Rethinking blood safety: how APAC blood banks can stay ahead of transfusion risks

Contents:

1. Introduction
2. From antibodies to RNA: how blood screening evolved
3. Donor questionnaires: the first line of defence
4. Serological testing: the second screen
5. Nucleic acid testing: the molecular milestone
6. Nucleic acid testing is a game changer in medium to high endemic countries
7. The expanding threat list: why blood screening continues to evolve
8. The next wave of viral infections
9. Parasites: rare but high-stakes
10. Conclusion

Introduction

Every unit of donated blood holds the potential to save a life, but it also carries a risk.

Blood transfusion is one of the most critical and life-saving interventions in medicine. It supports patients during surgery, trauma, cancer treatment, childbirth, and severe anaemia. But because blood is a biological product, it reflects not only the health of the donor but also the epidemiological risks of the region.

While global systems have evolved to make transfusions safer than ever, the risk of transfusion-transmitted infections (TTIs) hasn’t been eliminated – only managed.

Management depends on three key factors: how carefully we select donors, how rigorously we screen blood, and how well-prepared we are for the next infectious threat.

Over the last four decades, the introduction of serological testing for HIV, hepatitis B (HBV), and hepatitis C (HCV) has lowered transmission risks. However, these tests have “window periods”, the time after infection when a donor is infectious but still tests negative [1]. This creates gaps in detection, particularly in regions with a high population disease prevalence or seasonal outbreaks of vector-borne diseases, such as dengue and Zika [2]. Therefore, blood safety will depend not only on what we screen blood for but also on how quickly we respond to emerging threats.

From antibodies to RNA: how blood screening evolved

The blood screening system we rely on today wasn’t built overnight. It was shaped by crisis, corrected by science, and refined through trial. Every new pathogen uncovered a blind spot. Every patient harmed became a case study in what needed to change.

What we have now is a three-layer defence system → Donor selection → Serological screening → Nucleic Acid Testing (NAT).

Donor questionnaires: the first line of defence

The first safeguard in blood safety starts with a conversation. Donor history questionnaires are a powerful frontline tool for assessing risk. They use structured, evidence-based questions to screen for factors such as recent illness, travel footprint in regions with different infection risks, medical history, and high-risk behaviours. This risk-based assessment helps prevent potentially infectious donations from entering the blood supply, often before any testing is done.

When well-designed and rigorously applied, these questionnaires can eliminate a large proportion of high-risk donors. However, they depend entirely on self-reported information, and no system based on disclosure can be completely failproof.

Even donors who meet all eligibility criteria can still carry undetected infections. For example, in rural northern Vietnam, nearly 45% of the population showed evidence of past hepatitis B virus (HBV) exposure, despite most blood donors being asymptomatic [3]. This highlights a key limitation: low-risk does not mean no-risk. While the donor questionnaire remains a critical filter, it must be supported by robust screening protocols that can catch infections missed during donor screening [4].

Serological testing: the second screen

The introduction of serological testing for hepatitis and HIV in the 1980s transformed blood safety. By enabling the detection of antibodies and surface antigens for HIV, hepatitis B (HBV), hepatitis C (HCV), and syphilis, it made every donation safer across the world.

Syphilis screening, in particular, has been part of donor protocols for decades. While often seen as an “old” or legacy test, its relevance has only grown. Global data show a resurgence of syphilis infections, making continued screening essential. In Thailand, for example, syphilis seroprevalence among blood donors remains at 0.42%, with higher rates in first-time and male donors [5,6].

Advances in serological screening have significantly reduced transfusion-transmitted infections (TTIs) worldwide. However, it is limited by the “window period”. If blood is donated during this period, infections may be missed, and a small but real risk of TTI remains. These limitations highlight the need for complementary technologies that can detect infections earlier in their course, particularly in regions with high disease prevalence or evolving epidemiological threats.

Nucleic acid testing: the molecular milestone

Since its introduction in the late 1990s, nucleic acid testing (NAT) has become the gold standard in countries with the infrastructure to support it.

