Disengagement from care and disease severity among people self-testing positive for hepatitis C in Nigeria, Cameroon, and South Africa: a multi-country cohort analysis of implementation studies.

This multi-country cohort analysis in Nigeria, Cameroon, and South Africa demonstrates that while Hepatitis C self-testing effectively identifies infected individuals, including those with severe disease, treatment uptake and retention vary significantly across settings, with South Africa showing notably lower engagement rates driven by HIV status compared to higher success in Cameroon and Nigeria, highlighting the urgent need to strengthen decentralized care pathways to ensure treatment access.

The Gist

Imagine Hepatitis C as a silent, invisible thief that slowly steals the health of your liver. For a long time, finding this thief was like looking for a needle in a haystack because the testing required a trip to a big, intimidating hospital. But recently, scientists introduced a new tool: Hepatitis C Self-Testing. It's like giving people a "detective kit" they can use right in their own living rooms to see if the thief is there.

This paper is a report card on how well this "detective kit" worked in three different African countries: Nigeria, Cameroon, and South Africa. The researchers wanted to know two things:

1. Did finding the thief actually lead to catching and defeating it (getting treatment)?
2. How "sick" was the thief when it was found?

Here is the story of what they discovered, told in simple terms.

1. The Setup: Three Different Neighborhoods

The researchers didn't just test one place; they tested three very different "neighborhoods" (countries) to see how the system worked in different environments.

• Cameroon (The Older Neighborhood): Here, the people testing positive were mostly older adults. The "thief" had been around for a long time, so many people had already developed serious liver damage (scarring).
• Nigeria (The Mixed Neighborhood): This area had a mix of people, including many who also had HIV (another virus). The system here was very organized, with doctors actively chasing down people who tested positive to make sure they got help.
• South Africa (The Young, High-Risk Neighborhood): Here, the people testing positive were mostly young men who used injected drugs. The system was different here: the testing happened in community vans and outreach spots, but the actual medicine to cure the disease was locked away in a central hospital, far away from where the testing happened.

2. The Great Escape: Who Stayed and Who Ran Away?

Once someone found the "thief" (tested positive), they had to go through a series of steps to get cured:

1. Go to a lab to confirm the test.
2. See a doctor.
3. Start taking the cure (pills).
4. Finish the course and get tested again to make sure the thief is gone.

The results were like a game of "Keep Away":

• Nigeria (The Best Catch): This was the most successful neighborhood. Once people found the thief, the system was like a friendly guide holding their hand. 91% of people who needed treatment actually started it. It was like having a dedicated coach who wouldn't let the player quit the game.
• Cameroon (The Steady Climb): This was also quite good. 98% of people started treatment. However, because the system was a bit less active in following up, about half of the people eventually "dropped out" of the care process before finishing.
• South Africa (The Great Escape): This was the saddest part of the story. Even though they found the thief in over 800 people, only 4% of them actually started treatment. It was like finding a fire, but the fire station was locked, the keys were missing, and the fire trucks were parked in a different city. Most people gave up and walked away because the path to the cure was too long and too hard to navigate.

Why did South Africa fail?
The researchers found that in South Africa, the medicine (the cure) wasn't even available in the community clinics until late in the study. People had to travel far to a central hospital to get it. Also, being HIV positive made it even harder for people to stick with the plan. It was a perfect storm of barriers.

3. How Sick Was the Thief?

The researchers also checked how much damage the thief had already done.

• In Cameroon, the thief was old and nasty. Many people had significant liver scarring or even cirrhosis (severe scarring).
• In South Africa, the thief was new and active. Most people had the virus in their blood, but because they were younger, their livers hadn't been destroyed yet.
• In Nigeria, the damage was in the middle, but because so many people also had HIV, the liver damage was progressing faster.

The Big Lesson (The "Aha!" Moment)

The main takeaway from this paper is a simple metaphor: Giving someone a key to a door is useless if the door leads to a locked room.

• Self-testing (The Key): It worked perfectly! It found the people who needed help, including those who were very sick or living in hard-to-reach places.
• The Path to Care (The Door): This is where things broke down.
  • In Nigeria and Cameroon, the "door" was open, and the path was clear, so people got cured.
  • In South Africa, the "door" led to a maze with locked gates and long detours. Even though the medicine exists, if it's not available right where the testing happens, people will give up.

The Bottom Line

The study proves that self-testing is a brilliant idea for finding Hepatitis C. It's like a flashlight in the dark. But a flashlight doesn't fix the problem; it just shows you where the problem is.

To actually cure the disease, we need to build a straight, paved road from the test to the medicine. If we test people in their communities, we must be able to give them the cure in that same community. Otherwise, we are just finding sick people and sending them on a journey they can't finish.

Technical Summary

1. Problem Statement

Despite the availability of highly effective Direct-Acting Antivirals (DAAs) that can cure over 95% of Hepatitis C Virus (HCV) infections, global access to testing and treatment remains critically low, particularly in Africa where an estimated 8 million people live with HCV but only 13% are diagnosed and 3% treated.

• The Gap: Traditional centralized laboratory testing models and overburdened health systems hinder scale-up.
• The Proposed Solution: HCV Self-Testing (HCVST) is a WHO-endorsed strategy to decentralize diagnosis. However, unlike HIV self-testing (which was implemented in established care ecosystems), HCV self-testing is being introduced in contexts with limited existing HCV programming.
• The Research Question: Does HCVST effectively link individuals to confirmatory testing and treatment across diverse African epidemic contexts, and what is the profile of disease severity among those reached?

