Rickettsial Infection


Article Author:
Jessica Snowden


Article Editor:
Kevin King


Editors In Chief:
Jessica Snowden
Asif Noor
H Davies


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
6/4/2019 8:13:27 PM

Introduction

Rickettsia is a group of vector-borne organisms that cause acute febrile illnesses throughout the world. While the clinical presentations of rickettsial infection are similar, the causative species and epidemiology can vary depending on the region. It is important to recognize both the typical symptoms and the epidemiology of a given region to correctly diagnose and treat these infections promptly, as they can be associated with significant morbidity and mortality.[1][2][3]

Etiology

Rickettsial infections are caused by a variety of obligate intracellular bacteria in the genus Rickettsia and are grouped into one of four categories: the spotted fever group (SFG) rickettsiae, typhus group rickettsiae, the ancestral group, and the transitional group. Rickettsia rickettsii causes Rocky Mountain Spotted Fever, the most severe and most well known of the rickettsial infections in North America. However, it is important to recognize that other species are common in other parts of the world, including Rickettsia africae, the cause of African Tick Bite Fever in sub-Saharan Africa, and Rickettsia conorii which causes Mediterranean Spotted Fever in Europe and North Africa. Rickettsia prowazekii and Rickettsia typhi present as typhus syndromes. Researchers continue to discover new species of Rickettsia as  molecular techniques advance.[4][5][6][7]

Epidemiology

Rickettsia is typically vector-borne, transmitted by ticks, body lice, and fleas. In most cases, humans are thought to be accidental hosts. The transmitting ticks vary depending on the region and organism, with Dermacentor variabilis (American dog tick), Dermacentor andersoni (Rocky Mountain wood tick), and Amblyomma americanum (Lone Star tick) associated with most cases of Rocky Mountain Spotted Fever in the United States. Alternatively, Amblyomma cajennense has been associated with spotted fever in South America and Amblyomma hebraeum or Amblyomma variegatum in South Africa. Because of the association with ticks and other vectors, infections with Rickettsiae are more common during warmer months and in people exposed to the outdoor and outdoor activities. Epidemic typhus, R. prowazekii, is transmitted by body lice and associated with crowded conditions and poor hygiene. Murine typhus (R. typhi) is most commonly reported in tropical and subtropical areas and is associated with flea bites.[8][9][10][11]

Pathophysiology

Rickettsia preferentially infects the vascular endothelial cells lining the small and medium vessels throughout the body, causing the systemic symptoms and high mortality seen with these diseases. The infection of endothelial cells leads to disseminated inflammation, loss of barrier function and altered vascular permeability throughout the body. This leads to the fever, myalgias, central nervous system symptoms such as a headache and confusion, rash, and cardiovascular instability that can be seen in patients with rickettsial infection, as well as leading to mortality in severe cases. The mechanisms involved in the rapid entry of the organisms into the cell and the downregulation of immune pathways allowing for persistence of infection are being studied to identify new therapeutic targets in these illnesses.

History and Physical

Patients typically present with symptoms four to ten days after exposure to the Rickettsia via a flea or tick bite. Symptoms classically include the triad of fever, headache, and a petechial or maculopapular rash. Symptoms may also include lymphadenopathy, central nervous system changes such as confusion or nuchal rigidity, an eschar at the inoculation site, myalgias and arthralgias, hepatitis, vomiting, and cardiovascular instability. It is important to have a high index of suspicion for rickettsial infection when patients present with these "influenza-like" symptoms during the summer months, regardless of known tick or insect exposure, as the tick or insect exposure may be brief and unnoticed by the patient. Importantly, the classic triad of symptoms is largely consistent across rickettsial species, although clinical judgments as to specific etiologies can be refined based on geographic exposure and specific symptoms. A detailed history of travel and other outdoor exposure is essential in diagnosing the specific cause of these symptoms.

Evaluation

Currently, most rickettsial infections are diagnosed based on serologic responses, such as IgG and IgM to R. rickettsiae, in conjunction with a high degree of clinical suspicion. While rickettsia can be cultured in the microbiology laboratory, this approach is not often used for clinical diagnosis as the technique is difficult and requires a high level of biosafety containment due to the risk of exposure. Other diagnostic options include molecular tests, such as PCR, in some centers and skin biopsy. In addition to suggestive or positive serologic tests, patients with rickettsial infections may also have thrombocytopenia, hyponatremia, and cerebrospinal fluid pleocytosis. On a peripheral white blood cell count, it is important to note that this may be elevated, normal, or low and thus may not help to rule out rickettsial infection. A high index of suspicion is crucial given the high morbidity and mortality associated with rickettsial infection and the potential for negative serologic testing early in the course of illness. Negative testing should not preclude treatment if the clinical scenario is suggestive of rickettsial infection due to symptoms and exposure history.

