Aninfection is the invasion oftissues bypathogens, their multiplication, and the reaction ofhost tissues to the infectious agent and thetoxins they produce.[1] Aninfectious disease, also known as atransmissible disease orcommunicable disease, is anillness resulting from an infection.
Treatment for infections depends on the type of pathogen involved. Common medications include:
Antibiotics for bacterial infections.
Antivirals for viral infections.
Antifungals for fungal infections.
Antiprotozoals for protozoan infections.
Antihelminthics for infections caused by parasitic worms.
Infectious diseases remain a significant global health concern, causing approximately 9.2 million deaths in 2013 (17% of all deaths).[3] The branch ofmedicine that focuses on infections is referred to asinfectious diseases.[4]
Arthropods such asticks,mites,fleas, andlice, can also cause human disease, which conceptually are similar to infections, but invasion of a human or animal body by these macroparasites is usually termedinfestation.
Thesigns and symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such asfatigue, loss of appetite, weight loss,fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skinrashes,coughing, or arunny nose.[9]
In certain cases, infectious diseases may beasymptomatic 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 anasymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host.[10]
As 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] Distinguishing the two is important, since viral infections cannot be cured byantibiotics whereas bacterial infections can.[12]
In 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 viralconjunctivitis or "pink eye" and herpes. Only a few viral infections are painful, likeherpes. 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. Anear 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.[13]
Chain of infection; the chain of events that lead to infection
There is a general chain of events that applies to infections, sometimes called thechain of infection[14] ortransmission chain. 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]
Infection of aningrown 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 with compromised or weakened immune systems have an increased susceptibility to chronic or persistent infections. Individuals who have a suppressedimmune system are particularly susceptible toopportunistic infections. Entrance to the host athost–pathogen interface, generally occurs through themucosa in orifices like theoral 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.[16]
Wound colonization refers to non-replicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue is injured.[17] Allmulticellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either amutualistic orcommensal relationship with the host. An example of the former is theanaerobic bacteria species, which colonizes themammaliancolon, and an example of the latter are the various species ofstaphylococcus that exist onhuman 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 mostvirulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such asCorynebacteria sp. andViridans streptococci, prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with the host, preventing infection and speedingwound healing.
This image depicts the steps of pathogenic infection.[18][19][20]
The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include:
the route of entry of thepathogen and the access to host regions that it gains
As an example, severalstaphylococcal species remain harmless on the skin, but, when present in a normallysterile space, such as in the capsule of ajoint or theperitoneum, multiply without resistance and cause harm.[21]
An interesting fact thatgas 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 nearlysterile. 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 theJournal of the American Medical Association's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection.[22] 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 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, andstaphylococcus releases toxins that produce shock andsepsis. Not all infectious agents cause disease in all hosts. For example, less than 5% of individuals infected withpolio develop disease.[23] On the other hand, some infectious agents are highly virulent. Theprion causingmad cow disease andCreutzfeldt–Jakob disease invariably kills all animals and people that are infected.[24]
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.[25]
Persistent infections cause millions of deaths globally each year.[26] Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries.[27][28]
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:[29]
Droplet contact, also known as therespiratory route, and the resultant infection can be termedairborne disease. If an infected person coughs or sneezes on another person the microorganisms, suspended in warm, moist droplets, may enter the body through the nose, mouth or eye surfaces.
Fecal-oral transmission, wherein foodstuffs or water become contaminated (by people not washing their hands before preparing food, or untreated sewage being released into a drinking water supply) and the people who eat and drink them become infected. Commonfecal-oral transmitted pathogens includeVibrio cholerae,Giardia species,rotaviruses,Entamoeba histolytica,Escherichia coli, andtape worms.[30] Most of these pathogens causegastroenteritis.
Oral transmission, diseases that are transmitted primarily by oral means may be caught through direct oral contact such askissing, or by indirect contact such as by sharing a drinking glass or a cigarette.
Transmission by direct contact, Some diseases that are transmissible by direct contact includeathlete's foot,impetigo andwarts.
