Q Fever Research Articles

Pregnancy Complicated by Q fever

Pregnancy Complicated by Q fever

Seroprevalence of rickettsial infections and Q fever in Bhutan.

BackgroundWith few studies conducted to date, very little is known about the epidemiology of rickettsioses in Bhutan. Due to two previous outbreaks and increasing clinical cases, scrub typhus is better recognized than other rickettsial infections and Q fever.MethodologyA descriptive cross-sectional serosurvey was conducted from January to March 2015 in eight districts of Bhutan. Participants were 864 healthy individuals from an urban (30%) and a rural (70%) sampling unit in each of the eight districts. Serum samples were tested by microimmunofluorescence assay for rickettsial antibodies at the Australian Rickettsial Reference Laboratory.ResultsOf the 864 participants, 345 (39.9%) were males and the mean age of participants was 41.1 (range 13–98) years. An overall seroprevalence of 49% against rickettsioses was detected. Seroprevalence was highest against scrub typhus group (STG) (22.6%) followed by spotted fever group (SFG) rickettsia (15.7%), Q fever (QF) (6.9%) and typhus group (TG) rickettsia (3.5%). Evidence of exposure to multiple agents was also noted; the commonest being dual exposure to STG and SFG at 5%. A person’s likelihood of exposure to STG and SFG rickettsia significantly increased with age and farmers were twice as likely to have evidence of STG exposure as other occupations. Trongsa district appeared to be a hotspot for STG exposure while Punakha district had the lowest STG exposure risk. Zhemgang had the lowest exposure risk to SFG rickettsia compared to other districts. People living at altitudes above 2000 meters were relatively protected from STG infections but this was not observed for SFG, TG or QF exposure.ConclusionThis seroprevalence study highlights the endemicity of STG and SFG rickettsia in Bhutan. The high seroprevalence warrants appropriate public health interventions, such as diagnostic improvements and clinical treatment guidelines. Future studies should focus on vector profiles, geospatial, bio-social and environmental risk assessment and preventive and control strategies.

Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for the seroscreening of acute Q fever in human cases.

Background & objectives:Seroprevalence of Q fever (QF) caused by Coxiella burnetii has been reported from different parts of India. Usually serological/molecular tests are employed for detection of infection. The present study was undertaken to verify the validity of three different QF phase II IgM ELISA kits for acute QF diagnosis by comparing with the gold standard indirect fluorescent antibody assay (IFA).Methods:Fifty eight serum samples collected from 42 patients (26 patients provided acute sample only and 16 both acute and convalescent samples) which were examined by all three commercial kits, were cross-checked with QF Phase II IgM IFA for confirmation.Results:Eleven patients were positive for C. burnetii antibodies by IFA in acute and/or convalescent serum samples. Taking IFA as a reference, percentages of sensitivity, specificity, positive predictive value and negative predictive value for Virion-Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03, 84.62 and 100, 25.81, 32.35, 100 per cent, respectively.Interpretation & conclusions:The three different ELISA kits exhibited poor agreement amongst them and unacceptable level of false positivity. IFA remains to be the only option for diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA results needs confirmation by C. burnetii DNA detection in real-time polymerase chain reaction.

Seroprevalence and risk factors for Coxiella burnetii, the causative agent of Q fever in the dromedary camel (Camelus dromedarius) population in Algeria.

Query (Q) fever is a globally distributed zoonotic disease caused by Coxiella burnetii, a bacterial agent for which ruminants are the most prevalent natural reservoir. Data regarding Q fever infection in camels in Algeria are limited. Therefore, a survey to detect seroprevalence of C. burnetii antibodies was conducted among healthy camel populations in a vast area in southeastern Algeria to determine distribution of the Q fever causative organism and to identify risk factors associated with infection. Between January and March 2016, blood samples were collected from 184 camels and serum samples were subsequently analysed using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. At the time of blood collection, a questionnaire investigating 13 potential predisposing factors associated with C. burnetii seropositivity was completed for every dromedary camel and herd. Results were analysed by a chi-square (χ2) test and multivariate logistic regression. The seroprevalence of C. burnetii at the animal level was 71.2% (95% CI: 65.2–78.3) and 85.3% (95% CI: 72.8–97.8) at the herd level. At the animal level, differences in seroprevalence were observed because of herd size, animal age, animal sex, presence of ticks and contact with other herds. A multivariable logistic regression model identified three main risk factors associated with individual seropositivity: (1) age class > 11 years (OR = 8.81, 95% CI: 2.55–30.41), (2) herd size > 50 head (OR = 4.46, 95% CI: 1.01–19.59) and (3) infestation with ticks (OR 2.2; 95% CI: 1.1–4.5). This study of seroprevalence of C. burnetii infection in camels in Algeria revealed a high seroprevalence of Q fever in camel populations in southeastern Algeria and provided strong evidence that Q fever represents an economic, public health and veterinary concern. Appropriate measures should be taken to prevent the spread of C. burnetii and to reduce the risk of Q fever in farm animals and humans in this agro-ecologically and strategically important region of North Africa.

