Usability and acceptability of self-testing for hepatitis C virus infection among the general population in the Nile Delta region of Egypt

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. An estimated 71 million individuals are chronically infected with HCV, and there is a disproportionately high burden of this disease in low- and middle-income countries (LMICs) [1]. The global response to HCV has been transformed with the introduction of curative, short-course, pan-genotypic direct-acting antiviral (DAA) therapy. This has led to the adoption of a “treat all” approach for HCV-infected persons, regardless of disease stage, and available at low cost in most LMICs. In 2016, the World Health Organization (WHO) launched the Global Health Sector Strategy on Hepatitis 2016–2021, with the ambitious goal to eliminate HCV as a public health threat by 2030 [2]. There has been considerable scale-up of testing and treatment in several champion countries, in particular Egypt [3]; however, globally, less than 20% of all persons with HCV infection have been tested and less than one-quarter of diagnosed patients have been treated [1]. This gap in diagnosis and treatment is even higher in many LMICs that have a high burden of HCV. This is particularly true in rural or hard to reach settings and among some high-risk groups, such as people who inject drugs (PWID) and men who have sex with men (MSM).

WHO recommends focused screening for HCV infection in the most affected populations in all settings and routine testing of all adults, adolescents and children in settings with ≥2% HCV antibody prevalence in the general population [4, 5]. In addition, WHO recommends a single rapid diagnostic test (RDT) followed by prompt HCV RNA viral load test to confirm viremia and staging of liver disease prior to initiating treatment [4, 5]. Lack of access to HCV testing services and confirmatory viral load testing remain significant barriers to expanding treatment efforts. To expand access to HCV testing and treatment will require greater decentralization of testing and treatment services to primary care and harm reduction sites [6], in addition to the adoption of innovative and convenient testing approaches, including self-testing [7].

Self-testing, where people collect their own specimen, perform a simple rapid test, and interpret the result, has been recommended by WHO since 2016 [8], as an accurate, safe, and acceptable approach to reach people with human immunodeficiency virus (HIV) who may not otherwise access testing, including high-risk populations [9‐12]. Most untrained lay users can perform HIVST as effectively as trained providers, and adverse events are rare [13, 14]. HIV self-testing (HIVST) national policy uptake has grown rapidly - 88 countries had HIVST friendly polices as of July 2020, and 41 of them were routinely implementing HIVST [15]. In 2019, WHO updated its guidance on HIVST, highlighting service delivery models and support tools to assist further implementation and scale-up [16].

Self-testing for HCV antibody (HCVST) may be an additional strategy to support elimination as it could increase the coverage of HCV testing reaching individuals missed by conventional facility or community-based testing modalities. Self-testing offers privacy and convenience. However, HCVST also raises important concerns particularly with challenges in conduct and interpretation of test results due to user errors, and in linking individuals with positive self-test results to further confirmatory testing and care. Current experience with HCVST remains limited to small pilot or research studies. These include a qualitative study of self-sampling among 22 PWID in London [17] and two studies, conducted in the United States and China, on the accuracy of oral fluid-based HCV antibody tests adapted for self-testing [18, 19]. These studies showed high agreement between results obtained by untrained users and healthcare provider-delivered testing [18, 19]. The use of HCVST has not yet been recommended by WHO, and as yet there have been no products approved by a stringent regulatory authority in any country or prequalified by WHO. However, several professional-use HCV RDTs already prequalified by WHO could potentially be adapted by the manufacturers for self-testing use. Further studies on the usability and acceptability of HCVST in different population groups and settings are needed to inform global guidelines and policy development.