Vehicle transmission, transmission by an inanimate reservoir (food, water, soil).[31]
Vector-borne transmission, transmitted by avector, which is anorganism that does not causedisease itself but that transmits infection by conveyingpathogens from onehost to another.[32]
The relationship betweenvirulence versus transmissibility is complex; with studies have shown that there were no clear relationship between the two.[33][34] There is still a small number of evidence that partially suggests a link between virulence and transmissibility.[35][36][37]
Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly.[38] In practice most minor infectious diseases such aswarts,cutaneousabscesses,respiratory system infections anddiarrheal 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.[39]
Diagnosis of infectious disease is nearly always initiated bymedical 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.[39]
Many infectious organisms are identified without culture and microscopy. This is especially true for viruses, which cannot grow in culture. For some suspected pathogens, doctors may conduct tests that examine a patient's blood or other body fluids forantigens orantibodies that indicate presence of a specific pathogen that the doctor suspects.[39]
Other techniques (such asX-rays,CAT scans,PET scans orNMR) 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 boneabscess or aspongiform encephalopathy produced by aprion.[40]
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 likely to bebenign.[41]
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 calledpathognomonic signs; but these are rare. Not all infections are symptomatic.[42]
In children the presence ofcyanosis, rapid breathing, poor peripheral perfusion, or apetechial rash increases the risk of a serious infection by greater than 5 fold.[43] Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C.[43]
Many diagnostic approaches depend onmicrobiological culture to isolate a pathogen from the appropriate clinical specimen.[44] In a microbial culture, agrowth 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. Many pathogenicbacteria are easily grown on nutrientagar, a form of solid medium that supplies carbohydrates and proteins necessary for growth, along with copious amounts of water. A single bacterium will grow into a visible mound on the surface of the plate called acolony, 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 (itsstrain), 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 ofviruses: 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".Eukaryoticparasites may also be grown in culture as a means of identifying a particular agent.[45]
In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such asMycobacterium leprae andTreponema 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 inembryonated 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 thevector of the Chagas agentT. cruzi, an uninfectedtriatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth ofT. cruzi within its gut.[46]
Another principal tool in the diagnosis of infectious disease ismicroscopy.[47] 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 compoundlight microscope, or with instruments as complex as anelectron 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 withbiochemicalstaining techniques, and can be made exquisitely specific when used in combination withantibody based techniques. For example, the use of antibodies made artificiallyfluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specificantigens present on a pathogen. Afluorescence 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.[48]
Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basicdyes due to theelectrostatic 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 asGiemsa stain orcrystal 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 thetaxonomic classification of microbes as well. Two methods, theGram stain and theacid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groupsBacillota andActinomycetota, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota generaMycobacterium andNocardia.[49]
Biochemical tests used in the identification of infectious agents include the detection ofmetabolic orenzymatic products characteristic of a particular infectious agent. Since bacteria fermentcarbohydrates in patterns characteristic of theirgenus andspecies, the detection offermentation products is commonly used in bacterial identification.Acids,alcohols andgases are usually detected in these tests when bacteria are grown inselective liquid or solid media.[50]
The isolation ofenzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neitherRNA replicases norreverse transcriptase, and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral proteinhemagglutinin to bindred blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not anenzyme and has no metabolic function.[51]
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 requirerefrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive.[10]
Complex serological techniques have been developed into what are known asimmunoassays. 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.
Nucleic acid testing conducted using an Abbott Laboratories ID Now device
Technologies based upon thepolymerase 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 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 thegenomes of infectious agents, and with time those genomes will be known if they are not already.[52]
Thus, the technological ability to detect any infectious agent rapidly and specifically is 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 theclostridial diseases (tetanus andbotulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potentneurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.[52]
Given the wide range of bacterial, viral, fungal, protozoal, and helminthic pathogens that cause debilitating and life-threatening illnesses, the ability to quickly identify the cause of infection is important yet often challenging. For example, more than half of cases ofencephalitis, a severe illness affecting the brain, remain undiagnosed, despite extensive testing using the standard of care (microbiological culture) and state-of-the-art clinical laboratory methods.Metagenomic sequencing-based diagnostic tests are currently being developed for clinical use and show promise as a sensitive, specific, and rapid way to diagnose infection using a single all-encompassing test.[53] This test is similar to current PCR tests; however, an untargeted whole genome amplification is used rather thanprimers for a specific infectious agent. This amplification step is followed bynext-generation sequencing orthird-generation sequencing,alignment comparisons, andtaxonomic classification using large databases of thousands of pathogen and commensalreference genomes. Simultaneously,antimicrobial resistance genes within pathogen andplasmid genomes are sequenced and aligned to the taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous toantibiotic sensitivity testing – to facilitateantimicrobial stewardship and allow for the optimization of treatment using the most effective drugs for a patient's infection.
