Reasonable Rascal
12-27-01, 14:45
PLAGUE
SUMMARY
Signs and Symptoms: Pneumonic plague incubates 2-3 days. High fever, chills, headache, hemoptysis, and toxemia, progressing rapidly to dyspnea, stridor, and cyanosis. Death from respiratory failure, circulatory collapse, and a bleeding diathesis. Bubonic plague incubates 2-10 days. Malaise, high fever, and tender
lymph nodes (buboes); may progress spontaneously to the septicemic form, with spread to the CNS, lungs, etc.
Diagnosis: Presumptive diagnosis can be made by Gram or Wayson stain of lymph node aspirates, sputum, or CSF. Plague bacilli may also be cultured on standard media.
Treatment: Early administration of antibiotics is very effective. Supportive therapy is required.
Prophylaxis: A licensed, killed vaccine is available. Primary series of an initial dose followed by a second smaller dose 1-3 months later, and a third dose 5-6 months after the second dose. Give 3 booster doses at 6 month intervals following dose 3 of the primary series then every 1-2 years. This vaccine is effective against bubonic plague, but probably not against aerosol exposure.
Isolation and Decontamination: Standard Precautions for healthcare workers exposed to bubonic plague. Droplet Precautions for healthcare workers exposed to pneumonic plague. Heat, disinfectants (2-5%
hypochlorite) and exposure to sunlight renders bacteria harmless.
OVERVIEW
Yersinia pestis, a rod-shaped, non-motile, non-sporulating, gram-negative, bipolar staining, facultative anaerobic bacterium. It causes plague, normally a zoonotic disease of rodents (e.g., rats, mice, ground squirrels). Fleas which live on the rodents can sometimes pass the bacteria to human beings, who then suffer from the bubonic form of plague. The pneumonic form of the disease would be seen as the primary form after purposeful aerosol dissemination of the organisms. The bubonic form would be seen after purposeful dissemination through the release of infected fleas. All human populations are susceptible. Recovery from the disease may be followed by temporary immunity. The organism will probably remain viable in water and moist meals and grains for several weeks. At near freezing temperatures, it will remain alive from months to years but is killed by 15 minutes exposure to 72 ° C. It also remains viable for some time in dry sputum, flea feces, and buried bodies but is killed within several hours of exposure to sunlight.
HISTORY AND SIGNIFICANCE
The United States worked with Y. pestis as a potential biowarfare agent in the 1950's and 1960's before the old offensive biowarfare program was terminated, and other countries are suspected of weaponizing this organism. During World War II, there is reported evidence that Japan investigated the use of Y. pestis as a biological weapon. It was reported that they worked on a plan for attacking enemy troops with the organism by releasing plague-infected fleas. This bacterium could be delivered theoretically as an aerosol.
CLINICAL FEATURES
Plague normally appears in three forms in man; bubonic, primary septicemic, and pneumonic. The buboes in the bubonic form are normally seen in the inguinal lymph nodes as the legs are the most commonly "flea-bitten" part of the human body. Septicemia is common, as greater than 80 percent of blood cultures are positive for the organism in bubonic plague, although primary septicemia may occur without lymphadenopathy. The pneumonic form is an infection of the lungs due either to inhalation of the organisms (primary pneumonic plague), or spread to the lungs from septicemia (secondary pneumonic plague). In man, the mortality of untreated bubonic plague is approximately 50 percent, whereas in pneumonic plague the mortality rate is 100 percent.
DIAGNOSIS
After an incubation period varying from 2-3 days for primary pneumonic plague, onset is acute and often fulminant. The presentation is one of malaise, high fever, chills, headache, myalgia, cough with production of a bloody sputum, and toxemia. The chest X-ray reveals a patchy or consolidated bronchopneumonia. The pneumonia progresses rapidly, resulting in dyspnea, stridor, and cyanosis. The terminal event is one of
respiratory failure, circulatory collapse, and a bleeding diathesis. In bubonic plague the incubation period ranges from 2 to 10 days with the onset also being acute and often fulminant. The presentation is one of malaise, high fever, and one or more tender lymph nodes. The liver and spleen are often tender and palpable. One quarter of patients will have various types of skin lesions. Occasionally a pustule, vesicle, eschar or papule containing leukocytes and bacteria will be apparent in the bubo distribution and presumably represents the site of the inoculating flea bite. Bubonic plague may progress spontaneously to the septicemic form with organisms spreading to the central nervous system, lungs, and elsewhere. Black necrotic and purpuric lesions caused by endotoxemia are also often present.
