1. Background {#s0005}
=============

Q fever (Q stands for query), caused by the highly pathogenic bacteria called *Coxiella burnetii*, is a zoonotic disease \[[@bb0075]\] and has worldwide distribution \[[@bb0140]\]. Since its discovery and description in Australia in 1937 \[[@bb0050],[@bb0065]\] there have been several Q fever outbreaks reported internationally and the disease is considered endemic in most regions of the world \[[@bb0060],[@bb0110],[@bb0140],[@bb0215]\]. The Netherlands is the country which experienced the highest ever reported Q fever outbreak \[[@bb0175]\]. Intensive farming of dairy goats and dairy sheep was the main reason for the outbreaks that occurred in The Netherlands \[[@bb0170]\].

Domestic ruminants and pets and in Australia, native marsupials, are the main reservoirs of infection \[[@bb0040],[@bb0045],[@bb0185],[@bb0200]\]. Transmission to humans occurs mainly through inhalation of contaminated aerosols originating from parturient animals and their birth products \[[@bb0075],[@bb0145]\]. Humans are considered accidental and dead-end hosts as there is no evidence of human-to-human transmission \[[@bb0075]\]. The seroprevalence of *C. burnetii* infection can range from 30% to 70% in people working in high-risk occupations such as farmers, veterinarians and abattoir workers \[[@bb0020]\].

Prevention of Q fever in Australia is through targeted immunization especially in those working in, or associated with the meat industry using the locally produced Q Vax vaccine (Seqirus, Australia), which has high efficacy in adults \[[@bb0125],[@bb0130]\]. Q Vax is reported to provide up to 93% immune protection \[[@bb0160]\] with long-lived immune responses to *C. burnetii* \[[@bb0115]\]. However, the incidence of Q fever in people working in the red meat industry remains relatively high. Therefore, the current review provides information on the variability of the prevalence of Q fever exposure and risk factors for exposure in this occupational group.

