Blood as a life-saving source of data
Engela Duvenage
The academic gown that Dr Marion Vermeulen will don when she receives her PhD degree in virology during Stellenbosch University’s (SU’s) December graduation ceremony later this year will be as red as the topic of her thesis: blood.
Dr Marion Vermeulen | Photo by Stefan Els
Vermeulen, transfusion medicine and technical services executive at the South African National Blood Service (SANBS), has been doing work on this topic for close to 35 years.
Her PhD dissertation is titled ‘The impact of individual donation nucleic acid testing for HIV and HBV on blood safety in South Africa’. Her research shows that the hepatitis B virus (HBV), which causes life-threatening liver damage, is nowadays only detected in 0,14% of the blood donations made by South Africans born after 1995, compared to 1,29% in the blood of donors born after 1985 but before 1995. (All infected blood donations are, of course, discarded, Vermeulen notes, ever mindful of the safety precautions that protect recipients of blood products.)
She ascribes this drop in prevalence to the inclusion of the HBV vaccine in the country’s routine childhood immunisation programme since April 1995.
Collecting data, one blood bag at a time
Vermeulen did not pursue her research in a lab, using the best possible microscopes to view the detail of white and red blood cells, platelets and plasma contained in a drop of blood. Rather, she dissected the detail contained in the megabytes of electronic data collected each time a 450-milliliter unit of whole blood is donated in South Africa.
This is no mean feat, given that SANBS, on average, collects around 3 000 units of blood per day. Its goal is to collect at least 950 000 whole blood donations, 20 000 platelet apheresis (or ‘separation’) donations, and 40 000 source plasma donations annually. The provision of potentially life-saving blood products is a service that has been delivered to South Africa’s health sector for the past 80 years.
As a first line of safety screening, a nurse takes an on-the-spot measurement of the haemoglobin levels in the blood of prospective donors whenever they heed the call to volunteer blood. This iron-rich protein, carried in red blood cells, helps to transport oxygen throughout the body.
Each time they volunteer blood, prospective donors must also complete a questionnaire that captures information about their gender, age and race,” says Vermeulen.
“The questions in the questionnaire aim to ensure that the donor is healthy enough to donate and that the blood donated will be safe for a patient. Some questions are there to protect the donor, such as ones about their general well-being and medications used. Other questions, for instance, focus on donors’ travel history and sexual partners to protect the recipients of transfusions.”
Looking back at studies in which SANBS staff were involved in recent years, Vermeulen says: “Donors’ questionnaire answers have proven to be a valuable source of retrospective data.”
New technology boosts transfusion safety
The data she used for her PhD studies was limited to include only those entries into the SANBS donor database logged after September 2005. Vermeulen explains why:
"On Monday 3 October 2005, SANBS started using high-throughput individual donation nucleic acid testing (ID-NAT) technology to do universal screening of each unit of blood donated, instead of screening in pools. This allows for the direct detection of viruses of public health importance, such as HIV and hepatitis B and C, at very early stages of infection, without having to wait for a detectable level of antibody response to show up in donors’ samples.
“Worldwide, South Africa was the first country to use ID-NAT technology.
“The technology is extremely sensitive and has reduced the window period for detection to between 3 and 15 days after infection, depending on the virus.”
In the past, because of the nature of the available tests, these viruses could potentially go undetected for between 21 and 80 days after infection occurred.
SANBS acquired ID-NAT technology to give patients receiving life-saving transfusions peace of mind that they are, as far as possible, receiving safe units of blood. Such safety measures are paramount, given the high prevalence of HIV and hepatitis infections in South Africa.
ID-NAT also provided SANBS with a platform to expand its donor base, making it more representative of the South African population.
In 2018, Vermeulen was the lead author of a paper in Transfusion that showed how, thanks to ID-NAT’s increased sensitivity, the proportion of donations from black South Africans increased fivefold from 43 269 in 2005, when this technology was first used, to 246 686 in 2015, and from 6% of the initial pool of donors to 30%.
It also halved the residual risk of the SANBS blood supply, that is to say the risk that remains after controls are accounted for.
“Over the ten-year period, HIV was detected in 0,2% of donated blood, and there was only one confirmed case of HIV transmission via blood transfusion,” Vermeulen said in a statement made upon the release of the Transfusion article. “This is still extremely unfortunate, but it is a substantial improvement over the one to two confirmed cases per year between the years 2000 and 2005.
“Such findings highlight the importance of full disclosure during the answering of the donor questionnaire.”
The most recent study that Vermeulen was the lead author of, published in Viruses in 2022, provides reassurance that SANBS’ high-throughput testing system is sensitive enough to detect HIV, even in cases where an HIV-positive person started antiretroviral treatment very early.
Vermeulen says research findings have helped SANBS assess trends in residual HIV and HBV transfusion transmission risk in South Africa, make management decisions accordingly, and improve their education programmes.
“SANBS provides extensive education, particularly to the youth, about safe sexual practices.”
Forging a partnership
Over the past 15 years, Vermeulen has seen SANBS’ research outputs grow, the numerous academic articles published in top journals and her PhD being cases in point.
One of SANBS’ key research collaborators is the DSI-NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), based at SU. SACEMA specialises in the mathematical modelling of diseases prevalent in South Africa.