Metagenomic sequencing could prove especially useful for diagnosis when the patient isimmunocompromised. 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 a clinical diagnosis based on presentation more difficult. Thirdly, diagnostic methods that rely on the detection of antibodies are more likely to fail. A rapid, sensitive, specific, and untargeted test for all known human pathogens that detects the presence of the organism's DNA rather than antibodies is therefore highly desirable.
A temporary drive-in testing site for COVID-19 set up with tents in a parking lot
There is usually anindication 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 ofAZT for the treatment ofAIDS, 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 ofHIV in specific communities permitted the advancement ofhypotheses 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 specificserological diagnostic identification, and latergenotypic or molecular identification, of HIV also enabled the development of hypotheses as to thetemporal andgeographical origins of the virus, as well as a myriad of other hypothesis.[10] The development of molecular diagnostic tools have enabled physicians and researchers to monitor the efficacy of treatment withanti-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.
Symptomatic infections areapparent andclinical, whereas an infection that is active but does not produce noticeable symptoms may be calledinapparent,silent,subclinical, oroccult. An infection that is inactive or dormant is called alatent infection.[54] An example of a latent bacterial infection islatent tuberculosis. Some viral infections can also be latent, examples oflatent viral infections are any of those from theHerpesviridae family.[55]
The wordinfection candenote any presence of a particular pathogen at all (no matter how little) but also is often used in asense implying aclinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates someambiguity or prompts someusage discussion; to get around this it is common forhealth professionals to speak ofcolonization (rather thaninfection) when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present.[56]
Different terms are used to describe how and where infections present over time. In anacute infection, symptoms develop rapidly; its course can either be rapid or protracted. Inchronic infection, symptoms usually develop gradually over weeks or months and are slow to resolve.[57] Insubacute infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. Afocal infection is an initial site of infection from which organisms travelvia the bloodstream to another area of the body.[58]
Among the many varieties ofmicroorganisms, relatively few cause disease in otherwise healthy individuals.[59] Infectious disease results from the interplay between those fewpathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depend 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 asprimary pathogens or asopportunistic pathogens.[60]
Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsicvirulence (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.[61]
While a primary infection can practically be viewed as theroot cause of an individual's current health problem, a secondary infection is asequela orcomplication of that root cause. For example, an infection due to aburn orpenetrating trauma (the root cause) is a secondary infection. Primary pathogens often cause primary infection and often cause secondary infection. Usually, opportunistic infections are viewed as secondary infections (because immunodeficiency orinjury was the predisposing factor).[60]
Other types of infection consist of mixed,iatrogenic,nosocomial, and community-acquired infection. A mixed infection is an infection that is caused by two or more pathogens. An example of this isappendicitis, which is caused byBacteroides fragilis andEscherichia coli. The second is an iatrogenic infection. This type of infection is one that is transmitted from a health care worker to a patient. A nosocomial infection is also one that occurs in a health care setting. Nosocomial infections are those that are acquired during a hospital stay. Lastly, a community-acquired infection is one in which the infection is acquired from a whole community.[58]
One manner of proving that a given disease is infectious, is to satisfyKoch's postulates (first proposed byRobert Koch), which require that first, theinfectious agent be identifiable only in patients who have the disease, and not in healthy controls, and second, that patients who contract the infectious agent also develop the disease. These postulates were first used in the discovery thatMycobacteria species causetuberculosis.[62]
However, Koch's postulates cannot usually be tested in modern practice for ethical reasons. Proving them would require experimental infection of a healthy individual with apathogen produced as a pure culture. Conversely, even clearly infectious diseases do not always meet the infectious criteria; for example,Treponema pallidum, the causativespirochete ofsyphilis, cannot beculturedin vitro – however the organism can be cultured in rabbittestes. 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.[63]
