Lymphatics ultimately drain into the bloodstream, so the plague bacteria may enter the blood and travel to almost any part of the body. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation (DIC), causing tiny clots throughout the body and possibly ischaemic necrosis (tissue death due to lack of circulation/perfusion to that tissue) from the clots. DIC results in depletion of the body's clotting resources, so that it can no longer control bleeding. Consequently, there is bleeding into the skin and other organs, which can cause red and/or black patchy rash and hemoptysis/hematemesis (coughing up/ vomiting of blood). There are bumps on the skin that look somewhat like insect bites; these are usually red, and sometimes white in the center. Untreated, septicemic plague is usually fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. People who die from this form of plague often die on the same day symptoms first appear.

The best-known symptom of bubonic plague is one or more infected, enlarged, and painful lymph nodes, known as buboes. After being transmitted via the bite of an infected flea, the "Y. pestis" bacteria become localized in an inflamed lymph node where they begin to colonize and reproduce. Buboes associated with the bubonic plague are commonly found in the armpits, upper femoral, groin and neck region. Acral gangrene (i.e., of the fingers, toes, lips and nose) is another common symptom.

Because of its bite-based mode of transmission, the bubonic plague is often the first of a progressive series of illnesses. Bubonic plague symptoms appear suddenly a few days after exposure to the bacterium. Symptoms include:

- Chills

- General ill feeling (malaise)

- High fever (39 °C; 102 °F)

- Muscle cramps

- Seizures

- Smooth, painful lymph gland swelling called a bubo, commonly found in the groin, but may occur in the armpits or neck, most often near the site of the initial infection (bite or scratch)

- Pain may occur in the area before the swelling appears

- Gangrene of the extremities such as toes, fingers, lips and tip of the nose.

Other symptoms include heavy breathing, continuous vomiting of blood (hematemesis), aching limbs, coughing, and extreme pain caused by the decay or decomposition of the skin while the person is still alive. Additional symptoms include extreme fatigue, gastrointestinal problems, lenticulae (black dots scattered throughout the body), delirium, and coma.

The pneumonic form of plague arises from infection of the lungs. It causes coughing and sneezing and thereby produces airborne droplets that contain bacterial cells and are likely to infect anyone inhaling them. The incubation period for pneumonic plague is short, usually two to four days, but sometimes just a few hours. The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness and spitting or vomiting of blood. The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases mortality is nearly 100%.

The usual symptoms are:

- Abdominal pain

- Bleeding under skin due to blood clotting problems

- Bleeding from mouth, nose or rectum

- Diarrhea

- Fever

- Chills

- Low blood pressure

- Nausea

- Organ failure

- Vomiting

- Shock

- Death of tissue (gangrene) causing blackening in extremities, mostly fingers, toes and nose

- Difficulty breathing

However, septicemic plague may cause death before any symptoms occur. Also, the above symptoms are common to many human illnesses, and are not considered diagnostic of any form of plague.

Depending on the site of infection, tularemia has six characteristic clinical variants: ulceroglandular (the most common type representing 75% of all forms), glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal.

The incubation period for tularemia is one to 14 days; most human infections become apparent after three to five days. In most susceptible mammals, the clinical signs include fever, lethargy, loss of appetite, signs of sepsis, and possibly death. Nonhuman mammals rarely develop the skin lesions seen in people. Subclinical infections are common, and animals often develop specific antibodies to the organism. Fever is moderate or very high, and tularemia bacilli can be isolated from blood cultures at this stage. The face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever.

The most apparent symptom of pneumonic plague is coughing, often with hemoptysis (coughing up blood). With pneumonic plague, the first signs of illness are fever, headache, weakness and rapidly developing pneumonia with shortness of breath, chest pain, cough and sometimes bloody or watery sputum.

The pneumonia progresses for two to four days and may cause respiratory failure and shock. Patients will die without early treatment, some within 36 hours.

Initial pneumonic plague symptoms can often include the following:

- Fever

- Weakness

- Headaches

- Nausea

Rapidly developing pneumonia with:

- Shortness of breath

- Chest pain

- Cough

- Bloody or watery sputum (saliva and discharge from respiratory passages).

Septicemic plague is one of the three main forms of plague. It is caused by "Yersinia pestis", a gram-negative species of bacterium. Septicemic plague is a life-threatening infection of the blood, most commonly spread by bites from infected fleas.

Like some other forms of gram-negative sepsis, septicemic plague can cause disseminated intravascular coagulation, and is almost always fatal when untreated (the mortality rate in medieval times was 99–100 percent). However, it only occurs in a minority of cases of "Yersinia" infection, so that fewer than 5,000 people a year acquire the disease. It is the rarest of the three plague varieties; the other forms are bubonic and pneumonic plague.

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.

Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium "Francisella tularensis". Symptoms may include fever, skin ulcer, and enlarged lymph nodes. Occasionally a form that results in pneumonia or a threat infection may occur.

The bacterium is typically spread by ticks, deer flies, or contact with infected animals. It may also be spread by drinking contaminated water or breathing in contaminated dust. It does not spread directly between people. Diagnosis is by blood tests or cultures of the infected site.

Prevention is by using insect repellent, wearing long pants, rapidly removing ticks, and not disturbing dead animals. Treatment is typically with the antibiotic streptomycin. Gentamicin, doxycycline, or ciprofloxacin may also be used.

Between the 1970s and 2015 around 200 cases are reported in the United States a year. Males are affected more often than females. It occurs most frequently in the young and the middle aged. In the United States most cases occur in the summer. The disease is named after Tulare County, California were the disease was discovered in 1911. A number of other animals, such as rabbits, may also be infected.

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

Pneumonic plague is a severe lung infection caused by the bacterium "Yersinia pestis". Symptoms include fever, headache, shortness of breath, chest pain, and cough. They typically start about three to seven days after exposure. It is one of three forms of plague, the other two being septicemic plague and bubonic plague.

The pneumonic form may occur following an initial bubonic or septicemic plague infection. It may also result from breathing in airborne droplets from another person or cat infected with pneumonic plague. The difference between the forms of plague is the location of infection; in pneumonic plague the infection is in the lungs, in bubonic plague the lymph nodes, and in septicemic plague within the blood. Diagnosis is by testing the blood, sputum, or fluid from a lymph node.

While vaccines are being worked on, in most countries they are not yet commercially available. Prevention is generally by avoiding contact with rodents. It is recommended that those infected be isolated from others. Treatment of pneumonic plague is with antibiotics.

Plague is present among rodents in Africa, the Americas, and Asia. Pneumonic plague is more serious and less common than bubonic plague. The total reported number of all types of plague in 2013 was 783. Untreated pneumonic plague has a mortality of nearly 100%. Some hypothesize that the pneumonic version of the plague was mainly responsible for the Black Death that resulted in approximately 50 million deaths in the 1300s.

Sylvatic plague is an infectious bacterial disease caused by the bacterium "Yersinia pestis" that primarily affects rodents such as prairie dogs. It is the same bacterium that causes bubonic and pneumonic plague in humans. Sylvatic, or sylvan, means 'occurring in wildlife,' and refers specifically to the form of plague in rural wildlife. Urban plague refers to the form in urban wildlife.

It is primarily transmitted among wildlife through flea bites and contact with infected tissue or fluids. Sylvatic plague is most commonly found in prairie dog colonies and some mustelids like the black-footed ferret.

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.

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.

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.

Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters. The causative organism is "Rickettsia prowazekii", transmitted by the human body louse ("Pediculus humanus humanus").

Leptospiral infection in humans causes a range of symptoms, and some infected persons may have no symptoms at all. Leptospirosis is a biphasic disease that begins suddenly with fever accompanied by chills, intense headache, severe myalgia (muscle ache), abdominal pain, conjunctival suffusion (red eye), and occasionally a skin rash. The symptoms appear after an incubation period of 7–12 days. The first phase (acute or septic phase) ends after 3–7 days of illness. The disappearance of symptoms coincides with the appearance of antibodies against "Leptospira" and the disappearance of all the bacteria from the bloodstream. The patient is asymptomatic for 3–4 days until the second phase begins with another episode of fever. The hallmark of the second phase is meningitis (inflammation of the membranes covering the brain).

Ninety percent of cases of the disease are mild leptospirosis. The rest experience severe disease, which develops during the second stage or occurs as a single progressive illness. The classic form of severe leptospirosis is known as Weil's disease, which is characterized by liver damage (causing jaundice), kidney failure, and bleeding. Additionally, the heart and brain can be affected, meningitis of the outer layer of the brain, encephalitis of brain tissue with same signs and symptoms; and lung affected as the most serious and life-threatening of all leptospirosis complications. The infection is often incorrectly diagnosed due to the nonspecific symptoms.

Other severe manifestations include extreme fatigue, hearing loss, respiratory distress, and azotemia.

Most people who are infected develop sickness between five and 15 days after they are bitten. The symptoms may include a sudden fever, chills, headaches, muscle or joint aches, and nausea. A rash may also occur. These symptoms usually continue for two to 9 days, then disappear. This cycle may continue for several weeks if the person is not treated.

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.

A spotted fever is a type of tick-borne disease which presents on the skin. They are all caused by bacteria of the genus "Rickettsia". Typhus is a group of similar diseases also caused by "Rickettsia" bacteria, but spotted fevers and typhus are different clinical entities.

The phrase apparently originated in Spain in the seventeenth century and was ‘loosely applied in England to typhus or any fever involving petechial eruptions.’ During the seventeenth and eighteenth centuries, it was thought to be ‘“cousin-germane” to and herald of the bubonic plague’, a disease which periodically afflicted the city of London and its environs during the sixteenth and seventeenth centuries, most notably during the Great Plague of 1665.