Coxiella burnetii: Decline of antibody response in pluriparous dairy cows during dry period and maternal antibody levels in dairy calves in an endemically infected herd

Coxiella burnetii (C. burnetii), an intracellular zoonotic bacterium causing Q fever, is widely distributed in cattle herds. In this study, we investigated changes in antibody response during dry period in dairy cows and the course of maternal antibody levels in dairy calves by using a commercial ELISA. In a total of 35 pluriparous cows, the proportion of seropositive animals (65.7% vs. 42.9%) (p = 0.039) and the mean antibody score levels (2.8 ± 2.4 vs. 1.0 ± 1.4) (p < 0.001) declined significantly from dry cow therapy to calving. During this period, 2/12 (16.7%) formerly seronegative cows seroconverted, whereas in 10/23 (43.5%) of the seropositive animals a seronegativization occurred. C. burnetii DNA was detected by PCR in 15/35 (42.8%) of the vaginal swabs obtained immediately after calving. All twelve calves enclosed in this study were born seronegative and precolostral whole blood samples of the calves were tested negative by PCR for C. burnetii DNA. After colostrum intake, 7/12 (58.3%) of these calves seroconverted and stayed seropositive until day 33. Afterwards, the proportion of seropositive calves and the antibody scores decreased gradually. From day 103 after birth on, all calves remained seronegative. In conclusion, we recommend the exclusion of cows for the period of colostrogenesis and calves after colostrum intake from seroepidemiological investigations to avoid bias.

Workshop on Q fever.

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Diagnosis of Acute Q Fever by Detection of Coxiella burnetii DNA using Real-Time PCR, Employing a Commercial Genesig Easy Kit.

Query (Q) fever is an important zoonosis and a cause of concern for humans, due to the potential bioterrorism threat posed by the causative agent, Coxiella burnetii. Because of the danger of contracting the illness, isolation attempts are seldom made. Serological and molecular diagnostic tests are the main option. To study the prevalence of acute Q fever in Puducherry and surrounding districts of Tamil Nadu, India, employing a new commercial Real-Time Polymerase Chain Reaction (RT-PCR) kit and confirming it by the gold standard Immunofluorescence Assay (IFA). Acute phase blood samples from 72 consecutive febrile patients and 24 healthy individuals were included in this prospective study. DNA was extracted from the buffy coats and preserved at -80°C. Detection of C. burnetii was carried out employing a commercial Real-Time PCR kit. Serum samples were tested for IgM (Phase I+II) and IgG (Phase I+II) by QM-120 and QG-120, Coxiella burnetii IFA Fuller Laboratories, California, USA. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were calculated keeping IFA as the reference. Presumptive diagnosis of acute Q fever was made in two febrile patients by the Genesig Easy kit (2.78%). In addition to these two PCR positive cases, one more patient was positive for both Phase II IgM and Phase II IgG antibodies by the gold standard IFA. All 24 healthy controls were negative for Q fever by both PCR and IFA. The sensitivity, specificity, NPV and PPV for Genesig Easy kit PCR were: 66.67%, 100%, 100% and 98.57 % respectively against IFA as the reference. The true prevalence of Q fever in India and other developing countries is poorly understood, owing to the difficulties in the diagnosis of this infection. Since molecular diagnostic tests have good specificity and are mandated for confirmation of single acute samples, validation of commercial Q fever PCR kits is the need of the hour. Genesig Easy kit in our hands was found to be reliable with the moderate sensitivity and high specificity. Performing both PCR (with acute specimens) and IFA (with paired sera) would be ideal for Q fever diagnosis.

