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  1. Oyong DA, Wilson DW, Barber BE, William T, Jiang J, Galinski MR, et al.
    J Infect Dis, 2019 11 06;220(12):1950-1961.
    PMID: 31419296 DOI: 10.1093/infdis/jiz407
    BACKGROUND: Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.

    METHODS: Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.

    RESULTS: The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.

    CONCLUSION: Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

  2. Oyong DA, Loughland JR, SheelaNair A, Andrew D, Rivera FDL, Piera KA, et al.
    Malar J, 2019 Sep 18;18(1):312.
    PMID: 31533836 DOI: 10.1186/s12936-019-2962-0
    BACKGROUND: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection.

    METHODS: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated.

    RESULTS: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM.

    CONCLUSIONS: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

  3. Murdiyarso LS, Rajahram GS, Tan AF, Piera KA, William T, Oyong DA, et al.
    Am J Trop Med Hyg, 2024 Nov 12.
    PMID: 39531730 DOI: 10.4269/ajtmh.24-0264
    Zoonotic malaria presents a major public health challenge in Southeast Asia. Plasmodium cynomolgi coinfects the same macaque hosts and mosquito vectors as the most common cause of zoonotic malaria, Plasmodium knowlesi. Plasmodium cynomolgi appears morphologically similar to Plasmodium vivax on microscopy and can amplify P. vivax polymerase chain reaction (PCR) assays, confounding transmission estimates. We screened 2,103 samples for P. cynomolgi across all 26 districts in Sabah, Malaysia, from 2010 to 2021. Samples comprised 1,425 P. knowlesi, 256 P. vivax, 293 P. falciparum, and 31 Plasmodium malariae PCR-confirmed malaria cases and 100 malaria microscopy-positive and species-specific PCR-negative samples. A nested PCR assay targeting P. cynomolgi-specific 18S small subunit ribosomal ribonucleic acid with a detection limit of ∼2 parasites/µL was conducted on whole blood samples. No P. cynomolgi infections were detected. Symptomatic P. cynomolgi co-infections appear rare in Malaysia, although prevalence may be underestimated owing to the absence of routine molecular screening and the sensitivity of available assays.
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