Spotted fever can be very difficult to diagnose in its early stages, and even experienced doctors who are familiar with the disease find it hard to detect.

People infected with "R. rickettsii" usually notice symptoms following an incubation period of one to two weeks after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and non-infectious diseases.

Initial symptoms:

- Fever

- Nausea

- Emesis (vomiting)

- Severe headache

- Muscle pain

- Lack of appetite

- Parotitis in some cases (somewhat rare)

Later signs and symptoms:

- Maculopapular rash

- Petechial rash

- Abdominal pain

- Joint pain

- Conjunctivitis

- Forgetfulness

The classic triad of findings for this disease are fever, rash, and history of tick bite. However, this combination is often not identified when the patient initially presents for care. The rash has a centripetal, or "inward" pattern of spread, meaning it begins at the extremities and courses towards the trunk.

The rash first appears two to five days after the onset of fever, and it is often quite subtle. Younger patients usually develop the rash earlier than older patients. Most often the rash begins as small, flat, pink, non-itchy spots (macules) on the wrists, forearms, and ankles. These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted (petechial) rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after onset of symptoms, but this type of rash occurs in only 35 to 60% of patients with Rocky Mountain spotted fever. The rash involves the palms or soles in as many as 80% of the patients. However, this distribution may not occur until later on in the course of the disease. As many as 15 percent of patients may never develop a rash.

African tick bite fever is often asymptomatic or mild in clinical presentation and complications are rare. The onset of illness is typically 5–7 days after the tick bite, although in some cases it may take up to 10 days for symptoms to occur. Symptoms can persist for several days to up to three weeks. Common presenting symptoms include:

- Fever

- Headache

- Muscle aches

- Inoculation eschar, which is dead, often black, tissue around a bite site (see photo above)

- Eschars may or may not be present. "Amblyomma" ticks actively attack cattle or humans and can bite more than once. In African tick bite fever, unlike what is typically seen with other Rickettsial spotted fevers when only one eschar is identified, multiple eschars may be seen and are considered pathognomonic.

- Swollen lymph nodes near the site of the bite

- Maculopapular and/or vesicular rash

Complications are rare and are not life-threatening. No deaths due to African tick bite fever have been reported. Reported complications include:

- Prolonged fever > 3 weeks in duration

- Reactive arthritis

- Moderate to severe headache

Rocky Mountain spotted fever (RMSF), also known as blue disease, is the most lethal and most frequently reported rickettsial illness in the United States. It has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” (Colombia), “São Paulo fever” or “"febre maculosa"” (Brazil), and “"fiebre manchada"” (Mexico). It is distinct from the viral tick-borne infection, Colorado tick fever. The disease is caused by "Rickettsia rickettsii", a species of bacterium that is spread to humans by "Dermacentor" ticks. Initial signs and symptoms of the disease include sudden onset of fever, headache, and muscle pain, followed by development of rash. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment it can be fatal.

The name “Rocky Mountain spotted fever” is something of a misnomer. The disease was first identified in the Rocky Mountain region, but beginning in the 1930s, medical researchers realized that it occurred in many other areas of the United States. It is now recognized that the disease is broadly distributed throughout the contiguous United States and occurs as far north as Canada and as far south as Central America and parts of South America. Between 1981 and 1996, the disease was reported from every state of the United States except for Hawaii, Vermont, Maine, and Alaska.

Rocky Mountain spotted fever remains a serious and potentially life-threatening infectious disease. Despite the availability of effective treatment and advances in medical care, approximately three to five percent of patients who become ill with Rocky Mountain spotted fever die from the infection. However, effective antibiotic therapy has dramatically reduced the number of deaths caused by Rocky Mountain spotted fever. Before the discovery of tetracycline and chloramphenicol during the latter 1940s, as many as 30% of those infected with "R. rickettsii" died.

Most people who are infected develop sickness between five and 15 days after they are bitten. The symptoms may include a sudden fever, chills, headaches, muscle or joint aches, and nausea. A rash may also occur. These symptoms usually continue for two to 9 days, then disappear. This cycle may continue for several weeks if the person is not treated.

A few days after the infective bite, a feeling of lassitude, abdominal distress and chills develop followed by fever of 39 °C to 40 °C, severe frontal headaches, muscle and joint aches, flushing of the face and a fast heart rate. After two days the fever begins to subside and the temperature returns to normal. Fatigue, a slow heart rate and low blood pressure may persist from few days to several weeks but complete recovery is the rule.

The acute stage of the disease, occurring most often in the spring and summer, begins one to three weeks after infection and lasts for two to four weeks. Clinical signs include a fever, petechiae, bleeding disorders, vasculitis, lymphadenopathy, discharge from the nose and eyes, and edema of the legs and scrotum. There are no outward signs of the subclinical phase. Clinical signs of the chronic phase include weight loss, pale gums due to anemia, bleeding due to thrombocytopenia, vasculitis, lymphadenopathy, dyspnea, coughing, polyuria, polydipsia, lameness, ophthalmic diseases such as retinal hemorrhage and anterior uveitis, and neurological disease. Dogs that are severely affected can die from this disease.

