Since human plague is rare in most parts of the world, routine vaccination is not needed other than for those at particularly high risk of exposure, nor for people living in areas with enzootic plague, meaning it occurs at regular, predictable rates in populations and specific areas, such as the western United States. It is not even indicated for most travellers to countries with known recent reported cases, particularly if their travel is limited to urban areas with modern hotels. The CDC thus only recommends vaccination for: (1) all laboratory and field personnel who are working with "Y. pestis" organisms resistant to antimicrobials; (2) people engaged in aerosol experiments with "Y. pestis"; and (3) people engaged in field operations in areas with enzootic plague where preventing exposure is not possible (such as some disaster areas).

A systematic review by the Cochrane Collaboration found no studies of sufficient quality to make any statement on the efficacy of the vaccine.

Human "Yersinia" infections most commonly result from the bite of an infected flea or occasionally an infected mammal, but like most bacterial systemic diseases, the disease may be transmitted through an opening in the skin or by inhaling infectious droplets of moisture from sneezes or coughs. In both cases septicemic plague need not be the result, and in particular, not the initial result, but it occasionally happens that bubonic plague for example leads to infection of the blood, and septicemic plague results. If the bacteria happen to enter the bloodstream rather than the lymph or lungs, they multiply in the blood, causing bacteremia and severe sepsis. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation (DIC), where tiny blood clots form throughout the body, commonly resulting in localised ischemic necrosis, tissue death from lack of circulation and perfusion.

DIC results in depletion of the body's clotting resources, so that it can no longer control bleeding. Consequently, the unclotted blood bleeds into the skin and other organs, leading to red or black patchy rash and to hematemesis (vomiting blood) or hemoptysis (spitting blood). The rash may cause bumps on the skin that look somewhat like insect bites, usually red, sometimes white in the center.

Untreated septicemic plague is almost always fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. Death is almost inevitable if treatment is delayed more than about 24 hours, and some people may even die on the same day they with the disease.

Septicemic plague is caused by horizontal and direct transmission. Horizontal transmission is the transmitting of a disease from one individual to another regardless of blood relation. Direct transmission occurs from close physical contact with individuals, through common air usage, from direct bite from a flea or an infected rodent. Most common rodents may carry the bacteria and so may Leporidae such as rabbits:

Significant carriers of the bacteria in the United States include:

- Rats

- Prairie dogs

- Squirrels

- Chipmunks

- Rabbits

The bacteria are cosmopolitan, mainly in rodents in all continents except Australia and Antarctica. The greatest frequency of human plague infections occur in Africa. The bacteria most commonly appear in rural areas and wherever there is poor sanitation, overcrowding, and high rodent populations in urban areas. Outdoor activities such as hiking, camping, or hunting where plague-infected animals may be found, increase the risk of contracting septicemic plague, and so do certain occupations such as veterinary or other animal-related work.

Transmission of "Y. pestis" to an uninfected individual is possible by any of the following means.

- droplet contact – coughing or sneezing on another person

- direct physical contact – touching an infected person, including sexual contact

- indirect contact – usually by touching soil contamination or a contaminated surface

- airborne transmission – if the microorganism can remain in the air for long periods

- fecal-oral transmission – usually from contaminated food or water sources

- vector borne transmission – carried by insects or other animals.

"Yersinia pestis" circulates in animal reservoirs, particularly in rodents, in the natural foci of infection found on all continents except Australia. The natural foci of plague are situated in a broad belt in the tropical and sub-tropical latitudes and the warmer parts of the temperate latitudes around the globe, between the parallels 55 degrees North and 40 degrees South.

Contrary to popular belief, rats did not directly start the spread of the bubonic plague. It is mainly a disease in the fleas ("Xenopsylla cheopis") that infested the rats, making the rats themselves the first victims of the plague. Infection in a human occurs when a person is bitten by a flea that has been infected by biting a rodent that itself has been infected by the bite of a flea carrying the disease. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to starve. The flea then bites a host and continues to feed, even though it cannot quell its hunger, and consequently the flea vomits blood tainted with the bacteria back into the bite wound. The bubonic plague bacterium then infects a new person and the flea eventually dies from starvation. Serious outbreaks of plague are usually started by other disease outbreaks in rodents, or a rise in the rodent population.

