Chapter 4 Tick-borne bacterial zoonoses.
Rickettsioses are infections caused by Rickettsiae in which animals are the hosts and arthropods are the vectors. Rickettsiae are named after Dr. Howard Ricketts (1871-1910), who was the scientist that first identified them and described the transmission of one rickettsial species via its tick vector. Rickettsiae are bacteria with atypical morphology, physiology, and behavior. In general they are small, gram-negative, pleomorphic (cocci or small bacilli) bacteria that are obligate intracellular parasites of eukaryotic cells. Some species that originally were classified in the Rickettsiaceae family have been reassigned to different families. Rickettsia, Orientia, Ehrlichia, Anaplasma, and Neorickettsia are all small obligate intracellular bacteria which were once thought to be part of the same family; however, they are currently considered to be distinct unrelated bacteria. There are several genera in the Rickettsiaceae family including Rickettsia and Orientia and several genera in the Anaplasmataceae family including Anaplasma, Neorickettsia, and Ehrlichia. Typically these bacteria are not transmissible directly from person to person (other than by blood transfusion or organ transplantation); transmission typically occurs via an infected arthropod vector or through exposure to an infected animal reservoir host.
All rickettsioses are zoonoses with the exceptions of epidemic typhus and trench fever in which humans are the hosts and lice are the vectors. Rickettsioses may cause relatively mild disease (rickettsialpox, cat scratch disease, and African tick-bite fever) or they may cause severe disease (epidemic typhus, RMSF, and Oroya fever). They can also vary in duration from those that are self-limiting to chronic or those that recur.
Rickettsiaceae are small bacteria in the family Rickettsiaceae and are fastidious, nonmotile, aerobic, gram-negative, obligate intracellular bacteria that survive only briefly outside the host. They multiply by binary fission intracellularly in host cells. Rickettsiae are among the smallest cells, ranging in size from 0.3 to 0.6 [micro]m wide and from 0.8 to 2.0 [micro]m long. The nutritional requirements of Rickettsiae are based on the host cell because of their inability to metabolize a precursor to the energy producing molecule ATP (adenosine triphosphate). Most Rickettsiae have life cycles that depend on an exchange between blood-sucking arthropod and vertebrate host. Humans are often accidental (dead end) hosts. The mechanism by which Rickettsiae cause disease is not clearly understood; however, most infections target the endothelial lining of small blood vessels.
For years Rickettsiae were believed to be related to viruses because they are very small and can only multiply in living host cells.
Epizootiology and Public Health Significance
Table 4-3 summarizes the distribution of rickettsiosis, which varies with the disease.
The taxonomy of this group of organisms has recently changed and will likely change again.
Rickettsial zoonoses may occur sporadically or endemically. Rarely do they occur in epidemics (such as Q fever as a result of its aerosol transmission). The incidence of rickettsial disease varies, but in general is uncommon in humans (but when they occur can cause serious disease).
Rickettsioses are transmitted by arthropod vectors that vary with the disease. These arthropod vectors feed on the blood or tissue fluid of the vertebrate host. The rickettsial bacterium is transmitted in a variety of ways including through direct inoculation with arthropod saliva, direct inoculation into the skin lesion as they feed, release of the rickettsiae onto the skin or into a wound via the smashing of the vector or the arthropod defecating into the area, or other means (such as fomites, animal products, and food).
A common target in most rickettsioses is the endothelial lining of small blood vessels such as venules and capillaries. Rickettsiae recognize, enter, and multiply in endothelial cells causing necrosis. In an effort to repair the necrotic endothelium, the host responds by proliferating endothelial cells that eventually block the vascular lumen (center of the blood vessel). Pathologic changes such as vasculitis, perivascular infiltration by inflammatory cells, increased vascular permeability resulting in fluid leakage, and thrombosis are common conditions seen with rickettsioses. Specific organ involvement would depend on the blood vessels affected. For example, intravascular clotting of blood cells in vessels supplying blood to the brain results in changes in mentation and other neurologic signs that may occur with some diseases. Target organs of rickettsial diseases include skin, lung tissue, heart, brain, gastrointestinal tract, pancreas, liver, coagulation system, and kidney.
Clinical Signs in Animals
Typically there are not clinical signs of rickettsial infection in animals and animals serve as reservoir hosts of the bacterium.
Clinical Signs in Humans
Clinical signs of rickettsial illnesses vary in humans, but typical early nonspecific signs include fever, headache, and lethargy. Rashes and eschars (black scabs) may be associated with some rickettsioses.
Diagnosis in Animals
Diagnosis of rickettsioses is typically not done in animals.
Diagnosis in Humans
Rickettsioses are diagnosed based on clinical signs, history of arthropod exposure, development of specific acute and convalescent antibody levels reactive for a specific pathogen or antigenic group, a positive result for a serologic test method, such as PCR, IFA, or ELISA test, or isolation of the rickettsial bacterium.
Treatment in Animals
Animals are not routinely treated for rickettsioses.
Treatment in Humans
Treatment of rickettsioses is similar and includes antibiotics (most often doxycycline, tetracycline, or chloramphenicol) and supportive care (antipyretics, analgesics, and fluid therapy). Treatment is initiated based on clinical signs and arthropod exposure prior to obtaining test results.
Management and Control in Animals
The best way to prevent domestic animals from contracting rickettsioses is to limit their exposure to arthropods, particularly ticks. Inspection for ticks and tick removal and the use of topical agents or tick collars are effective methods of tick control. Vaccines that protect against rickettsiosis in the United States are not available (other than Neorickettsia risticii, the agent of equine monocytic ehrlichiosis, more commonly known as Potomac horse fever).
Management and Control in Humans
The best way to prevent humans from contracting rickettsioses is to limit their exposure to arthropods as previously described. There are no commercially licensed vaccines for rickettsioses available in the United States. Vaccinations to prevent rickettsial infections are not required by any country as a condition for entry.
Rickettsioses are infections caused by Rickettsiae in which animals are the hosts and arthropods are the vectors. Rickettsiae are bacteria with atypical morphology, physiology, and behavior and are typically small, gram-negative, pleomorphic bacteria that are obligate intracellular parasites of eukaryotic cells. There are two families of bacteria that cause rickettsioses: Rickettsiaceae (Rickettsia and Orientia) and Anaplasmataceae (Anaplasma, Neorickettsia, and Ehrlichia). Typically these bacteria are transmitted via an infected arthropod vector or through exposure to an infected animal reservoir host.
All rickettsioses are zoonoses with the exceptions of epidemic typhus and trench fever in which humans are the hosts and lice are the vectors. Rickettsioses may range from those that cause relatively mild disease to those that cause severe disease. Typically there are not clinical signs of rickettsial infection in animals and animals serve as reservoir hosts of the bacterium. Clinical signs of rickettsial illnesses vary in humans, but typical early nonspecific signs include fever, headache, and lethargy. Rashes and eschars may be associated with some rickettsioses.
Rickettsioses are diagnosed based on clinical signs, history of arthropod exposure, development of specific acute and convalescent antibody levels reactive for a specific pathogen or antigenic group, a positive result for a serologic test method such as IFA or ELISA testing, isolation of the rickettsial bacterium, or PCR testing. Treatment of rickettsiosis includes antibiotics and supportive care. The best way to prevent domestic animals and humans from contracting rickettsioses is to limit their exposure to arthropods--particularly ticks.
Ehrlichioses and Anaplasmoses are tick-borne diseases caused by small, intracellular bacteria belonging to the Rickettsiaceae family and originally belonging to the Ehrlichia genus. Ehrlichiosis was first described in Algerian (Africa) dogs in 1935 (caused by Ehr. canis). The next outbreak of canine ehrlichiosis was in military guard dogs stationed in Vietnam during the 1960s in which a large number of dogs became ill and died because of hemorrhagic complications of the disease. Ehrlichiosis in humans was first described in 1954 in Japan and was called Sennetsu fever. Sennetsu fever, caused by Ehr. sennetsu, occurs in limited areas of the Far East (primarily Japan) and is extremely rare. Sennetsu fever was the only form of ehrlichiosis known to afflict humans for many years until 1986 when a Detroit man became sick after being exposed to ticks in rural Arkansas. From that time on, cases of human ehrlichiosis have been diagnosed in the United States annually primarily in the southeastern and southcentral states. Originally human cases of ehrlichiosis were attributed to Ehr. canis, but in 1990, the CDC isolated a new species of Ehrlichia from the blood of a U.S. Army reservist training at Fort Chaffee, Arkansas. This new species of Ehrlichia was named Ehr. chaffeensis. In 1956, American C. B. Philip gave the name Ehrlichieae to this family of bacteria, after Paul Ehrlich, who initially described a disease associated with small, gram-negative bacteria known to infect cattle, sheep, goats, and dogs. Ehr. ewingii was named in 1992 after Sidney Ewing, a veterinary pathologist and investigator of ehrlichioses, who found the organism in neutrophils of a febrile dog.