The Epidemiology and Characteristics of Q fever and Co‐infections with Scrub Typhus, Murine Typhus or Leptospirosis in Taiwan: A Nationwide Database Study

Q fever (QF) is a worldwide zoonosis associated with outbreaks. Only a few nationwide studies regarding the surveillance and epidemiology of human QF have been reported. Although QF is endemic in Taiwan, a nationwide database investigation of the epidemiology and characteristics of QF and its associations with scrub typhus (ST), murine typhus (MT) and leptospirosis (LS) has never been reported. We analysed nationwide databases of suspected QF, ST, MT and LS cases from October 2007 to December 2014 obtained from the Centers for Disease Control, Taiwan. A total of 468 (4.2%) QF cases were identified among 11109 suspected QF cases. QF cases were mainly distributed in the southern and Kaohsiung-Pingtung regions but rarely in the eastern region. Compared to non-QF cases, QF cases had significantly higher percentages of males (88.7 versus 66.2%) and high-risk occupations (farming, animal husbandry or veterinary medicine) (16.2 versus 10.5%). But the percentages of specific animal contact, including cattle (0.6 versus 0.8%) and goats (0.9 versus 1.0%), were low in both. The majority of suspected QF cases (89.4%) were simultaneously suspected with ST, MT or LS, and the combinations of suspected diseases differed between regions. The number of suspected QF cases from the eastern region decreased since 2009, which was not observed in other regions. A total of 1420 (12.8%) cases had confirmed diseases, including QF (453, 4.1%), QF+ST (7, 0.06%), QF+MT (4, 0.04%), QF+LS (4, 0.04%), MT (186, 1.7%), ST (545, 4.9%), ST+LS (11, 0.1%) and LS (210, 1.9%). Compared to cases of unknown disease, QF cases had larger percentages of high-risk occupations (16.2 versus 9.6%) but similar histories of animal contact (29.8 versus 25.1%). QF is an endemic disease in southern Taiwan. It is difficult to differentiate QF from ST, MT or LS only by high-risk occupations and history of animal contact, and co-infection of QF with these diseases should be considered.

From Q Fever to Coxiella burnetii Infection: a Paradigm Change.

Coxiella burnetii is the agent of Q fever, or "query fever," a zoonosis first described in Australia in 1937. Since this first description, knowledge about this pathogen and its associated infections has increased dramatically. We review here all the progress made over the last 20 years on this topic. C. burnetii is classically a strict intracellular, Gram-negative bacterium. However, a major step in the characterization of this pathogen was achieved by the establishment of its axenic culture. C. burnetii infects a wide range of animals, from arthropods to humans. The genetic determinants of virulence are now better known, thanks to the achievement of determining the genome sequences of several strains of this species and comparative genomic analyses. Q fever can be found worldwide, but the epidemiological features of this disease vary according to the geographic area considered, including situations where it is endemic or hyperendemic, and the occurrence of large epidemic outbreaks. In recent years, a major breakthrough in the understanding of the natural history of human infection with C. burnetii was the breaking of the old dichotomy between "acute" and "chronic" Q fever. The clinical presentation of C. burnetii infection depends on both the virulence of the infecting C. burnetii strain and specific risks factors in the infected patient. Moreover, no persistent infection can exist without a focus of infection. This paradigm change should allow better diagnosis and management of primary infection and long-term complications in patients with C. burnetii infection.