Across the Asia Pacific region, NAT adoption remains inconsistent, with many blood services still relying solely on serology. This leaves critical gaps in safety, particularly in countries with high prevalence of transfusion-transmissible infections such as HIV, HBV, and HCV, or where other emerging infections are on the rise [7].

Nucleic acid testing is a game changer in medium to high endemic countries

Each layer of the screening process exists to catch what the last one misses. But when the first layer (donor questionnaires) may miss recent or asymptomatic infections, and the second layer (serological testing) is limited by the window period, the third layer (NAT) becomes critical.

By directly detecting viral RNA or DNA, NAT closes the diagnostic window period – the days or weeks when a donor is infected but still tests negative by conventional serology. In doing so, NAT has become a critical tool in preventing TTIs, especially for HBV,HCV, and HIV.

NAT vs. Serology:

HIV
The median window period lasts approximately 18 days from infection and generally ranges between 10 and 24 days [8]. Depending on the sensitivity of the RNA assay, the RNA may be detected as early as 5 to 10 days after the transmission of HIV [9].

HCV
Anti-HCV tests have about an eight to 11-week window period from HCV exposure to detection of HCV antibodies. HCV RNA is detectable approximately 1-2 weeks after HCV exposure [10].

HBV
HBV DNA may be the only marker detectable in the first two weeks, whereas HBsAg appears in the serum two to 10 weeks after exposure, before symptom onset and elevated aminotransferases [11,12].

Since introducing NAT in 2005, South Korea has reduced the residual risk of HCV transmission to just 0.27 per million donations [13].

In Vietnam, screening for HBV surface antigen (HBsAg) is standard practice across blood centres. However, studies show that 0.3% of HBsAg-negative donors still carry detectable HBV DNA, indicating occult hepatitis B infection (OBI). These cases are not detectable by serology and can only be identified using NAT [14].

The expanding threat list: why blood screening continues to evolve

Most blood safety systems were built around four pathogens: HIV, HBV, HCV, and Syphilis. However, that list no longer accurately reflects the true scope of TTI risks, especially in regions like Asia Pacific, where climate, migration, and outbreak frequency are reshaping epidemiology.

Dengue: high prevalence, low visibility

Dengue isn’t new, but its transfusion risks are becoming harder to ignore. Across endemic APAC countries, the virus spreads widely and silently.

Up to 87% of dengue infections are asymptomatic. Hence, the risk of transmission may not be identified through the donor history questionnaire. Viraemia lasts up to 9 days, and RNA has been detected in eligible donors during outbreaks [2].

In Vietnam, dengue RNA was detected in approximately 0.3% of blood donor samples, while no cases of chikungunya or Zika were found. In Thailand, dengue was detected in 0.07% of samples, chikungunya in 0.03%, and Zika in 0.02%. While the overall prevalence of viraemia in blood donors was low, the key takeaway is the measurable presence of viraemia in asymptomatic donors. These findings highlight the potential risk of transfusion-transmitted infections and reinforce the case for implementing routine screening in blood donors, especially in dengue-endemic regions [15].

During dengue epidemics, antibody-based tests often miss early-stage infections, while NAT, which detects viral RNA, is considered the most appropriate method for donor screening and may significantly reduce transfusion-related transmission [2].

Documented transfusion-transmitted dengue cases have occurred in Hong Kong, Singapore, Brazil, and Puerto Rico, from asymptomatic donors [2]. Yet routine screening for dengue RNA is not widely implemented in the region, which may leave a potential gap in current safety protocols, particularly during outbreaks.

Zika: low profile, real risk

Zika’s transfusion threat became undeniable during the 2015 – 2016 outbreak in the Americas. In Puerto Rico, Zika RNA was found in over 1% of blood donations during active outbreak periods – all from asymptomatic donors . At least one transfusion-transmitted Zika case has been documented in Brazil, involving an immunocompromised recipient [13].

Although Zika and dengue share common mosquito vectors, the key concern for blood services is not ongoing transmission but the potential for transfusion risk during outbreaks. As a result, universal Zika testing is no longer recommended by most regulatory authorities. Instead, targeted NAT screening during outbreaks is considered a more practical and risk-based approach.