2. Methodology

Study Design:
A multi-country cohort study nested within HCVST implementation programs in Cameroon, Nigeria, and South Africa (May 2023 – May 2024). The study followed adults (≥18 years) who received a positive HCV self-test result through the care cascade.

Implementation Contexts (Models of Care):
The three countries represented distinct epidemiological and structural contexts:

• Cameroon: Generalized epidemic (1–4%); older adults most affected. Testing occurred in hospitals (OPD/ART) and Community-Based Organizations (CBOs).
• Nigeria: Generalized epidemic (1–2.2%); elevated risk in Key Populations (KPs) and People Living with HIV (PLHIV). Testing in rural/urban sites, including CBOs and HIV clinics.
• South Africa: Concentrated epidemic (<1%); driven by extremely high rates among People Who Inject Drugs (PWID) in urban settings. Testing via a centralized clinic and mobile van targeting PWID.

Data Collection & Outcomes:

• Primary Outcomes:
  1. Cascade Progression: Treatment initiation among those with confirmed viraemia and Sustained Virological Response (SVR) among those with documented outcomes.
  2. Disengagement from Care: Cumulative incidence of dropping out of the care cascade, estimated using Bayesian competing-risks survival models (Weibull regression).
• Secondary Outcome: Disease severity assessed via AST-to-platelet ratio index (APRI) for fibrosis and cirrhosis staging.
• Statistical Analysis: Analyses were conducted in R using brms and cmdstanr. South Africa was analyzed separately due to structural differences; Cameroon and Nigeria were pooled. Site-level random effects were included to account for heterogeneity.

3. Key Contributions

• Comparative Implementation Science: This is one of the first studies to compare HCVST implementation across three distinct African epidemic contexts (generalized vs. concentrated, different risk groups, and varying health system structures).
• Advanced Statistical Modeling: The use of Bayesian competing-risks survival models allows for a nuanced understanding of disengagement over time, accounting for censoring and site-level heterogeneity, rather than simple cross-sectional drop-off rates.
• Disease Severity Profiling: The study characterizes the clinical severity of the population reached by self-testing, revealing that HCVST successfully identifies individuals with advanced liver disease who might otherwise remain undiagnosed.

4. Key Results

Participant Demographics & Virology:

• Total Positive HCVST: 1,341 participants (Cameroon: 117; Nigeria: 226; South Africa: 998).
• Viraemia: High rates of active infection were found (82.2% overall).
  • South Africa: 85.6% viraemic (young, predominantly male PWID).
  • Nigeria: 77.9% viraemic (high HIV co-infection rate of 69%).
  • Cameroon: 61.5% viraemic (older population, 71.8% aged ≥55).

Cascade Progression (Treatment & Cure):

• Cameroon: Highest success. Treatment initiation: 98.6% (71/72); SVR: 96.4% (53/55).
• Nigeria: High success. Treatment initiation: 90.8% (168/185); SVR: 91.8% (56/62).
• South Africa: Critically low success. Treatment initiation: 4.3% (37/854); SVR: 60.6% (3/5).

Disengagement from Care:

• Cumulative Incidence (End of Study):
  • Nigeria: 24.4% (Lowest).
  • Cameroon: 52.4%.
  • South Africa: 77.9% (Highest).
• Predictors of Disengagement:
  • South Africa: HIV positive status was the strongest predictor of disengagement (HR 1.96). Male sex and older age (45–54) also showed trends toward higher disengagement.
  • Cameroon/Nigeria: Individual demographics (age, gender, education) showed minimal association with disengagement. Instead, site-level heterogeneity was the dominant factor.
  • Facility Type: In Cameroon and Nigeria, specialist hospital sites (ART/OPD) had significantly lower disengagement than Community-Based Organizations (CBOs).

Disease Severity:

• Cameroon: Highest burden of advanced disease. Fibrosis: 8.3%; Cirrhosis: 6.9%.
• Nigeria: Moderate burden (Fibrosis: 9.8%; Cirrhosis: 4.9%), though data was heavily missing (54%).
• South Africa: Lowest burden of scarring (Fibrosis: 2.9%; Cirrhosis: 1.6%), consistent with a younger cohort.

5. Significance and Implications

• Context Matters: HCVST is effective at detecting cases across diverse populations (older adults, PLHIV, PWID), but linkage to care is entirely dependent on the implementation model.
• The "Last Mile" Barrier: In South Africa, despite a well-integrated testing strategy within harm reduction services, the centralization of treatment (DAAs only available at one clinic, delayed availability until Dec 2023, and requirement for Directly Observed Therapy) created insurmountable structural barriers, leading to >75% disengagement.
• Community vs. Facility: In Cameroon and Nigeria, community sites (CBOs) showed higher disengagement than hospital-based sites. This suggests that while community testing reaches the "last mile," the care pathways from community testing to treatment initiation are not yet optimized for HCV, unlike the established pathways for HIV.
• Policy Recommendations:
  1. Decentralize Treatment: To realize the benefits of HCVST, confirmatory testing and treatment initiation must be decentralized (e.g., same-day treatment, onsite PCR) rather than relying on central referral.
  2. Integration: HCV services must be integrated into existing high-volume platforms (ART clinics, harm reduction) but with specific "low-threshold" pathways designed for HCV, not just adapted from HIV models.
  3. Sustainability: The study highlights that program performance under donor-funded implementation conditions may not reflect sustainable national scale-up, especially given current funding gaps (PEPFAR/Global Fund).

Conclusion: HCV self-testing successfully identifies individuals with severe disease in diverse African settings, but without optimized, decentralized treatment pathways, the strategy fails to translate diagnosis into cure, particularly in concentrated epidemic settings with structural barriers to care.