Examining unsafe injection practices associated with auto-disable (AD) syringes: a systematic review

ABSTRACT

Auto-disable (AD) syringes are specifically designed to prevent syringe reuse. However, the notion that specific AD syringe designs may be unsafe due to reuse concerns related to the syringe’s activation point has surfaced. We conducted a systematic review for evidence on the association between AD syringe design and syringe reuse, adverse events following immunization (AEFI), or blood borne virus (BBV) transmission. We found no evidence of an association between AD syringe design and unsafe injection practices including syringe reuse, AEFIs, or BBVs. Authors of three records speculated about the possibility of AD syringe reuse through intentionally defeating the disabling mechanism, and one hinted at the possibility of reuse of larger-than-required syringes, but none reported any actual reuse instance. In contrast to AD syringes, standard disposable syringes continue to be reused; therefore, the global health community should expand the use of AD syringes in both immunization and therapeutic context as an essential strategy for curbing BBV transmission.

KEYWORDS:

• Auto–disable syringe
• disposable syringe
• syringe reuse
• unsafe injection practices
• bloodborne diseases
• activation point
• adverse events following immunization
• syringe design

Introduction

Syringe reuse, along with other unsafe injection practices, is a major contributor to a widespread spectrum of adverse effects including the global burden of blood borne diseases.^1–5 Despite substantial improvement in injection safety over the past two decades, unsafe injections remain prevalent, particularly in the Eastern Mediterranean region.⁵ In 2010, an estimated 1.67 million hepatitis B virus (HBV) cases, 315,120 hepatitis C virus (HCV) cases, and 33,877 human immunodeficiency virus (HIV) cases were attributable to unsafe injection practices.⁵ To curb the spread of blood borne diseases induced by unsafe injections, the World Health Organization (WHO), United Nations International Children’s Emergency Fund (UNICEF), United Nations Population Fund (UNFPA), and the International Federation of Red Cross and Red Crescent Societies (IFRC) jointly recommended the exclusive use of auto–disable (AD) syringes for immunization in 1999, which was updated in 2019.^6,7 AD syringes incorporate a reuse prevention feature, which is meant to render the syringe unusable following the delivery of a single dose and thereby eliminate the risk of reuse. AD syringes are, therefore, a critical tool for combatting the spread of blood borne diseases. Despite the widespread use of AD syringes for the past two decades, there is limited research examining how well they have performed in the field with regard to eliminating the practice of syringe reuse.

WHO developed AD syringe specifications in the 1990s, which, in a process driven by WHO, was translated into an ISO standard in 2005; ISO 7886-3 Sterile hypodermic syringes for single use (Part 3: Auto-disable syringes for fixed-dose immunization).⁸ In May 2020, an updated version of the ISO was released. However, both the 2005 and the 2020 ISO explicitly leave the syringe’s disabling feature’s design to manufacturer discretion.^8,9 Therefore, although all AD syringes have an in-built disabling mechanism, syringes made by different manufacturers differ in terms of their specific design; for example, whereas in some AD syringes, the plunger breaks off to prevent reuse, others are disabled by a metal clip.¹⁰ AD syringes also differ in terms of the disabling feature’s activation point, with the activation mechanism engaging at different points of injection administration.¹⁰ As of August 2020, there were 46 AD syringes prequalified by WHO.¹¹ The WHO specification and subsequent ISO standard catalyzed the extensive use of AD syringes across the globe. Between 2001 and 2010, AD syringes were used to vaccinate 900 million persons across 60 countries through the Gavi supported Measles Initiative.¹² In 2017, UNICEF supplied >600 million 0.5 ml AD syringes¹³ and, at present, supplies AD syringes to 89 countries (either as a donation or through procurement services). In 2017, 65 million children were vaccinated through Gavi supported programs alone.¹⁴

Although several studies have pursued essential questions pertaining to AD syringes, such as how cost-effective they are,^15,16 and how they can be leveraged to improve vaccination coverage,¹⁷ studies showing the impact of different designs of AD syringes on unsafe injection practices, including syringe reuse, currently do not exist. The notion that specific AD syringe designs are unsafe due to reuse concerns and should be disqualified warrants a comprehensive review for empirical evidence; the decision to discontinue any of the AD syringe designs should not be made lightly due to global health policy implications, including inadvertently leading to manufacturer monopoly in the domain.

We sought to conduct a systematic literature review of published literature with the primary objective to identify any evidence of unsafe injection practices associated with any AD syringe design or activation point, including syringe reuse, Adverse Events Following Immunization (AEFI), and syringe-associated blood borne virus (BBV) transmission. As a secondary objective, to ensure a robust and thorough literature review, evidence of unsafe injection practices associated with standard disposable syringes including syringe reuse, AEFI, and BBV transmission was also included.

Methods

To comprehensively capture all adverse events and unsafe practices, we included disposable syringes and AD/RUP (Re-use prevention) syringes for both therapeutic and immunization purposes in our review. We searched research databases using preselected keywords and inclusion criteria.