2. Materials and methods {#s0010}
========================

A search for published articles was conducted using several strategies (see details in [Table 1](#t0005){ref-type="table"}, [Table 2](#t0010){ref-type="table"}, [Table 3](#t0015){ref-type="table"} and supporting files 1--2 and [Fig. 2](#f0010){ref-type="fig"}): an online search of PubMed, MEDLINE-EMBASE, and Scopus databases was conducted using the terms Q fever, *Coxiella burnetii*, seroprevalence, sero-epidemiology, serology, incidence, prevalence, abattoir, abattoir workers, slaughterhouse, slaughterhouse workers, and butcher and meat workers. Further key words were then obtained from an initial review of reports of outbreak investigations in various countries.Table 1Characteristics of studies that included abattoir and slaughterhouse workers.Table 1Author (Year)OutbreakCountrySettingSize (n)SeropositivePrevalence (%)Lab methodGilroy \[[@bb0085]\]YesAustraliaAbattoir682943CFTAbebe \[[@bb0005]\]NoEthiopiaAbattoir465306.5CFTAdesiyun \[[@bb0010]\]NoTrinidadAbattoir8544.7ELISAKhalili \[[@bb0120]\]NoIranSlaughterhouse755168ELISAMarrie \[[@bb0135]\]NoCanadaSlaughterhouse961212.5CFTEsmaeili \[[@bb0070]\]NoIranSlaughterhouse1904322.5ELISAAflatoonian \[[@bb0015]\]NoIranSlaughterhouse6457.8ELISAPerez-Trallero \[[@bb0165]\]NoSpainSlaughterhouse363391.7IFABerktaş \[[@bb0035]\]NoTurkeySlaughterhouse412765.9ELISAHtwe \[[@bb0105]\]NoJapanAbattoir1071211.2IFACDC \[[@bb6550]\]YesUSAAbattoir421945.2CFTBeech \[[@bb9515]\]YesAustraliaAbattoir516509.7CFTSchnurrenberger \[[@bb9055]\]NoUSAAbattoir20911045CFTSchonell \[[@bb4445]\]NoUKAbattoir962128.1CFTRiemann \[[@bb6865]\]NoBrazilAbattoir1444229AGGLUTINATIONMcKelvie \[[@bb0150]\]YesAustraliaAbattoir1392215.8CFTCDNANZ \[[@bb9405]\]YesAustraliaAbattoir1001818CFTDonaghy \[[@bb0055]\]YesUKAbattoir2284921.5NAWilson \[[@bb0210]\]YesUKSlaughterhouse1797541.9IFABerktaş \[[@bb0035]\]NoTurkeyButcher house773342.9ELISA[^1]Table 2PubMed search strategy: Articles search history and strategy for abattoirs and slaughterhouse workers.Table 2SearchQueryItems found\#12Search (((q fever) OR coxiella burnetii)) AND (((((((seroprevalence) OR seroepidemiology) OR serology) OR serological) OR prevalence) OR incidence) OR epidemiology)2864\#11Search ((((((seroprevalence) OR seroepidemiology) OR serology) OR serological) OR prevalence) OR incidence) OR epidemiology2,745,738\#10Search (q fever) OR coxiella burnetii5865\#9Search epidemiology1,970,371\#8Search incidence2,343,722\#7Search prevalence2,189,454\#6Search serological56,243\#5Search serology194,892\#4Search seroepidemiology1336\#3Search seroprevalence25,616\#2Search coxiella burnetii3157\#1Search q fever4994Table 3MEDLIN-EMBASE search history: Articles search history and strategy for abattoirs and slaughterhouse workers.Table 3No.QueryResults\#11'q fever'/exp. OR 'coxiella burnetii'/exp. AND ('seroprevalence'/exp. OR 'seroepidemiology'/exp. OR 'serology'/exp. OR 'prevalence'/exp. OR 'incidence'/exp. OR 'epidemiology'/exp)2246\#10'seroprevalence'/exp. OR 'seroepidemiology'/exp. OR 'serology'/exp. OR 'prevalence'/exp. OR 'incidence'/exp. OR 'epidemiology'/exp2,687,691\#9'q fever'/exp. OR 'coxiella burnetii'/exp6631\#8'epidemiology'/exp2,514,169\#7'incidence'/exp313,776\#6'prevalence'/exp520,913\#5'serology'/exp202,792\#4'seroepidemiology'/exp2906\#3'seroprevalence'/exp15,639\#2'coxiella burnetii'/exp3640\#1'q fever'/exp5152

One reviewer individually screened all study titles identified through database searches. An initial review of abstracts was performed to identify articles for a more detailed full text review. The final articles were selected if they met the following criteria: 1) if the full text or abstract is available, 2) articles that are published in a peer-reviewed or refereed archival journal in English, 3) articles that are based on original data; i.e., not a review article or meta-analysis, 4) articles that contained reported prevalence estimates from statistical analyses, and 5) articles of studies that were conducted on people working in the meat industry (slaughterhouse and abattoir workers, and butchers). Meta-analysis was done for abattoir and slaughterhouse workers with a total of 19 studies which met the inclusion criteria. Details of the studies\' characteristics along with the number of studies included in each are summarized in supporting information [Table 1](#t0005){ref-type="table"}.

Articles with extreme reported seroprevalence rates, that is, 0.0% and 100%, have been included in order to minimize the publication bias especially for positive findings. The prevalence of exposure was selected as the outcome variable in each of the various sub-groups. Odds and risk ratios were also extracted as measures of the strength of association between Q fever and exposures to different risk factors. Initial data extraction was done using Microsoft Excel and compiled data was imported to Stata version 13 \[[@bb0195]\].