Epidemiology, or the study and analysis of who, why and where disease occurs, and what determines whether various populations have a disease, is another important tool used to understand infectious disease. Epidemiologists may determine differences among groups within a population, such as whether certain age groups have a greater or lesser rate of infection; whether groups living in different neighborhoods are more likely to be infected; and by other factors, such as gender and race. Researchers also may assess whether a diseaseoutbreak is sporadic, or just an occasional occurrence;endemic, with a steady level of regular cases occurring in a region;epidemic, with a fast arising, and unusually high number of cases in a region; orpandemic, which is a global epidemic. If the cause of the infectious disease is unknown, epidemiology can be used to assist with tracking down the sources of infection.[64]
Infectious diseases are sometimes calledcontagious diseases 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. All contagious diseases are infectious, but not vice versa.[65][66] Other types of infectious, transmissible, or 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 calledquarantine) of those affected. 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 direct contact are through person to person anddroplet 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. Thebasic reproduction number of an infectious disease measures how easily it spreads through direct or indirect contact.[67][68]
Washing one's hands, a form ofhygiene, is an effective way to prevent the spread of infectious disease.[71]
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. Frequenthand washing remains the most important defense against the spread of unwanted organisms.[72] There are other forms of prevention such as avoiding the use of illicit drugs, using acondom, 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.[citation needed]
disinfectants, which destroy microorganisms found on non-living objects.
antibiotics, calledprophylactic when given as prevention rather as treatment of infection. However, long term use of antibiotics leads to resistance of bacteria. While humans do not become immune to antibiotics, the bacteria does. Thus, avoiding using antibiotics longer than necessary helps preventing bacteria from forming mutations that aide in antibiotic resistance.
One of the ways to prevent or slow down the transmission of infectious diseases is to recognize the different characteristics of various diseases.[73] Some critical disease characteristics that should be evaluated includevirulence, distance traveled by those affected, and level of contagiousness. The human strains ofEbola virus, for example, incapacitate those infected extremely quickly and kill them soon after. As a result, those affected by this disease do not have the opportunity to travel very far from the initial infection zone.[74] Also, this virus must spread through skin lesions or permeable membranes such as the eye. Thus, the initial stage ofEbola 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, thehuman immunodeficiency virus (HIV) kills its victims very slowly by attacking their immune system.[10] 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 anepidemic.[citation needed]
Another effective way to decrease the transmission rate of infectious diseases is to recognize the effects ofsmall-world networks.[73] 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 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.[75] Another example is the use of ring culling or vaccination of potentially susceptible livestock in adjacent farms to prevent the spread of thefoot-and-mouth virus in 2001.[76]
A general method to prevent transmission ofvector-borne pathogens ispest control.
In cases where infection is merely suspected, individuals may bequarantined until the incubation period has passed and the disease manifests itself or the person remains healthy. Groups may undergo quarantine, or in the case of communities, acordon sanitaire may be imposed to prevent infection from spreading beyond the community, or in the case ofprotective sequestration, into a community. Public health authorities may implement other forms ofsocial distancing, such as school closings,lockdowns or temporary restrictions (e.g.circuit breakers)[77] to control an epidemic.
Mary Mallon (a.k.a. Typhoid Mary) was an asymptomatic carrier oftyphoid 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.[59] This process requiresimmune mechanisms to kill or inactivate theinoculum of the pathogen. Specific acquiredimmunity against infectious diseases may be mediated byantibodies and/orT lymphocytes. Immunity mediated by these two factors may be manifested by:
a direct effect upon a pathogen, such as antibody-initiatedcomplement-dependent bacteriolysis,opsonoization,phagocytosis and killing, as occurs for some bacteria,
neutralization of viruses so that these organisms cannot enter cells,
or by T lymphocytes, which will kill a cell parasitized by a microorganism.