Although people can get ehrlichiosis, dogs do not transmit the bacteria to humans; rather, ticks pass on the "ehrlichia" organism. Clinical signs of human ehrlichiosis include fever, headache, eye pain, and gastrointestinal upset. It is quite similar to Rocky Mountain spotted fever, but rash is not seen in patients.

Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus "Borrelia", which are transmitted through the bites of lice or soft-bodied ticks (genus "Ornithodoros").

Depending on the site of infection, tularemia has six characteristic clinical variants: ulceroglandular (the most common type representing 75% of all forms), glandular, oropharyngeal, pneumonic, oculoglandular, and typhoidal.

The incubation period for tularemia is one to 14 days; most human infections become apparent after three to five days. In most susceptible mammals, the clinical signs include fever, lethargy, loss of appetite, signs of sepsis, and possibly death. Nonhuman mammals rarely develop the skin lesions seen in people. Subclinical infections are common, and animals often develop specific antibodies to the organism. Fever is moderate or very high, and tularemia bacilli can be isolated from blood cultures at this stage. The face and eyes redden and become inflamed. Inflammation spreads to the lymph nodes, which enlarge and may (mimicking bubonic plague). Lymph node involvement is accompanied by a high fever.

"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.

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.

Three serotypes of Phlebovirus are known as the causative agents: Naples virus, Sicilian virus and Toscana virus.

Half of all children and a quarter of previously healthy adults are asymptomatic with "Babesia" infection. When people do develop symptoms, the most common are fever and hemolytic anemia, symptoms that are similar to those of malaria. People with symptoms usually become ill 1 to 4 weeks after the bite, or 1 to 9 weeks after transfusion of contaminated blood products. A person infected with babesiosis gradually develops malaise and fatigue, followed by a fever. Hemolytic anemia, in which red blood cells are destroyed and removed from the blood, also develops. Chills, sweats, and thrombocytopenia are also common symptoms. Symptoms may last from several days to several months.

Less common symptoms and physical exam findings of mild-to-moderate babesiosis:

In more severe cases, symptoms similar to malaria occur, with fevers up to 40.5 °C (105 °F), shaking chills, and severe anemia (hemolytic anemia). Organ failure may follow, including adult respiratory distress syndrome. Severe cases occur mostly in people who have had a splenectomy. Severe cases are also more likely to occur in the very young, very old, and persons with immunodeficiency, such as HIV/AIDS patients.

A reported increase in human babesiosis diagnoses in the 2000s is thought to be caused by more widespread testing and higher numbers of people with immunodeficiencies coming in contact with ticks, the disease vector. Little is known about the occurrence of "Babesia" species in malaria-endemic areas, where "Babesia" can easily be misdiagnosed as "Plasmodium". Human patients with repeat babesiosis infection may exhibit premunity.

Symptoms are different for every person depending on the type of rat-bite fever with which the person is infected. Both spirillary and streptobacillary rat-bite fever have a few individual symptoms, although most symptoms are shared. Streptobacillosis is most commonly found in the United States and spirillary rat-bite fever is generally diagnosed in patients in Africa. Rat-bite symptoms are visually seen in most cases and include inflammation around the open sore. A rash can also spread around the area and appear red or purple. Other symptoms associated with streptobacillary rat-bite fever include chills, fever, vomiting, headaches, and muscle aches. Joints can also become painfully swollen and pain can be experienced in the back. Skin irritations such as ulcers or inflammation can develop on the hands and feet. Wounds heal slowly, so symptoms possibly come and go over the course of a few months.

Symptoms associated with spirillary rat-bite fever include issues with the lymph nodes, which often swell or become inflamed as a reaction to the infection. The most common locations of lymph node swelling are in the neck, groin, and underarm. Symptoms generally appear within 2 to 10 days of exposure to the infected animal. It begins with the fever and progresses to the rash on the hands and feet within 2 to 4 days. Rash appears all over the body with this form, but rarely causes joint pain.

A combination of clinical signs, symptoms, and laboratory tests can confirm the likelihood of having CTF. Some tests include complement fixation to Colorado tick virus, immunofluorescence for Colorado tick fever, and some other common laboratory findings suggestive of CTF, including leucopenia, thrombocytopenia, and mildly elevated liver enzyme levels.

Detection of viral antibodies on red blood cells is possible.

After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black ulcerous crust (tache noire). Around the fourth day of the illness, a widespread rash appears, first macular and then maculopapular and sometimes petechial.

