Prevalence and clinical presentation of Rickettsia, Coxiella, Leptospira, Bartonella and chikungunya virus infections among hospital-based febrile patients from December 2008 to November 2009 in Bangladesh.

BACKGROUND: We conducted a study to identify Rickettsia, Coxiella, Leptospira, Bartonella, and Chikungunya virus infections among febrile patients presenting at hospitals in Bangladesh. METHODS: We collected blood samples from patients at six tertiary hospitals from December 2008 to November 2009 and performed laboratory tests at the United States Centers for Disease Control and Prevention (CDC). RESULTS: Out of 720 enrolled patients, 263 (37%) were infected with Rickettsia; 132 patients had immunofluorescence antibody titer >64 against spotted fever, 63 patients against scrub typhus fever and 10 patients against typhus fever. Ten patients were identified with Coxiella. We isolated Leptospira from two patients and Bartonella from one patient. Ten patients had antibodies against Chikungunya virus. The proportion of patients who died was higher with rickettsial fever (5%) compared to those without a diagnosis of rickettsial infection (2%). None of the patients were initially diagnosed with rickettsial fever. CONCLUSIONS: Rickettsial infections are frequent yet under-recognized cause of febrile illness in Bangladesh. Clinical guidelines should be revised so that local clinicians can diagnose rickettsial infections and provide appropriate drug treatment.

Genotyping and Axenic Growth of Coxiella burnetii Isolates Found in the United States Environment.

Coxiella burnetii is a gram-negative bacterium that is the etiologic agent of the zoonotic disease Q fever. Common reservoirs of C. burnetii include sheep, goats, and cattle. These animals shed C. burnetii into the environment, and humans are infected by inhalation of aerosols. A survey of 1622 environmental samples taken across the United States in 2006-2008 found that 23.8% of the samples contained C. burnetii DNA. To identify the strains circulating in the U.S. environment, DNA from these environmental samples was genotyped using an SNP-based approach to derive sequence types (ST) that are also compatible with multispacer sequence typing methods. Three different sequence types were observed in 31 samples taken from 19 locations. ST8 was associated with goats and ST20 with dairy cattle. ST16/26 was detected in locations with exposure to various animals and also in locations with no direct animal contact. Viable isolates were obtained for all three sequence types, but only the ST20 and ST16/26 isolates grew in acidified citrate cysteine medium (ACCM)-2 axenic media. Examination of a variety of isolates with different sequence types showed that ST8 and closely related isolates did not grow in ACCM-2. These results suggest that a limited number of C. burnetii sequence types are circulating in the U.S. environment and these strains have close associations with specific reservoir species. Growth in ACCM-2 may not be suitable for isolation of many C. burnetii strains.

A Mixed Outbreak of Epidemic Typhus Fever and Trench Fever in a Youth Rehabilitation Center: Risk Factors for Illness from a Case-Control Study, Rwanda, 2012.

In August 2012, laboratory tests confirmed a mixed outbreak of epidemic typhus fever and trench fever in a male youth rehabilitation center in western Rwanda. Seventy-six suspected cases and 118 controls were enrolled into an unmatched case-control study to identify risk factors for symptomatic illness during the outbreak. A suspected case was fever or history of fever, from April 2012, in a resident of the rehabilitation center. In total, 199 suspected cases from a population of 1,910 male youth (attack rate = 10.4%) with seven deaths (case fatality rate = 3.5%) were reported. After multivariate analysis, history of seeing lice in clothing (adjusted odds ratio [aOR] = 2.6, 95% confidence interval [CI] = 1.1-5.8), delayed (≥ 2 days) washing of clothing (aOR = 4.0, 95% CI = 1.6-9.6), and delayed (≥ 1 month) washing of beddings (aOR = 4.6, 95% CI = 2.0-11) were associated with illness, whereas having stayed in the rehabilitation camp for ≥ 6 months was protective (aOR = 0.20, 95% CI = 0.10-0.40). Stronger surveillance and improvements in hygiene could prevent future outbreaks.

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis - United States.