In 2001, the taxonomy of this group changed with some species of Ehrlichia being reclassified into the genera Anaplasma or Neorickettsia. All of these organisms were placed in the Anaplasmataceae family. Anaplasma phagocytophilum now contains the bacteria known as Ehr. equi and Ehr. phagocytophila.
Ehrlichiosis is a term historically used to describe three tick-borne diseases caused by intracellular bacteria of the genus Ehrlichia. Ehrlichiosis was originally named according to the host species and type of white blood cell most often infected. Human monocytic ehrlichiosis (HME) was described in 1986 and is caused by Ehr. chaffeensis; human granulocytic anaplasmosis (HGA), which was formerly known as human granulocytic ehrlichiosis (HGE) was described in 1993 and is caused by Ana. phagocytophilum (formerly Ehr. phagocytophilis); and Ehr. ewingii ehrlichiosis caused by Ehr. ewingii was first described in St. Louis, MO, in 1999. Canine monocytic ehrlichiosis is caused by Ehr. canis and occasionally Ehr. chaffeensis; canine granulocytic ehrlichiosis is caused by Ana. phagocytophilum (formerly Ehr. phagocytophilis) and Ehr. ewingii; equine granulocytic ehrlichiosis is caused by Ana. phagocytophilum; and equine monocytic ehrlichiosis/Potomac horse fever is caused by Neorickettsia risticii (formerly Ehr. risticii). Zoonotic species include Ehr. chaffeensis, Ehr. ewingii, Ana. phagocytophilum, and Neorickettsia sennetsu (Ehr. canis may also be zoonotic, but this is not confirmed).
The family Anaplasmataceae now contains four genera: Ehrlichia, Anaplasma, Neorickettsia, and Wolbachia (found only in arthropods). The zoonotic species of this group of organisms include Ehr. chaffeensis, Ehr. ewingii, Ana. phagocytophilum, and N. sennetsu. Ehr. canis may be zoonotic. The organisms currently believed not to be zoonotic are Ehr. bovis (causes bovine petechial fever in cattle in the Middle East and Africa), Ehr. muris (found in rodents in Japan and does not cause disease), Ehr. ondiri (found in cattle and wild ruminants in Africa), Ehr. ovina (found in sheep in the Middle East), Ehr. ruminantium (causes heartwater disease in ruminants), Ana. platys (causes cyclic canine thrombocytopenia in the United States, Taiwan, Greece, and Israel), and N. risticii (causes Potomac horse fever/equine monocytic ehrlichiosis in the United States). The bacteria in this group of organisms are small, pleomorphic, nonmotile, gram-negative, obligate, intracellular bacilli (they parasitize leukocytes). These bacteria survive only briefly outside the host (reservoir or vector) and only multiply intracellularly (Figure 4-18).
Ana. phagocytophilum contains the organism formerly known as Ehr. equi and Ehr. phagocytophila.
Within a cell, small elementary bodies develop into larger initial bodies and eventually into intracytoplasmic inclusion bodies called morulae (which are diagnostic in blood smears). These organisms do not grow well on routine culture media and are typically cultured in embryonated eggs and in tissue culture.
[FIGURE 4-18 OMITTED]
Epizootiology and Public Health Significance
Ehr. chaffeensis, Ehr. canis, and Ana. phagocytophilum have worldwide distribution. In the United States, Ehr. chaffeensis occurs in more than 30 states (particularly Missouri, Tennessee, Oklahoma, Texas, Arkansas, Virginia, and Georgia). In the United States Ana. phagocytophilum is endemic is Wisconsin, Minnesota, Connecticut, and Massachusetts. Ehr. ewingii has only been found in the southeastern and southcentral United States. N. sennetsu has been reported mainly in Japan, but is probably found in other parts of Asia as well. In some cases, particular diseases are not reported from the bacterium's entire geographic range (for example Ana. phagocytophilum is found worldwide, but only causes tick-borne fever in ruminants in Europe, India, and South Africa).
Approximately 1,200 cases of ehrlichiosis/anaplasmosis were reported in the United States from 1986 to 1997. Human monocytic ehrlichiosis is most commonly seen in the Southeast and Midwest United States; human granulocytic anaplasmosis is most commonly seen in the Northeast and upper Midwest United States. Most cases of ehrlichiosis occur from April to September. Approximately half of all people with human monocytic ehrlichiosis require hospitalization.
About 2% to 3% of human monocytic ehrlichiosis cases, 7% of human granulocytic anaplasmosis cases, and 5% to 10% of Ehr. chaffeensis infections are fatal. Infection with Ehr. ewingii is rare and most people recover without complications. Sennetsu fever is usually a mild illness and is not a significant cause of disease in the United States.
Ehrlichiosis is a tick-borne disease and is transmitted by ticks in the family Ixodidae.
The following bacteria are transmitted by the following hard ticks (Figure 4-19):
* Ehr. chaffeensis is transmitted mainly by Amblyomma americanum (Lone Star tick), but has also been seen in De. variabilis (American dog tick).
* Ana. phagocytophila is transmitted by I. scapularis (the black-legged tick) in the eastern United States, I. pacificus (western United States), and I. ricinus (Europe).
* Ehr. canis is transmitted mainly by Ri. sanguineus (brown dog-tick; refer to Figure 4-1) and also by De. variabilis (American dog tick; refer to Figure 4-2).
* Ehr. ewingii is transmitted by Amb. americanum.
* N. sennetsu has an unknown vector but may be transmitted by consumption of raw fish infested with helminths or by a tick.
Transovarial transmission is not believed to occur with members of the Ehrlichia genus; ticks appear to become infected as larvae or nymphs.
[FIGURE 4-19 OMITTED]
Most cases of ehrlichiosis/anaplasmosis are acquired during the months of highest tick activity, which is typically April to October with maximum activity occurring in June and July.
Transmission can also occur by blood transfusion. Viable bacteria have been found in refrigerated samples at 4[degrees]C for up to a week.
Bacteria that cause ehrlichiosis/anaplasmosis bind to the cell surface of leukocytes (a different leukocyte is preferred by different bacteria) and invade and live in these cells ultimately altering the immune system of the infected animal/person, thereby lessening the body's ability to fight secondary infections. These bacteria live and reproduce in the cytoplasm and are most frequently found clustered together as aggregates of many organisms. These clusters are berry-like in appearance and are called morulae. Little is known about how the infection spreads from the initial tick bite site, what cells or tissues are involved, what causes illness, and how tissue damage occurs.
The ticks that transmit Bo. burgdorferi and Bab. microti also transmit ehrlichiosis.
Clinical Signs in Animals
Ehrlichia infections have been reportable to the CDC since 1998.
The variety of different bacteria in this group can cause a variety of clinical signs in a variety of animals. Ehr. chaffeensis can infect dogs, coyotes, red foxes, deer, goats, and lemurs (causing disease in dogs and lemurs). The reservoir hosts for Ehr. chaffeensis are deer. Ehr. ewingii causes disease in dogs. Dogs may also be the reservoir host. Ehr. canis infects dogs, wolves, and jackals; these animals are also the reservoir hosts. Ana. phagocytophilum causes disease in dogs, horses, llamas, cats, cattle, sheep, goats, and nonhuman primates. Reservoir hosts are deer, elk, and rodents.
Diseases in animals caused by bacteria in this group include:
* Canine monocytic ehrlichiosis. Most cases of canine monocytic ehrlichiosis are caused by Ehr. canis (however, Ehr. chaffeensis infections are possible and are clinically indistinguishable from Ehr. canis) and are reported throughout the year (the tick vector can survive indoors and the disease course is prolonged in dogs). There are three stages of this disease: acute, subclinical, and chronic, which are difficult to differentiate in naturally-infected dogs.
