Rickettsia Akari

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Continuing Education Activity

Rickettsia akari, an intracellular, gram-negative pathogen, is the etiologic agent of rickettsialpox, which is transmitted by the house mouse mite. Rickettsialpox presents with a triad of a vesicular rash, fever, and eschar. This is a self-limited disease, but the use of antibiotics can shorten the duration of systemic symptoms. This activity describes the pathophysiology, presentation, diagnosis, and management of rickettsialpox and reviews the role of the interprofessional team in improving care for patients with this condition.


  • Identify the epidemiology of Rickettsia akari.
  • Review the presentation of Rickettsia akari.
  • Describe the treatment and management options available for Rickettsia akari.
  • Summarize the importance of improving care coordination among the interprofessional team members to promptly detect and treat this condition, which will improve outcomes for patients affected by rickettsialpox.


Rickettsia akari is the etiologic agent of rickettsialpox. R. akari is transmitted by the house mouse mite, Liponyssoides sanguineus. One week after a mite bite, a vesicle appears, which dries up, leaving an eschar. The rash is often papular but can also be vesicular, hence the name rickettsialpox. Like other rickettsiae in the genus, R. akari is an intracellular gram-negative pathogen with features intermediate between viruses and bacteria. R. akari was initially classified as a member of the spotted fever group (SFG) of rickettsia, but it is now placed in the transitional group, which has features of both the spotted fever group and the typhus group (TG) of rickettsiae. R. akari has a DNA plasmid-like Rickettsia felis of the transitional group.[1][2][3]


R. akari is transmitted by the bite of Liponyssoides sanguineus, the mouse mite. In Greek, akari means mite, hence the name. Unlike other rickettsiae which target endothelial cells, R. akari targets the macrophage. R. akari infections were first reported in 1946 in New York City and caused vesicular lesions resembling chickenpox. Therefore, the disease caused by R. akari became known as rickettsialpox. There may be another identified vector besides the mouse mite as there is a high seroprevalence of R. akari found in dogs in New York City and domesticated cats in California.[4][5]


Rickettsialpox was initially described in New York City and has been reported in other US towns and states. Cases have been reported from all continents including Europe (Croatia), Asia (Korea), Africa (South Africa), and South America. Rickettsialpox has been described in intravenous drug users and the homeless population. A high seroprevalence of R. akari has been reported in intravenous drug users in Baltimore and Los Angeles County. In a review of the literature on the seroprevalence of vector-borne diseases amongst the urban homeless, R. akari was the second most common infection after Bartonella quintana.[6][7][8]

At present, rickettsialpox is not a notifiable disease. Rodents are the reservoir. The colorless, bloodsucking mouse mite transmits infection from rodents to humans. In laboratory settings, infection due to inhalation has occurred. The usual annual incidence of rickettsialpox in New York City is about five cases.

Interestingly, the mouse mite does not bite humans when there are many mice. Any attempt to lower a mouse population increases bites to the humans, thereby increasing the transmission back to baseline. The incubation period is about seven to 14 days.


Rickettsiae have one of the smallest genomes in the bacterial world and seem to have evolved with genomic reduction and adaptation for intracellular life. The rickettsial genome can code for effective transport systems for ATP, amino acids, and phosphorylated sugars as well as metabolic enzymes. The R. akari genome is unique when compared to other rickettsiae as the genome is highly conserved. The protein profiles of isolates from the United States, Ukraine, and Croatia are identical. The R. akari isolates from the 1940s are identical to the strains isolated in 2001 through 2003. There is likely a single ancestral strain circulating globally.

The adult male and female mites obtain multiple blood meals, whereas nymphal stages feed only once before molting. Since mites do not defecate during a blood meal, researchers hypothesize that the rickettsiae are introduced into the host by inoculation, at the time of the feeding via infected salivary secretions. R. akari can be transmitted vertically, and therefore it is present in all stages of the mite’s life cycle, namely egg, larva, protonymph, deutonymph, and adult. The bites of a house mouse mite are painless and, therefore, go unnoticed. 

