Q fever or ‘Query fever’ was first identified in 1937 after an outbreak of febrile illness in abattoir workers in Queensland, Australia (Derrick, 1937). Q fever is a bacterial infection caused by the Gram-negative bacteria Coxiella burnetii, which has a wide host range including humans, ruminant livestock, companion animals, wildlife and ticks. Q fever is considered to be a neglected zoonosis which has been historically misdiagnosed and under-reported at the global scale (Boone et al, 2017). Advances in diagnostic technologies have enabled new insights into its prevalence, distribution and epidemiology in the past decade. Q fever has a near worldwide distribution (Maurin and Raoult, 1999) but profound knowledge gaps – particularly regarding variation in the human health and livestock production impacts of this disease – persist in many global contexts.
Q fever typically refers to clinical manifestation of disease in humans, whereas coxiellosis refers to an infection in animals, that may or may not be symptomatic. These terms are often used interchangeably, but the authors will follow the above distinction throughout this article. In livestock, C. burnetii infection often remains clinically inapparent, except in cases of abortion and early-stage pregnancy loss, which are reported more frequently in goats and sheep than cattle (Van den Brom et al, 2015a). In humans, infection can cause either a self-limiting acute or, more rarely, a chronic disease (Gikas et al, 2010). Acute human infections are also often asymptomatic, but the most common clinical manifestation are non-specific flu-like symptoms and pneumonia (Marrie, 2010). Of particular clinical concern is chronic infection, which is estimated to occur in about 1–5% of Q fever cases, and this may cause long-term health complications or even death (Maurin and Raoult, 1999).
Within the UK, there has been relatively limited interest in the disease due to the small number of reported cases of human Q fever and livestock coxiellosis. However, recent changes in livestock reporting to bring the UK into alignment with EU Animal Health Regulation requirements have made coxiellosis a reportable disease (Department for Environment, Food and Rural Affairs, 2021). Coxiellosis itself is not reportable in all EU countries, however as the UK is a third country wishing to export live animals into the EU it becomes reportable here. Alongside a general increased interest and awareness of zoonotic disease, this change is contributing to a new impetus from academia and the veterinary profession to understand the potential health impacts of C. burnettii on both humans and livestock within the UK. This article aims to summarise the current understanding of Q fever and coxiellosis, both in general and in a UK context.
Q fever in humans
Approximately 40% of people infected with C. burnetii will develop symptoms of acute Q fever, of which the majority will present as a non-specific, self-limiting illness (Raoult et al, 2005). In more severe cases clinical symptoms include fever, headache, chills, atypical pneumonia and hepatitis (Raoult et al, 2005). Acute episodes are rarely fatal. In the Netherlands outbreak (2007–2010), a mortality rate of 1.2% within 1 month of hospitalisation was observed; however, in all these cases severe underlying medical conditions were noted (Kampschreur et al, 2010). Chronic Q fever develops in less than 5% of people exposed to the infection and symptoms may only manifest years after the initial infection. Clinical symptoms of chronic Q fever include non-specific fatigue, fever, weight loss, night sweats, hepatosplenomegaly and vascular complications as well as endocarditis (Raoult et al, 2005; van der Hoek et al, 2012; Wegdam-Blans et al, 2012). Aneurysm and endocarditis are relatively common and directly contribute to the 25% mortality rates in chronic Q fever sufferers (van Roeden et al, 2018).
A further manifestation of infection is Q fever fatigue syndrome (QFS) which is thought to occur in approximately 20% of acute Q fever sufferers (Morroy et al, 2016a). While the symptoms are poorly defined, sufferers experience significant long-term impaired health status and reduced quality of life similar to that observed in chronic fatigue syndrome (Morroy et al, 2016b). Hospitalisation as a result of acute Q fever appears to be a significant risk factor (Morroy et al, 2011).
