Rocky Mountain spotted fever (RMSF) and other tick-borne diseases

There are many tick-borne diseases. However, the five that result in the most significant medical issues – either because of potential severity or relative frequency – are: RMSF, ehrlichia, anaplasma, babesia and Lyme disease (LD). All share the “flu-like” presentation of fever, headache, and myalgias. RMSF, ehrlichia, and anaplasma are all in the Rickettsia family, babesia is a protozoan parasite, and LD is due to a bacterium, Borrelia burgdorferi. Ehrlichia and anaplasma are in the Rickettsia family and have tick vectors. Babesia is a protozoan parasite with a tick vector. All of these illnesses can have a similar presentation of a “flu-like” syndrome in the warmer months (where the vector is around). LD is also a tick-transmitted disease and characteristically produces a different syndrome with a typical rash.

1. Description of the problem

Clinical features


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Rickettsial diseases occur throughout the world. RMSF is seen only in the Western Hemisphere and is transmitted by wood and dog ticks (larger hard ticks). RMSF is the only rickettsial disease where the rash starts peripherally and the only one where there is no eschar identifying the initial bite site of the vector. Many people do not give a specific history of a tick bite, but should give a history of a possible exposure to ticks. The incubation period averages about a week (range 3-14 days).

The disease presents with non-specific symptoms of fever, headache, and myalgias. It is critical to note that only 15% of patients have a rash at the time of presentation; it typically develops on the 3rd or 4th day of illness. The rash is typically petechial and begins on the wrists and ankles with centripetal spread. Untreated the disease often progresses to multiorgan failure and death.

Ehrlichia and anaplasma

These diseases are transmitted by bites of the Lone Star tick and the ixodes tick, respectively. The latter is also the vector for babesiosis and LD. The incubation and sudden onset of headache, fevers, and myalgias is identical to RMSF. A rash is less common with these diseases, occurring in about 30% of the former and less than 5% of the latter. When it is present it is much less characteristic than RMSF. It is primarily on the trunk and is macular or maculo-papular. These diseases are usually self-limited, but severe, life-threatening infection can occur.


Is a protozoan parasite that infects erythrocytes. It is transmitted by ixodes ticks and is seen primarily in the Northeast United States, though cases have extended as far south as southern New Jersey. Most patients have asymptomatic infection. Symptomatic disease is identical to that described for the diseases already mentioned. Occasionally severe, life-threatening disease develops. This is particularly likely in splenectomized patients.

Lyme Disease

The vector is the ixodes tick. It generally causes a disease that is much less severe and dramatic than the other tick-borne diseases mentioned. After an incubation period of 1-3 weeks most patients (90%) develop a characteristic rash. The most consistent feature of the rash is that it is a large red patch that is minimally symptomatic. Target lesions are seen in only 30%, and 5% will have a vesiculating center. This disease is also generally self-limited. Unusual presentations include a facial nerve palsy, aseptic meningitis, and heart block. Late LD can present as an oligo- or pauciarticular inflammatory arthritis.

Key Management Points
  • RMSF, ehrlichia, anaplasma, babesia: The most important thing is to think of these illnesses since they have a non-specific presentation. They must be considered and treatment initiated on suspicion of the diagnosis. DO NOT WAIT FOR THE RASH.

  • RMSF, ehrlichia, anaplasma, babesia: Mortality is directly related to delay in treatment. RMSF is unquestionably the most severe and most important to consider the diagnosis early. For RMSF, if patients are started on treatment in the first 5 days, mortality is 6%. If treatment is begun after that, it is as high as 25%. As these infections progress they can result in multi-organ failure, seizures and coma.

  • LD: many patients have no systemic symptoms, and if they do they are rarely severely ill. The more cutaneous lesions (primary disseminated LD), the more likely there will be some fever and achiness. Untreated acute LD resolves in 2-3 weeks.

  • Meningococcemia with the petechial rash is difficult to clinically distinguish from RMSF and should also be considered.

2. Emergency Management

For RMSF, ehrlichia, anaplasma, and babesia, treatment should be initiated on suspcion of the diagnosis. Do not wait for confimation or for the characteristic rash. When the patient has a petechial rash It is often prudent to also treat for meningococcemia until that diagnosis can be ruled out.

There is no medical emergency for LD. Delayed treatment is not associated with a worse prognosis, and in fact for most people symptoms resolve without treatment.

