Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as
warts,
cutaneous abscesses,
respiratory system infections and
diarrheal diseases are diagnosed by their clinical presentation and treated without knowledge of the specific causative agent. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. 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. 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.
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. 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. Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C. 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, 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, which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its
strain), and the environment that supports its growth. Other ingredients are often added to the plate to aid in identification. Plates may contain substances that permit the growth of some bacteria and not others, or that change color in response to certain bacteria and not others. Bacteriological plates such as these are commonly used in the clinical identification of infectious bacterium. Microbial culture may also be used in the identification of
viruses: the medium, in this case, being cells grown in culture that the virus can infect, and then alter or kill. In the case of viral identification, a region of dead cells results from viral growth, and is called a "plaque".
Eukaryotic parasites may also be grown in culture as a means of identifying a particular agent. In the absence of suitable plate culture techniques, some microbes require culture within live animals. Bacteria such as
Mycobacterium leprae and
Treponema pallidum can be grown in animals, although serological and microscopic techniques make the use of live animals unnecessary. Viruses are also usually identified using alternatives to growth in culture or animals. Some viruses may be grown in
embryonated eggs. Another useful identification method is Xenodiagnosis, or the use of a vector to support the growth of an infectious agent.
Chagas disease is the most significant example, because it is difficult to directly demonstrate the presence of the causative agent,
Trypanosoma cruzi in a patient, which therefore makes it difficult to definitively make a diagnosis. In this case,
xenodiagnosis involves the use of the
vector of the Chagas agent
T. cruzi, an uninfected
triatomine bug, which takes a blood meal from a person suspected of having been infected. The bug is later inspected for growth of
T. cruzi within its gut.
Microscopy Another principal tool in the diagnosis of infectious disease is
microscopy. Virtually all of the culture techniques discussed above rely, at some point, on microscopic examination for definitive identification of the infectious agent. Microscopy may be carried out with simple instruments, such as the compound
light microscope, or with instruments as complex as an
electron microscope. Samples obtained from patients may be viewed directly under the light microscope, and can often rapidly lead to identification. Microscopy is often also used in conjunction with
biochemical staining techniques, and can be made exquisitely specific when used in combination with
antibody based techniques. For example, the use of antibodies made artificially
fluorescent (fluorescently labeled antibodies) can be directed to bind to and identify a specific
antigens present on a pathogen. A
fluorescence microscope is then used to detect fluorescently labeled antibodies bound to internalized antigens within clinical samples or cultured cells. This technique is especially useful in the diagnosis of viral diseases, where the light microscope is incapable of identifying a virus directly. Other microscopic procedures may also aid in identifying infectious agents. Almost all cells readily stain with a number of basic
dyes due to the
electrostatic attraction between negatively charged cellular molecules and the positive charge on the dye. A cell is normally transparent under a microscope, and using a stain increases the contrast of a cell with its background. Staining a cell with a dye such as
Giemsa stain or
crystal violet allows a microscopist to describe its size, shape, internal and external components and its associations with other cells. The response of bacteria to different staining procedures is used in the
taxonomic classification of microbes as well. Two methods, the
Gram stain and the
acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups
Bacillota and
Actinomycetota, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinomycetota genera
Mycobacterium and
Nocardia.
Biochemical tests Biochemical tests used in the identification of infectious agents include the detection of
metabolic or
enzymatic products characteristic of a particular infectious agent. Since bacteria ferment
carbohydrates in patterns characteristic of their
genus and
species, the detection of
fermentation products is commonly used in bacterial identification.
Acids,
alcohols and
gases are usually detected in these tests when bacteria are grown in
selective liquid or solid media. The isolation of
enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither
RNA replicases nor
reverse transcriptase, and the presence of these enzymes are characteristic., of specific types of viral infections. The ability of the viral protein
hemagglutinin to bind
red blood cells together into a detectable matrix may also be characterized as a biochemical test for viral infection, although strictly speaking hemagglutinin is not an
enzyme and has no metabolic function.