The immune system response to a microorganism often causes symptoms such as a highfever andinflammation, and has the potential to be more devastating than direct damage caused by a microbe.[10]
Resistance to infection (immunity) may be acquired following a disease, byasymptomatic carriage of the pathogen, by harboring an organism with a similar structure (crossreacting), or byvaccination. Knowledge of the protective antigens and specific acquired host immune factors is more complete for primary pathogens than foropportunistic pathogens. There is also the phenomenon ofherd 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.[78]
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 naturalserum antibodies to the surfacepolysaccharides of some agents although they have had little or no contact with the agent, these natural antibodies confer specific protection to adults and arepassively transmitted to newborns.
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.[79]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 1hepatitis C treated withPegylated interferon-alpha-2a orPegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined withribavirin, 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 inNature,[80] 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 fromNature[81] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.
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; includingantitubercular),antiviral,antifungal andantiparasitic (includingantiprotozoal andantihelminthic) agents. Depending on the severity and the type of infection, the antibiotic may be given by mouth or by injection, or may be appliedtopically. Severe infections of thebrain are usually treated withintravenous antibiotics. Sometimes, multiple antibiotics are used in case there isresistance 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 includepenicillin,cephalosporins,aminoglycosides,macrolides,quinolones andtetracyclines.[82][83]
Not all infections require treatment, and for manyself-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.[84]
Pandemics such asCOVID-19 show that people dramatically differ in their susceptibility to infection. This may be because of general health, age, or their immune status, e.g. when they have been infected previously. However, it also has become clear that there are genetic factor which determine susceptibility to infection. For instance, up to 40% ofSARS-CoV-2 infections may be asymptomatic, suggesting that many people are naturally protected from disease.[85] Large genetic studies have defined risk factors for severe SARS-CoV-2 infections, andgenome sequences from 659 patients with severe COVID-19 revealed genetic variants that appear to be associated with life-threatening disease. One gene identified in these studies is type Iinterferon (IFN). Autoantibodies against type I IFNs were found in up to 13.7% of patients with life-threatening COVID-19, indicating that a complex interaction between genetics and theimmune system is important for natural resistance to Covid.[86]
Similarly, mutations in theERAP2 gene, encoding endoplasmic reticulum aminopeptidase 2, seem to increase the susceptibility to theplague, the disease caused by an infection with the bacteriaYersinia pestis. People who inherited two copies of a complete variant of the gene were twice as likely to have survived the plague as those who inherited two copies of a truncated variant.[87]
Susceptibility also determined the epidemiology of infection, given that different populations have different genetic and environmental conditions that affect infections.
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 areHIV/AIDS,TB andmalaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases includepertussis,poliomyelitis,diphtheria,measles andtetanus. 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.[96]
TheGreat Plague of Marseille in 1720 killed 100,000 people in the city and the surrounding provinces.
With their potential for unpredictable and explosive impacts, infectious diseases have been major actors in humanhistory.[97] Apandemic (or globalepidemic) is a disease that affects people over an extensive geographical area. For example:
Plague of Justinian, from 541 to 542, killed between 50% and 60% of Europe's population.[98]
TheBlack Death of 1347 to 1352 killed 25 million in Europe over five years. The plague reduced the old world population from an estimated 450 million to between 350 and 375 million in the 14th century.
The introduction ofsmallpox, measles, andtyphus to the areas of Central and South America by European explorers during the 15th and 16th centuries caused pandemics among the native inhabitants. Between 1518 and 1568 disease pandemics are said to have caused the population ofMexico to fall from 20 million to 3 million.[99]
The first Europeaninfluenza epidemic occurred between 1556 and 1560, with an estimated mortality rate of 20%.[99]
Smallpox killed an estimated 60 million Europeans during the 18th century[100] (approximately 400,000 per year).[101] Up to 30% of those infected, including 80% of the children under 5 years of age, died from the disease, and one-third of the survivors went blind.[102]
In the 19th century,tuberculosis killed an estimated one-quarter of the adult population of Europe;[103] by 1918 one in six deaths in France were still caused by TB.
The Influenza Pandemic of 1918 (or theSpanish flu) killed 25–50 million people (about 2% of world population of 1.7 billion).[104] TodayInfluenza kills about 250,000 to 500,000 worldwide each year.
