The epidemic of Q fever in 2018 to 2019 in Zhuhai city of China determined by metagenomic next-generation sequencing.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Cb). From January 2018 to November 2019, plasma samples from 2,382 patients with acute fever of unknown cause at a hospital in Zhuhai city of China were tested using metagenomic next-generation sequencing (mNGS). Of those tested, 138 patients (5.8%) were diagnosed with Q fever based on the presence of Cb genomic DNA detected by mNGS. Among these, 78 cases (56.5%) presented from Nov 2018 to Mar 2019, suggesting an outbreak of Q fever. 55 cases with detailed clinical information that occurred during the outbreak period were used for further analysis. The vast majority of plasma samples from those Cb-mNGS-positive patients were positive in a Cb-specific quantitative polymerase chain reaction (n = 38) and/or indirect immunofluorescence assay (n = 26). Mobile phone tracing data was used to define the area of infection during the outbreak. This suggested the probable infection source was Cb-infected goats and cattle at the only official authorized slaughterhouse in Zhuhai city. Phylogenic analysis based on genomic sequences indicated Cb strains identified in the patients, goat and cattle were formed a single branch, most closely related to the genomic group of Cb dominated by strains isolated from goats. Our study demonstrates Q fever was epidemic in 2018-2019 in Zhuhai city, and this is the first confirmed epidemic of Q fever in a contemporary city in China.

Molecular Detection of Coxiella burnetii in Unstandardized Minas Artisanal Cheese Marketed in Southeastern Brazil.

Q fever is a zoonotic disease caused by Coxiella burnetii. The causative pathogen has been detected in dairy products, which raises the possibility of consumption of dairy products as a possible route of transmission; however, this has not been adequately described. Therefore, the aim of the present study was to investigate the presence of C. burnetii in 87 samples of artisanal cheeses made from unpasteurized raw milk sold in Minas Gerais, southeastern Brazil. The cheese samples were analyzed using quantitative real-time PCR (qPCR), and the products from positive samples were sequenced. In addition, 150 people were interviewed to outline the profile of consumers and the consumption of non-inspected dairy products. The results showed that 4.6% (4/87) of the samples were positive for C. burnetii, with 99.84% identity with the reference 16S gene. Responses from consumer interviews indicate that 95.3% (143/150) of respondents consume milk and dairy products; 50% (75/150) consume fresh Minas artisanal cheese and milk at least once a day; 64.58% (93/144) do not check the inspection stamps on the packaging at the time of purchase; and 81.56% (122/146) do not know the meaning of these stamps. Thus, the presence of C. burnetii DNA in the analyzed cheeses and the consumption of unstandardized dairy products raise an alert for the risk of transmission of Q fever in the population that consumes them.

Real-time PCR biochip for on-site detection of Coxiella burnetii in ticks.

BACKGROUND: Q fever, a zoonosis caused by Coxiella burnetii, has adverse effects on public health. Ticks are vectors of C. burnetii and they contribute to the transmission of the pathogen. A tool for rapid, sensitive, and accurate detection of C. burnetii from ticks is important for the prevention of Q fever. METHODS: Ultra-rapid real-time PCR (UR-qPCR) as a chip-based real-time PCR system was developed for the detection of C. burnetii from ticks. The UR-qPCR system was established and evaluated for the rapidity, sensitivity, and specificity of C. burnetii detection. RESULTS: C. burnetii was detected using UR-qPCR from 5644 larval, nymphal, and adult ticks from 408 pools collected from livestock and epidemiologically linked environments in two provinces, Gangwon and Jeju, in Korea. Ticks from three species were identified; Haemaphysalis longicornis accounted for the highest number, present in 333 of 408 pools (81.62%), followed by Haemaphysalis flava in 62 pools (15.19%) and Ixodes nipponensis in 13 pools (3.19%). The rapidity and sensitivity of PCR detection was demonstrated with the sufficient amplification and detection of approximately 56 copies of C. burnetii DNA with only 20 min of PCR amplification. The kappa value for the diagnostic agreement between UR-qPCR and stationary qPCR was in perfect agreement (κ = 1). PCR detection and sequencing indicated that C. burnetii was present in 5 of the 408 pools (1.23%), in which four pools contained H. longicornis and one pool contained H. flava. The infection rates of C. burnetii in the tick pools collected from Gangwon and Jeju Provinces were 1.70% and 0.58%, respectively. Phylogenetic analysis indicated a close relationship between the detected C. burnetii and those originating from goats, humans, and ticks in different countries, such as the USA, France, Germany, and Serbia. CONCLUSIONS: The methods described in this study could be important for the prevention and control of Q fever in the two provinces. The UR-qPCR, with its features of mobility, sensitivity, and rapidity, is helpful for constructing early alert systems in the field for C. burnetii in ticks and could help alleviate the transmission of and economic damage due to Q fever.

