Wednesday, 27 August 2014

Infection

Infection


Infectious disease
Classification and external resources
Malaria.jpg
A false-colored electron micrograph shows amalaria sporozoite migrating through themidgut epithelia.


Infection is the invasion of a host organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to these organisms and the toxins they produce. Infectious diseases, also known as transmissible diseases orcommunicable diseases, comprise clinically evident illness (i.e., characteristic medical signs and/or symptoms of disease) resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism.
Infections are caused by infectious agents such as viruses, viroids, and prions, microorganisms such as bacteria, nematodes such asroundworms and pinworms, arthropods such as ticks, mites, fleas, and lice, fungi such as ringworm, and other macroparasites such as tapeworms.
Hosts can fight infections using their immune system. Mammalian hosts react to infections with an innate response, often involvinginflammation, followed by an adaptive response. Pharmaceuticals can also help fight infections.
The branch of medicine that focuses on infections and pathogens is infectious disease medicine.

Classification

Bacterial infections are classified by the causative agent as well as the symptoms and medical signs produced.
Symptomatic infections are apparent, whereas an infection that is active, but does not produce noticeable symptoms, may be calledinapparent, silent, or subclinical. An infection that is inactive or dormant is called a latent infection.
A short-term infection is an acute infection. A long-term infection is a chronic infection.

Primary versus opportunistic

Among the vast varieties of microorganisms, relatively few cause disease in otherwise healthy individuals.[4] Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen, depends upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. Clinicians therefore classify infectious microorganisms or microbes according to the status of host defenses - either as primary pathogens or as opportunistic pathogens:

Occult infection

Occult infection is a hidden infection first recognized by secondary manifestations. Fran Giampietro discovered this type, and coined the term "occult infection" in the late 1930s.

Infectious or not

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

Contagiousness

Infectious diseases are sometimes called "contagious disease" when they are easily transmitted by contact with an ill person or their secretions (e.g., influenza). Thus, acontagious disease is a subset of infectious disease that is especially infective or easily transmitted. Other types of infectious/transmissible/communicable diseases with more specialized routes of infection, such as vector transmission or sexual transmission, are usually not regarded as "contagious," and often do not require medical isolation (sometimes loosely called quarantine) of victims. However, this specialized connotation of the word "contagious" and "contagious disease" (easy transmissibility) is not always respected in popular use.

By anatomic location

Infections can be classified by the anatomic location or organ system that is infected, including:
In addition, locations of inflammation where infection is the most common cause include pneumonia, meningitis and salpingitis.

Signs and symptoms

The symptoms of an infection depend on the type of disease. Some signs of infection affect the whole body generally, such as fatigue, loss of appetite, weight loss, fevers, night sweats, chills, aches and pains. Others are specific to individual body parts, such as skin rashes, coughing, or a runny nose.
In certain cases, infectious diseases may be asymptomatic for much or even all of their course in a given host. In the latter case, the disease may only be defined as a "disease" (which by definition means an illness) in hosts who secondarily become ill after contact with an asymptomatic carrier. An infection is not synonymous with an infectious disease, as some infections do not cause illness in a host.[5]

Bacterial or viral

Bacterial and viral infections can both cause the same kinds of symptoms. It can be difficult to distinguish which is the cause of a specific infection.[6] It's important to distinguish, because viral infections cannot be cured by antibiotics.
Comparison of viral and bacterial infection
CharacteristicViral infectionBacterial infection
Typical symptomsIn general, viral infections are systemic. This means they involve many different parts of the body or more than one body system at the same time; i.e. a runny nose, sinus congestion, cough, body aches etc. They can be local at times as in viral conjunctivitis or "pink eye" and herpes. Only a few viral infections are painful, like herpes. The pain of viral infections is often described as itchy or burning.[6]The classic symptoms of a bacterial infection are localized redness, heat, swelling and pain. One of the hallmarks of a bacterial infection is local pain, pain that is in a specific part of the body. For example, if a cut occurs and is infected with bacteria, pain occurs at the site of the infection. Bacterial throat pain is often characterized by more pain on one side of the throat. An ear infection is more likely to be diagnosed as bacterial if the pain occurs in only one ear.[6] A cut that produces pus and milky-colored liquid is most likely infected.[8]
CausePathogenic virusesPathogenic bacteria