Laboratory findings include a leukocytosis, with a total WBC count up to 20,000 cells with increased bands, and greater than 80 percent polymorphonuclear cells. One also often finds increased fibrin split
products in the blood indicative of a low-grade DIC, and the ALT, AST, and bilirubin are also elevated.
A presumptive diagnosis can be made microscopically by identification of the gram-negative coccobacillus with safety-pin bipolar staining in Gram or Wayson's stained smears from a lymph node needle aspirate, sputum, or cerebrospinal fluid sample. When available, immunofluorescent staining is very useful. A definitive diagnosis can be readily made by culturing the organism from blood, sputum, and bubo aspirates. The organism grows slowly at normal incubation temperatures, and may be misidentified by automated systems because of delayed biochemical reactions. It may be cultured on blood agar, MacConkey agar or infusion broth. Most naturally occurring strains of Y. pestis produce an F1-antigen in vivo, which can be detected in serum samples by immunoassay. A four-fold rise in antibody titer in patient serum is also diagnostic.
MEDICAL MANAGEMENT
Use Standard Precautions for healthcare workers exposed to bubonic plague and Droplet Precautions for healthcare workers exposed to pneumonic plague until the patient has been on antibiotic therapy for at least 48 hours and there has been a favorable clinical response to treatment. Streptomycin, tetracycline, chloramphenicol, and gentamicin are highly effective, especially if begun early (within 24 hours of onset of symptoms). Plague pneumonia is almost always fatal if treatment is not initiated within 24 hours of the onset of symptoms. Streptomycin remains the drug of choice and is given 30 mg/kg/day (IM) in two divided doses for ten days. Gentamicin is acceptable if streptomycin is unavailable. While the patient is typically afebrile after 3 days, the extra week of therapy prevents relapses. Intravenous doxycycline 200 mg initially, followed by 100 mg every 12 hours for 10-14 days is also effective. Results obtained from laboratory animal, but not human, experience, indicate that quinolone antibiotics, such as ofloxacin and ciprofloxacin, may also be effective. The addition of chloramphenicol is required for the treatment of plague meningitis.
Usual supportive therapy required includes IV crystalloids and hemodynamic monitoring. Although low-grade DIC may occur, clinically significant hemorrhage is uncommon as is the need to treat with heparin. Finally, buboes rarely require incision and drainage or any form of local care, but instead recede with systemic antibiotic therapy. In fact, incision and drainage may pose a risk to others in contact with the patient.
PROPHYLAXIS
Vaccine: A licensed, killed whole cell vaccine is available for use in those considered to be at risk of exposure. The primary series consists of three doses. The initial dose of 1.0 ml IM followed by 0.2 ml IM at 1 and 6 months. Three booster doses of 0.2 ml IM are given at 6 month intervals following the third dose of the primary series and then every 1-2 years thereafter. The current vaccine offers protection against bubonic plague, but is probably not effective against aerosolized Y. pestis. Presently, 8-10 percent of inoculations result in local reactions which include erythema, induration, tenderness and edema at the site of injection. These typically resolve within 48 hours. Approximately 7-10 percent of inoculations will result in systemic symptoms including malaise, lymphadenopathy, fever and very rarely anaphylaxis, tachycardia, urticaria, or hypotension.
Antibiotics: Because of oral administration and relative lack of toxicity, the choice of antibiotic for prophylaxis or for use in face-to-face contacts of patients with pneumonic plague or after a confirmed or
suspected plague BW attack is doxycycline 100 mg orally twice daily, for seven days or the duration of risk of exposure, whichever is longer. Ciprofloxacin has also shown to be effective in preventing disease in exposed mice, and may be more available in a wartime setting as it is also distributed in blister-packs for anthrax post-exposure prophylaxis.
Q FEVER
SUMMARY
Signs and Symptoms: Fever, cough, and pleuritic chest pain may occur as early as ten days after exposure. Patients are not generally critically ill, and the illness lasts from 2 days to 2 weeks.
