|Year : 2017 | Volume
| Issue : 4 | Page : 341-347
Serosurvey of Coxiella burnetii in high risk population in Turkey, endemic to Crimean-Congo haemorrhagic fever virus
Rahşan Erturk1, ÷mer Poyraz1, Turabi Güneş2
1 Faculty of Medicine, Laboratory of Microbiology, Cumhuriyet University, Sivas, Turkey
2 Vocational School of Health Services, Cumhuriyet University, Sivas, Turkey
|Date of Submission||04-Aug-2016|
|Date of Acceptance||21-Nov-2017|
|Date of Web Publication||19-Feb-2018|
Vocational School of Health Services (SHMYO), Cumhuriyet University, Sivas–58140
Source of Support: None, Conflict of Interest: None
Background & objectives: Q fever caused by Coxiella burnetii is a zoonotic infection that spreads to human beings from animals. This study was aimed to demographically examine the C. burnetii seroprevalence in the people living in villages where Crimean-Congo haemorrhagic fever virus (CCHFV) is endemic, in terms of various risk factors such as tick bites, tick contact, and occupational groups.
Methods: A total of 440 serum samples from those living in rural areas of Sivas and Tokat regions in Turkey were included in the study as a risk group; 387of them were serologically CCHFV positive (as confirmed in our previous research). Serums of the control group composed of 110 people living in urban areas. In all serum samples, IgG antibodies of C. burnetii against phase-I and phase-II antigens were diagnosed using the ELISA method.
Results: Coxiella burnetii seropositivity was detected in 19.09% of those living in rural areas and 4.55% of those living in urban areas (p < 0.001, OR = 4.96). In terms of their approach to the ticks, no statistical difference was observed between the risk groups in the chi-square test (p = 0.787). However, according to univariate analysis, the absorbance means of antibodies reactive to C. burnetii was statistically higher for the rural people who have made contact with ticks than those who have not (p = 0.017). No seroepidemiological relation was found between CCHFV and C. burnetii serology (p = 0.787), and the rate of co-seropositivity between them was 5.43% (21/387).
Interpretation & conclusion: The findings of the study showed that C. burnetii infection is epidemic especially in the people living in rural areas. Contact with ticks in various ways might have resulted in the increased risk of C. burnetii infection in the study. Personal protective measures against tick bites may be important for reducing Q fever risk as in other tick-borne infectious disease.
Keywords: Coxiella burnetii; Crimean-Congo haemorrhagic fever virus; Q fever; tick bite
|How to cite this article:|
Erturk R, Poyraz ÷, Güneş T. Serosurvey of Coxiella burnetii in high risk population in Turkey, endemic to Crimean-Congo haemorrhagic fever virus. J Vector Borne Dis 2017;54:341-7
|How to cite this URL:|
Erturk R, Poyraz ÷, Güneş T. Serosurvey of Coxiella burnetii in high risk population in Turkey, endemic to Crimean-Congo haemorrhagic fever virus. J Vector Borne Dis [serial online] 2017 [cited 2018 May 21];54:341-7. Available from: http://www.jvbd.org/text.asp?2017/54/4/341/225839
| Introduction|| |
Coxiella burnetii, the causative agent of Q fever, is an obligate intracellular bacterium that looks like gramnegative coccobacillus. It is the only member of Coxiella genus, and it can survive even in inappropriate living conditions,. It displays antigenic variations during growth similar to smooth-rough variation in the family Enterobacteriaceae. Phase variation is related mainly to mutational variation in the lipopolysaccharides synthesised by the bactera,. The most contagious antigenic form, which infects animals, ticks, and humans, is phase-I (natural form). Phase-II, which generally forms as a result of spontaneous mutations (grown in cell cultures), is not very infectious. Even though phase-II antibodies are dominant in acute Q fever, high titres of phase-I antibodies are almost always detected in chronic forms,. Humans are commonly infected by inhalation of aerosols, generated from infected animal urine, excrements, placenta, and other bodily fluids and by contaminated environments,. Other rare contamination means are contact with ticks and oral consumption of infected raw milk, fresh cheese, and similar dairy products. About 60% of infections with C. burnetii are asymptomatic, while others develop symptomatic acute Q fever, a flu-like illness, which is mostly self-limiting and does not require any special treatment. However, some of the cases may progress to severe chronic infections eventually leading to death. Conditions, such as pregnancy, immune deficiency, cardiac valve lesions and vascular anomalies are important risk factors for chronic Q fever,,,.