* Acute disease typically lasts for one to four weeks and can display a wide variety of clinical signs ranging from mild to severe with nonspecific signs such as fever, lethargy, anorexia, lymphadenopathy, splenomegaly, and weight loss. Bleeding disorders such as anemia and petechial hemorrhages may be seen. Ocular lesions such as anterior uveitis, oculonasal discharge, corneal opacity, and subretinal hemorrhages may occur. Other signs that may be seen include vomiting, diarrhea, lameness, neurologic signs (ataxia, seizures, and vestibular dysfunction), coughing, and dyspnea.
* Subclinical disease occurs when dogs recover from the acute phase and remain infected for months or years. Dogs with subclinical disease can remain infected without showing clinical signs, may clear the infection, or may progress to the chronic phase.
* Chronic disease presents as chronic weight loss, weakness, fever, peripheral edema, bleeding disorders (pale mucous membranes, petechial hemorrhages, hematuria, and melena), ocular lesions (anterior uveitis, retinal disease, and blindness), arthritis, renal failure, and pneumonia. Neurologic signs such as ataxia, hyperesthesia, head tremors, paresis, and seizures may be seen. Death may occur as a consequence of hemorrhages or secondary infections. Canine monocytic ehrlichiosis is difficult to cure once it has reached the chronic stage.
* Canine granulocytic anaplasmosis (formerly canine granulocytic ehrlichiosis). This disease is caused by the organisms Ana. phagocytophilum and Ehr. ewingii and resembles monocytic ehrlichiosis. The most commonly seen sign with canine granulocytic ehrlichiosis is polyarthritis (it is uncommon with monocytic ehrlichiosis). Moderate to severe anemia has also been seen with this disease process.
* Equine granulocytic ehrlichiosis. Equine granulocytic ehrlichiosis is caused by the organism Ana. phagocytophilum and the disease varies from a mild infection with fever to severe disease. Clinical signs are more severe in older animals and include fever, anorexia, ataxia, jaundice, petechial hemorrhages, and peripheral edema (mainly hind limb). Equine granulocytic ehrlichiosis is most commonly seen in California, with sporadic cases occurring in other states. Most cases are seen in late fall, winter, and spring. Illness is more severe in older horses and animals are immune for at least two years following recovery.
* Equine monocytic ehrlichiosis (Potomac horse fever). Equine monocytic ehrlichiosis is caused by N. risticii and is a serious illness of horses first described in the area around the Potomac River in Maryland in 1979 (it is now recognized throughout the United States and other countries). After the organism is ingested, it multiplies in the intestinal tract, where it can cause marked inflammation. Clinical signs include fever, depression, poor appetite, and diarrhea. Some horses will develop laminitis and pregnant mares can abort.
* Tick-borne fever. Tick-borne fever is seen in domestic and wild ruminants especially sheep and cattle and is caused by the organism Ana. phagocytophilum.
Most ruminants will recover from this disease within 2 weeks, but relapses may occur. Tick-borne fever usually occurs in the spring and early summer when dairy cattle are turned out onto pasture. Impaired immunity seen with this disease will make the animals more susceptible to concurrent infections with some infections persisting for up to 2 years following clinical recovery. After one or two bouts of tick-borne fever sheep and cattle can develop immunity that can last for several months, but will decrease rapidly once the animal is removed from an endemic region. Death is rare.
* Sheep. Tick-borne fever in sheep is mainly seen in young lambs born in tick-infested areas and in newly introduced older sheep. The main clinical sign is sudden fever that lasts for 4 to 10 days; other signs include weight loss, lethargy, coughing, tachypnea, and tachycardia. Pregnant ewes introduced onto infected pastures during the last stages of pregnancy can abort. Abortion is usually seen 2 to 8 days after fever onset. Infected rams may develop reduced sperm quality.
* Cattle. Tick-borne fever is usually seen in dairy cattle turned out onto pasture with animals displaying a variety of clinical signs and severity of signs. Anorexia, decreased milk production, dyspnea, coughing, abortions, and reduced semen quality can be seen with tick-borne fever; abortions resulting in reduced milk yield and respiratory disease are the most common clinical findings in cattle.
* Sennetsu fever. Dogs have been experimentally infected with N. sennetsu developing fever as the only clinical sign. Mice have been experimentally infected with the same organism causing diarrhea, weakness, lymphadenopathy, and death.
* Ehrlichiosis in cats. Documented cases of ehrlichiosis in cats are rare. Cats infected with Ana. phagocytophilum have had clinical signs of fever, anorexia, lethargy, dehydration, and tachycardia.
* Ehrlichiosis in nonhuman primates. Ehr. chaffeensis has caused naturally-occurring infection in captive ring-tailed and red ruffed lemurs. Clinical signs included anorexia, fever, lethargy, and lymphadenopathy.
Clinical Signs in Humans
Human infections with Anaplasmataceae organisms have been reported since the 1950s (N. sennetsu); however, most cases of infection were found in the 1980s (Ehr. chaffeensis, Ehr. ewingii, and Ana. phagocytopyhilum). Ehr. canis has been isolated from only one asymptomatic person.
* Ehrlichiosis in humans consists of the clinically similar diseases human monocytic ehrlichiosis (HME) (Figure 4-20), which affects monocytic cells and is caused by Ehr. chaffeensis; human granulocytic anaplasmosis (HGA) (Figure 4-21), which affects neutrophils and is caused by Ana. phagocytophilum; and Ehr. ewingii ehrlichiosis caused by Ehr. ewingii. Human disease caused by Ehr. ewingii has only been reported in a few immunocompromised patients. Ehrlichiosis in people resembles RMSF (with or without the rash) with clinical signs beginning approximately 7 to 10 days after infection. The rash occurs in 20% to 40% of cases particularly in children and tends to be spotted in nature and is less prominent than that seen in RMSF. The rash can involve the trunk, legs, arms, and face, but usually spares the hands and feet. In people, symptoms vary greatly in severity, ranging from mild infection where no medical attention is needed, to a severe, life-threatening condition. Early symptoms are nonspecific and include high fever, headache, chills, and muscle pain (which mimics the early symptoms of many other tick-borne diseases). Other signs include vomiting, diarrhea, abdominal pain, anorexia, photophobia, conjunctivitis, joint pain, coughing, and mental confusion. Severe symptoms are seen in immunocompromised people and include fever, renal failure, opportunistic infections, hemorrhages, multisystem organ failure, cardiomegaly, seizures, and coma. Complications are more commonly seen in human granulocytic anaplasmosis.
* Sennetsu fever (caused by N. sennetsu) in people is a mild infection resembling mononucleosis. Clinical signs include fever, lethargy, anorexia, lymphadenopathy, hepatosplenomegaly, chills, headache, and backache. Circulating mononuclear cells and atypical lymphocytes are often increased. People with Sennetsu fever rarely have a rash and deaths from this disease have not been reported.
* Ehr. canis may be rarely zoonotic and its zoonotic potential needs to be confirmed.
[FIGURE 4-20 OMITTED]
[FIGURE 4-21 OMITTED]
Diagnosis in Animals
Ehrlichiosis/anaplasmosis in animals can be suspected based on clinical signs and gross pathology. Dogs with canine ehrlichiosis develop nonspecific gross lesions that include splenomegaly, lymphadenopathy, and congested, discolored lungs. Animals may be emaciated, have pale mucous membranes, and hemorrhages of the gastrointestinal tract, heart, urinary bladder, lungs, and eyes. Lymph nodes may be enlarged and discolored. Ascites and edema of the legs may also be seen. Horses with equine granulocytic ehrlichiosis may have petechial hemorrhages, subcutaneous edema, edema of the legs, and interstitial pneumonia. Sheep and cattle with tick-borne fever may abort. Complete blood count (CBC) abnormalities include thrombocytopenia (most common), anemia, and leukopenia. Diagnosis can also be supported by a response to treatment.
Unlike Rickettsiae, Ehrlichiae do not cause vasculitis, but cause multisystem diseases and can be found in many organs by lymphohistolytic (lymphocytes and macrophages) infiltrates (such as gastrointestinal, kidney, hearts, bone marrow, liver, spleen, meninges, and CNS).