Update on prevalence and distribution pattern of tick-borne diseases among humans in India: a review.

In the present scenario, tick-borne diseases (TBDs) are well known for their negative impacts on humans as well as animal health in India. The reason lies in their increased incidences due to global warming, environmental and ecological changes, and availability of suitable habitats. On a global basis, they are now considered a serious threat to human as well as livestock health. The major tick-borne diseases in India include Kyasanur forest disease (KFD), Crimean-congo hemorrhagic fever (CCHF), Lyme disease (LD), Q fever (also known as coxiellosis), and Rickettsial infections. In recent years, other tick-borne diseases such as Babesiosis, Ganjam virus (GANV), and Bhanja virus (BHAV) infections have also been reported in India. The purpose of this paper is to review the history and the current state of knowledge of tick-borne diseases in the country. The conclusion of this review is extending the requirement of greater efforts in research and government management for the diagnosis and treatment and as well as prevention of these diseases so that tick-borne disease burden should be minimizing in India.

Serological evidence of single and mixed infections of Rift Valley fever virus, Brucella spp. and Coxiella burnetii in dromedary camels in Kenya.

Camels are increasingly becoming the livestock of choice for pastoralists reeling from effects of climate change in semi-arid and arid parts of Kenya. As the population of camels rises, better understanding of their role in the epidemiology of zoonotic diseases in Kenya is a public health priority. Rift Valley fever (RVF), brucellosis and Q fever are three of the top priority diseases in the country but the involvement of camels in the transmission dynamics of these diseases is poorly understood. We analyzed 120 camel serum samples from northern Kenya to establish seropositivity rates of the three pathogens and to characterize the infecting Brucella species using molecular assays. We found seropositivity of 24.2% (95% confidence interval [CI]: 16.5-31.8%) for Brucella, 20.8% (95% CI: 13.6-28.1%) and 14.2% (95% CI: 7.9-20.4%) for Coxiella burnetii and Rift valley fever virus respectively. We found 27.5% (95% CI: 19.5-35.5%) of the animals were seropositive for at least one pathogen and 13.3% (95% CI: 7.2-19.4%) were seropositive for at least two pathogens. B. melitensis was the only Brucella spp. detected. The high sero-positivity rates are indicative of the endemicity of these pathogens among camel populations and the possible role the species has in the epidemiology of zoonotic diseases. Considering the strong association between human infection and contact with livestock for most zoonotic infections in Kenya, there is immediate need to conduct further research to determine the role of camels in transmission of these zoonoses to other livestock species and humans. This information will be useful for designing more effective surveillance systems and intervention measures.

Risk of seropositivity to Coxiella burnetii in humans living in areas with endemically infected cattle: No way for specific prevention.

Q fever, a zoonotic disease caused by Coxiella burnetii, is endemic among cattle in Western France. However, studies assessing the risk of human infection in such areas are lacking to date, while they may provide information about key specific preventive actions which could be advised to the human populations living with or close to cattle. Therefore, we conducted a cross-sectional study in two departments of Western France during the 2017/18 winter in order to explore possible risk factors for seropositivity among two distinct populations, i) an occupational risk group, that is, the cattle farmers, and ii) the general adult population (approached by blood donors). Sera were collected in 176 cattle farmers and 347 blood donors respectively, and tested for phase I and II antibodies using an indirect immunofluorescence antibody assay. Each participant was asked to fill in a questionnaire containing socio-demographic characteristics, occupational and non-occupational risk exposure. Identified risk factors were: in the general population, working in contact with ruminants, comparatively to any other activity (OR = 4.41; 95% CI: [1.59-6.55]); among farmers, managing an itself infected cattle herd (OR = 3.20; 95% CI: [1.59-6.55]). No other controllable risk factor (lifestyle, outdoor activities, proximity to pets and livestock animals, occupational practices) was here evidenced. In areas with endemically infected cattle, human exposure to Coxiella burnetii is to some extent unavoidable. This strengthens the need for physicians' awareness of the symptoms of Q fever and the appropriateness of general biosecurity measures, especially among at-risk groups living there.

Vector competence of the African argasid tick Ornithodoros moubata for the Q fever agent Coxiella burnetii.