Tickborne rickettsial diseases continue to cause severe illness and death in otherwise healthy adults and children, despite the availability of low-cost, effective antibacterial therapy. Recognition early in the clinical course is critical because this is the period when antibacterial therapy is most effective. Early signs and symptoms of these illnesses are nonspecific or mimic other illnesses, which can make diagnosis challenging. Previously undescribed tickborne rickettsial diseases continue to be recognized, and since 2004, three additional agents have been described as causes of human disease in the United States: Rickettsia parkeri, Ehrlichia muris-like agent, and Rickettsia species 364D. This report updates the 2006 CDC recommendations on the diagnosis and management of tickborne rickettsial diseases in the United States and includes information on the practical aspects of epidemiology, clinical assessment, treatment, laboratory diagnosis, and prevention of tickborne rickettsial diseases. The CDC Rickettsial Zoonoses Branch, in consultation with external clinical and academic specialists and public health professionals, developed this report to assist health care providers and public health professionals to 1) recognize key epidemiologic features and clinical manifestations of tickborne rickettsial diseases, 2) recognize that doxycycline is the treatment of choice for suspected tickborne rickettsial diseases in adults and children, 3) understand that early empiric antibacterial therapy can prevent severe disease and death, 4) request the appropriate confirmatory diagnostic tests and understand their usefulness and limitations, and 5) report probable and confirmed cases of tickborne rickettsial diseases to public health authorities.

Development of a TaqMan Array Card for Acute-Febrile-Illness Outbreak Investigation and Surveillance of Emerging Pathogens, Including Ebola Virus.

Acute febrile illness (AFI) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. Convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. We developed a real-time PCR-based TaqMan array card (TAC) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 AFI-associated organisms, including 15 viruses (chikungunya, Crimean-Congo hemorrhagic fever [CCHF] virus, dengue, Ebola virus, Bundibugyo virus, Sudan virus, hantaviruses [Hantaan and Seoul], hepatitis E, Marburg, Nipah virus, o'nyong-nyong virus, Rift Valley fever virus, West Nile virus, and yellow fever virus), 8 bacteria (Bartonella spp., Brucella spp., Coxiella burnetii, Leptospira spp., Rickettsia spp., Salmonella enterica and Salmonella enterica serovar Typhi, and Yersinia pestis), and 3 protozoa (Leishmania spp., Plasmodium spp., and Trypanosoma brucei). Two extrinsic controls (phocine herpesvirus 1 and bacteriophage MS2) were included to ensure extraction and amplification efficiency. Analytical validation was performed on spiked specimens for linearity, intra-assay precision, interassay precision, limit of detection, and specificity. The performance of the card on clinical specimens was evaluated with 1,050 blood samples by comparison to the individual real-time PCR assays, and the TAC exhibited an overall 88% (278/315; 95% confidence interval [CI], 84% to 92%) sensitivity and a 99% (5,261/5,326, 98% to 99%) specificity. This TaqMan array card can be used in field settings as a rapid screen for outbreak investigation or for the surveillance of pathogens, including Ebola virus.

National Surveillance of Spotted Fever Group Rickettsioses in the United States, 2008-2012.

Spotted fever group (SFG) rickettsioses are notifiable conditions in the United States caused by the highly pathogenic Rickettsia rickettsii and less pathogenic rickettsial species such as Rickettsia parkeri and Rickettsia sp. 364D. Surveillance data from 2008 to 2012 for SFG rickettsioses are summarized. Incidence increased from 1.7 cases per million person-years (PY) in 2000 to 14.3 cases per million PY in 2012. During 2008-2012, cases of SFG rickettsiosis were more frequently reported among males, persons of white race, and non-Hispanic ethnicity. Overall, case fatality rate (CFR) was low (0.4%), however, risk of death was significantly higher for American Indian/Alaska Natives (relative risk [RR] = 5.4) and Asian/Pacific Islanders (RR = 5.7) compared with persons of white race. Children aged < 10 years continue to experience the highest CFR (1.6%). Higher incidence of SFG rickettsioses and decreased CFR likely result from increased reporting of tick-borne disease including those caused by less pathogenic species. Recently, fewer cases have been confirmed using species-specific laboratory methods (such as cell culture and DNA detection using polymerase chain reaction [PCR] assays), causing a clouded epidemiological picture. Use of PCR and improved documentation of clinical signs, such as eschars, will better differentiate risk factors, incidence, and clinical outcomes of specific rickettsioses in the future.