FIND (Foundation for Innovative New Diagnostics), in collaboration with WHO, has recently undertaken an initial series of pilot studies to examine the usability and acceptability of HCVST in a range of different settings across five countries – Egypt (general population in a high burden country), China (MSM), Vietnam (PWID and MSM), Georgia (PWID and MSM), and Kenya (PWID). These sites and populations were selected for these small pilot studies (less than 150 individuals) based on existing collaborative partnerships on HCV testing and treatment, and not on the intended prioritisation of these countries for implementation and promotion of HCVST. We report here an assessment of the usability and acceptability of HCVST among the general population in a semi-rural setting in Egypt. Egypt has among the highest prevalence and burden of HCV infection worldwide, with a generalized epidemic, largely as a result of poor injection safety and other unsafe medical practices [20]. In 2015, the estimated national prevalence of chronic viremic HCV infection was 7% in those aged 15 to 59 years [21]. The national government and the Ministry of Health and Population (MOHP) [22] established an early, effective viral hepatitis response, with the goal of eliminating HCV infection from Egypt [23]. In October 2018, the Egypt government initiated mass screening of the population to improve case-finding, under the Presidential Initiative “100 Million Healthy Lives”. As of December 2019, more than 50 million Egyptians had been tested [23], almost two-thirds of the national population, and a total of 3 million people have been treated with DAAs since 2014.

This is one of the first studies globally to report on the usability and acceptability of an oral fluid-based HCV antibody self-test among the general population in an LMIC setting. The 116 study participants were enrolled from attendees at two outpatient clinics in the Nile Delta region of Egypt, a region with a high HCV prevalence but also a high level of awareness of HCV infection. Overall, our study showed high usability and acceptability of HCVST. The majority of participants were able to correctly perform HCVST, following a short one-to-one demonstration on how to use the test. Although most participants (88%) conducted the HCVST process without any mistakes and interpreted the results correctly, more than half (53.4%) were observed to have difficulties with at least one step, and some participants (12%) requested assistance (four required assistance with more than one step in the testing process). The most common errors were incorrect handling of the test device (i.e., a participant touched the flat pad), incorrect timekeeping, and misinterpretation of test results. The most frequently observed difficulties related to removing the cap from the test tube and sliding the tube into the stand.

Our findings are broadly consistent with those from earlier, comparable studies of HIVST [30‐33]. In a 2014 study of the usability of five different HIV self-test devices in unsupervised settings in Kenya, Malawi, and South Africa, 15% of participants made more than one error with an oral fluid self-test [34]. Similar user errors and difficulties have been reported in other HIVST studies [12, 13, 28], especially with early prototype test kits and instructions for use that were not yet optimized for self-testing [30]. The most common errors with oral fluid HIVST kits were incorrect swabbing of the gums and misinterpretation of the results, particularly those with faint positive lines. With blood-based HIVST kits, difficulties in sample collection were documented in 5 to 31% of participants, especially among those from high-risk populations [12, 31]. Generally, fewer user errors were reported when there was in-person observation, video recording of participants, provision of additional training, or direct supervision [12].

In the present study, overall inter-reader agreement was 86%, with a Cohen’s kappa value of 0.6. Three participants yielded invalid self-test results, although they had all collected their sample correctly and read the results after waiting for the appropriate length of time (Additional File 2). Five participants reported positive test results as negative and four reported negative results as positive. More than half of these misinterpretations (5 out of 9) were among participants with low levels of education or literacy (Additional File 2). The two participants who were unable to interpret their test results were both aged more than 60 years and had only received primary school education. The inter-operator concordance (i.e., comparing self-test results with the results of a rapid test performed by a provider) was 92.7%, with a Cohen’s kappa value of 0.75. These values fall within the range of 85.4 to 100% and 0.28 to 0.99, respectively, reported in a previous systematic review of HIVST studies [13]. The pooled kappa value in this systematic review also showed comparable results for directly assisted (0.98, 95% CI 0.96–0.99) and unassisted HIVST (0.97, 0.96–0.98), suggesting that self-testers can perform HIVST as well as trained providers. In an HIVST study with relatively low levels of agreement (kappa value 0.47, − 0.04 to 0.97), conducted in rural Zimbabwe, the study investigators attributed the poor performance to both low levels of literacy in the population tested and suboptimal instructions for use [13]. While in our study the overall concordance rate was high, we found three false-negative and three false-positive results, indicating that additional support for self-testers may be needed in the initial phases of implementation.