Pathophysiology

There is a general chain of events that applies to infections. For infections to occur, a given chain of events must occur.[9] 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.[10]

Colonization


Infection of a toe with an ingrown toenail; there is pus (yellow) and resultant inflammation (redness and swelling around the nail).
Infection begins when an organism successfully colonizes by entering the body, growing and multiplying. Most humans are not easily infected. Those who are weak, sick, malnourished, have cancer or are diabetic have increased susceptibility to chronic or persistent infections. Individuals who have a suppressed immune system are particularly susceptible to opportunistic infections. Entrance to the host at host-pathogen interface, generally occurs through the mucosa in orifices like the oral cavity, nose, eyes, genitalia, anus, or the microbe can enter through open wounds. While a few organisms can grow at the initial site of entry, many migrate and cause systemic infection in different organs. Some pathogens grow within the host cells (intracellular) whereas others grow freely in bodily fluids.
Wound colonization refers to nonreplicating microorganisms within the wound, while in infected wounds, replicating organisms exist and tissue is injured. All multicellular organisms are colonized to some degree by extrinsic organisms, and the vast majority of these exist in either a mutualistic or commensal relationship with the host. An example of the former is the anaerobic bacteria species, which colonizes the mammalian colon, and an example of the latter is various species of staphylococcus that exist on human skin. Neither of these colonizations are considered infections. The difference between an infection and a colonization is often only a matter of circumstance. Non-pathogenic organisms can become pathogenic given specific conditions, and even the most virulent organism requires certain circumstances to cause a compromising infection. Some colonizing bacteria, such as Corynebacteria sp. and viridans streptococci, prevent the adhesion and colonization of pathogenic bacteria and thus have a symbiotic relationship with the host, preventing infection and speeding wound healing.
The variables involved in the outcome of a host becoming inoculated by a pathogen and the ultimate outcome include:
  • the route of entry of the pathogen and the access to host regions that it gains
  • the intrinsic virulence of the particular organism
  • the quantity or load of the initial inoculant
  • the immune status of the host being colonized
As an example, the staphylococcus species remains harmless on the skin, but, when present in a normally sterile space, such as in the capsule of a joint or the peritoneum, multiplies without resistance and creates a burden on the host.
It can be difficult to know which chronic wounds are infected. Despite the huge number of wounds seen in clinical practice, there are limited quality data for evaluated symptoms and signs. A review of chronic wounds in the Journal of the American Medical Association's "Rational Clinical Examination Series" quantified the importance of increased pain as an indicator of infection.[11] The review showed that the most useful finding is an increase in the level of pain [likelihood ratio (LR) range, 11-20] makes infection much more likely, but the absence of pain (negative likelihood ratio range, 0.64-0.88) does not rule out infection (summary LR 0.64-0.88).

Disease

Disease can arise if the host's protective immune mechanisms are compromised and the organism inflicts damage on the host. Microorganisms can cause tissue damage by releasing a variety of toxins or destructive enzymes. For example, Clostridium tetani releases a toxin that paralyzes muscles, and staphylococcus releases toxins that produce shock and sepsis. Not all infectious agents cause disease in all hosts. For example less than 5% of individuals infected with polio develop disease[citation needed]. On the other hand, some infectious agents are highly virulent. The prion causing mad cow disease and Creutzfeldt–Jakob disease kills almost all animals and people that are infected.
Persistent infections occur because the body is unable to clear the organism after the initial infection. Persistent infections are characterized by the continual presence of the infectious organism, often as latent infection with occasional recurrent relapses of active infection. There are some viruses that can maintain a persistent infection by infecting different cells of the body. Some viruses once acquired never leave the body. A typical example is the herpes virus, which tends to hide in nerves and become reactivated when specific circumstances arise.
Persistent infections cause millions of deaths globally each year.[12] Chronic infections by parasites account for a high morbidity and mortality in many underdeveloped countries.