Increasing Incidence of Ehrlichiosis in the United States: A Summary of National Surveillance of Ehrlichia chaffeensis and Ehrlichia ewingii Infections in the United States, 2008-2012.

Human ehrlichiosis is a potentially fatal disease caused by Ehrlichia chaffeensis and Ehrlichia ewingii. Cases of ehrlichiosis are reported to Centers for Disease Control and Prevention through two national surveillance systems: Nationally Notifiable Diseases Surveillance System (NNDSS) and Case Report Forms. During 2008-2012, 4,613 cases of E. chaffeensis infections were reported through NNDSS. The incidence rate (IR) was 3.2 cases per million person-years (PYs). The hospitalization rate (HR) was 57% and the case fatality rate (CFR) was 1%. Children aged < 5 years had the highest CFR of 4%. During 2008-2012, 55 cases of E. ewingii infection were reported through NNDSS. The national IR was 0.04 cases per million PY. The HR was 77%; no deaths were reported. Immunosuppressive conditions were reported by 26% of cases. The overall rate for ehrlichiosis has increased 4-fold since 2000. Although previous literature suggests E. ewingii primarily affects those who are immunocompromised, this report shows most cases occurred among immunocompetent patients. This is the first report to show children aged < 5 years with ehrlichiosis have an increased CFR, relative to older patients. Ongoing surveillance and reporting of tick-borne diseases are critical to inform public health practice and guide disease treatment and prevention efforts.

Massive dispersal of Coxiella burnetii among cattle across the United States.

Q-fever is an underreported disease caused by the bacterium Coxiella burnetii, which is highly infectious and has the ability to disperse great distances. It is a completely clonal pathogen with low genetic diversity and requires whole-genome analysis to identify discriminating features among closely related isolates. C. burnetii, and in particular one genotype (ST20), is commonly found in cow's milk across the entire dairy industry of the USA. This single genotype dominance is suggestive of host-specific adaptation, rapid dispersal and persistence within cattle. We used a comparative genomic approach to identify SNPs for high-resolution and high-throughput genotyping assays to better describe the dispersal of ST20 across the USA. We genotyped 507 ST20 cow milk samples and discovered three subgenotypes, all of which were present across the entire country and over the complete time period studied. Only one of these sub-genotypes was observed in a single dairy herd. The temporal and geographic distribution of these sub-genotypes is consistent with a model of large-scale, rapid, frequent and continuous dissemination on a continental scale. The distribution of subgenotypes is not consistent with wind-based dispersal alone, and it is likely that animal husbandry and transportation practices, including pooling of milk from multiple herds, have also shaped the patterns. On the scale of an entire country, there appear to be few barriers to rapid, frequent and large-scale dissemination of the ST20 subgenotypes.

Human granulocytic anaplasmosis in the United States from 2008 to 2012: a summary of national surveillance data.

Human granulocytic anaplasmosis is an acute, febrile illness transmitted by the ticks Ixodes scapularis and Ixodes pacificus in the United States. We present a summary of passive surveillance data for cases of anaplasmosis with onset during 2008-2012. The overall reported incidence rate (IR) was 6.3 cases per million person-years. Cases were reported from 38 states and from New York City, with the highest incidence in Minnesota (IR = 97), Wisconsin (IR = 79), and Rhode Island (IR = 51). Thirty-seven percent of cases were classified as confirmed, almost exclusively by polymerase chain reaction. The reported case fatality rate was 0.3% and the reported hospitalization rate was 31%. IRs, hospitalization rates, life-threatening complications, and case fatality rates increased with age group. The IR increased from 2008 to 2012 and the geographic range of reported cases of anaplasmosis appears to have increased since 2000-2007. Our findings are consistent with previous case series and recent reports of the expanding range of the tick vector I. scapularis.

Serological Evidence of Coxiella burnetii Infection in Cattle and Goats in Bangladesh.