The following steps and precautions should be used to avoid infection of the septicemic plague:

- Caregivers of infected patients should wear masks, gloves, goggles and gowns

- Take antibiotics if close contact with infected patient has occurred

- Use insecticides throughout house

- Avoid contact with dead rodents or sick cats

- Set traps if mice or rats are present around the house

- Do not allow family pets to roam in areas where plague is common

- Flea control and treatment for animals (especially rodents)

Bubonic plague is an infection of the lymphatic system, usually resulting from the bite of an infected flea, "Xenopsylla cheopis" (the rat flea). In very rare circumstances, as in the septicemic plague, the disease can be transmitted by direct contact with infected tissue or exposure to the cough of another human. The flea is parasitic on house and field rats, and seeks out other prey when its rodent hosts die. The bacteria remain harmless to the flea, allowing the new host to spread the bacteria. The bacteria form aggregates in the gut of infected fleas and this results in the flea regurgitating ingested blood, which is now infected, into the bite site of a rodent or human host. Once established, bacteria rapidly spread to the lymph nodes and multiply.

"Y. pestis" bacilli can resist phagocytosis and even reproduce inside phagocytes and kill them. As the disease progresses, the lymph nodes can haemorrhage and become swollen and necrotic. Bubonic plague can progress to lethal septicemic plague in some cases. The plague is also known to spread to the lungs and become the disease known as the pneumonic plague.

There are no safe, available, approved vaccines against tularemia. However, vaccination research and development continues, with live attenuated vaccines being the most thoroughly researched and most likely candidate for approval. Sub-unit vaccine candidates, such as killed-whole cell vaccines, are also under investigation, however research has not reached a state of public use.

Optimal preventative practices include limiting direct exposure when handling potentially infected animals, such as wearing gloves and face masks while handling potentially infected animals (importantly when skinning deceased animals).

Since the invention of antibiotics, the rate of death associated with tularemia has decreased from 60% to less than 4%.

Pneumonic plague can be caused in two ways: primary, which results from the inhalation of aerosolised plague bacteria, or secondary, when septicaemic plague spreads into lung tissue from the bloodstream. Pneumonic plague is "not" exclusively vector-borne like bubonic plague; instead it can be spread from person to person. There have been cases of pneumonic plague resulting from the dissection or handling of contaminated animal tissue. This is one type of the plague formerly known as the Black Death.

Sylvatic plague is most commonly found in prairie dog colonies; the flea that feeds on prairie dogs (and other mammals) serves as the vector for transmission to the new host.

Sylvatic plague is primarily transmitted among wildlife through flea bites and contact with contaminated fluids or tissue, through predation or scavenging. Humans can contract plague from wildlife through flea bites and handling animal carcasses.

Bubonic plague is one of three types of plague caused by bacterium "Yersinia pestis". One to seven days after exposure to the bacteria, flu like symptoms develop. These include fever, headaches, and vomiting. Swollen and painful lymph nodes occur in the area closest to where the bacteria entered the skin. Occasionally the swollen lymph nodes may break open.

The three types of plague are the result of the route of infection: bubonic plague, septicemic plague, and pneumonic plague. Bubonic plague is mainly spread by infected fleas from small animals. It may also result from exposure to the body fluids from a dead plague infected animal. In the bubonic form of plague, the bacteria enter through the skin through a flea bite and travel via the lymphatic vessels to a lymph node, causing it to swell. Diagnosis is made by finding the bacteria in the blood, sputum, or fluid from lymph nodes.

