The pathogenic agent is found everywhere except New Zealand. The bacterium is extremely sustainable and virulent: a single organism is able to cause an infection. The common source of infection is inhalation of contaminated dust, contact with contaminated milk, meat, or wool, and particularly birthing products. Ticks can transfer the pathogenic agent to other animals. Transfer between humans seems extremely rare and has so far been described in very few cases.

Some studies have shown more men to be affected than women, which may be attributed to different employment rates in typical professions.

“At risk” occupations include:

- Veterinary personnel

- Stockyard workers

- Farmers

- Sheep shearers

- Animal transporters

- Laboratory workers handling potentially infected veterinary samples or visiting abattoirs

- People who cull and process kangaroos

- Hide (tannery) workers

Currently, no vaccine against relapsing fever is available, but research continues. Developing a vaccine is very difficult because the spirochetes avoid the immune response of the infected person (or animal) through antigenic variation. Essentially, the pathogen stays one step ahead of antibodies by changing its surface proteins. These surface proteins, lipoproteins called variable major proteins, have only 30–70% of their amino acid sequences in common, which is sufficient to create a new antigenic "identity" for the organism. Antibodies in the blood that are binding to and clearing spirochetes expressing the old proteins do not recognize spirochetes expressing the new ones. Antigenic variation is common among pathogenic organisms. These include the agents of malaria, gonorrhea, and sleeping sickness. Important questions about antigenic variation are also relevant for such research areas as developing a vaccine against HIV and predicting the next influenza pandemic.

It is estimated that seven to ten million people are infected by leptospirosis annually. One million cases of severe leptospirosis occur annually, with 58,900 deaths. Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in tropical climates. This leads to a lower number of registered cases than likely exists.

The number of new cases of leptospirosis is difficult to estimate since many cases of the disease go unreported. There are many reasons for this, but the biggest issue is separating the disease from other similar conditions. Laboratory testing is lacking in many areas.

In context of global epidemiology, the socioeconomic status of many of the world’s population is closely tied to malnutrition; subsequent lack of micronutrients may lead to increased risk of infection and death due to leptospirosis infection. Micronutrients such as iron, calcium, and magnesium represent important areas of future research.

Outbreaks that occurred after the 1940's have happened mostly in the late summer seasons, which happens to be the driest part of the year. The people at the highest risk for leptospirosis are young people whose age ranges from 5-16 years old, and can also range to young adults.

The amount of cases increase during the rainy season in the tropics and during the late summer or early fall in Western countries. This happens because leptospires survive best in fresh water, damp alkaline soil, vegetation, and mud with temperatures higher that 22° C. This also leads to increased risk of exposure to populations during flood conditions, and leptospire concentrations to peak in isolated pools during drought. There is no evidence of leptospirosis having any effect on sexual and age-related differences. However, a major risk factor for development of the disease is occupational exposure, a disproportionate number of working-aged males are affected. There have been reported outbreaks where more than 40% of people are younger than 15. “Active surveillance measures have detected leptospire antibodies in as many as 30% of children in some urban American populations.” Potential reasons for such cases include children playing with suspected vectors such as dogs or indiscriminate contact with water.

They are usually spread by eating or drinking food or water contaminated with the feces of an infected person. They may occur when a person who prepares food is infected. Risk factors include poor sanitation as is found among poor crowded populations. Occasionally they may be transmitted by sex. Humans are the only animal infected.

Paratyphoid B is more frequent in Europe. It can present as a typhoid-like illness, as a severe gastroenteritis or with features of both. Herpes labialis, rare in true typhoid fever, is frequently seen in paratyphoid B. Diagnosis is with isolation of the agent in blood or stool and demonstration of antibodies antiBH in the Widal test. The disease responds well to chloramphenicol or co-trimoxazole.

Protection is offered by Q-Vax, a whole-cell, inactivated vaccine developed by an Australian vaccine manufacturing company, CSL Limited. The intradermal vaccination is composed of killed "C. burnetii" organisms. Skin and blood tests should be done before vaccination to identify pre-existing immunity, because vaccinating people who already have an immunity can result in a severe local reaction. After a single dose of vaccine, protective immunity lasts for many years. Revaccination is not generally required. Annual screening is typically recommended.

In 2001, Australia introduced a national Q fever vaccination program for people working in “at risk” occupations. Vaccinated or previously exposed people may have their status recorded on the Australian Q Fever Register, which may be a condition of employment in the meat processing industry. An earlier killed vaccine had been developed in the Soviet Union, but its side effects prevented its licensing abroad.