Search strategy and selection criteria

We followed PRISMA guidelines for systematic review and reporting.¹⁸ We searched the following nine databases between November 28, 2019, and March 31, 2020, without any date filters: PubMed, Cochrane, Medline, Google Scholar, EMBASE, Web of Science, Clinical trials registry, Vaccine Resource Library (VRL), and SYSVAC. We used the following search terms to identify literature on the intervention and outcomes of interest ‘auto-disable syringes’, ‘AD syringes’, ‘auto-lock syringes’, ‘auto-destruct syringes’, ‘disposable syringe’, ‘standard disposable syringes’, ‘non reusable syringes’, ‘reuse prevention syringes’, ‘RUP’, ‘RUP syringe’, ‘reuse’, ‘syringe reuse’, ‘unsafe syringe’, ‘unsafe immunization injection’, ‘unsafe injection practices’, ‘used syringe’, ‘blood borne diseases’, ‘blood borne virus’, ‘blood borne infection’, ‘HIV’, ‘HCV’, ‘HBV’, ‘adverse events’, ‘adverse effects’, ‘adverse events following immunization’, ‘AEFI’ and ‘side effects’. To ensure we captured syringe reuse in all contexts of health service provision (drug and insulin use by individuals in non-clinical settings were deemed outside the scope of this review), we added the following terms: ‘immunization’, ‘childhood immunization’, ‘routine immunization’, ‘childhood vaccination’, ‘medical injections’, ‘therapeutic injections’. We also conducted searches with terms such as ‘unnecessary injections’, ‘overuse of injections’, ‘irrational injections’, ‘shortage of injection equipment’, ‘stock out of injection equipment’, ‘unsterile injection equipment’, ‘sterile injection equipment’, ‘safe injection practices’, and ‘safety syringe’, to excavate any remaining relevant literature. We discarded results that were not in English. We included all study types in the review, including case-report, case-series, case-control, cohort, pre-post intervention, time-series analysis, qualitative analysis, randomized and non-randomized studies. We also examined clinical observations, scientific meeting abstracts, conference abstracts, papers and proceedings, fact sheets, dissertations, letters and commentaries, product patents, and policy documents identified through our searches. We defined records that were not studies and were searchable only through Google Scholar as gray literature, and removed them from our analysis.

Further clarity is required regarding the nomenclature of different types of syringes. Immunization syringes with a reuse prevention feature are often called auto-disable (AD) syringes, while therapeutic syringes with a reuse prevention feature are referred to as reuse prevention (RUP) syringes. A syringe with a sharp injury protection feature is called a sharp injury protection (SIP) syringe. However, many users, procurers, and even subject specialists mix these terms, and “AD syringe” remains a popular umbrella term for all syringes with a reuse prevention feature. These terms have been used in the WHO 2015 injection safety guidelines page #6 under the abbreviation and acronyms section.¹⁹

Each record that remained after the titles and abstract had been screened independently by two researchers (Fatima Miraj (FM) and Mehr Munir (MM)) was evaluated further by performing a word search and examining the context in which keywords had been used to establish relevance. Bibliographies of all papers that fit our research criteria were examined to ensure no papers were missed. All studies that were retained and deemed necessary for full-text review by either one or both independent researchers by this point were reviewed in full by a third independent researcher (Anokhi Ali Khan (AAK)). Studies that met our inclusion criteria were summarized (Supplementary Table 1) and then graded using an adapted criterion from Atkin et al.²⁰ (Supplementary Table 2), which takes into account methodology variation between and within studies. Our scoring system allowed us to evaluate the quality of each included study according to the following components: (1) research rigor, demonstrated by a clearly defined research question, description of study design, sampling strategy, and method of data collection; (2) description of study context and assessment of generalizability of results; (3) clear description of analysis methods; (4) credibility of results in light of the evidence generated; (5) depth and richness of findings demonstrated by a sustained reflection on the different perspectives, an examination of underlying factors, and discussion of conceptual linkages; and (6) relevance in terms of a discussion on AD syringes. In addition, we included criterion of study type in the scoring, with a double blinded clinical trial scoring the highest and commentary the lowest. Robustness and validity of statistical methods were also evaluated based on whether confounders were taken into account and if study power was calculated. The maximum possible score for a single study was 19. The scoring criteria were used to distinguish between records in terms of rigor, relevance, and credibility of results and allowed us to compare results and conclusions objectively.

This study was registered with PROSPERO, CRD42020165528.

Results

We identified 6,063 articles, and following de-duplication, 2,018 articles were reviewed (Figure 1). We excluded 1,758 records based on title or abstract screening. Of the 260 articles on the list, 196 were removed following the third reviewer’s full-text review as they did not meet our inclusion criteria. The final review included 64 records, of which 55 were original research articles, and nine were commentaries,^21,22 editorials,²³ news reports^24,25 or bulletins,^26,27 essays,²⁸ or WHO guidelines.¹⁹

Figure 1. Method of reviewing and selecting articles based on our inclusion criteria* using PRISMA