In the Asia Pacific region, routine NAT screening for Zika virus is not currently practised [7]. Still, outbreak-responsive protocols may offer a more efficient way to manage risk in affected areas.

The next wave of viral infections

Between 2002 and 2013, over 30 cases of West Nile Virus (WNV) transmission through blood transfusion were reported in the United States, all during periods of active local transmission [13]. In response, the U.S. implemented seasonal NAT screening, which led to a significant reduction in WNV-related TTIs [16].

While WNV is not endemic across most of the Asia Pacific region, this example underscores the importance of flexible, risk-informed screening strategies. As new pathogens emerge – or as existing ones expand due to climate and vector shifts – targeted testing based on regional epidemiology can help prevent transfusion-transmitted infections without overburdening the system.

Parasites: rare but high-stakes

Babesia microti, a tick-borne parasite, poses a serious risk to transfusion recipients, especially the immunocompromised. Transfusion-transmitted babesiosis (TTB) carries a ~19% morbidity and mortality rate [17].

As TTB cases rose in the U.S., it triggered over a decade of donor surveillance, assay development, and research. This led to the implementation of regional blood donor screening in endemic areas, which employed both serological and molecular tests.

In a study of over 89,000 blood donations, Babesia microti screening identified 0.38% as positive, including PCR-positive cases detected year-round and 13% that were antibody-negative. In screened regions like Connecticut and Massachusetts, no transfusion-transmitted babesiosis (TTB) cases were reported, compared to one in every 18,074 donations from unscreened blood, demonstrating an eightfold reduction in risk [18].

Malaria transmission through blood transfusion is rare but preventable, and increasingly relevant for blood services in endemic regions.

Detection of malarial parasites by thick film is often used; however, the technique is time-consuming, highly operator-dependent, and prone to error. In endemic countries, the use of a highly sensitive enzyme immunoassay (EIA) for the detection of malaria antigen is also recommended by the WHO [19]. Thick film microscopy and EIA antigen tests may detect only around 100 parasites/µL, or 45 million parasites in a 450 mL blood donation [20,21].

These tests are designed to detect symptomatic infection, and not to prevent transmission from units of blood with low-level parasitaemia. More recently, NAT-based assays have emerged that may be more suitable in the blood donor screening setting. Tests for ribosomal RNA (rRNA) have been developed, with some advantages over DNA-based tests. Ribosomal RNA is much more abundant than genomic nucleic acid, with 1 × 10^4 rRNA copies per ring-stage parasite of P. falciparum [22].

Using rRNA, detection of very low levels of parasitemia can be achieved. NAT-based assays may play a role in preventing transfusion-transmitted malaria in both endemic and non-endemic countries.

In Indonesia, 4.5% of donors had malaria antibodies, and 1.2% were PCR-positive [23]. A review of 13 transfusion-transmitted malaria (TTM) cases in non-endemic countries since 2010 found that DNA-based PCR detected Plasmodium infection in 10 of 12 source donors tested, with the two negative results linked to degraded, stored samples. In contrast, antibody EIAs were positive in only three of seven donors, missing more than half of the cases. These findings highlight the limited reliability of serological methods, especially in asymptomatic donors. Newer rRNA-based molecular assays, which are approximately1000 times more sensitive than DNA PCR, offer even greater potential to prevent TTM through early detection, supporting PCR as the method of choice, particularly in endemic areas where antibody tests are less useful [24].

Conclusion

What this shows is clear: testing panels based on historical risk are no longer enough. Every outbreak, climate shift, and vector migration creates new potential entry points for pathogens into the blood supply.

Donor screening strategies must be based on local conditions, and take into account outbreaks and the shifting disease prevalence, not just legacy markers.

For APAC blood services, the path forward lies in routine review of regional risk, outbreak-responsive screening protocols, and the use of the right test for the right pathogen – whether serology or NAT.

Adopting flexible, evidence-based strategies will be key to strengthening blood safety across diverse epidemiological landscapes.

References

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