Laboratory tests for ehrlichiosis include serology or detection of the organism. Co-infection and cross-reactions may make diagnosis of this disease difficult. Bacterial culture is not used because these organisms can be difficult to culture and can take up to 30 days to grow. Detection of the organism is done by finding morulae in peripheral blood smears or impression smears from fresh tissues stained with Giemsa or by immunofluorescence. The morulae are typically seen in monocytes or granulocytes. Detection of organisms is more useful in cases of equine granulocytic ehrlichiosis than in cases of canine ehrlichiosis. Serologic tests include indirect immunofluroescent antibody tests (equine granulocytic ehrlichiosis, canine ehrlichiosis/anaplasmosis, and tick-borne fever), ELISA tests (canine monocytic ehrlichiosis and canine granulocytic anaplasmosis), and immunoblotting techniques such as Western blotting (research use). Disease is usually confirmed by the presence of rising antibody titers; in dogs, a single positive titer is evidence of exposure. PCR assays that detect antigens in blood are available for equine ehrlichiosis and may become available for canine ehrlichiosis/anaplasmosis.
Diagnosis in Humans
Diagnosis in people is based on history, clinical signs, and abnormalities on blood work (CBC and serum chemistry panels). Bacterial culture is difficult and time-consuming (Ana. phagocytophilum and Ehr. chaffeensis have been isolated from the blood of acutely ill people using various cell lines). Detection of the organism can be done by finding morulae in neutrophils or mononuclear cells. Disease confirmation is done through serologic testing which consists of indirect immunofluorescence assay (human monocytic ehrlichiosis or human granulocytic anaplasmosis and Sennetsu fever). The current case definition by the CDC for human ehrlichiosis/anaplasmosis is a fourfold rise or fall in antibody titer. ELISA tests are being developed for ehrlichiosis. PCR testing is available; immunohistochemistry and in situ hybridization has been done on tissue samples such as the spleen and lymph nodes.
Treatment in Animals
Ehrlichiosis/anaplasmosis is treated with tetracycline antibiotics. Early treatment of equine granulocytic ehrlichiosis and tick-borne fever are usually effective. Early treatment is critical for canine ehrlichiosis and uncomplicated cases respond well. Treatment of the chronic severe form in dogs is difficult and may require combination therapies (glucocorticoids, chemotherapy drugs such as vincristine, and hematopoietic growth factors).
Treatment in Humans
Treatment of ehrlichiosis/anaplasmosis in humans involves the use of tetracycline antibiotics; the current drug of choice is doxycycline. Early treatment is critical and prolonged treatment may be needed for severe or complicated cases.
Management and Control in Animals
The best way to prevent dogs from contracting ehrlichiosis is to limit their tick exposure. Dogs should be inspected daily for ticks and any ticks that are found should be removed quickly and safely with a gloved hand. Topical agents (such as fiprinol or permethrin) and tick collars containing amitraz are effective methods of tick control.
Vaccines are not available for canine ehrlichiosis, equine granulocytic ehrlichiosis, or tick-borne fever. There is a vaccine for equine monocytic ehrlichiosis (Potomac horse fever). Prophylactic antibiotics are sometimes used to prevent tick-borne fever in ruminants.
Management and Control in Humans
The best way to prevent ehrlichiosis or anaplasmosis in people also includes tick control. Strategies to reduce ticks include area-wide application of acaricides (chemicals that will kill ticks and mites), application of tick repellent with DEET, and control of tick habitats. Prompt removal of ticks is also essential. Tick control has been covered in the tick biology section and should be referred to. There is no vaccine for ehrlichiosis.
Ehrlichiosis and anaplasmosis are tick-borne diseases that are transmitted by ticks in the family Ixodidae. The various types of ehrlichioses/anaplasmosis are named according to their host species and white blood cell type infected. Human monocytic ehrlichiosis is caused by Ehr. chaffeensis; human granulocytic anaplasmosis is caused by Ana. phagocytophilum; and Ehr. ewingii ehrlichiosis is caused by Ehr. ewingii. Canine monocytic ehrlichiosis is caused by Ehr. canis and occasionally Ehr. chaffeensis; canine granulocytic ehrlichiosis is caused by Ana. phagocytophilum and Ehr. ewingii; equine granulocytic ehrlichiosis is caused by Ana. phagocytophilum; equine monocytic ehrlichiosis/Potomac horse fever is caused by N. risticii; tick-borne fever is caused by Ana. phagocytophilum; Sennetsu fever is caused by N. sennetsu; ehrlichiosis in cats is caused by Ana. phagocytophilum, and ehrlichiosis in nonhuman primates is caused by Ehr. chaffeensis. Zoonotic species include Ehr. chaffeensis, Ehr. ewingii, Ana. phagocytophilum, and N. sennetsu (Ehr. canis has been zoonotic, but this is not confirmed). The bacteria in this group of organisms are small, pleomorphic, nonmotile, gram-negative, obligate, intracellular bacilli (they parasitize leukocytes). These bacteria survive only briefly outside the host (reservoir or vector) and only multiply intracellularly. Ehr. chaffeensis, Ehr. canis, and Ana. phagocytophilum have worldwide distribution. Ehr. ewingii has only been found in the southeastern and southcentral United States. N. sennetsu has been reported mainly in Japan, but is probably found in other parts of Asia as well. Laboratory tests for ehrlichiosis or anaplasmosis in animals and people include serology or detection of the organism. Bacterial culture is not used because these organisms can be difficult to culture and can take up to 30 days to grow. Detection of the organism is done by finding morulae in peripheral blood smears or impression smears from fresh tissues stained with Giemsa or by immunofluorescence. Serologic tests in animals include indirect immunofluroescent antibody tests (equine granulocytic ehrlichiosis, canine ehrlichiosis/anaplasmosis, and tick-borne fever), ELISA tests (canine monocytic ehrlichiosis and canine granulocytic anaplasmosis), immunoblotting techniques such as Western blotting (research use). PCR assays that detect antigens in blood are available for some types of ehrlichiosis. Human monocytic ehrlichiosis and human granulocytic anaplasmosis are diagnosed by a fourfold rise or fall in antibody titer via immunofluorescence assay. Ehrlichiosis/anaplasmosis are treated with tetracycline antibiotics in both animals and people. The best way to prevent contracting ehrlichiosis/anaplasmosis is to limit tick exposure.
Ticks that are removed from animals people should be kept frozen in a plastic bag for identification in case of illness.
Q fever, also known as query fever, was first described in 1935 in Australia by Dr. Edward Derrick who was investigating abattoir fever in a group of 800 Brisbane slaughterhouse workers who had symptoms of fever, headache, shivers, and sweats. He called the disease query fever because its causative agent was unknown. In 1936, Drs. Burnet and Freeman successfully identified rickettsial bacteria as the infectious agent of Q fever based on agglutination of infected animal tissues with convalescent sera obtained from Q fever patients. Dr. Derrick named the organism Rickettsia burnetti in honor of Dr. Burnet. In the United States around the same time period, scientists at the Rocky Mountain Laboratory in Montana were conducting research on the Nine Mile agent, a microbe transmitted by ticks. Dr. Herald Rae Cox is credited with identifying the "nine mile agent" as a rickettsial bacterium. In the United States, Dr. Cox called the organism Ri. diaporica in recognition of its ability to pass through filters used in those times to distinguish between bacteria (impermeable) and viruses (permeable). The bacterium has since been reclassified placing it genus on its own called Coxiella, within the family of Legionellaceae. The bacterium's name, Coxiella burnetii, honors the contributions of both Dr. Burnet and Dr. Cox.
Q fever has been known as abattoir fever (because of the epidemic among
slaughterhouse workers), Balkan grippe (because of the epidemic among soldiers in the Balkans), and goat boat fever (because the disease commonly occurred among boat crews transporting infected goats). Allied forces experienced Q fever outbreaks in Italy and other Mediterranean countries during World War II.
Explosive outbreaks of Q fever occurred in slaughterhouses in Texas and Chicago in the 1940s and the disease is still recognized as an occupational hazard among slaughterhouse workers.
Cox. burnetii can survive for months and even years in dust or soil.