SANBS and SACEMA’s first study together, on which they published a paper in PLOS ONE in 2011, included collaborators from the Vitalant Research Institute (VRI) – an American non-profit blood collection service – and the American Red Cross. The study was led by Dr Reshma Kassanjee, a SACEMA associate.
The results showed how the abundance of data obtained from donated blood can, with a little extra effort in the lab and the use of statistical analysis, shed light on how the strength of a diagnostic marker grows over time post infection. This, in turn, supports large-scale surveillance of populations: While it is difficult to directly observe new infections as they occur, one can estimate the rate of infections by using suitable, well-characterised tests.
Since their first joint publication, the two entities’ researchers and other collaborators have contributed to papers on, among other topics, the percentage of South African donors who are iron deficient, the use of blood products in the country’s health sector, and the prevalence of HIV and hepatitis B and C virus among donors.
The working relationship between SANBS and SACEMA came about through the intervention of one of the world’s leading experts on matters related to blood banks, Dr Mike Busch of the VRI.
If SACEMA research associate Prof Alex Welte’s version of events is anything to go by, Busch’s suggestion, made in a chance meeting at a workshop during the International AIDS Conference in Mexico in 2008, went something like this: “You need to work together. You will enjoy it, and the relationship will be mutually beneficial and fruitful.”
This turned out to be an accurate prediction.
“Back then, SACEMA was still a newish entity, having only been established around 2006, with Prof John Hargrove as director. We were still finding our feet,” remembers Welte. It was under his watch as SACEMA’s director between 2010 and 2016 that the working research relationship, which lasts to this day, was cemented.
“We had an in-house statistician, but the work we were doing was not at the level of the maths and epidemiological modelling that SACEMA could do,” Vermeulen remembers in turn. “Collaborating on blood utilisation studies with SACEMA and other research entities has since allowed us to be more productive and develop into a much more research-intensive organisation.”
This collaboration is also what led Vermeulen to tackling a PhD in virology, Welte having made a valuable introductory phone call to Prof Gert van Zyl of SU’s Division of Medical Virology. The two subsequently became her co-supervisor and supervisor, respectively.
Blood donations help track the pandemic
Work on her PhD formally started in 2017. Like so many other things, however, its completion was stalled until 2022 by the first two years of the COVID-19 pandemic and the various demands related to it.
During this time, Vermeulen became the principal investigator at SANBS in an ongoing study on the extent to which the SARS-CoV-2 infection is estimated to be present, at any given time, in the South African population at large and per region. These estimations are based on the analysis of samples of residual blood – the blood that is left over after the standard tests on donated blood have been completed.
A selection of blood donors’ residual samples is tested at various time points using the Roche Elecsys antinucleocapsid assay. The latter determines the prevalence of antibodies (‘seroprevalence’) against SARS-CoV-2, the virus that causes COVID-19 disease. Testing with this assay has proven to be one of the more cost-effective methods to understand the extent of SARS-CoV-2 infections in populations worldwide.
Various sets of preliminary findings based on the analysis of samples of blood donations from different provinces have subsequently helped to alert other researchers, decision-makers and the general public to the extent to which the relevant population is exposed.
This study is being conducted by Vermeulen and her colleagues at SANBS, in conjunction with the Western Cape Blood Service. Researchers at SACEMA and the VRI are also assisting with the necessary number-crunching to make sense of the data.
Vermeulen says blood services worldwide have a history of quickly picking up on the presence of known or new pathogens, and on the possibility of disease outbreaks. In the mid-2010s, for instance, routine surveillance work by European blood services first alerted the world to a possible hepatitis E outbreak. It was therefore only natural that, amid the COVID-19 pandemic, blood donations would be considered a convenient source of surveillance data.
“This ongoing project will hopefully lead to a publication summarising our various preliminary reports,” says Welte, whose SACEMA associates on the project include Dr Eduard Grebe (now at the VRI) and Dr Laurette Mhlanga (now at Northwestern University in the USA).
As the pandemic matures and more people are vaccinated, it is becoming increasingly difficult to interpret the prevalence estimates gained from the testing of residual samples of donated blood. Fortunately, the team will not let this stop them in their efforts to understand the movement of the pandemic before the world has escaped the COVID-19 red zone.
Who uses the blood?
A 2021 paper in the South African Medical Journal reflected on how red blood cell products were used by South Africa’s private and public health sectors between 2014 and 2019. The paper’s lead author was SACEMA researcher Dr Larisse Bolton. Her co-authors included SACEMA’s current director, Prof Juliet Pulliam, and Dr Karin van den Berg, SANBS’ medical director.
Of the 2 356 441 units of red blood cell transfusions given during this five-year period, the public sector used 65,9% and the private sector 34,1%. Public-sector patients tended to be younger, between 22 and 49 years of age, compared to private-sector recipients who were typically aged between 37 and 68. Most transfusions were given to women.
However, between 2014 and 2019, the annual per capita use of red blood cell products decreased from 11,9 to 11 per population of 1 000 in the public sector, but increased from 34,8 to 38,2 per population of 1 000 in the private sector.
“Possible drivers for these differences may be healthcare access, differing patient populations and prescriber habits. Better understanding of these drivers may help inform equitable public health policy,” the authors noted.