Editing Infection (section)

==Diagnosis==
Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly.<ref>{{cite journal | vauthors = Seventer JM, Hochberg NS | title = Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control | journal = International Encyclopedia of Public Health | date=October 2016 | pages = 22–39 | doi= 10.1016/B978-0-12-803678-5.00516-6 | pmc = 7150340 | isbn = 9780128037089 }}</ref> In practice most minor infectious diseases such as [[wart]]s, [[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.<ref name=":1">{{Cite web |last=Vazquez-Pertejo |first=Maria T. |date=October 2022 |title=Diagnosis of Infectious Disease - Infections |url=https://www.merckmanuals.com/home/infections/diagnosis-of-infectious-disease/diagnosis-of-infectious-disease |archive-url=https://web.archive.org/web/20240102154139/https://www.merckmanuals.com/home/infections/diagnosis-of-infectious-disease/diagnosis-of-infectious-disease |archive-date=2024-01-02 |access-date=2024-01-02 |website=Merck Manuals Consumer Version |language=English}}</ref>

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.<ref name=":1" />

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 for [[antigen]]s or [[Antibody|antibodies]] that indicate presence of a specific pathogen that the doctor suspects.<ref name=":1" />

Other techniques (such as [[X-ray]]s, [[CAT scans]], [[PET scan]]s 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]].<ref>{{Cite journal |last1=Weaver |first1=Jennifer S. |last2=Omar |first2=Imran M. |last3=Mar |first3=Winnie A. |last4=Klauser |first4=Andrea S. |last5=Winegar |first5=Blair A. |last6=Mlady |first6=Gary W. |last7=McCurdy |first7=Wendy E. |last8=Taljanovic |first8=Mihra S. |date=2022-03-05 |title=Magnetic resonance imaging of musculoskeletal infections |journal=Polish Journal of Radiology |volume=87 |pages=e141–e162 |doi=10.5114/pjr.2022.113825 |issn=1733-134X |pmc=9047866 |pmid=35505859}}</ref>

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 be [[benign]].<ref>{{Cite journal |last1=Pinsky |first1=B. A. |last2=Hayden |first2=R. T. |date=2019-08-26 |title=Cost-Effective Respiratory Virus Testing |journal=Journal of Clinical Microbiology |volume=57 |issue=9 |pages=e00373–19 |doi=10.1128/JCM.00373-19 |issn=0095-1137 |pmc=6711893 |pmid=31142607}}</ref>

===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.<ref name=Sternak>{{cite journal|last1=Ljubin-Sternak|first1=Suncanica|last2=Mestrovic|first2=Tomislav|title=Review: Chlamydia trachonmatis and Genital Mycoplasmias: Pathogens with an Impact on Human Reproductive Health|journal=Journal of Pathogens|page=3 |date=2014|volume=2014|issue=183167|doi=10.1155/2014/183167|pmid=25614838|pmc=4295611|doi-access=free}}</ref>

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.<ref name=Lancet10>{{cite journal |vauthors=Van den Bruel A, Haj-Hassan T, Thompson M, Buntinx F, Mant D | title = Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review | journal = Lancet | volume = 375 | issue = 9717 | pages = 834–45 | date = March 2010 | pmid = 20132979 | doi = 10.1016/S0140-6736(09)62000-6 | s2cid = 28014329 }}</ref> Other important indicators include parental concern, clinical instinct, and temperature greater than 40&nbsp;°C.<ref name=Lancet10/>

===Microbial culture===
[[File:K pneumoniae M morganii providencia styphimuriuma.JPG|thumb|200px|Four [[nutrient agar]] plates growing colonies of common [[Gram negative]] bacteria]]
Many diagnostic approaches depend on [[microbiological culture]] to isolate a pathogen from the appropriate clinical specimen.<ref>{{cite book |last1=Murray |first1=Patrick R. |title=Medical Microbiology |date=2021 |publisher=Elsevier |location=Philadelphia |isbn=978-0-323-67450-8 |edition=9th |chapter=Laboratory Diagnosis of Bacterial Diseases}}</ref> 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. Many pathogenic [[bacteria]] are easily grown on nutrient [[Agar#Microbiology|agar]], 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 a [[Colony (biology)|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 (biology)|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 [[virus]]es: 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.<ref>{{Cite journal |last1=Joyce |first1=Bradley R. |last2=Queener |first2=Sherry F. |last3=Wek |first3=Ronald C. |last4=Sullivan |first4=William J. |date=2010-10-05 |title=Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=107 |issue=40 |pages=17200–17205 |doi=10.1073/pnas.1007610107 |issn=0027-8424 |pmc=2951449 |pmid=20855600|bibcode=2010PNAS..10717200J |doi-access=free }}</ref>