There was a high level of pre- and post-test acceptability of HCVST in our study, consistent with reports for HIVST [10, 12]. The majority of study participants rated the HCVST procedure as easy or very easy and stated that they would be willing to use a self-test again and recommend it to their friends and family. The most common reasons expressed for preferring to use a self-test were greater privacy and the possibility to perform a self-test at any time. The majority of participants were also aware of the need to contact health services for confirmatory viral load testing and to determine their eligibility for treatment. Although we used an oral fluid-based test, 24% of participants expressed a preference for blood-based assays. While the reasons for this preference were not sought in our study, extensive research into HIVST has shown that people express no clear preference for blood versus oral fluid HIVST kits. Some people express a preference for oral fluid tests because they are pain-free and easy to perform, while others prefer blood-based tests because of their perceived greater accuracy [12, 35‐37]. Recent WHO guidance on HIVST encourages country programs to offer a choice in the type of self-test kits offered and sample types collected, promote supplier diversity, and address the preferences of different population groups [11]. Further work is ongoing to assess the usability of blood-based self-tests for HCV.

This study has several limitations that must be considered when interpreting the findings. The sample size of 116 participants was small, and the study was based on the use of an oral fluid test only. The findings may therefore not be generalizable to the larger HCV-infected population in the community in Egypt, or to other sample types. About 75% of the participants enrolled in this study had at least completed secondary school, however, education and literacy levels in other rural populations in Egypt may be lower. The rates of errors and difficulties with self-testing procedure could be higher in populations with lower educational levels. The provision of an initial in-person demonstration for all participants in this study, combined with the observation of participants during the HCVST process and availability of assistance, may also have influenced how the HCVST procedure was conducted, resulting in fewer errors and difficulties. Egypt has a well-established, effective, and free national HCV testing, care, and treatment program [3]. High levels of awareness about this disease and ready access to confirmatory testing and treatment in Egypt is likely to have contributed to higher levels of acceptability than in settings and populations without such a program. For example, a recent study among PWID in the UK found a lower acceptability of HCVST; perceived barriers in access to confirmatory testing and treatment, as well as a lack of post-testing counselling and the need to cope with test results in isolation, were among the key concerns expressed [17].

What are the implications of our findings for future HCVST implementation projects in other countries and settings? First, there is a need to minimize errors and difficulties related to self-testing, by simplifying test procedures, improving test devices, optimizing instructions for use, and providing support tools. This may include the use of instructional videos as well as virtual and even in-person assistance for some individuals or populations, for example those with low literacy levels. Additional support tools to accompany further roll-out of HCVST and linkage to care may include telephone hotlines, interactive resources in social media, and mobile apps. Such tools have been developed and successfully implemented during the roll-out of HIVST [8, 11].

Self-testing provides a convenient alternative to provider-delivered testing, however, its higher cost, lack of face-to-face counselling and poor linkage and access to further care may be important barriers to HCVST implementation. Although randomized clinical trials have shown that HIVST can achieve linkage rates comparable with standard testing following a reactive result [11], HCV diagnosis requires a two-step process, with viral load confirmation following positive serology test result, and HCVST will require specific strategies and messaging to promote linkage to care.

In addition to the four other recently completed HCVST studies that used the same protocol as this study, in high-risk populations in Vietnam, China, Georgia, and Kenya, there is a need to evaluate a range of oral fluid- and blood-based HCVST assays in different populations and settings. Additional studies are needed to compare the HCVST approach with other community- and facility-based HCV testing to identify the optimal positioning of self-testing for promoting access to testing and treatment.

Overall, our small pilot study demonstrated the feasibility of assisted self-testing for HCV in a general population sample from a semi-rural setting in the high HCV prevalence Nile Delta region. Importantly, this study does not inform the wider acceptability and applicability of HCVST to the generalised HCV epidemic in Egypt. There has already been a substantial investment in HCV case-finding as part of the national HCV programme in Egypt, with more than 60 million people tested through the recent national campaign, demonstrating the feasibility and success of a comprehensive population-wide screening approach to achieve disease elimination. However, HCVST may still have a potential role to play in promoting access to testing among those not yet reached. This could include young people, college students, and certain marginalized populations, such as MSM and PWID, who may not wish to test through existing testing services, or those with limited geographic access to healthcare facilities.