Rocky Mountain spotted fever
Rocky Mountain spotted fever is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally made up of small spots of bleeding and starts on the wrists and ankles. Other symptoms may include muscle pains and vomiting. Long-term complications following recovery may include hearing loss or loss of part of an arm or leg.
The disease is caused by Rickettsia rickettsii, a type of bacterium that is primarily spread to humans by American dog ticks, Rocky Mountain wood ticks, and brown dog ticks. Rarely the disease is spread by blood transfusions. Diagnosis in the early stages is difficult. Several laboratory tests can confirm the diagnosis but treatment should be begun based on symptoms. It is within a group known as spotted fever rickettsiosis, together with Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox.
Treatment of RMSF is with the antibiotic doxycycline. It works best when started early and is recommended in all age groups, as well as during pregnancy. Antibiotics are not recommended for prevention. Approximately 0.5% of people who are infected die as a result. Before the discovery of tetracycline in the 1940s, more than 10% of those with RMSF died.
Fewer than 5,000 cases are reported annually in the United States, usually in June and July. It has been diagnosed throughout the contiguous United States, Western Canada, and parts of Central and South America. Rocky Mountain spotted fever was first identified in the 1800s in the Rocky Mountains.
Signs and symptoms
Spotted fever can be challenging to diagnose in its early stages, due to the similarity of symptoms with many different diseases. People infected with R. rickettsii usually notice symptoms following an incubation period of one to two weeks after a tick bite. The early clinical presentation of Rocky Mountain spotted fever is nonspecific and may resemble a variety of other infectious and noninfectious diseases.Initial symptoms:
Later signs and symptoms:
- Maculopapular rash
- Petechial rash
- Abdominal pain
- Joint pain
- Conjunctivitis
- Forgetfulness
Rash
The rash first appears two to five days after the onset of fever, and it is often quite subtle. Younger patients usually develop the rash earlier than older patients. Most often, the rash begins as small, flat, pink, non-itchy spots on the wrists, forearms, and ankles. These spots turn pale when pressure is applied and eventually become raised on the skin. The characteristic red, spotted rash of Rocky Mountain spotted fever is usually not seen until the sixth day or later after the onset of symptoms. This type of rash occurs in only 35-60% of patients with Rocky Mountain spotted fever. The rash involves the palms or soles in as many as 80% of people. However, this distribution may not occur until later on in the course of the disease. As many as 15% of patients may never develop a rash.Complications
People can develop permanent disabilities including "cognitive deficits, ataxia, hemiparesis, blindness, deafness, or amputation following gangrene".Cause
Ticks are the natural hosts of the disease, serving as both reservoirs and vectors of R. rickettsii. Ticks transmit the bacteria primarily through their bites. Less commonly, infections may occur following exposure to crushed tick tissues, fluids, or tick feces.A female tick can transmit R. rickettsii to her eggs in a process called transovarial transmission. Ticks can also become infected with R. rickettsii while feeding on blood from the host in either the larval or nymphal stage. After the tick develops into the next stage, the R. rickettsii may be transmitted to the second host during the feeding process. Furthermore, male ticks may transfer R. rickettsii to female ticks through body fluids or spermatozoa during the mating process. These types of transmission represent how generations or life stages of infected ticks are maintained. Once infected, the tick can carry the pathogen for life.
Rickettsiae are transmitted through saliva injected while a tick is feeding. Unlike Lyme disease and other tick-borne pathogens that require a prolonged attachment period to establish infection, a person can become infected with R. rickettsii in a feeding time as short as 2 hours. In general, about 1-3% of the tick population carries R. rickettsii, even in areas where the majority of human cases are reported. Therefore, the risk of exposure to a tick carrying R. rickettsii is low.
The disease is spread by the American dog tick, Rocky Mountain wood tick, brown dog tick, and Amblyomma sculptum. Not all of these are of equal importance, and most are restricted to certain geographic areas.