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 [[embryo]]nated 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 (epidemiology)|vector]] of the Chagas agent ''T. cruzi'', an uninfected [[Triatominae|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.<ref>{{Cite journal |last1=Elliot |first1=Simon L. |last2=Rodrigues |first2=Juliana de O. |last3=Lorenzo |first3=Marcelo G. |last4=Martins-Filho |first4=Olindo A. |last5=Guarneri |first5=Alessandra A. |date=2015 |title=Trypanosoma cruzi, etiological agent of Chagas disease, is virulent to its triatomine vector Rhodnius prolixus in a temperature-dependent manner |journal=PLOS Neglected Tropical Diseases |volume=9 |issue=3 |pages=e0003646 |doi=10.1371/journal.pntd.0003646 |issn=1935-2735 |pmc=4368190 |pmid=25793495 |doi-access=free }}</ref>

===Microscopy===
Another principal tool in the diagnosis of infectious disease is [[microscopy]].<ref>{{cite book |last1=Murray |first1=Patrick R. |title=Medical Microbiology |date=2021 |publisher=Elsevier |location=Philadelphia |isbn=978-0-323-67450-8 |edition=9th |chapter=Microscopy and In Vitro Culture}}</ref> 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 [[antigen]]s 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.<ref>{{Cite journal |last1=Parveen |first1=Nagma |last2=Borrenberghs |first2=Doortje |last3=Rocha |first3=Susana |last4=Hendrix |first4=Jelle |date=2018-05-10 |title=Single Viruses on the Fluorescence Microscope: Imaging Molecular Mobility, Interactions and Structure Sheds New Light on Viral Replication |journal=Viruses |volume=10 |issue=5 |pages=250 |doi=10.3390/v10050250 |issn=1999-4915 |pmc=5977243 |pmid=29748498|doi-access=free }}</ref>

Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basic [[dye]]s 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 [[Bacillota]] and [[Actinomycetota]], both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera ''[[Mycobacterium]]'' and ''[[Nocardia]]''.<ref>{{Cite journal |last1=Saubolle |first1=Michael A. |last2=Sussland |first2=Den |date=2003 |title=Nocardiosis |journal=Journal of Clinical Microbiology |volume=41 |issue=10 |pages=4497–4501 |doi=10.1128/JCM.41.10.4497-4501.2003 |issn=0095-1137 |pmid=14532173|pmc=254378 }}</ref>

===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 [[carbohydrate]]s in patterns characteristic of their [[genus]] and [[species]], the detection of [[Fermentation (biochemistry)|fermentation]] products is commonly used in bacterial identification. [[Acids]], [[alcohols]] and [[gases]] are usually detected in these tests when bacteria are grown in [[Growth medium#Selective media|selective]] liquid or solid media.<ref>{{Cite journal |last1=Flint |first1=Harry J. |last2=Scott |first2=Karen P. |last3=Duncan |first3=Sylvia H. |last4=Louis |first4=Petra |last5=Forano |first5=Evelyne |date=2012-07-01 |title=Microbial degradation of complex carbohydrates in the gut |journal=Gut Microbes |volume=3 |issue=4 |pages=289–306 |doi=10.4161/gmic.19897 |issn=1949-0976 |pmc=3463488 |pmid=22572875}}</ref>

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 replicase]]s 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.<ref>{{Cite journal |last1=Makkoch |first1=Jarika |last2=Prachayangprecha |first2=Slinporn |last3=Payungporn |first3=Sunchai |last4=Chieochansin |first4=Thaweesak |last5=Songserm |first5=Thaweesak |last6=Amonsin |first6=Alongkorn |last7=Poovorawan |first7=Yong |date=2012 |title=Erythrocyte Binding Preference of Human Pandemic Influenza Virus A and Its Effect on Antibody Response Detection |journal=Annals of Laboratory Medicine |volume=32 |issue=4 |pages=276–282 |doi=10.3343/alm.2012.32.4.276 |issn=2234-3806 |pmc=3384809 |pmid=22779069}}</ref>