Coxiellosis in livestock
The most common clinical presentation of coxiellosis in livestock species is late-term abortion, which is observed in goats, sheep and cattle. There is some debate (but a lack of robust evidence from many contexts) as to whether the infection may also be associated with other reproductive anomalies such as stillbirth, infertility, uterine diseases such as metritis and endometritis, and mastitis in cattle (Agerholm, 2013; Lopez-Helguera et al, 2013; De Biase et al, 2018). Infected placentae harbour the highest concentrations of C. burnetii either after abortion or after livebirth (Roest et al, 2012). The infection is often clinically inapparent in non-pregnant individuals and as abortion occurs most frequently in the last third of gestation, without any preceding clinical symptoms (Arricau-Bouvery and Rodolakis, 2005), the disease status of a herd or flock may not be known until after an abortion event. Furthermore, abortion and stillbirth, but also the birth of strong and lively kids, can occur after Q fever infection of pregnant animals (Arricau-Bouvery and Rodolakis, 2005; Roest et al, 2012; Garcia-Ispierto et al, 2013).
In infected livestock, C. burnetii may be shed in significant amounts in birth products, vaginal mucus, urine, faeces or milk (Garcia-Ispierto et al, 2013). Given the particularly high bacterial load in birth products, these are a potent source of infection and contamination; however, given the highly infectious nature of the bacteria (1–10 bacteria required for infection) other routes cannot be discounted, and sporadic shedding of C. burnetii has been observed to occur throughout the year in cattle (Guatteo et al, 2007). Infectious organisms may persist for many months after shedding, and can be detectable in the immediate environment (i.e. lambing pen) and also on the wool of infected sheep (Wattiau et al, 2011). Close proximity to the initial contamination source (kidding/lambing pen) is correlated with a high risk of infection, although infectious organisms can be transferred to other areas of the farm mainly through human activity (Kersh et al, 2013). Mathematical models using experimental data to understand the transmission of the infection within the UK dairy system estimate that the spread of C. burnetii is significantly greater within housed environments compared to more extensive outdoor grazing systems due to high infectious pressure caused by the intermittent shedding and environmental stability of the organism and constant exposure to naïve animals (Patsatzis et al, 2022).
Aerosolised transmission is a potential route of spread between infected herds/flocks and both naïve herds/flocks and human populations. This route of transmission is often associated with specific environmental conditions that favour dispersal, including wind speed and the topography of the landscape (Mori and Roest, 2018). Low but consistent wind speed was a significant factor in the dispersal and transmission of C. burnetii in a flat area of the North Brabant region of the Netherlands during the outbreak in 2007–2010 (van Leuken et al, 2015). Seemingly contradictorily, high wind speeds, but open landscapes, high animal densities and high temperatures were identified as risk-factors for transmission of coxiellosis between Swedish dairy cattle herds (Nusinovici et al, 2017).
C. burnetii DNA has been found in milk samples obtained from sheep, goats and cattle (Ahmadinezhad et al, 2022). Analyses of bulk-milk cattle samples have detected C. burnetii DNA in 29% of UK bulk milk samples (Velasova et al, 2017) consistent with the results of other studies both within European and non-European countries (Rabaza et al, 2020). However, C. burnetii is readily inactivated by pasteurisation (Wittwer et al, 2022) and ingestion of even unpasteurised dairy products are not seen as a primary route of transmission (Gale et al, 2015; Cherry et al, 2022).
Wild-life, companion animals and ticks
C. burnetii has been identified in a wide variety of wildlife species, where they have been hypothesised to be a potential source of infection for livestock and humans (Celina and Cerny, 2022). However, to date there have been only a limited number of human Q fever cases where wildlife have been implicated (Flint et al, 2016; Pommier de Santi et al, 2018). Within the UK there is limited data on C. burnetii carriage in wildlife, however high prevalence of exposure has been shown in serological studies of wild rodents and predator species (Meredith et al, 2015).
Dogs and cats have also been implicated as the source of human infection (Ma et al, 2020). Cases of Q fever pneumonia have been associated with exposure to birth products of either aborting or asymptomatic cats (Kosatsky, 1984; Langley et al, 1988; Marrie et al, 1988; Kopecny et al, 2013; Malo et al, 2018). While the number of cases associated with dogs are few, serological evidence suggests C. burnetii infection in dogs is prevalent internationally (Boni et al, 1998; Cooper et al, 2011; Chitanga et al, 2018).
