Malaria is a life-threatening parasitic disease caused by some species of Plasmodium parasites that are transmitted through the bites of infected female Anopheles mosquitoes. In 2017, it was estimated that 3.2 billion people – nearly half of the entire world’s population – were at risk and that 91 countries and territories had ongoing malaria transmission [1]. WHO world malaria report, 2019 highlights there has not been significant progress in reducing global malaria cases over the past 4 years. In Ghana for instance, half a million more cases of malaria was recorded in 2018 compared to 2017 [2]. The burden of malaria still remains huge; in 2018 alone, 405,000 deaths due to malaria occurred worldwide [2]. Sub-Saharan Africa continues to carry a disproportionately high share of the global malaria burden. According to WHO World Malaria report in 2019, approximately 85% of all malaria deaths occurred in 20 countries all of which are in the Sub-Saharan Africa region except India. Nigeria and Ghana respectively accounted for 24% and 3% of all malaria deaths globally in the year 2018 [2].
In Ghana, a study revealed it costs households between US$5.70 (for uncomplicated malaria) and US$48.73 (for severe malaria) to treat malaria [3]. It is recorded that AngloGold Ashanti spent up to US$55,000 every month on the treatment of malaria in its employees and their dependents and this excluded the valued loss in productivity as a result of absenteeism [4]. The total cost of malaria to businesses in Ghana was estimated in 2014 to be US$6.58 million, 90% of which were direct costs [5]. It is therefore not surprising that, the 33 richest countries in the world are all malaria free [6].
Other studies have put forward that the economic benefits associated with significantly reducing or eliminating malaria are very huge. It is estimated that even with cost of investing in malaria elimination being very high (estimated US$208.6 billion between 2016 and 2030, as well as another US$673 million in research and development annually), the benefits to be harnessed in such an investment could be 40:1 worldwide and 60:1 in Sub-Saharan Africa. This means that, for every US$1 invested in malaria eradication, economic gains of US$40 worldwide and US$60 in Sub-Saharan Africa will be made [7].
Among the 5 species of Plasmodium namely P. falciparum, P. malariae, P. ovale, P. vivax, P. knowlesi, which cause malaria, P. falciparum is known to cause the greatest morbidity and mortality.
Examination of Giemsa-stained thick and thin blood smears by light microscopy, a technique introduced in 1904, continues to be the standard for malaria diagnosis in most clinical settings. Microscopy as a modality of malaria diagnosis allows for detection and identification to the species level of all species, it makes room for parasite quantification and it can be used for monitoring parasite clearance following therapy.
Notwithstanding, microscopy as blood – based test is invasive and the pain associated with the needle prick in the course of drawing blood ward off patients. This could be challenging particularly in paediatric patients. Microscopy requires trained personnel and this could be a hindrance to rapid malaria diagnosis and treatment especially in human resource constrained settings. Carrying out blood film microscopy in settings without electricity as the case is in many rural areas in Sub-Saharan Africa could be very challenging. The use of needles in blood-based tests raises the risk of accidental transmission of infectious diseases. These techniques can also encounter difficulty with patient compliance particularly when blood collection is required from young children and in communities with cultural objections or blood taboos [8]. According to the Ghana Health Service Standard Treatment and Guidelines, the management of malaria requires initial test to confirm diagnosis and a repeated test post treatment to ensure parasite clearance. Such repeated blood sampling could complicate in phlebitis and cellulitis and this could have serious consequences especially in the immunocompromised such as diabetic and AIDS patients.
To circumvent the challenges associated with microscopy as a means of malaria diagnosis, researchers as well as clinicians have explored alternative diagnostic modality. The most outstanding of such alternative in malaria diagnostics is the introduction of Malaria (Plasmodium) antigen – based Rapid Diagnostic Test Kits (RDTs) in the mid – 1990s. RDTs detect parasite antigens from a small volume (usually 5 to 15 µL) of blood using an immunochromatographic assay impregnated on a test strip. The earliest RDTs employed primary antibodies to detect Plasmodium falciparum histidine-rich protein 2 (Pf HRP2) [9]. Today, commercial tests are tailored to local malaria epidemiology with different combinations of target antigens including genus-specific aldolases, and species-specific HRP2 and Plasmodium lactate dehydrogenase (pLDH). RDTs have proven to be very useful in rapid presumptive diagnosis of malaria especially in settings where blood film microscopy could not be easily carried out. However, RDTs also utilize blood and are not free from the challenges associated with blood – based tests. In contrast to blood, saliva presents a reduced biohazard [10] and can be painlessly collected in relatively large quantities by individuals with less training. Blood-borne biomarkers that cross from local vasculature into the salivary glands can in principle be detected in saliva [11]. Indeed, the diagnostic utility of saliva has been demonstrated in immunoassays for infectious diseases such as hepatitis, Ebola virus, measles, rubella, and HIV.
Potential biomarkers for malaria have also been identified in saliva [12]. The inconvenience associated with the traditional blood – based malaria test coupled with the low sensitivity of these tests as reported by many studies [13, 14, 15, 16] necessitates the exploration for alternative non-invasive potential sample for malaria diagnosis. This study therefore seeks to compare the diagnostic accuracy of saliva – borne Plasmodium falciparum histidine – rich protein 2 (PfHRP2) and Plasmodium Lactate Dehydrogenase (pLDH) with blood film microscopy in malaria case definition and advocate for the development of special RDTs with impregnated anti-bodies manufactured in a manner that can detect malaria antigens in saliva thereby overcoming the challenges associated with the traditional blood-based tests.