Q fever, caused by the obligate intracellular bacterium Coxiella burnetii, is a widespread zoonosis of significant global public health concern. Characterised by its extraordinary environmental resilience, C. burnetii can survive for extended periods outside a host. This increases its potential for transmission through aerosolised particles and contaminated environments. Humans generally represent incidental hosts, becoming infected primarily by inhalation of contaminated aerosols originating from domestic ruminants such as sheep, goats, and cattle.1
The relevance of Q fever in Spain varies widely depending on the region in question. Differences in livestock density, climate, and healthcare pathways contribute to uneven detection, so national epidemiology remains incompletely characterised.2
Whereas large clinical series have been reported in northern regions such as the Basque Country and Galicia, other areas offer only limited data, which hampers precise estimates of incidence and risk.2
Despite its clinical significance, Q fever remains considerably underestimated, reflecting a global trend of underdiagnosis and insufficient epidemiological vigilance. Several factors contribute to this underestimation: non-specific symptomatology, limited awareness among clinicians,3 the difficulty of confirming infection early in the course of disease and the absence of a mandatory reporting system for Q fever.4
In Majorca (Balearic Islands, Spain), acute Q fever (AQF) has emerged as a significant yet often overlooked public health concern. In their retrospective study conducted between 2017 and 2022 and presented in this issue of EIMC, García-Gasalla et al. provide a clearer view of the actual disease burden emphasising the high morbidity and considerable diagnostic delays observed in clinical practice. These findings underscore the critical gap between the actual disease burden and current surveillance capabilities.4
The COVID-19 pandemic period provided unique insights into potential alternative transmission pathways. Despite stringent mask mandates aimed primarily at reducing respiratory disease transmission, García-Gasalla et al. reported ongoing acute Q fever cases, suggesting possible transmission mechanisms beyond aerosol inhalation from livestock sources.4 Indeed, indirect transmission routes such as exposure to pets, particularly dogs and cats, or consumption of unpasteurised dairy products may contribute to Q fever's persistent endemicity, although these hypotheses remain insufficiently explored.5 Interestingly, these epidemiological peculiarities observed in Majorca contrast with findings from other regions of Spain, where aerosolised transmission linked directly to ruminant livestock remains dominant.2,6
Clinical manifestations range from asymptomatic infections to severe and sometimes life-threatening conditions, most often pneumonia or hepatitis, but also myocarditis or endocarditis.1 The marked heterogeneity of acute presentations reflects differences in host susceptibility, inoculum size, route of transmission, and geographical location.7 Although progression to chronic Q fever is uncommon, it can have serious consequences. Risk factors include pregnancy, immunosuppression, heart valve lesions and vascular abnormalities. Early recognition of these risk factors is essential in order to plan structured follow-up where appropriate.7
The clinical presentation of Q fever varies greatly from series to series and depends on the geographic origin of the infection.7 For example, pneumonia is more common than hepatitis in eastern Canada, while in southern Spain pneumonia is rare, and hepatitis is very common.7
Within Spain, the north (e.g., Galicia, Basque Country, La Rioja) is characterised by a predominance of pneumonia as the main clinical presentation of Q fever, with rates as high as 71–87% in some series. In contrast, in central and southern Spain, isolated febrile illness and hepatitis are more common, with pneumonia representing a minority of cases (17–18%) and hepatitis and fever accounting for the majority (up to 40% and 38%, respectively).2,8 These regional differences are consistent across multiple studies and are also reflected in seasonal patterns, with pneumonic forms more frequent in colder months.8
The study by García-Gasalla et al.4 reported prolonged febrile syndrome as the most frequent clinical diagnosis (49%), followed by pneumonia with/without pleural effusion (22%), acute hepatitis (17.0%), pericarditis and/or myocarditis (2.7%). Three patients developed endocarditis (one in the acute phase, two others during follow-up).4
This heterogeneity invites a biological explanation beyond ascertainment bias. One plausible contributor is pathogen diversity. Molecular epidemiology has, in several contexts, linked ruminant and human cases through shared genotypes, suggesting that strain ecology can shape clinical patterns.9,10
Experimental and epidemiological data link specific genomic groups (GGs) and genotypes to variation in virulence and clinical severity. Depending on the microbiological method used, six to eight GGs are recognised. For example, GG I strains show increased virulence in animal models with more severe disease, while GG II (MST 33) is most consistently associated with large-scale outbreaks – particularly goat-to-human transmission – whereas other groups display intermediate or low virulence. Comparative genomics and outbreak investigations, such as those involving Dutch outbreak strains, have identified genotype-specific gene content and mutations in genes associated with virulence, supporting the concept of genotype-specific pathogenicity and epidemic potential.11,12
Recent molecular epidemiology studies have demonstrated high genetic diversity of C. burnetii in Spain, with multiple genotypes circulating and some evidence of geographical clustering of genotypes that may correlate with clinical manifestations.13–15 Although robust genotype–phenotype associations for clinical syndromes are not yet established, these data support the hypothesis that regional differences in circulating genotypes could modulate the clinical spectrum observed across Spanish cohorts and merit systematic evaluation using standardized typing schemes integrated with clinical metadata.14–16García-Gasalla et al.4 diagnosed the reported AQF cases using clinical course and serology only, without including PCR-based assays targeting C. burnetii DNA in blood or tissue. While this approach simplifies implementation, it carries the risk of delayed confirmation and misclassification, particularly near symptom onset. In this series, information on the circulating groups and genotypes of the isolates was not provided.