Coxiella burnetii has been reported in arthropods, fish, birds, rodents, marsupials and farm animals. More than 40 tick species in 12 genera in five continents are naturally infected with this bacterium. Q fever is a common zoonosis with a worldwide distribution,,,. The main vector tick for C. burnetii is the species Rhipicephalus sanguineus. It has been also isolated from many other tick species including the genus Hyalomma,,,. The main vectors of Crimean-Congo haemorrhagic fever virus (CCHFV) are tick species within the genus Hyalomma, which has been isolated from 31 tick species, two of which are soft ticks. It has been shown that C. burnetii can also be isolated from some tick species in which CCHFV have existed,,,. Nearly half of the tick species from which both C. burnetii and CCHFV were isolated are found in various climatic regions of Turkey, including Tokat and Sivas regions,. Serologic studies, both on animals and humans show that C. burnetii infections can be seen commonly in Turkey,,,,.
For serological diagnosis of C. burnetii, different tests like, microagglutination, complement fixation, indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), radio immunoassay (RIA), dot blot and western blot tests are used. Although IFA test is considered as the recommended reference test, ELISA test also has high levels of sensitivity and specificity,,,. The present study was aimed to determine the existence of antibodies against C. burnetii in various risk groups living in rural areas of Sivas and Tokat, and to reveal whether these antibodies are associated with tick bites and tick contacts or not. Furthermore, it was also aimed to determine whether there is a seroepidemiological relationship between C. burnetii and CCHFV which is another tickborne infection.
| Material & Methods|| |
Ticks and tick-borne zoonoses are commonly seen in Tokat and Sivas regions of Turkey and these regions are endemic especially in terms of CCHFV infections,,. Sivas City is geographically located in Central Anatolia Region between 35° 50′ – 38° 14′ Eastern longitudes and 38° 32′ – 40° 16′ Northern latitudes. Tokat City is located in the mid-Black Sea region of Anatolia, between 35° 27′– 37° 39′ Eastern longitudes and 39° 52′- 40° 55′ Northern latitudes [Figure 1]. Both cities have adaptable vegetation for wild animals and domestic animals that can shelter ticks. The diversity of tick and animal fauna means appropriate reproduction conditions for C. burnetii.
|Figure 1: Geographic location of Tokat and Sivas regions, Turkey, and operating points where blood samples were collected from humans.|
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Collection of blood samples
For calculating the size of samples in this study, C. burnetii antibody prevalence was assumed as 30%,,,,. Size of samples required to be collected within a 95% confidence interval and according to ± 5% error was calculated to be 383. In between April and October 2006, and 2010, a total of 1093 blood samples were collected from people living in rural areas in Tokat and Sivas regions. Serum samples were collected from different risk groups, who were in contact with ticks in various ways, and who were animal holders, living in 56 villages affiliated with 14 districts in Tokat and Sivas [Figure 1]. The risk group of people who were in contact with ticks had no complaints and symptoms associated with tick-borne infections at the time of sampling, and these people had reported to have at least one tick bite and tick-contact stories in the past four years. Since, it was not possible to bring serum samples to the laboratory within 2–3 h, blood samples were collected by venipuncture, drained into sterile blood collection tubes (10 ml each) and allowed to clot at ambient temperature and kept in a cold environment at 4–8°C until reaching the laboratory. Serum samples were obtained by centrifugation and kept in a refrigerator at –80°C. Antibody positivity against CCHFV was investigated in 782 of the 1093 sera in our previous study. A total of 440 samples from the 1093 were chosen to represent four risk groups each consisting 110 samples [Table 1]. The samples included the 387 serums investigated in our previous study in view of CCHFV serology. The risk groups included people (i) who were bitten by ticks, (ii) who used to clean/remove ticks from their own farm animals, (iii) who were bitten both by ticks and have cleaned ticks from their farm animals, and (iv) who were living in the village and had no contact with ticks. In the sampling, sex distribution included similar numbers of males and females, i.e. 219 and 221, respectively. An equal number of samples were chosen from Tokat and Sivas regions (220 each). Ages of the subjects were between 8 and 85 yr (average 40.48 ± 17.54, with a median of 40). Based on the median value, two age groups were formed: < 40 and >40 yr. The control group also included 110 people living in Tokat and Sivas regions and not associated with rural areas and animals. They were selected from those who have been admitted to the hospital for various reasons having coherent age and gender to the risk groups.