A list of all included records is provided in Table 1, along with their associated region and year of data collection. Study characteristics are summarized in Supplementary Table 1 (Appendix). The score range of included records is 0–15, with individual scores provided in Supplementary Table 2 (Appendix). Included studies’ year of completion ranged from 1991 to 2019, with 18 of the 55 research studies having been performed before the GAVI Alliance’s safety support program was initiated in 2002 (to introduce/increase the use of AD syringes in national immunization programs).²⁹ Of the included research studies, 28 studies were prospective, while 27 were retrospective. Furthermore, 27 studies incorporated a substantial qualitative component,^30–56 encompassing structured observations of healthcare facility practices and vaccine administration, and/or interviews with health-care workers (HCWs). Research sites of included studies were spread across eighteen countries, including China,^42,52,57 Swaziland,³⁶ Egypt,^38,51,58 Pakistan,^{21,40,43,48,53,54,59–63} Cameroon,⁴⁵ Burkina Faso,⁶⁴ India,^{37,46,49,50,65–71} Mongolia,⁴¹ Nepal,^31,39 Ethiopia,^32,47 Ghana,⁵⁵ Moldova,⁷² Korea,^73,74 Yemen,⁷⁵ Cambodia,⁷⁶ Nigeria,^30,56 Bangladesh,³⁵ and Kenya.^33,34,44 Additionally, a multi-country evaluation of injection practices was included in our review.^2,5,77–79 The total number of injections observed by the combined studies was an estimated 38,000, and the total HCWs interviewed were more than 5,000. The range of prevalence rates of syringe reuse, AEFIs, and syringe-associated BBVs is provided in Table 2.

Table 1. Overview of included records by region, timeline and key topics covered

Region/Country	First author (Reference)	Year of publication	Year of reporting/data collection	Topic(s) discussed
African Region (AFRO)
Burkina Faso	Fitzner^Citation1	2004	2000	Reuse of disposable equipment
Burkina Faso, Cameroon, Chad, Cote d’Ivoire, Ethiopia, Guinea–Bissau, Kenya, Rwanda, Senegal, Swaziland, Uganda, United Republic of Tanzania, and Zambia	Dicko^Citation2	2000	1995–1998	Reuse of disposable syringe and injection related abscesses
Cameroon	Okwen^Citation3	2011	2009	Reuse of disposable syringe
Ethiopia	Priddy^Citation4	2004	2002	Reuse of disposable syringe and needle
	Birhanu^Citation5	2018	2018	Reuse of disposable syringe
Ghana	Cronin^Citation6	1993	1991	Reuse of disposable syringe and needle
Kenya	Chemoiwa^Citation7	2014	N/A	Reuse of disposable syringe
	Mweu^Citation8	2015	2011-2012	Reuse of disposable syringe
	Chemoiwa^Citation9	2018	2011	Reuse of disposable syringe and needle
Nigeria	Musa^Citation10	2006	N/A	Reuse of disposable syringe
	Abubakr^Citation11	2019	N/A	Reuse of disposable syringe
Swaziland	Daly^Citation12	2004	1996	Reuse of disposable syringe and needle
South-East Asia Region (SEARO)
Bangladesh	Chowdhury^Citation13	2011	2008–2009	Reuse of disposable syringe and needle
India	Singh^Citation14	2000	1995–1998	Blood borne viruses associated with reuse of disposable syringe/needle
	Lakshman^Citation15	2000	N/A	Reuse of disposable syringe and needle
	Rajasekaran^Citation16	2003	2001	Transmission of blood borne diseases through reuse of disposable syringes
	Atul^Citation17	2004	2003	Reuse of disposable syringe and risk of infection due to unsafe injection practices
	Sharma^Citation18	2004	N/A	Reuse of plastic syringes
	Kermode^Citation19	2005	2002	Reuse of disposable syringe and needle
	Correa^Citation20	2006	2005	Reuse of disposable syringe and needle
	Pandit^Citation21	2008	2004	Reuse of disposable syringe and adverse events
	Arora^Citation22	2012	2003–2004	Unsafe injection practice and potential of transmitting blood borne diseases
	Gupta^Citation23	2013	2009	Reuse of disposable syringe
	Garapati^Citation24	2014	2010–2011	Reuse of disposable syringe
	Shah^Citation25	2014	2012–2013	Reuse of disposable syringe
Korea	Chung^Citation26	2018	2008-2015	Reuse of syringe and multi–dose vial
	Lee^Citation27	2019	2016	Misconceptions that reuse is safe
Nepal	Bhattarai^Citation28	2000	2000	Reuse of disposable syringe and serious adverse events
	Kaphle^Citation29	2014	2013-2014	Reuse of disposable syringe and needle
European Region (EURO)
Moldova	Hutin^Citation30	1999	1994–1995	Reuse of disposable syringe and needle observed
Eastern Mediterranean Region (EMRO)
Egypt	Talaat^Citation31	2003	2001	Reuse of disposable syringe and adverse events
	Ismail^Citation32	2007	2003–2004	Reuse of disposable syringe
	Kandeel^Citation33	2012	2007–2008	Reuse of syringe and association with transmission of nfections
Pakistan	Steinglass^Citation34	1995	N/A	Potential for reuse of a type of AD syringe (SoloShot) due to design failure
	Khan^Citation35	2000	1995	Reuse of disposable syringe and needle observed
	Raglow^Citation36	2001	1995	Reuse of disposable syringe and needle which increases the risk of blood borne diseases
	Atlaf^Citation37	2004	2001	Reuse of disposable syringe
	Ahmad^Citation38	2006	N/A	Reuse of syringes
	Janjua^Citation39	2006	N/A	Reuse of disposable syringe
	Aziz^Citation40	2010	2007-2008	Link between transmission of Hepatitis B and C with unsafe injections
	Qureshi^Citation41	2010	2007–2008	Association of reused syringe with hepatitis B and C
	Mustufa^Citation42	2010	2008	Reuse of disposable syringe
	Hoeve^Citation43	2012	2011–2012	Reuse of disposable syringe and needles, and transmission of infections
	Yousafzai^Citation44	2013	2005	Reuse of disposable syringe
	Ahmed^Citation45	2013	2007–2008	Reuse of disposable syringe
	Zakar^Citation46	2013	NA	Reuse of disposable syringe
	Altaf^Citation47	2013	N/A	Potential for reuse of AD syringe
	Janjua^Citation48	2014	2006–2007	Reuse of disposable syringe
	Khan^Citation49	2019	2009	Reuse of disposable syringe
	Dyer^Citation50	2019	N/A	Reuse of syringes
Yemen	Abdo Abdo Abkar^Citation51	2013	2006	Reuse of disposable syringe
Western Pacific Region (WPRO)
Cambodia	Vun^Citation52	2016	2014-2015	Development of blood borne diseases due to injections
China	Murakami^Citation53	2003	2000	Possible reuse of AD syringe
	Yan^Citation54	2006	2004	Transmission of HIV,HCV & HBV through contaminated syringe and needle
	Wu^Citation55	2013	2010	Reuse of disposable syringe
Mongolia	Logez^Citation56	2001	2001	Reuse of single use syringes reported
Multi-region or region not applicable
Developing and transitional economies	Pepin^Citation57	2013	2000–2010	Unsafe injection practices common
DHS data available countries	Hayashi^Citation58	2019	2011-2015	Reuse of injection equipment
Low and lower middle-income countries, Sub–Saharan African countries	Deuchert^Citation59	2007	2003–2004	Nonuse of AD syringe is linked to higher prevalence of HIV
LMICs in DHS	Adewuyi^Citation60	2019	2010-2017	Unsafe injection practices
No country specified/not applicable	Miller^Citation61	1999	N/A	Unsafe injections are associated with BBVs like hepatitis B and C
	Bandyopadhyay^Citation62	2005	N/A	Possibility of reuse of AD syringe
	Gisselquist^Citation63	2013	N/A	Risks associated with reuse of injection equipment
	WHO^Citation64	2015	N/A	Possibility of reuse of AD syringe

