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.

Doxycycline and minocycline are the medications of choice. For people allergic to antibiotics of the tetracycline class, rifampin is an alternative. Early clinical experience suggested that chloramphenicol may also be effective, however, in vitro susceptibility testing revealed resistance.

No human vaccine is available for ehrlichiosis. Tick control is the main preventive measure against the disease. However, in late 2012 a breakthrough in the prevention of CME (canine monocytic ehrlichiosis) was announced when a vaccine was accidentally discovered by Prof. Shimon Harrus, Dean of the Hebrew University of Jerusalem's Koret School of Veterinary Medicine.

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.

Ticks should be removed promptly and carefully with tweezers and by applying gentle, steady traction. The tick's body should not be crushed when it is removed and the tweezers should be placed as close to the skin as possible to avoid leaving tick mouthparts in the skin; mouthparts left in the skin can allow secondary infections. Ticks should not be removed with bare hands. Hands should be protected by gloves and/or tissues and thoroughly washed with soap and water after the removal process.

A match or flame should not be used to remove a tick. This method, once thought safe, can cause the tick to regurgitate, expelling any disease it may be carrying into the bite wound.

African tick bite fever is usually mild, and most patients do not need more than at-home treatment with antibiotics for their illness. However, because so few patients with this infection visit a doctor, the best antibiotic choice, dose and length of treatment are not well known. Typically doctors treat this disease with antibiotics that have been used effectively for the treatment of other diseases caused by bacteria of similar species, such as Rocky Mountain Spotted Fever.

For mild cases, people are usually treated with one of the following:

- doxycycline

- chloramphenicol

- ciprofloxacin

If a person has more severe symptoms, like a high fever or serious headache, the infection can be treated with doxycycline for a longer amount of time. Pregnant women should not use doxycycline or ciprofloxacin as both antibiotics can cause problems in fetuses. Josamycin has been used effectively for treatment of pregnant women with other rickettsial diseases, but it is unclear if it has a role in the treatment of ATBF.

No specific treatment for CTF is yet available. The first action is make sure the tick is fully removed from the skin, then acetaminophen and analgesics can be used to help relieve the fever and pain. Aspirin is not recommended for children, as it has been linked to Reye’s syndrome in some viral illnesses. Salicylates should not be used because of thrombocytopenia, and the rare occurrence of bleeding disorders. People who suspect they have been bitten by a tick or are starting to show signs of CTF should contact their physicians immediately.

Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment. The best way to prevent HGA is to prevent getting tick bites.

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.

Treatment of asymptomatic carriers should be considered if parasites are still detected after 3 months. In mild-to-moderate babesiosis, the treatment of choice is a combination of atovaquone and azithromycin. This regimen is preferred to clindamycin and quinine because side effects are fewer. The standard course is 7 to 10 days, but this is extended to at least 6 weeks in people with relapsing disease. Even mild cases are recommended to be treated to decrease the chance of inadvertently transmitting the infection by donating blood. In life-threatening cases, exchange transfusion is performed. In this procedure, the infected red blood cells are removed and replaced with uninfected ones.

Imizol is a drug used for treatment of babesiosis in dogs.

Extracts of the poisonous, bulbous plant "Boophone disticha" are used in the folk medicine of South Africa to treat equine babesiosis. "B. disticha" is a member of the daffodil family Amaryllidaceae and has also been used in preparations employed as arrow poisons, hallucinogens, and in embalming. The plant is rich in alkaloids, some of which display an action similar to that of scopolamine.

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.

Supportive care must be provided to animals that have clinical signs. Subcutaneous or intravenous fluids are given to dehydrated animals, and severely anemic dogs may require a blood transfusion. Treatment for ehrlichiosis involves the use of antibiotics such as tetracycline or doxycycline for a period of at least six to eight weeks; response to the drugs may take one month. Treatment with macrolide antibiotics like clarithromycin and azithromycin is being studied. In addition, steroids may be indicated in severe cases in which the level of platelets is so low that the condition is life-threatening.

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

Rickettsialpox is treated with tetracyclines (doxycycline is the drug of choice). Chloramphenicol is a suitable alternative.

Appropriate antibiotic treatment should be started immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiological findings. Treatment should not be delayed until laboratory confirmation is obtained. In fact, failure to respond to a tetracycline argues against a diagnosis of Rocky Mountain spotted fever. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in healthy patients who have had recent tick bites is not recommended and may, in fact, only delay the onset of disease.

Doxycycline (a tetracycline) (for adults at 100 milligrams every 12 hours, or for children under at 4 mg/kg of body weight per day in two divided doses) is the drug of choice for patients with Rocky Mountain spotted fever, being one of the only instances doxycycline is used in children. Treatment should be continued for at least three days after the fever subsides, and until there is unequivocal evidence of clinical improvement. This will be generally for a minimum time of five to ten days. Severe or complicated outbreaks may require longer treatment courses. Doxycycline/ tetracycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble those of Rocky Mountain spotted fever.

Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever, specifically in pregnancy. However, this drug may be associated with a wide range of side effects, and careful monitoring of blood levels can be required.

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.

There are no safe, available, approved vaccines against tularemia. However, vaccination research and development continues, with live attenuated vaccines being the most thoroughly researched and most likely candidate for approval. Sub-unit vaccine candidates, such as killed-whole cell vaccines, are also under investigation, however research has not reached a state of public use.

Optimal preventative practices include limiting direct exposure when handling potentially infected animals, such as wearing gloves and face masks while handling potentially infected animals (importantly when skinning deceased animals).

There is currently no treatment for AHS.

Control of an outbreak in an endemic region involves quarantine, vector control and vaccination. To prevent this disease, the affected horses are usually slaughtered, and the uninfected horses are vaccinated against the virus. Three vaccines currently exist, which include a polyvalent vaccine, a monovalent vaccine, and a monovalent inactivated vaccine. This disease can also be prevented by destroying the insect vector habitats using insecticides.

African horse sickness was diagnosed in Spain in 1987–90 and in Portugal in 1989, but was eradicated using slaughter policies, movement restrictions, vector eradication, and vaccination.

Vaccines against anaplasmosis are available. Carrier animals should be eliminated from flocks. Tick control may also be useful although it can be difficult to implement.

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 is the treatment of choice. If anaplasmosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been shown to improve outcomes. Presentation during early pregnancy can complicate treatment. Doxycycline compromises dental enamel during development. Although rifampin is indicated for post-delivery pediatric and some doxycycline-allergic patients, it is teratogenic. Rifampin is contraindicated during conception and pregnancy.

If the disease is not treated quickly, sometimes before the diagnosis, the person has a high chance of mortality. Most people make a complete recovery, though some people are intensively cared for after treatment. A reason for a person needing intensive care is if the person goes too long without seeing a doctor or being diagnosed. The majority of people, though, make a complete recovery with no residual damage.

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

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

Since the invention of antibiotics, the rate of death associated with tularemia has decreased from 60% to less than 4%.