Transmission

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:
  • Droplet contact, also known as the respiratory route, and the resultant infection can be termed airborne 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. Common fecal-oral transmitted pathogens include Vibrio cholerae, Giardia species,rotaviruses, Entameba histolytica, Escherichia coli, and tape worms.[13] Most of these pathogens cause gastroenteritis.
  • Sexual transmission, with the resulting disease being called sexually transmitted disease
  • Oral transmission; Diseases that are transmitted primarily by oral means may be caught through direct oral contact such as kissing, 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 include athlete's foot, impetigo and warts
  • Vertical transmission'; directly from the mother to an embryo, fetus or baby during pregnancy or childbirth. It can occur when the mother gets an infection as an intercurrent disease in pregnancy.
  • Iatrogenic transmission, due to medical procedures such as injection or transplantation of infected material.

Culex mosquitos (Culex quinquefasciatus shown) are biological vectors that transmit West Nile Virus.
  • Vector-borne transmission, transmitted by a vector, which is an organism that does not cause disease itself but that transmits infectionby conveying pathogens from one host to another.[14]
The relationship between virulence versus transmissibility is complex; if a disease is rapidly fatal, the host may die before the microbe can get passed along to another host.

Prevention


Washing one's hands, a form ofhygiene, is an effective way to prevent the spread of infectious disease.[citation needed]
Techniques like hand washing, wearing gowns, and wearing face masks can help prevent infections from being passed from the surgeon to the patient or vice versa. Frequent hand washingremains the most important defense against the spread of unwanted organisms.[15] Nutrition must be improved and one has to make changes in life style- such as avoiding the use of illicit drugs, using a condom, and entering an exercise program. Cooking foods well and avoiding foods that have been left outside for a long time is also important.
Antimicrobial substances used to prevent transmission of infections include:
One of the ways to prevent or slow down the transmission of infectious diseases is to recognize the different characteristics of various diseases.[17] Some critical disease characteristics that should be evaluated include virulence, distance traveled by victims, and level of contagiousness. The human strains of Ebola virus, for example, incapacitate their victims extremely quickly and kill them soon after. As a result, the victims of this disease do not have the opportunity to travel very far from the initial infection zone.[18] Also, this virus must spread through skin lesions or permeable membranes such as the eye. Thus, the initial stage of Ebola is not very contagious since its victims experience only internal hemorrhaging. As a result of the above features, the spread of Ebola is very rapid and usually stays within a relatively confined geographical area. In contrast, the Human Immunodeficiency Virus (HIV) kills its victims very slowly by attacking their immune system.[5] As a result, many of its victims transmit the virus to other individuals before even realizing that they are carrying the disease. Also, the relatively low virulence allows its victims to travel long distances, increasing the likelihood of an epidemic.
Another effective way to decrease the transmission rate of infectious diseases is to recognize the effects of small-world networks.[17] In epidemics, there are often extensive interactions within hubs or groups of infected individuals and other interactions within discrete hubs of susceptible individuals. Despite the low interaction between discrete hubs, the disease can jump to and spread in a susceptible hub via a single or few interactions with an infected hub. Thus, infection rates in small-world networks can be reduced somewhat if interactions between individuals within infected hubs are eliminated (Figure 1). However, infection rates can be drastically reduced if the main focus is on the prevention of transmission jumps between hubs. The use of needle exchange programs in areas with a high density of drug users with HIV is an example of the successful implementation of this treatment method. [6] Another example is the use of ring culling or vaccination of potentially susceptible livestock in adjacent farms to prevent the spread of the foot-and-mouth virus in 2001.[19]
A general method to prevent transmission of vector-borne pathogens is pest control.