Table 2. Range of prevalence rates of syringe reuse, AEFIs, and syringe–associated BBVs reported by included records

	In 2002* or earlier	In 2003 or later
Method of determining prevalence
	Reuse of disposable syringe/needle (%)
Observation
Injections	12-94.4^Citation4,Citation35,Citation56,	0.1 – 44.8^Citation8,Citation9,Citation13,Citation24,Citation25,Citation28,Citation51,Citation54,
Healthcare workers	0.4^Citation34	0.0 – 14.3^Citation7,Citation24,Citation29,Citation55
Healthcare facility	8 – 35^Citation12	0.42 – 80^Citation10,Citation55
Patients/Public	-	14^Citation33
Interview & Questionnaires
Injections	8.4^Citation31	-
Healthcare workers	0.6 – 31.5^Citation53,Citation56	0.02 – 74.8^Citation3,Citation5,Citation10,Citation11,Citation29,Citation44
Healthcare facility	15 – 39^Citation2	1.7 – 4.4^Citation32,Citation51
Patient/Public	-	8.3 – 6.8^Citation41,Citation42
Focus Group discussions
Injections	-	4^Citation48
Healthcare workers	40^Citation53	-
	Adverse events following immunization (%)
Observation
Healthcare facility	40^Citation2	-
Interview & Questionnaires
Healthcare workers	25^Citation12	30.7 – 74.8^Citation10,Citation44
Patients/Public	1.6^Citation31	3 – 26^Citation21
	Disposable syringe reuse associated blood borne virus (BBV) transmission (%)
Observation
Injections	-	2.3 – 89.9^Citation40
Patients/Public	–	44^Citation22,Citation23
Interview & Questionnaires
Healthcare workers	56-86^Citation19,Citation53	-
Focus Group discussions
Patients/Public	–	3-6.8^Citation41
Healthcare workers	84.6^Citation53	-

*In 2002, the Gavi Alliance initiative safety support programme was initiated with the purpose to introduce/increase the use of AD syringes in national immunization programmes.

