Rocky Mountain spotted fever: Difference between revisions
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For patient information click Rocky Mountain spotted fever (patient information)|here]].
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| Rickettsia rickettsii Wolbach, 1919 |
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Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States, and has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” (Colombia), “São Paulo fever” or “febre maculosa” (Brazil), and “fiebre manchada” (Mexico). It should not be confused with the viral tick-borne infection, Colorado tick fever. The disease is caused by Rickettsia rickettsii, a species of bacteria that is spread to humans by ixodid ticks (Dermacentor). Initial signs and symptoms of the disease include sudden onset of fever, headache, and muscle pain, followed by development of rash. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment it can be fatal.
The name “Rocky Mountain spotted fever” is somewhat of a misnomer. Beginning in the 1930s, it became clear that this disease occurred in many areas of the United States other than the Rocky Mountain region. It is now recognized that this disease is broadly distributed throughout the continental United States, and occurs as far north as Canada and as far south as Central America, Mexico, and parts of South America. Between 1981 and 1996, this disease was reported from every U.S. state except Hawaii, Vermont, Maine, and Alaska.
Rocky Mountain spotted fever remains a serious and potentially life-threatening infectious disease today. Despite the availability of effective treatment and advances in medical care, approximately 3% to 5% of individuals who become ill with Rocky Mountain spotted fever still die from the infection. However, effective antibiotic therapy has dramatically reduced the number of deaths caused by Rocky Mountain spotted fever; before the discovery of tetracycline and chloramphenicol in the late 1940s, as many as 30% of persons infected with R. rickettsii died.
Natural history
Rocky Mountain spotted fever, like all rickettsial infections, is classified as a zoonosis. Zoonoses are diseases of animals that can be transmitted to humans. Many zoonotic diseases require a vector (e.g., a mosquito, tick, or mite) in order to be transmitted from the animal host to the human host. In the case of Rocky Mountain spotted fever, ticks are the natural hosts, serving as both reservoirs and vectors of R. rickettsii. Ticks transmit the organism to vertebrates primarily by their bite. 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 to a vertebrate host through saliva while a tick is feeding. It usually takes several hours of attachment and feeding before the rickettsiae are transmitted to the host. The risk of exposure to a tick carrying R. rickettsii is low. In general, about 1%-3% of the tick population carries R. rickettsii, even in areas where the majority of human cases are reported.
There are 2 major vectors of R. rickettsii in the United States, the American dog tick and the Rocky Mountain wood tick. American dog ticks (Dermacentor variabilis) are widely distributed east of the Rocky Mountains and also occurs in limited areas on the Pacific Coast. Dogs and medium-sized mammals are the preferred hosts of adult D. variabilis, although it feeds readily on other large mammals, including humans. This tick is the most commonly identified species responsible for transmitting R. rickettsii to humans. Rocky Mountain wood ticks (Dermacentor andersoni) are found in the Rocky Mountain states and in southwestern Canada. The life cycle of this tick may require up to 2 to 3 years for completion. Adult ticks feed primarily on large mammals. Larvae and nymphs feed on small rodents.
Other tick species have been shown to be naturally infected with R. rickettsii or serve as experimental vectors in the laboratory. However, these species are likely to play only a minor role in the ecology of R. rickettsii.
Pathophysiology & Etiology
Rocky Mountain spotted fever is caused by Rickettsia rickettsii, a small bacterium that grows inside the cells of its hosts. These bacteria range in size from 0.2 x 0.5 micrometers to 0.3 x 2.0 micrometers. They are difficult to see in tissues by using routine histologic stains and generally require the use of special staining methods.
In the human body, rickettsiae live and multiply primarily within cells that line small- to medium-sized blood vessels. Spotted fever group rickettsiae can grow in the cytoplasm or in the nucleus of the host cell. Once inside the host the rickettsiae multiply, resulting in damage and death to these cells. This causes blood to leak through tiny holes in vessel walls into adjacent tissues. This process causes the rash that is traditionally associated with Rocky Mountain spotted fever and also causes damage to organs and tissues.
