Without treatment, the disease is often fatal. Since the use of antibiotics, case fatalities have decreased from 4–40% to less than 2%.

The drug most commonly used is doxycycline or tetracycline, but chloramphenicol is an alternative. Strains that are resistant to doxycycline and chloramphenicol have been reported in northern Thailand. Rifampicin and azithromycin are alternatives. Azithromycin is an alternative in children and pregnant women with scrub typhus, and when doxycycline resistance is suspected. Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage.

Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism.

The infection is treated with antibiotics. Intravenous fluids and oxygen may be needed to stabilize the patient. There is a significant disparity between the untreated mortality and treated mortality rates: 10-60% untreated versus close to 0% treated with antibiotics within 8 days of initial infection. Tetracycline, Chloramphenicol, and doxycycline are commonly used. Infection can also be prevented by vaccination.

Some of the simplest methods of prevention and treatment focus on preventing infestation of body lice. Complete change of clothing, washing the infested clothing in hot water, and in some cases also treating recently used bedsheets all help to prevent typhus by removing potentially infected lice. Clothes also left unworn and unwashed for 7 days also cause both lice and their eggs to die, as they have no access to their human host. Another form of lice prevention requires dusting infested clothing with a powder consisting of 10% DDT, 1% malathion, or 1% permethrin, which kill lice and their eggs.

The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.

Typhoid fever, when properly treated, is not fatal in most cases. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin, have been commonly used to treat typhoid fever in microbiology. Treatment of the disease with antibiotics reduces the case-fatality rate to about 1%.

Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms and, occasionally, pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in up to 10–20% of cases. The highest case fatality rates are reported in children under 4 years. Around 2–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.

Control requires treatment of antibiotics and vaccines prescribed by a doctor. Major control treatments for paratyphoid fever include ciprofloxacin for ten days, ceftriaxone/cefotaxime for 14 days, or aziththromycin.

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

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.

Effective antibiotics include penicillin G, ampicillin, amoxicillin and doxycycline. In more severe cases cefotaxime or ceftriaxone should be preferred.

Glucose and salt solution infusions may be administered; dialysis is used in serious cases. Elevations of serum potassium are common and if the potassium level gets too high special measures must be taken. Serum phosphorus levels may likewise increase to unacceptable levels due to kidney failure.

Treatment for hyperphosphatemia consists of treating the underlying disease, dialysis where appropriate, or oral administration of calcium carbonate, but not without first checking the serum calcium levels (these two levels are related). Administration of corticosteroids in gradually reduced doses (e.g., prednisolone) for 7–10 days is recommended by some specialists in cases of severe hemorrhagic effects. Organ-specific care and treatment are essential in cases of kidney, liver, or heart involvement.

Surgery is usually indicated in cases of intestinal perforation. Most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations.

If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is not always successful in eradicating the carrier state because of persisting hepatic infection.

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.

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.

Those diagnosed with Type A of the bacterial strain rarely die from it except in rare cases of severe intestinal complications. With proper testing and diagnosis, the mortality rate falls to less than 1%. Antibiotics such as azithromycin are particularly effective in treating the bacteria.

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.

The American Public Health Association recommends treatment based upon clinical findings and before culturing confirms the diagnosis. Without treatment, death may occur in 10 to 60 percent of patients with epidemic typhus, with patients over age 60 having the highest risk of death. In the antibiotic era, death is uncommon if doxycycline is given. In one study of 60 hospitalized patients with epidemic typhus, no patient died when given doxycycline or chloramphenicol. Some patients also may need oxygen and intravenous (IV) fluids.

Doxycycline has been used in the treatment of rickettsial infection.

As of 2017 there is no commercially available vaccine. A vaccine has been in development for scrub typhus known as the scrub typhus vaccine.

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.

Doxycycline has been provided once a week as a prophylaxis to minimize infections during outbreaks in endemic regions. However, there is no evidence that chemoprophylaxis is effective in containing outbreaks of leptospirosis, and use of antibiotics increases antibiotics resistance. Pre-exposure prophylaxis may be beneficial for individuals traveling to high-risk areas for a short stay.

Effective rat control and avoidance of urine contaminated water sources are essential preventive measures. Human vaccines are available only in a few countries, such as Cuba and China. Animal vaccines only cover a few strains of the bacteria. Dog vaccines are effective for at least one year.

Antiviral drugs, that target infections with RRV. Patients are usually managed with simple analgesics, anti-inflammatories, anti-pyretics and rest while the illness runs its course.

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.

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.

No licensed vaccines are available.

An early attempt to create a scrub typhus vaccine occurred in the United Kingdom in 1937 (with the Wellcome Foundation infecting around 300,000 cotton rats in a classified project called "Operation Tyburn"), but the vaccine was not used. The first known batch of scrub typhus vaccine actually used to inoculate human subjects was dispatched to India for use by Allied Land Forces, South-East Asia Command in June 1945. By December 1945, 268,000 cc had been dispatched. The vaccine was produced at Wellcome′s laboratory at Ely Grange, Frant, Sussex. An attempt to verify the efficacy of the vaccine by using a placebo group for comparison was vetoed by the military commanders, who objected to the experiment.

Enormous antigenic variation in "Orientia tsutsugamushi" strains is now recognized, and immunity to one strain does not confer immunity to another. Any scrub typhus vaccine should give protection to all the strains present locally, to give an acceptable level of protection. A vaccine developed for one locality may not be protective in another, because of antigenic variation. This complexity continues to hamper efforts to produce a viable vaccine.

There is currently no vaccine available. The primary method of disease prevention is minimizing mosquito bites, as the disease is only transmitted by mosquitoes. Typical advice includes use of mosquito repellent and mosquito screens, wearing light coloured clothing, and minimising standing water around homes (e.g. removing Bromeliads, plant pots, garden ponds). Staying indoors during dusk/dawn hours when mosquitos are most active may also be effective. Bush camping is a common precipitant of infection so particular care is required.

Treatment is primarily supportive in nature. Early supportive care with rehydration and symptomatic treatment improves survival. Rehydration may be via the oral or by intravenous route. These measures may include management of pain, nausea, fever and anxiety. The World Health Organization recommends avoiding the use of aspirin or ibuprofen for pain due to the bleeding risk associated with use of these medications.

Blood products such as packed red blood cells, platelets or fresh frozen plasma may also be used. Other regulators of coagulation have also been tried including heparin in an effort to prevent disseminated intravascular coagulation and clotting factors to decrease bleeding. Antimalarial medications and antibiotics are often used before the diagnosis is confirmed, though there is no evidence to suggest such treatment helps. A number of experimental treatments are being studied.

If hospital care is not possible, the World Health Organization has guidelines for care at home that have been relatively successful. In such situations, recommendations include using towels soaked in bleach solutions when moving infected people or bodies and applying bleach on stains. It is also recommended that the caregivers wash hands with bleach solutions and cover their mouth and nose with a cloth.

The infection is treated with antibiotics. Tetracyclines and chloramphenicol are the drugs of choice for treating patients with psittacosis. Most persons respond to oral therapy doxycycline, tetracycline hydrochloride, or chloramphenicol palmitate. For initial treatment of severely ill patients, doxycycline hyclate may be administered intravenously. Remission of symptoms usually is evident within 48–72 hours. However, relapse can occur, and treatment must continue for at least 10–14 days after fever abates.

No specific treatment is currently approved. The Food and Drug Administration (FDA) advises people to be careful of advertisements making unverified or fraudulent claims of benefits supposedly gained from various anti-Ebola products.