[[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.<ref name=Sherris/>

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===
[[File:ID Now testing (51038387158).jpg|thumb|Nucleic acid testing conducted using an Abbott Laboratories ID Now device]]
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 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, [[Primer (molecular biology)|primers]], are derived from the [[genomes]] of infectious agents, and with time those genomes will be known if they are not already.<ref name="auto">{{Cite journal |last1=Kozera |first1=Bartłomiej |last2=Rapacz |first2=Marcin |date=2013 |title=Reference genes in real-time PCR |journal=Journal of Applied Genetics |volume=54 |issue=4 |pages=391–406 |doi=10.1007/s13353-013-0173-x |issn=1234-1983 |pmc=3825189 |pmid=24078518}}</ref>

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 the [[clostridia]]l diseases ([[tetanus]] and [[botulism]]). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent [[neurotoxin]]s. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.<ref name="auto"/>

===Metagenomic sequencing===
{{Citations needed|date=September 2024}}
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 of [[encephalitis]], 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.<ref>{{cite web |last1=Lee |first1=Rose |title=Metagenomic Next Generation Sequencing: How Does It Work and Is It Coming to Your Clinical Microbiology Lab? |url=https://asm.org/articles/2019/november/metagenomic-next-generation-sequencing-how-does-it |website=American Society for Microbiology |access-date=17 September 2024}}</ref> This test is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than [[Primer (molecular biology)|primers]] for a specific infectious agent. This amplification step is followed by [[next-generation sequencing]] or [[third-generation sequencing]], [[Sequence alignment|alignment comparisons]], and [[taxonomic classification]] using large databases of thousands of pathogen and commensal [[reference genome]]s. Simultaneously, [[antimicrobial resistance]] genes within pathogen and [[plasmid]] genomes are sequenced and aligned to the taxonomically classified pathogen genomes to generate an antimicrobial resistance profile – analogous to [[antibiotic sensitivity testing]] – to facilitate [[antimicrobial 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 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 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.

===Indication of tests===
[[File:BGSU COVID-19 Drive-Thru Testing Site Close Up.jpg|thumb|A temporary drive-in testing site for COVID-19 set up with tents in a parking lot]]
There is usually an [[indication (medicine)|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 [[Zidovudine|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 [[Time|temporal]] and [[geographic]]al origins of the virus, as well as a myriad of other hypothesis.<ref name=Sherris/> 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.

===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 infection|subclinical]]'', or [[wikt:occult#Adj1|occult]]. An infection that is inactive or dormant is called a ''latent infection''.<ref>{{cite book |author1=Kayser, Fritz H |author2=Kurt A Bienz |author3=Johannes Eckert |author4=Rolf M Zinkernagel | title = Medical microbiology | publisher = Georg Thieme Verlag | location = Stuttgart | year = 2005 | page = 398 | isbn = 978-3-13-131991-3 }}</ref> An example of a latent bacterial infection is [[latent tuberculosis]]. Some viral infections can also be latent, examples of [[virus latency|latent viral infections]] are any of those from the ''[[Herpesviridae]]'' family.<ref>{{Cite journal|last=Grinde|first=Bjørn|date=2013-10-25|title=Herpesviruses: latency and reactivation – viral strategies and host response|journal=Journal of Oral Microbiology|volume=5|pages=22766|doi=10.3402/jom.v5i0.22766|issn=0901-8328|pmc=3809354|pmid=24167660}}</ref>

The word ''infection'' can [[denotation|denote]] any presence of a particular pathogen at all (no matter how little) but also is often used in a [[word sense|sense]] implying a ''clinically apparent'' infection (in other words, a case of infectious disease). This fact occasionally creates some [[ambiguity]] or prompts some [[usage]] discussion; to get around this it is common for [[health professional]]s to speak of ''[[#Colonization|colonization]]'' (rather than ''infection'') when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present.<ref>{{Cite journal |last=Dani |first=Arpad |date=2014 |title=Colonization and infection |journal=Central European Journal of Urology |volume=67 |issue=1 |pages=86–87 |doi=10.5173/ceju.2014.01.art19 |issn=2080-4806 |pmc=4074726 |pmid=24982790}}</ref>

