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A Comparative Study of Seroprevalence of 17
Common Pathogens Among Airline Pilots and
Office Workers
Andrés Santiago Sáez , Ángel García Martín , Manuel Gómez Serrano , Miryam Liaño Riera , Piercarlo
Minoretti
1. Legal Medicine, Hospital Clinico San Carlos, Madrid, ESP 2. Legal Medicine, Psychiatry, and Pathology, Complutense
University of Madrid, Madrid, ESP 3. General Direction, Studio Minoretti, Oggiono, ITA
Corresponding author: Piercarlo Minoretti, scientific.direction@studiominoretti.it
Abstract
Background
The variation in infection risk among individuals is thought to be partially influenced by occupational
factors. This study aims to investigate the seropositivity rates of 17 common infectious agents in male
airline pilots (APs), a professional group known to experience a high prevalence of cardiovascular and
gastrointestinal diseases.
Methodology
In our study, we employed a case-control design with 100 male APs as cases, matched by age, sex, and
tenure (i.e., at least five years of service) to 100 male office workers (OWs) who served as controls. We
measured the IgG antibody levels to 17 pathogens using specific enzyme-linked immunosorbent assays,
including herpes simplex virus 1, herpes simplex virus 2, varicella-zoster virus, Epstein-Barr virus,
cytomegalovirus, human herpesvirus 6, human herpesvirus 7, Kaposi’s sarcoma-associated herpesvirus,
Toxoplasma gondii, human T-lymphotropic virus 1, BK virus, John Cunningham virus, Merkel cell
polyomavirus, human papillomavirus 16, human papillomavirus 18, Chlamydia trachomatis, and Helicobacter
pylori. The determination of seropositivity cutoffs for each pathogen was made in accordance with the
guidelines provided by the respective kit manufacturers.
Results
The seropositivity rates for the 17 pathogens ranged from 1% for human T-lymphotropic virus 1 to 94% for
varicella-zoster virus and were similar in both professions, except for herpes simplex virus 1 and Helicobacter
pylori, which were more prevalent in APs.
Conclusions
Our findings suggest a higher prevalence of previous infections with herpes simplex virus 1 and Helicobacter
pylori in APs compared to OWs. These infections may be associated with the prevalence of specific non-
communicable diseases in this professional group. However, additional longitudinal studies are needed to
substantiate this hypothesis.
Categories: Infectious Disease, Occupational Health
Keywords: airline pilots, occupational medicine, infections, seroprevalence, office workers
Introduction
Persistent infections caused by various pathogens, including viruses, bacteria, and parasites, have been
identified as a contributing factor to the development of non-communicable diseases (NCDs) such as
cardiovascular disease (CVD) and cancer in the general population [1]. In addition, research indicates a
correlation between persistent pathogen-induced inflammation and the progression of atherosclerotic
vascular disease [2]. The concept of pathogen burden, which refers to the cumulative exposure to different
infectious agents [3], has emerged as a potential determinant of NCD risk. Seropositivity, determined
through IgM and/or IgG antibody testing, is commonly used to assess infection prevalence within a
community [4]. Interestingly, various factors including education levels, socioeconomic status, and
occupational factors have been found to influence seropositivity rates [3,5]. These rates depict the
proportion of individuals who test positive for specific pathogen antibodies relative to the total number of
individuals tested.
Airline pilots (APs) encounter various occupational hazards that can have adverse effects on their health
and well-being [6]. The nature of their work, which involves irregular flight schedules, shift work, and travel
1, 2 2 2 2
3
Open Access Original
Article DOI: 10.7759/cureus.50778
How to cite this article
Santiago Sáez A, García Martín Á, Gómez Serrano M, et al. (December 19, 2023) A Comparative Study of Seroprevalence of 17 Common
Pathogens Among Airline Pilots and Office Workers. Cureus 15(12): e50778. DOI 10.7759/cureus.50778
across different time zones, often disrupts their natural body rhythms. In addition, pilots may suffer from
fatigue, exposure to cosmic radiation, irregular meal times, disrupted sleep patterns, and even symptoms of
depression [6-10]. The sedentary nature of their job and the cabin environment, characterized by noise and
vibrations [11], further compound these challenges. Previous studies have indicated a higher prevalence of
malignant melanoma [12] among pilots compared to the general population. Additionally, this professional
group exhibits a significant incidence of cardiometabolic risk factors [8] and functional gastrointestinal
disorders (FGIDs) [13]. However, the potential impact of infectious pathogens on exacerbating these health
issues remains uncertain due to the lack of seroepidemiological investigations specifically focused on
common infectious pathogens among APs. Consequently, there is a dearth of data on seropositivity rates for
viruses, bacteria, and parasites that may be associated with NCDs within this particular population.