3. Diagnosis

RMSF: Initially, this is a clinical diagnosis. It can be confirmed serologically but it generally takes several weeks for antibodies to develop, so they are not helpful in the initial management of a patient.

Ehrlichia and anaplasma: Initially it is a clinical diagnosis. Diagnosis can often be made quickly by looking for the characteristic WBC inclusions called morula. They are seen in mononuclear cells in ehrlichia and polymorphonuclear leucocytes in anaplasma.

Babesia: The parasite can usually be seen on a “malaria” smear. Morphologically it can be difficulty to distinguish from P. falciparum; however, the epidemiology generally allows distinction. There is a PCR test on the blood for difficult diagnostic cases. A convalescent serology can also be useful in confirming the diagnosis.

LD: If a person has the characteristic erythematous patch, erythema migrans, the diagnosis can and should be made clinically. Serology can confirm the diagnosis, but is often negative during the acute disease. Persons with chronic infection will have a positive serology; a negative serology other than during the acute illness effectively rules out LD. Once the serology test is positive it generally stays positive for years, if not for life, even with adequate treatment. Follow-up testing has no utility for determining the adequacy of treatment or activity of disease. PCR testing has only been validated for joint fluid and cerebrospinal fluid and should not be used on other clinical specimens.

Normal lab values

RMSF, ehrlichia, anaplasma, babesia: The WBC count is often normal but can be elevated. Thrombocytopenia is expected in all of these diagnoses. Hyponatremia is typical – especially in RMSF. As these diseases progress, laboratory manifestations of acute kidney injury and hepatic involvement appear and can progress to multi-organ failure.

How do I know this is what the patient has?

Other than for LD you don’t at the time you need to treat the patient. You find out after the fact when, hopefully, the patient has improved.

4. Specific Treatment

RMSF, ehrlichia, anaplasma: The treatment is doxycycline. This should be given even to children since it is the only proven effective therapy and these diseases have a high mortality and morbidity. Chloramphenicol is the alternate choice and there are some promising case reports with rifampin.

Babesiosis: Atovaquone and azithromycin has replaced quinine and clindamycin and is the regimen of choice because it is better tolerated. It should be given for 10 days.

LD: Doxycycline is the drug of choice and nothing has been shown to be more effective. Amoxicillin is the alternative.

Drugs and dosages

RMSF, ehrlichia, anaplasma: Doxycycline 100 mg every twelve hours in adults; in children 2.2-mg/kg dose every twelve hours. Alternative: chloramphenicol 12.5 mg/kg every 6 hours. Treatment should be continued for a few days after the patient is afebrile. This is generally a week.

Babesia: Atovoquone 750 mg every 12 hours; in children 20 mg/kg every 12 hours PLUS azithromycin 1000 mg day one, then 250 mg/day; in children 10 mg/kg day one, then 5 mg/kg/day.

Refractory cases

Severely ill patients with multi-organ system failure will need intensive care support.

5. Disease monitoring, follow-up and disposition

Expected response to treatment

If initiated early the response to treatment is prompt, with clear improvement in 24-48 hours.

When should I suspect I've made the wrong diagnosis?

If no improvement in 48 hours


RMSF, ehrlichia, anaplasma, LD: Once the patient has recovered from the acute illness the only follow-up is related to monitoring the recovery of specifically damaged organs.

Babesia: Can relapse. There is no specific recommendation for how to follow such patients, but the clinician should be aware of the possibility should the patient present with a febrile illness in the subsequent month.

LD: Treatment for LD is extremely effective. There is rarely, if ever, an indication for additional treatment. As mentioned above serology stays positive. A misunderstanding of how to interpret serology has resulted in the myth of chronic LD.


RMSF is an infection caused by Rickettsia rickettsii. It is fundamentally an infection of endothelial cells, an infectious vasculitis.

Ehrlichia is an infection caused by E. chaffeensis and anaplasma is due to Anaplasma phagocytophilum. They grow in mononuclear cells and phagocytes, respectively.


RMSF is seen throughout the Western Hemisphere. Most of the cases in the United States are reported from the southeastern and south central regions.

Ehrlichia and anaplasma have both been primarily reported in the United States, but there have been cases from Europe and other countries in the Western Hemisphere.


RMSF, ehrlichia, anaplasma, and babesia can have significant morbidity and mortality. LD rarely results in any significant acute or chronic disability.

Special considerations for nursing and allied health professionals.

There are case reports of ehrlichia, anaplasma, and babesia that have been transmitted through blood products and maternal-child.

What's the evidence?