Beyond mammalian hosts, arthropods have been suggested as potential vectors for C. burnetii transmission. The Nine Mile strain of C. burnetii was first isolated in 1935 from the tick Dermacentor andersoni in Montana (Davis et al, 1938), and since then C. burnettii or at least its DNA has been identified in over 40 hard bodied and 14 soft bodied species of tick (Eldin et al, 2017). The prevalence of C. burnetii in ticks appears to be geographically variable and as yet there is no evidence of C. burnettii DNA detection in ticks within Northern Europe (Körner et al, 2021).
Human-to-human transmission
Human-to-human transmission of C. burnetii can occur but is rare. As with livestock, birth products from infected women may be a source of infection, to both hospital staff (Raoult and Stein, 1994), and other pregnant women within the same unit (Amit et al, 2014). There is also limited evidence for sexual transmission (Milazzo et al, 2001). C. burnetii is stable in blood samples for at least 6 weeks at 1–6°C (Kersh et al, 2013), though the risks of transmission via blood products has been estimated to be low (Oei et al, 2014).
Coxiellosis and Q fever within the UK
Coxiellosis
C. burnetii is endemic in the UK. There is evidence for its presence in livestock, wildlife and companion animals. Dairy cattle in particular demonstrate a particularly high herd prevalence with up to 80% of British (Velasova et al, 2017) and over 48% of Northern Irish (McCaughey et al, 2010) dairy farms showing serological evidence of exposure detected in bulk milk samples. The prevalence amongst UK sheep and goats is estimated to be much lower at 10% and 3% of sheep and goat holdings respectively (Lambton et al, 2016). Despite this relatively high seroprevalence, reported numbers of diagnosed cases of infection and of abortion attributed to C. burnetii remain low. However, accurate diagnostics of ruminant abortion, particularly bovine, remains challenging and a diagnosis is not reached in the majority of submissions (Mee, 2020). A retrospective study of livestock placenta samples from abortion events submitted to regional Animal and Plant Health Agency labs in 2010 revealed the presence of C. burnetii DNA in 7 out of 124 cattle and 1 of 9 goat abortion samples but none of the 194 sheep samples tested (Pritchard et al, 2011). These findings of C. burnetii DNA in placenta samples do not confirm attribution of coxiellosis as the cause of the abortion. However, the findings highlight the importance of appropriate biosecurity precautions around the handling of ruminant abortion material and birth products. Another potential reason for the apparent lack of symptomatic coxiellosis in the UK may be due to genetic differences in C. burnetii types found in different livestock species (and also different geographic regions). During the Netherlands outbreak it was determined that goat- and sheep-associated types were the cause of both human clinical Q fever and cases of cattle abortion (Tilburg et al, 2012a; 2012b). Conversely the dominant strains present in cattle did not appear to be associated with overt cattle disease or human infection (Tilburg et al, 2012a; 2012b). Although the C. burnetii types responsible for the disease outbreaks in the Netherlands have been identified in British livestock abortion samples (Hemsley et al, 2023), demonstrating that they are present.
Q fever
The number of diagnosed cases of Q fever across the UK is relatively low, with most cases related to exposure on farms, or to livestock or livestock products (Halsby et al, 2017). While most human Q fever cases in the UK are sporadic in nature, occasional outbreaks have been reported periodically since the 1950s (Harvey et al, 1951). Most are directly associated with livestock exposures such as in Scotland in 2006 where 138 abattoir workers were affected (Pollock et al, 2007). Where direct contact with livestock is not a recognised factor in human case investigations, aerosolised transmission has been suggested such as the 1989 Birmingham outbreak where 147 diagnosed cases of acute Q fever were reported within a 44-mile square area of the city, which was traced back to a farming intensive area where outdoor lambing was taking place, after particularly strong winds (Hawker et al, 1998). On a more local level, disturbance of contaminated straw board during renovations was hypothesised by health officials to be the most likely cause of an outbreak in a factory complex in South Wales in 2002 (van Woerden et al, 2004).