Immunity


Mary Mallon (a.k.a. Typhoid Mary) was an asymptomatic carrier of typhoid fever. Over the course of her career as a cook, she infected 53 people, three of whom died.
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.[4] This process requires immune mechanisms to kill or inactivate the inoculum of the pathogen. Specific acquiredimmunity against infectious diseases may be mediated by antibodies and/or T lymphocytes. Immunity mediated by these two factors may be manifested by:
  • a direct effect upon a pathogen, such as antibody-initiated complement-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 high fever and inflammation, and has the potential to be more devastating than direct damage caused by a microbe.[5]
Resistance to infection (immunity) may be acquired following a disease, by asymptomatic carriage of the pathogen, by harboring an organism with a similar structure (crossreacting), or by vaccination. Knowledge of the protective antigens and specific acquired host immune factors is more complete for primary pathogens than for opportunistic pathogens.
Immune resistance to an infectious disease requires a critical level of either antigen-specific antibodies and/or T cells when the host encounters the pathogen. Some individuals develop natural serum antibodies to the surface polysaccharides of some agents although they have had little or no contact with the agent, these natural antibodies confer specific protection to adults and are passively transmittedto newborns.

Host genetic factors

The clearance of the pathogens, either treatment-induced or spontaneous, it can be influenced by the genetic variants carried by the individual patients. For instance, for genotype 1 hepatitis C treated with Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) combined with ribavirin, it has been shown that genetic polymorphisms near the human IL28B gene, encoding interferon lambda 3, are associated with significant differences in the treatment-induced clearance of the virus. This finding, originally reported in Nature,[20] showed that genotype 1 hepatitis C patients carrying certain genetic variant alleles near the IL28B gene are more possibly to achieve sustained virological response after the treatment than others. Later report from Nature[21] demonstrated that the same genetic variants are also associated with the natural clearance of the genotype 1 hepatitis C virus.

Diagnosis

Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such as warts, cutaneousabscesses, respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is benign.
Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. Other techniques (such as X-rays, CAT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by aprion.

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.
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.[22] Other important indicators include parental concern, clinical instinct, and temperature greater than 40 °C.[22]

Microbial culture


Four nutrient agar plates growing colonies of common Gram negative bacteria.
Microbiological culture is a principal tool used to diagnose infectious disease. In a microbial culture, a growth medium is provided for a specific agent. A sample taken from potentially diseased tissue or fluid is then tested for the presence of an infectious agent able to grow within that medium. Most pathogenic bacteria are easily grown on nutrient agar, a form of solid medium that supplies carbohydrates and proteins necessary for growth of a bacterium, along with copious amounts of water. A single bacterium will grow into a visible mound on the surface of the plate called a colony, which may be separated from other colonies or melded together into a "lawn". The size, color, shape and form of a colony is characteristic of the bacterial species, its specific genetic makeup (its strain), and the environment which 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 lepraeand 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 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 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 ofantibodies 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 stainand the acid-fast stain, are the standard approaches used to classify bacteria and to diagnosis of disease. The Gram stain identifies the bacterial groups Firmicutes andActinobacteria, both of which contain many significant human pathogens. The acid-fast staining procedure identifies the Actinobacterial genera Mycobacterium and Nocardia.

Biochemical tests

Biochemical tests used in the identification of infectious agents include the detection of metabolic or enzymatic products characteristic of a particular infectious agent. Since bacteria ferment carbohydrates in patterns characteristic of their genus and species, the detection of fermentation products is commonly used in bacterial identification. Acids,alcohols and gases are usually detected in these tests when bacteria are grown in selective liquid or solid media.
The isolation of enzymes from infected tissue can also provide the basis of a biochemical diagnosis of an infectious disease. For example, humans can make neither RNA replicases nor reverse transcriptase, and the presence of these enzymes are characteristic of specific types of viral infections. The ability of the viral protein hemagglutinin to 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 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 patients 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.[5]
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 which 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.