Taxonomy
The genus Rickettsia is included in the bacterial tribe Rickettsieae, family Rickettsiaceae, and order Rickettsiales. This genus includes many other species of bacteria associated with human disease, including those in the spotted fever group and in the typhus group. More than 20 species are currently recognized in genus Rickettsia but not all are known to cause disease in humans. Other genotypes are also known but they have not been classified yet as valid species and new agents are being discovered in many areas of the world.
Epidemiology
Rocky Mountain spotted fever has been a reportable disease in the United States since the 1920s. In the last 50 years, approximately 250-1200 cases of Rocky Mountain spotted fever have been reported annually, although it is likely that many more cases go unreported. CDC compiles the number of cases reported by the state health departments. To ensure standardization of reporting across the country, CDC advises that a consistent case definition be used by all states.
Seasonal Distribution of Rocky Mountain Spotted Fever
Over 90% of patients with Rocky Mountain spotted fever are infected during April through September. This period is the season for increased numbers of adult and nymphal Dermacentor ticks. A history of tick bite or exposure to tick-infested habitats is reported in approximately 60% of all cases of Rocky Mountain spotted fever.
Geography of Rocky Mountain Spotted Fever
Over half of Rocky Mountain spotted fever infections are reported from the south-Atlantic region of the United States (Delaware, Maryland, Washington D.C., Virginia, West Virginia, North Carolina, South Carolina, Georgia, and Florida). Infection also occurs in other parts of the United States, namely the Pacific region (Washington, Oregon, and California) and west south-central (Arkansas, Louisiana, Oklahoma, and Texas) region.
The states with the highest incidences of Rocky Mountain spotted fever are North Carolina and Oklahoma; these two states combined accounted for 35% of the total number of U.S. cases reported to CDC during 1993 through 1996. Although Rocky Mountain spotted fever was first identified in the Rocky Mountain states, less than 3% of the U.S. cases were reported from that area during the same interval (1993-1996).
Worldwide Infection
Infection with Rickettsia rickettsii has also been documented in Argentina, Brazil, Colombia, Costa Rica, Mexico, and Panama. Some synonyms for Rocky Mountain spotted fever in other countries include tick typhus, Tobia fever (Colombia), São Paulo fever and fiebre maculosa (Brazil), and fiebre manchada (Mexico). Closely related organisms cause other types of spotted fevers in other parts of the world.
Demographics
The frequency of reported cases of Rocky Mountain spotted fever is highest among males, Caucasians, and children. Two-thirds of the Rocky Mountain spotted fever cases occur in children under the age of 15 years, with the peak age being 5 to 9 years old. Individuals with frequent exposure to dogs and who reside near wooded areas or areas with high grass may also be at increased risk of infection.
Infection with Rickettsia rickettsii has also been documented in Argentina, Brazil, Colombia, Costa Rica, Mexico, and Panama. Closely related organisms cause other types of spotted fevers in other parts of the world.
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 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 non-infectious diseases.
Initial symptoms may include:
Later signs and symptoms include:
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. 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. 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.
Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include thrombocytopenia, hyponatremia, or elevated liver enzyme levels.
Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because R. rickettsii infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or renal system. Host factors associated with severe or fatal Rocky Mountain spotted fever include advanced age, male sex, African-American race, chronic alcohol abuse, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Deficiency of G6PD is a sex-linked genetic condition affecting approximately 12% of the U.S. African-American male population; deficiency of this enzyme is associated with a high proportion of severe cases of Rocky Mountain spotted fever. This is a rare clinical course that is often fatal within 5 days of onset of illness.
Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations.
Diagnosis
A diagnosis of Rocky Mountain spotted fever is based on a combination of clinical signs and symptoms and specialized confirmatory laboratory tests. Other common laboratory findings suggestive of Rocky Mountain spotted fever include thrombocytopenia, hyponatremia, and elevated liver enzyme levels.
Laboratory Findings
Although it is technically feasible, specific rapid laboratory confirmation of early Rocky Mountain spotted fever is rarely done. Therefore, treatment decisions should be based on epidemiologic and clinical clues, and should never be delayed while waiting for confirmation by laboratory results. Fundamental understanding of the signs, symptoms, and epidemiology of the disease is crucial in guiding requests for tests for Rocky Mountain spotted fever, sample collection and submission, and interpretation of laboratory results.