====Course of infection====
Different terms are used to describe how and where infections present over time. In an ''acute'' infection, symptoms develop rapidly; its course can either be rapid or protracted. In ''chronic'' infection, symptoms usually develop gradually over weeks or months and are slow to resolve.<ref>{{Citation|last1=Boldogh|first1=Istvan|title=Persistent Viral Infections|date=1996|url=http://www.ncbi.nlm.nih.gov/books/NBK8538/|work=Medical Microbiology|editor-last=Baron|editor-first=Samuel|edition=4th|publisher=University of Texas Medical Branch at Galveston|isbn=978-0-9631172-1-2|pmid=21413348|access-date=2020-01-23|last2=Albrecht|first2=Thomas|last3=Porter|first3=David D.|archive-date=2020-04-14|archive-url=https://web.archive.org/web/20200414121324/https://www.ncbi.nlm.nih.gov/books/NBK8538/|url-status=live}}</ref> In ''subacute'' infections, symptoms take longer to develop than in acute infections but arise more quickly than those of chronic infections. A ''focal'' infection is an initial site of infection from which organisms travel [[bloodborne pathogen|via the bloodstream]] to another area of the body.<ref name=":0">{{Cite book|title= Microbiology|last=Foster|first=John|publisher=Norton|year=2018|isbn=978-0-393-60257-9|location=New York|pages=39}}</ref>

====Primary versus opportunistic====

{{See also|Coinfection}}
{{anchor|Primary versus secondary}}<!-- This section is linked from Primary infection, Secondary infection and Acute infection-->
Among the many varieties of [[microorganisms]], relatively few cause disease in otherwise healthy individuals.<ref name=Baron>This section incorporates [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed public domain] {{Webarchive|url=https://web.archive.org/web/20090629132331/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed |date=2009-06-29 }} materials included in the text: [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mmed.TOC&depth=10 Medical Microbiology] {{Webarchive|url=https://web.archive.org/web/20090701213330/https://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mmed.TOC&depth=10 |date=2009-07-01 }} Fourth Edition: [https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.594 Chapter 8] {{Webarchive|url=https://web.archive.org/web/20090219005050/https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.594 |date=2009-02-19 }} (1996). Baron, Samuel MD. The University of Texas Medical Branch at Galveston. {{cite book |url=https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed |title=Medical Microbiology |access-date=2013-11-27 |url-status=live |archive-url=https://web.archive.org/web/20090629132331/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed |archive-date=June 29, 2009 |isbn=9780963117212 |publisher=University of Texas Medical Branch at Galveston |year=1996 |pmid=21413252 |last1=Baron |first1=S. }}</ref> Infectious disease results from the interplay between those few [[pathogen]]s 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 as ''primary pathogens'' or as ''[[opportunistic infection|opportunistic pathogens]]''.<ref name="pmid29135922">{{cite journal |vauthors=Patil NK, Guo Y, Luan L, Sherwood ER |title=Targeting Immune Cell Checkpoints during Sepsis |journal=International Journal of Molecular Sciences |volume=18 |issue=11 |date=November 2017 |page=2413 |pmid=29135922 |pmc=5713381 |doi=10.3390/ijms18112413 |url=|doi-access=free }}</ref>

===== 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.<ref name="pmid31027668">{{cite journal |vauthors=McArthur DB |title=Emerging Infectious Diseases |journal=The Nursing Clinics of North America |volume=54 |issue=2 |pages=297–311 |date=June 2019 |pmid=31027668 |pmc=7096727 |doi=10.1016/j.cnur.2019.02.006 |url=}}</ref>

===== Opportunistic pathogens =====

{{main|Opportunistic infection}}
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 [[Major trauma|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 ''[[Clostridioides difficile]]'' [[colitis]]) or from the environment as a result of [[Physical trauma|traumatic]] introduction (as in [[surgical]] wound infections or [[compound fracture]]s). An opportunistic disease requires impairment of host defenses, which may occur as a result of [[genetic defect]]s (such as [[chronic granulomatous disease]]), exposure to [[antimicrobial]] drugs or [[immunosuppressive]] chemicals (as might occur following [[poison]]ing 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.<ref name=Sherris/>

===== Secondary infection =====
While a primary infection can practically be viewed as the [[root cause analysis|root cause]] of an individual's current health problem, a secondary infection is a [[sequela]] or [[complication (medicine)|complication]] of that root cause. For example, an infection due to a [[burn]] or [[penetrating 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 or [[injury]] was the predisposing factor).<ref name="pmid29135922"/>

===== Other types of infection =====
Other types of infection consist of mixed, [[Iatrogenic infections|iatrogenic]], [[Hospital-acquired infection|nosocomial]], and community-acquired infection. A mixed infection is an infection that is caused by two or more pathogens. An example of this is [[appendicitis]], which is caused by ''[[Bacteroides fragilis]]'' and ''[[Escherichia 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.<ref name=":0" />