Cox. burnetii is a small, aerobic, gram-negative coccobacillus that is an obligate intracellular parasite in eukaryotic cells; however, unlike other rickettsial bacteria it multiplies in the acidic environment of phagosomes. Cox. burnetii forms an internal, stable, resistant infective body (sometimes called a spore) that is similar in structure and function to an endospore of some gram-positive bacilli. This infective body allows the bacterium to survive harsh environmental conditions. Cox. burnetii exists in two antigenic states: phase I (the virulent form which is also known as the smooth phase) and phase II (the avirulent form which is also known as the rough phase). The different states relate to its cell coating (changes in lipopolysaccharides) and antigenic, pathogenic, and immunogenic properties. Phase I bacteria possess a full complement of lipopolysaccharides, whereas phase II bacteria posses a simpler structure. The phase I bacterium is the form isolated from animals and is highly infectious; the phase II bacterium is isolated in cultured cell lines and is not infectious.
Epizootiology and Public Health Significance
Cox. burnetii does not replicate in bacteriologic culture media.
Cox. burnetii is distributed worldwide except in New Zealand. It has been found in various wild and domestic mammals, arthropods, and birds. Domestic cattle, sheep, goats, dogs, and cats are susceptible to infection, and the disease is found in most areas where these animals are kept. Both Ixodidae (hard) and Argasidae (soft) ticks can be reservoirs of the organism with greater than 40 species of ticks serving as natural reservoirs that remain infected throughout life and can transmit the bacterium transovarially. Infected animals shed this bacterium in urine, feces, reproductive tissues/fluid, and milk.
In 1999, Q fever became a notifiable disease in many U.S. states but reporting is not required in many other countries. In the United States Q fever is a reportable disease in all states except Delaware, Iowa, Oklahoma, Vermont, and West Virginia. In 2001, 26 cases of Q fever were reported to the CDC and in 2002, 61 cases of Q fever were reported to the CDC (0.05 per 100,000 people). The incidence of Q fever worldwide varies in frequency and presentation from country to country.
The mortality rate with acute Q fever is reportedly as high as 2.4%. People at greatest risk for infection are veterinarians, farmers, sheep and dairy workers, and laboratory workers who work with this organism.
Cox. burnetii is transmitted via inhalation, direct or indirect contact with infected animals, or direct or indirect contact with their dried excretions. People typically contract Q fever by inhaling contaminated droplets of the highly infectious phase I spore forms excreted by infected animals. Consumption of raw milk has also been associated with infection. Infected ruminants can shed Cox. burnetii in their milk and amniotic fluid, and animals or humans can be infected by inhaling aerosols from the amniotic fluid or from unpasteurized infected milk. Pregnancy stimulates the replication of bacteria in reproductive and mammary gland tissues of many mammals. The amniotic fluid of infected animals carries high numbers of bacteria and is particularly dangerous. Person-to-person transmission is extremely rare. As a result of its inhalational route of transmission, it can be used as a biological agent and is classified as a category B agent.
The most important transmission route from domestic ruminants to humans is through airborne transmission of particles from reproductive fluids.
Transmission occurs among wild and domestic animals by the bites of ticks (humans are not typically infected by tick bites, although it may be possible). Animal-to-animal transmission can also be through airborne particles or direct contact and ingestion of reproductive tissues/fluids or milk.
Once inside the body, Cox. burnetii is phagocytized by host cells and replicates within vacuoles. The incubation period varies from 9 to 40 days (average 18 to 21 days) during which time bacteria proliferate in the lungs, are engulfed by macrophages, and are transported to the lymph nodes. From the lymph nodes bacteria are carried to the bloodstream where they reach many areas of the body.
As few as ten Cox. burnetii can initiate infection.
Clinical Signs in Animals
Goats, sheep, and cattle are the primary domestic reservoirs of Cox. burnetii (Figure 4-22). Inapparent infection is typical in these animals since clinical signs of infection rarely develop in infected livestock. If the infected animal is pregnant, abortion sometimes results. Occasionally an abortion storm (series of abortions) occurs when Q fever passes through a previously uninfected flock or herd. If a flock or herd is infected, most animals in the group will be infected.
[FIGURE 4-22 OMITTED]
Clinical Signs in Humans
In people, Q fever can present as an inapparent, acute, or chronic disease.
* Inapparent Q fever is seen in about half of the people infected with Cox. burnetii and these people do not show any clinical signs.
* Acute Q fever is a generalized disease that presents like influenza. The incubation period is 2 to 4 weeks (average is 20 days). Clinical signs include sudden fever, chills, lethargy, muscle and joint pain, headache, and photophobia. This flu-like syndrome is usually self-limiting and lasts up to three weeks. Pneumonia can occur in about one third of people. Hepatitis can also occur alone or concurrently with pneumonia. Less common features of acute Q fever include rashes, meningitis, myocarditis, and pericarditis.
* Chronic Q fever develops in individuals who have been infected for over 6 months without effective treatment. Its main feature is endocarditis and/or chronic hepatitis. Clinical signs include prolonged fever, night sweats, chills, fatigue, and shortness of breath.
Diagnosis in Animals
Necropsy lesions in animals with Q fever are nonspecific and of little value in diagnosing the disease. Cox. burnetii cannot be cultured using current bacteriologic media. Serologic testing is the diagnostic tool of choice with complement fixation, IFA, and ELISA tests available.
Diagnosis in Humans
In people, Q fever is confirmed by serology using IFA (most widely used). Immunohistochemical staining methods and PCR tests are also available. Because Cox. burnetii exists in two antigenic phases, assessing both phase I and phase II levels are important in diagnosis; therefore, baseline and 3- to 4-week samples are taken for analysis. In acute Q fever, the antibody level to phase II is usually higher than phase I and is generally first detectable during the second week of illness. A fourfold rise in complement-fixing antibodies against phase II antigen confirms acute Q fever. In acute Q fever, patients will have IgG antibodies to phase II and IgM antibodies to phases I and II. In chronic Q fever, high levels of antibody to phase I in combination with constant or falling levels of phase II antibodies are found. Antibodies to both phase I and II antigens have been shown to last for months or years after initial infection. Increased IgG and IgA antibodies to phase I are often indicative of chronic Q fever.
Treatment in Animals
In animals, tetracycline antibiotic treatment is effective for treating Q fever. Separation of pregnant animals and burning or burying infective reproductive tissues/ fluids can reduce the spread of bacteria. Resistance to physical and chemical agents makes ridding the environment of Cox. burnetii difficult. Recommended disinfectants include a formulation of two quaternary ammonium compounds, 70% ethanol, and 1:10 bleach solution.
Antibodies to phase I antigens generally take longer to appear and indicate continued exposure to Cox. burnetii.
Treatment in Humans
Antibiotics are used to treat both acute and chronic Q fever. The most common treatment is doxycycline for acute Q fever and combinations of doxycycline plus an additional antibiotic such as fluoroquinolone, rifampin, or trimethoprimsulfamethoxazole for chronic Q fever. Chronic Q fever antibiotic treatment is recommended for 3 years. Disinfection of contaminated areas is also important.
Management and Control in Animals
There is not a vaccine to protect animals from acquiring Cox. burnetii. Proper hygiene, especially around birthing animals, is important in preventing animal-toanimal spread of disease.
Management and Control in Humans
A formalin inactivated phase I whole cell vaccine is licensed in Australia and Eastern Europe (a single dose provides greater than 95% protection against naturally occurring Q fever within 3 weeks and lasts for at least 5 years). A live attenuated vaccine (Strain M44) has been used in the former USSR. In the United States, a noncommercial inactivated vaccine is available for at risk laboratory personnel through the U.S. Army Medical Research Institute. Standard precautions are recommended for health care workers taking care of patients with suspicion or diagnosis of Q fever.
CDC recommendations for preventing Q fever include:
* Disposing appropriately of the placenta, birth products, fetal membranes, and aborted fetuses at facilities housing sheep and goats.
* Restricting access to barns and laboratories used in housing potentially infected animals.
* Using only pasteurized milk and milk products.
* Using appropriate procedures for bagging, autoclaving, and washing of laboratory clothing.
* Vaccinating (where possible) individuals engaged in research involving pregnant sheep or live Cox. burnetii.
* Quarantining imported animals.
* Ensuring that sheep holding facilities are located away from populated areas. Animals should be routinely tested for antibodies to Cox. burnetii, and measures should be implemented to prevent airflow to other occupied areas.
* Counseling persons at highest risk for developing chronic Q fever, especially persons with pre-existing cardiac valvular disease or individuals with vascular grafts.