Types of spotted fevers include:

- Mediterranean spotted fever

- Rocky Mountain spotted fever

- Queensland tick typhus

- Helvetica Spotted fever

Leptospirosis is an infection caused by corkscrew-shaped bacteria called "Leptospira". Signs and symptoms can range from none to mild such as headaches, muscle pains, and fevers; to severe with bleeding from the lungs or meningitis. If the infection causes the person to turn yellow, have kidney failure and bleeding, it is then known as Weil's disease. If it also causes bleeding into the lungs then it is known as severe pulmonary hemorrhage syndrome.

Up to 13 different genetic types of "Leptospira" may cause disease in humans. It is transmitted by both wild and domestic animals. The most common animals that spread the disease are rodents. It is often transmitted by animal urine or by water or soil containing animal urine coming into contact with breaks in the skin, eyes, mouth, or nose. In the developing world the disease most commonly occurs in farmers and poor people who live in cities. In the developed world it most commonly occurs in those involved in outdoor activities in warm and wet areas of the world. Diagnosis is typically by looking for antibodies against the bacterium or finding its DNA in the blood.

Efforts to prevent the disease include protective equipment to prevent contact when working with potentially infected animals, washing after this contact, and reducing rodents in areas people live and work. The antibiotic doxycycline, when used in an effort to prevent infection among travellers, is of unclear benefit. Vaccines for animals exist for certain type of "Leptospira" which may decrease the risk of spread to humans. Treatment if infected is with antibiotics such as: doxycycline, penicillin, or ceftriaxone. Weil's disease and severe pulmonary haemorrhage syndrome result in death rates greater than 10% and 50%, respectively, even with treatment.

It is estimated that seven to ten million people are infected by leptospirosis per year. The number of deaths this causes is not clear. The disease is most common in tropical areas of the world but may occur anywhere. Outbreaks may occur in slums of the developing world. The disease was first described by physician Adolf Weil in 1886 in Germany. Animals which are infected may have no symptoms, mild symptoms, or severe symptoms. Symptoms may vary by the type of animal. In some animals "Leptospira" live in the reproductive tract, leading to transmission during mating.

Classically, the course of untreated typhoid fever is divided into four distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.

- In the first week, the body temperature rises slowly, and fever fluctuations are seen with relative bradycardia (Faget sign), malaise, headache, and cough. A bloody nose (epistaxis) is seen in a quarter of cases, and abdominal pain is also possible. A decrease in the number of circulating white blood cells (leukopenia) occurs with eosinopenia and relative lymphocytosis; blood cultures are positive for "Salmonella" Typhi or "S. paratyphi". The Widal test is usually negative in the first week.

- In the second week, the person is often too tired to get up, with high fever in plateau around and bradycardia (sphygmothermic dissociation or Faget sign), classically with a dicrotic pulse wave. Delirium is frequent, often calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. Rhonchi are heard in lung bases.

- The abdomen is distended and painful in the right lower quadrant, where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green, comparable to pea soup, with a characteristic smell. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and liver transaminases are elevated. The Widal test is strongly positive, with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.

- (The major symptom of this fever is that the fever usually rises in the afternoon up to the first and second week.)

- In the third week of typhoid fever, a number of complications can occur:

- Intestinal haemorrhage due to bleeding in congested Peyer's patches; this can be very serious, but is usually not fatal.

- Intestinal perforation in the distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.

- Encephalitis

- Respiratory diseases such as pneumonia and acute bronchitis

- Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.

- Metastatic abscesses, cholecystitis, endocarditis, and osteitis

- The fever is still very high and oscillates very little over 24 hours. Dehydration ensues, and the patient is delirious (typhoid state). One-third of affected individuals develop a macular rash on the trunk.

- Platelet count goes down slowly and risk of bleeding rises.

- By the end of third week, the fever starts subsiding

Yellow fever begins after an incubation period of three to six days. Most cases only cause a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to four days.

In 15% of cases, however, people enter a second, toxic phase of the disease with recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, the eyes, and the gastrointestinal tract cause vomit containing blood, hence the Spanish name for yellow fever, "vómito negro" ("black vomit"). There may also be kidney failure, hiccups, and delirium.

The toxic phase is fatal in about 20 to 50% of cases, making the overall fatality rate for the disease about 3.0 to 7.5%. However, the fatality rate of those with the toxic phase of the disease may exceed 50%.

Surviving the infection provides lifelong immunity, and normally no permanent organ damage results.

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.

"Bartonella quintana" is transmitted by contamination of a skin abrasion or louse-bite wound with the faeces of an infected body louse ("Pediculus humanus corporis"). There have also been reports of an infected louse bite passing on the infection.