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.

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.

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.

Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. WHO now states that a single dose of vaccination is sufficient to confer lifelong immunity against yellow fever disease." The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The World Health Organization (WHO) recommends routine vaccinations for people living in affected areas between the 9th and 12th month after birth.

Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine–associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.

The Yellow Fever Initiative, launched by WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI Alliance, and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.

In March 2017, WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil.

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.

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.

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.

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.

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.

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.

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.

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.

Five families of RNA viruses have been recognised as being able to cause hemorrhagic fevers.

- The family "Arenaviridae" include the viruses responsible for Lassa fever (Lassa virus), Lujo virus, Argentine (Junin virus), Bolivian (Machupo virus), Brazilian (Sabiá virus), Chapare hemorrhagic fever (Chapare virus) and Venezuelan (Guanarito virus) hemorrhagic fevers.

- The family "Bunyaviridae" include the members of the "Hantavirus" genus that cause hemorrhagic fever with renal syndrome (HFRS), the Crimean-Congo hemorrhagic fever (CCHF) virus from the "Nairovirus" genus, Garissa virus and Ilesha virus from the "Orthobunyavirus" and the Rift Valley fever (RVF) virus from the "Phlebovirus" genus.

- The family "Filoviridae" include Ebola virus and Marburg virus.

- The family "Flaviviridae" include dengue, yellow fever, and two viruses in the tick-borne encephalitis group that cause VHF: Omsk hemorrhagic fever virus and Kyasanur Forest disease virus.

- In September 2012 scientists writing in the journal PLOS Pathogens reported the isolation of a member of the "Rhabdoviridae" responsible for 2 fatal and 2 non-fatal cases of hemorrhagic fever in the Bas-Congo district of the Democratic Republic of Congo. The non-fatal cases occurred in healthcare workers involved in the treatment of the other two, suggesting the possibility of person-to-person transmission. This virus appears to be unrelated to previously known Rhabdoviruses.

The pathogen that caused the cocoliztli epidemics in Mexico of 1545 and 1576 is still unknown.

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.

Pontiac fever is known to have a short incubation period of 1 to 3 days. No fatalities have been reported and cases resolve spontaneously without treatment. It is often not reported. Age, gender, and smoking do not seem to be risk factors. Pontiac fever seems to affect young people in the age medians of 29, 30, and 32. Pathogenesis of the Pontiac fever is poorly known.

Pontiac fever does not spread from person to person. It is acquired through aersolization of water droplets and/or potting soil containing "Legionella" bacteria.

Viral hemorrhagic fevers (VHFs) are a diverse group of animal and human illnesses in which fever and hemorrhage are caused by a viral infection. VHFs may be caused by five distinct families of RNA viruses: the families "Arenaviridae", "Filoviridae", "Bunyaviridae", "Flaviviridae", and "Rhabdoviridae". All types of VHF are characterized by fever and bleeding disorders and all can progress to high fever, shock and death in many cases. Some of the VHF agents cause relatively mild illnesses, such as the Scandinavian "nephropathia epidemica" (a Hantavirus), while others, such as Ebola virus, can cause severe, life-threatening disease.

Prognosis is generally poor. If a patient survives, recovery may be prompt and complete, or protracted with sequelae, such as orchitis, hepatitis, uveitis, parotitis, desquamation or alopecia. Importantly, MARV is known to be able to persist in some survivors and to either reactivate and cause a secondary bout of MVD or to be transmitted via sperm, causing secondary cases of infection and disease.

Of the 252 people who contracted Marburg during the 2004–2005 outbreak of a particularly virulent serotype in Angola, 227 died, for a case fatality rate of 90%.

Although all age groups are susceptible to infection, children are rarely infected. In the 1998–2000 Congo epidemic, only 8% of the cases were children less than 5 years old.