Prevention is through public health measures such as not handling dead animals in areas where plague is common. Vaccines have not been found to be very useful for plague prevention. Several antibiotics are effective for treatment including streptomycin, gentamicin, and doxycycline. Without treatment it results in the death of 30% to 90% of those infected. Death, if it occurs, is typically within ten days. With treatment the risk of death is around 10%. Globally there are about 650 documented cases a year which result in ~120 deaths. The disease is most common in Africa.

The plague is believed to be the cause of the Black Death that swept through Asia, Europe, and Africa in the 14th century and killed an estimated 50 million people. This was about 25% to 60% of the European population. Because the plague killed so many of the working population, wages rose due to the demand for labor. Some historians see this as a turning point in European economic development. The term "bubonic" is derived from the Greek word , meaning "groin". The term "buboes" is also used to refer to the swollen lymph nodes.

Common vectors for urban plague are house mice, black rats, and Norway rats.

Since 2002, the World Health Organization (WHO) has reported seven plague outbreaks, though some may go unreported because they often happen in remote areas. Between 1998 and 2009, nearly 24,000 cases have been reported, including about 2,000 deaths, in Africa, Asia, the Americas, and Eastern Europe. Ninety-eight percent of the world's cases occur in Africa.

Urban plague is an infectious disease among rodent species that live in close association with humans in urban areas. It is caused by the bacterium Yersinia pestis which is the same bacterium that causes bubonic and pneumonic plague in humans. Plague was first introduced into the United States in 1900 by rat–infested steamships that had sailed from affected areas, mostly from Asia. Urban plague spread from urban rats to rural rodent species, especially among prairie dogs in the western United States.

Crayfish plague, "Aphanomyces astaci", is a water mold that infects crayfish, most notably the European "Astacus" which dies within a few weeks of being infected. When experimentally tested, species from Australia, New Guinea and Japan were also found to be susceptible to the infection.

Occupations at risk include veterinarians, slaughterhouse workers, farmers, sailors on rivers, sewer maintenance workers, waste disposal facility workers, and people who work on derelict buildings. Slaughterhouse workers can contract the disease through contact with infected blood or body fluids. Rowers, kayakers and canoeists also sometimes contract the disease. It was once mostly work-related but is now often also related to adventure tourism and recreational activities.

Crayfish plague first arrived in Europe in Italy in 1859, either with imported crayfish from North America, or in ballast water. After its original introduction in Italy in 1860, it spread quickly through Europe and was discovered in Sweden in 1907, in Spain in 1972, in Norway in 1971, in Great Britain in 1981, in Turkey in 1984 and in Ireland in 1987.

In 1959, to bolster dwindling stocks of native crayfish, the signal crayfish was introduced to Sweden. The signal crayfish was known to be resistant, and it was not recognised at that time that it was a carrier of the disease. After 150 years of contact, no resistance has been discovered in native European crayfish.

This species was studied and named by the German Mycologist, Friedrich Schikora (1859–1932), from a type specimen in Germany in 1906.

Feeding on a human who carries the bacterium infects the louse. "R. prowazekii" grows in the louse's gut and is excreted in its feces. The disease is then transmitted to an uninfected human who scratches the louse bite (which itches) and rubs the feces into the wound. The incubation period is one to two weeks. "R. prowazekii" can remain viable and virulent in the dried louse feces for many days. Typhus will eventually kill the louse, though the disease will remain viable for many weeks in the dead louse.

Epidemic typhus has historically occurred during times of war and deprivation. For example, typhus killed hundreds of thousands of prisoners in Nazi concentration camps during World War II. The deteriorating quality of hygiene in camps such as Auschwitz, Theresienstadt, and Bergen-Belsen created conditions where diseases such as typhus flourished. Situations in the twenty-first century with potential for a typhus epidemic would include refugee camps during a major famine or natural disaster. In the periods between outbreaks, when human to human transmission occurs less often, the flying squirrel serves as a zoonotic reservoir for the "Rickettsia prowazekii" bacterium.

