian physician Girolamo Fracastoro. [54]

Anton van Leeuwenhoek (1632–1723) advanced the science of microscopy by being the first to observe microorganisms, allowing for easy visualization of bacteria.

In the mid-19th century John Snow and William Budd did important work demonstrating the contagiousness of typhoid and cholera through contaminated water. Both are credited with decreasing epidemics of cholera in their towns by implementing measures to prevent contamination of water. [55]

Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine for rabies.

Robert Koch, provided the study of infectious diseases with a scientific basis known as Koch's postulates.

Edward Jenner, Jonas Salk and Albert Sabin developed effective vaccines for smallpox and polio, which would later result in the eradication and near-eradication of these diseases, respectively.

Alexander Fleming discovered the world's first antibiotic, Penicillin, which Florey and Chain then developed.

Gerhard Domagk developed sulphonamides, the first broad spectrum synthetic antibacterial drugs.

Medical specialists

The medical treatment of infectious diseases falls into the medical field of Infectious Disease and in some cases the study of propagation pertains to the field of Epidemiology. Generally, infections are initially diagnosed by primary care physicians or internal medicine specialists. For example, an "uncomplicated" pneumonia will generally be treated by the internist or the pulmonologist (lung physician). The work of the infectious diseases specialist therefore entails working with both patients and general practitioners, as well as laboratory scientists, immunologists, bacteriologists and other specialists.

An infectious disease team may be alerted when:

Society and culture

A number of studies have reported associations between pathogen load in an area and human behavior. Higher pathogen load is associated with decreased size of ethnic and religious groups in an area. This may be due high pathogen load favoring avoidance of other groups, which may reduce pathogen transmission, or a high pathogen load preventing the creation of large settlements and armies that enforce a common culture. Higher pathogen load is also associated with more restricted sexual behavior, which may reduce pathogen transmission. It also associated with higher preferences for health and attractiveness in mates. Higher fertility rates and shorter or less parental care per child is another association that may be a compensation for the higher mortality rate. There is also an association with polygyny which may be due to higher pathogen load, making selecting males with a high genetic resistance increasingly important. Higher pathogen load is also associated with more collectivism and less individualism, which may limit contacts with outside groups and infections. There are alternative explanations for at least some of the associations although some of these explanations may in turn ultimately be due to pathogen load. Thus, polygny may also be due to a lower male:female ratio in these areas but this may ultimately be due to male infants having increased mortality from infectious diseases. Another example is that poor socioeconomic factors may ultimately in part be due to high pathogen load preventing economic development. [56]

Fossil record

Herrerasaurus skull. Herrerasaurus1.JPG
Herrerasaurus skull.

Evidence of infection in fossil remains is a subject of interest for paleopathologists, scientists who study occurrences of injuries and illness in extinct life forms. Signs of infection have been discovered in the bones of carnivorous dinosaurs. When present, however, these infections seem to tend to be confined to only small regions of the body. A skull attributed to the early carnivorous dinosaur Herrerasaurus ischigualastensis exhibits pit-like wounds surrounded by swollen and porous bone. The unusual texture of the bone around the wounds suggests they were afflicted by a short-lived, non-lethal infection. Scientists who studied the skull speculated that the bite marks were received in a fight with another Herrerasaurus. Other carnivorous dinosaurs with documented evidence of infection include Acrocanthosaurus , Allosaurus , Tyrannosaurus and a tyrannosaur from the Kirtland Formation. The infections from both tyrannosaurs were received by being bitten during a fight, like the Herrerasaurus specimen. [57]

Outer space

A 2006 Space Shuttle experiment found that Salmonella typhimurium , a bacterium that can cause food poisoning, became more virulent when cultivated in space. [58] On April 29, 2013, scientists in Rensselaer Polytechnic Institute, funded by NASA, reported that, during spaceflight on the International Space Station, microbes seem to adapt to the space environment in ways "not observed on Earth" and in ways that "can lead to increases in growth and virulence". [59] More recently, in 2017, bacteria were found to be more resistant to antibiotics and to thrive in the near-weightlessness of space. [60] Microorganisms have been observed to survive the vacuum of outer space. [61] [62]

See also

Notes and references

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Classification
D

Related Research Articles

A human pathogen is a pathogen that causes disease in humans.

Antiviral drugs are a class of medication used specifically for treating viral infections rather than bacterial ones. Most antivirals are used for specific viral infections, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development.

Kochs postulates four criteria showing a causal relationship between a causative microbe and a disease

Koch's postulates are four criteria designed to establish a causative relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884, based on earlier concepts described by Jakob Henle, and refined and published by Koch in 1890. Koch applied the postulates to describe the etiology of cholera and tuberculosis, but they have been controversially generalized to other diseases. These postulates were generated prior to understanding of modern concepts in microbial pathogenesis that cannot be examined using Koch's postulates, including viruses or asymptomatic carriers. They have largely been supplanted by other criteria such as the Bradford Hill criteria for infectious disease causality in modern public health.

Virulence is a pathogen's or microbe's ability to infect or damage a host.