Stratification based on serological test type and whether the study reported findings of an outbreak investigation was performed to determine the presence of heterogeneity in terms of the seroprevalence and potential reporting bias. Random effects meta-analysis was conducted using the *metaprop* Stata package that pools proportions and presents weighted sub-group and overall pooled estimates with inverse-variance weights obtained from a random-effects model \[[@bb0155]\] (see supporting File 2). A forest plot with error bars to indicate the 95% confidence interval around each of the \[true\] prevalence estimates was constructed and Higgin\'s I2 was used to quantify the amount of heterogeneity in the prevalence estimates, across studies \[[@bb0095],[@bb0100]\]. The *I*^2^ is calculated using the following formula *I*^2^ = 100% × (*Q* − df)/*Q*, where *Q* is Cochran\'s heterogeneity statistic and df the degrees of freedom \[[@bb0100]\].

Moreover, we used metafor R statistical package \[[@bb0205]\] for running meta-regression analysis for assessing presence of heterogeneity in the seroprevalences between outbreak and non-outbreak situations.

3. Results {#s0015}
==========

A total of 7110 articles were identified in the initial searches of PubMed (2864), MEDLINE - EMBASE (2246) and Scopus (2000) databases. After removing duplicate articles, the title and abstracts of 4685 articles were reviewed to identify a total of 185 research articles that met our initial selection criteria. After the final screen 19 seroprevalence studies were included which met the inclusion criteria. Details on the characteristics of included studies are provided in [Table 1](#t0005){ref-type="table"}.

Reported seroprevalence rates ranging from 4.7% to 91.7% among abattoir and slaughterhouse workers have been reported \[[@bb0005], [@bb0010], [@bb0015],[@bb0035],[@bb0070],[@bb0085],[@bb0105],[@bb0120],[@bb0135],[@bb0165]\]. The magnitude ranged from 4.7% in Trinidad \[[@bb0010]\] to 43.0% among abattoirs in Australia \[[@bb0005],[@bb0010],[@bb0085]\], and 7.8% in Iran -- 91.7% in Spain among slaughterhouse workers \[[@bb0015],[@bb0035],[@bb0120],[@bb0165]\].

The outputs of the random effects meta-analysis on the seroprevalence of *C. burnetii* among abattoirs and slaughterhouse workers stratified by outbreak status is shown in [Fig. 1](#f0005){ref-type="fig"}. This figure presents the study specific proportions with 95% exact confidence intervals for each study, the sub-group and overall pooled estimate with 95% Wald confidence intervals and the *I*^2^ statistic which provides a measure of the total amount of variation (as a percentage) in the prevalence estimates that is due to variation at the individual study level.Fig. 1Forest plot of seroprevalence of C. burnetii among abattoirs and slaughterhouse workers in 19 included studies stratified by outbreak status. Note: CFT = Complement Fixation Test, IFA = Immunofluorescence Assay, and ELISA = Enzyme-Linked Immunosorbent Assay. Also, ES(95% CI) refers to the seroprevalence point estimate (ES) with 95% CI. P = p-value and *I*^2^ describes the percentage of total variation across studies that is due to heterogeneity rather than chance.Fig. 1Fig. 2Search strategy decision tree.A total of 7110 articles were found from PubMed (2864), MEDLINE - EMBASE (2246) and Scopus (2000) databases. See [Table 2](#t0010){ref-type="table"}, [Table 3](#t0015){ref-type="table"}, supporting Files 1 and 2, and [Fig. 2](#f0010){ref-type="fig"} for detailed search histories and strategies. After removing duplicated articles, 4685 articles were found and further refinement using title and abstract skimming, a total of 185 researches have retained. Finally, a total of 19 studies which fulfil the eligibility criteria were included in the meta-analysis.Fig. 2

The result of the meta-analysis shown in [Fig. 1](#f0005){ref-type="fig"} indicates the absence of inter-group heterogeneity on the seroprevalence of *C. burnetii* (p = 0.932, *I*^*2*^ = 97.33%), both during outbreak and non-outbreak situations, supporting the pooling of all studies into one summary measure: 26% (95%, CI: 17--35%). However, the seroprevalence estimates showed significant intra-group heterogeneity for the three serological tests with *I*^2^ exceeding 94% (p \< 0.001) for both outbreak and non-outbreak situations.

