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

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.

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.

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.

Doxycycline has been used in the treatment of rickettsial infection.

Rickettsioses can be divided into a spotted fever group (SPG) and typhus group (TG).

In the past, rickettsioses were considered to be caused by species of Rickettsia. However, scrub typhus is still considered a rickettsiosis, even though the causative organism has been reclassified from "Rickettsia tsutsugamushi" to "Orientia tsutsugamushi".

Examples of rickettsioses include typhus, both endemic and epidemic, Rocky Mountain spotted fever, and Rickettsialpox.

Organisms involved include Rickettsia parkeri.

Many new causative organisms have been identified in the last few decades.

Most are in the genus Rickettsia, but scrub typhus is in the genus Orientia.

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.

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

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.

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.

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

Tick control is the most effective method of prevention, but tetracycline at a lower dose can be given daily for 200 days during the tick season in endemic regions.

Humans contract the disease after a bite by an infected tick of the species "Amblyomma americanum".

Those with an underlying immunodeficiency (such as HIV) appear to be at greater risk of contracting the disease. Compared to HME, ewingii ehrlichiosis has a decreased incidence of complications.

Like "Anaplasma phagocytophilum", the causative agent of human granulocytic ehrlichiosis, Ehrlichia ewingii infects neutrophils. Infection with "E. ewingii" may delay neutrophil apoptosis.

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.

The prognosis is good for dogs with acute ehrlichiosis. For dogs that have reached the chronic stage of the disease, the prognosis is guarded. When bone marrow suppression occurs and there are low levels of blood cells, the animal may not respond to treatment.

"A. phagocytophilum" is transmitted to humans by "Ixodes" ticks. These ticks are found in the US, Europe, and Asia. In the US, "I. scapularis" is the tick vector in the East and Midwest states, and "I. pacificus" in the Pacific Northwest. In Europe, the "I. ricinus" is the main tick vector, and "I. persulcatus" is the currently known tick vector in Asia.

The major mammalian reservoir for "A. phagocytophilum" in the eastern United States is the white-footed mouse, "Peromyscus leucopus". Although white-tailed deer and other small mammals harbor "A. phagocytophilum", evidence suggests that they are not a reservoir for the strains that cause HGA. A tick that has a blood meal from an infected reservoir becomes infected themselves. If an infected tick then latches onto a human the disease is then transmitted to the human host and "A." "phagocytophilum" symptoms can arise.

"Anaplasma phagocytophilum" shares its tick vector with other human pathogens, and about 10% of patients with HGA show serologic evidence of coinfection with Lyme disease, babesiosis, or tick-borne meningoencephalitis.

Boutonneuse fever (also called Mediterranean spotted fever, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, or African tick-bite fever) is a fever as a result of a rickettsial infection caused by the bacterium "Rickettsia conorii" and transmitted by the dog tick "Rhipicephalus sanguineus". Boutonneuse fever can be seen in many places around the world, although it is endemic in countries surrounding the Mediterranean Sea. This disease was first described in Tunisia in 1910 by Conor and Bruch and was named "boutonneuse" (French for "spotty") due to its papular skin rash characteristics.

Omsk hemorrhagic fever is caused by the Omsk hemorrhagic fever virus (OHFV), a member of the Flavivirus family. The virus was discovered by Mikhail Chumakov and his colleagues between 1945 and 1947 in Omsk, Russia. The infection is found in western Siberia, in places including Omsk, Novosibirsk, Kurgan, and Tyumen. The virus survives in water and is transferred to humans via contaminated water or an infected tick.

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

From the first reported case in 1994 until 2010, HGA's rates of incidence have exponentially increased. This is likely because HGA is found where there are ticks that carry and transmit Lyme disease, also known as Borrelia burgdorferi, and babesiosis, which is found in the northeastern and midwestern parts of the United States, which has seemingly increased in the past couple of decades. Before 2000, there were less than 300 cases reported per year. In 2000, there were only 350 reported cases. From 2009-2010, HGA experienced a 52% increase in the number of cases reported.

Infections are treated with antibiotics, particularly doxycycline, and the acute symptoms appear to respond to these drugs.