====Infectious or not====
One manner of proving that a given disease is infectious, is to satisfy [[Koch's postulates]] (first proposed by [[Robert Koch]]), which require that first, the [[infectious 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 that [[Mycobacteria]] species cause [[tuberculosis]].<ref name="pmid28515626">{{cite journal |vauthors=Barberis I, Bragazzi NL, Galluzzo L, Martini M |title=The history of tuberculosis: from the first historical records to the isolation of Koch's bacillus |journal=Journal of Preventive Medicine and Hygiene |volume=58 |issue=1 |pages=E9–E12 |date=March 2017 |pmid=28515626 |pmc=5432783 |doi= |url=}}</ref>

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 a [[pathogen]] produced as a pure culture. Conversely, even clearly infectious diseases do not always meet the infectious criteria; for example, ''[[Treponema pallidum]]'', the causative [[spirochete]] of [[syphilis]], cannot be [[microbiological culture|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.<ref name="pmid31440916">{{cite journal |vauthors=Hosainzadegan H, Khalilov R, Gholizadeh P |title=The necessity to revise Koch's postulates and its application to infectious and non-infectious diseases: a mini-review |journal=European Journal of Clinical Microbiology & Infectious Diseases|volume=39 |issue=2 |pages=215–218 |date=February 2020 |pmid=31440916 |doi=10.1007/s10096-019-03681-1 |s2cid=201283277 |url=}}</ref>

[[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 disease [[outbreak]] is sporadic, or just an occasional occurrence; [[endemic (epidemiology)|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; or [[pandemic]], 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.<ref name="pmid31325286">{{cite journal |vauthors=Riley LW |title=Differentiating Epidemic from Endemic or Sporadic Infectious Disease Occurrence |doi-access=free |s2cid-access=free |journal=Microbiology Spectrum |volume=7 |issue=4 |pages= |date=July 2019 |pmid=31325286 |doi=10.1128/microbiolspec.AME-0007-2019 |s2cid=198135563 |url=|pmc=10957193 }}</ref>

====Contagiousness====
Infectious diseases are sometimes called [[contagious disease]]s 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.<ref>{{cite web|url=https://equine.ca.uky.edu/content/science-sleuths-science-shapes-diagnostic-tests-infectious-or-contagious-%E2%80%93-which-it|title=Science Sleuths: the Science that Shapes Diagnostic Tests: Infectious or Contagious – Which Is It?|publisher=Ag Equine Programs|access-date=2025-01-03}}</ref><ref>{{cite web|url=https://www.britannica.com/dictionary/eb/qa/The-Difference-between-Contagious-and-Infectious-|title=The Difference between 'Contagious' and 'Infectious'|publisher=Britannica}}</ref> 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 called [[quarantine]]) 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 and [[respiratory droplet|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. The [[basic reproduction number]] of an infectious disease measures how easily it spreads through direct or indirect contact.<ref>Higurea & Pietrangelo 2016 {{page needed|date=August 2020}}</ref><ref>{{cite web|url=https://globalhealth.harvard.edu/understanding-predictions-what-is-r-naught/|title=Understanding Predictions: What is R-Naught?|publisher=Harvard|date=February 7, 2020}}</ref>

====By anatomic location====
Infections can be classified by the [[Anatomy|anatomic]] location or [[organ system]] infected, including:<ref>{{Cite web |last=Dahal |first=Prashant |date=2023-04-16 |title=Common Human Infections and Causative Agents |url=https://microbenotes.com/human-infections/ |access-date=2025-02-25 |website=microbenotes.com |language=en-US}}</ref>{{citation needed|date=July 2021}}
* [[Urinary tract infection]]
* [[Skin infection]]
* [[Respiratory tract infection]]
* [[Odontogenic infection]] (an infection that originates within a [[tooth]] or in the closely surrounding tissues)
* [[Vaginal infections]]
* [[Intra-amniotic infection]]
In addition, locations of [[inflammation]] where infection is the most common cause include [[pneumonia]], [[meningitis]] and [[salpingitis]].<ref>{{Cite web |last=CDC |date=2024-12-09 |title=Chapter 17: Pneumococcal Disease |url=https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html |access-date=2025-02-25 |website=Epidemiology and Prevention of Vaccine-Preventable Diseases |language=en-us}}</ref>