Viral and parasitic pathogen burden and the association with stroke in a population-based cohort

Abstract

Background

Higher cumulative burden of viral and bacterial pathogens may increase the risk of stroke, but the contribution of parasitic infections in relation to cumulative pathogen burden and risk of stroke has rarely been examined.

Aim

To estimate the association of multiple persistent viral and parasitic infections with stroke in a representative sample of adults in the United States.

Methods

Serological evidence of prior infection was categorized as positive for 0–1, 2, 3, or 4–5 infections based on immunoglobulin G seropositivity to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. in 13,904 respondents from the National Health and Nutrition Examination Survey III. Regression analysis was used to estimate the cross-sectional association between serological evidence of prior infection and history of stroke adjusting for demographic risk factors, and potential mediators of stroke.

Results

Age-adjusted models that included serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. showed that adults in the highest serological evidence of prior infection category (4–5 infections) had a higher prevalence of stroke (5.50%, 95% confidence interval 2.44–10.46%) than those in the lowest serological evidence of prior infection categories (1.49%, 95% confidence interval 1.01–2.11%), and a trend test suggested a graded association between serological evidence of prior infection and stroke (p = 0.02). In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio = 1.4, p = 0.01) but was only significant among those aged 20–59 (odds ratio = 2.0, p = 0.005) and not among those aged 60–69 (p = 0.78) or 70 and older (p = 0.43).

Conclusion

We found support for a connection between serological evidence of prior infection to cytomegalovirus, hepatitis A virus, hepatitis B virus, Toxoplasma gondii, and Toxocara spp. and stroke among those aged 20–59. There may be a need to consider common parasitic infections in addition to viral and bacterial pathogens when calculating serological evidence of prior infection in relation to cerebrovascular disease.

Keywords

Epidemiology infection hepatitis virus cytomegalovirus

Get full access to this article

View all access options for this article.

References

Zhang

Yang

Ding

Xie

. Association between Helicobacter pylori infection and stroke: a meta-analysis of prospective observational studies. J Stroke Cerebrovasc Dis 2014; 23: 2233–2239.

Luna

Elkind

Infectious burden and risk of stroke. In: Chen

Stenzel-Poore

Zhang

(eds). Immunological mechanisms and therapies in brain injuries and stroke, Heidelberg: Springer, 2014, pp. 177–210.

Elkind

Ramakrishnan

Moon

et al.

Infectious burden and risk of stroke: the northern Manhattan study. Arch Neurol 2010; 67: 33–38.

Corrado

Rizzo

Tantillo

et al.

Markers of inflammation and infection influence the outcome of patients with baseline asymptomatic carotid lesions: a 5-year follow-up study. Stroke 2006; 37: 482–486.

Kis

Sas

Gyulai

et al.

Chronic infections and genetic factors in the development of ischemic stroke. Microbiol Q J Microbiol Sci 2007; 30: 213–220.

Smieja

Gnarpe

Lonn

et al.

Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Multiple infections and subsequent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 2003; 107: 251–257.

Haider

Wilson

Larson

et al.

The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective study. J Am Coll Cardiol 2002; 40: 1408–1413.

Jones

Kruszon-Moran

Sanders-Lewis

Wilson

. Toxoplasma gondii infection in the United States, 1999 2004, decline from the prior decade. Am J Trop Med Hyg 2007; 77: 405–410.

Won

Kruszon-Moran

Schantz

Jones

. National seroprevalence and risk factors for zoonotic Toxocara spp. infection. Am J Trop Med Hyg 2008; 79: 552–557.

10.

Dupont

Christian

Hunter

. Immune response and immunopathology during toxoplasmosis. In: Seminars in immunopathology 2012; 34: 793–813.

11.

Fan

Liao

Cheng

. Factors affecting disease manifestation of toxocarosis in humans: genetics and environment. Vet Parasitol 2013; 193: 342–352.

12.

Sealy-Jefferson

Gillespie

Aiello

Haan

Morgenstern

Lisabeth

. Antibody levels to persistent pathogens and incident stroke in Mexican Americans. PLoS ONE 2013; 8: e65959.

13.

Goldstein

Bushnell

Adams

et al.

Guidelines for the primary prevention of stroke a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42: 517–584.

14.

NCHS. Sample design: Third National Health and Nutrition Examination Survey. In: U.S. Department of Health and Human Services, ed. Vol Publication No. (PHS) 92–1387. Washington, DC: US GPO, 1992.

15.

Staras

Dollard

Radford

Flanders

Pass

Cannon

. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin Infect Dis 2006; 43: 1143–1151.

16.

McQuillan

Coleman

Kruszon-Moran

Moyer

Lambert

Margolis

. Prevalence of hepatitis B virus infection in the United States: the National Health and Nutrition Examination Surveys, 1976 through 1994. Am J Publ Health 1999; 89: 14–18.

17.

Jones

Kruszon-Moran

Wilson

McQuillan

Navin

McAuley

. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am J Epidemiol 2001; 154: 357–365.

18.

Bell

Kruszon-Moran

Shapiro

Lambert

McQuillan

Margolis

. Hepatitis A virus infection in the United States: serologic results from the third National Health and Nutrition Examination Survey. Vaccine 2005; 23: 5798–5806.

19.

Web resource: http://cdc.gov/nchs/nhanes/nh3data.htm (accessed 4 March 2015).

20.

Mohadjer LWJ. National Health and Nutrition Examination Survey III: weighting and estimation methodology. In: National Center for Health Statistics, Hyattsville, MD, https://cdc.gov/nchs/Data/Nhanes3/Manuals/wgt_exec.pdf (1996, accessed 4 March 2015).

21.

Ezzati TKM. Nonresponse adjustment in a National Health Survey. In: 1992 Proceedings of the section on survey research methods. Alexandria, VA: American Statistical Association, 1993, pp.339–344.

22.

Korn

Graubard

. Confidence intervals for proportions with small expected number of positive counts estimated from survey data. Surv Meth 1998; 24: 193–201.

23.

Fernández-Real

López-Bermejo

Vendrell

Ferri

Recasens

Ricart

. Burden of infection and insulin resistance in healthy middle-aged men. Diabetes Care 2006; 29: 1058–1064.

24.

Cuthbert

. Hepatitis A: old and new. Clin Microbiol Rev 2001; 14: 38–58.

25.

Trépo

Chan

Lok

. Hepatitis B virus infection. Lancet 2014; 384: 2053–2063.

26.

Ebrahimi

Nabipour

Vahdat

et al.

High sensitivity C-reactive protein is associated with the metabolic syndrome independent to viral and bacterial pathogen burden. Diabetes Res Clin Pract 2009; 84: 296–302.

27.

Perlstein

Pande

Creager

Weuve

Beckman

. Serum total bilirubin level, prevalent stroke, and stroke outcomes: NHANES 1999–2004. Am J Med 2008; 121: 781–788. e781.

28.

Griffiths

Sturm

. Epidemiology and etiology of young stroke. Stroke Res Treat 2011; 2011: 209370, 9.

29.

Carod-Artal

Gascon

. Chagas disease and stroke. Lancet Neurol 2010; 9: 533–542.

30.

Selvaraj

Poinsatte

Torres

Ortega

Stowe

. Heterogeneity of B cell functions in stroke-related risk, prevention, injury, and repair. Neurotherapeutics 2016; 13: 729–747.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.20 MB