|Table 1: Demographic characteristics of Coxiella burnetii seropositivity in people living in rural areas of Tokat and Sivas, in 2006|
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An ethical approval was obtained for the study from the Ethics Committee of the Medical School of Cumhuriyet University: 2010-06/26. The informed consent was obtained from all the participants involved in this study.
Coxiella burnetii phase-I and phase-II IgG antibodies were investigated in all the patients and control sera samples by ELISA method using Serion brand kits of the Institute Virion\Serion, GmbH (Germany). According to the manufacturer’s protocol, inactivated C. burnetii (Nine Mile Strain) phase-I or phase-II antigen was used for microtest plates of ELISA kit. The experiments were conducted in accordance with the user’s manual within the kits. All the test sera and ready for use cut-off control sera were tested by ELISA kits. The micro-plaques were read by ELISA micro-plaque reader (Bio-Tek Instruments, Inc. Winooski, Vermont, USA) at 405 nm of wavelength, and absorbance values of test sera and cut-off serum were determined. The cut-off value was calculated by considering the absorbent values obtained from control and standard serums. The absorbent values of the risk and control groups were compared with this cut-off control serum value, and the sera higher than cut-off absorbent values were considered positive.
The data were statistically evaluated by using the SPSS14.0 for windows (SPSS, Inc., Chicago, IL). Chi-square test, independent-samples t-test and univariate analysis were used to find if there were any differences between the variables considered. The risk rates (Odds) among the variables were determined by Binary logistic regression analysis. The confidence interval was 95% and p < 0.05 was the threshold for statistical significance.
| Results|| |
In total 550 (440 in risk groups and 110 controls) participants were included in the study. The average age of the 550 participants was 40.84 ± 17.54, and 89 of the participants (16.18%) were diagnosed IgG antibody positive against C. burnetii [Table 1].
Total 84 out of the 440 people in risk groups (19.09%) and five out of the 110 people in control group (4.55%) were diagnosed seropositive with C. burnetii antibody, and the difference between the groups was found to be statistically significant (p < 0.001). When they were evaluated regarding risk rate, it was observed that the people in rural areas carry 4.96 times more C. burnetii infection risk compared to the control group people in urban areas (Risk rate = Odds ratio [OR] = 4.96).
The antibodies reactive with C. burnetii were found positive in 22 out of 110 people (20%) who were bitten by ticks; in 24 out of 110 people (21.82%) who have cleaned ticks from their own farm animals; in 19 out of 110 people (17.27%) who were both bitten by ticks and have cleaned ticks from their farm animals; and in 19 out of 110 people (17.27%) who lived in rural areas and had no contact with ticks [Table 1].When the risk groups were compared between each other regarding their approach against ticks, no statistical difference was observed (p = 0.787). Coxiella burnetii antibody was found positive in 53 out of 220 people (24.09%) in risk group in Sivas, and 31 out of 220 people (14.09%) in Tokat, and the difference was statistically significant (p = 0.008, [OR] = 1.94).
Antibodies reactive against C. burnetii were detected in 42 of 225 (18.66%) people aged ≤40 and 42 of 215 (19.53%) people aged over 40 yr; and no statistical difference was observed between these two age groups (p = 0.817) [Table 1]. When examined statistically for any difference based on other parameters, no difference was observed between the distributions of C. burnetii antibody seropositivity and gender (p = 0.133), occupational groups (p = 0.832), milking (p = 0.177) and fresh cheese consumption (p = 0.344) [Table 1].