Diagnosis: Q fever is not a clinically distinct illness and may resemble a viral illness or other types of atypical pneumonia. The diagnosis is confirmed serologically.
Treatment: Q fever is generally a self-limited illness even without treatment. Tetracycline or doxycycline are the treatments of choice and are given orally for 5 to 7 days. Q fever endocarditis (rare) is much more difficult to treat.
Prophylaxis: Treatment with tetracycline during the incubation period may delay but not prevent the onset of symptoms. An inactivated whole cell vaccine is effective in eliciting protection against exposure, but severe local reactions to this vaccine may be seen in those who already possess immunity.
Isolation and Decontamination: Standard Precautions are recommended for healthcare workers. Person-to-person transmission is rare. Patients exposed to Q fever by aerosol do not present a risk for secondary contamination or re-aerosolization of the organism. Decontamination is accomplished with soap and water or after a 30 minute contact time with 5% microchem plus (quaternary ammonium compound) or 70% ethyl alcohol.
OVERVIEW
The endemic form of Q fever is a zoonotic disease caused by a rickettsia, Coxiella burnetii. Its natural reservoirs are sheep, cattle and goats, and grows to especially high concentrations in placental tissues. Exposure to infected animals at parturition is an important risk factor for endemic disease. The organisms are also excreted in animal milk, urine, and feces. Humans acquire the disease by inhalation of aerosols contaminated with the organisms. Farmers and abattoir workers are at greatest risk occupationally. A biological warfare attack with Q fever would cause a disease similar to that occurring naturally. Q fever is also a significant hazard in laboratory personnel who are working with the organism.
HISTORY AND SIGNIFICANCE
Q fever was first described in Australia: it was called "Query fever" because the causative agent was initially unknown. Coxiella burnetii, the causative agent, was discovered in 1937. This organism is a rickettsial agent that is resistant to heat and desiccation and highly infectious by the aerosol route. A single inhaled organism may produce clinical illness. For all of these reasons, Q fever could be used as a biological warfare agent. This organism could be employed by an adversary as an incapacitating agent due to its highly infectious nature and likelihood of causing disease if delivered by the respiratory route.
CLINICAL FEATURES
Following the usual incubation period of 2-14 days (average 7 days), Q fever generally occurs as a self-limiting febrile illness lasting 2 days to 2 weeks. The incubation period varies according to the numbers of organisms inhaled, with longer periods between exposure and illness with lower numbers of inhaled organisms (up to forty days in some cases). The disease generally presents as an acute nondifferentiated febrile illness, with headaches, fatigue, and myalgias as prominent symptoms. Pneumonia manifested by an abnormal chest X-ray occurs in half of all patients, but only half of these, or 25 percent of patients, will
have a cough (usually non-productive) or rales. Pleuritic chest pain occurs in about one-fourth of patients with Q fever pneumonia. Chest radiograph abnormalities, when present, are patchy infiltrates that may resemble viral or mycoplasma pneumonia. Rounded opacities and adenopathy have also been described.
Uncommon complications include chronic hepatitis, culture-negative endocarditis, aseptic meningitis, encephalitis and osteomyelitis. Most patients who develop endocarditis have pre-existing valvular heart disease.
DIAGNOSIS
Routine Laboratory Findings: The white blood cell count is elevated in one third of patients. Most patients with Q fever have a mild elevation of hepatic transaminase levels.
Differential Diagnosis: As Q fever usually presents as an undifferentiated febrile illness, or a primary atypical pneumonia, it may be difficult to distinguish from viral illnesses and must be differentiated from pneumonia caused by Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci, and Chlamydia pneumoniae (TWAR). More rapidly progressive forms of Q fever pneumonia may look like bacterial pneumonias such as tularemia or plague. Significant numbers of soldiers (from the same geographic area) presenting over a one to two week period with a nonspecific febrile illness, with
associated pneumonic symptoms in about half of cases, should trigger the possibility of an attack with aerosolized Q fever in the minds of the treating physicians. The diagnosis will often rest on the clinical and epidemiologic picture in the setting of a possible biowarfare attack.
