More than half a million lives have been lost to the North American opioid crisis [1–4]. While opioid-related mortality is staggering, opioid-associated morbidity often garners much less attention, despite its major health and economic burden to society [5, 6]. In particular, the prevention of acquisition and transmission of opioid use associated infections (OUAI) requires more attention by society and health care providers [7–10].
People who use illegally obtained pharmaceutical or non-pharmaceutical opioids , especially persons who inject drugs, are at high risk of serious infectious such as infective endocarditis, septic arthritis, osteomyelitis, meningitis, cellulitis, abscesses, and bacteremia, resulting in prolonged and expensive hospital stays [12, 13]. Hepatitis C (HCV) and human immunodeficiency virus (HIV) are two commonly cited OUAIs associated with a substantial burden for individuals and society: approximately 10–20% of HCV-infected individuals are at risk of hepatic cirrhosis, hepatocellular carcinoma, and hepatic failure in the 20–30 years post-viral acquisition . Likewise, HIV infection causes a wide range of immunological problems, including infectious and oncological diseases, cardiovascular, bone, hepatic, and renal diseases, as well as chronic pain . The risk of OUAI, however, is not limited to illegal opioid consumption only. Patients treated with pharmaceutical opioids  appear more susceptible to viral, fungal, and bacterial infections when compared to patients not treated with opioids [16–21]. In higher doses, prolonged therapeutic use of opioids seems to facilitate virus entry and replication (hepatitis A, B, C, and HIV) and increase the risk of opportunistic bacterial, fungal, and parasitic infections [20, 21].
To prevent OUAIs in persons who inject drugs, the Centers for Disease Control and Prevention guideline  recommends screening for infectious complications and use of various preventive measures to reduce acquisition and transmission of HCV, HIV, hepatitis B virus, Herpes Simplex Virus type 2, Human Papillomavirus, tuberculosis, and common sexually transmitted diseases. In addition, The Best Practice Recommendations for Canadian Harm Reduction Programs  highlight the importance of routine skin care to prevent bacterial and fungal infections in persons who inject drugs. For people who use opioids, additional risks for infections transmission and acquisition are related to opioids’ immunosuppressive properties. Thus, the risks are multi-factorial, and a variety of effective interventions aimed to prevent OUAI are of paramount importance to the individuals, public, healthcare decision makers, and policy advisers.
We, therefore, propose to conduct a systematic review (SR) of SRs (SR of SRs) to describe the scope and evaluate the effectiveness of the interventions to prevent OUAIs. The SR of SRs is a type of overview of reviews that are intended to inform guidelines and clinical practices  “…to provide…summaries of the breadth of research relevant to a decision without decision makers needing to assimilate the results of multiple systematic reviews themselves” [25–27].
To identify a potential scope of existing interventions to curb opioid crisis, an initial search was performed for an overarching research study (Canadian Institutes of Health Research [CIHR] grant #EOC-162067). Among others, this search revealed eighteen SRs [28–45] on OUAIs prevention. The identified literature was limited to the HCV and HIV prevention, treatment, or integrated care, and targeted population of persons who inject drugs only. Therefore, some SRs devoted to other types of OUAI prevention may have been missed.
Thus, the goal of the present SR of SRs is to synthesize SR-level evidence regarding interventions with evaluated effectiveness in prevention of OUAIs. We will include all categories of opioids use, legal and illegal/mixed (see Methods, Definitions section). All types of pharmaceutical and non-pharmaceutical opioids and all routes of use (injecting and non-injecting) will be eligible. Finally, for SRs studying the population of illegal/mixed opioid users, we will ensure that use or co-use of opioids was confirmed among study participants.
Review goal and objectives
The overarching question for the SR of SRs in this protocol is: What is the SR evidence concerning the scope and effectiveness of interventions to prevent OUAIs?
The three specific objectives are: 1) To describe SR-level of evidence for the scope of interventions with evaluated effectiveness in prevention of OUAIs; 2) To synthesize the SR-level evidence on the effectiveness of interventions to prevent OUAIs; and 3) To identify knowledge gaps in this area.