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.

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.

The disease can be fatal if left untreated, but endemic typhus is highly treatable with antibiotics. Most people recover fully, but death may occur in the elderly, severely disabled or patients with a depressed immune system. The most effective antibiotics include tetracycline and chloramphenicol. In United States, CDC recommends solely doxycycline.

It is caused by the bacteria "Rickettsia typhi", and is transmitted by the fleas that infest rats. While rat fleas are the most common vectors, cat fleas and mouse fleas are less common modes of transmission. These fleas are not affected by the infection. Human infection occurs because of flea-fecal contamination of the bites on human skin. Rats, cats, opossums maintain the rickettsia colonization by providing it with a host for its entire life cycle. Rats can develop the infection, and help spread the infection to other fleas that infect them, and help multiply the number of infected fleas that can then infect humans.

Less often, endemic typhus is caused by "Rickettsia felis" and transmitted by fleas carried by cats or opossums.

In the United States of America, murine typhus is found most commonly in southern California, Texas and Hawaii. In some studies, up to 13% of children were found to have serological evidence of infection.

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.

Prevention of ATBF centers around protecting oneself from tick bites by wearing long pants and shirt, and using insecticides like DEET on the skin. Travelers to rural areas in Africa and the West Indies should be aware that they may come in contact with ATBF tick vectors. Infection is more likely to occur in people who are traveling to rural areas or plan to spend time participating in outdoor activities. Extra caution should be taken in November - April, when "Amblyomma" ticks are more active. Inspection of the body, clothing, gear, and any pets after time outdoors can help to identify and remove ticks early.

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

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.

Tick-borne relapsing fever is found primarily in Africa, Spain, Saudi Arabia, Asia, and certain areas of Canada and the western United States. Other relapsing infections are acquired from other "Borrelia" species, which can be spread from rodents, and serve as a reservoir for the infection, by a tick vector.

- "Borrelia crocidurae" – occurs in Egypt, Mali, Senegal, Tunisia; vectors – "Carios erraticus", "Ornithodoros sonrai"; animal host – shrew ("Crocidura stampflii")

- "Borrelia duttoni", transmitted by the soft-bodied African tick "Ornithodoros moubata", is responsible for the relapsing fever found in central, eastern, and southern Africa.

- "Borrelia hermsii"

- "Borrelia hispanica"

- "Borrelia miyamotoi"

- "Borrelia parkeri"

- "Borrelia turicatae"

"B. hermsii" and "B. recurrentis" cause very similar diseases. However, one or two relapses are common with the disease associated with "B. hermsii", which is also the most common cause of relapsing disease in the United States. (Three or four relapses are common with the disease caused by "B. recurrentis", which has longer febrile and afebrile intervals and a longer incubation period than "B. hermsii".)

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

Scrub typhus is transmitted by some species of trombiculid mites ("chiggers", particularly "Leptotrombidium deliense"), which are found in areas of heavy scrub vegetation. The bite of this mite leaves a characteristic black eschar that is useful to the doctor for making the diagnosis.

Scrub typhus is endemic to a part of the world known as the tsutsugamushi triangle (after "O. tsutsugamushi"). This extends from northern Japan and far-eastern Russia in the north, to the territories around the Solomon Sea into northern Australia in the south, and to Pakistan and Afghanistan in the west. It may also be endemic in parts of South America, too.

The precise incidence of the disease is unknown, as diagnostic facilities are not available in much of its large native range which spans vast regions of equatorial jungle to the subtropics. In rural Thailand and Laos, murine and scrub typhus account for around a quarter of all adults presenting to hospital with fever and negative blood cultures. The incidence in Japan has fallen over the past few decades, probably due to land development driving decreasing exposure, and many prefectures report fewer than 50 cases per year.

It affects females more than males in Korea, but not in Japan, and which may be because sex-differentiated cultural roles have women tending garden plots more often, thus being exposed to vegetation inhabited by chiggers.

The incidence is increasing in the southern part of the Indian subcontinent and in northern areas around Darjeeling.

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.