Specific Laboratory Diagnosis: Identification of organisms by examination of the sputum is not helpful. Isolation of the organism is impractical, as the organism is difficult to culture and a significant hazard to
laboratory workers. Serological tests for Q fever include identification of antibody to C. burnetii by indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), and complement fixation. Specific IgM antibodies may be detectable as early as the second week after onset of illness. ELISA testing is available at USAMRIID. A single serum specimen can be used to reliably diagnose acute Q fever with this test as early as 1 1/2 - 2 weeks into the illness. The most commonly available serologic test is the complement fixation test (CF) which is relatively insensitive and may not be useful if sera have intrinsic anti-complement activity.
MEDICAL MANAGEMENT
Standard Precautions are recommended for healthcare workers. Most cases of acute Q fever will eventually resolve without antibiotic treatment. Tetracycline 500 mg every 6 hr or doxycycline 100 mg every 12 hr for 5-7 days will shorten the duration of illness, and fever usually disappears within one to two days after treatment is begun. Successful treatment of Q fever endocarditis is much more difficult. Tetracycline or doxycycline given in combination with trimethoprim-sulfamethoxazole (TMP-SMX) or rifampin for 12 months or longer has been successful in some cases. However, valve replacement is often required to achieve a cure.
PROPHYLAXIS
Vaccine: A formalin-inactivated whole cell vaccine is available for immunization of at-risk personnel on an investigational basis, although a Q fever vaccine is licensed in Australia. Vaccination with a single dose of this killed suspension of C. burnetii provides complete protection against naturally occurring Q fever, and greater than 95 percent protection against aerosol exposure. Protection lasts for at least 5 years. The vaccine is generally safe in nonsensitized individuals. However, administration of this vaccine in immune individuals may cause severe local reactions including large areas of induration, sterile abscess formation, and even necrosis at the inoculation site. Newer vaccines are under development for use in sensitized persons.
Antibiotics: Tetracycline or doxycycline given prophylactically after exposure can delay the onset of disease, or even prevent symptoms if administered late in the incubation period. When prophylaxis is
started one day after exposure and continued for 5 days, clinical disease has been shown to occur about three weeks after stopping therapy. If prophylaxis is begun 8 to 12 days post-exposure and continued for 5 days, clinical disease will not occur after treatment is discontinued.
SUMMARY
Signs and Symptoms: Pneumonic plague incubates 2-3 days. High fever, chills, headache, hemoptysis, and toxemia, progressing rapidly to dyspnea, stridor, and cyanosis. Death from respiratory failure, circulatory collapse, and a bleeding diathesis. Bubonic plague incubates 2-10 days. Malaise, high fever, and tender
lymph nodes (buboes); may progress spontaneously to the septicemic form, with spread to the CNS, lungs, etc.
Diagnosis: Presumptive diagnosis can be made by Gram or Wayson stain of lymph node aspirates, sputum, or CSF. Plague bacilli may also be cultured on standard media.
Treatment: Early administration of antibiotics is very effective. Supportive therapy is required.
Prophylaxis: A licensed, killed vaccine is available. Primary series of an initial dose followed by a second smaller dose 1-3 months later, and a third dose 5-6 months after the second dose. Give 3 booster doses at 6 month intervals following dose 3 of the primary series then every 1-2 years. This vaccine is effective against bubonic plague, but probably not against aerosol exposure.
Isolation and Decontamination: Standard Precautions for healthcare workers exposed to bubonic plague. Droplet Precautions for healthcare workers exposed to pneumonic plague. Heat, disinfectants (2-5%
hypochlorite) and exposure to sunlight renders bacteria harmless.
OVERVIEW
Yersinia pestis, a rod-shaped, non-motile, non-sporulating, gram-negative, bipolar staining, facultative anaerobic bacterium. It causes plague, normally a zoonotic disease of rodents (e.g., rats, mice, ground squirrels). Fleas which live on the rodents can sometimes pass the bacteria to human beings, who then suffer from the bubonic form of plague. The pneumonic form of the disease would be seen as the primary form after purposeful aerosol dissemination of the organisms. The bubonic form would be seen after purposeful dissemination through the release of infected fleas. All human populations are susceptible. Recovery from the disease may be followed by temporary immunity. The organism will probably remain viable in water and moist meals and grains for several weeks. At near freezing temperatures, it will remain alive from months to years but is killed by 15 minutes exposure to 72 ° C. It also remains viable for some time in dry sputum, flea feces, and buried bodies but is killed within several hours of exposure to sunlight.