Meta-regression analysis (summarized in [Table 4](#t0020){ref-type="table"}) indicated absence of statistical significant heterogeneity (p-value \>0.05) between outbreak and among serological methods in the seroprevalence of *C. burnetii*. Hence, we conclude that pooling the seroprevalences for outbreak and non-outbreak situations is supported through a meta-regression.Table 4Table Mixed-effects meta-regression model results on the seroprevalence of Q fever in abattoir and slaughterhouses.Table 4Source of variationCategoryEstimateSEZP-Value95% CI*I*^*2*^R^2^LowerUpperOutbreakIntercept0.270.093.050.000.100.4599.06%0.02%Outbreak0.010.110.080.94−0.210.23Diagnosis methodIntercept0.180.121.570.12−0.050.4198.90%26.86%CFT0.010.140.060.96−0.260.27ELISA0.220.161.400.16−0.090.52IFA0.300.171.780.08−0.030.62[^2]

4. Discussion {#s0020}
=============

The result of the seroprevalence studies showed that Q fever is endemic in meat processing industries such as abattoirs and slaughterhouses. The result of the meta-analysis indicated that, the seroprevalence of *C. burnetii* infection remained relatively constant regardless of outbreak situations. A strong association with the meat industry is confirmed \[[@bb0080]\]. This is in accordance with studies that have shown that abattoir workers are notable at-risk group for Q fever who should be fully protected from this occupational disease \[[@bb0030]\].

The overall seroprevalence of *C. burnetii* (26%) determined in this meta-analysis falls within the range of values (30--70%) reported in studies of high risk groups elsewhere \[[@bb0020]\]. Gilroy et al. \[[@bb0085]\] indicated that up to sixty-eight (66%) of employees in abattoirs are considered susceptible to primary infection and that unscreened, unvaccinated, non-immune workers developed Q fever after exposure to *C. burnetii* \[[@bb0085]\]. Furthermore, Perez-Trallero et al. showed that \>86% of slaughterhouse workers in one study had evidence of previous infection by *C. burnetii* using skin testing and serology? \[[@bb0165]\].

The detection of higher prevalence of antibodies to *C. burnetii* in abattoir workers and those who had minimal contact with animals is an indication of presence of pre-existing immunity rather than recent infection \[[@bb0010],[@bb0085]\]. Infection with *C. burnetii* among abattoir and slaughterhouse workers occurs independent of the age, sex, race, years of occupational experience or the types of duties performed in the abattoir or in the offices by the workers \[[@bb0010],[@bb0070],[@bb0120]\]. In addition, the absence of association between seropositivity for *C. burnetii* and work history, work type, splashing of animal secretions on face or body and occupational injury have also been identified \[[@bb0070]\]. However, the results of two studies (Wilson et al. \[[@bb0210]\]; Marrie and Fraser \[[@bb0135]\]) suggest that being male \[OR = 6.4, 95% CI: 1.8--23.4\] is independently statistically significantly associated with an increased risk of testing positive for infection with *C. burnetii* \[[@bb0135],[@bb0210]\].

The greatest risk of infection was associated with working in areas where cattle, sheep and swine are slaughtered \[[@bb0055],[@bb0150]\]. Marrie and Fraser \[[@bb0135]\] showed that slaughtering cattle (working on the kill floor) was a significant risk factor for positive antibody titers among slaughterhouse workers \[[@bb0135]\]. Furthermore, A previous study by Perez-Trallero et al., \[[@bb0165]\] reported 19.25 higher \[OR = 19.25, 95% CI: 5.34, 102.74\] odds of Q fever infection for those working in slaughterhouses \[[@bb0165]\].

In addition, people who work in other occupations in rural settings and that have contact with animals, especially the operators of the livestock industry (veterinarians, tanners, and wool carders) are also at higher risk of seropositivity \[[@bb0120],[@bb0180]\].