Henrique da Rocha Lima in 1916 then proved that the bacterium "Rickettsia prowazekii" was the agent responsible for typhus; he named it after H. T. Ricketts and Stanislaus von Prowazek, two zoologists who had died from typhus while investigating epidemics. Once these crucial facts were recognized, Rudolf Weigl in 1930 was able to fashion a practical and effective vaccine production method by grinding up the insides of infected lice that had been drinking blood. It was, however, very dangerous to produce, and carried a high likelihood of infection to those who were working on it.

A safer mass-production-ready method using egg yolks was developed by Herald R. Cox in 1938. This vaccine was widely available and used extensively by 1943.

Contagious bovine pleuropneumonia (CBPP - also known as lung plague), is a contagious bacterial disease that afflicts the lungs of cattle, buffalo, zebu, and yaks.

It is caused by the bacterium "Mycoplasma mycoides", and the symptoms are pneumonia and inflammation of the lung membranes. The incubation period is 20 to 123 days. It was particularly widespread in the United States in 1879, affecting herds from several states. The outbreak was so severe that it resulted in a trade embargo by the British government, blocking U.S. cattle exports to Britain and Canada. This prompted the United States to establish the Bureau of Animal Industry, set up in 1884 to eradicate the disease, which it succeeded in doing by 1892.

Louis Willems, a Belgian doctor, began pioneering work in the 1850s on animal inoculation against the disease.

The bacteria are widespread in Africa, the Middle East, Southern Europe, as well as parts of Asia. It is an airborne species, and can travel up to several kilometres in the right conditions.

The overall case-fatality rate for ordinary-type smallpox is about 30 percent, but varies by pock distribution: ordinary type-confluent is fatal about 50–75 percent of the time, ordinary-type semi-confluent about 25–50 percent of the time, in cases where the rash is discrete the case-fatality rate is less than 10 percent. The overall fatality rate for children younger than 1 year of age is 40–50 percent. Hemorrhagic and flat types have the highest fatality rates. The fatality rate for flat-type is 90 percent or greater and nearly 100 percent is observed in cases of hemorrhagic smallpox. The case-fatality rate for variola minor is 1 percent or less. There is no evidence of chronic or recurrent infection with variola virus.

In fatal cases of ordinary smallpox, death usually occurs between the tenth and sixteenth days of the illness. The cause of death from smallpox is not clear, but the infection is now known to involve multiple organs. Circulating immune complexes, overwhelming viremia, or an uncontrolled immune response may be contributing factors. In early hemorrhagic smallpox, death occurs suddenly about six days after the fever develops. Cause of death in hemorrhagic cases involved heart failure, sometimes accompanied by pulmonary edema. In late hemorrhagic cases, high and sustained viremia, severe platelet loss and poor immune response were often cited as causes of death. In flat smallpox modes of death are similar to those in burns, with loss of fluid, protein and electrolytes beyond the capacity of the body to replace or acquire, and fulminating sepsis.

Symptoms include severe headache, a sustained high fever, cough, rash, severe muscle pain, chills, falling blood pressure, stupor, sensitivity to light, delirium and death. A rash begins on the chest about five days after the fever appears, and spreads to the trunk and extremities. A symptom common to all forms of typhus is a fever which may reach 39 °C (102 °F).

Brill-Zinsser disease, first described by Nathan Brill in 1913 at Mount Sinai Hospital in New York City, is a mild form of epidemic typhus which recurs in someone after a long period of latency (similar to the relationship between chickenpox and shingles). This recurrence often occurs in times of relative immunosuppression, which is often in the context of malnutrition and other illnesses. In combination with poor sanitation and hygiene which leads to a greater density of lice, this reactivation is why typhus forms epidemics in times of social chaos and upheaval.

Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as the urine is still moist. Although "Leptospira" has been detected in reptiles and birds, only mammals are able to transmit the bacterium to humans and other animals. Rats, mice, and moles are important primary hosts—but a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, swine, raccoons, opossums, skunks, and certain marine mammals carry and transmit the disease as secondary hosts. In Africa, the banded mongoose has been identified as a carrier of the pathogen, likely in addition to other African wildlife hosts. Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle.