Evidence of Coxiella burnetii in Punjab province, Pakistan

Coxiella burnetii causes query (Q) fever, an important zoonotic disease with worldwide significance. The role of environment in the ecology of C. burnetti, and its influence on seroconversion in animals has not been elucidated in Pakistan. We carried out a cross-sectional study in Punjab province to (1) determine the prevalence and distribution of C. burnetii in soil using an ISIIII gene-based real time-polymerase chain reaction (RT-PCR) assay, (2) analyze association between the occurrence of C. burnetii in soil and its predictors i.e. soil characteristics (macro- and micro-nutrients) and several likely risk factors including the seroconversion in small ruminants at places where its genome had or had not been detected, and (3) predict homology and genetic diversity of the identified strains using sequences originated from different hosts worldwide. A total of 2425 soil samples from nine districts of Punjab province were processed. C. burnetii DNA was detected in 47 samples (1.94%, 95% CI: ±0.55) originating from 35 villages of studied districts (7.22%, 95% CI: ±2.30). The highest prevalence was found in Attock (7.11%, 95% CI: ±3.36), followed by Lahore (4.83%, 95% CI: ±3.49), Sahiwal (4.70%, 95% CI: ±2.6), Dera Ghazi Khan (2.33%, 95% CI: ±2.02), Faisalabad (1.35%, 95% CI: ±1.18) and Sheikhupura (0.68%, 95% CI: ±0.94). The odds of detecting bacterial DNA in soil was increased with a unit increase in organic matter [2.511 (95% CI: 1.453–4.340), p=0.001] and sodium [1.013 (95% CI: 1.005–1.022), p=0.001], whereas, calcium [0.984 (95% CI: 0.975–0.994), p=0.002] and potassium [0.994 (95% CI: 0.990–0.999), p=0.011] had protective effect where a unit increase in each analyte decreased odds for its occurrence by 1.0% approximately. Likewise, for categorical variables (risk factors), the odds of detecting C. burnetii were higher at locations >500m away from a main road [1.95 (95% CI: 1.06–3.78), p=0.04]. The enzyme-linked immunosorbent assay (ELISA) revealed an increased prevalence of antibodies in sheep (17.9%, 95% CI: ±5.54) compared with goats (16.4%, 95% CI: ±4.34). When determining the association between soil DNA and C. burnetii antibodies in small ruminants, the odds of detecting these antibodies were significant in sheep at the livestock barns [2.81 (95% CI: 1.20–7.37), p=0.02]. The IS1111 gene-based sequence analysis revealed a clustering of the DNA into two distinct groups with much genetic divergence (0.76–68.70%): the first group that contained sequences from Lahore district clustered with human and buffalo origin isolates, whereas the second group that contained the sequences from the remaining study districts clustered with goat-, rodent- and human-origin isolates. This study provides the first evidence of the presence of C. burnetii in the environment in Punjab province, Pakistan. Future studies are needed to ascertain the bacteria’s molecular epidemiology over a wide geographical area, type the isolates, and evaluates the potential risks to human populations, particularly farmers and veterinarians.

Molecular investigation of Coxiella burnetii infections in aborted sheep in eastern Turkey.

Q fever is a zoonotic disease that occurs worldwide and is caused by the obligate intracellular bacterium Coxiella burnetii. The aim of this study was to investigate the presence of C. burnetii infection in aborted sheep in eastern Turkey using PCR. A total of 200 fetuses were collected from aborted sheep belonging to 200 herds in different locations in the eastern part of Turkey. Foetal organ samples such as liver, spleen, lung and stomach were taken and the DNA was purified from two hundred pooled samples. PCR analysis of C. burnetii presence in infected organs was performed, and 4 samples (2%) were found positive. In addition, the pooled organ suspensions were inoculated to embryonated chicken eggs, and PCR analysis of yolk sacs showed C. burnetii DNA in 5 samples (2.5%). This study shows that C. burnetii infection has an important role in sheep abortions in eastern Anatolia region.

The inhibition of the apoptosis pathway by the Coxiella burnetii effector protein CaeA requires the EK repetition motif, but is independent of survivin

ABSRTACTCoxiella burnetii is an obligate intracellular bacterium that causes Query (Q) fever, a zoonotic disease. It requires a functional type IV secretion system (T4SS) which translocate bacterial effector proteins into the host cell cytoplasm and thereby facilitates bacterial replication. To date, more than 130 effector proteins have been identified, but their functions remain largely unknown. Recently, we demonstrated that one of these proteins, CaeA (CBU1524) localized to the host cell nucleus and inhibited intrinsic apoptosis of HEK293 or CHO cells. In the present study we addressed the question whether CaeA also affects the extrinsic apoptosis pathway.Ectopic expression of CaeA reduced extrinsic apoptosis and prevented the cleavage of the executioner caspase 7, but did not impair the activation of initiator caspase 9. CaeA expression resulted in an up-regulation of survivin (an inhibitor of activated caspases), which, however, was not causal for the anti-apoptotic effect of CaeA. Comparing the sequence of CaeA from 25 different C. burnetii isolates we identified an EK (glutamic acid/ lysine) repetition motif as a site of high genetic variability. The EK motif of CaeA was essential for the anti-apoptotic activity of CaeA. From these data, we conclude that the C. burnetii effector protein CaeA interferes with the intrinsic and extrinsic apoptosis pathway. The process requires the EK repetition motif of CaeA, but is independent of the upregulated expression of survivin.