The disease is classically a five-day fever of the relapsing type, rarely exhibiting a continuous course. The incubation period is relatively long, at about two weeks. The onset of symptoms is usually sudden, with high fever, severe headache, pain on moving the eyeballs, soreness of the muscles of the legs and back, and frequently hyperaesthesia of the shins. The initial fever is usually followed in a few days by a single, short rise but there may be many relapses between periods without fever. The most constant symptom is pain in the legs. Recovery takes a month or more. Lethal cases are rare, but in a few cases "the persistent fever might lead to heart failure". Aftereffects may include neurasthenia, cardiac disturbances and myalgia.

Ehrlichiosis (; also known as canine rickettsiosis, canine hemorrhagic fever, canine typhus, tracker dog disease, and tropical canine pancytopenia is a tick-borne disease of dogs usually caused by the organism "Ehrlichia canis". "Ehrlichia canis" is the pathogen of animals. Humans can become infected by "E. canis" and other species after tick exposure. German Shepherd Dogs are thought to be susceptible to a particularly severe form of the disease, other breeds generally have milder clinical signs. Cats can also be infected.

Queensland tick typhus (or Australian tick typhus or (Rickettsial) spotted fever) is a condition caused by a bacterium "Rickettsia australis".

It is transmitted by "Ixodes holocyclus" and "Ixodes tasmani".

Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium "Francisella tularensis". Symptoms may include fever, skin ulcer, and enlarged lymph nodes. Occasionally a form that results in pneumonia or a threat infection may occur.

The bacterium is typically spread by ticks, deer flies, or contact with infected animals. It may also be spread by drinking contaminated water or breathing in contaminated dust. It does not spread directly between people. Diagnosis is by blood tests or cultures of the infected site.

Prevention is by using insect repellent, wearing long pants, rapidly removing ticks, and not disturbing dead animals. Treatment is typically with the antibiotic streptomycin. Gentamicin, doxycycline, or ciprofloxacin may also be used.

Between the 1970s and 2015 around 200 cases are reported in the United States a year. Males are affected more often than females. It occurs most frequently in the young and the middle aged. In the United States most cases occur in the summer. The disease is named after Tulare County, California were the disease was discovered in 1911. A number of other animals, such as rabbits, may also be infected.

Rat-bite fever is an acute, febrile human illness caused by bacteria transmitted by rodents, in most cases, which is passed from rodent to human by the rodent's urine or mucous secretions. Alternative names for rat-bite fever include streptobacillary fever, streptobacillosis, spirillary fever, bogger, and epidemic arthritic erythema. It is a rare disease spread by infected rodents and can be caused by two specific types of bacteria. Most cases occur in Japan, but specific strains of the disease are present in the United States, Europe, Australia, and Africa.

Some cases are diagnosed after patients were exposed to the urine or bodily secretions of an infected animal. These secretions can come from the mouth, nose, or eyes of the rodent. The majority of cases are due to the animal's bite. It can also be transmitted through food or water contaminated with rat feces or urine. Other animals can be infected with this disease, including weasels, gerbils, and squirrels. Household pets such as dogs or cats exposed to these animals can also carry the disease and infect humans.

If a person is bitten by a rodent, it is important to quickly wash and cleanse the wound area thoroughly with antiseptic solution to reduce the risk of infection.

The most common symptoms include headache, muscle aches, and fatigue. A rash may occur, but is uncommon. Ehrlichiosis can also blunt the immune system by suppressing production of TNF-alpha, which may lead to opportunistic infections such as candidiasis.

Most of the signs and symptoms of ehrlichiosis can likely be ascribed to the immune dysregulation that it causes. A "toxic shock-like" syndrome is seen in some severe cases of ehrlichiosis. Some cases can present with purpura and in one such case the organisms were present in such overwhelming numbers that in 1991 Dr. Aileen Marty of the AFIP was able to demonstrate the bacteria in human tissues using standard stains, and later proved that the organisms were indeed Ehrlichia using immunoperoxidase stains.

Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.

3% of human monocytic ehrlichiosis cases result in death; however, these deaths occur "most commonly in immunosuppressed individuals who develop respiratory distress syndrome, hepatitis, or opportunistic nosocomial infections."

In general, specific laboratory tests are not available to rapidly diagnose tick-borne diseases. Due to their seriousness, antibiotic treatment is often justified based on clinical presentation alone.

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

Signs and symptoms include fever, headache, muscle pain, cough, and gastrointestinal symptoms. More virulent strains of "O. tsutsugamushi" can cause hemorrhaging and intravascular coagulation. Morbilliform rash, eschar, splenomegaly, and lymphadenopathies are typical signs. Leukopenia and abnormal liver function tests are commonly seen in the early phase of the illness. Pneumonitis, encephalitis, and myocarditis occur in the late phase of illness.

Acute scrub typhus appears to improve viral loads in patients with HIV. This interaction is challenged by an "in vitro" study.