HISTORY AND SIGNIFICANCE
The United States worked with Y. pestis as a potential biowarfare agent in the 1950's and 1960's before the old offensive biowarfare program was terminated, and other countries are suspected of weaponizing this organism. During World War II, there is reported evidence that Japan investigated the use of Y. pestis as a biological weapon. It was reported that they worked on a plan for attacking enemy troops with the organism by releasing plague-infected fleas. This bacterium could be delivered theoretically as an aerosol.
CLINICAL FEATURES
Plague normally appears in three forms in man; bubonic, primary septicemic, and pneumonic. The buboes in the bubonic form are normally seen in the inguinal lymph nodes as the legs are the most commonly "flea-bitten" part of the human body. Septicemia is common, as greater than 80 percent of blood cultures are positive for the organism in bubonic plague, although primary septicemia may occur without lymphadenopathy. The pneumonic form is an infection of the lungs due either to inhalation of the organisms (primary pneumonic plague), or spread to the lungs from septicemia (secondary pneumonic plague). In man, the mortality of untreated bubonic plague is approximately 50 percent, whereas in pneumonic plague the mortality rate is 100 percent.
DIAGNOSIS
After an incubation period varying from 2-3 days for primary pneumonic plague, onset is acute and often fulminant. The presentation is one of malaise, high fever, chills, headache, myalgia, cough with production of a bloody sputum, and toxemia. The chest X-ray reveals a patchy or consolidated bronchopneumonia. The pneumonia progresses rapidly, resulting in dyspnea, stridor, and cyanosis. The terminal event is one of
respiratory failure, circulatory collapse, and a bleeding diathesis. In bubonic plague the incubation period ranges from 2 to 10 days with the onset also being acute and often fulminant. The presentation is one of malaise, high fever, and one or more tender lymph nodes. The liver and spleen are often tender and palpable. One quarter of patients will have various types of skin lesions. Occasionally a pustule, vesicle, eschar or papule containing leukocytes and bacteria will be apparent in the bubo distribution and presumably represents the site of the inoculating flea bite. Bubonic plague may progress spontaneously to the septicemic form with organisms spreading to the central nervous system, lungs, and elsewhere. Black necrotic and purpuric lesions caused by endotoxemia are also often present.
Laboratory findings include a leukocytosis, with a total WBC count up to 20,000 cells with increased bands, and greater than 80 percent polymorphonuclear cells. One also often finds increased fibrin split
products in the blood indicative of a low-grade DIC, and the ALT, AST, and bilirubin are also elevated.
A presumptive diagnosis can be made microscopically by identification of the gram-negative coccobacillus with safety-pin bipolar staining in Gram or Wayson's stained smears from a lymph node needle aspirate, sputum, or cerebrospinal fluid sample. When available, immunofluorescent staining is very useful. A definitive diagnosis can be readily made by culturing the organism from blood, sputum, and bubo aspirates. The organism grows slowly at normal incubation temperatures, and may be misidentified by automated systems because of delayed biochemical reactions. It may be cultured on blood agar, MacConkey agar or infusion broth. Most naturally occurring strains of Y. pestis produce an F1-antigen in vivo, which can be detected in serum samples by immunoassay. A four-fold rise in antibody titer in patient serum is also diagnostic.
MEDICAL MANAGEMENT
Use Standard Precautions for healthcare workers exposed to bubonic plague and Droplet Precautions for healthcare workers exposed to pneumonic plague until the patient has been on antibiotic therapy for at least 48 hours and there has been a favorable clinical response to treatment. Streptomycin, tetracycline, chloramphenicol, and gentamicin are highly effective, especially if begun early (within 24 hours of onset of symptoms). Plague pneumonia is almost always fatal if treatment is not initiated within 24 hours of the onset of symptoms. Streptomycin remains the drug of choice and is given 30 mg/kg/day (IM) in two divided doses for ten days. Gentamicin is acceptable if streptomycin is unavailable. While the patient is typically afebrile after 3 days, the extra week of therapy prevents relapses. Intravenous doxycycline 200 mg initially, followed by 100 mg every 12 hours for 10-14 days is also effective. Results obtained from laboratory animal, but not human, experience, indicate that quinolone antibiotics, such as ofloxacin and ciprofloxacin, may also be effective. The addition of chloramphenicol is required for the treatment of plague meningitis.