In this study, we conducted an extensive analysis of sera collected from APs to determine the rates of
seropositivity (IgG antibodies) for 17 pathogens, including herpes simplex virus 1 (HSV-1), herpes simplex
virus 2 (HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human
herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), Kaposi’s sarcoma-associated herpesvirus (KSHV),
Toxoplasma gondii (T. gondii), human T-lymphotropic virus 1 (HTLV-1), BK virus (BKV), John
Cunningham virus (JCV), Merkel cell polyomavirus (MCV), human papillomavirus 16 (HPV-16), human
papillomavirus 18 (HPV-18), Chlamydia trachomatis (C. trachomatis), and Helicobacter pylori (H. pylori). While
most infections caused by these pathogens generally result in mild or subclinical symptoms, there are cases
where they can lead to severe manifestations and, more importantly, increase the risk of NCDs. To compare
the findings, we selected a control group of office workers (OWs) who were matched for age, sex, and tenure
(i.e., at least five years of service).
Materials And Methods
Participants
In our study, we employed a case-control design with 100 male APs as cases, matched by age, sex, and
tenure (i.e., at least five years of service) to 100 male OWs who served as controls. The subjects were
voluntarily recruited during routine occupational health assessments at outpatient clinics, with invitations
to participate disseminated by an occupational health physician. To ensure accurate results, we matched
each OW with an AP in terms of age, sex, and tenure, with a minimum requirement of five years of service.
Office professionals who were subjected to shift work, extensive travel, or disruptions to their circadian
rhythm were not eligible for inclusion. We excluded women due to their limited representation within the AP
population. Participants with a history of diabetes, CVDs, malignancies, or recent drug therapy were also
excluded. Additionally, none of the participants were using dietary supplements, and they all appeared to be
in good physical health. All procedures were conducted at outpatient facilities owned by Studio Minoretti Srl
(Oggiono, Italy). The research adhered to the ethical standards outlined by the Declaration of Helsinki and
received approval from the local ethics committee (Studio Minoretti; reference number: 2021/12SES). We
obtained written informed consent from each participant before including them in the study.
Serological testing and definitions
Participants provided a fasting venous blood sample of 10 mL, which was collected into serum collection
tubes. The sera were then analyzed using commercially available enzyme-linked immunosorbent assay
antibody test kits to detect IgG antibodies against 17 common pathogens (HSV-1, HSV-2, VZV, EBV, CMV,
HHV-6, HHV-7, KSHV, T. gondii, HTLV-1, BKV, JCV, MCV, HPV-16, HPV-18, C. trachomatis, and H. pylori). The
manufacturers’ protocols were followed to determine the seropositivity cutoffs for each pathogen, and the
results were reported as either positive or negative. Out of the 17 pathogens, five (EBV, HTLV-1, H. pylori,
HPV-16, and HPV-18) are classified as group I human carcinogens by the International Agency for Research
on Cancer [3]. The pathogen burden was assessed based on the percentage of individuals within each
professional group who tested positive for more than 10 infectious pathogens [3] and more than two
oncogenic pathogens [3].
Statistical analysis
The normality of continuous data was assessed using the Kolmogorov-Smirnov test, which revealed that all
variables followed a normal distribution. This confirms the appropriateness of using parametric statistical
methods. Continuous variables were presented as mean ± standard deviation (SD), while categorical data
were expressed as counts and percentages. To compare the two professions, the Student’s t-test was used for
continuous data, and the chi-squared test was applied for categorical variables, including seropositivity
counts. Crude odds ratios (ORs) were calculated to describe the associations between the seropositivity
status and each professional category. The statistical analyses were conducted using SPSS software version
20.0 (IBM Corp., Armonk, NY, USA), and all tests were two-sided with a significance level of 5%.
