Rickettsial Diseases,

Rickettsial Diseases, including Typhus and Rocky Mountain Spotted Fever

·         The Rickettsiae are small (0.3-0.5 x 0.8-2.0 um), Gram-negative, aerobic, coccobacilli that are obligate intracellular parasites of eucaryotic cells.

·         They may reside in the cytoplasm or within the nucleus of the cell that they invade. They divide by binary fission and they metabolize host-derived glutamate via aerobic respiration and the citric acid (TCA) cycle. They have typical Gram-negative cell walls, and they lack flagella. The rickettsiae frequently have a close relationship with arthropod vectors that may transmit the organism to mammalian hosts

·         The rickettsiae, in spite of their small size and obligate intracellular habitat, are a group of alphaproteobacteria,  which include many well-known organisms such as Acetobacter, Rhodobacter, Rhizobium and Agrobacterium. Very few of the alphaproteobacteria are pathogens of humans. Brucella, Bartonella, Rickettsia, and a related intracellular parasite, Ehrlichia, are the main exceptions.

·         The rickettsiae that are pathogens of humans are subdivided into three major groups based on clinical characteristics of disease: 1. spotted fever group; 2. typhus group; and 3. scrub typhus group.

·         Spotted Fever Group (SFG)
Rickettsia rickettsii is the cause of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae.  Rickettsia rickettsii is found in the Americas and is transmitted to humans through the bite of infected ticks. The bacterium infects human vascular endothelial cells, producing an inflammatory response. The pathogenesis of RMSF is discussed in some detail below.

·         Scrub Typhus Group (STG)
Orientia (Rickettsia) tsutsugamushi is the cause of scrub typhus. Originally called Rickettsia tsutsugamushi, this organism was given its own genus designation because it is phylogenetically distinct from the other rickettsiae, though closely related. Orientia tsutsugamushi is transmitted to humans by the bite of trombiculid mites (chiggers), which are the vector and host. Scrub typhus occurs throughout much of Asia and Australia.

·         Typhus Group (TG)
Rickettsia prowazekii is the cause of epidemic or louse-borne typhus and is the prototypical bacterium from the typhus group of rickettsiae. R. prowazekii infects human vascular endothelial cells, producing widespread vasculitis. In contrast to RMSF, louse-borne typhus tends to occur in the winter. Infection usually is transmitted from person to person by the body louse and, therefore, tends to manifest under conditions of crowding and poor hygiene. The southern flying squirrel is apparently the reservoir in the United States, but the vector involved in transmission from the flying squirrel to humans is unknown. The disease has a worldwide distribution.

·          Signs and Symptoms
Rocky Mountain spotted fever can be very difficult to diagnose in its early stages, even among experienced physicians who are familiar with the disease. Patients infected with R. rickettsii generally visit a physician in the first week of their illness, following an incubation period of about 5-10 days after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and non-infectious diseases.

·          Initial symptoms may include fever, nausea, vomiting, severe headache, muscle pain, and lack of appetite. Later signs and symptoms include rash, abdominal pain, joint pain and diarrhea.

·          The classic triad of findings for this disease are fever, rash, and history of tick bite. However, this combination is often not identified when the patient initially presents for care. The rash first appears 2-5 days after the onset of fever and is often not present or may be very subtle when the patient is initially seen by a physician. Younger patients usually develop the rash earlier than older patients. Most often it begins as small, flat, pink, non-itchy spots (macules) on the wrists, forearms, and ankles (Figure 13). These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted (petechial) rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after onset of symptoms, and this type of rash occurs in only 35% to 60% of patients with Rocky Mountain spotted fever (Figure 14). The rash involves the palms or soles in as many as 50% to 80% of patients; however, this distribution may not occur until later in the course of the disease. As many as 10% to 15% of patients may never develop a rash.

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·         If the patient is treated within the first 4-5 days of the disease, fever generally subsides within 24-72 hours after treatment with an appropriate antibiotic (usually a tetracycline)

·         Doxycycline (100 mg every 12 hours for adults or 4 mg/kg body weight per day in two divided doses for children under 45 kg [100 lb.]) is the drug of choice for patients with Rocky Mountain spotted fever. Therapy is continued for at least 3 days after fever subsides and until there is unequivocal evidence of clinical improvement, generally for a minimum total course of 5 to 10 days. Severe or complicated disease may require longer treatment courses. Doxycycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble Rocky Mountain spotted fever.