Usual supportive therapy required includes IV crystalloids and hemodynamic monitoring. Although low-grade DIC may occur, clinically significant hemorrhage is uncommon as is the need to treat with heparin. Finally, buboes rarely require incision and drainage or any form of local care, but instead recede with systemic antibiotic therapy. In fact, incision and drainage may pose a risk to others in contact with the patient.
PROPHYLAXIS
Vaccine: A licensed, killed whole cell vaccine is available for use in those considered to be at risk of exposure. The primary series consists of three doses. The initial dose of 1.0 ml IM followed by 0.2 ml IM at 1 and 6 months. Three booster doses of 0.2 ml IM are given at 6 month intervals following the third dose of the primary series and then every 1-2 years thereafter. The current vaccine offers protection against bubonic plague, but is probably not effective against aerosolized Y. pestis. Presently, 8-10 percent of inoculations result in local reactions which include erythema, induration, tenderness and edema at the site of injection. These typically resolve within 48 hours. Approximately 7-10 percent of inoculations will result in systemic symptoms including malaise, lymphadenopathy, fever and very rarely anaphylaxis, tachycardia, urticaria, or hypotension.
Antibiotics: Because of oral administration and relative lack of toxicity, the choice of antibiotic for prophylaxis or for use in face-to-face contacts of patients with pneumonic plague or after a confirmed or
suspected plague BW attack is doxycycline 100 mg orally twice daily, for seven days or the duration of risk of exposure, whichever is longer. Ciprofloxacin has also shown to be effective in preventing disease in exposed mice, and may be more available in a wartime setting as it is also distributed in blister-packs for anthrax post-exposure prophylaxis.
Q FEVER
SUMMARY
Signs and Symptoms: Fever, cough, and pleuritic chest pain may occur as early as ten days after exposure. Patients are not generally critically ill, and the illness lasts from 2 days to 2 weeks.
Diagnosis: Q fever is not a clinically distinct illness and may resemble a viral illness or other types of atypical pneumonia. The diagnosis is confirmed serologically.
Treatment: Q fever is generally a self-limited illness even without treatment. Tetracycline or doxycycline are the treatments of choice and are given orally for 5 to 7 days. Q fever endocarditis (rare) is much more difficult to treat.
Prophylaxis: Treatment with tetracycline during the incubation period may delay but not prevent the onset of symptoms. An inactivated whole cell vaccine is effective in eliciting protection against exposure, but severe local reactions to this vaccine may be seen in those who already possess immunity.
Isolation and Decontamination: Standard Precautions are recommended for healthcare workers. Person-to-person transmission is rare. Patients exposed to Q fever by aerosol do not present a risk for secondary contamination or re-aerosolization of the organism. Decontamination is accomplished with soap and water or after a 30 minute contact time with 5% microchem plus (quaternary ammonium compound) or 70% ethyl alcohol.
OVERVIEW
The endemic form of Q fever is a zoonotic disease caused by a rickettsia, Coxiella burnetii. Its natural reservoirs are sheep, cattle and goats, and grows to especially high concentrations in placental tissues. Exposure to infected animals at parturition is an important risk factor for endemic disease. The organisms are also excreted in animal milk, urine, and feces. Humans acquire the disease by inhalation of aerosols contaminated with the organisms. Farmers and abattoir workers are at greatest risk occupationally. A biological warfare attack with Q fever would cause a disease similar to that occurring naturally. Q fever is also a significant hazard in laboratory personnel who are working with the organism.
HISTORY AND SIGNIFICANCE
Q fever was first described in Australia: it was called "Query fever" because the causative agent was initially unknown. Coxiella burnetii, the causative agent, was discovered in 1937. This organism is a rickettsial agent that is resistant to heat and desiccation and highly infectious by the aerosol route. A single inhaled organism may produce clinical illness. For all of these reasons, Q fever could be used as a biological warfare agent. This organism could be employed by an adversary as an incapacitating agent due to its highly infectious nature and likelihood of causing disease if delivered by the respiratory route.