Detection of Coxiella burnetii in Cattle

Coxiella burnetii is an obligate intracellular rickettsial organism and the causative agent of Query fever, a zoonosis that occurs worldwide. In Korea, C. burnetii infection had occurred in humans and animals. However, the studies were only conducted in geographically limited area for detection of C. burnetii. The objective of this study was to detect C. burnetii in Korean native cattle and dairy cattle nationwide by real-time PCR. The total of 807 blood samples from 622 Korean native cattle and 185 dairy cows, 170 individual milk samples of dairy cows, and 348 bulk tank milk samples of dairy herds were collected nationwide. From blood samples, C. burnetii was detected in 17 (2.7%) out of 622 Korean native cattle and 2 (1.1%) of 185 dairy cows. From milk samples, C. burnetii was detected in 27 (15.9%) out of 170 individual milk samples of dairy cows. And C. burnetii was detected in 84 (24.1%) of 348 bulk tank milk samples. In conclusion, this study revealed that the detection rates are considerably high in cattle and the infection of C. burnetii has been continuously occurring in cattle of Korea. In order to prevent the hazards of a zoonosis Q-fever that occur both humans and domestic animals, further studies are needed to clarify the epidemiology of Q-fever of domestic animals and humans in Korea.

Lymphoma Linked to Q Fever Bacterium; Screening Urged

Lymphoma Linked to Q Fever Bacterium; Screening Urged

First Report of Coxiella burnetii Seroprevalence in Tibetan Sheep in China.

Query (Q) fever is a vector-borne zoonosis caused by the obligate intracellular pathogen Coxiella burnetii. Animals, including dogs, cats, cattle, and sheep, can be infected by C. burnetii. However, little information is available about C. burnetii infection in Tibetan sheep in China. Antibodies against C. burnetii in Tibetan sheep serums, which were collected from Maqu County, Tianzhu County and Nyingchi Prefecture, China, between 2011 and 2013, were examined by enzyme-linked immunosorbent assay (ELISA). Overall, 14.39% (304/2112, 95% confidence interval [CI] 12.90-15.89) of the examined Tibetan sheep were positive for C. burnetii infection. The C. burnetii seroprevalence in male and female Tibetan sheep was 12.94% (95% CI 10.26-15.61) and 14.98% (95% CI 13.18-16.78), respectively. The seroprevalence varied from 13.19% (95% CI 10.08-16.30) to 14.96% (95% CI 12.31-17.62) in Tibetan sheep in different areas. In addition, the seroprevalence ranged from 13.16% (95% CI 9.83-16.50) to 15.10% (95% CI 13.15-17.04) in different age groups. The results of the present survey indicate that C. burnetii infection is highly prevalent in Tibetan sheep in China. This is the first report of C. burnetii infection in Tibetan sheep in China, extending the host range for C. burnetii. Further studies are warranted to understand better the epidemiological situation of C. burnetii transmission in these areas and elsewhere.

First serologic survey of Q fever in free-range yaks in China.

The objective of the present investigation was to determine the seroprevalence of Coxiella burnetii infection in free-range yaks in China. A total of 552 serum samples were collected from yaks in Gansu province, northwest China between April 2013 and January 2014, and antibodies against C. burnetii were evaluated using enzyme-linked immunosorbent assay (ELISA). Overall, 13.59% (75/552, 95% CI: 10.73-16.45) of the examined animals were positive for C. burnetii antibodies. There was no significant difference in C. burnetii seroprevalence between female yaks (13.78%, 95% CI: 10.36-17.19) and male yaks (13.13%, 95% CI: 7.89-18.36) (P>0.05). Coxiella burnetii seroprevalence in yaks in different age groups ranged from 10.88% to 15.26%, but the difference was not statistically significant (P>0.05). Coxiella burnetii seroprevalence in yaks sampled in different seasons ranged from 12.06% (autumn) to 18.33% (summer), but the difference was not statistically significant (P>0.05). This is the first report of C. burnetii seroprevalence in free-range yaks in China, indicating the need for measures to be taken to control C. burnetii infection in free-range yaks in China.

Molecular detection of Coxiella burnetii using an alternative loop-mediated isothermal amplification assay (LAMP).

Q fever, caused by Coxiella burnetii, is a worldwide zoonosis with important consequences for human and animal health. In livestock, the diagnosis, using direct and indirect techniques, is challenging even if to tackle coxiellosis in domesticated animals a rapid diagnosis is crucial. In the recent years, new molecular methods have been developed to overcome these issues. Several polymerase chain reaction (PCR) assays have been studied, but loop mediated isothermal amplification (LAMP) has not been fully developed. This new methodology is emerging due to simplicity and speed in diagnosis of microbial diseases. In this study, we design a new LAMP assay against C. burnetii targeting the com1 gene as an actual alternative to conventional PCR. The assay was specific to C. burnetii reactive with sensitivity comparable to standard PCR. The application of the com1 LAMP on 10 clinical samples from water buffalo, sheep, and goats, previously tested positive, confirmed the presence of C. burnetii. To our knowledge, this study is the first report of LAMP targeting C. burnetii in Europe and the results also suggest that it may be an useful and cost-effective tool for the clinical and epidemiological surveillance of Q Fever.