We tested 1149 ruminant sera conveniently collected from three districts of Bangladesh to identify the serological evidence of Coxiella burnetii infection in cattle and goats by enzyme-linked immunosorbent assay. We found that 0.7% (8/1149) of ruminants had detectable immunoglobulin G for C. burnetii: 0.65% (4/620) in cattle and 0.76% (4/529) in goats. A sub-set of ruminant samples was retested and confirmed by immunofluorescence assay (18/112). Although we cannot rule out false-positive reactions, our study suggests the presence of C. burnetii in cattle and goats in Bangladesh. Further studies are required to estimate disease burden at the population level and identify risk factors for Q fever in ruminants in Bangladesh.

Q fever in the United States: summary of case reports from two national surveillance systems, 2000-2012.

Q fever is a worldwide zoonosis historically associated with exposure to infected livestock. This study summarizes cases of Q fever, a notifiable disease in the United States, reported to the Centers for Disease Control and Prevention through two national surveillance systems with onset during 2000-2012. The overall incidence rate during this time was 0.38 cases per million persons per year. The reported case fatality rate was 2.0%, and the reported hospitalization rate was 62%. Most cases (61%) did not report exposure to cattle, goats, or sheep, suggesting that clinicians should consider Q fever even in the absence of livestock exposure. The prevalence of drinking raw milk among reported cases of Q fever (8.4%) was more than twice the national prevalence for the practice. Passive surveillance systems for Q fever are likely impacted by underreporting and underdiagnosis because of the nonspecific presentation of Q fever.

Community-based control of the brown dog tick in a region with high rates of Rocky Mountain spotted fever, 2012-2013.

Rocky Mountain spotted fever (RMSF) transmitted by the brown dog tick (Rhipicephalus sanguineus sensu lato) has emerged as a significant public health risk on American Indian reservations in eastern Arizona. During 2003-2012, more than 250 RMSF cases and 19 deaths were documented among Arizona's American Indian population. The high case fatality rate makes community-level interventions aimed at rapid and sustained reduction of ticks urgent. Beginning in 2012, a two year pilot integrated tick prevention campaign called the RMSF Rodeo was launched in a ∼ 600-home tribal community with high rates of RMSF. During year one, long-acting tick collars were placed on all dogs in the community, environmental acaricides were applied to yards monthly, and animal care practices such as spay and neuter and proper tethering procedures were encouraged. Tick levels, indicated by visible inspection of dogs, tick traps and homeowner reports were used to monitor tick presence and evaluate the efficacy of interventions throughout the project. By the end of year one, <1% of dogs in the RMSF Rodeo community had visible tick infestations five months after the project was started, compared to 64% of dogs in Non-Rodeo communities, and environmental tick levels were reduced below detectable levels. The second year of the project focused on use of the long-acting collar alone and achieved sustained tick control with fewer than 3% of dogs in the RMSF Rodeo community with visible tick infestations by the end of the second year. Homeowner reports of tick activity in the domestic and peridomestic setting showed similar decreases in tick activity compared to the non-project communities. Expansion of this successful project to other areas with Rhipicephalus-transmitted RMSF has the potential to reduce brown dog tick infestations and save human lives.

High prevalence and two dominant host-specific genotypes of Coxiella burnetii in U.S. milk.

BACKGROUND: Coxiella burnetii causes Q fever in humans and Coxiellosis in animals; symptoms range from general malaise to fever, pneumonia, endocarditis and death. Livestock are a significant source of human infection as they shed C. burnetii cells in birth tissues, milk, urine and feces. Although prevalence of C. burnetii is high, few Q fever cases are reported in the U.S. and we have a limited understanding of their connectedness due to difficulties in genotyping. Here, we develop canonical SNP genotyping assays to evaluate spatial and temporal relationships among C. burnetii environmental samples and compare them across studies. Given the genotypic diversity of historical collections, we hypothesized that the current enzootic of Coxiellosis is caused by multiple circulating genotypes. We collected A) 23 milk samples from a single bovine herd, B) 134 commercial bovine and caprine milk samples from across the U.S., and C) 400 bovine and caprine samples from six milk processing plants over three years. RESULTS: We detected C. burnetii DNA in 96% of samples with no variance over time. We genotyped 88.5% of positive samples; bovine milk contained only a single genotype (ST20) and caprine milk was dominated by a second type (mostly ST8). CONCLUSIONS: The high prevalence and lack of genotypic diversity is consistent with a model of rapid spread and persistence. The segregation of genotypes between host species is indicative of species-specific adaptations or dissemination barriers and may offer insights into the relative lack of human cases and characterizing genotypes.