Treatment / Management

The drug of choice for Rickettsial infections is doxycycline, with the dosing and length of therapy dependent on the specific causative organism. In the case of allergy and severe disease, chloramphenicol may also be an option. In milder disease, macrolides such as clarithromycin may also be considered. Fluoroquinolones have been associated with worsened outcomes and are not recommended for the treatment of rickettsial disease. It is important to note than in severe rickettsial disease, such as Rocky Mountain Spotted Fever, mortality rates are as high as 20% to 30% without prompt antibiotic treatment. Additionally, while doxycycline is not routinely utilized in children younger than age 8, it is indicated for certain rickettsial infections in this age group due to the high mortality associated with the severe rickettsial disease. Thus, treatment should not be delayed while awaiting confirmatory laboratory testing in a patient with suspected rickettsial infection.

Enhancing Healthcare Team Outcomes

Rickettsial infections are best managed by a multidisciplinary team that includes pharmacists and nurses. The key to rickettsial infections is prevention. Prevention of Rickettsial infection relies on avoidance of exposure to tick and flea bites, particularly when residing or traveling to endemic areas. There is currently not a vaccine for prevention of Rocky Mountain Spotted Fever or other Rickettsial infections and antibiotic prophylaxis is not routinely recommended in the United States. Careful checks for insects after outdoor activities and use of long-sleeved clothing and insect repellant are all advised to a minimum the risk of rickettsial infection.

 


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Rickettsial Infection - Questions

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A 16-year-old boy is admitted with sepsis and petechiae. He has a history of recent camping and tick bites. Physical examination reveals a maculopapular rash on her trunk as well as multiple eschars surrounding the bite site. Which of the following is the most appropriate diagnostic test?



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What is the primary site of proliferation of rickettsial organisms?



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A patient presents with fever, headache, and petechial rash. You suspect a rickettsial infection. Which element of history is needed to determine the most likely specific cause of illness?



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A patient presents with fever, headache, and a rash. A rickettsial infection is suspected. What other information is needed to narrow the diagnosis?



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A patient presents with fever, headache, and a petechial rash. What is the appropriate empiric therapy?



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Rickettsial Infection - References

References

Adem PV, Emerging and re-emerging rickettsial infections. Seminars in diagnostic pathology. 2019 Apr 16;     [PubMed]
Tello-Martin R,Dzul-Rosado K,Zavala-Castro J,Lugo-Caballero C, Approaches for the successful isolation and cell culture of American {i}Rickettsia{/i} species. Journal of vector borne diseases. 2018 Oct-Dec;     [PubMed]
Satjanadumrong J,Robinson MT,Hughes T,Blacksell SD, Distribution and Ecological Drivers of Spotted Fever Group Rickettsia in Asia. EcoHealth. 2019 Apr 15;     [PubMed]
Dehhaghi M,Kazemi Shariat Panahi H,Holmes EC,Hudson BJ,Schloeffel R,Guillemin GJ, Human Tick-Borne Diseases in Australia. Frontiers in cellular and infection microbiology. 2019;     [PubMed]
Diop A,Raoult D,Fournier PE, Paradoxical evolution of rickettsial genomes. Ticks and tick-borne diseases. 2019 Feb;     [PubMed]
Laroche M,Raoult D,Parola P, Insects and the Transmission of Bacterial Agents. Microbiology spectrum. 2018 Oct;     [PubMed]
Hardstone Yoshimizu M,Billeter SA, Suspected and Confirmed Vector-Borne Rickettsioses of North America Associated with Human Diseases. Tropical medicine and infectious disease. 2018 Jan 3;     [PubMed]
Khamesipour F,Dida GO,Anyona DN,Razavi SM,Rakhshandehroo E, Tick-borne zoonoses in the Order Rickettsiales and Legionellales in Iran: A systematic review. PLoS neglected tropical diseases. 2018 Sep;     [PubMed]
Weitzel T,Aylwin M,Martínez-Valdebenito C,Jiang J,Munita JM,Thompson L,Abarca K,Richards AL, Imported scrub typhus: first case in South America and review of the literature. Tropical diseases, travel medicine and vaccines. 2018;     [PubMed]
Eldin C,Parola P, Update on Tick-Borne Bacterial Diseases in Travelers. Current infectious disease reports. 2018 May 22;     [PubMed]
Moreira J,Bressan CS,Brasil P,Siqueira AM, Epidemiology of acute febrile illness in Latin America. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2018 Aug;     [PubMed]

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