Abstract
BackgroundMalaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Serological surveillance will be particularly important in areas of low or periodic transmission because patient antibody responses can provide a measure of historical exposure. While methods for detecting host antibody responses to Plasmodium falciparum and Plasmodium vivax are well established, development of serological assays for Plasmodium knowlesi, Plasmodium ovale and Plasmodium malariae have been inhibited by a lack of immunodiagnostic candidates due to the limited availability of genomic information.MethodsUsing the recently completed genome sequences from P. malariae, P. ovale and P. knowlesi, a set of 33 candidate cell surface and secreted blood-stage antigens was selected and expressed in a recombinant form using a mammalian expression system. These proteins were added to an existing panel of antigens from P. falciparum and P. vivax and the immunoreactivity of IgG, IgM and IgA immunoglobulins from individuals diagnosed with infections to each of the five different Plasmodium species was evaluated by ELISA. Logistic regression modelling was used to quantify the ability of the responses to determine prior exposure to the different Plasmodium species.ResultsUsing sera from European travellers with diagnosed Plasmodium infections, antigens showing species-specific immunoreactivity were identified to select a panel of 22 proteins from five Plasmodium species for serological profiling. The immunoreactivity to the antigens in the panel of sera taken from travellers and individuals living in malaria-endemic regions with diagnosed infections showed moderate power to predict infections by each species, including P. ovale, P. malariae and P. knowlesi. Using a larger set of patient samples and logistic regression modelling it was shown that exposure to P. knowlesi could be accurately detected (AUC = 91%) using an antigen panel consisting of the P. knowlesi orthologues of MSP10, P12 and P38.ConclusionsUsing the recent availability of genome sequences to all human-infective Plasmodium spp. parasites and a method of expressing Plasmodium proteins in a secreted functional form, an antigen panel has been compiled that will be useful to determine exposure to these parasites.
Highlights
Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures
With the aim of identifying antigens that could be used for serological markers of infection for Plasmodium parasites that infect humans, 12 proteins from P. falciparum and 10 proteins from P. vivax which were previously shown to be highly immunoreactive to sera from patients living in endemic regions were selected [12, 18] (Table 1)
8 that were produced at high levels in the expression system (CyRPA, GAMA, MSP10, MSP4, MSP5, P12, P38, P41) were selected to identify the orthologous proteins from the genome sequences of P. knowlesi [22], P. ovale and P. malariae [23, 24] (Table 1)
Summary
Malaria remains a global health problem and accurate surveillance of Plasmodium parasites that are responsible for this disease is required to guide the most effective distribution of control measures. Malaria is an infectious disease that remains a global health problem causing an estimated 219 million clinical cases resulting in 435,000 deaths in 2017 [1]. Müller‐Sienerth et al Malar J (2020) 19:31 is caused by parasites of the genus Plasmodium and several species are known to regularly infect humans. Much less is known about the other human-infective Plasmodium species, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi both in terms of their global distribution and clinical impact. Plasmodium knowlesi, a parasite typically found in macaques, is a significant cause of human malaria in Southeast Asia, causing a spectrum of disease ranging from mild to fatal infections [3]. Malaysia has the highest incidence of P. knowlesi malaria with over 6700 cases reported in the last 2 years compared to only 85 cases of indigenous human malaria (unpublished data from the Ministry of Health, Malaysia)
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