Mixed cryoglobulinemia and secondary membranoproliferative glomerulonephritis associated with ehrlichiosis.

Ehrlichiosis is a tick-borne disease with diverse clinical presentations, ranging in severity from a flu-like illness with fever and myalgias to a serious systemic disease with multisystem organ failure. Nephrotic syndrome has been reported previously in two cases of human ehrlichiosis. A kidney biopsy revealed minimal change disease in one of those patients. Herein, we present the case of a 40-year-old man with ehrlichiosis who developed nephrotic syndrome, cryoglobulinemia, and secondary membranoproliferative glomerulonephritis (MPGN). The patient originally presented with shortness of breath, diffuse myalgias, headache, and lower extremity edema. He subsequently developed acute kidney injury and underwent kidney biopsy which showed MPGN and acute tubular injury. A tick-borne disease panel was positive for IgM and IgG to Ehrlichia chaffeensis. Serum testing revealed type 3 mixed cryoglobulinemia with no evidence of hepatitis C infection. The cryoprecipitate contained IgM and IgG antibodies to E. chaffeensis. Cryoglobulinemia is frequently associated with infections, particularly hepatitis C; however, our case is the first to describe ehrlichiosis associated with cryoglobulinemia and secondary MPGN.

Survey of laboratory animal technicians in the United States for Coxiella burnetii antibodies and exploration of risk factors for exposure.

Little is known about the prevalence of zoonotic infections among laboratory animal care technicians (LAT). Q fever, a disease caused by Coxiella burnetii, is a known occupational hazard for persons caring for livestock. We sought to determine the seroprevalence of C. burnetii antibodies among LAT and to identify risk factors associated with C. burnetii seropositivity. A survey was administered and serum samples collected from a convenience sample of 97 LAT. Samples were screened by using a Q fever IgG ELISA. Immunofluorescent antibody assays for phase I and phase II IgG were used to confirm the status of samples that were positive or equivocal by ELISA; positive samples were titered to endpoint. Antibodies against C. burnetii were detected in 6 (6%) of the 97 respondents. In our sample of LAT, seropositivity to C. burnetii was therefore twice as high in LAT as compared with the general population. Age, sex, and working with sheep regularly were not associated with seropositivity. Risk factors associated with seropositivity included breeding cattle within respondent's research facility, any current job contact with waste from beef cattle or goats, and exposure to animal waste during previous jobs or outside of current job duties. Only 15% of responding LAT reported being aware that sheep, goats, and cattle can transmit Q fever. Research facilities that use cattle or goats should evaluate their waste-management practices and educational programs in light of these findings. Additional efforts are needed to increase awareness among LAT regarding Q fever and heightened risk of exposure to infectious materials. Physicians should consider the risk of infection with C. burnetii when treating LAT with potential occupational exposures.

Etiology of severe non-malaria febrile illness in Northern Tanzania: a prospective cohort study.

INTRODUCTION: The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. METHODS AND FINDINGS: We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. CONCLUSIONS: Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts.

When outgroups fail; phylogenomics of rooting the emerging pathogen, Coxiella burnetii.