CLINICAL FEATURES
Following the usual incubation period of 2-14 days (average 7 days), Q fever generally occurs as a self-limiting febrile illness lasting 2 days to 2 weeks. The incubation period varies according to the numbers of organisms inhaled, with longer periods between exposure and illness with lower numbers of inhaled organisms (up to forty days in some cases). The disease generally presents as an acute nondifferentiated febrile illness, with headaches, fatigue, and myalgias as prominent symptoms. Pneumonia manifested by an abnormal chest X-ray occurs in half of all patients, but only half of these, or 25 percent of patients, will
have a cough (usually non-productive) or rales. Pleuritic chest pain occurs in about one-fourth of patients with Q fever pneumonia. Chest radiograph abnormalities, when present, are patchy infiltrates that may resemble viral or mycoplasma pneumonia. Rounded opacities and adenopathy have also been described.
Uncommon complications include chronic hepatitis, culture-negative endocarditis, aseptic meningitis, encephalitis and osteomyelitis. Most patients who develop endocarditis have pre-existing valvular heart disease.
DIAGNOSIS
Routine Laboratory Findings: The white blood cell count is elevated in one third of patients. Most patients with Q fever have a mild elevation of hepatic transaminase levels.
Differential Diagnosis: As Q fever usually presents as an undifferentiated febrile illness, or a primary atypical pneumonia, it may be difficult to distinguish from viral illnesses and must be differentiated from pneumonia caused by Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci, and Chlamydia pneumoniae (TWAR). More rapidly progressive forms of Q fever pneumonia may look like bacterial pneumonias such as tularemia or plague. Significant numbers of soldiers (from the same geographic area) presenting over a one to two week period with a nonspecific febrile illness, with
associated pneumonic symptoms in about half of cases, should trigger the possibility of an attack with aerosolized Q fever in the minds of the treating physicians. The diagnosis will often rest on the clinical and epidemiologic picture in the setting of a possible biowarfare attack.
Specific Laboratory Diagnosis: Identification of organisms by examination of the sputum is not helpful. Isolation of the organism is impractical, as the organism is difficult to culture and a significant hazard to
laboratory workers. Serological tests for Q fever include identification of antibody to C. burnetii by indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), and complement fixation. Specific IgM antibodies may be detectable as early as the second week after onset of illness. ELISA testing is available at USAMRIID. A single serum specimen can be used to reliably diagnose acute Q fever with this test as early as 1 1/2 - 2 weeks into the illness. The most commonly available serologic test is the complement fixation test (CF) which is relatively insensitive and may not be useful if sera have intrinsic anti-complement activity.
MEDICAL MANAGEMENT
Standard Precautions are recommended for healthcare workers. Most cases of acute Q fever will eventually resolve without antibiotic treatment. Tetracycline 500 mg every 6 hr or doxycycline 100 mg every 12 hr for 5-7 days will shorten the duration of illness, and fever usually disappears within one to two days after treatment is begun. Successful treatment of Q fever endocarditis is much more difficult. Tetracycline or doxycycline given in combination with trimethoprim-sulfamethoxazole (TMP-SMX) or rifampin for 12 months or longer has been successful in some cases. However, valve replacement is often required to achieve a cure.
PROPHYLAXIS
Vaccine: A formalin-inactivated whole cell vaccine is available for immunization of at-risk personnel on an investigational basis, although a Q fever vaccine is licensed in Australia. Vaccination with a single dose of this killed suspension of C. burnetii provides complete protection against naturally occurring Q fever, and greater than 95 percent protection against aerosol exposure. Protection lasts for at least 5 years. The vaccine is generally safe in nonsensitized individuals. However, administration of this vaccine in immune individuals may cause severe local reactions including large areas of induration, sterile abscess formation, and even necrosis at the inoculation site. Newer vaccines are under development for use in sensitized persons.
Antibiotics: Tetracycline or doxycycline given prophylactically after exposure can delay the onset of disease, or even prevent symptoms if administered late in the incubation period. When prophylaxis is
started one day after exposure and continued for 5 days, clinical disease has been shown to occur about three weeks after stopping therapy. If prophylaxis is begun 8 to 12 days post-exposure and continued for 5 days, clinical disease will not occur after treatment is discontinued.