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.

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.

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

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.

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.

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.

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.

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

Occupations at risk include veterinarians, slaughterhouse workers, farmers, sailors on rivers, sewer maintenance workers, waste disposal facility workers, and people who work on derelict buildings. Slaughterhouse workers can contract the disease through contact with infected blood or body fluids. Rowers, kayakers and canoeists also sometimes contract the disease. It was once mostly work-related but is now often also related to adventure tourism and recreational activities.

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.

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

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.

Along with "Rickettsia prowazekii" and "Bartonella quintana", "Borrelia recurrentis" is one of three pathogens of which the body louse ("Pediculus humanus humanus") is a vector. Louse-borne relapsing fever is more severe than the tick-borne variety.

Louse-borne relapsing fever occurs in epidemics amid poor living conditions, famine and war in the developing world. It is currently prevalent in Ethiopia and Sudan.

Mortality rate is 1% with treatment and 30–70% without treatment. Poor prognostic signs include severe jaundice, severe change in mental status, severe bleeding and a prolonged QT interval on ECG.

Lice that feed on infected humans acquire the "Borrelia" organisms that then multiply in the gut of the louse. When an infected louse feeds on an uninfected human, the organism gains access when the victim crushes the louse or scratches the area where the louse is feeding. "B. recurrentis" infects the person via mucous membranes and then invades the bloodstream. No non-human, animal reservoir exists.

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.

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.

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

The infections are acquired through rat bites or scratches. It can occur as nosocomial infections (i.e., acquired from hospitals), or due to exposure or close associations with animals preying on rats, mice, squirrels, etc. Sodoku is mostly seen in Asia. The incubation period is 4 to 28 days.

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.

"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.

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.

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.

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.

Sodoku (鼠毒) is a bacterial zoonotic disease. It is caused by the Gram-negative rod "Spirillum minus" (also known as "Spirillium minor"). It is a form of rat-bite fever (RBF).

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.