Unsafe practices associated with AD syringe or AD syringe activation point, including reuse, AEFI, and BBV transmission

Of the 55 studies accepted in our review, none reported successful or attempted reuse of AD or RUP syringes in the field, or any correlation between AD/RUP syringes and AEFI and BBV transmission. One study (grade = 12) conducted in Karachi, Pakistan, mentioned AD syringe reuse in experimental settings, reporting that when vaccinators were specifically challenged to defeat the disabling mechanism of an AD syringe called SoloShot, a few were successful in doing so by removing the locking clip.⁵⁹ A quality control issue regarding SoloShot was also noted, as 0.4% of 2,400 AD syringes were missing the locking clip, rendering them potentially reusable. The study was conducted prior to the ISO, in 1995, and stated that modifications in design have since been made to eliminate AD syringe tampering possibilities. The authors concluded AD syringes are safe and effective regardless of the vaccinator’s experience or training. The study did not comment on the syringe’s activation point. Bandyopadhyay et al. (grade = 3) reviewed two different designs of AD syringes in 2005 and reported a possibility of reuse by not activating or disabling the locking device in the two designs of AD syringes. However, this was a low-scoring article, where the author only discussed hypothetical ways to defeat the locking mechanism of different designs, instead of citing any evidence. Additionally, the article was published prior to the introduction of WHO ISO standards in 2005.²⁶

In an opinion piece from 2013, Altaf (grade = 1) expressed concerns that someone may intentionally avoid fully pulling the plunger of an AD syringe, thus preventing the locking mechanism from being triggered.²² However, this record scored low on our grading criteria, and the activation point of AD syringes was also not discussed. Murakami et al. (grade = 14) similarly speculated that if AD syringes of all sizes become commercially available, vaccinators could intentionally obtain larger-than–required syringes and potentially reuse them between clients.⁴² Even though this study was evaluated as a higher quality study according to our grading criteria, the author did not study reuse or find any evidence associated with it, but only hypothesized that the potential for reuse might exist in reference to different sized AD syringes.

In contrast, authors of three studies confirmed the effectiveness of AD syringes in limiting reuse and reducing BBV transmission through directly examining AD syringes’ impact on disease trends and injection practices.^2,52,57 They were relatively high-quality studies that scored the grades of 14 and 15 according to our criteria. Authors of 10 additional studies called for the expansion of AD syringe use based on their findings regarding syringe reuse and BBV disease prevalence, but did not themselves investigate or quantify AD syringes’ impact on injection safety.^{21,33,36,50,52,54,62,64,79,80}

Furthermore, among the editorials, commentaries, news reports and bulletins included in our review, five supported the adoption of AD syringes as an effective strategy for combatting unsafe injections.^{23,24,27,28,81}

Unsafe practices associated with disposable syringes including reuse, AEFI, and BBV transmission

The reuse rates for standard disposable syringes reported by the included studies ranged from 0.1% to 94.4% (Table 2). The highest reported reuse (94.4%) was from a study conducted across 18 health facilities in Karachi, Pakistan, in 1995 (grade = 14).⁴⁰ The figure was derived from data obtained through questionnaires and observations conducted at 18 health facilities with 135 patients. An additional ten studies from Pakistan, conducted between 1995 and 2013^{43,48,53,54,60–62,80,82,83} reported high rates of disposable syringe reuse, and drew attention to the persistence of unsafe injection practices in the country. The most recent study was by Yousafzai et al. in 2013 (grade = 12),⁵³ which reported a syringe reuse rate of 74.8%, based on interviews of 317 practitioners in Karachi, Pakistan. In addition to syringe reuse, unsafe injection practices found by authors of two additional studies (grades 12 and 13) included attempts at sterilizing disposable syringes with water, alcohol swabs, or disinfectant.^48,82

Studies examining injection practices in India, conducted between 1995 and 2013,^{37,46,49,50,65–70} also reported high rates of reuse. Prevalence of unsafe injection practices, including disposable syringe reuse, reported by Pandit et al. (grade = 10), was 77.0%. The study was performed in Gujarat State in 2004, and data was collected through questionnaires circulated amongst 510 families and it was found that unsafe injection practices were more common in government facilities (84.0%), as compared to private (71.0%) setups.⁴⁶ In another study from 2004, Arora et al. (grade = 14) estimated that of the 3 billion injections given in India annually, 1.89 billion were unsafe.⁶⁵ The majority of unsafe practices were occurring in immunization clinics, where 74.0% of the injections either carried a potential risk of BBV transmission or were administered with a faulty technique.⁶⁵ The most recent study from India was conducted in Gujarat in 2013 by Shah et al. (grade = 15), in which 6.8% of health-care workers mentioned having used an open or already used syringe or needle. The authors noted that during the study, 96.8% of the 251 participating HCWs had access to AD syringes.⁵⁰

In the earliest of the three studies from China,^42,52,57 Murakami et al. reviewed the prevalence of unsafe injection practices and contributing factors among vaccinators in North–Western China in 2000. The authors reported an estimated rate of 7.2–55.0% of syringe/needle reuse without sterilization, and an 8.9-23.3% rate of inappropriate use of disposable syringes/needles. The annual number of HBV infections in children due to unsafe immunization injections was estimated at 135– 3,120 per 100,000 fully immunized children.⁴² In a study conducted ten years later, in 2010, Wu et al. (grade = 15) reported significant progress had been achieved in immunization safety as a result of a five-year financial support plan by GAVI, which helped to accelerate the introduction and uptake of AD syringes in the country. Over 70.0% of facilities in Western and Central China, and 25.0% in Eastern China, were using AD syringes. Of the 251 health-care providers included in the study, less than 0.5% attempted to re-sterilize disposable syringes. This was a higher graded study where reuse or attempted re-sterilization of AD syringes was not reported.⁵⁷

