Clinical implications of addiction related immunosuppression

doi:10.1016/j.jinf.2008.03.003

Journal of Infection

Volume 56, Issue 6, June 2008, Pages 437-445

https://doi.org/10.1016/j.jinf.2008.03.003 Get rights and content

Summary

Objectives

Despite increasing evidence suggesting that drug addicts have compromised immunity, vigorous discussion continues. One way to examine this clinically is to compare the rates of infections presenting to a clinic which sees both non-substance dependent (N-SUD) and opiate addicted (SUD) patients.

Methods

A survey was conducted amongst our patients of all infectious presentations.

Results

Four-hundred and thirty SUD and 116 N-SUD patients of similar ages (mean ± SD 30.81 ± 7.77 years vs. 32.91 ± 14.41 respectively) were reviewed. SUD had fewer acute infections (120/430, 28% vs. 51/116 44%, OR = 0.60 95% CI 0.40–0.84, P = 0.0034) but their severity was greater (P < 0.00001). The pattern of infections was also different with respiratory infections predominating in N-SUD (32/50 infections, 64%; seasonally invariant) vs. dental (74/114, 64%) and skin infections (18/114, 16%) in SUD. SUD had significantly more dental infections (74/430 patients 21% vs. 3/116 3%, P = 0.0001). In multivariate analysis, group membership was the only variable which explained the variance of “Infection”. Chronic hepatitis C (60% vs. 1%, P < 0.00001) was more frequent in the SUD but there was no difference in hepatitis B or HIV.

Conclusion

These data are consistent with clinical immunosuppression in SUD and may reflect immunostimulation and immunosenescence.

Introduction

There is increasing interest in the immunosuppressive activities of addictive drugs1, 2, 3, 4, 5, 6, 7, 8, 9 from the point of view of predisposition to HIV and other blood borne viral infections, and also from the health burden and acute major infections such as bacterial endocarditis seen in intravenous drug users (IVDU). The cellular mechanisms however appear to be complex and involve an interaction with drug withdrawal10, 11 and with stress.12, 13 All commonly abused addictive agents appear to be implicated in this immune suppression.1, 14 Whilst many mechanistic links have been described in both the cellular and cytokine–humoural immune systems, and detailed investigations are being conducted in many laboratories, there are relatively few reports on the direct implications for clinical practice of this immunosuppression.¹⁵ Whilst higher rates of health service consumption¹⁶ and decline in general health¹⁷ have been identified for substance dependent patients for several years, the contribution of altered immune states to such general health declines has not been considered in detail.

Many age related diseases such as atherosclerosis,18, 19, 20 Alzheimer's dementia21, 22, 23 and osteoporosis24, 25, 26 are increasingly understood to have important inflammatory components. Indeed in the ageing literature the term “inflamm-aging” has been coined to express this concept.27, 28, 29 Similar problems have been recently described in the context of addiction medicine with elevated rates of co-morbid psychological illnesses,30, 31, 32 neuroinflammatory syndromes in addiction,33, 34, 35, 36 drug related osteoporosis37, 38 and high rates of atherosclerotic change identified both in the literature39, 40 and amongst our own patients (unpublished observations). A recent analysis of biochemical and haematological data from this clinic confirmed not only the presence of the well described immune related gammopathy, but also that it tracked differently in addicted populations to the well characterized changes which are known to accompany normal ageing.⁴¹ This showed that addicts exhibit a more rapid rise of inflammatory biomarkers associated with ageing than a control (medical) population. Such studies suggest that the immunosuppression of addiction is associated with a hyperactive or possibly hyperstimulated immune activation, which may be in part compensatory either to the raised antigenic challenge involved in chronic on-going IVDU, the chronic illnesses which so frequently accompany it, or both. Again in the context of a known inflammatory component to the major age related disorders, a hyperstimulated immune is of potential concern, particularly where evidence suggests it might also be dysfunctional.¹²

The polyclonal gammopathy which has long been known to be associated with intravenous drug use,³ and which is presumably of multifactorial aetiology, parallels that reported in elderly patients of advanced age.42, 43, 44 It is particularly seen in the frail and unwell elderly, and has been reported as a powerful independent predictor of mortality amongst the very elderly.45, 46 In addition to the above noted illnesses, other disorders of old age are more common in drug dependent populations including advanced dental disease,⁴⁹ grey hair⁵⁰ and depressed sperm counts.51, 52 Hence the suggestion that inflammatory stimulation is a prime driver of the ageing process, in the context of those same illnesses identified amongst addicted populations, is potentially of great relevance not only to our understanding of the toxicology of addiction probably including long term agonist pharmacotherapies and their infectious complications, but also to the understanding of the ageing process as it occurs in the general population.

For these reasons more detailed medical as well as molecular descriptions of the pathology and clinical consequences of addiction related immunosuppression and immunosenescence are of great importance not only to addiction management but also to our understanding of the mechanisms of the ageing process and the possible causal contribution of immunosuppression–immunostimulation–immunosenescence to that process. Seasonal variation in the comparative incidence of common infectious conditions would appear to be an obvious way to study the clinical impact of such processes, but to our knowledge no studies have been published examining this factor. This paper addresses the clinical presentations which underlie these important immunological imperatives.

Section snippets

Patient recruitment, survey and sampling

This primary care medical centre operates in inner city Brisbane, Australia, and sees both general medical (N-SUD) and drug addicted (SUD) patients. Most of our work involves the treatment of opiate addicted persons, and this is undertaken predominantly with the buprenorphine/naloxone combination sublingual tablet. Surveys of consecutive patients presenting to our centre were performed. Patients were asked a range of questions relating to the variables of interest. Notes were taken directly

Results

This study was performed as a survey of infectious presentations. All opiate addicted patients were treated with the buprenorphine/naloxone combination. Age and sex and some drug use data is presented in Table 1. A total of 431 SUD and 195 N-SUD patients were surveyed. However as the mean ages were significantly older in the N-SUD patients (mean ± SD) 30.98 ± 7.87 vs. 46.62 ± 20.90 years (P < 0.0001), the age range was restricted to 19–53 years. When the comparison was restricted to this range the mean ±

Discussion

The present study compared the rate of infectious presentations in an opiate addicted sample to a general medical patient population presenting to our primary care clinic. The main findings were a reduced frequency of infective disorders in opiate dependent patients overall which was related primarily to a lower incidence of upper and lower respiratory tract illnesses. This reduction in respiratory infections was noted despite an increased number of dental infections seen in opiate addicted

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View full text

Clinical implications of addiction related immunosuppression

Summary

Objectives

Methods

Results

Conclusion

Introduction

Section snippets

Patient recruitment, survey and sampling

Results

Discussion

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