After entry into the host, R. akari targets the CD68 macrophages. This is a unique feature among the rickettsiae, which usually target the vascular endothelial cells. The interactions that lead to infection of the macrophages are unknown. R. akari causes self-phagocytosis like other rickettsiae and escapes the phagosome before fusion with lysosomes can occur. R. akari multiplies by binary fission without initially disrupting the cellular architecture.

R. akari shows actin-based motility inside the cells and can propel themselves into the nucleus, adjacent cells, or invaginate into the cell membrane, ultimately bursting into the extracellular space. Once in the extracellular space, motility is due to Brownian motion only. This actin-based directed mobility inside the cell and tissues is a common feature of SFG of rickettsia and is not present in TG.

Experimental data suggest that T-cell mediated activation of macrophages is key to controlling and clearing the infection due to R. akari. The kinetics of cytokine release is different from that due to R. typhi infection. Elevated levels of tumor necrosis factor-alpha (TNF-alpha) but not interferon-gamma have been identified with R. akari infections. Overall, the immune response to R. akari infection in humans has not fully been characterized.

History and Physical

R. akari infection presents with a triad of fever, vesicular rash, and eschar. This triad was found in 92% of patients investigated in New York City. Only a few doctors diagnosed the cases found in New York (three physicians diagnosed 75% of cases). Therefore, the knowledge of these infections is not very common among physicians. A high index of suspicion based upon a good epidemiological and exposure history is required. Headache and myalgias may be present at the onset of illness. The eschar appears a week after the mite bite. Since the mouse mite bites are painless, it is hard to ascertain the incubation period. Eschar is the clinical hallmark of the disease. It initially appears as a papule, then a vesicle appears in the center, which dries leaving a brown or black eschar. There is regional lymphadenopathy. The rash begins on day three or four and is, at first, papular in appearance. Furthermore, the rash can be present on day one or appear by day ten, making the clinical diagnosis all the more difficult. The rash undergoes transformation to papulovesicular lesions. The vesicles dry, leaving a black crust. Usually, there are about 30 to 40 skin lesions. These lesions heal without scarring. The palms and soles are not involved. The rash resolves in two to three weeks. While a vesicular rash is typical, it is not present in all patients. The vesicular rash was noted in 92% of cases in one study consisting of 13 patients. The rash could be of any morphologic type, as noted in two other published studies composed of 178 patients. 

In the largest case series (n = 144), the reported clinical features were a triad of fever, rash, and eschar (99.9%) and headache in 90%. Abnormalities on cell blood counts were transient; leucopenia or thrombocytopenia had been reported. An abnormal transient rise in aminotransferases was also reported.

The disease is self-limiting, lasting 7 to 10 days. There was a case of a patient with human immunodeficiency virus (HIV) who recovered from the disease with doxycycline. In one series (N=34), 32% of the patients were hospitalized, most likely to exclude more serious diseases such as cutaneous anthrax and chickenpox.


The most common method of diagnosis of R. akari infections in clinical practice is to detect a four-fold rise in the convalescent titers of complement fixation or indirect fluorescent antibodies using spotted fever group antigens, as Rickettsia akari is linked genetically to the SFG of Rickettsiae. These tests are available through the Centers for Disease Control and Prevention (CDC). R. akari does not produce Weil-Felix agglutinins. Like other members of the genus Rickettsia, R. akari are not evident on blood smears and do not stain with most conventional stains. There are no rapid tests to diagnose rickettsial infections, including R. akari infection.[2][9][10]

Immunohistochemical stains of the skin biopsy from the eschar can be used, but these tests cannot identify the rickettsial organisms to the species level. Additionally, these tests are labor-intensive and require a high level of expertise.

There is a real-time, multiplex, polymerase chain reaction (PCR) technique that can accurately identify R. akari in formalin-fixed, paraffin-embedded skin biopsy specimens and distinguish it from R. rickettsii and Rickettsia parkeri. Swabs of the eschar can suffice as the clinical specimen for these molecular techniques. Eschar specimens are more likely to yield R. akari organisms or antigens where they are abundantly present when compared to fluid from vesiculopapular lesions.