Routine clinical laboratory findings suggestive of Rocky Mountain spotted fever may include abnormal white blood cell count, thrombocytopenia, hyponatremia, or elevated liver enzyme levels (see Glossary for definitions of terms). Serologic assays are the most widely available and frequently used methods for confirming cases of Rocky Mountain spotted fever. The indirect immunofluorescence assay (IFA) (see figure) is generally considered the reference standard in Rocky Mountain spotted fever serology and is the test currently used by CDC and most state public health laboratories, but other well validated assays including ELISA, latex agglutination, and dot immunoassays can be used.
IFA can be used to detect either IgG or IgM antibodies. Blood samples taken early (acute) and late (convalescent) in the disease are the preferred specimens for evaluation. Most patients demonstrate increased IgM titers by the end of the first week of illness. Diagnostic levels of IgG antibody generally do not appear until 7-10 days after the onset of illness. It is important to consider the amount of time it takes for antibodies to appear when ordering laboratory tests, especially because most patients visit their physician relatively early in the course of the illness, before diagnostic antibody levels may be present. The value of testing two sequential serum or plasma samples together to show a rising antibody level is very important in confirming acute infection with rickettsial agents because antibody titers may persist in some individuals for years after the original exposure to any of a number rickettsial agents. IgG antibodies are more specific and reliable since other bacterial infections can also cause elevations in riskettsial IgM antibody titers.
The most rapid and specific diagnostic assays for Rocky Mountain spotted fever rely on molecular methods like PCR which can detect DNA present in 5-10 rickettsiae in a sample. While organisms can be detected in whole blood samples obtained at the acute onset of illness in a few hours, rickettsial DNA is most readily detected in fresh skin biopsies like those used in immunostaining procedures. PCR can also be done on the fixed tissues used in immunostaining, but it is less sensitive than with unfixed tissues. PCR methods can be R. rickettsii-specific but are usually confirmed by DNA sequencing of the amplified gene fragments. Consequently, this procedure is more specific than antibody-based methods which are often only genus or spotted fever group-specific. Specified diagnosis can also be confirmed by isolation of R. rickettsii from clinical samples like whole blood and biopsies. Materials can be shipped unfrozen or frozen and on dry ice to ensure optimal chances of isolation at the CDC. Isolation may require several weeks, but isolates are very important for investigating differences in the pathogenic properties and antimicrobial resistance of rickettsiae which cause disease in different parts of the United States.
Another approach to Rocky Mountain spotted fever diagnostics is immunostaining. This method is used by taking a skin biopsy of the rash from an infected patient prior to therapy or within the first 48 hours after antibiotic therapy has been started. Because rickettsiae are focally distributed in lesions of Rocky Mountain spotted fever, this test may not always detect the agent. Even in laboratories with expertise in performing this test, the sensitivity is only about 70% on biopsied tissues because of the scarcity of organisms in some samples. This assay may also be used to test tissues obtained at autopsy and has been used to confirm Rocky Mountain spotted fever in otherwise unexplained deaths (see figure). Immunostaining for spotted fever group rickettsiae is offered by the CDC, a few state health departments, and some university-based hospitals and commercial laboratories in the United States.
Treatment
Appropriate antibiotic treatment should be initiated immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiologic findings. Treatment should not be delayed until laboratory confirmation is obtained.
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 in the tetracycline class). In fact, failure to respond to a tetracycline antibiotic argues against a diagnosis of RMSF. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in non-ill patients who have had recent tick bites is not recommended and may, in fact, only delay the onset of disease.
What is the best way to remove a tick?
- Use fine-tipped tweezers or notched tick extractor, and protect your fingers with a tissue, paper towel, or latex gloves. Persons should avoid removing ticks with bare hands.
- Grasp the tick as close to the skin surface as possible and pull upward with steady, even pressure. Do not twist or jerk the tick; this may cause the mouthparts to break off and remain in the skin. (If this happens, remove mouthparts with tweezers. Consult your health care provider if illness occurs.)
- After removing the tick, thoroughly disinfect the bite site and wash your hands with soap and water.
- Do not squeeze, crush, or puncture the body of the tick because its fluids may contain infectious organisms. Skin accidentally exposed to tick fluids can be disinfected with iodine scrub, rubbing alcohol, or water containing detergents.