The reuse of disposable syringes on the same patient was reported in three studies. Of these, one was conducted in Mongolia in 2001 (grade = 13),⁴¹ the second in Yemen in 2006 (grade = 13),⁷⁵ and the third in Nepal in 2014 (grade = 14).³⁹ These studies scored relatively higher on our grading criteria and attributed reuse to health-care workers’ lack of knowledge regarding reuse and blood borne infection. Abkar et al. from Yemen (grade = 13), despite recording one of the lowest rates of reuse (0.1% of 919 injections observed in health centers, and 1.2% of 827 injections observed in hospitals), 4.4% of injection providers stated they reused the syringe when providing multiple injections to the same patient.⁷⁵ Workers from Nepal also mentioned the sale of used syringes in the market.³⁹ A study showing needle reuse on three consecutive patients, especially among poorer patients in Bangladesh (grade = 15), reported that the lower–income groups were at a higher risk of BBV due to needle reuse.³⁵

Of the 11 studies from Africa, conducted between 1991 and 2019^{30,32,33,36,44,45,47,55,56,64,77} reported rate of reuse of disposable syringes ranged from 2.0-60.0%. One study by Dicko et al. (grade = 9) compared survey results of the AFRO Logistics Project across 13 African countries, including Burkina Faso, Cameroon, Chad, Cote d’Ivoire, Ethiopia, Guinea-Bissau, Kenya, Rwanda, Senegal, Swaziland, Uganda, United Republic of Tanzania, and Zambia.⁷⁷ The importance of injection safety policy was highlighted, as disposable syringe reuse was reported to be more than double in Swaziland (39.0%), which had no injection safety policy, compared to Cote d’Ivoire (15.0%) where a policy was in place; with both countries reporting no shortage of equipment. Injection-related abscess was also reported in Cote d’Ivoire. In the remaining countries, the use of both disposable/sterilizable equipment was reported, with Chad being the poorest performer, at 60.0% reuse without sterilization or inappropriate sterilization of disposable injection equipment.⁷⁷ This was a relatively lower quality study, with no mention of the reuse of AD syringes.

Across the region, in Ethiopia,^32,47 a 10.0% drop in reported disposable syringe reuse (from 12.0% to 2.0%) was noted between 2002 and 2018. The studies were given scores of nine and twelve, respectively. Studies from Kenya, in contrast, indicated an increase of syringe reuse being reported.^33,44 These studies were also evaluated to be of higher quality than those conducted in Ethiopia, according to our grading criteria. In 2011, Chemoiwa et al. (grade = 15) reported that among 355 injections observed, 5.1% were with reused disposable syringes and new needles, and 2.8% were with reuse of both needle and syringe.³³ In a later study, conducted by Mweu et al. (grade = 12) in 2012, a higher reuse rate of 11.1% was reported, also based on direct observations.⁴⁴ In a 2006 study, performed by Musa et al. (grade = 12) in Nigeria, reuse was observed at nine of the thirteen immunization centers in the study, and the authors emphasized the importance of health education of workers.⁵⁶ In another study from Nigeria, published in 2019, Abubakar et al. (grade = 15) echoed the need for adequate training on injection practices, and reported that of 80 health workers, 37.5% did not always use a new syringe and needle.³⁰

In a study conducted in Egypt by Ismail et al. in 2003 (grade = 13), 13.2% of the 11,000 HCWs interviewed reported reusing syringe or needle, even though 95.7% of the injections observed by study investigators were with new disposable syringes. In addition, most providers did not adhere to other safe injection practices, as open containers and overflowing bins were seen in the preparation areas.⁵⁸ Among the studies reporting low reuse rates,^74,75 one was conducted in Korea by Lee et al. (grade = 15), showing a 1.3% reuse rate of injections while replacing needles,⁷⁴ and the other one was by Abkar et al. in Yemen, who observed a 0.1% reuse rate in health centers, and a 1.2% reuse rate in hospitals.⁷⁵

Six studies,^{54,61,72,73,76,80} of which three were from Pakistan, examined the association between syringe reuse and risk of blood borne infection (BBI). In one of the studies from Pakistan, Ahmed et al. (grade = 14) reported a 4.5 times higher risk of BBI in patients having received >10 therapeutic injections over the past 10 years.⁸⁰ The case-control study by Hutin et al. (grade = 12), conducted in Moldova in 1995, reported that children who were HBsAg positive were more likely to have received injections from a hospital in the six months before illness compared to controls (stratified Odds ratio 5.2).⁷² One study from Korea in 2015 (grade = 11),⁷³ and one from Cambodia in 2016 (grade = 7),⁷⁶ linked HCV and HIV outbreaks to possible syringe reuse. When studying patients with HIV in India (2005), Correa et al. reported 80% of the HIV positive patients had received up to 300 injections in the previous five years before testing positive, with one patient noting that a nurse retained the disposable syringe for reuse.⁶⁶ The study scored 14 according to our grading criteria and was considered to be of higher quality.