The disease develops from March to September, with the highest infections occurring in June. The disease is found almost exclusively in the western United States and Canada, mostly in high mountain areas such as Colorado and Idaho. The CTFV was first isolated from human blood in 1944.

The American Public Health Association recommends treatment based upon clinical findings and before culturing confirms the diagnosis. Without treatment, death may occur in 10 to 60 percent of patients with epidemic typhus, with patients over age 60 having the highest risk of death. In the antibiotic era, death is uncommon if doxycycline is given. In one study of 60 hospitalized patients with epidemic typhus, no patient died when given doxycycline or chloramphenicol. Some patients also may need oxygen and intravenous (IV) fluids.

Measures to reduce contact between the vesper mouse and humans may have contributed to limiting the number of outbreaks, with no cases identified between 1973 and 1994. Although there are no cures or vaccine for the disease, a vaccine developed for the genetically related Junín virus which causes Argentine hemorrhagic fever has shown evidence of cross-reactivity to Machupo virus, and may therefore be an effective prophylactic measure for people at high risk of infection. Post infection (and providing that the person survives the infection), those that have contracted BHF are usually immune to further infection of the disease.

Ehrlichiosis is a nationally notifiable disease in the United States. There have been cases reported in every month of the year, but most cases are reported during April–September. These months are also the peak months for tick activity in the United States.

From 2008-2012, the average yearly incidence of ehrlichiosis was 3.2 cases per million persons. This is more than twice the estimated incidence for the years 2000-2007. The incidence rate increases with age, with the ages of 60–69 years being the highest age-specific years. Children of less than 10 years and adults aged 70 years and older, have the highest case-fatality rates. There is a documented higher risk of death among persons who are immunosuppressed.

Babesiosis is a vector-borne illness usually transmitted by "Ixodes scapularis" ticks. "B. microti" uses the same tick vector as Lyme disease, and may occur in conjunction with Lyme. The organism can also be transmitted by blood transfusion. Ticks of domestic animals, especially "Rhipicephalus (Boophilus) microplus" and "R. (B.) decoloratus" transmit several species of "Babesia" to livestock, causing considerable economic losses to farmers in tropical and subtropical regions.

In the United States, the majority of babesiosis cases are caused by "B. microti", and occur in the Northeast and northern Midwest from May through October. Areas with especially high rates include eastern Long Island, Fire Island, Nantucket Island, and Martha's Vineyard.

In Europe, "B. divergens" is the primary cause of infectious babesiosis and is transmitted by "I. ricinus".

Babesiosis has emerged in Lower Hudson Valley, New York, since 2001.

In Australia, babesiosis of types "B. duncani" and "B. microti" has recently been found in symptomatic patients along the eastern coastline of the continent. A similar disease in cattle, commonly known as tick fever, is spread by "Babesia bovis" and "B. bigemina" in the introduced cattle tick "Rhipicephalus microplus". This disease is found in eastern and northern Australia.

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

A table of isolated cases of babesiosis, which may be underestimated given how widely distributed the tick vectors are in temperate latitudes.

Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite "Orientia tsutsugamushi", a Gram-negative α-proteobacterium of family Rickettsiaceae first isolated and identified in 1930 in Japan.

Although the disease is similar in presentation to other forms of typhus, its pathogen is no longer included in genus "Rickettsia" with the typhus bacteria proper, but in "Orientia". The disease is thus frequently classified separately from the other typhi.

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.

Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.

The structure of the attachment glycoprotein has been determined by X-ray crystallography and this glycoprotein is likely to be an essential component of any successful vaccine.

Colorado tick fever (CTF) (also called mountain tick fever, American tick fever, and American mountain tick fever) is a viral infection (Coltivirus) transmitted from the bite of an infected Rocky Mountain wood tick ("Dermacentor andersoni"). It should not be confused with the bacterial tick-borne infection, Rocky Mountain spotted fever.

The type species of the genus "Coltivirus", Colorado tick fever virus (CTFV) infects haemopoietic cells, particularly erythrocytes, which explains how the virus is transmitted by ticks and also accounts for the incidence of transmission by blood transfusion.