Preliminary results suggest vaccination of animals may be a method of control. Published trials proved that use of a registered phase vaccine (Coxevac) on infected farms is a tool of major interest to manage or prevent early or late abortion, repeat breeding, anoestrus, silent oestrus, metritis, and decreases in milk yield when "C. burnetii" is the major cause of these problems.

Doxycycline has been provided once a week as a prophylaxis to minimize infections during outbreaks in endemic regions. However, there is no evidence that chemoprophylaxis is effective in containing outbreaks of leptospirosis, and use of antibiotics increases antibiotics resistance. Pre-exposure prophylaxis may be beneficial for individuals traveling to high-risk areas for a short stay.

Effective rat control and avoidance of urine contaminated water sources are essential preventive measures. Human vaccines are available only in a few countries, such as Cuba and China. Animal vaccines only cover a few strains of the bacteria. Dog vaccines are effective for at least one year.

Cases of African tick bite fever have been more frequently reported in the literature among international travelers. Data examining rates in local populations are limited. Among locals who live in endemic areas, exposure at a young age and mild symptoms or lack of symptoms, as well as decreased access to diagnostic tools, may lead to decreased diagnosis. In Zimbabwe, where "R. africae" is endemic, one study reported an estimated yearly incidence of 60-80 cases per 10,000 patients.

Looking at published data over the past 35 years, close to 200 confirmed cases of African tick bite fever in international travelers have been reported. The majority (~80%) of these cases occurred in travelers returning from South Africa.

Relapsing fever is easily treated with a one- to two-week-course of antibiotics, and most people improve within 24 hours. Complications and death due to relapsing fever are rare.

Tetracycline-class antibiotics are most effective. These can, however, induce a Jarisch–Herxheimer reaction in over half those treated, producing anxiety, diaphoresis, fever, tachycardia and tachypnea with an initial pressor response followed rapidly by hypotension. Recent studies have shown tumor necrosis factor-alpha may be partly responsible for this reaction.

Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because "R. rickettsii" infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or kidneys.

Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations

"Rickettsia africae" is a gram-negative, obligate intracellular, pleomorphic bacterium. It belongs to the "Rickettsia" genus, which includes many bacterial species that are transmitted to humans by arthropods.

A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin, but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade. About 60% of circulating strains of the group A "Streptococcus" which cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, says Professor Kwok-yung Yuen, head of Hong Kong University's microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years.

When proper treatment is provided for patients with rat-bite fever, the prognosis is positive. Without treatment, the infection usually resolves on its own, although it may take up to a year to do so. A particular strain of rat-bite fever in the United States can progress and cause serious complications that can be potentially fatal. Before antibiotics were used, many cases resulted in death. If left untreated, streptobacillary rat-bite fever can result in infection in the lining of the heart, covering over the spinal cord and brain, or in the lungs. Any tissue or organ throughout the body may develop an abscess.

While obviously preventable by staying away from rodents, otherwise hands and face should be washed after contact and any scratches both cleaned and antiseptics applied. The effect of chemoprophylaxis following rodent bites or scratches on the disease is unknown. No vaccines are available for these diseases.

Improved conditions to minimize rodent contact with humans are the best preventive measures. Animal handlers, laboratory workers, and sanitation and sewer workers must take special precautions against exposure. Wild rodents, dead or alive, should not be touched and pets must not be allowed to ingest rodents.

Those living in the inner cities where overcrowding and poor sanitation cause rodent problems are at risk from the disease. Half of all cases reported are children under 12 living in these conditions.

Tetracycline-group antibiotics (doxycycline, tetracycline) are commonly used. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver malfunction, kidney deficiency, in children under nine years and in pregnant women. The drug is administered for seven to ten days.

The treatment for bacillary angiomatosis is erythromycin given for three to four months.

Trench fever (also known as "five-day fever", "quintan fever" ("febris quintana" in Latin), and "urban trench fever") is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, Russia and Egypt in World War I. Three noted sufferers during WWI were the authors J.R.R. Tolkien, A. A. Milne, and C.S. Lewis. From 1915 to 1918 between one-fifth and one-third of all British troops reported ill had trench fever while about one-fifth of ill German and Austrian troops had the disease. The disease persists among the homeless. Outbreaks have been documented, for example, in Seattle and Baltimore in the United States among injection drug users and in Marseille, France, and Burundi.

Trench fever is also called Wolhynia fever, shin bone fever, Meuse fever, His disease and His–Werner disease (after Wilhelm His, Jr. and Heinrich Werner).