Three studies^5,78,79 constituted a review and analysis of District Health Surveys (DHS) from lower middle-income countries (LMICs). Though a drop of 34.3% in syringe reuse had been recorded between 2000-2010,⁵ in 2017, one in every 29 injections given in LMICs was considered unsafe. The Eastern Mediterranean Region had the highest unsafe injections per person per year, and Pakistan and Afghanistan had the least reliable access to new syringes.^78,79 These studies were regarded as moderate to high quality based on their scores ranging from 11 to 14.

Additionally, a recent news article from British Medical Journal (BMJ) reported an HIV outbreak in Pakistan in 2019, which was linked to syringe and IV reuse, and affected >900 children.²⁵ However, as a news article, this record scored the lowest (zero) on our grading criteria.

Discussion

In this systematic review, we found no empirical or anecdotal evidence of an association between AD syringes of any design, and risk of syringe reuse, AEFI, or BBV transmission. Despite some speculation about the possibility of AD syringe reuse, actual reuse of an AD syringe of any design has never been reported, even after billions of AD syringe-administered injections over two decades globally. A specific discussion regarding AD syringes’ activation point does not appear at all in the literature, and of authors who recommend increased use of AD syringes, none mention any preference with regard to syringe design, including in terms of the activation point. Our review confirms that AD syringes are reliable and effective, and concerns regarding the safety of specific designs, including those related to the activation point, are not backed by the evidence. Regarding standard disposable syringes, however, our review demonstrates unsafe injection practices abound in LMICs, and risk of BBV transmission remains high. Millions of new BBV cases are attributed to unsafe injections each year, with over 1.6 million cases of hepatitis B virus alone.^1,5,84

There is sufficient evidence in the literature, based on higher quality studies from our review (grades 14 and 15), that highlight the importance of AD syringe in preventing/eliminating reuse.^{33,50,52,54,64,80} However, some authors have nevertheless speculated that the reuse of AD syringes by vaccinators and other health personnel could occur.^22,26,42 In the discussion section of their paper, Murakami et al. briefly discuss the possibility of AD syringe reuse, expressing the concern that if AD syringes are made commercially available, vaccinators may deliberately use larger volume RUP therapeutic syringes, and reuse the syringe between infants without activating the locking mechanism.⁴² There is, however, no empirical evidence that leads the authors to consider this possibility, and therefore remains a conjecture. In a commentary on unsafe injections in Pakistan (grade = 1), Altaf et al. raise a similar concern, stating that someone who wishes to reuse an AD syringe may intentionally pull the plunger only partially during the first injection, and then reuse the syringe.²² However, the authors’ concerns are centered on quality deficiencies and lack of manufacturer compliance with ISO standards rather than the activation point. The article by Bandyopadhyay et al. (grade = 3) critiques two AD syringes of different designs, one of which seems to have a late activation point, though the term ‘activation point’ is not used.²⁶ The authors contend that the plunger may be pulled back up for one of the two designs if the health worker deliberately does not deliver a full dose when administering the first dose. And for the other design, it may be possible to defeat the locking mechanism by applying pressure to the syringe at a particular angle. However, the article does not cite any actual instance of reuse of AD syringes of any design and precedes the introduction of the ISO standards. Additionally, the authors do not suggest changing the syringe’s activation point, recommending instead that inability to pull the plunger back up should be ensured for one of the designs, and a different plastic material should be considered for the other design.

Another study that briefly discusses AD syringe safety in terms of reuse probability is an early trial conducted by Steinglass et al. in Karachi in 1995.⁵⁹ In the trial, the authors investigated the safety, effectiveness, and ease of use of a RUP called SoloShot. According to the study, although reuse was not observed during any actual injection, vaccinators were able to remove the syringe’s safety clip when specifically challenged to do so. However, Steinglass et al. concluded that AD syringes should replace disposable injection devices in immunization programs, noting that the design had been modified to prevent reuse. Furthermore, another trial that tested the SoloShot in the context of an immunization campaign in Indonesia evaluated the device highly positively, noting its contribution to injection safety as well as vaccine savings.⁸⁵ In total, only four (two of which were low-scoring) of the 64 records made any reference to AD syringe reuse;^22,26,42,59 two discussed the potential of design flaws conducive to reuse practices, but they were prior to the introduction of ISO standards,^42,59 and one of the two studies specifically noted that the syringe’s design has since been rectified.