Q fever is a widespread zoonotic disease caused by the intracellular bacterium Coxiella burnetii. While transmission is primarily but not exclusively airborne, ticks are usually thought to act as vectors on the basis of early microscopy studies. However, recent observations revealed that endosymbionts of ticks have been commonly misidentified as C. burnetii, calling the importance of tick-borne transmission into question. In this study, we re-evaluated the vector competence of the African soft tick Ornithodoros moubata for an avirulent strain of C. burnetii. To this end, we used an artificial feeding system to initiate infection of ticks, specific molecular tools to monitor further infections, and culture assays in axenic and cell media to check for the viability of C. burnetii excreted by ticks. We observed typical traits associated with vector competence: The exposure to an infected blood meal resulted in viable and persistent infections in ticks, trans-stadial transmissions of infection from nymphs to adults and the ability of adult ticks to transmit infectious C. burnetii. However, in contrast to early studies, we found that infection differed substantially between tick organs. In addition, while adult female ticks were infected, we did not observe C. burnetii in eggs, suggesting that transovarial transmission is not effective. Finally, we detected only a sporadic presence of C. burnetii DNA in tick faeces, but no living bacterium was further isolated in culture assays, suggesting that excretion in faeces is not a common mode of transmission in O. moubata.

Molecular investigation, isolation and phylogenetic analsysis of Coxiella burnetii from aborted fetus and ticks.

Q fever is a zoonotic infection threatening human health, causing abortions in cattle, sheep and goats. Coxiella burnetii (C. burnetii) also causes serious problems such as low birth weight, infertility. This study is the first exemplary for analysis of Q fever around Black Sea region in Turkey. In the study, a total of 270 aborted fetuses (171 cattle, 79 sheep, 20 goats) and 1069 tick samples were aimed to be searched by PCR method. C. burnetii DNA was detected in 8 (2.96 %) of 270 sheep specimens while it could not be found in cattle and goat specimens. 406 sample pools were created from 1069 tick samples (490 male, 579 female) collected from 254 farm animals (187 cattle, 54 sheep, 13 goats) and 11 of these were stated positive. Tick species determined as C. burnetii positive were Hyalomma marginatum, Hyalomma anoliticum excavatum, Hyalomma detritum and Boophilus annulatus. Agent isolation was carried out within embryonated eggs. Agents were stained with Giemsa and was showed. Sequence analysis was performed for TUR/SAM/coxiella_1 (MN917207) isolate and phylogenetic tree was created. This tree, created in compliance with IS1111 transposon gene, did not form different branches in regard to host affiliation (goat, sheep, tick, human) and geographical distribution. As a result, an important zoonotic agent, C. burnetii was diagnosed in sheep aborted fetuses and the infection was proved to have spread among sheep herds in Black Sea region. Besides, 4 separate tick species found in our region hosted the agent and were found important for infection.

Coxiella burnetii infection in humans: to what extent do cattle in infected areas free from small ruminants play a role?

Domestic ruminants (cattle, goats and sheep) are considered to be the main reservoirs for human Coxiella burnetii infection. However, there is still a need to assess the specific contribution of cattle. Indeed, most seroprevalence studies in humans were carried out in areas comprising both cattle and small ruminants, the latter being systematically implicated in human Q fever outbreaks. Therefore, we conducted a cross-sectional study in areas where C. burnetii infection in cattle was endemic, where the density of cattle and small ruminant farms were respectively high and very low. The aim was to estimate the seroprevalence rates among two occupational (cattle farmers and livestock veterinarians), and one non-occupational (general adult population) risk groups. Sera were collected in 176 cattle farmers, 45 veterinarians and 347 blood donors, and tested for phase I and II antibodies using immunofluorescence assay. Seroprevalence rates were 56.3% among cattle farmers, 88.9% among veterinarians and 12.7% among blood donors. This suggests that a specific risk for acquiring C. burnetii infection from cattle in endemically infected areas exists, mainly for occupational risk groups, but also for the general population. Further research is needed to identify risk factors for C. burnetii infection in humans in such areas.

Q Fever (Coxiella Burnetii).