In medicine, public health, and biology, transmission is the passing of a pathogen causing communicable disease from an infected host individual or group to a particular individual or group, regardless of whether the other individual was previously infected.

An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria and antifungals are used against fungi. They can also be classified according to their function. Agents that kill microbes are called microbicidal, while those that merely inhibit their growth are called biostatic. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. Tick-borne illnesses are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. Because individual ticks can harbor more than one disease-causing agent, patients can be infected with more than one pathogen at the same time, compounding the difficulty in diagnosis and treatment. As of 2016, 16 tick-borne diseases of humans are known.

Opportunistic infection

An opportunistic infection is an infection caused by pathogens that take advantage of an opportunity not normally available, such as a host with a weakened immune system, an altered microbiota, or breached integumentary barriers. Many of these pathogens do not cause disease in a healthy host that has a normal immune system. However, a compromised immune system, which is seriously debilitated and has lowered resistance to infection, a penetrating injury, or a lack of competition from normal commensals presents an opportunity for the pathogen to infect.

Murine typhus typhus transmitted by fleas (Xenopsylla cheopis), usually on rats

Murine typhus is a form of typhus transmitted by fleas, usually on rats. Murine typhus is an under-recognized entity, as it is often confused with viral illnesses. Most people who are infected do not realize that they have been bitten by fleas.

Vertically transmitted infection infection caused by pathogens that uses mother-to-child transmission

A vertically transmitted infection is an infection caused by pathogens that uses mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother gets an infection as an intercurrent disease in pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infection.

Community-acquired pneumonia refers to pneumonia contracted by a person with little contact with the healthcare system. The chief difference between hospital-acquired pneumonia (HAP) and CAP is that patients with HAP live in long-term care facilities or have recently visited a hospital. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.

Meningoencephalitis central nervous system disease that involves encephalitis which occurs along with meningitis

Meningoencephalitis, also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.

Antigenic variation refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters its surface proteins in order to avoid a host immune response. It is related to phase variation. Immune evasion is particularly important for organisms that target long-lived hosts, repeatedly infect a single host and are easily transmittable. Antigenic variation not only enables immune evasion by the pathogen, but also allows the microbes to cause re-infection, as their antigens are no longer recognized by the host's immune system. When an organism is exposed to a particular antigen an immune response is stimulated and antibodies are generated to target that specific antigen. The immune system will then "remember" that particular antigen, and defenses aimed at that antigen become part of the immune system’s acquired immune response. If the same pathogen tries to re-infect the same host the antibodies will act rapidly to target the pathogen for destruction. However, if the pathogen can alter its surface antigens, it can evade the host's acquired immune system. This will allow the pathogen to re-infect the host while the immune system generates new antibodies to target the newly identified antigen. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. There are many molecular mechanisms behind antigenic variation, including gene conversion, site-specific DNA inversions, hypermutation, as well as recombination of sequence cassettes. In all cases, antigenic variation and phase variation result in a heterogenic phenotype of a clonal population. Individual cells either express the phase-variable protein(s) or express one of multiple antigenic forms of the protein. This form of regulation has been identified mainly, but not exclusively, for a wide variety of surface structures in pathogens and is implicated as a virulence strategy.

Host tropism is the infection specificity of certain pathogens to particular hosts and host tissues. This type of tropism explains why most pathogens are only capable of infecting a limited range of host organisms.

Medical microbiology medical specialty

Medical microbiology , the large subset of microbiology that is applied to medicine, is a branch of medical science concerned with the prevention, diagnosis and treatment of infectious diseases. In addition, this field of science studies various clinical applications of microbes for the improvement of health. There are four kinds of microorganisms that cause infectious disease: bacteria, fungi, parasites and viruses, and one type of infectious protein called prion.

Introduction to viruses A non-technical introduction to the subject.

A virus is a biological agent that reproduces inside the cells of living hosts. When infected by a virus, a host cell is forced to produce thousands of identical copies of the original virus at an extraordinary rate. Unlike most living things, viruses do not have cells that divide; new viruses are assembled in the infected host cell. But unlike still simpler infectious agents, viruses contain genes, which gives them the ability to mutate and evolve. Over 5,000 species of viruses have been discovered.

Airborne disease disease that is caused by pathogens and transmitted through the air

An airborne disease is any disease that is caused by pathogens that can be transmitted through the air. Such diseases include many of considerable importance both in human and veterinary medicine. The relevant pathogens may be viruses, bacteria, or fungi, and they may be spread through breathing, talking, coughing, sneezing, raising of dust, spraying of liquids, toilet flushing or any activities which generates aerosol particles or droplets. Human airborne diseases do not include conditions caused by air pollution such as Volatile Organic Compounds (VOCs), gases and any airborne particles, though their study and prevention may help inform the science of airborne disease transmission.

The host-pathogen interaction is defined as how microbes or viruses sustain themselves within host organisms on a molecular, cellular, organismal or population level. This term is most commonly used to refer to disease-causing microorganisms although they may not cause illness in all hosts. Because of this, the definition has been expanded to how known pathogens survive within their host, whether they cause disease or not.