Results
Table 1 provides an overview of the key characteristics observed among the participants.
2023 Santiago Sáez et al. Cureus 15(12): e50778. DOI 10.7759/cureus.50778 2 of 7
Variable Airline pilots (n = 100) Office workers (n = 100) P-value
Men 100 (100%) 100 (100%) ns
Age, years 39.8 ± 4.7 40.3 ± 5.0 ns
Length of service, years 10.1 ± 4.2 10.4 ± 4.5 ns
Current smoking, n (%) 18 (18.0%) 21 (21.0%) ns
Body mass index, kg/m224.7 ± 2.9 25.1 ± 3.1 ns
Total cholesterol, mg/dL 216 ± 15 224 ± 19 ns
Fasting plasma glucose, mg/dL 94 ± 11 96 ± 12 ns
TABLE 1: General characteristics of the study participants.
Data are expressed as means ± standard deviations unless otherwise indicated.
ns: not significant
The two groups did not differ significantly in various aspects, including age, service duration, current
smoking habits, body mass index, total cholesterol, and fasting plasma glucose levels. Table 2 provides an
overview of the seropositivity rates for each pathogen, with percentages ranging from 1% for HTLV-1 to 94%
for VZV.
2023 Santiago Sáez et al. Cureus 15(12): e50778. DOI 10.7759/cureus.50778 3 of 7
Positive IgG serology, n (%) Airline pilots (n = 100) Office workers (n = 100) P-value
HSV-1 78 (78%) 60 (60%) 0.006
HSV-2 12 (12%) 10 (10%) ns
VZV 94 (94%) 92 (92%) ns
EBV 78 (78%) 74 (74%) ns
CMV 61 (61%) 57 (57%) ns
HHV-6 77 (77%) 81 (81%) ns
HHV-7 90 (90%) 87 (87%) ns
KSHV 15 (15%) 11 (11%) ns
T. gondii 21 (21%) 16 (16%) ns
HTLV-1 2 (2%) 1 (%) ns
BKV 88 (88%) 90 (90%) ns
JCV 61 (61%) 56 (56%) ns
MCV 58 (58%) 60 (60%) ns
HPV-16 5 (5%) 3 (3%) ns
HPV-18 3 (3%) 2 (2%) ns
C. trachomatis 19 (19%) 16 (16%) ns
H. pylori 38 (38%) 21 (21%) 0.009
TABLE 2: Seropositivity for 17 different pathogens in airline pilots and office workers.
Pathogens classified as group I human carcinogens by the International Agency for Research on Cancer are marked in bold.
ns: not significant; HSV-1: herpes simplex virus 1; HSV-2: herpes simplex virus 2; VZV: varicella-zoster virus; EBV: Epstein-Barr virus; CMV:
cytomegalovirus; HHV-6: human herpesvirus 6; HHV-7: human herpesvirus 7; KSHV: Kaposi’s sarcoma-associated herpesvirus; T. gondii: Toxoplasma
gondii; HTLV-1: human T-lymphotropic virus 1; BKV: BK virus; JCV: JC virus; MCV: Merkel cell polyomavirus; HPV-16: human papillomavirus type 16;
HPV-18: human papillomavirus type 18; C. trachomatis: Chlamydia trachomatis; H. pylori: Helicobacter pylori
The prevalence rates were comparable between both professions, with the exception of HSV-1 and H. pylori,
which were more common among APs. The crude ORs showed that APs were 2.35 times more likely to be
seropositive for HSV-1 (95% confidence interval (CI) = 1.27-4.39, p = 0.006) and 2.30 times more likely to be
seropositive for H. pylori (95% CI = 1.23-4.32, P = 0.009) compared to OWs.
All participants tested positive for at least one pathogen. Among them, 23 APs (23%) and 13 OWs (13%)
exhibited seropositivity for over 10 pathogens, suggesting a potentially higher pathogen burden in APs.
However, this difference did not reach statistical significance (crude OR = 1.83, 95% CI = 0.88-3.81, p = 0.10).
A similar non-significant trend was observed for seropositivity for more than two oncogenic pathogens.