The two major vectors of R. rickettsii in the United States are the American dog tick and the Rocky Mountain wood tick. American dog ticks are widely distributed east of the Rocky Mountains, and they also occur in limited areas along the Pacific Coast. Dogs and medium-sized mammals are the preferred hosts of an adult American dog tick, although it feeds readily on other large mammals, including human beings. This tick is the most commonly identified species responsible for transmitting R. rickettsii to humans. Rocky Mountain wood ticks are found in the Rocky Mountain states and southwestern Canada. The lifecycle of this tick takes up to three years to complete. Adult ticks feed primarily on large mammals. The larvae and nymphs feed on small rodents.
Other tick species are naturally infected with R. rickettsii or serve as experimental vectors in the laboratory. These species are likely to play only a minor role in the ecology of R. rickettsii.
Pathophysiology
Entry into host
Rickettsia rickettsii can be transmitted to human hosts through the bite of an infected tick. As with other bacteria transmitted via ticks, the process generally requires a period of attachment of 4 to 6 hours. However, in some cases, a Rickettsia rickettsii infection was contracted by contact with tick tissues or fluids. Then, the bacteria induce their internalization into host cells via a receptor-mediated invasion mechanism.Researchers believe that this mechanism is similar to that of Rickettsia conorii. This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called Ku70. It has previously been reported that Ku70 migrates to the host cell surface in the presence of "Rickettsia". Then, Ku70 is ubiquitinated by c-Cbl, an E3 ubiquitin ligase. This triggers a cascade of signal transduction events resulting in the recruitment of Arp2/3 complex. CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the alteration of local host cytoskeletal actin at the entry site as part of a zipper mechanism. Then, the bacteria is phagocytosized by the host cell and enveloped by a phagosome.
Studies have suggested that rOmpB is involved in this process of adhesion and invasion. Both rOmpA and rOmpB are members of a family of surface cell antigens which are autotransporter proteins; they act as ligands for the Omp proteins and are found throughout the rickettsiae.
Exit from host cell
The cytosol of the host cell contains nutrients, adenosine triphosphate, amino acids, and nucleotides, which are used by the bacteria for growth. For this reason, as well as to avoid phagolysosomal fusion and death, rickettsiae must escape from the phagosome. To escape from the phagosome, the bacteria secrete phospholipase D and hemolysin C. This disrupts the phagosomal membrane and allows the bacteria to escape. Following generation time in the cytoplasm of the host cells, the bacteria utilize actin-based motility to move through the cytosol.RickA, expressed on the rickettsial surface, activates Arp2/3 and causes actin polymerization. The rickettsiae use the actin to propel themselves throughout the cytosol to the surface of the host cell. This causes the host cell membrane to protrude outward and invaginate the membrane of an adjacent cell. The bacteria are then taken up by the neighboring cell in a double membrane vacuole that the bacteria can subsequently lyse, enabling spread from cell to cell without exposure to the extracellular environment.
Consequences of infection
Rickettsia rickettsii initially infects blood vessel endothelial cells, but eventually migrates to vital organs, such as the brain, skin, and the heart, via the bloodstream. Bacterial replication in host cells causes endothelial cell proliferation and inflammation, resulting in mononuclear cell infiltration into blood vessels and subsequent red blood cell leakage into surrounding tissues. The characteristic rash observed in Rocky Mountain spotted fever is the direct result of this localized replication of Rickettsia in blood vessel endothelial cells.Diagnosis
This disease can be diagnosed by a doctor with or without the use of lab testing. Lab tests are not always relied upon because treatment may be necessary before the results are returned.Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include a low platelet count, low blood sodium concentration, or elevated liver enzyme levels. Serology testing and skin biopsy are considered to be the best methods of diagnosis. Although immunofluorescent antibody assays are considered some of the best serology tests available, most antibodies that fight against R. rickettsii are undetectable on serology tests during the first seven days after infection.
Differential diagnosis includes dengue, leptospirosis, chikungunya, and Zika fever.