Molecular diagnostics

Technologies based upon the polymerase chain reaction (PCR) method will become nearly ubiquitous gold standards of diagnostics of the near future, for several reasons. First, the catalog of infectious agents has grown to the point that virtually all of the significant infectious agents of the human population have been identified. Second, an infectious agent must grow within the human body to cause disease; essentially it must amplify its own nucleic acids in order to cause a disease. This amplification of nucleic acid in infected tissue offers an opportunity to detect the infectious agent by using PCR. Third, the essential tools for directing PCR, primers, are derived from the genomes of infectious agents, and with time those genomes will be known, if they are not already.
Thus, the technological ability to detect any infectious agent rapidly and specifically are currently available. The only remaining blockades to the use of PCR as a standard tool of diagnosis are in its cost and application, neither of which is insurmountable. The diagnosis of a few diseases will not benefit from the development of PCR methods, such as some of the clostridial diseases (tetanus and botulism). These diseases are fundamentally biological poisonings by relatively small numbers of infectious bacteria that produce extremely potent neurotoxins. A significant proliferation of the infectious agent does not occur, this limits the ability of PCR to detect the presence of any bacteria.

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 AZTfor 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.[5] 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.

Anti-infective treatments

When infection attacks the body, anti-infective drugs can suppress the infection. Four types of anti-infective or drugs exist: antibacterial (antibiotic), antiviral, antitubercular, andantifungal.[23][better source needed] Depending on the severity and the type of infection, the antibiotic may be given by mouth, injection or may be applied topically.[24][bare URL]Severe infections of the brain are usually treated with intravenous antibiotics. Sometimes, multiple antibiotics are used to decrease the risk of resistance and increase efficacy. Antibiotics only work for bacteria and do not affect viruses. Antibiotics work by slowing down the multiplication of bacteria or killing the bacteria. The most common classes of antibiotics used in medicine include penicillin, cephalosporins, aminoglycosides, macrolides, quinolones and tetracyclines.

Epidemiology


Disability-adjusted life year for infectious and parasitic diseases per 100,000 inhabitants in 2004.[26]
  no data
  ≤250
  250-500
  500-1000
  1000-2000
  2000-3000
  3000-4000
  4000-5000
  5000-6250
  6250-12500
  12500-25000
  25000-50000
  ≥50000
The World Health Organization collects information on global deaths by International Classification of Disease (ICD) code categories. The following table lists the top infectious disease killers which caused more than 100,000 deaths in 2002 (estimated). 1993 data is included for comparison.
Worldwide mortality due to infectious diseases
RankCause of deathDeaths 2002
(in millions)		Percentage of
all deaths		Deaths 1993
(in millions)		1993 Rank
N/AAll infectious diseases14.725.9%16.432.2%
1Lower respiratory infections[29]3.96.9%4.11
2HIV/AIDS2.84.9%0.77
3Diarrheal diseases[30]1.83.2%3.02
4Tuberculosis (TB)1.62.7%2.73
5Malaria1.32.2%2.04
6Measles0.61.1%1.15
7Pertussis0.290.5%0.367
8Tetanus0.210.4%0.1512
9Meningitis0.170.3%0.258
10Syphilis0.160.3%0.1911
11Hepatitis B0.100.2%0.936
12-17Tropical diseases (6)[31]0.130.2%0.539, 10, 16-18
Note: Other causes of death include maternal and perinatal conditions (5.2%), nutritional deficiencies (0.9%),
noncommunicable conditions (58.8%), and injuries (9.1%).
The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases include pertussis, poliomyelitis, diphtheria, measles and tetanus. Children also make up a large percentage of lower respiratory and diarrheal deaths.

