Q Fever Endocarditis and New Coxiella burnetii Genotype, Saudi Arabia

To the Editor. Q fever is a worldwide zoonosis caused by an obligate intracellular bacterium, Coxiella burnetii (1). Q fever endocarditis is associated with surgery for 15%–73% of patients, causes death for 5%–65% of patients, and induces a large number of relapses when the endocarditis is inadequately treated (1). The most serious risk factor for endocarditis is a substantial underlying valvulopathy, but progression to endocarditis is also found in patients with clinically silent, previously undiagnosed, valvulopathies (1). Since the 1960s, Q fever has been recognized as a public health problem in Saudi Arabia, and studies have shown that coxiellosis occurs in livestock (2,3). Only a few cases of Q fever endocarditis in Saudi Arabia have been reported (4–6). We report 2 new cases of Q fever endocarditis and detection of a new C. burnetii genotype in this country. 
 
The first case was detected in 2007 in a 45-year-old man in Saudi Arabia who had fever, pneumonia, and asthenia. A transesophageal echocardiogram showed endocarditis. Results of an immunofluorescence assay were positive for C. burnetii; phase I titers for IgG, IgM, and IgA were 51,200, 100, and 25, respectively, and phase II titers were 102,400, 200, and 50, respectively. Serum and blood samples were negative for C. burnetii by real-time PCR for the IS1111 and the IS30A spacers (7). For each sample, the quality of DNA extraction was verified by real-time PCR for a housekeeping gene encoding β-actin (7). The aortic valve was surgically replaced, and C. burnetii–specific PCR results for the valve were positive. According to multispacer sequence typing (8), this C. burnetii isolate was a new genotype, MST51 (Figure). A C. burnetii isolate was cultured from the valve of this patient by the shell-vial method that used human embryonic lung cells (7). IgG anticardiolipin testing results were negative (9). The patient was given 200 mg oral doxycycline daily and 200 mg oral hydroxychloroquine 3 times daily for 18 months. 
 
 
 
Figure 
 
Neighbor-joining tree of Coxiella burnetii genotypes determined by multispacer sequence typing. Arrow indicates new genotype in Saudi Arabia. 
 
 
 
The second case was detected in 2012 in a 13-year-old boy in Saudi Arabia who had tetralogy of Fallot, a prosthetic pulmonary valve, 2 intracardiac stents, and long-term fever. Serologic testing results were positive for C. burnetii; phase I titers for IgG, IgM, and IgA were 51,200, 400, and 200, respectively, and phase II titers were 102,400, 800, and 400, respectively. Whereas serum and blood samples were negative for C. burnetii by real-time PCR for the IS1111 and the IS30A spacers, the β-actin control was positive (cycle threshold <30). For this patient, we did not receive any material for culture. The patient was given 200 mg oral doxycycline daily and 200 mg oral hydroxychloroquine 3 times daily for 18 months. 
 
To the best of our knowledge, before the 2 cases presented here, only 3 cases of Q fever endocarditis in Saudi Arabia have been described; all patients were from rural regions of Saudi Arabia and had an underlying valvulopathy (4–6). Moreover, Q fever was not immediately suspected, and as a result, 1 patient died (6). However, for 2 other patients, valve replacement was necessary (4,5). Q fever is prevalent in Saudi Arabia, and the very high prevalence of Q fever among camels was proposed as the reason Q fever is endemic among humans in Saudi Arabia (2,3). Camels were also suspected as the probable source of acute Q fever in US soldiers returning from Saudi Arabia (10). We identified a new C. burnetii genotype in the aortic valve of the first patient reported here. More epidemiologic studies are needed to determine whether this novel genotype circulating in Saudi Arabia is endemic to Saudi Arabia and whether it plays a major role in the origin of Q fever and in public health in this country. 
 
Our studies of Q fever cases in southern France have shown that >16% of patients with acute Q fever have endocarditis and that ≈16%–37% of patients with Q fever endocarditis could have had previous symptomatic acute Q fever infection (1). Thus, many cases of endocarditis might be avoided if patients with acute Q fever receive antimicrobial drugs as prophylaxis (1). For patients >40 years of age, transthoracic echocardiography should be performed because of the increased prevalence of valvulopathy and Q fever endocarditis in this population (9). As a result, more studies are needed to determine whether our data can affect local clinical practice.