Q fever is a zoonotic infectious disease caused by the Coxiella burnetii bacterium. It is an obligate intracellular pathogen with a high infection capacity that proliferates exclusively in an acidified medium, forming a lysosome-like vacuole. It presents a peculiar phenomenon called "antigenic phase variation," produced by a modification in the complexity of the membrane lipopolysaccharides. Q fever can be found worldwide and presents variable clinical features and geographical distribution. It mostly affects people in rural areas who are in contact with animals. The most common type of transmission to humans is via the inhalation of aerosols containing the pathogen, especially those formed from placental derivatives. Wild animals, domestic animals, and ticks are the principal reservoirs.Diagnosis is mainly made by indirect methods such as serology or by direct methods such as microbiological cultures or tests that detect the specific DNA. Typically, there are two clinical presentations: the acute disease, which is more frequent and often asymptomatic, and a persistent focalized infection in 4 to 5% of patients, generally with a poor evolution. Treatment of the acute form in both children and adults consists of administering doxycycline, while persistent focalized infection should be treated with at least two antibiotics, such as doxycycline and hydroxychloroquine. Several measures should be undertaken to minimize exposure among people working with animals or handling birth products. Different vaccines have been developed to prevent infection, though few data are available.

A sporadic case of acute Q fever and identification of the animal source of the infection.

Q fever is a zoonosis. Humans are infected through the inhalation of Coxiella burnetii particles that are dispersed into the air from the birth products or faeces of ruminants. Major outbreaks can occur in association with farming activities. C. burnetii can be disseminated by wind up to several tens of kilometres and infect humans far from its zoonotic source. As a result, the sources of sporadic cases are rarely identified. We report a sporadic case of acute Q fever in a French farmer returning from a cruise in the Caribbean. Careful examination found that the infection was not associated with travel, and a veterinary investigation identified C. burnetii DNA (MST genotype 8) in the faeces, nasal and vaginal swabs of several ewes from her herd of sheep. As a consequence, the herd was slaughtered to avoid dissemination of the infection.

Molecular Investigation of the Status of Ticks on Infected Cattle for Coxiella burnetii in India.

PURPOSE: In Indian subcontinent, the epidemiological studies on the status of ticks in the transmission of Coxiella burnetii have not been explored comprehensively. The objective of the present study was to investigate the status of ticks for C. burnetii among coxiellosis positive cattle. METHODS: The present study was carried out in three locations of the northern states of India. A total of 1648 tick samples were collected from the tick infested cattle (n = 146) that were tested positive for coxiellosis by indirect serum-ELISA assay and/or the trans-PCR assay. The tick samples were screened using the trans-PCR assay targeting species-specific IS1111 transposase gene of C. burnetii. The sequencing of PCR products was planned to differentiate C. burnetii and Coxiella-like bacteria (CLB). RESULTS: The collected ticks were identified as Rhipicephalus microplus (n = 1049), Hyalomma anatolicum (n = 416), and Hyalomma spp. (n = 183). On molecular investigation, none of the collected tick samples were found to be positive for the IS1111 gene. CONCLUSION: The findings of the present study ruled out the involvement of ticks in circulation of the pathogen within the cattle population that were screened. However, extensive epidemiological studies are needed to conclusively rule out or establish the role of ticks as a competent vector for C. burnetii transmission in cattle and other hosts.

A Deterministic Model for Q Fever Transmission Dynamics within Dairy Cattle Herds: Using Sensitivity Analysis and Optimal Controls.

This paper presents a differential equation model which describes a possible transmission route for Q fever dynamics in cattle herds. The model seeks to ascertain epidemiological and theoretical inferences in understanding how to avert an outbreak of Q fever in dairy cattle herds (livestock). To prove the stability of the model's equilibria, we use a matrix-theoretic method and a Lyapunov function which establishes the local and global asymptotic behaviour of the model. We introduce time-dependent vaccination, environmental hygiene, and culling and then solve for optimal strategies. The optimal control strategies are necessary management practices that may increase animal health in a Coxiella burnetii-induced environment and may also reduce the transmission of the disease from livestock into the human population. The sensitivity analysis presents the relative importance of the various generic parameters in the model. We hope that the description of the results and the optimality trajectories provides some guidelines for animal owners and veterinary officers on how to effectively minimize the bacteria and control cost before/during an outbreak.

Q fever: Evidence of a massive yet undetected cross-border outbreak, with ongoing risk of extra mortality, in a Dutch-German border region.