R. akari can be cultured in a Vero cell system inoculated with the blood or eschar specimen. The cytopathic effect occurs very late in the Vero cell system; therefore, the plates should be kept for several weeks. This method of diagnosis does not help make treatment decisions in real-time. However, rickettsial isolation in culture is unnecessary, laborious, and hazardous to laboratory personnel, as rickettsial infection can be transmitted by inhalation and contact with skin abrasions. Rickettsia, when attached to respiratory mucosa, can directly penetrate the host cell membrane and access the cytoplasm by inducing self-phagocytosis.

Treatment / Management

Rickettsialpox is a self-limited disease; however, the treatment with antibiotics will shorten the duration of systemic symptoms from approximately seven to ten days without treatment to less than 48 hours with therapy. The drug of choice to treat R. akari is doxycycline. Doxycycline 100 mg orally, twice daily, for 2 to 5 days or 48 hours post defervescence is sufficient. Some experts recommend seven days of therapy. Defervescence occurs within one day of therapy.

Children older than eight years of age can be prescribed doxycycline at 2.2 mg/kg per day orally in divided twice-daily doses. The duration of treatment is the same as for adults. The maximum daily dose should not exceed 200 mg. No treatment is advised in pregnancy or children less than eight years of age. 

As in infections due to other rickettsial species, chloramphenicol has been used to treat R. akari infection. In vitro susceptibility studies for R. akari were done using dye uptake and plaque assays. Amongst the macrolides, josamycin has the lowest minimum inhibitory concentrations (MIC) of 0.5 microgram/m to 1 microgram/ml. Doxycycline MICs were 0.06 microgram/m to 0.125 microgram/ml. Tetracycline and chloramphenicol are bacteriostatic in mice models even though these antibiotics are used clinically to treat R. akari infections. In vitro, penicillin, aminoglycosides, and vancomycin are all bacteriostatic at very high concentrations. In experimental mice, rickettsial multiplication will not stop even at a very high concentration of penicillin.

Differential Diagnosis

Differential diagnosis includes any febrile illness with rash, which could be due to viral etiology such as infectious mononucleosis, chickenpox, to bacterial diseases such as Lyme disease and streptococcal infection. Connective tissue disorders such as systemic lupus erythematosus should be considered as well. Infections due to other rickettsiae that present with rash or eschar, ehrlichial infections which present with fever and thrombocytopenia, Orientia infections, which produces eschar, and leptospiral infections, which present with fever and abnormal liver enzymes are all part of the differential diagnosis. Febrile illness with multisystem involvement such as dengue should also be considered.


Assuming antibiotic therapy is begun at once, the majority of patients will show clinical improvement in two days. However, a delay in antibiotic treatment is the primary factor in poor prognosis in patients with Rickettsia akari infection. The treatment should be started even if there is only clinical suspicion without waiting for the lab results to improve outcomes.


Rickettsialpox is generally a benign disease with spontaneous recovery within 2-3 weeks. It is rare for the patient to develop complications and death from this condition.

Deterrence and Patient Education

Patients should be educated about the etiology of the condition and advised to use pesticides to get rid of the mites. Several steps should be taken to ensure that homes remain free from mice, such as clearing tall grass and brush from around homes, removing trash, blocking holes, or other places where mice can hide.

Pearls and Other Issues

The pathogenesis of R. akari infection is still unknown. More research is needed. It is unclear how R. akari acquired the plasmid. It can be a potentially powerful tool for future genetic manipulation, to study the yet unknown facets of the host cell interactions as well as mechanisms of immune evasion employed by this group of organisms.

Enhancing Healthcare Team Outcomes

R.akari is best managed by an interprofessional team that includes infectious disease specialists, pathologists, and nurses. Because the condition is self-limited, no treatment is generally required.  However, treatment with antibiotics will decrease the duration of systemic symptoms from approximately seven to ten days without treatment to less than 48 hours with therapy. The drug of choice to treat R. akari is doxycycline. The majority of patients see a clinical improvement in 24 to 48 hours.

Article Details

Article Author

Sami M. Akram

Article Author

Radia T. Jamil

Article Editor:

William Gossman


2/25/2023 9:06:48 PM



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