- Save the tick for identification in case you become ill. This may help your doctor to make an accurate diagnosis. Place the tick in a sealable plastic bag and put it in your freezer. Write the date of the bite on a piece of paper with a pencil and place it in the bag.
Do folklore remedies work?
No. Folklore remedies, such as the use of petroleum jelly or hot matches, do little to encourage a tick to detach from skin. In fact, they may make matters worse by irritating the tick and stimulating it to release additional saliva or regurgitate gut contents, increasing the chances of transmitting the pathogen. These methods of tick removal should be avoided.
Pharmacotherapy
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 lbs]) 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.
Tetracyclines are usually not the preferred drug for use in pregnant women because of risks associated with malformation of teeth and bones in unborn children. Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever; however, this drug may be associated with a wide range of side effects and may require careful monitoring of blood levels.
Prevention
Primary Prevention
Limiting exposure to ticks reduces the likelihood of infection with Rocky Mountain spotted fever. In persons exposed to tick-infested habitats, prompt careful inspection and removal of crawling or attached ticks is an important method of preventing disease. It may take extended attachment time before organisms are transmitted from the tick to the host.
It is unreasonable to assume that a person can completely eliminate activities that may result in tick exposure. Therefore, prevention measures should emphasize personal protection when exposed to natural areas where ticks are present:
- Wear light-colored clothing which allows you to see ticks that are crawling on your clothing.
- Tuck your pants legs into your socks so that ticks cannot crawl up the inside of your pants legs.
- Apply repellents to discourage tick attachment. Repellents containing permethrin can be sprayed on boots and clothing, and will last for several days. Repellents containing DEET (n, n-diethyl-m-toluamide) can be applied to the skin, but will last only a few hours before reapplication is necessary. Use DEET with caution on children. Application of large amounts of DEET on children has been associated with adverse reactions.
- Conduct a body check upon return from potentially tick-infested areas by searching your entire body for ticks. Use a hand-held or full-length mirror to view all parts of your body. Remove any tick you find on your body.
- Parents should check their children for ticks, especially in the hair, when returning from potentially tick-infested areas. *Ticks may also be carried into the household on clothing and pets and only attach later, so both should be examined carefully to exclude ticks.
Secondary Prevention
Tick Control
Strategies to reduce populations of vector ticks through area-wide application of acaricides (chemicals that will kill ticks and mites) and control of tick habitats (e.g., leaf litter and brush) have been effective in small-scale trials. New methods being developed include applying acaricides to animal hosts by using baited tubes, boxes, and feeding stations in areas where these pathogens are endemic. Biological control with fungi, parasitic nematodes, and parasitic wasps may play supportive roles in integrated tick control efforts. Community-based, integrated, tick-management strategies may prove to be an effective public health response to reduce the incidence of tick-borne infections. However, limiting exposure to ticks is currently the most effective method of prevention of tick-transmitted diseases.
History
Rocky Mountain spotted fever was first recognized in 1896 in the Snake River Valley of Idaho and was originally called “black measles” because of the characteristic rash. It was a dreaded and frequently fatal disease that affected hundreds of people in this area. By the early 1900s, the recognized geographic distribution of this disease grew to encompass parts of the United States as far north as Washington and Montana and as far south as California, Arizona, and New Mexico.
Howard T. Ricketts was the first to establish the identity of the infectious organism that causes this disease. He and others characterized the basic epidemiological features of the disease, including the role of tick vectors. Their studies found that Rocky Mountain spotted fever is caused by Rickettsia rickettsii. This species is maintained in nature by a complex cycle involving ticks and mammals; humans are considered to be accidental hosts and are not involved in the natural transmission cycle of this pathogen. Tragically—and ironically—Dr. Ricketts died of typhus (another rickettsial disease) in Mexico in 1910, shortly after completing his remarkable studies on Rocky Mountain spotted fever.
References
http://www.cdc.gov/ncidod/diseases/submenus/sub_rmsf.htm
External links
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Wikimedia Commons has media related to Rocky Mountain spotted fever. |
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- Association of State and Territorial Directors of Health Promotion and Public Health Education
- Centers for Disease Control - Rocky Mountain spotted fever
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