BACKGROUND: Following outbreaks in other parts of the Netherlands, the Dutch border region of South Limburg experienced a large-scale outbreak of human Q fever related to a single dairy goat farm in 2009, with surprisingly few cases reported from neighbouring German counties. Late chronic Q fever, with recent spikes of newly detected cases, is an ongoing public health concern in the Netherlands. We aimed to assess the scope and scale of any undetected cross-border transmission to neighbouring German counties, where individuals unknowingly exposed may carry extra risk of overlooked diagnosis. METHODS: (A) Seroprevalence rates in the Dutch area were estimated fitting an exponential gradient to the geographical distribution of notified acute human Q fever cases, using seroprevalence in a sample of farm township inhabitants as baseline. (B) Seroprevalence rates in 122 neighbouring German postcode areas were estimated from a sample of blood donors living in these areas and attending the regional blood donation centre in January/February 2010 (n = 3,460). (C) Using multivariate linear regression, including goat and sheep densities, veterinary Q fever notifications and blood donor sampling densities as covariates, we assessed whether seroprevalence rates across the entire border region were associated with distance from the farm. RESULTS: (A) Seroprevalence in the outbreak farm's township was 16.1%. Overall seroprevalence in the Dutch area was 3.6%. (B) Overall seroprevalence in the German area was 0.9%. Estimated mean seroprevalence rates (per 100,000 population) declined with increasing distance from the outbreak farm (0-19 km = 2,302, 20-39 km = 1,122, 40-59 km = 432 and ≥60 km = 0). Decline was linear in multivariate regression using log-transformed seroprevalence rates (0-19 km = 2.9 [95% confidence interval (CI) = 2.6 to 3.2], 20 to 39 km = 1.9 [95% CI = 1.0 to 2.8], 40-59 km = 0.6 [95% CI = -0.2 to 1.3] and ≥60 km = 0.0 [95% CI = -0.3 to 0.3]). CONCLUSIONS: Our findings were suggestive of widespread cross-border transmission, with thousands of undetected infections, arguing for intensified cross-border collaboration and surveillance and screening of individuals susceptible to chronic Q fever in the affected area.

Transmission of Coxiella burnetii by ingestion in mice.

Coxiella burnetii, the causative agent of Q fever, is widely present in dairy products around the world. It has been isolated from unpasteurised milk and cheese and can survive for extended periods of time under typical storage conditions for these products. Although consumption of contaminated dairy products has been suggested as a potential route for transmission, it remains controversial. Given the high prevalence of C. burnetii in dairy products, we sought to examine the feasibility of transmitting the major sequence types (ST16, ST8 and ST20) of C. burnetii circulating in the United States. We delivered three strains of C. burnetii, comprising each sequence type, directly into the stomachs of immunocompetent BALB/c mice via oral gavage (OG) and assessed them for clinical symptoms, serological response and bacterial dissemination. We found that mice receiving C. burnetii by OG had notable splenomegaly only after infection with ST16. A robust immune response and persistence in the stomach and mesenteric lymph nodes were observed in mice receiving ST16 and ST20 by OG, and dissemination of C. burnetii to peripheral tissues was observed in all OG infected mice. These findings support the oral route as a mode of transmission for C. burnetii.

Spatial transmission risk during the 2007-2010 Q fever epidemic in The Netherlands: Analysis of the farm-to-farm and farm-to-resident transmission.

Between 2007 and 2010 a Q fever epidemic in Dutch dairy goat farms caused a large Q fever outbreak in human residents in the southern part of the Netherlands. Here we characterize the transmission of Coxiella burnetii, the aetiological agent of Q fever, between infected and susceptible dairy goat farms by estimating a spatial transmission kernel. In addition, we characterize the zoonotic transmission of C. burnetii by estimating the spatial kernel for transmission from infected farms to neighbouring residents. Whereas the range of between-farm transmission is comparable to the scale of the Netherlands, likely due to long-range between-farm contacts such as animal transport, the transmission risk from farms to humans is more localized, although still extending to 10 km and beyond. Within a range of about 10 km, the transmission risk from an infected goat farm to a single resident is of the same order of magnitude as the farm-to-farm transmission risk per animal in a receiving farm. We illustrate how, based on the estimated kernels, spatial patterns of transmission risks between farms and from farms to residents can be calculated and visualized by means of risk maps, offering further insight relevant to policy making in a one-health context.

Uptake and fecal excretion of Coxiella burnetii by Ixodes ricinus and Dermacentor marginatus ticks.