Serology-only diagnostic pathways are limited by the window period, the variability of IgM assays and the requirement for paired convalescent sera to confirm seroconversion. These factors often result in patients being lost to follow-up. The best approach is to combine serology with PCR in the first weeks of illness. PCR testing of whole blood or serum often yields positive results soon after symptom onset, before antibodies can be detected. However, sensitivity declines as antibodies rise and following antibiotic exposure.17,18 Studies comparing the two methods show that adding PCR to acute-phase testing substantially increases the early diagnostic yield versus serology alone, particularly within the first 2–3 weeks.18
Where available, targeted or metagenomic sequencing can complement PCR in seronegative early disease and in patients with atypical exposures or severe presentations. Beyond confirming cases, multispacer sequence typing (MST) and multilocus variable-number tandem-repeat analysis (MLVA) – or, when bacterial load permits, whole-genome sequencing – enables the linkage of human, animal and environmental isolates. This supports source attribution and provides an empirical framework to test genotype–phenotype hypotheses and trace local transmission pathways.9,10,13
In endemic areas, Q fever most often presents as sporadic cases associated with recognised risk activities, such as farming, working in a slaughterhouse, or rural tourism. Occasionally, small clusters, often familial, emerge following exposure to a shared source (e.g., parturient dogs or cats carrying C. burnetii).1 These patterns highlight the close link between human infection and animal/environmental reservoirs, meaning that clinical diagnosis and management must be considered alongside prevention.
Veterinary measures such as herd surveillance, careful management of reproductive waste and enhanced biosecurity during lambing and kidding are central to reducing environmental contamination. Monitoring air and dust in conjunction with meteorological data can help to anticipate high-risk periods. Real-time PCR analysis of dust and aerosol samples can detect C. burnetii and estimate the bacterial load. This enables the identification of high-prevalence herds or areas, the prioritisation of interventions and the evaluation of the impact of control measures.19 Combining these approaches with molecular genotyping and geospatial mapping can trace sources of farm contamination and link them to human outbreaks.
In addition to livestock, wildlife also plays a role in transmission, with studies indicating that mammalian biodiversity modulates risk. Furthermore, non-ruminant mammals, birds and reptiles also play a role in the circulation of C. burnetii.16
These observations reinforce the need for an integrated ‘One Health’ approach, as well as for stronger surveillance. This should include mandatory notification and the establishment of sentinel networks, as well as the incorporation of veterinary and environmental monitoring into human health programmes. Only then will we be able to accurately determine the true burden of Q fever and effectively guide preventive strategies.20
The underestimation of Q fever reflects not only diagnostic limitations, but also structural weaknesses in surveillance. Reporting remains incomplete in many countries, including Spain, and environmental monitoring is rarely incorporated into public health frameworks.2 A more realistic assessment requires sentinel systems, mandatory notification, and the systematic integration of veterinary and environmental data.2 Similarly, investment in laboratory capacity, access to molecular diagnostics, and clinician training is essential for earlier detection and treatment.17 Without such efforts, Q fever will continue to be overlooked despite its potential to cause large-scale outbreaks and chronic complications.10
Ultimately, the Majorca series turns a local signal into a national mandate. Spain can move from underestimation to prevention by diagnosing earlier using PCR and serology in the first few weeks, completing coverage of notifiable disease with sentinel and environmental monitoring, and linking human, veterinary and environmental data within a One Health framework. Where feasible, molecular typing or whole-genome sequencing should be used to support source attribution and outbreak investigation. These pragmatic steps, coupled with sustained investment in laboratory capacity and clinician training, can transform Q fever from a recurrent surprise into a preventable problem.
FundingNo additional funding was received in performing this editorial.
Conflict of interestsThe authors declare that they do not have conflict of interests.