Serological methods are highly sensitive, specific and often extremely rapid tests used to identify microorganisms. These tests are based upon the ability of an antibody to bind specifically to an antigen. The antigen, usually a protein or carbohydrate made by an infectious agent, is bound by the antibody. This binding then sets off a chain of events that can be visibly obvious in various ways, dependent upon the test. For example, "
Strep throat" is often diagnosed within minutes, and is based on the appearance of antigens made by the causative agent,
S. pyogenes, that is retrieved from a patient's throat with a cotton swab. Serological tests, if available, are usually the preferred route of identification, however the tests are costly to develop and the reagents used in the test often require
refrigeration. Some serological methods are extremely costly, although when commonly used, such as with the "strep test", they can be inexpensive. 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
clostridial diseases (
tetanus and
botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent
neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria. This test is similar to current PCR tests; however, an untargeted whole genome amplification is used rather than
primers for a specific infectious agent. This amplification step is followed by
next-generation sequencing or
third-generation sequencing,
alignment comparisons, and
taxonomic classification using large databases of thousands of pathogen and commensal
reference genomes. 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 There is usually an
indication for a specific identification of an infectious agent only when such identification can aid in the treatment or prevention of the disease, or to advance knowledge of the course of an illness prior to the development of effective therapeutic or preventative measures. For example, in the early 1980s, prior to the appearance of
AZT for the treatment of
AIDS, the course of the disease was closely followed by monitoring the composition of patient blood samples, even though the outcome would not offer the patient any further treatment options. In part, these studies on the appearance of
HIV in specific communities permitted the advancement of
hypotheses as to the route of transmission of the virus. By understanding how the disease was transmitted, resources could be targeted to the communities at greatest risk in campaigns aimed at reducing the number of new infections. The specific
serological diagnostic identification, and later
genotypic or molecular identification, of HIV also enabled the development of hypotheses as to the
temporal and
geographical origins of the virus, as well as a myriad of other hypothesis. An example of a latent bacterial infection is
latent tuberculosis. Some viral infections can also be latent, examples of
latent viral infections are any of those from the
Herpesviridae family. The word
infection can
denote any presence of a particular pathogen at all (no matter how little) but also is often used in a
sense implying a
clinically apparent infection (in other words, a case of infectious disease). This fact occasionally creates some
ambiguity or prompts some
usage discussion; to get around this it is common for
health professionals to speak of
colonization (rather than
infection) when they mean that some of the pathogens are present but that no clinically apparent infection (no disease) is present.
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. 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
via the bloodstream to another area of the body.
Primary versus opportunistic Among the many varieties of
microorganisms, relatively few cause disease in otherwise healthy individuals. Infectious disease results from the interplay between those few
pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen 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 pathogens.
Primary pathogens Primary pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic
virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however, many serious diseases are caused by organisms acquired from the environment or that infect non-human hosts.
Opportunistic pathogens Opportunistic pathogens can cause an infectious disease in a host with depressed resistance (
immunodeficiency) or if they have unusual access to the inside of the body (for example, via
trauma).
Opportunistic infection may be caused by microbes ordinarily in contact with the host, such as
pathogenic bacteria or fungi in the
gastrointestinal or the
upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in
Clostridioides difficile colitis) or from the environment as a result of
traumatic introduction (as in
surgical wound infections or
compound fractures). An opportunistic disease requires impairment of host defenses, which may occur as a result of
genetic defects (such as
chronic granulomatous disease), exposure to
antimicrobial drugs or
immunosuppressive chemicals (as might occur following
poisoning or
cancer chemotherapy), exposure to
ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with
measles,
malaria or
HIV disease). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host. 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
cultured in vitro – however the organism can be cultured in rabbit
testes. It is less clear that a pure culture comes from an animal source serving as host than it is when derived from microbes derived from plate culture.
Epidemiology, 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, 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.
Contagiousness Infectious diseases are sometimes called
contagious 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. 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
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.
By anatomic location Infections can be classified by the
anatomic location or
organ system infected, including: •
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. ==Prevention==