Despite the infrequent nature of outbreaks, there is evidence that at least in some parts of the UK there may be high levels of human exposure. A cross-sectional study of 265 working age patients within a rural general practice in Wales, identified a seroprevalence of 7.9% overall, with farmers exhibiting a significantly higher seroprevalence (15.1%) than non-farmers (4.2%) (Davies et al, 1997). Similarly in a large population-based survey of 2850 individuals carried out in Northern Ireland, a mean seroprevalence of 12.8% was observed (McCaughey et al, 2008) with farmers again exhibiting a significantly higher seroprevalence than the overall population, with 49% demonstrating antibodies to the infection (McCaughey et al, 2008). Highlighted within this study was the observation that seropositive women were significantly more likely to have experienced a still-birth or miscarriage (McCaughey et al, 2008). Despite these findings, it has to be borne in mind that other risk factors, including exposure to other zoonotic infections, cannot be discounted, and the data on Q fever as a cause of human pregnancy loss remain ambiguous. Further studies investigating targeted cohorts of pregnant women in the UK have not observed the same correlations of C. burnetii exposure and adverse pregnancy outcome (Baud et al, 2009; Wheelhouse et al, 2022). Despite the absence of definitive evidence for a role of Q fever in pregnancy complications, there remains a potential risk and appropriate care should be taken in reducing the exposure of pregnant women to livestock (Plummer et al, 2018).
Treatment and prevention of Q fever and coxiellosis
Treatment and prevention strategies in livestock are aimed at reducing rates of abortion and bacterial shedding. The primary method for prevention of clinical disease is vaccination. Commercial vaccines are thought to be most effective when administered to naïve non-pregnant animals, and there is less evidence that vaccination has significant effects on reducing abortion or shedding of previously infected animals (Guatteo et al, 2008; De Cremoux et al, 2012). There has been some limited work on the effects of antibiotics. While oxytetracycline administration has been suggested to have some positive impact on reducing abortion in animals when administered in the latter stages of pregnancy to sheep within a flock with a history of Q fever (Astobiza et al, 2010), there is little evidence that antibiotic treatment reduces bacterial shedding in either cattle or sheep (Astobiza et al, 2010; Taurel et al, 2014).
C. burnetii can be shed in vaginal secretions and birth fluids as well as sporadically in faeces (Guatteo et al, 2007; Roest et al, 2012). Efficient composting is thought to be sufficient to inactivate the organism in faeces prior to application on land (van den Brom et al, 2015b). In lambing/calving pens, good hygiene practice is essential and over 90% of reduction in infectivity can be achieved with prolonged (over 30 minutes) exposure to disinfectants based on hypochlorite, quaternary ammonium or hydrogen peroxide (Plummer et al, 2018). For humans, the primary source of risk is around handling of livestock birth products, even of those animals that are apparently uninfected. Appropriate personal and protective equipment including gloves, protective clothing and respiratory protection should be used when lambing or calving, with frequent attention being paid to hand washing after handling animals (Plummer et al, 2018; Winter et al, 2021).
Conclusions
C. burnetii the causative agent of coxiellosis and Q fever is endemic in livestock across the UK. The number of reported human and livestock cases of disease remain low; however, many cases are asymptomatic and the often-mild symptoms of the disease, described frequently as ‘flu-like’, may be mistaken for other infections. It is therefore likely that the number of animal and human clinical cases are higher than currently reported and there is a real need to investigate exposure and clinical impacts in human populations, particularly those handling livestock and livestock products. Vaccination of livestock may offer a long-term control strategy, but while there is strong evidence that it is effective in the control of clinical disease within flocks/herds, it does not remove the risk of shedding and exposure. Therefore, while we currently do not have a full assessment of risk, as with other zoonoses, it is imperative – particularly at times of lambing/calving – that suitable precautions are taken including the use of personal protective equipment.
KEY POINTS
- Coxiella burnetii (the causative agent of Q fever) is endemic in UK livestock.
- In April 2021, livestock Coxiellosis became a reportable disease.
- The number of reported cases of human Q fever and livestock coxiellosis in the UK is low.
- Handling livestock or livestock products are the single largest risk factors for Q fever infection in humans.
- Control of animal infection is primarily via vaccination of livestock.