A Case of Person-to-Person Transmission of Q Fever from an Active Duty Serviceman to His Spouse

Case Reports

I n January 2008, a 49-year-old male U.S. Army officer returning from Iraq presented with high fever, severe headache, and mild abdominal pain. He described the acute onset of these symptoms just before his return flight home. His clinical condition worsened during the 72-h plane trip back home.

He was stationed in Kirkuk, Iraq, from July 2007 until January 10, 2008. He lived in well-constructed, hardened barracks, where he worked as a computer information specialist. He reported no tick bites and no direct contact with livestock or animals. His immunizations were up-to-date, including hepatitis A and B, typhoid fever, yellow fever, and most recently an anthrax booster given 48 h before departure from Iraq.

On physical examination, the patient appeared acutely ill, with a temperature of 103.7°F. The result of chest examination was normal. There was mild tenderness in the right upper quadrant of the abdomen. There was no hepato-splenomegaly. Kernig and Brudzinski's signs were also negative.

Initial laboratory studies revealed leukocytes 3.8 × 10³ cells/μL (normal: 4–10.6 × 10³ cells/μL), platelets 79 × 10³ cells/μL (normal: 150–400 × 10³ cells/μL), aspartate amino-transferase 143 IU/L (normal: 17–59 IU/L), alanine amino-transferase 197 IU/L (normal: 21–72 IU/L), and lactate dehydrogenase 2329 IU/L (normal: 300–670 IU/L). Contrasted computed tomography of the chest demonstrated small bilateral pleural effusions and a tree-in-bud pattern of opacification in the right upper lobe. Lumbar puncture was performed and the result of cerebral spinal fluid (CSF) examination was normal.

Serological testing was performed for viral hepatitis, brucellosis, rickettsioses, and Q fever. Despite high fevers, the patient defervesced after 72 h of empiric therapy with ceftriaxone and doxycycline. He was discharged with a 21-day course of doxycycline due to a clinical suspicion of acute Q fever. Three weeks later, he remained asymptomatic with normal liver function tests. Initial Q fever phase II IgM obtained on admission was borderline positive at 1:16 (cutoff >1:16). Phase I and II IgG and phase I IgM were negative. Q fever serology was repeated 3 weeks later and the patient exhibited Q fever seroconversion to phase II IgM antibody (1:1024); serology repeated 5 months later also demonstrated a seroconversion to phase I and II IgG at 1:1024 (Table 1). Of note, all the clinical work-up described was performed in the New Mexico Veterans Healthcare System (Albuquerque, NM).

Five months after her husband's diagnosis, his wife was admitted to the same hospital with acute onset of fever up to 105°F, chills, headache, and 3-day history of watery diarrhea. The physical exam revealed mild abdominal tenderness in the right upper quadrant. There was no hepato-splenomegaly and no meningeal signs.

Initial laboratory studies revealed leukocytes 5.3 × 10³ cells/μL (normal: 4–10.6 × 10³ cells/μL), platelets 93 × 10³ cells/μL (normal: 150–400 × 10³ cells/μL), aspartate amino-transferase 81 IU/L (normal: 17–59 IU/L), alanine amino-transferase 70 IU/L (normal: 21–72 IU/L), and lactate dehydrogenase 1230 IU/L (normal: 300–670 IU/L). The patient was suspected of having acute Q fever, due to her husband's recent diagnosis. The patient defervesced after 72 h of empiric therapy with doxycycline. She was discharged with a 21-day course of doxycycline. Acute Q fever was confirmed on the basis of seroconversion (Table 1).

Exposure to Q fever from a vector or aerosolized sources could not be established for the wife. Acute Q fever infection is uncommonly reported in New Mexico with only three confirmed cases in 2006 and four cases in 2007 (New Mexico State Department of Health, personal communication). She reported washing her husband's clothing within several days of his arrival back home. She and her husband live in a suburban community with no direct animal exposure. They deny any recent visits to diaries, farms, or petting zoos. Her occupation is an office-based administrative assistant. The husband and wife resumed sexual intercourse approximately 28 days after resolution of his symptoms. Condoms or other forms of protection were not used. No other risk factors for Q fever were identified, and her only overt exposure appeared to be sexual contact with her convalescent husband. The results of polymerase chain reaction (PCR) testing to detect the presence of Coxiella burnetii in semen and cervical brush samples were negative.

Both patients underwent an extensive additional work-up for evidence of chronic Q fever manifestations as both patients had elevated phase II IgG (1:1024) postconvalescence (Table 1). Liver function tests indicated no hepatic inflammation, and total body bone scans and trans-esophageal echocardiograms revealed no evidence of osteomyelitis or endocarditis, respectively. The index patient remained asymptomatic with his wife reporting a residual complaint of generalized fatigue and listlessness.