To the Editor. Q fever is a worldwide zoonosis caused by an obligate intracellular bacterium, Coxiella burnetii (1). Q fever endocarditis is associated with surgery for 15%-73% of patients, causes death for 5%-65% of patients, and induces a large number of relapses when the endocarditis is inadequately treated (1). The most serious risk factor for endocarditis is a substantial underlying valvulopathy, but progression to endocarditis is also found in patients with clinically silent, previously undiagnosed, valvulopathies (1). Since the 1960s, Q fever has been recognized as a public health problem in Saudi Arabia, and studies have shown that coxiellosis occurs in livestock (2,3). Only a few cases of Q fever endocarditis in Saudi Arabia have been reported (4)(5)(6). We report 2 new cases of Q fever endocarditis and detection of a new C. burnetii genotype in this country.
The first case was detected in 2007 in a 45-year-old man in Saudi Arabia who had fever, pneumonia, and asthenia. A transesophageal echocardiogram showed endocarditis. Results of an immunofluorescence assay were positive for C. burnetii; phase I titers for IgG, IgM, and IgA were 51,200, 100, and 25, respectively, and phase II titers were 102,400, 200, and 50, respectively. Serum and blood samples were negative for C. burnetii by real-time PCR for the IS1111 and the IS30A spacers (7). For each sample, the quality of DNA extraction was verified by real-time PCR for a housekeeping gene encoding β-actin (7). The aortic valve was surgically replaced, and C. burnetii-specific PCR results for the valve were positive. According to multispacer sequence typing (8), this C. burnetii isolate was a new genotype, MST51 ( Figure). A C. burnetii isolate was cultured from the valve of this patient by the shell-vial method that used human embryonic lung cells (7). IgG anticardiolipin testing results were negative (9). The patient was given 200 mg oral doxycycline daily and 200 mg oral hydroxychloroquine 3 times daily for 18 months.
The second case was detected in 2012 in a 13-year-old boy in Saudi Arabia who had tetralogy of Fallot, a prosthetic pulmonary valve, 2 intracardiac stents, and long-term fever. Serologic testing results were positive for C. burnetii; phase I titers for IgG, IgM, and IgA were 51,200, 400, and 200, respectively, and phase II titers were 102,400, 800, and 400, respectively. Whereas serum and blood samples were negative for C. burnetii by real-time PCR for the IS1111 and the IS30A spacers, the β-actin control was positive (cycle threshold <30). For this patient, we did not receive any material for culture. The patient was given 200 mg oral doxycycline daily and 200 mg oral hydroxychloroquine 3 times daily for 18 months.
To the best of our knowledge, before the 2 cases presented here, only 3 cases of Q fever endocarditis in Saudi Arabia have been described; all patients were from rural regions of Saudi Arabia and had an underlying valvulopathy (4)(5)(6). Moreover, Q fever was not immediately suspected, and as a result, 1 patient died (6). However, for 2 other patients, valve replacement was necessary (4,5). Q fever is prevalent in Saudi Arabia, and the very high prevalence of Q fever among camels was proposed as the reason Q fever is endemic among humans in Saudi Arabia (2,3). Camels were also suspected as the probable source of acute Q fever in US soldiers returning from Saudi Arabia (10). We identified a new C. burnetii genotype in the aortic valve of the first patient reported here. More epidemiologic studies are needed to determine whether this novel genotype circulating in Saudi Arabia is endemic to Saudi Arabia and whether it plays a major role in the origin of Q fever and in public health in this country.
Our studies of Q fever cases in southern France have shown that >16% of patients with acute Q fever have endocarditis and that ≈16% 37% of patients with Q fever endocarditis could have had previous symptomatic acute Q fever infection (1). Thus, many cases of endocarditis might be avoided if patients with acute Q fever receive antimicrobial drugs as prophylaxis (1). For patients >40 years of age, transthoracic echocardiography should be performed because of the increased prevalence of valvulopathy and Q fever endocarditis in this population (9). As a result, more studies are needed to determine whether our data can affect local clinical practice.  Committee advised all countries (particularly those with returning pilgrims) to strengthen their surveillance capacities and ensure robust reporting of any identified cases (2).

Emmanouil Angelakis, Sameer Johani, Azeem Ahsan, Ziad Memish, and Didier Raoult
We report the results of a prospective cohort study conducted in Saudi Arabia in October 2013. Participants in the survey were adult Hajj pilgrims who traveled together in a group (through 1 travel agency in Marseille, France) from October 3 through October 24, 2013. Pilgrims were included in the study on a voluntary basis and were asked to sign a written consent form. All pilgrims received advice about individual prevention measures against respiratory tract infection before departing, and follow-up was conducted during the journey by a medical doctor who systematically documented travel-associated diseases. Nasal swab specimens were obtained just before the pilgrims left Saudi Arabia, frozen <48 hours after sampling, and processed (3,4). Each sample was tested for MERS-CoV (upE and ORF1a genes) (5,6)  reported fever, and 61 (47.3%) had conditions that met the criteria for influenza-like illness (ILI; i.e., the association of cough, sore throat, and subjective fever) (Figure) (4). One patient was hospitalized during travel (undocumented pneumonia). Nasal swab specimens were obtained from 129 pilgrims on October 23, 2013 (week 43), 1 day before pilgrims left Saudi Arabia for France; 90 (69.8%) pilgrims were still symptomatic. All PCRs were negative for MERS-CoV.
Eight pilgrims tested positive for influenza A(H3N2), 1 for influenza A(H1N1), and 1 for influenza B virus. No dual infections were reported. 70 (54.3%) pilgrims were seen 3-5 weeks after they returned to France, and the remaining were lost to followup. Fifty-five (78.6%) had experienced respiratory symptoms since their return, including cough (50 [71.4%]) and sore throat (14 [20.0%]); 12 (17.1%) reported fever, and illness in 5 (7.1%) pilgrims met the criteria for ILI. The 10 pilgrims who had positive test The Public Health Image Library (PHIL), Centers for Disease Control and Prevention, contains thousands of public healthrelated images, including high-resolution (print quality) photographs, illustrations, and videos.
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