The disease is caused by the bacterium "Bartonella quintana" (older names: "Rochalimea quintana", "Rickettsia quintana"), found in the stomach walls of the body louse. "Bartonella quintana" is closely related to "Bartonella henselae", the agent of cat scratch fever and bacillary angiomatosis.

There are only between 500 and 2500 cases of Rocky Mountain spotted fever reported in the United States per year, and in only about 20% can the tick be found.

Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African or Caribbean background, chronic alcohol abuse, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a genetic condition affecting about 12 percent of the Afro-American male population. Deficiency in this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever. This is a rare clinical complication that is often fatal within five days of the onset of the disease.

In the early 1940´s, outbreaks were described in the Mexican states of Sinaloa, Sonora, Durango, and Coahuila driven by dogs and Rhipicephalus sanguineus sensu lato, the brown dog tick. Over the ensuing 100 years case fatality rates were 30%–80%. In 2015, there was an abrupt rise in Sonora cases with 80 fatal cases. From 2003 to 2016, cases increased to 1394 with 247 deaths.

The bacterium that causes typhoid fever may be spread through poor hygiene habits and public sanitation conditions, and sometimes also by flying insects feeding on feces. Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease. According to statistics from the United States Centers for Disease Control and Prevention (CDC), the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the United States.

Scarlet fever occurs equally in both males and females. Children are most commonly infected, typically between 5–15 years old. Although streptococcal infections can happen at any time of year, infection rates peak in the winter and spring months, typically in colder climates.

The morbidity and mortality of scarlet fever has declined since the 18th and 19th century when there were epidemics caused by this disease. Around 1900 the mortality rate in multiple places reached 25%. In The improvement in prognosis can be attributed to the use of penicillin in the treatment of this disease. The frequency of scarlet fever cases has also been declining over the past century however, there have been several reported outbreaks of the disease in various countries in the past decade. The reason for these recent increases remains unclear in the medical community.

The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides or fluoroquinolones.

As of 2017 there is no commercially available vaccine. A vaccine has been in development for scrub typhus known as the scrub typhus vaccine.

Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of disease and 30,000 deaths a year occur; the number of officially reported cases is far lower.

Haverhill fever (or epidemic arthritic erythema) is a form of "rat-bite fever" caused by the bacterium "Streptobacillus moniliformis", an organism common in rats and mice. Symptoms begin to appear two to ten days after a rat bite injury. The illness resembles a severe influenza, with a moderate fever (38-40 °C, or 101-104 °F), chills, joint pain, and a diffuse red rash, located mostly on the hands and feet. The causative organism can be isolated by blood culture, and penicillin is the most common treatment. Treatment is usually quite successful, although the body can clear the infection by itself in most cases. Complications are rare, but can include endocarditis and meningitis.

Despite its name, it can present without being bitten by a rat.

The disease was recognized from an outbreak which occurred in Haverhill, Massachusetts in January, 1926. The organism "S. moniliformis" was isolated from the patients. Epidemiology implicated infection via consumption of milk from one particular dairy.

Severe disease is more common in babies and young children, and in contrast to many other infections, it is more common in children who are relatively well nourished. Other risk factors for severe disease include female sex, high body mass index, and viral load. While each serotype can cause the full spectrum of disease, virus strain is a risk factor. Infection with one serotype is thought to produce lifelong immunity to that type, but only short-term protection against the other three. The risk of severe disease from secondary infection increases if someone previously exposed to serotype DENV-1 contracts serotype DENV-2 or DENV-3, or if someone previously exposed to DENV-3 acquires DENV-2. Dengue can be life-threatening in people with chronic diseases such as diabetes and asthma.

Polymorphisms (normal variations) in particular genes have been linked with an increased risk of severe dengue complications. Examples include the genes coding for the proteins known as TNFα, mannan-binding lectin, CTLA4, TGFβ, DC-SIGN, PLCE1, and particular forms of human leukocyte antigen from gene variations of HLA-B. A common genetic abnormality, especially in Africans, known as glucose-6-phosphate dehydrogenase deficiency, appears to increase the risk. Polymorphisms in the genes for the vitamin D receptor and FcγR seem to offer protection against severe disease in secondary dengue infection.

The study of RRF has been recently facilitated by the development of a mouse model. Mice infected with RRV develop hind-limb arthritis/arthralgia which is similar to human disease. The disease in mice is characterized by an inflammatory infiltrate including macrophages which are immunopathogenic and exacerbate disease. Furthermore, mice deficient in the C3 protein do not suffer from severe disease following infection. This indicates that an aberrant innate immune response is responsible for severe disease following RRV infection.