BACKGROUND: The bacterium Coxiella burnetii is the etiological agent of Q fever and is mainly transmitted via inhalation of infectious aerosols. DNA of C. burnetii is frequently detected in ticks, but the role of ticks as vectors in the epidemiology of this agent is still controversial. In this study, Ixodes ricinus and Dermacentor marginatus adults as well as I. ricinus nymphs were fed on blood spiked with C. burnetii in order to study the fate of the bacterium within putative tick vectors. METHODS: Blood-feeding experiments were performed in vitro in silicone-membrane based feeding units. The uptake, fecal excretion and transstadial transmission of C. burnetii was examined by quantitative real-time PCR as well as cultivation of feces and crushed tick filtrates in L-929 mouse fibroblast cells and cell-free culture medium. RESULTS: Ticks successfully fed in the feeding system with engorgement rates ranging from 29% (D. marginatus) to 64% (I. ricinus adults). Coxiella burnetii DNA was detected in the feces of both tick species during and after feeding on blood containing 105 or 106 genomic equivalents per ml blood (GE/ml), but not when fed on blood containing only 104 GE/ml. Isolation and cultivation demonstrated the infectivity of C. burnetii in shed feces. In 25% of the I. ricinus nymphs feeding on inoculated blood, a transstadial transmission to the adult stage was detected. Females that molted from nymphs fed on inoculated blood excreted C. burnetii of up to 106 genomic equivalents per mg of feces. CONCLUSIONS: These findings show that transstadial transmission of C. burnetii occurs in I. ricinus and confirm that I. ricinus is a potential vector for Q fever. Transmission from both tick species might occur by inhalation of feces containing high amounts of viable C. burnetii rather than via tick bites.

Prevalence of Coxiella burnetii (Legionellales: Coxiellaceae) Infection Among Wildlife Species and the Tick Hyalomma lusitanicum (Acari: Ixodidae) in a Meso-Mediterranean Ecosystem.

Q fever is a worldwide zoonosis caused by Coxiella burnetii (Derrick) Philip. It is a major cause of abortion among sheep and may be responsible for reproductive losses in red deer in Spain. Airborne transmission is the most widespread; however, some studies suggested that ticks may play a role, but little is known about their actual involvement in the C. burnetii cycle. The aim of this study was to determine the role that Hyalomma lusitanicum (Koch) tick plays in the maintenance of this agent among wildlife in the meso-Mediterranean areas. We processed by PCR 53 swabs from wild rabbits, 21 liver samples from red deer, and 236 ticks collected at different stages. Coxiella burnetii DNA was detected in 43.40% of wild rabbits and 38.09% of red deer, supporting the hypothesis that these animals are quite likely to serve as a reservoir in the field. We also found a high prevalence of C. burnetii in ticks (55.66%). It is worth noting that 50.45% of positive ticks were collected from negative hosts, suggesting that the pathogen probably was acquired at a previous tick stage. Our results suggest transstadial transmission, and the presence of bacterial DNA in the offspring of positive female ticks is the first evidence of the transovarial transmission of C. burnetii by H. lusitanicum. Thus, this tick species seems to play an important role as a bridge of infection in the wildlife cycle, although further studies are needed to confirm vector competence.

Q fever during pregnancy: a narrative review.

BACKGROUND: Coxiella burnetii, the causative agent of Q fever, causes abortions in animals. Its effects on pregnancy in humans and the management of Q fever in pregnancy are uncertain. OBJECTIVES: To summarize data on the effects of Q fever on pregnancy in women, the effects of pregnancy on Q fever complications and the optimal screening and management of Q fever during pregnancy. SOURCES: We searched for studies reporting on Q fever during pregnancy in women. We included randomized and observational studies, seroprevalence studies, case series and case reports, including clinical and histopathological studies. CONTENT: The accumulating data seems convincing that Q fever increases the risk of abortions in early pregnancy and prematurity or intrauterine fetal demise in late pregnancy. Data are based on sero-epidemiological associations of Q fever and adverse pregnancy outcomes and case reports showing the presence and effects of C. burnetii on the placenta and the fetus. Based on observational studies, acquisition of Q fever during pregnancy also increases the risk for maternal chronic Q fever. Treatment of recently infected women seems to improve these outcomes, based on case series only, but the optimal duration of treatment has not been studied. The efficacy of active surveillance during pregnancy, timing and frequency have not been determined in high-endemicity settings. Obstetricians should be aware of the risk for transmission of the disease during delivery. Currently available data are based mostly on case series and case reports, with some discrepancy between the French experience in chronic endemicity settings and Dutch experience in outbreak settings. IMPLICATIONS: Since infection with Q fever is largely asymptomatic, we believe that the accumulating information linking Q fever to adverse pregnancy outcomes justifies screening in the high-endemicity setting and treatment of infected women. High-quality research addressing the questions raised by this review is needed to determine the optimal public health policy.