Comparison Between Emerging Q Fever in French Guiana and Endemic Q Fever in Marseille, France
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Am. J. Trop. Med. Hyg., 90(5), 2014, pp. 915–919 doi:10.4269/ajtmh.13-0164 Copyright © 2014 by The American Society of Tropical Medicine and Hygiene Comparison between Emerging Q Fever in French Guiana and Endemic Q fever in Marseille, France Sophie Edouard,† Aba Mahamat,† Magalie Demar, Philippe Abboud, Felix Djossou, and Didier Raoult* Aix Marseille Universite´, Marseille, France; Department of Infectious and Tropical Disease, Centre Hospitalier Andre´e Rosemon, Cayenne, French Guiana Abstract. Q fever is an emergent disease in French Guiana. We compared the incidence clinical and serologic profiles between patients from Cayenne, French Guiana and Marseille in metropolitan France during a four-year period. The annual incidence of diagnosed acute Q fever was significantly higher in Cayenne (17.5/100,000) than in Marseille (1.9/100,000) (P = 0.0004), but not the annual incidence of endocarditis (1.29 versus 0.34/100,000). Most patients had fever (97%) and pneumonia (83%) in Cayenne versus 81% and 8% in Marseille (P < 0.0001 and P < 0.0001, respectively) but transaminitis was more common in patients from Marseille (54% versus 32%; P < 0.0001). The proportion of patients with cardiovascular infections was significantly lower in Cayenne (7%) than in Marseille (17%) (P = 0.017), although they showed a stronger immune response with higher levels of phase I IgG (P = 0.024). The differing epidemiology, clinical, and sero- logic responses of patients from Cayenne and Marseille suggest a different source of infection and a different strain of Coxiella burnetii. INTRODUCTION lent phase II is correlated with a partial loss of lipopolysac- charides.2 Phase II antibodies have been observed in acute Coxiella burnetii is an obligate intracellular bacterium that Q fever, and high levels of phase I IgG are observed in is responsible for Q fever, a worldwide zoonosis that was first 9 1 patients with cardiovascular infections. described in Australia in 1935. A wide variety of wild and Coxiella burnetii was first identified in French Guiana in domestic mammals, birds, and arthropods may be infected by 10 2 1955. Only sporadic cases were reported until 1996, when this bacterium. Coxiella burnetii is principally transmitted to three patients with acute respiratory distress syndrome were humans by aerosols from the parturient fluid of the infected hospitalized in an intensive care unit.11 One patient died and cattle, goats, and sheep that constitute the main reservoir for 3 many cases of Q fever were concurrently diagnosed in the the bacteria. Q fever is characterized by its clinical polymor- general population. A retrospective seroepidemiologic study phisms; this bacterium may cause acute and chronic infections showed a significant increase in the incidence rate of C. burnetii in humans. Acute Q fever occurs during the first infection by infection in 1996, particularly in Cayenne, which is the main C. burnetii. Most (60%) cases in described outbreaks are asymp- urban center in which more than half of the population is tomatic. Isolated fever, atypical pneumonia, and transaminitis, 12 4 concentrated. These data are surprising because Q fever are the most frequently observed symptoms. occurs more frequently in rural areas, and urban cases are not The severity of acute Q fever depends on the strain of C. 5 linked to the classical sources of infection (goats, sheep, burnetii that infects the patient. In most cases, patients with and cattle). The low infection rate of livestock in Guiana with an acute infection recover spontaneously. However, endocar- C. burnetii confirms this particular epidemiology. Another – ditis and vascular infections develop in 1 5% of patients; study has confirmed these data; during 1996–2000, 132 cases of these complications occur most commonly in patients with C. burnetii infection localized around Cayenne were confirmed underlying cardiovascular abnormalities, vascular prosthesis, 13 6,7 by serologic analysis. or immunosuppression. All strains of C. burnetii appear to The emergence of Q fever in Cayenne was sudden. In be capable of causing cardiovascular infections, although 1996, the annual incidence of acute Q fever was 37 cases/ these subsequent infections are mainly related to host factors 100,000 inhabitants, and the incidence increased to a peak of and are independent of the clinical manifestations of acute Q 150 cases/100,000 inhabitants in 2005.14 No link between fever. Therefore, although the strain influences the severity of livestock and infection was found, but other risk factors acute Q fever, the incidence of diagnosed acute Q fever does 8 were reported, including the presence of a forest or wild not really reflect the incidence of Q fever. The occurrence mammals near the house, exposure to the aerosols generated of cardiovascular infection may be more indicative of the real by earthworks or gardening, and the presence of air condi- incidence of Q fever. tioning in vehicles (Table 1).13 Clinically, the most common Because C. burnetii is a fastidious bacteria, the most com- presentation of acute Q fever is pneumonia, and C. burnetii monly used method for the diagnosis of Q fever is serologic 9 was present in 24% of community-acquired pneumonia analysis. The phenomenon of phase variation that is exhibited cases in French Guiana.15 The prevalence of C. burnetii in by C. burnetii constitutes the basis for the interpretation of pneumonia in French Guiana was the highest of any country serologic test results. The shift from virulent phase I to aviru- reported worldwide. In metropolitan France, Q fever is endemic, and patients most commonly have fever and transaminitis (Table 1).2 In our laboratory, we tested samples from patients from metro- * Address correspondence to Didier Raoult, Aix Marseille Universite´, politan France and French Guiana and observed that for sev- Unite´ des Rickettsies, Unite´ de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM63, CNRS 7278, IRD198, INSERM eral years, the phase I IgG titers of patients from French 1095, Marseille, France. E-mail: [email protected] Guiana have been more strongly increased, without an † These authors contributed equally to this article. increase in the prevalence of cardiovascular infection, than 915 916 EDOUARD, MAHAMAT AND OTHERS Table 1 Epidemiology of Q fever in metropolitan France and French Guiana Variable Metropolitan France Reference French Guiana Reference Male sex, % 66% 28 70% 13 Age (years) 46.2 28 38.6 13 Predominant clinical Transaminitis 21 Pneumonia 13,15 presentation of acute Q fever Location of cases Rural area Urban area 13,29 Annual incidence 1.9/100,000 inhabitants 28 37–150/100,000 inhabitants 14 Seasonality Spring, summer 28 March/April–August/September 13 Risk factors Contact with parnutrients of 2,28 Living near a forest, presence of 13 infected livestock; contact bats, marsupials, or other wild with farm animals, raw milk animals near the residence; and cheese consumption; and terracing and gardening work; arthropod-borne transmission and air-conditioned vehicles for patients from metropolitan France. The aim of this study was performed on the positive serum samples as described.9 was to compare clinical symptoms, immune responses, and Serologic screening and quantification for patients from the prevalence of cardiovascular infections between patients with Marseille area was performed in our laboratory. Screening for Q fever from French Guiana and metropolitan France. Q fever serologic results for the patients from Cayenne was performed at the Pasteur Institute of Cayenne, and phase I and phase II antibody titers for these patients were quantified MATERIALS AND METHODS in our laboratory in Marseille. Study design. As a national reference center for Q fever, Polymerase chain reaction. DNA was extracted by using a our laboratory routinely receives human samples from all QIAamp Tissue Kit (QIAGEN, Hilden, Germany), and quan- parts of France, including French Guiana. We retrospectively titative real time PCR (qPCR) was performed in a CFX96 compared clinical findings, serological profiles, and preva- thermocycler (Bio-Rad, Marnes-la-Coquette, France) using primers and probes specific for intergenic sequences IS1111 lence of cardiovascular infection in patients who had been 16 diagnosed with Q fever living in the Cayenne area to similar and IS30a as described. DNA from the C. burnetii Nine Mile data from patients living in the Marseille area, in southern II strain was used as a positive control and sterile water was France, where our laboratory is located. We also compared used as negative control. The PCR was routinely performed in C. burnetii DNA detection in serum samples from these two our laboratory for negative serum samples, and preceding evi- groups. The study was approved by the local IFR48 Ethic dence of seroconversion, and on serum samples whose titer of Committee (no. 13-001). phase I IgG first reached 800; we suspected that these infec- Inclusion criteria and case definitions. We included all tions were evolving to the chronic form of the disease. patients from the Cayenne and Marseille areas who had been Statistical analysis. The Student’s t-test, Fisher’s exact test, newly diagnosed with Q fever during January 2008–December Mann-Whitney test, or chi-square test and standard statistical 2011 and who had positive serologic results for Q fever in our software (GraphPad Prism 5; GraphPad, San Diego, CA) were < laboratory. We included patients with phase II antibody titers used for statistical analyses of the data. A P value 0.05 was that were consistent with acute Q fever (IgG II ³ 200 and IgM considered significant. II ³ 50) or with increased phase I antibody titers (IgGI ³ 800) and patients who seroconverted with a four-fold increase of RESULTS phase II antibodies. Clinical data. Clinical data were obtained by phone contact In our study, we included 115 patients from the Cayenne with the physician in charge of the patients who were included area and 182 patients from the Marseille area who had been in our study.