Historic pandemics


Great Plague of Marseille in 1720 killed 100,000 people in the city and the surrounding provinces
A pandemic (or global epidemic) is a disease that affects people over an extensive geographical area.
  • Plague of Justinian, from 541 to 750, killed between 50% and 60% of Europe's population.[32]
  • The Black Death of 1347 to 1352 killed 25 million in Europe over 5 years. The plague reduced the world population from an estimated 450 million to between 350 and 375 million in the 14th century.
  • The introduction of smallpox, measles, and typhus 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 of Mexico to fall from 20 million to 3 million.[33]
  • The first European influenza epidemic occurred between 1556 and 1560, with an estimated mortality rate of 20%.[33]
  • Smallpox killed an estimated 60 million Europeans during the 18th century[34] (approximately 400,000 per year).[35] 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.[36]
  • In the 19th century, tuberculosis killed an estimated one-quarter of the adult population of Europe;[37] by 1918 one in six deaths in France were still caused by TB.
  • The Influenza Pandemic of 1918 (or the Spanish Flu) killed 25-50 million people (about 2% of world population of 1.7 billion).[38] Today Influenza kills about 250,000 to 500,000 worldwide each year.

Emerging diseases

In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host.
  1. Coevolution between parasite and host can lead to hosts becoming resistant to the parasites or the parasites may evolve greater virulence, leading to immunopathological disease.
  2. Human activity is involved with many emerging infectious diseases, such as environmental change enabling a parasite to occupy new niches. When that happens, apathogen that had been confined to a remote habitat has a wider distribution and possibly a new host organism. Parasites jumping from nonhuman to human hosts are known as zoonoses. Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host.[39]
Several human activities have led to the emergence of zoonotic human pathogens, including viruses, bacteria, protozoa, and rickettsia,[40] and spread of vector-bornediseases,[39] see also Globalization and Disease and Wildlife disease:
  • Encroachment on wildlife habitats. 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.[41]
  • Changes in agriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases.
  • The destruction of rain 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.
  • Uncontrolled urbanization. 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.
  • Modern transport. 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.

History


East German postage stampsdepicting four antique microscopes. Advancements in microscopy were essential to the early study of infectious diseases.
Ideas of contagion became more popular in Europe during the Renaissance, particularly through the writing of the Italian physicianGirolamo Fracastoro.[42]
Anton van Leeuwenhoek (1632–1723) advanced the science of microscopy by being the first to observe microorganisms, allowing for easy visualization of bacteria.
In the mid-19th century John Snow and William Budd did important work demonstrating the contagiousness of typhoid and cholera through contaminated water. Both are credited with decreasing epidemics of cholera in their towns by implementing measures to prevent contamination of water.[43]
Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine for rabies.
Robert Koch, provided the study of infectious diseases with a scientific basis known as Koch's postulates.
Edward Jenner, Jonas Salk and Albert Sabin developed effective vaccines for smallpox and polio, which would later result in the eradicationand near-eradication of these diseases, respectively.
Alexander Fleming discovered the world's first antibiotic Penicillin which Florey and Chain then developed.
Gerhard Domagk developed sulphonamides, the first broad spectrum synthetic antibacterial drugs.

Medical specialists

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

Society and culture

A number of studies have reported associations between pathogen load in an area and human behavior. Higher pathogen load is associated with decreased size of ethnic and religious groups in an area. This may be due high pathogen load favoring avoidance other groups which may reduce pathogen transmission or a high pathogen load preventing the creation of large settlements and armies which enforce a common culture. Higher pathogen load is also associated with more restricted sexual behavior which may reduce pathogen transmission. It also associated with higher preferences for health and attractiveness in mates. Higher fertility rates and shorter or less parental care per child is another association which may be a compensation for the higher mortality rate. There is also an association with polygyny which may be due to higher pathogen load making selecting males with a high genetic resistance increasingly important. Higher pathogen load is also associated with more collectivism and less individualism which may limit contacts with outside groups and infections. There are alternative explanations for at least some of the associations although some of these explanations may in turn ultimately be due to pathogen load. Thus, polygny may also be due to a lower male:female ratio in these areas but this may ultimately be due to male infants having increased mortality from infectious diseases. Another example is that poor socioeconomic factors may ultimately in part be due to high pathogen load preventing economic development.[44]

Fossil record


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







































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