When the seroepidemiological relationship between C. burnetii and CCHFV was examined; C. burnetii- CCHFV co-seropositivity was detected in 21 of 387 (5.43%) people whose serology was known in terms of CCHFV. Antibody positivity against C. burnetii was detected in 21 of 118 (17.80%) people showing CCHFV seropositivity and 51 of 269 (18.96%) CCHFV seronegative people; however, the difference was found statistically insignificant (p = 0.787) [Table 1]. In other words, no seroepidemiological relation was found between CCHFV and C. burnetii in the people living in rural areas.
The results were also evaluated to determine if there were any significant differences in the means of the ELISA absorbance values (Optical density; OD) in all the groups by using the univariate analysis and the independent-samples t-test. The OD means of antibodies to C. burnetii were statistically higher for the people who have contacted the ticks in various ways [Group (i), (ii), and (iii)] than those who lived in the village but had not contacted the ticks [Group (iv)] (p = 0.017) contrarily to the results obtained from chi-square tests. The statistical results for both the comparison of OD means (univariate analysis) and chi-square tests were in the same direction considering all other parameters such as the village and city dwellers, the gender and the milking [Table 1].
| Discussion|| |
Q fever is a common zoonotic disease seen throughout the world. People are mostly infected by inhalation of contaminated aerosols dispersed through metabolism products and placentas of infected animals. Therefore, it is seen more frequently in the people living in rural areas and who are engaged in animal breeding than those living in the cities,.
Coxiella burnetii seroprevalence generally varies between 10 and 60% in people living in rural areas, especially among veterinarians, slaughterhouse workers, and animal breeders,,. It’s seropositivity in urban dwellers, where contact with animals and animal products is limited, and in healthy blood donors is generally between 1 and 20%,,. The studies conducted in Turkey also show that seroprevalence changes in accordance with the risk groups and many regions are at risk of infection,,,. The IgG positivity against C. burnetii in the risk group of this study was 19.09%, while it was 4.54% in control group. This result shows that the people living in Tokat and Sivas regions have the risk of C. burnetii infection, and those living in rural areas are five times more likely to be infected (OR= 4.96) than urban dwellers.
According to some epidemiologic studies, C. burnetii seroprevalence might vary from country-to-country and even from region-to-region in similar risk groups,,,,. In this study, the fact that the rate of C. burnetii seropositivity was higher in Sivas than Tokat can be related with the number of animals in two regions. According to the data from Turkish Statistical Institute (2007), the ovine and bovine numbers per person in Sivas is two times more than in Tokat. In this study, Q fever seropositivity in rural areas of Sivas was approximately two-times higher than in Tokat (OR = 1.94), parallel to the numbers of animals per person in both the regions.
Coxiella burnetii has been isolated from many species of ticks,,,,. Even then, the role ofticks in causing infection to humans is considered unimportant. According to the present study, no statistical difference was observed between the risk groups which were and were not exposed to tick bites and tick contacts [Groups (i), (ii), and (iii) vs Group (iv)] in terms of C. burnetii seropositivity in the chi-square test. However, the OD mean of antibodies reactive to C. burnetii for the Groups (i), (ii), and (iii) was statistically higher than Group (iv), according to the results of independent-samples t-test and univariate analysis. When the samples considered as negative (according to cut-off value) were analyzed for their OD value, it was observed that the serum samples representing Groups (i), (ii), and (iii) had an absorbance value usually clustered just below the cut-off value. However, these serums were at a level that can not be considered positive with regard to cut-off value. Both phase-I and -II antibodies have been known to persist for months or years after initial infection,,,,.
The fact that the livestock activity of Groups (i), (ii), and (iii) are higher than the Group (iv), might have caused an increase in the OD values for the people who were exposed to ticks compared to those not exposed to ticks. According to the findings of this study, some people in the risk Groups (i), (ii), and (iii) might have been infected by C. burnetii as a result of tick bites, tick contact and livestock activity in much earlier years of their lives, and their antibody levels may have decreased over the years. Additionally, these people might be the target mass of other infectious agents, which can cross-react with C. burnetii, such as Bartonella quintana, B. henselae, Ehrlichia spp., Rickettsia spp.,,; which needs additional research for confirmation.
