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Discussion
The main finding in this study was the lack of association between the risk factors tick bites and Borrelia antibodies with the outcomes subjective health complaints, reduced general function and reduced physical fitness. On the contrary, we found a positive association between tick bites and good physical fitness, and between presence of Borrelia IgG and low occurrence of "pseudoneurological" complaints. For most complaints, however, we found no association.
The risk factor "number of tick bites" was included in this study to explore the possibility that seronegative LB or other tick-borne infectious agents not tested for, e.g. Anaplasma phagocytophilum, Rickettsia spp., etc., could give rise to chronic health problems of some magnitude.
IgG and IgM antibodies to B. burgdorferi s.l. verified by blot were chosen as risk factors in this study in order to avoid including false positive ELISA results. However, biologically false positive IgM blot results still are a problem, and American guidelines thus argue against using IgM blot in the second-tier testing when disease duration is longer than one month. A proportion of the IgM blot positive specimens in this study are probably biologically false positive, as discussed elsewhere. Also, many will lose their antibodies after a while, whether treated or not. However, antibodies against B. burgdorferi s.l., especially IgG, should be an indicator of former or present infection with this organism.
In several studies of symptoms after LB, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) has been used. In addition, several questionnaires for assessing somatic symptoms in the general population exist. The unique contribution of the current study was to include the SHC questionnaire, which was designed to measure common and prevalent health complaints in the general population, and has been used in several studies of the general population as well as different patients groups.
Compared to other surveys using the SHC Inventory in the general population, summarised by Eriksen et al. in 1999, and for a working population more recently by Ihlebæk and co-workers, the proportion of subjects with any complaint were lower in our material for most complaints, reflecting the overall healthy status of the blood donors (Additional file 1 http://www.biomedcentral.com/1471-2458/15/657/additional).
Comparing our results to those of other studies is not straight forward, of two main reasons. Firstly, the selection of study population differs between studies, e.g., blood donors, subjects having been bitten by ticks, patients having suffered from LB, patients having suffered from LNB, etc. Secondly, the choice of questionnaire also varies. We are not aware of other studies using the SHC inventory in blood donors or in relation to LB. Nevertheless, in the following, a tentative comparison is attempted.
In a study of 1156 male military recruits in Germany, Treib and co-workers found that Borrelia IgG positive subjects reported significantly more fatigue, general malaise and limb pain, compared to seronegatives. This is in contrast to our findings, where musculoskeletal pain in different locations as well as "tiredness", "reduced general function" and "reduced physical fitness" was reported as often by seronegatives as by seropositives for IgG.
Studies by Shadic and co-workers from 1994 and 1999 found that persons with a history of LB had more musculoskeletal impairment and a higher prevalence of verbal memory impairment when compared with those without a history of LB. As these reports are based on a different study population as well as a different questionnaire, they are not directly comparable with our present study. However, our results do not corroborate these findings, as musculoskeletal pain and reduced general function were not found associated with seropositivity or number of tick bites.
In agreement with our results, Seltzer and co-workers reported that persons having suffered from LB generally did not report more symptoms than controls, including memory problems, numbness, fatigue, swollen joints, headaches, neck pain, or problems with sleeping and exercise. Also, supporting our findings, in two recent Slovenian studies of patients treated for erythema migrans, the researchers did not find any association between cases and controls in non-specific symptoms 6 months after treatment. In long-term follow-up of patients with culture-confirmed LB, Wormser and co-workers did not find evidence of severe fatigue or fibromyalgia attributable to LB, and summary scores of physical and mental health were similar to those of the general population.
As part of the Swedish "STING-study", Fryland and co-workers compared symptoms in patients bitten by ticks infected with Borrelia burgdorferi sensu lato with patients bitten with non-infected ticks. They found a higher frequency of patients reporting any symptom in the former group, but no differences between the groups when comparing the frequency of each of several symptoms. In the present study, we found that the count of subjective health complaints had no relation with any of the risk factors (Table 3).
In a prospective investigation of patients treated for LNB in Norway, Eikeland and co-workers found that LNB-treated patients scored lower on all the SF-36 subscores except on bodily pain, and they reported fatigue, memory problems and concentration difficulties more often than matched controls. Notable was that in contrast to the results from Shadic et al., pain was not more common among LNB-treated patients than among controls, neither assessed by direct question nor by SF-36. These data are not comparable to our study, as very few, if any, of our study subjects have suffered from LNB.
According to alternative views on LB, there are many undiagnosed patients with nonspecific chronic symptoms attributable to the disease. Among the listed symptoms, some are included in the SHC inventory. The prevalence of these was not significantly higher for any of the risk factors tick bites, IgG or IgM in our study. However, a number of symptoms are not explicitly included in the SHC inventory. If these symptoms were of any significance in our study population, it should be reflected in the score on "reduced general function" in subjects with the risk factors. This was, however, not the case.
The clear correlation between the number of tick bites and physical fitness is not surprising. Persons more exposed to ticks are presumably more involved in outdoors activities such as hiking and hunting, and are in a generally good physical condition.
The negative association of "pseudoneurological" complaints and Borrelia IgG antibodies, but not number of tick bites or IgM, is difficult to explain. Also here, a spurious relationship connected to confounding lifestyle factors can be suspected.
The strength of this study is the relatively large representation of healthy subjects from Sogn and Fjordane county, the good response rate, and the frequent occurrence of tick bites and seropositivity to B. burgdorferi s.l., as well as the scope of the questionnaire, covering a broad range of health complaints. Thus, major chronic health effects of tick bites and seropositivity to B. burgdorferi s.l. should be detected.
On the other hand, blood donors are not completely representative of the general population. They are healthy, and children and persons over 70 years are not represented. There was, however, a fair distribution regarding gender and age groups. According to Norwegian blood bank regulations, persons that have been bitten by ticks should not donate blood within four weeks of the bite, and persons with suspected or verified LB should not donate until six months after adequate treatment has been given. Donors with recent tick bites and/or LB may therefore be underrepresented. Not all tick bites are recognized by the bitten person, and thus will not be reported in a questionnaire survey like this (i.e., information bias). This is supported by the seroprevalence rate for immunoblot verified IgG antibodies to B. burgdorferi s.l. of 2.4 % in subjects not reporting any tick bite.
It is to be expected that persons with significant chronic health problems do not volunteer as blood donors, or will be excluded. Persons of this category are therefore probably underrepresented in this material. However, given the commonness of these "soft" symptoms also in blood donors (Table 2), one would expect that mild degrees of such complaints should be represented.
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