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.

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

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

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".)

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.

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.

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

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.

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.

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.

Those dwelling in urban areas (which typically experience rodent problems) have a higher risk of contracting Rickettsialpox.

Pappataci fever is prevalent in the subtropical zone of the Eastern Hemisphere between 20°N and 45°N, particularly in Southern Europe, North Africa, the Balkans, Eastern Mediterranean, Iraq, Iran, Pakistan, Afghanistan and India.

The disease is transmitted by the bites of phlebotomine sandflies of the Genus "Phlebotomus", in particular, "Phlebotomus papatasi", "Phlebotomus perniciosus" and "Phlebotomus perfiliewi". The sandfly becomes infected when biting an infected human in the period between 48 hours before the onset of fever and 24 hours after the end of the fever, and remains infected for its lifetime. Besides this «horizontal» virus transmission from man to sandfly, the virus can be transmitted in insects transovarially, from an infected female sandfly to its offspring.

Pappataci fever is seldom recognised in endemic populations because it is mixed with other febrile illnesses of childhood, but it is more well-known among immigrants and military personnel from non-endemic regions.

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.

Carrión's disease, or Oroya fever, or Peruvian wart is a rare infectious disease found only in Peru, Ecuador, and Colombia. It is endemic in some areas of Peru, is caused by infection with the bacterium "Bartonella bacilliformis", and transmitted by sandflies of genus "Lutzomyia".

Cat scratch disease occurs worldwide. Cats are the main reservoir of "Bartonella henselae", and the bacterium is transmitted to cats by the cat flea "Ctenocephalides felis". Infection in cats is very common with a prevalence estimated between 40-60%, younger cats being more commonly infective. Cats usually become immune to the infection, while dogs may be very symptomatic. Humans may also acquire it through flea or tick bites from infected dogs, cats, coyotes, and foxes.

Trench fever, produced by "Bartonella quintana" infection, is transmitted by the human body louse "Pediculus humanus corporis". Humans are the only known reservoir. Thorough washing of clothing may help to interrupt the transmission of infection.

A possible role for ticks in transmission of "Bartonella" species remains to be elucidated; in November 2011, "Bartonella rochalimae", "B. quintana", and "B. elizabethae" DNA was first reported in "Rhipicephalus sanguineus" and "Dermacentor nitens" ticks in Peru.

Prevention of sandfly bites, and control of sandflies and their breeding grounds with insecticides are the principal methods for prevention. Mosquito nets may not be sufficient to prevent sandfly bites.

Most notifications are from Queensland, tropical Western Australia and the Northern Territory. Geographical risk factors include areas of higher rainfall and higher maximal tides. In the tropics, Ross River fever is more prevalent during the summer/autumn "wet season", particularly January—March, when mosquito populations numbers are high. In southern parts of Australia, this time period may shift to earlier in the year during spring/summer. Areas noted of common place contraction of the virus include townships and along the River Murray areas. Backwaters and Lagoons are breeding grounds for mosquitos and local medical treating facilities report higher cases than cities away from the river around the riverina areas.

Areas near suitable mosquito breeding grounds—marshes, wetlands, waterways and farms with irrigation systems—are high risk areas for outbreaks. As such, the disease is more characteristic of rural and regional areas. Infection is most common in adults aged 25–44 years old, with males and females equally affected. Ross River Fever is on the Australian Department of Health and Ageing's list of notifiable diseases.

Rickettsialpox is generally mild and resolves within 2–3 weeks if untreated. There are no known deaths resulting from the disease.

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.

Members of the genus "Bartonella" are facultative intracellular bacteria, alpha 2 subgroup Proteobacteria. The genus comprises:

No serious long-term effects are known for this disease, but preliminary evidence suggests, if such symptoms do occur, they are less severe than those associated with Lyme disease.

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.

Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends an Integrated Vector Control program consisting of five elements:

1. Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened;

2. Collaboration between the health and other sectors (public and private);

3. An integrated approach to disease control to maximize use of resources;

4. Evidence-based decision making to ensure any interventions are targeted appropriately; and

5. Capacity-building to ensure an adequate response to the local situation.

The primary method of controlling "A. aegypti" is by eliminating its habitats. This is done by getting rid of open sources of water, or if this is not possible, by adding insecticides or biological control agents to these areas. Generalized spraying with organophosphate or pyrethroid insecticides, while sometimes done, is not thought to be effective. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effects from insecticides and greater logistical difficulties with control agents. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective). However, these methods appear not to be sufficiently effective, as the frequency of outbreaks appears to be increasing in some areas, probably due to urbanization increasing the habitat of "A. aegypti". The range of the disease appears to be expanding possibly due to climate change.

To avoid tick bites and infection, experts advise:

- Avoid tick-infested areas, especially during the warmer months.

- Wear light-colored clothing so ticks can be easily seen. Wear a long sleeved shirt, hat, long pants, and tuck pant legs into socks.

- Walk in the center of trails to avoid overhanging grass and brush.

- Clothing and body parts should be checked every few hours for ticks when spending time outdoors in tick-infested areas. Ticks are most often found on the thigh, arms, underarms, and legs. Ticks can be very small (no bigger than a pinhead). Look carefully for new "freckles".

- The use of insect repellents containing DEET on skin or permethrin on clothing can be effective. Follow the directions on the container and wash off repellents when going indoors.

- Remove attached ticks immediately.

Contracting the CTF virus is thought to provide long-lasting immunity against reinfection. However, it is always wise to be on the safe side and try to prevent tick bites.

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

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.