Q fever is an infection caused by the bacterium Cox. burnetii, a small, aerobic, gram-negative coccobacillus that is an obligate intracellular parasite in eukaryotic cells. Cox. burnetii forms an internal, stable, resistant infective body that allows the bacterium to survive harsh environmental conditions. Cox. burnetii exists in two antigenic states: the highly infectious phase I (the virulent form which is also known as the smooth phase) and the noninfectious phase II (the avirulent form which is also known as the rough phase). Cox. burnetii does not replicate in bacteriologic culture media.
Cattle, sheep, and goats are the primary reservoirs of Cox. burnetii. Clinical disease is rare in these animals, although abortion in pregnant ruminants may occur. Organisms are excreted in milk, urine, and feces of infected animal; and high numbers of bacteria are shed in amniotic fluids and the placenta. Infection of humans usually occurs by inhalation of these organisms from air that contains airborne particles contaminated by infected animals. Ingestion of contaminated milk is a less common mode of transmission. In people Q fever can cause flu-like signs, pneumona, and hepatitis in its early form, and endocarditis in its chronic form. Q fever is diagnosed by serology and treated with antibiotics such as doxycycline. In the United States, Q fever outbreaks have resulted mainly from occupational exposure involving veterinarians, slaughterhouse workers, sheep and dairy workers, livestock farmers, and laboratory workers. Prevention and control efforts should be directed primarily toward these groups and environments.
ROCKY MOUNTAIN SPOTTED FEVER
Rocky Mountain spotted fever (RMSF), originally known as black measles because of its characteristic rash and referred to as tick typhus outside the United States, is the most important rickettsiosis in the western hemisphere. RMSF is one of the spotted fevers, a large group of arthropod-borne infections caused by closely related Rickettsiae bacteria. Rickettsiae are small, gram-negative, pleomorphic (cocci or small bacilli) bacteria that are obligate intracellular parasites of eukaryotic cells. Rickettsioses are rickettsial infections in which mammals are the hosts and arthropods are the vectors.
RMSF was first recognized in 1896 in Idaho as a frequently fatal disease affecting hundreds of people in the Snake River Valley area. Outbreaks of RMSF spread rapidly and by the early 1900s, its geographic distribution in the United States went as far north as Washington and Montana and as far south as California, Arizona, and New Mexico. In response to its rapid spread and severity of clinical signs, the Rocky Mountain Laboratory was established in Hamilton, Montana (it is currently part of the National Institute of Allergy and Infectious Diseases, National Institutes of Health).
RMSF is caused by the bacterium Rickettsia rickettsii, named after Dr. Howard T. Ricketts, the first person to identify the infectious organism causing this disease in blood smears of infected animals and humans. Ricketts and his researchers also identified the cycle of infection involving ticks and mammals with humans considered accidental hosts and not a critical component in the natural transmission cycle of Ri. rickettsii. In 1910 after completing his work on RMSF, Ricketts died of typhus, a different rickettsial disease.
In the 1930s, it became clear that RMSF occurred in many areas of the United States other than the Rocky Mountain region. This vast distribution is a result of the ticks that serve as vector and reservoir of the disease: Dermacentor variabilis (commonly known as the American dog tick) in the eastern United States and Dermacentor andersoni (commonly known as the Rocky Mountain wood tick) in the western United States. The majority of RMSF cases are currently concentrated in the southeast and eastern seaboard regions of the United States as well as southern Canada, Central America, Mexico, and parts of South America.
RMSF is caused by Ri. rickettsii, a small bacterium in the family Rickettsiaceae (which consists of genera: Rickettsia and Orientia). Rickettsiae are fastidious, nonmotile, aerobic, gram-negative, obligate intracellular bacteria that survive only briefly outside the host. They only multiply intracellularly in the cytoplasm of host cells. Rickettsiae have cell walls consisting of small amounts of peptidoglycan (making them seem as though they lack a cell wall) and an outer lipopolysaccharide membrane that has little endotoxin activity. The bacterium is surrounded by a loosely organized slime layer causing them not to react well to Gram stain; hence they stain a pale pink. This slime layer is believed to play a role in transmission. Tick feeding results in growth of the slime layer (called reactivation) and is believed to attribute to the bacterium's virulence. To better visualize these bacteria Giemsa stain is routinely used. Rickettsiae consist of three groups of bacteria: the spotted fever group, the typhus group, and the scrub typhus group. More than 20 species of Rickettsia are known and not all of them cause disease.
Over 90% of RMSF infections occur between April and September when increased numbers of adult and nymphal Dermacentor ticks are seen. Infection can occur during winter in warmer regions such as Central and South America.
Epizootiology and Public Health Significance
The distribution of Rickettsiae is limited to the geographic region of their arthropod hosts. RMSF was originally found in the western United States; however, in the last 100 years there has been a shift to the eastern United States with the occurrence of disease highest in the south-Atlantic region (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, such as the Pacific region (Washington, Oregon, and California) and west south-central region (Arkansas, Louisiana, Oklahoma, and Texas). The states with the highest incidences of RMSF are North Carolina and Oklahoma.
Ri. rickettsii infection has also been reported in Argentina, Brazil (called Sao Paulo fever and fiebre maculosa), Colombia (called Tobia fever), Costa Rica, Mexico (called fiebre manchada), and Panama. RMSF does not exist in Europe, Africa, or Asia.
RMSF has been a reportable disease in the United States since the 1920s. Approximately 600 to 800 cases of RMSF are reported annually in the United States, although many cases go unreported. RMSF is highest among males, Caucasians, and children with two-thirds of the cases occurring in children younger than 15 years of age (peak age being 5 to 9 years old). People with frequent exposure to dogs and who reside near wooded areas or areas with high grass are at increased risk of infection. Seasonal outbreaks parallel tick activity with 90% of cases reported from April 1 to September 30 (peaks seen in May and June). Human RMSF mortality rates are approximately 4%, with death usually occurring 8 days after onset of symptoms.
In general, about 1% to 3% of the tick population carries Ri. rickettsii making the risk of exposure low even in areas where the majority of human cases are reported.
Ri. rickettsii bacteria typically infect and are transmitted by Ixodidae (hard) ticks. Ri. rickettsii is most frequently transmitted to a vertebrate host through saliva while the tick feeds. It usually takes several hours (between 6 and 10) of attachment and feeding before Ri. rickettsii is transmitted to the host. After an immature tick develops into the next stage, Ri. rickettsii may be transmitted to a second host during the feeding process. This bacterium may also be transmitted to a vertebrae host through contact with infected tick hemolymph or excrement when engorged ticks are crushed.
There are two major Ixodidae tick vectors of Ri. rickettsii in the United States: Dermacentor variabilis and De. andersoni. De. variabilis is found east of the Rocky Mountains and in limited areas on the Pacific Coast (Figure 4-23 and Figure 4-2). Dogs and medium-sized mammals are the preferred hosts of adult De. variabilis ticks. De. variabilis also feeds on other large mammals (including humans) and is the tick most commonly responsible for transmitting Ri. rickettsii to humans. De. andersoni is found in the Rocky Mountain states and in southwestern Canada. Adult ticks feed primarily on large animals, whereas larvae and nymphs feed on small rodents. The life cycle of this tick may require up to 2 to 3 years for completion.
[FIGURE 4-23 OMITTED]
The ticks Rhipicephalus sanguineus (in Mexico) (Figure 4-1) and Amblyomma cajennense (in Central and South America) have been shown to be naturally and experimentally infected with Ri. rickettsii. Although these species play only a minor role in the transmission of Ri. rickettsii in the United States, they are important vectors of RMSF in Central and South America.
Ticks become infected with Ri. rickettsii by two methods. One way ticks acquire the bacterium is by feeding on infective small mammals reservoirs such as chipmunks and squirrels. Dogs and humans may also serve as reservoirs for RMSF; however, they are incidental hosts and are the only reservoirs that show clinical signs. The larva and nymph forms of Dermacentor ticks feed on small mammals, whereas the adult ticks feed on larger mammalian hosts. Larger mammals rarely achieve the level of organisms in blood necessary to transmit disease to a feeding tick; therefore, it is the larva and nymph stages that are frequently infected with Ri. rickettsii during feeding on small mammals.
The second way ticks can become infected with Ri. rickettsii is via other ticks. Transstadial spread of RMSF occurs through the transfer of bodily fluids or spermatozoa during mating from one tick to another. Transovarial spread of RMSF occurs from the pregnant female tick to her eggs. Transovarial infection is the primary means by which Ri. rickettsii is spread in nature.