In view of the literature reviewed for this study and cited above, it is pertinent to mention that specific user-intent to misuse an AD syringe can render it re-usable, therefore effectively meaning that these devices’ AD mechanism can be intentionally defeated.^26,59 The trial by Steinglass et al.⁵⁹ in Karachi demonstrated how vaccinators could be challenged to intentionally defeat the AD locking mechanism. An additional instance of intentional misuse can occur if the user administers a first large dose less than the maximum dose, creating an opportunity for potential reuse of the syringe before the locking mechanism is activated.⁵⁹ Intentional misuse can therefore render the AD syringe inoperable; however, in the absence of such malpractice, on the whole, AD syringes can reliably prevent reuse, with odds of reuse of AD syringes being much lower than standard disposable syringes. Taken in its entirety, therefore, the review on AD syringes suggests that the activation point is not a matter of concern, and the focus should lie on ensuring compliance with the ISO standard rather than modifying it. Unless there is a quality control failure, ISO-compliant AD syringes significantly improve the chances of safe injection practices, meeting the WHO criterion of causing no harm to recipient or provider. Concerns that linger after AD syringe introduction are about waste disposal, unregulated markets, financial constraints, irrational injections, and lack of monitoring rather than activation point.^6,27,86–91 Injection safety experts have therefore called for global and national programs to address these issues, through better policies, and implementing strategies such as bundling (AD syringes, vaccines, and safety boxes supplied as a bundle), behavior change interventions, and enforcement of safe waste management protocols.^{6,27,86–88,92}

Despite the near-universal endorsement of AD syringes, a risk assessment study has been proposed to investigate whether the timing of the activation point is associated with the risk of reuse.¹³ Risk of reuse will be determined by asking participating health workers which of the three different designs of syringes being tested (with disabling mechanism activation points at the beginning, middle, and end of injection) can be reused, demonstrating how each syringe can be reused, and then asking the participants to attempt reuse. However, in addition to lacking a rationale and relying on a methodology that assumes all designs of AD syringes are potentially reusable, such a study would run counter to the principles of risk assessment and WHO’s infection control policy, which recommends beginning with an initial assessment such as this review.⁸⁸

Given the research findings on AD syringes and the prevalence of standard disposable syringe reuse with widespread breaches of WHO guidelines regarding safe injection practices,⁹³ clear priorities emerge for a holistic injection safety strategy. Firstly, quality control mechanisms and provider monitoring tools need to be established, which include market regulation. Every injection device that is available in the market must be registered and adhere to stringent quality control standards to ensure ISO standard compliance. Policies and regulations must also consider informal providers, including traditional healers and birth attendants.⁸⁹ Secondly, waste disposal methods must be standardized and enforced. The problem of unsafe disposal could escalate when AD syringes become more prevalent, putting the community at increased risk.^30,36,90 Additionally, donors and international agencies need to facilitate the use and safe disposal of AD syringes in LMICs, through mitigating cost concerns, enabling the transfer of production technology, and adopting the ‘bundling’ policy. Finally, educational and community-level approaches are required to curb irrational use of injections, counter unawareness of both patients and providers, and change the norms which cause syringe reuse to persist.

The present review is a comprehensive study designed to systematically examine whether unsafe injection practices or AEFIs have any association with AD syringes’ activation point. However, it does have some limitations. Firstly, we were unable to obtain English-language translations of 48 records found through our literature search. However, the non-English papers that could not be reviewed constitute less than 1% of total records found. Furthermore, papers included in our review cover LMICs from all regions; therefore, it is unlikely that we missed evidence from a particular region or country due to the language barrier. In addition to the language limitation, differences in study design, methods, and populations made inference of change in reuse behavior over time in the same region difficult.

Conclusion

Our comprehensive systematic review confirms AD syringes are safe and effective irrespective of design, including activation point. No empirical or anecdotal evidence exists of the reuse of AD syringes of any design by any injection provider. However, the risk for reuse of standard disposable syringes in LMICs remains considerably high. We recommend that the global health community should stay focused on achieving universal and exclusive use of AD syringes in both immunization and therapeutic contexts, without prioritizing any AD syringe design based on its activation point. Additionally, safe waste disposal mechanisms, strict market checks, and strategies for rationale injection use should be adopted.

Disclosure of potential conflicts of interest

All authors report no conflict of interest. The funder of this study had no role in study design, analysis, interpretations, or writing of the manuscript.

Author contributions

SC conceptualized and designed the study. AAK developed the methodology for data extraction. FM and MM undertook the literature review and shortlisted records for full-text review; SI assisted with the literature search. AAK, MM, and FM assessed the eligibility of shortlisted records, and AAK made the final decision regarding inclusion in this study. FM extracted relevant data from all included records graded by AAK, MM, and FM. AAK, MM, and FM wrote the first draft of the manuscript, with input from SC and DAS. SC, AAK, MM, and DAS finalized the manuscript with input from all authors.

Acronyms

Table

AD	Auto-disable
AEFIs	Adverse events following immunization
BBV	Blood borne virus
HBV	Hepatitis B virus
HCV	Hepatitis C virus
HIV	Human immunodeficiency virus
WHO	World Health Organization
UNICEF	United Nations International Children’s Emergency Fund
UNFPA	United Nations Population Fund
IFRC	International Federation of Red Cross and Red Crescent Societies
RUP	Reuse prevention
VRL	Vaccine resource library
SIP	Sharp injury protection
HCWs	Healthcare workers
DHS	District health survey
LMICs	Lower middle income countries

Additional information

Funding

This study was supported by World Health Organization [WHO PO 202445113].