Specifically, nine APs (9%) and three OWs (3%) had this condition, resulting in a crude OR of 3.16 (95% CI =
0.83-12.04, p = 0.09).
Discussion
This study is the first to compare the seropositivity rates of 17 common infectious agents in two distinct
groups: APs, a professional category commonly affected by NCDs [6,8], and OWs. Additionally, it provides
valuable insights into specific oncogenic pathogens. The study revealed three key findings. First, APs
exhibited higher prevalence rates of HSV-1 and H. pylori compared to OWs. Second, although not
statistically significant, there was a tendency toward a higher pathogen burden in APs, defined as
seropositivity for more than 10 pathogens. Lastly, a similar trend was observed for the seroprevalence of
more than two oncogenic pathogens.
Human infection with HSV-1, a member of the herpesviridae family, poses a significant public health
concern [14]. In 2016, global estimates indicated that approximately 3.752 billion individuals were infected
with HSV-1, accounting for a worldwide incidence of 66.6% in the age group between 0 and 49 years [15].
2023 Santiago Sáez et al. Cureus 15(12): e50778. DOI 10.7759/cureus.50778 4 of 7
Our study findings align with this epidemiological trend, revealing a seroprevalence of 78% among APs and
60% among OWs. Primary infection with HSV-1 is usually asymptomatic, but in rare cases, it can result in
severe encephalitis [16]. Following the primary infection, the virus enters a latent phase where it remains
inactive within neurons. Reactivation of the virus is usually triggered by stress-related immune system
dysregulation and can manifest as grouped vesicular papules with inflammatory components on the oral,
corneal, and/or genital mucocutaneous surfaces [16]. Additionally, the host’s immune response, specifically
cytokine-mediated immunologic reactions, can also contribute to the development of systemic diseases
associated with HSV-1 [16]. Intriguingly, studies have demonstrated a potential association between the
seroprevalence of anti-HSV-1 antibodies and CVD [17-19]. Remarkably, the burden of cardiovascular risk
factors appears to be significantly elevated among APs [7,8,20]. In a cohort study conducted by Siscovick et
al. [17] in the United States, it was discovered that older individuals with IgG antibodies against HSV-1 were
twice as likely to experience myocardial infarction and cardiovascular mortality. Similarly, Jafarzadeh et al.
[18] found that Iranian patients with ischemic heart disease had significantly higher anti-HSV-1 antibody
seroprevalence compared to a healthy control group. Additionally, a meta-analysis by Wu et al. [19] of 17
studies revealed a 1.77-fold increased risk of atherosclerosis in patients infected with HSV-1. Despite these
findings, the role of HSV-1 in CVD remains a matter of debate due to inconsistent results in the published
literature [21]. It is also worth noting that gastric HSV-1 infection has also been linked to FGIDs [22], which
have been previously reported in APs [13]. Unlike space flight, where HSV-1 infections have been more
thoroughly investigated [23,24], the reasons behind the higher HSV-1 seroprevalence in APs compared to
OWs are currently speculative as this finding is reported for the first time. However, pilots’ immune system
dysregulation due to high fatigue and circadian disruption [6,10] as well as factors related to local air
recirculation in current airliner cabins [11] may represent plausible explanations. Although acute HSV-1
infections do not affect pilots’ fitness to fly, medical advice should be given regarding the shedding of viral
DNA from saliva and oral secretions.
H. pylori, a gram-negative and spiral-shaped bacterium that predominantly colonizes and proliferates within
the gastric mucosa, has been linked to both peptic ulcer disease [25] and FGIDs [26]. In our study, we
observed a significantly higher prevalence of H. pylori IgG antibodies in APs compared to OWs. Regulatory
authorities have established guidelines for aeromedical examiners, stipulating that pilots with stable and
effectively managed peptic disease may be granted fitness-to-fly certifications. Nonetheless, individuals
who have experienced an active ulcer must demonstrate a minimum of three months of stability, devoid of
symptoms. In cases where the ulcer has resulted in bleeding, a six-month period of stability is required.