In 2021, COVID-19 emerged as a major global health crisis, directly causing 8.7 million deaths, making it one of the leading causes of mortality worldwide.[105]
In most cases, microorganisms live in harmony with their hosts viamutual orcommensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host.
Human activity is involved with manyemerging infectious diseases, such asenvironmental change enabling a parasite to occupy newniches. When that happens, apathogen that had been confined to a remote habitat has a wider distribution and possibly a newhost organism. Parasites jumping from nonhuman to human hosts are known aszoonoses. Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host.[106]
Encroachment on wildlifehabitats. The construction of new villages and housing developments in rural areas force animals to live in dense populations, creating opportunities for microbes to mutate and emerge.[108]
Changes inagriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases.
The destruction ofrain forests. As countries make use of their rain forests, by building roads through forests and clearing areas for settlement or commercial ventures, people encounter insects and other animals harboring previously unknown microorganisms.
Uncontrolledurbanization. The rapid growth of cities in many developing countries tends to concentrate large numbers of people into crowded areas with poor sanitation. These conditions foster transmission of contagious diseases.
Moderntransport. Ships and other cargo carriers often harbor unintended "passengers", that can spread diseases to faraway destinations. While with international jet-airplane travel, people infected with a disease can carry it to distant lands, or home to their families, before their first symptoms appear.
A basic form of contagion theory was proposed byPersian physicianIbn Sina (known as Avicenna in Europe) inThe Canon of Medicine (1025), which later became the most authoritative medical textbook in Europe up until the 16th century. In Book IV of theCanon, Ibn Sina discussedepidemics, outlining the classicalmiasma theory and attempting to blend it with his own early contagion theory. He mentioned that people can transmit disease to others by breath, noted contagion withtuberculosis, and discussed the transmission of disease through water and dirt.[115] The concept of invisible contagion was later discussed by severalIslamic scholars in theAyyubid Sultanate who referred to them asnajasat ("impure substances"). Thefiqh scholarIbn al-Haj al-Abdari (c. 1250–1336), while discussingIslamic diet andhygiene, gave warnings about how contagion can contaminate water, food, and garments, and could spread through the water supply, and may have implied contagion to be unseen particles.[116]
When theBlack Deathbubonic plague reachedAl-Andalus in the 14th century, the Arab physicians Ibn Khatima (c. 1369) andIbn al-Khatib (1313–1374) hypothesised that infectious diseases were caused by "minute bodies" and described how they can be transmitted through garments, vessels and earrings.[117] Ideas of contagion became more popular in Europe during theRenaissance, particularly through the writing of the Italian physicianGirolamo Fracastoro.[118]Anton van Leeuwenhoek (1632–1723) advanced the science ofmicroscopy by being the first to observe microorganisms, allowing for easy visualization of bacteria.
In the mid-19th centuryJohn Snow andWilliam 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.[119]Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine forrabies.Robert Koch provided the study of infectious diseases with a scientific basis known asKoch's postulates.Edward Jenner,Jonas Salk andAlbert Sabin developed effective vaccines forsmallpox andpolio, which would later result in theeradication and near-eradication of these diseases, respectively.Alexander Fleming discovered the world's firstantibiotic,penicillin, which Florey and Chain then developed.Gerhard Domagk developedsulphonamides, the first broad spectrumsynthetic antibacterial drugs.[citation needed]
Several 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. Higherfertility 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 withpolygyny 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, polygyny 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.[121]
Evidence of infection infossil remains is a subject of interest forpaleopathologists, 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 dinosaurHerrerasaurus ischigualastensis exhibits pit-like wounds surrounded by swollen and porous bone. The unusual texture of the bone around the wounds suggests they were affected by a short-lived, non-lethal infection. Scientists who studied the skull speculated that the bite marks were received in a fight with anotherHerrerasaurus. Other carnivorous dinosaurs with documented evidence of infection includeAcrocanthosaurus,Allosaurus,Tyrannosaurus and a tyrannosaur from theKirtland Formation. The infections from both tyrannosaurs were received by being bitten during a fight, like theHerrerasaurus specimen.[122]
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