What is Rickettsiosis?

What is Rickettsiosis?

Rickettsiosis refers to a group of life-threatening bacterial infections caused by obligate intracellular bacteria in the order Rickettsiales, transmitted primarily by arthropod vectors including ticks, fleas, lice, and mites. 1

Causative Organisms and Classification

Rickettsiae are small, Gram-negative bacilli that can only replicate within the cytoplasm of eukaryotic host cells. 2 The major disease-causing groups include:

• Spotted Fever Group (SFG) rickettsiae - including Rickettsia rickettsii (Rocky Mountain spotted fever), R. parkeri, R. conorii (Mediterranean spotted fever), and R. africae (African tick bite fever) 3
• Typhus group - transmitted by lice and fleas 4
• Scrub typhus - caused by Orientia tsutsugamushi, transmitted by mites (chiggers) 5
• Other rickettsial pathogens - including Ehrlichia and Anaplasma species 3

Transmission and Epidemiology

Ticks serve as both vectors and reservoirs for rickettsiae, maintaining these bacteria through transstadial (larva to nymph to adult) and transovarial (generation to generation) transmission. 3 The geographic distribution of rickettsioses is determined by the distribution and seasonal activity of their arthropod vectors. 3

In the United States:

• Most cases occur during April-September, coinciding with peak tick activity 3
• 63% of SFG rickettsiosis cases during 2008-2012 originated from five states: Arkansas, Missouri, North Carolina, Oklahoma, and Tennessee 3
• Reported incidence has increased substantially over the past two decades 3

Pathophysiology

When transmitted to humans, pathogenic rickettsiae multiply in endothelial cells and cause vasculitis, which is responsible for all clinical and laboratory abnormalities. 3, 2 This microvasculitis leads to microinfarcts in various organs, producing the diverse clinical manifestations of disease. 6

Clinical Presentation

Early signs and symptoms are nonspecific, and most cases are misdiagnosed at the patient's first visit, even in high-awareness areas. 1 The classic presentation includes:

• Fever, headache, and myalgia - typically beginning 6-10 days after arthropod bite 3, 5
• Rash - maculopapular or petechial, may involve palms and soles (varies by species) 3
• Eschar ("tache noire") - a characteristic necrotic lesion with black crust at the bite site, though not always present 3, 5, 2
• Regional lymphadenopathy 3

Additional manifestations may include:

• Gastrointestinal symptoms, hepatosplenomegaly 6
• Thrombocytopenia, leukocyte abnormalities, elevated hepatic enzymes 3

Severe complications include encephalitis, ARDS, myocarditis, renal failure, and vascular collapse. 6

Critical Treatment Principles

Doxycycline is the treatment of choice for adults and children of all ages with suspected rickettsial disease and must be initiated immediately when rickettsiosis is suspected. 1, 4 Delay in recognition and treatment is the most important factor associated with risk for death from RMSF and other severe rickettsial diseases. 1

Dosing:

• Adults: 100 mg twice daily (orally or IV) 1, 5
• Children under 45 kg: 2.2 mg/kg body weight twice daily (orally or IV) 1, 5
• Continue for at least 3 days after fever subsides; minimum 5-7 days total 5

Treatment should never be delayed while awaiting laboratory confirmation. 5 The historical concern about dental staining in children under 8 years should not prevent short-course doxycycline use. 5

Chloramphenicol can be used as an alternative agent (12.5-25 mg/kg every 6 hours IV) when doxycycline is contraindicated. 5, 7

Diagnostic Approach

Because rickettsiae are obligate intracellular organisms, they cannot be grown on artificial media and require tissue cell cultures for isolation. 2 Practical diagnostic methods include:

• Serology (indirect immunofluorescence assay) - gold standard, but reactive antibodies are seldom present during early illness 8
• PCR-based molecular methods - provide sensitive and specific detection 2
• Skin biopsy from eschar - often yields better results than blood samples 2

A four-fold rise in antibody titer between acute and convalescent sera (2 weeks apart) confirms diagnosis. 3

Key Clinical Pitfalls

• Do not wait for laboratory confirmation before starting treatment - empiric doxycycline should be initiated based on clinical suspicion alone 1, 5
• Do not withhold doxycycline from children - the benefits far outweigh theoretical risks of dental staining 5
• Consider rickettsiosis in any febrile patient with tick exposure, even without rash or eschar 1
• Patients typically respond within 24-48 hours - lack of response should prompt consideration of alternative diagnoses 5