Post-transfusion Hepatitis C Virus Infection and the Hidden Burden of Warm Blood Transfusion in a Resource-Limited Setting: An Analytical Cross-Sectional Study from Mbujimayi, Democratic Republic of Congo

Introduction

Blood transfusion is an essential therapeutic procedure that prolongs survival and improves the quality of life of patients managed for hematological, surgical and obstetric conditions. Despite these clinical benefits, transfusion remains associated with the transmission of major bloodborne infections, particularly the human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and therefore represents a persistent public health challenge in many regions of the world.¹ Within national health systems, blood transfusion services are expected to ensure the safety, adequacy, accessibility and effectiveness of the blood supply at every level of care.²

Each year, transfusion saves millions of lives, and blood remains one of the most vital components of medical and surgical care because no artificial substitute is available.³ Nevertheless, the procedure carries inherent risks: several infectious agents, including HBV, HCV, HIV, Treponema pallidum and Plasmodium spp., can be transmitted from an infected donor to the recipient, the donor being the primary source of transfusion-transmitted infections (TTIs).^4,5

HCV infection is recognized as a major global public health problem. It is estimated to affect more than 200 million individuals worldwide, corresponding to approximately 3% of the global population, and is responsible for a substantial proportion of chronic liver disease. The virus is mainly transmitted through blood and body fluids. In countries where systematic donor screening is not performed, the risk of HCV acquisition through transfusion ranges between 20% and 40%, depending on the local prevalence of the infection and the cumulative number of transfusions received. Approximately 92 million blood donations are collected annually worldwide,^6,7 of which around 1.6 million are discarded because of the presence of infectious markers.⁸

The risks of transfusion are intrinsically linked to its biological nature. On the one hand, the transfer of a biological fluid from one individual to another is a direct route of transmission for several infectious diseases, a risk that became central to transfusion safety with the emergence of the HIV and HCV epidemics. On the other hand, the crossing of the immunological boundary between donor and recipient exposes patients to alloimmunization and its complications.^2,9–12

Several determinants modulate the infectious risk associated with transfusion: the prevalence of the pathogen among blood donors, the haematogenic dynamics of the agent, regulatory screening requirements, blood-product preparation techniques, the immunological status of the recipient, and post-transfusion surveillance. Acute hepatitis is common in many parts of the world, and chronic morbidity frequently arises after HBV or HCV infection. In Latin America, hepatitis A, B and D have all been documented,^13–17 while hepatitis E has been associated with both endemic and epidemic icteric outbreaks.^2,10,11

In the DRC, the seroprevalence of HCV in rural areas is estimated at 3.5%.¹⁸ Several studies have provided indirect estimates of the transfusion-related risk of acquiring HCV, with marked geographical variability: 1/2,380 in Lubumbashi¹⁹ and 105/5,016 in Bukavu.²⁰ In Mbujimayi, a survey of 522 blood donors reported an HCV seroprevalence of 2.1%.²¹ Nationally, the prevalence among donors is also estimated at approximately 2.1% and tends to be higher among replacement donors.²²

In a context of constrained resources, transfusions are often performed under economic pressure, with limited adherence to standard biosafety procedures. Warm transfusion—defined here as the administration of a blood unit before complete validation of mandatory infectious screening—may therefore favour immuno-allergic reactions and the transmission of severe infections such as HCV, with potentially life-threatening consequences. The DRC is characterized by a low proportion of voluntary blood donors (approximately 17%), and more than 90% of transfusions are performed under warm conditions, that is, in circumstances where the probability of complete and reliable testing of the donated unit is reduced.

Despite these alarming structural features, robust national data quantifying the additional risk of HCV transmission attributable specifically to warm transfusion remain scarce. Generating such evidence is essential to inform transfusion policy, guide donor recruitment strategies and prioritise investments in laboratory infrastructure. Accordingly, the general objective of this study was to estimate the additional risk of HCV transmission associated with warm blood transfusion in Mbujimayi and to identify the sociodemographic and clinical factors independently associated with post-transfusion HCV seropositivity, in order to contribute to the improvement of transfusion safety in resource-limited African settings.

Materials and Methods

Results

Discussion

The present analysis was designed to quantify the additional infectious risk that warm transfusion adds to the routine therapeutic use of blood in a high-burden. Resource-limited African setting. The post-transfusion HCV seroprevalence of 4.9% documented in Mbujimayi must be interpreted as a substantial. Preventable epidemiological signal rather than as a marginal observation. In a cohort whose median age was only 11 years. Almost one in twenty patients had already acquired anti-HCV reactivity after a single therapeutic exposure. Indicating that even a limited number of warm transfusions is sufficient to introduce a clinically meaningful viral burden into a young population.

Two independent determinants of HCV seropositivity emerged from the multivariable model: cumulative exposure to transfusion and absence of a remunerated occupation. These two predictors converge on a single underlying mechanism structural vulnerability. Multi-transfusion mechanically multiplies the probability of encountering an undetected viremic donor. Particularly in a system where rapid tests with limited sensitivity are sometimes the only screening tool available. Unemployment. in turn. Captures a wider socioeconomic reality: unemployed patients are less able to mobilize voluntary donors from their network. Are more frequently exposed to family or paid donors of uncertain serological status. and depend on facilities where pre-tested cold units are less consistently available. Interpreted together. These findings suggest that in our setting. The HCV transmission risk is shaped less by individual biological factors than by the interaction between repeated exposure to inadequately validated blood and socioeconomic precarity.