Analysis of C. burnetii PCR

Analysis of C. burnetii PCR was done on two clinical samples: semen and cervical swab (brush). DNA was purified from semen using the Qiagen (Valencia, CA) QIAamp DNA mini kit using the tissue protocol according to manufacturer's instructions. For the cervical brushing, 460 μL physiological saline, 460 μL Qiagen lysis buffer ATL, and 80 μL of a Qiagen proteinase K solution were added to the swab in a 15 mL conical tube, followed by vortexing, and overnight incubation at 56°C. Next, the sample was split into four equal parts, and the DNA purification proceeded using the tissue protocol from the Qiagen QIAamp kit. PCR for the IS1111 repeat element normally found in C. burnetii was performed. Both samples were run for 40 cycles and were found to be negative. This PCR assay can detect as low as two genome equivalents. Coxiella standards spanning from 2000 to two genome equivalents were run at the same time as the two clinical samples. The standards were positive and showed the expected linear relationship (Loftis et al. 2006).

Discussion

C. burnetii is resistant to heat, drying, and most disinfectants. Primary reservoirs are cattle, sheep, and goats. In animals, high organism numbers are found in amniotic fluid and the placenta (Oda and Yoshiie 1995, Hirai and To 1998). Human transmission occurs most frequently via dust or aerosols from infected animals (Manfredi Selvaggi et al. 1996, Hawker et al. 1998, Lyytikainen et al. 1998, Tissot-Dupont et al. 1999). Consuming cheese made from raw milk from dairy animals shedding C. burnetii also constitutes a risk factor for the acquisition of Q fever (Rodolakis 2009). Cases of person-to-person and sexual transmission of Q fever have also been rarely reported (Oliphant et al. 1949, Kruszewska et al. 1996, Milazzo et al. 2001).

This case of an active duty U.S. serviceman returning from Iraq with acute Q fever and the subsequent infection of his wife raises several questions, including the source of C. burnetii in Iraq and the method of transmission to the wife. Q fever is currently classified as a category B agent of bioterrorism as a potential aerosolized pathogen although no attacks have been reported to date (Raoult et al. 2005). Natural outbreaks of Q fever among U.S. military personnel deployed in Iraq have been previously reported (Leung-Shea and Danaher 2006, Raoult 2009). Our index case appears to be an isolated episode since no other cases of Q fever or any other acute febrile illnesses were reported in this patient's unit at the time of presentation. The primary method of transmission of Q fever is via aerosolization. Other reported modes of transmission include consumption of raw milk, transplacental transmission, blood transfusion, tick bites, and, of particular relevance in this case, contaminated clothing and sexual transmission (Oliphant et al. 1949, Marrie et al. 1989, Manfredi Selvaggi et al. 1996, Milazzo et al. 2001). Contaminated clothing has been cited as the source of transmissions in the case of laundry workers exposed to the laundry of laboratory workers in the NIH in Hamilton, Montana (Oliphant et al. 1949). A second report circumstantially links a worker with clothing contaminated by contact with newborn kittens as subsequently infecting 13 coworkers (Marrie et al. 1989). In our report, the wife of the index case was exposed to his military clothing, which she laundered shortly after his return. Acquisition of infection by aerosolization from clothing appears unlikely as she did not develop clinical disease until 4 months after this exposure, well exceeding the usual incubation interval for Q fever.

Male-to-female sexual transmission of Q fever has been established. The presence of Q fever in the semen from transmitted cases has been demonstrated by electron microscopy (Kruszewska et al. 1996) and PCR (Milazzo et al. 2001). Milazzo et al. reported the sexual transmission of C. burnetii from a man with occupationally acquired Q fever to his wife. C. burnetii DNA sequences were detected by PCR performed on semen samples obtained from the husband at 4 and 15 months after the onset of acute Q fever (Milazzo et al. 2001). The husband and wife in our case resumed regular sexual activity within 1 month of his treatment of acute Q fever. Noteworthy, the sensitivity and specificity of the PCR assays for C. burnetii have not been completely determined, and a negative result indicates only the absence of detectable pathogen DNA in the sample tested but does not exclude the diagnosis. Thus, despite the negative PCR study on the semen and cervical cells, we believe that sexual transmission remains the most likely explanation of her infection.

Although the mode of transmission of Q fever cannot be established by the evidence presented, it is of public health significance that this infection can be transmitted directly by sexual contact with a convalescent patient and/or indirectly by contact with contaminated fomites. Current data indicate that Q fever poses a threat to U.S. military forces (Leung-Shea and Danaher 2006). A better understanding of the epidemiology and various forms of transmission of this pathogen is critical to identify the population at risk. In addition, further studies to determine the actual incidence of Q fever transmission from sexual contact or from contaminated clothing among the U.S. military personnel and their families are clearly warranted.