in december 2006 , 1 week after returning from iraq , a 22-year - old white male army national guard member was seen at a new hampshire hospital , with flulike symptoms , pleuritic chest pain , and mild abdominal pain .
his initial examination noted temperature of 38.3c , leukocytes 3.3  10 cells/l ( normal 4.510.5  10 cells/l ) , platelets 121  10 cells/l ( normal 150450  10 cells/l ) , aspartate aminotransferase ( ast ) 144 iu / l ( normal 1546
iu / l ) , and alanine aminotransferase ( alt ) 154 iu / l ( reference 1166 iu / l ) .
although his fever decreased within 48 h , he had persistent abdominal pain , worsening liver function test results ( ast 779 , alt 993 , alkaline phosphatase 269 u / l [ reference 38126 u / l ] ) , and increasing shortness of breath .
an ultrasound examination of the right upper quadrant showed hepatosplenomegaly and a thickened gall bladder wall without evidence of cholelithiasis . despite initially normal chest radiographic results , a repeat radiographic examination showed bilateral pulmonary infiltrates .
ceftriaxone therapy was discontinued , pipercillin / tazobactam therapy was started , and azithromycin was continued .
after consultation with wramc , the patient was given a dose of doxycycline and gentamicin before being transferred to a new hampshire medical center .
blood cultures and serologic tests for epstein barr virus and cytomegalovirus were pending . a computed tomographic ( ct ) examination of the chest , abdomen , and pelvis ( figure , left panel ) showed gall bladder wall thickening ( 10 mm ) without ductal dilatation , hepatosplenomegaly , and bilateral ground glass pulmonary infiltrates .
serologic tests were negative for hepatitis b and c. thick and thin smears were negative for parasitic disease . despite the findings on ct scan
, the patient began to improve clinically and had resolution of abdominal pain and shortness of breath .
a presumptive diagnosis of q fever was made , and he was discharged to complete a 14-day course of doxycycline .
serologic tests for c. burnettii were positive with a phase 2 immunoglobulin m ( igm ) titer of 256 ( negative < 1:64 ) , phase 2 igg titer of 128 ( negative < 16 ) , and negative phase 1 serologic results .
the second case occurred in december 2006 , when a previously healthy 24-year - old male army national guard member was admitted to the 28th combat support hospital ( csh ) in baghdad , iraq , with flulike symptoms , mild nausea , and a dry , 10-day cough . at admission ,
laboratory results included leukocytes 3.910 cells/l , platelets of 13010 cells/l , alkaline phosphatase 104 u / l , ast 824 u / l , alt 786 u / l , total bilirubin 1.2 mg / dl ( reference 0.21.3 mg / dl ) , and gamma glutamyl transferase ( ggt ) 97 ( reference 1258 ) .
initial erythrocyte sedimentation rate was within normal limits at 18 mm / hr ( reference < 20 mm / h ) .
results of blood cultures , monospot , and hepatitis b , c , and hiv screens were negative .
a ct scan showed diffuse enhancement of the gallbladder with gallbladder wall thickening ( figure , right panel ) .
a small amount of pericholecystic fluid was seen , but no distension of the gallbladder or gallstones were noted .
these findings prompted a general surgery evaluation for acute cholecystitis , but their examination results were not consistent with this diagnosis . given the patient s flulike symptoms and laboratory abnormalities , the diagnosis of q fever was considered . the patient had initially been treated with doxycycline and metronidazole , but metronidazole was discontinued when his physical examination results remained benign .
he was transferred out of theater to landstuhl regional medical center in germany for further evaluation .
q fever was confirmed with c. burnettii serum titers of 2,048 for phases 1 and 2 igm .
he improved with doxycycline , 100 mg twice a day for 14 days , and was subsequently returned to duty .
the third case occurred in july 2006 in a 34-year - old female active duty soldier with a history of asthma .
she was seen at the troop medical clinic in baghdad , iraq , with flulike symptoms .
she was given symptomatic treatment and released but returned with altered mental status , shortness of breath , and abdominal pain .
a ct scan of her chest showed a left lower lobe infiltrate and bilateral pleural effusions .
she remained febrile ( 39.8c ) and tachycardic and required 4 l / min of oxygen via nasal cannula to maintain an oxygen saturation of 96% .
results of laboratory tests conducted at the time of admission were unremarkable except for a mild transaminitis ( ast 139 and alt 96 ) . she was treated with levofloxacin , 500 mg per day intravenously , for suspected pneumonia .
she had rapid worsening of her respiratory status over the next 8 hours and required intubation .
antimicrobial drug coverage was broadened to include piperacillin / tazobactam 3.375 parenterally every 6 hours ; solumedrol was added , given her history of asthma .
her chest radiographs showed progression to acute respiratory distress syndrome ( ards ) , and arterial blood gas testing showed partial pressure of arterial oxygen to be 5060 mm hg .
she improved and was evacuated to wramc , where she was afebrile ( 37.2c ) at admission .
her serologic test results were positive for q fever with phase 2 igm titer of 1,024 .
fever , pneumonia , and/or hepatitis are the most common signs of acute infection with q fever ( 4,5 ) . in those in whom chronic disease develops
asymptomatic infection may occur in > 50% of infected patients ( 4,5 ) . despite its typical signs and symptoms ,
raoult described > 7 distinct presentations ( 6 ) : fever , pneumonia , hepatitis , meningitis , meningoencephalitis , pericarditis , and myocarditis .
only 12 cases of acute cholecystitis associated with q fever have been reported in the english medical literature ( 710 ) .
the largest and most detailed description is from a case series by rolain ( 7 ) , who described 9 patients whose initial sign of q fever was acute cholecystitis .
four of the 6 patients received doxycycline , 1 received ofloxacin , and 1 received no treatment .
q fever is often self - limiting ; yet treatment is recommended to shorten duration of symptoms and prevent chronic disease ( 5 ) .
reina - serrano recently suggested that patients with q fever  associated cholecystitis could be managed medically ( 8) .
two of our patients had evidence of cholecystitis on imaging studies but did not have evidence of peritonitis on physical examination .
we propose that for patients with acute acalculous cholecystitis and a high suspicion for q fever , doxycycline be given empirically .
the patients clinical response should be evident within 48 hours and surgery may be avoided .
if a patient has gallstones or acute abdominal pain , a standard approach for treating acute cholecystitis should be followed .
the third patient in our series progressed to ards , which has been reported , albeit rarely , with q fever ( 1,4,11,12 ) .
more typically , pneumonia secondary to acute q fever infection results in a dry to productive cough , pleuritic chest pain , and focal or bilateral infiltrates on chest radiographs ( 6 ) .
our patients denied having typical risk factors , including exposure to livestock or consumption of local meat or dairy products .
, who suggested that providers strongly consider adding doxycycline to the treatment regimen for deployed soldiers with severe pneumonia ( 1 ) .
q fever is a category b biologic agent and must be considered as a potential threat to deployed soldiers ( 13 ) .
the most likely mode of attack would be aerosolization ; given the low dose required for infection ( 110 organisms ) , multiple cases would follow .
we considered bioterrorism unlikely , given the limited number of clinically symptomatic cases and the lack of a cluster of cases .
it should be considered in the differential diagnosis of any deployed or recently deployed soldier with a febrile illness , especially when hepatitis or pneumonia is present .
 q fever is an emerging infectious disease among us soldiers serving in iraq . 
 three patients have had atypical manifestations , including 2 patients with acute cholecystitis and 1 patient with acute respiratory distress syndrome . 
 providers must be aware of q fever s signs and symptoms to avoid delays in treatment . 
The Patients
Conclusions