The strength of the association observed in the exposure-stratified analysis reinforces this interpretation. The ten-fold increase in odds of HCV reactivity among recipients of more than one warm transfusion (aOR = 10.03) is more than twice the magnitude of the association observed in the overall multivariable model (aOR = 5.41). This gradient is biologically plausible: each additional warm transfusion adds an independent probability of receiving a unit released before complete laboratory validation. and these probabilities accumulate multiplicatively across episodes. The clinical implication is that the pre-transfusion decision is not neutral: deciding to transfuse a patient with a unit of unverified serological status is. in this setting. an act that meaningfully contributes to the patient’s lifetime infectious risk.

The loss of statistical significance for jaundice and donor type after adjustment deserves a careful interpretative reading. Although these variables ceased to be statistically significant. The magnitude of their adjusted odds ratios (aOR = 4.59 for jaundice; aOR = 5.78 for non-voluntary donors) remained clinically substantial. With wide confidence intervals reflecting the limited statistical power of a 4.9% prevalence in a sample of 223 participants. Rather than indicating an absence of association. These confidence intervals signal an imprecise estimation of an association that is most likely real. Embedded in the broader pathway connecting repeated exposure. Donor type and viremic risk. The presence of jaundice in 18.2% of seropositive participants. Compared with only 1.4% of seronegative participants. is in itself an important clinical alert: post-transfusion icterus. When observed in this context. Should systematically trigger HCV testing rather than be attributed to the underlying disease.

The fact that 51.1% of donors were voluntary and non-remunerated could. at first sight. Appear reassuring; yet our data show that even within this preferred donor category. Residual transmission cannot be excluded. Since one of the eleven seropositive recipients had received voluntary blood. This nuance is consistent with the residual-risk literature and underscores that voluntary non-remuneration. While necessary is not sufficient on its own. The combination of voluntary donor recruitment. Donor fidelization. Systematic and high-sensitivity TTI screening and the formal prohibition of releasing unvalidated units constitutes the only operational pathway through which the residual risk can be brought towards acceptable levels.

The predominance of malaria (64.1%) and sickle-cell disease (17.5%) as transfusion indications interprets a critical structural reality: in Mbujimayi transfusion is a recurrent therapeutic act for populations who experience repeated transfusion needs across their lifetime. Children with sickle-cell disease in particular. Are structurally exposed to multi-transfusion. and our results indicate that these patients are also those at highest cumulative HCV risk. This converges with the known epidemiology of HCV in chronically transfused populations and reframes haemoglobinopathy programs not only as hematological care pathways but also as priority targets for transfusion-safety interventions. Including HCV monitoring. Vaccination against hepatitis B and access to direct-acting antiviral therapy.

Several elements published in the broader literature provide context for these findings. The 4.9% prevalence we report is markedly higher than the residual-risk estimates documented in better-resourced or better-organized transfusion systems ranging from 0.042% - 3.6%.^{13,18–20,23–31} but lower than the prevalences (7.1–59.3%) reported among multi-transfused thalassemic or chronic-care populations elsewhere.^1,32–37 Our finding therefore positions Mbujimayi in the upper range of post-transfusion HCV risk among populations transfused for acute conditions. a position that is consistent with the structural fragility of warm-transfusion practice. The similarity with prevalences reported in Pakistan^9,15 and in Lubumbashi blood donors³⁸ further supports the interpretation that the burden we observe reflects an entrenched. System-level vulnerability rather than a circumstantial finding.

Taken together the elements above support a single interpretative conclusion: in Mbujimayi. the additional risk imposed by warm transfusion is not theoretical. It translates into a measurable. Dose-dependent increase in HCV seropositivity. Amplified by socioeconomic vulnerability and concentrated in the very populations that depend most on transfusion for survival. Our data therefore make a case for a policy shift that treats access to fully validated cold blood units as a clinical priority equal to the transfusion act itself. Particularly in pediatric and chronic-care settings.

Conclusion

The continuously increasing demand for blood exposes recipients to infectious complications. of which HCV transmission is a major component. Rigorous donor selection combined with systematic. Sensitive and validated TTI screening remains the most effective strategy for preventing post-transfusion infections. Although transfusion saves millions of lives every year. Unvalidated blood continues to represent a tangible threat to recipients in low-resource settings. Access to safe blood should be regarded as a universal right and must be guaranteed by an uninterrupted quality-assured screening continuum.

In Mbujimayi. warm transfusion remains a non-negligible additional route of HCV transmission. Particularly when biosafety standards are not enforced. When voluntary blood donation remains insufficient. When blood-storage capacity is limited and when the supply of pre-tested units is unreliable. Although the post-transfusion HCV seroprevalence of 4.9% observed here is high. The absence of baseline serological data prevents the entire burden from being attributed solely to the transfusion act. Future longitudinal studies. Including baseline and follow-up serology with confirmatory HCV RNA testing. Are required to refine the magnitude of the transfusion-attributable risk and to evaluate the impact of policy interventions targeting voluntary donor recruitment and universal cold-unit release.

Ethical approval and consent to participate

Ethical authorization was granted by the ethics committee of the Official University of Mbujimayi, registered in number 002/2024/CERUOM/NKL. Informed consent to participate was obtained in writing from all participants, in both in both French and Tshiluba (the local national language), ensuring that they were fully aware of the study’s purpose, potential risks, and benefits. For participants under 18 years of age, written informed consent was obtained from a parent and/or legal guardian. The ethical principles outlined in the Declaration of Helsinki were followed throughout the study. The data were stored on a laptop computer with a password-protected and locked cabinet, and only the lead investigator and study supervisor had access to the data.

Consent for publication

Not applicable.