Ri. rickettsii enter the skin typically through a tick bite and undergoes a 3- to 14-day (usually 7 day) incubation period in which the organism replicates. Following the incubation period, bacteria spread via lymphatics to the bloodstream and attach to endothelial cells of venules and capillaries and begin replicating. This bacterial replication causes vasculitis and increased vascular permeability. Fluid moves to the interstitial spaces leading to edema (typically in the extremities including the scrotum, prepuce, and ears), hemorrhage, hypovolemia, shock, and vascular collapse. Severity of the vasculitis can be directly correlated to the infective dose. Vascular endothelial damage contributes to development of petechiae and ecchymotic hemorrhages as a result of the destruction of platelets in response to vasculitis. Petechial hemorrhages are often seen on exposed mucosal surfaces in the dog. Organ damage, secondary to vascular collapse, is common in the brain, skin, heart, and kidneys. Vascular leakage also triggers activation of the animal's platelets and coagulation system. In skin, vascular injury initially appears as erythematous (red) macules that are usually 1 to 5 mm in diameter and progress to the classic petechial rash of RMSF. Because of damage to the vascular system RMSF is a multisystem disease.
Once infected, a tick can carry Ri. rickettsii for life.
Clinical Signs in Animals
Ri. rickettsii causes disease in dogs. RMSF, also known as tick fever in dogs, is usually seen in dogs younger than 3 years old with a recent history of exposure to ticks or their habitat. RMSF is usually reported in dogs between the months of March and October when there is an increased prevalence of ticks in the environment. Early signs may include fever (up to 105[degrees]F), anorexia, lymphadenopathy, polyarthritis, coughing or dyspnea, abdominal pain, and edema of the face or extremities. In severe cases petechial hemorrhages may be seen on the mucous membranes. Neurologic signs, such as altered mental states, vestibular dysfunction, and hyperesthesia, are commonly seen with RMSF. Focal retinal hemorrhage is usually seen in the early stages of this disease.
Dogs are susceptible to RMSF and serve as excellent sentinels of the disease.
Clinical Signs in Humans
RMSF in humans typically presents with three classic signs: fever, rash, and history of tick bite. Initial clincial signs may include fever, nausea, vomiting, severe headache, muscle pain, and lack of appetite. The rash appears 2 to 5 days after the onset of fever and is often very subtle appearing as small, flat, pink, nonitchy macules (spots) on the wrists, forearms, and ankles (Figure 4-24). These macules turn pale when pressure is applied and eventually become raised on the skin. Younger people usually develop the rash earlier than older people. Clinical signs that appear later in the disease include rash, abdominal pain, joint pain, and diarrhea. The classic red, petechial rash of RMSF is usually not seen until the sixth day or later after disease onset and occurs in only 40% to 60% of patients. The rash usually involves the palms or soles.
[FIGURE 4-24 OMITTED]
Diagnosis in Animals
Laboratory abnormalities seen in dogs with RMSF include thrombocytopenia (platelet counts ranging from 23,000 to 220,000/[micro]l); a moderate leukocytosis with a mild left shift (a mild leucopenia occurs early in infection); normocytic, normochromic anemia; azotemia, elevated glucose, cholesterol, alkaline phosphatase (ALP) and alanine aminotransferase (ALT); and hyponatremia, hypocalcemia, and hypoalbuminemia (secondary to vasculitis). Definitive diagnosis of RMSF is through IFA serologic testing along with clinical signs. IFA can be used to detect either IgG or IgM antibodies. Blood samples taken early (known as the acute sample) and late (known as the convalescent sample) in the disease are the preferred specimens for evaluation. IgG antibody titers to Ri. rickettsii that increase or decrease fourfold are considered diagnostic for RMSF but may not be clinically useful because IgG antibody concentration does not increase until 2 to 3 weeks postinfection. A single high IgG titer (> 1024) is suggestive of exposure within the last tick season, whereas a single positive IgM titer (> 8) indicates a more recent exposure. Positive IgG titers may persist for 3 to 10 months following infection; however, positive IgM titers normally decrease after 4 weeks. Cross-reactivity to other spotted fever Rickettsiae exist and may affect test interpretation.
Diagnosis in Humans
Laboratory abnormalities suggestive of RMSF in humans may include abnormal white blood cell counts, thrombocytopenia, hyponatremia, or elevated liver enzyme levels. Serologic assays are most frequently used for confirming cases of RMSF, which include IFA, ELISA, latex agglutination, and immunoassays. In humans increased IgM titers appear by the end of the first week of illness and diagnostic levels of IgG antibody do not appear until 7 to 10 days after the onset of illness. The most rapid and specific diagnostic assays are PCR tests, which can detect DNA present in as few as 5 to 10 bacteria in a sample. PCR testing is done on fresh skin biopsies or fixed or unfixed tissues samples. Diagnosis can be confirmed by isolation of Ri. rickettsii from clinical samples such as whole blood and biopsies. Isolation may require several weeks and samples should be shipped unfrozen or frozen and on dry ice to the CDC. Immunostaining is another method used to identify Ri. rickettsii from a skin biopsy of the rash from an infected person prior to therapy, but may not always detect the bacterium as a result of its focally distributed lesions.
Treatment in Animals
In dogs, antibiotic treatment is initiated immediately after samples are taken for laboratory testing to reduce the disease signs. Tetracycle or doxycycline is the treatment of choice with chloramphenicol recommended in pregnant bitches and puppies younger than 6 months of age to avoid dental staining in growing fetuses/ puppies. Supportive care should be considered along with antibiotic administration; however, fluid therapy should be administered conservatively as a result of the vasculitis and potential for pulmonary and cerebral edema. Mild ocular lesions should resolve with systemic antibiotic therapy and the use of topical corticosteroids may help conditions such as uveitis. Dogs that have recovered from RMSF have protective immunity to further reinfection.
Treatment in Humans
Treatment of RMSF in humans involves the use of antibiotics such as doxycycline for at least 3 days after fever subsides. Tetracycline and chloramphenicol are alternative antibiotics used to treat RMSF; however, they are associated with side effects that limit their use.
Management and Control in Animals
The best way to prevent dogs from contracting RMSF is to limit their tick exposure particularly between the months of March through October. Dogs should be inspected daily for ticks and any ticks that are found should be removed quickly and safely with a gloved hand. Topical agents (such as fiprinol or permethrin) and tick collars containing amitraz are effective methods of tick control. There is not a vaccine for protection against Ri. rickettsii.
Management and Control in Humans
The best way to prevent RMSF in people also includes tick control. Strategies to reduce ticks include area-wide application of acaricides (chemicals that will kill ticks and mites), application of tick repellent with DEET, and control of tick habitats. Prompt removal of ticks is also essential. Tick control has been covered in a previous section and should be referred to.
RMSF is a clinical disease of humans and dogs (with small mammals occasionally infected) that is caused by Ri. rickettsii. Ri. rickettsii is a small, gram-negative bacterium that is spread to humans and dogs by the Ixodidae ticks De. andersoni and De. variabilis. Clinical signs in dogs include fever, anorexia, lymphadenopathy, polyarthritis, coughing or dyspnea, abdominal pain, edema of the face or extremities, petechial hemorrhages, neurologic signs, and retinal hemorrhage. Clinical signs in people include 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. RMSF is a seasonal disease and occurs throughout the United States during the months of April through September (peak tick times are March to October). Most of the cases occur in the south-Atlantic region of the United States (Delaware, Maryland, Washington D.C., Virginia, West Virginia, North Carolina, South Carolina, Georgia, and Florida) and the highest incidence rates have been found in North Carolina and Oklahoma. RMSF is diagnosed based on clinical signs and serologic testing such as IFA. Treatment involves the use of antibiotics such as doxycycline. Once a person or dog clears the infection it is believed that they have long lasting immunity to Ri. rickettsii. The disease is prevented by controlling ticks.
1. The tick-borne disease that manifests initially as erythema migrans and later as chronic arthritis is
a. Rocky Mountain spotted fever.
b. Lyme disease.
c. relapsing fever.
2. What is not a characteristic of the Rickettsiae
a. obligate intracellular organisms.
b. transmitted by arthropods.
c. gram-negative, pleomorphic bacilli.
d. multiply extracellularly.