Hence, H. pylori infection could potentially be an overlooked factor contributing to significant loss of work
hours in APs. Moreover, individuals infected with H. pylori may exhibit FGIDs, particularly if they also
experience dysbiosis of gut microbiota [27]. A study involving 212 male pilots from a prominent Chinese
airline revealed that an estimated 39% suffered from FGIDs [13], a figure strikingly similar to the H. pylori
seropositivity rate observed in our study (38%). In a recent investigation, we have also highlighted a notable
reduction in health-promoting bacterial species within the gut microbiota of APs [28]. This elevated H. pylori
infection rate, in conjunction with intestinal dysbiosis [28], could potentially account for the reported high
incidence of FGIDs within this occupational group. Furthermore, H. pylori infection has been linked to
various extraintestinal manifestations, such as CVD, obstructive sleep apnea syndrome, and metabolic
syndrome [29]. These are conditions that have been previously reported in the pilot population [6-8], adding
to the significance of this association. Another intriguing observation is the connection between H. pylori
and motion sickness. A retrospective study conducted among pilot trainees undergoing basic flight training
revealed that those who tested positive for H. pylori and received eradication therapy experienced a
temporary reduction in reported nausea during flight training [30]. Although the exact transmission routes
of H. pylori are not fully understood, it is hypothesized that overcrowding may serve as a transmission risk
factor [31]. Consequently, highly occupied spaces such as aircraft cabins [11] can make APs more susceptible
to contracting the infection. In addition, the recirculation of air within the cabin [11] could potentially
contribute to this risk. This factor could also explain the non-significant trends observed toward a higher
pathogen burden, including seropositivity for over 10 pathogens, as well as seropositivity for more than two
oncogenic pathogens in APs compared to OWs.
Our study boasts a notable strength in its thorough evaluation of IgG antibodies across various pathogens.
Furthermore, we made efforts to carefully match both occupational groups in terms of general
characteristics, effectively minimizing the influence of confounding variables on the seropositivity rates.
However, it is essential to acknowledge the limitations of our research. The relatively small sample size
introduces an element of uncertainty, preventing us from drawing definitive conclusions. Furthermore, the
voluntary participation of APs and OWs may introduce self-selection bias, limiting the generalizability of our
findings. The exclusion of female participants also hinders the applicability of our results to women.
Additionally, we did not collect data on potential determinants or correlates for infections, which are
typically not gathered during occupational health visits. Lastly, the absence of endoscopy data prevents us
from establishing a correlation between H. pylori seropositivity and the presence of peptic ulcer disease.
Conclusions
Our research indicates a significantly higher prevalence of prior infections with HSV-1 and H. pylori among
APs compared to OWs. These infections could potentially be linked to the high prevalence of certain NCDs
observed within this professional group. However, these findings are preliminary and should be interpreted
2023 Santiago Sáez et al. Cureus 15(12): e50778. DOI 10.7759/cureus.50778 5 of 7
with caution. To further validate this hypothesis and establish a more definitive causal relationship, it is
crucial to conduct additional longitudinal studies. These future investigations will provide a more
comprehensive understanding of the occupational health risks associated with these infections and inform
appropriate preventative measures.
Additional Information
Author Contributions
All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the
work.
Concept and design: Piercarlo Minoretti, Andrés Santiago Sáez
Acquisition, analysis, or interpretation of data: Piercarlo Minoretti, Andrés Santiago Sáez, Ángel García
Martín, Manuel Gómez Serrano, Miryam Liaño Riera
Drafting of the manuscript: Piercarlo Minoretti, Andrés Santiago Sáez
Supervision: Piercarlo Minoretti
Critical review of the manuscript for important intellectual content: Ángel García Martín, Manuel
Gómez Serrano, Miryam Liaño Riera
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Studio Minoretti issued
approval 2021/12SES. The research followed the ethical standards outlined by the Declaration of Helsinki
and received approval from the local ethics committee (Studio Minoretti; reference number: 2021/12SES).
Written informed consent was obtained from each participant before their inclusion in the study. Animal
subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conf licts of
interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from any
organization for the submitted work. Financial relationships: All authors have declared that they have no
financial relationships at present or within the previous three years with any organizations that might have
an interest in the submitted work. Other relationships: All authors have declared that there are no other
relationships or activities that could appear to have influenced the submitted work.
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