House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in the house. The type of habitats most likely to carry infective bacteria includes muddy riverbanks, ditches, gullies, and muddy livestock rearing areas where there is a regular passage of wild or farm mammals. The incidence of leptospirosis correlates directly with the amount of rainfall, making it seasonal in temperate climates and year-round in tropical climates.

Leptospirosis also transmits via the semen of infected animals.

Humans become infected through contact with water, food, or soil that contains urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact. The disease is not known to spread between humans, and bacterial dissemination in convalescence is extremely rare in humans. Leptospirosis is common among water-sport enthusiasts in specific areas, as prolonged immersion in water promotes the entry of this bacterium. Surfers and whitewater paddlers are at especially high risk in areas that have been shown to contain these bacteria, and can contract the disease by swallowing contaminated water, splashing contaminated water into their eyes or nose, or exposing open wounds to infected water.

Death rates during outbreaks were usually extremely high, approaching 100% in immunologically naïve populations. The disease was mainly spread by direct contact and by drinking contaminated water, although it could also be transmitted by air.

Initial symptoms include fever, loss of appetite, and nasal and eye discharges. Subsequently, irregular erosions appear in the mouth, the lining of the nose, and the genital tract. Acute diarrhea, preceded by constipation, is also a common feature. Most animals die six to twelve days after the onset of these clinical signs.

Rinderpest (also cattle plague or steppe murrain) was an infectious viral disease of cattle, domestic buffalo, and many other species of even-toed ungulates, including buffaloes, large antelope and deer, giraffes, wildebeests, and warthogs. The disease was characterized by fever, oral erosions, diarrhea, lymphoid necrosis, and high mortality. Death rates during outbreaks were usually extremely high, approaching 100% in immunologically naïve populations. Rinderpest was mainly transmitted by direct contact and by drinking contaminated water, although it could also be transmitted by air. After a global eradication campaign, the last confirmed case of rinderpest was diagnosed in 2011.

On 14 October 2010, the United Nations Food and Agriculture Organization (FAO) announced that field activities in the decades-long, worldwide campaign to eradicate the disease were ending, paving the way for a formal declaration in June 2011 of the global eradication of rinderpest. On 25 May 2011, the World Organisation for Animal Health announced the free status of the last eight countries not yet recognized (a total of 198 countries were now free of the disease), officially declaring the eradication of the disease. In June 2011, the United Nations FAO confirmed the disease was eradicated, making rinderpest only the second disease in history to be fully wiped out (outside laboratory stocks), following smallpox.

Rinderpest is believed to have originated in Asia, later spreading through the transport of cattle. The term "Rinderpest" is a German word meaning "cattle-plague". The rinderpest virus (RPV) was closely related to the measles and canine distemper viruses. The measles virus emerged from rinderpest as a zoonotic disease between 1000 and 1100 AD, a period that may have been preceded by limited outbreaks involving a virus not yet fully acclimated to humans.

Contact with farm animals can lead to disease in farmers or others that come into contact with infected animals. Glanders primarily affects those who work closely with horses and donkeys. Close contact with cattle can lead to cutaneous anthrax infection, whereas inhalation anthrax infection is more common for workers in slaughterhouses, tanneries and wool mills. Close contact with sheep who have recently given birth can lead to clamydiosis, or enzootic abortion, in pregnant women, as well as an increased risk of Q fever, toxoplasmosis, and listeriosis in pregnant or the otherwise immunocompromised. Echinococcosis is caused by a tapeworm which can be spread from infected sheep by food or water contaminated with feces or wool. Bird flu is common in chickens. While rare in humans, the main public health worry is that a strain of bird flu will recombine with a human flu virus and cause a pandemic like the 1918 Spanish flu. In 2017, free range chickens in the UK were temporarily ordered to remain inside due to the threat of bird flu. Cattle are an important reservoir of cryptosporidiosis and mainly affects the immunocompromised.