One published case control study confirmed the higher incidence of Q fever associated with increased level of exposure to a slaughterhouse (low exposure: OR = 3.0; moderate: OR = 4.7; high: OR = 15.0; chi2 for trend, p = 0.006) and high level of exposure to the slaughterhouse site (OR = 6.8, 95% CI: 1.1--40.3) \[[@bb0025]\]. A strong association with the meat industry was confirmed \[[@bb0080]\]. This is in accordance with studies that have shown that abattoir workers are a notable at-risk group for Q fever \[[@bb0030]\]. It is the study that supports the hypothesis of a sheep lairage being the source of potential exposure, Scottish co-located slaughterhouse and cutting plant. Passing through walkway by the sheep lairage was independently associated with an increased risk of testing positive. Those who passed through the stores were 3.2 (95% CI: 1.7--6.3) times as likely to be a confirmed case, those who passed through walkway by the sheep lairage were 2.1 (95% CI: 1.0--4.3) times as likely \[[@bb0210]\]. Bell, et al. \[[@bb0030]\] indicated that because the organism is transmitted in aerosols, it is important that not only abattoir employees but all workers who visit or work on an abattoir site are vaccinated against Q fever. This includes service providers such as electricians, plumbers, telecommunication workers, weights and measures inspectors and transport workers \[[@bb0030]\].

A randomized, blind, placebo-controlled trial of Q fever and influenza vaccines has been conducted in three Queensland abattoirs, showing occurrence of Q fever cases in unvaccinated workers in all three abattoirs during the follow-up period \[[@bb0190]\]. However, vaccination administered 10 or more days after the likely period of exposure showed no significant protective effect (RR = 0.57; 95% CI 0.13--2.57; p = 0.60) \[[@bb0085]\]. The study by Greig et al. \[[@bb0090]\] showed the average annual risk of infection among abattoir workers to be 45.0 per 1000 (95% CI 42.3--47.6), and 62.6 per 1000 (95% CI 57.5--67.7) over the first 10 years of exposure \[[@bb0090]\]. Up to 90% of new entrants in high-risk workplaces will be susceptible to Q fever and require vaccination \[[@bb0090]\].

In summary, the seroprevalence associated with *C. burnetii* infection ranged from 4.7% to 91.7% among abattoir and slaughterhouse workers was reported in the included studies. From the random effects meta-analysis, seropositivity for *C. burnetii* in abattoirs and slaughterhouses can be expected in more than a quarter of workers (26%; 95% CI: 17%--35%) regardless of evidence of an outbreak. In addition, seropositivity for *C. burnetii* is independent of age and years of occupational experience in meat abattoir and slaughterhouses but significantly associated with activities related to slaughtering of cattle, sheep and goats. Vaccination 10 days prior to exposure to environments where *C. burnetii* may be present was shown to be an effective prevention mechanism. Vaccination programmes for workers in high risk industries is highly recommended for mitigating the incidence of Q fever, and subsequent chronic sufferings and work day offs among abattoir and slaughterhouse workers.

Appendix A. Supplementary data {#s0025}
==============================

Scopus Search Strategy \[from Health and Life Sciences Subject Areas\]. Articles search history and strategy for abattoirs and slaughterhouse workers.Image 1*Metaprop* Stata Package for Running the Meta-AnalysisImage 2

We are highly indebted for the University of Queensland for offering this scholarship opportunity and providing us library facility for accessing articles from PubMed, MEDLINE-EMBASE, and Scopus databases through its library.

Supplementary data to this article can be found online at <https://doi.org/10.1016/j.onehlt.2018.09.002>.

[^1]: Note: CFT = Complement Fixation Test, IFA = Immunofluorescence Assay, and ELISA = Enzyme-Linked Immunosorbent Assay. NA refers to Not Available.

[^2]: Mixed-Effects Model (k = 19; tau\^2 (estimated amount of residual heterogeneity) estimator: ML (Maximum Likelihood)). I\^2 (residual heterogeneity/unaccounted variability). R\^2 (amount of heterogeneity accounted for).
