The Science Behind Saliva-Based Rapid Diagnostic Testing
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Dr Benji Pretorius, managing director of Erada Technology Alliance and practising emergency unit doctor, has faced the challenge of dealing with malaria throughout his career. The reality of the extremely thin line between survival and death hit close to home when Dr Pretorius himself contracted the disease.
Here, Dr Pretorius examines the use of saliva, rather than blood, in rapid diagnostic tests (RDT) for malaria and how this clinically informative biofluid could help to improve healthcare in the world’s poorest regions.
I will forever consider myself to be extremely lucky to have survived malaria without any permanent damage to my health. This is rarer than most people would believe; malaria can lead to long-term or permanent ill-health or disability, as well as affecting the patient’s career, education, family and income. The devastation malaria can cause is limitless and even for the lucky ones, the disease still leaves its mark; at the very least, there’s the psychological trauma of knowing that you may die within days, if not diagnosed or treated in time.
In recent years, national leaders, academics and scientists have come together to spearhead the fight against malaria. Pledges at the Global Fund’s sixth and most recent replenishment conference in 2019 raised more than US$14 billion in funds to fight malaria, tuberculosis and AIDS over the next three years1, The Lancet Commission devised and published a pathway to eliminate malaria across the globe by 20502 and malaria vaccine candidate RTS S/AS01 has prevented a substantial number of cases of clinical malaria over a 3–4 year period in young infants and children, although the vaccine is still undergoing development.3
Despite this fantastic progress, there was still an estimated 228 million cases of malaria and 405,000 deaths in 2018, with children under five years of age accounting for 67% of fatalities, according to the WHO’s World Malaria Report 2019.4
Malaria is one of the world’s oldest, deadliest diseases. Research has shown that the deadliest malaria parasite, Plasmodium Falciparum, may have the ability to evolve5, which may explain how the parasite can build resistance against treatments6 and preventative measures over time.
Those of us who hope to see the end of malaria within our lifetimes find ourselves consumed by the ultimate question:
How can we fight an old, deadly enemy that is as intent on survival as we are on destroying it?
My colleague, Dr Richard Schmidt, said: “Early detection of malaria is crucial to malaria eradication because individuals who carry the parasite without exhibiting symptoms, known as carriers, are the reservoir which leads to infection of mosquitoes and transmission of the disease. A parasite needs a host to survive. If you eliminate the source, you can eradicate it.”7
Malaria can act quickly. Early detection leads to early treatment, which ultimately means that the patient has a far better chance of survival. I know from my own personal experience of contracting malaria that if the parasite had been detected earlier in me, I could have been treated and cured before the disease made me unwell. This was precisely what spurred me on to work with Dr Schmidt in our small community in Musina, South Africa, together with a global team of scientists to develop SALVA!, the world’s first saliva-based RDT for malaria.
SALVA! is intended as a non-invasive option to existing RDTs; the kit detects subclinical carriage of Plasmodium Falciparum parasites from a single saliva sample. Malaria carriers can be spotted before they start to exhibit symptoms or fall ill and the results are available in five to twenty minutes without samples having to be sent back to a lab.
Why use saliva?
Oral fluid is an attractive alternate option to existing blood-sampling RDTs, given its inherently lower infection risk (absence of sharps during collection; lower risk of cross-contamination or additional contraction of infection/complications caused by poor hygiene.) Saliva is easy to collect and, although a challenge to stabilize and store, our technology has met these specific challenges and offers an alternative where a blood-sample RDT may offend cultural tradition (blood taboos).
Saliva is a “clinically informative, biological fluid (biofluid)” and is “ideal for early detection of disease as it contains specific soluble biological markers”.8 We believe that the potential utility of non-invasive biofluid sampling approaches for rapid malaria diagnosis has not been fully explored and, furthermore, that non-invasive RDTs that use saliva could be used to diagnose other parasitic diseases and could even lead the way in improving diagnostics in healthcare.
When vaccines are developed, their effectiveness needs to be tested. Using RDTs gives an indication of a vaccine’s effectiveness. Accurate diagnoses can also prevent drug wastage and can help to provide the necessary data to track the spread of malaria. Only by tracking the occurrence and spread of malaria can it be ensured that the currently limited resources and funds go where they are most needed.
For World Malaria Day 2020, the WHO joined with the RMB Partnership to End Malaria in promoting the ‘Zero malaria starts with me’ campaign that aims to “keep malaria high on the political agenda, mobilize additional resources, and empower communities to take ownership of malaria prevention and care”.9
While blood tests require equipment, an extremely high level of hygiene control and a trained medical professional to administer the test, RDTs that use saliva could be administered by anyone: teachers, community leaders or parents. Not only does this take the burden off of healthcare professionals and lets them focus on treatment, taking the diagnostic tool out of clinics and into the wider community could also promote awareness and education about malaria and other mosquito-borne diseases in rural communities which, in turn, could lead to more people in communities at risk taking preventative measures.
Now, during the COVID-19 pandemic, I believe that the availability of easy-to-use RDTs for malaria will be critical. Both malaria and COVID-19 can present with the symptom of fever – this not only causes confusion but could be life-threating should malaria be mistaken for COVID-19. The recommended advice for patients with mild cases of COVID-19, which may include symptoms of a cough and a fever, is to self-isolate at home unless serious symptoms develop, but if the fever is due to malaria, every hour lost is risking death or permanent disability.
Saliva-based RDTs that could be administered by parents at home could not only help to catch cases of malaria but also help to manage the risk of transmission of COVID-19, as a health professional would not have to go to a patient’s home for the purpose of diagnosing possible malaria cases.
There are many battles to be won in the fight against malaria – one such battle emerging is the climate crisis, as research shows that warmer temperatures and excess rain and flooding may increase the spread and cases of malaria.10 Widespread access to easy to use and non-invasive RDTs in the world’s poorest communities is just one step in winning the war against an ancient enemy, but an important one.
Further information about Erada and SALVA! can be found here.