3. What disease can be transmitted by aerosol inhalation?
a. Q fever
c. Rocky Mountain spotted fever
d. Lyme disease
4. A 19-year-old female is admitted to a local hospital with fever, chills, headache, and a rash on her palms and soles. The woman states that she has recently been bitten by a tick. The physician has ruled out babesiosis and Lyme disease based on laboratory tests. The probable cause of her symptoms is infection with
a. Coxiella burnetii.
b. Rickettsia rickettsii.
c. Ehrlichia canis.
d. Borrelia burgdorferi.
5. What is false regarding ticks?
a. They have long life cycles.
b. They consume large volumes of blood.
c. They produce large numbers of eggs.
d. They have three body regions: capitulum, idiosoma, and scutum.
6. All ticks undergo which basic stages?
a. egg, larva, nymph, adult
b. egg, nymph, adult
c. egg, larva, adult
d. egg, larva, nymph, instar
7. The process by which ticks crawl up a piece of grass or perch on leaf edges with their front legs extended is called
8. Transfer of an infectious agent from one tick life stage through molting to the next stage is called
a. horizontal transmission.
b. vertical transmission.
c. transovarial transmission.
d. transstadial transmission.
9. A common target in most rickettsioses is the
b. nervous system.
c. endothelial lining of small blood vessels.
d. lymphatic channels.
10. Bacteria that cause ehrlichiosis bind to and are named for the type of cell they infect. These cells are
Matching 11. --Rocky Mountain A. Argasidae spotted fever 12. --Q fever B. Francisella tularensis 13. --Lyme disease C. Rickettsia rickettsii 14. --TBRF (endemic D. Anaplasma phagocytophilum relapsing fever) 15. --LBRF (epidemic E. Ehrlichia chaffeensis relapsing fever) 16. --Tularemia F. Coxiella burnetii 17. --HME G. Borrelia recurrentis 18. --HGA H. Ixodidae 19. --hard tick I. Borrelia hermsi 20. --soft tick J. Borrelia burgdorferi
21. A 41-year-old man was admitted to the hospital complaining of severe headache, moderate fever, chest pain, and a productive cough. Swollen lymph nodes and a tender, enlarged liver were noted on the examination. This man is a professional furrier and trapper and had recently returned from an excursion on which he had trapped and skinned approximately 50 rabbits. Routine sputum and blood cultures were collected and revealed very faintly staining gram-negative bacilli on Gram stain and no growth on routine bacteriological media (blood agar and MacConkey) after 72 hours. After 6 days, growth was observed on chocolate agar plates.
a. Given this person's history and symptoms, what disease might he have?
b. What organism causes this disease?
c. Why did the organism grow on chocolate agar (what chemical does this organism need for growth)?
d. What special precautions need to be taken when handling this organism?
22. Almost 2 weeks after returning from a camping trip in the Grand Canyon, a 50-year-old man developed fever, chills, headache, muscle pain, and profuse sweating. These symptoms typically lasted for 2 days. Over the next 2 weeks he experienced three febrile relapses and was hospitalized. Physical examination and laboratory tests did not conclusively lead to a diagnosis. While in the hospital the patient had a fourth episode of fever during which time a peripheral blood sample was taken and examined. Spirochetes were observed and although the patient did not remember a tick bite, he was treated with tetracycline and recovered.
a. What disease did this patient most likely have?
b. What is the causative agent of this disease?
c. What is the vector of endemic relapsing fever?
d. What is the vector of epidemic relapsing fever?
23. A 3-year-old male Coonhound presented to the clinic with an acute fever (T=104[degrees]F), anorexia, and lameness. Physical examination reveals a swollen left rear hock.
a. What questions would you want to ask this owner when taking the animal's history?
b. What test would you recommend for this dog?
c. If this test comes back positive, what would be used to treat this dog?
d. What preventative measures could this owner take to prevent this disease?
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Table 4-3 Some Rickettsioses and Their Properties Antigenic Group Disease Bacterium Typhus Epidemic Rickettsia fevers typhus, Sylvatic prowazekii typhus Murine typhus Ri. typhi Spotted Rocky Mountain Ri. rickettsii fevers spotted fever Mediterranean Ri. conorii spotted fever African tick-bite Ri. africae fever North Asian tick Ri. sibirica typhus Oriental spotted Ri. japonica fever Rickettsialpox Ri. akari Tick-borne Ri. slovaca disease Aneruptive fever Ri. helvetica Cat flea Ri. felis rickettsiosis Queensland tick Ri. australis typhus Flinders Island Ri. honei spotted fever, Thai tick typhus Orientia Scrub typhus Orientia tsu- tsugamushi Ehrlichia Ehrlichiosis Ehr. chaffeensis Anaplasma Anaplasmosis Anaplasma phagocyto- philum Neorickettsia Sennetsu fever Neorickettsia sennetsu Antigenic Group Disease Predominant Signs Typhus Epidemic Headache, chills, fever, fevers typhus, Sylvatic prostration, confusion, typhus photophobia, vomiting, rash (generally starting on trunk) Murine typhus As above, generally less severe Spotted Rocky Mountain Headache, fever, abdominal pain, fevers spotted fever rash (generally starting on extremities) Mediterranean Fever, eschar, regional spotted fever adenopathy, rash on extremities African tick-bite Fever, eschar(s), regional fever adenopathy, rash subtle or absent North Asian tick As above typhus Oriental spotted As above fever Rickettsialpox Fever, eschar, adenopathy, disseminated vesicular rash Tick-borne Necrosis erythema, lymphadenopathy disease Aneruptive fever Fever, headache, myalgia Cat flea As murine typhus, generally rickettsiosis less severe Queensland tick Fever, eschar, regional typhus adenopathy, rash on extremities Flinders Island As above but milder; eschar and spotted fever, adenopathy are rare Thai tick typhus Orientia Scrub typhus Fever, headache, sweating, conjunctival injection, adenopathy, eschar, rash (starting on trunk), respiratory distress Ehrlichia Ehrlichiosis Fever, headache, nausea, occasionally rash Anaplasma Anaplasmosis Fever, headache, nausea, occasionally rash Neorickettsia Sennetsu fever Fever, chills, headache, sore throat, insomnia Vector or Antigenic Acquisition Animal Group Disease Mechanism Reservoir Typhus Epidemic Human body Humans, flying fevers typhus, Sylvatic louse, squirrels typhus squirrel (United States) flea and louse Murine typhus Rat flea Rats, mice Spotted Rocky Mountain Tick Rodents fevers spotted fever Mediterranean Tick Rodents spotted fever African tick-bite Tick Rodents fever North Asian tick Tick Rodents typhus Oriental spotted Tick Rodents fever Rickettsialpox Mite House mice Tick-borne Tick Lagomorphs, disease rodents Aneruptive fever Tick Rodents Cat flea Cat and Domestic rickettsiosis dog flea cats, opossums Queensland tick Tick Rodents typhus Flinders Island Tick Not defined spotted fever, Thai tick typhus Orientia Scrub typhus Mite Rodents Ehrlichia Ehrlichiosis Tick Various large and small mammals, including deer and rodents Anaplasma Anaplasmosis Tick Small mammals and rodents Neorickettsia Sennetsu fever Fish, fluke Fish Antigenic Group Disease Geographic Distribution Typhus Epidemic Cool mountainous regions of fevers typhus, Sylvatic Africa, Asia, and Central and typhus South America Murine typhus Worldwide Spotted Rocky Mountain United States, Mexico, Central fevers spotted fever and South America Mediterranean Africa, India, Europe, spotted fever Middle East, Mediterranean African tick-bite Sub-Saharan Africa fever North Asian tick Russia, China, Mongolia typhus Oriental spotted Japan fever Rickettsialpox Russia, South Africa, Korea Tick-borne Europe disease Aneruptive fever Old World Cat flea Europe, South America rickettsiosis Queensland tick Australia, Tasmania typhus Flinders Island Australia, Thailand spotted fever, Thai tick typhus Orientia Scrub typhus Indian subcontinent, Central, Eastern, and Southeast Asia and Australia Ehrlichia Ehrlichiosis Worldwide Anaplasma Anaplasmosis Europe, Asia, Africa Neorickettsia Sennetsu fever Japan, Malaysia
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|Title Annotation:||Part 2: RICKETTSIAL INFECTIONS-References|
|Author:||Romich, Janet Amundson|
|Publication:||Understanding Zoonotic Diseases|
|Article Type:||Disease/Disorder overview|
|Date:||Jan 1, 2008|
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