The consumption of unpasteurized milk and milk products may play a role in transmitting C. burnetii infection to human,,. Studies on volunteers have shown that contaminated milk induces seroconversion. But, there are also some epidemiologic studies where seroconversion was not detected,. The risk of C. burnetii infection, from raw milk products, is considered low, but it can not be ignored completely. The general view, however, is that dairy products may have little effect,,. Although, drinking of raw milk in Tokat and Sivas regions is not a traditional habit, the cheese is generally made without boiling the milk. In the present study, seropositivity was found in 20 and 15% of the people in the risk groups that consumed and not consumed fresh cheese (respectively) (p > 0.005). These findings indicate that transmission of C. burnetii is not very common through these ways. The reason that there was no difference among occupational groups may be related to the fact that 83.42% of the risk group population was involved in animal breeding.
In the present study, C. burnetii seropositivity rates were higher in men (21.92%) than women (16.29%) as also commonly observed in other studies, which might be due to the fact that men have frequent contact with animals than women; and statically there was no significant difference between the genders,,. However, in some of the studies conducted in Turkey, no relationships were found between gender and seropositivity,; which might be due to similar animal breeding activities between the men and women.
IgG type antibodies developed against C. burnetii phase-I and -II antigens may range in measurable levels for many years,. Coxiella burnetii seropositivity usually increases along with age because the risk probability also increases with the age,,,. In some of the studies conducted in Turkey, it has been stated that C. burnetii seropositivity increased with aging, however, in other studies, it has been reported that there is no any significant difference,,,. In this study also, contrary to the expectation, there was no statistically significant difference between the age groups in view of the seroprevalence of C. burnetii. People living in rural areas in these regions contribute to the family economy from their childhood. About 83.42% of the risk groups were involved in animal husbandry activities. These living conditions may contribute to the fact of similar C. burnetii seroprevalence across all the age groups.
Ticks and tick bites have a significant role in the epidemiology of CCHFV in people,,. When there are epidemiologic similarities between two tick-borne infectious agents in terms of vector, reservoir and risk groups; co-seroprevalence between both is expected. For example, in a study conducted in the Tokat region, antibody positivity against Rickettsia conorii (tick-borne infectious agent) was 25.82% in people seronegative for CCHFV; and 52.32% in people seropositive against CCHFV (p = 0.001). A similar positive correlation was expected serologically between C. burnetii and CCHFV infection in this study. There was no statistical difference between C. burnetii seroprevalence for the people who had, and had no antibodies against CCHFV. Although both CCHFV and C. burnetii are isolated from many species of ticks, the main vectors of both are different species of ticks,,,,,. This study has revealed that the main vector ticks for C. burnetii and CCHFV are more influential in the enzootic cycle of these infectious agents than other ticks, and also that there are very little connection between both the zoonoses as a vector.
| Conclusion|| |
In conclusion, tick contact and tick bite might contribute in raising the antibodies to C. burnetii, but no relation was found between C. burnetii and CCHFV seroepidemiology. Coxiella burnetii is an important infection, which can be seen in every age group and almost every region, particularly in people living in rural areas. Hence, Q fever must be taken into consideration in case of unknown origin fever, hepatitis, peripheral neuropathy, endocarditis, pneumonia, meningoencephalitis and vasculitis in people, who live in rural areas and engaged in animal husbandry along with use of suitable diagnostic tests.
Conflict of interest
There is no conflict of interest in this study.
| Acknowledgements|| |
This study was supported by the Cumhuriyet University, Presidency of Scientific Research Projects Commission (CUBAP) as a Postgraduate Thesis project (T-387) and research project (SHMYO-OO5). Thanks are also due to the nurse Zubeyde Gunes who helped in blood sampling during field surveys and to the Prof. (Dr) Zati Vatansever for contribution in the preparation of maps.
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