Rooting phylogenies is critical for understanding evolution, yet the importance, intricacies and difficulties of rooting are often overlooked. For rooting, polymorphic characters among the group of interest (ingroup) must be compared to those of a relative (outgroup) that diverged before the last common ancestor (LCA) of the ingroup. Problems arise if an outgroup does not exist, is unknown, or is so distant that few characters are shared, in which case duplicated genes originating before the LCA can be used as proxy outgroups to root diverse phylogenies. Here, we describe a genome-wide expansion of this technique that can be used to solve problems at the other end of the evolutionary scale: where ingroup individuals are all very closely related to each other, but the next closest relative is very distant. We used shared orthologous single nucleotide polymorphisms (SNPs) from 10 whole genome sequences of Coxiella burnetii, the causative agent of Q fever in humans, to create a robust, but unrooted phylogeny. To maximize the number of characters informative about the rooting, we searched entire genomes for polymorphic duplicated regions where orthologs of each paralog could be identified so that the paralogs could be used to root the tree. Recent radiations, such as those of emerging pathogens, often pose rooting challenges due to a lack of ingroup variation and large genomic differences with known outgroups. Using a phylogenomic approach, we created a robust, rooted phylogeny for C. burnetii. [Coxiella burnetii; paralog SNPs; pathogen evolution; phylogeny; recent radiation; root; rooting using duplicated genes.].

Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group.

Q fever, a zoonotic disease caused by the bacterium Coxiella burnetii, can cause acute or chronic illness in humans. Transmission occurs primarily through inhalation of aerosols from contaminated soil or animal waste. No licensed vaccine is available in the United States. Because many human infections result in nonspecific or benign constitutional symptoms, establishing a diagnosis of Q fever often is challenging for clinicians. This report provides the first national recommendations issued by CDC for Q fever recognition, clinical and laboratory diagnosis, treatment, management, and reporting for health-care personnel and public health professionals. The guidelines address treatment of acute and chronic phases of Q fever illness in children, adults, and pregnant women, as well as management of occupational exposures. These recommendations will be reviewed approximately every 5 years and updated to include new published evidence.

Presence and persistence of Coxiella burnetii in the environments of goat farms associated with a Q fever outbreak.

Q fever is a zoonotic disease caused by inhalation of the bacterium Coxiella burnetii. Ruminant livestock are common reservoirs for C. burnetii, and bacteria present in aerosols derived from the waste of infected animals can infect humans. The significance of infection from material deposited in the environment versus transmission directly from infected animals is not known. In 2011, an outbreak of Q fever cases on farms in Washington and Montana was associated with infected goats. A study was undertaken to investigate the quantity and spatial distribution of C. burnetii in the environment of these goat farms. Soil, vacuum, and sponge samples collected on seven farms epidemiologically linked to the outbreak were tested for the presence of C. burnetii DNA by quantitative PCR. Overall, 70.1% of the samples were positive for C. burnetii. All farms had positive samples, but the quantity of C. burnetii varied widely between samples and between farms. High quantities of C. burnetii DNA were in goat housing/birthing areas, and only small quantities were found in samples collected more than 50 m from these areas. Follow-up sampling at one of the farms 1 year after the outbreak found small quantities of C. burnetii DNA in air samples and large quantities of C. burnetii persisting in soil and vacuum samples. The results suggest that the highest concentrations of environmental C. burnetii are found in goat birthing areas and that contamination of other areas is mostly associated with human movement.

Long-Term immune responses to Coxiella burnetii after vaccination.

Q fever is a zoonotic disease caused by infection with the bacterium Coxiella burnetii. Infection with C. burnetii results in humoral and cellular immune responses, both of which are thought to contribute to protection against subsequent infection. Whole-cell formalin-inactivated vaccines have also been shown to induce both humoral and cellular immunity and provide protection. Whether measurement of cellular or humoral immunity is a better indicator of immune protection is not known, and the duration of immunity induced by natural infection or vaccination is also poorly understood. To better understand the measurement and duration of C. burnetii immunity, 16 people vaccinated against Q fever (0.2 to 10.3 years before analysis) and 29 controls with a low risk of Q fever exposure were tested for immune responses to C. burnetii by an indirect fluorescent-antibody test (IFA) to measure circulating antibody and by a gamma interferon release assay (IGRA) to measure cellular immunity. Among vaccinated subjects, the IFA detected antibodies in 13/16, and the IGRA also detected positive responses in 13/16. All of the vaccinated subjects had a positive response in at least one of the assays, whereas 8/29 control subjects were positive in at least one assay. There was not a correlation between time since vaccination and responses in these assays. These results show that IFA and IGRA perform similarly in detection of C. burnetii immune responses and that Q fever vaccination establishes long-lived immune responses to C. burnetii.