A sero-survey of major infectious causes of abortion in small ruminants in Morocco.

A serological survey was conducted to estimate the seroprevalence of 5 major abortive infections in 13 sheep flocks and 10 goat herds in 2 regions of Morocco. A total of 308 from aborted females (202 ewes and 106 does) and 197 sera (97 ewes and 99 does), were tested for brucellosis, chlamydiosis, Q fever, toxoplasmosis, and for 9 major serovars of Leptospira. An average abortion rate of 12.10% was found in ewes and 10.26% in does. The serological analyses revealed the presence of all 5 abortive infections, both in sheep and in goats. Ten (43%) herds/flocks were positive to brucellosis, 21 (91%) to chlamydiosis, 17 (74%) to toxoplasmosis, 13 (57%) to Q fever, and 5 (22%) to leptospirosis. Leptospira spp. serovars Copenhageni and Grypothyphosa were found in a single sheep flock, while Tarassovi and Copenhageni were detected in 4 goat herds. Of the 23 investigated herds/flocks, 22 (96%) showed mixed infections. The findings of this study confirmed the possible involvement of the 5 selected abortive infections in abortion outbreaks occurring in the investigated regions. Further investigations are needed to better understand the aetiology of infectious abortions in herds and flocks within investigated regions.

Reorganization of actin cytoskeleton in L929 cells infected with Coxiella burnetii strains isolated from placenta and foetal brain of sheep (Sardinia, Italy).

Coxiella burnetii, the etiological agent of Q Fever, is a zoonotic pathogen distributed worldwide. It has been reported that virulent strains of C. burnetii are poorly internalized by monocytes compared to avirulent variants. Virulence is also associated to the formation of pseudopodal extensions and transient reorganization of filamentous actin. In this article, we investigated the ability of 2 Coxiella strains isolated from ovine aborted samples to induce reorganization of the actin cytoskeleton in mouse fibroblast cells. Cells were exposed for 24 and 48 hours to ovine placenta and foetal brain tissue homogenates and then analysed by polymerase chain reaction (PCR) in order to detect Coxiella infection. The formation of pseudopodal extensions, the polarized distribution of F‑actin, and the involvement of C. burnetii strain in cytoskeleton reorganization have been assessed using a laser scanning confocal fluorescence microscope. Results indicate that similarly to the virulent reference strain, strains of C. burnetii isolated from foetal brain induced morphological changes - modification in F‑actin distribution and in the localization of bacteria. By contrast, C. burnetii strain isolated from ovine placenta did not induce any significant change in L929 cell morphology. In conclusion, both C. burnetii strains isolated from ovine placenta and foetal brain were pathogenic causing ovine abortion, but in vitro the C. burnetii strain isolated from brain only was able to induce F‑actin reorganization in L929 infected cells.

Prolonged Pyrexia and Hepatitis: Q fever

PRESENTATION Despite an ever-expanding spectrum of available tests, fever of unknown origin remains a diagnostic dilemma. A 40-year-old Nepalese man living in Rhode Island presented with a 1-week history of nausea, vomiting, fevers, and frontal headache. He denied neck stiffness, abdominal pain, diarrhea, rash, or urinary symptoms. In the emergency department, he had a temperature of 100.4 F (38.0 C) and was tachycardic to 108 beats per minute. His physical examination was otherwise normal. Lumbar puncture demonstrated no pleocytosis. Polymerase chain reaction testing of cerebrospinal fluid was negative for herpes simplex virus and enterovirus; a western blot was negative for Lyme IgM and IgG. Whole-body computed tomography was unrevealing. The patient was discharged but returned 4 days later with persistent headaches and fever, so he was admitted for further workup. His past medical history was notable for hypertension, for which he took chlorthalidone, and anxiety, for which he was prescribed paroxetine. Three years earlier, he had completed a 9-month course of isoniazid for latent tuberculosis infection. He lived with his wife and denied new sexual contacts, as well as use of any alcohol, tobacco, or illicit drugs. The patient had not travelled outside of New England following his emigration from Nepal 3 years before. He lived in an urban area and worked as a maintenance worker at a suburban warehouse where he had rodent contact and cut the grass but he denied tick bites. He had visited a farm