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Introduction
Publications
Publications (36)
The risk of severe malaria from the zoonotic parasite Plasmodium knowlesi approximates that from P. falciparum. In severe falciparum malaria, neutrophil activation contributes to inflammatory pathogenesis, including acute lung injury (ALI). The role of neutrophil activation in the pathogenesis of severe knowlesi malaria has not been examined. We ev...
Plasmodium vivax contributes significantly to global malaria morbidity. Key advances include the discovery of pathways facilitating invasion by P. vivax merozoites of nascent reticulocytes, crucial for vaccine development. Humanized mouse models and hepatocyte culture systems have enhanced understanding of hypnozoite biology. The spleen has emerged...
Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLD...
Splenomegaly frequently occurs in patients with Plasmodium falciparum (Pf) or P. vivax (Pv) malarial anemia, but mechanisms underlying this co‐occurrence are unclear. In malaria‐endemic Papua, Indonesia, we prospectively analyzed red blood cell (RBC) concentrations in the spleen and spleen‐mimetic retention in 37 subjects splenectomized for trauma...
In humans approximately 0.1-0.3% of circulating red blood cells (RBC) are present as platelet-RBC (P-RBC) complexes, and 1-2% in mice. Excessive P-RBC complexes are found in diseases that compromise RBC health (e.g. sickle cell disease and malaria) and contribute to pathogenesis. However, the physiological role of P-RBC complexes in healthy blood i...
Background and Objective
The importance of extracellular traps (ETs) in chronic respiratory conditions is increasingly recognized but their role in paediatric bronchiectasis is poorly understood. The specialized techniques currently required to study ETs preclude routine clinical use. A simple and cost‐effective ETs detection method is needed to su...
Severe malaria after splenectomy has been reported with infections with Plasmodium falciparum , Plasmodium knowlesi , and Plasmodium malariae, but is less well-characterized with Plasmodium vivax . We describe a case of severe P. vivax malaria with hypotension, prostration, and acute kidney injury occurring 2 months after splenectomy in Papua, Indo...
Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of Plasmodium vivax . It can also be used as a diagnostic biomarker. Quantitation of plasma PvLDH has been used as a measure of P. vivax biomass in clinical studies of uncomplicated and severe vivax malaria. With the increasing importance of PvLDH in stu...
Plasmodium knowlesi is the major cause of zoonotic malaria in Southeast Asia. Rapid and accurate diagnosis enables effective clinical management. A novel malaria diagnostic tool, Gazelle (Hemex Health, USA) detects haemozoin, a by-product of haem metabolism found in all Plasmodium infections. A pilot phase refined the Gazelle haemozoin identificati...
Objective
Glucose-6-phosphate dehydrogenase (G6PD) deficiency offers some protection against malaria; however, the degree of protection is poorly described and likely to vary with G6PD genotype and Plasmodium species. We present a novel approach to quantify the differential invasion rates of P. falciparum between G6PD deficient and normal red blood...
Background
Plasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for spe...
Background
Circulating myeloid-derived-suppressor-cells (MDSC) with immunosuppressive function are increased in human experimental Plasmodium falciparum infection, but have not been studied in clinical malaria.
Methods
Using flow-cytometry, circulating polymorphonuclear-MDSC were evaluated in cryopreserved samples from patients with uncomplicated...
Background
Plasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for spe...
Commercial point-of-care tests remain insufficient for accurately detecting and differentiating low-level malaria infections in regions co-endemic with multiple non-falciparum species, including zoonotic Plasmodium knowlesi (Pk). A 5-plex chemiluminescent assay simultaneously measures pan-Plasmodium lactate dehydrogenase (pLDH), P. falciparum (Pf)-...
Background
A very large biomass of intact asexual-stage malaria parasites accumulates in the spleen of asymptomatic human individuals infected with Plasmodium vivax. The mechanisms underlying this intense tropism are not clear. We hypothesised that immature reticulocytes, in which P. vivax develops, may display high densities in the spleen, thereby...
Plasmodium knowlesi is endemic across Southeast Asia, and is the commonest cause of zoonotic malaria. The spectrum of clinical disease from P. knowlesi infection ranges from asymptomatic infection, through to severe malaria and death. Over 90% of clinical disease occurs in adults, mostly living in forest edge areas undergoing intensive land use cha...
Genetic epidemiology can provide important insights into parasite transmission that can inform public health interventions. The current study compared long-term changes in the genetic diversity and structure of co-endemic Plasmodium falciparum and P. vivax populations. The study was conducted in Papua Indonesia, where high-grade chloroquine resista...
Background: Neutrophil activation results in Plasmodium parasite killing in vitro, but neutrophil products including neutrophil extracellular traps (NETs) mediate host organ damage and may contribute to severe malaria. The role of NETs in the pathogenesis of severe malaria has not been examined.
Methods: In Papua, Indonesia, we enrolled adults wit...
Key Points
Platelets directly interact with and kill circulating Plasmodium parasites in patients with malaria to help control parasitemia. In vitro platelet antiplasmodicidal activity against P knowlesi involves platelet–cell binding and intracellular accumulation of PF4.
Background:
Splenectomy increase the risk of severe and fatal infections, however the risk of Plasmodium vivax malaria is unknown. We quantified the Plasmodium species-specific risks of malaria and other outcomes following splenectomy in patients attending a hospital in Papua, Indonesia.
Methods:
Records of all patients attending Mitra-Masyaraka...
The surveillance of malaria is generally undertaken on the assumption that samples passively collected at health facilities are comparable to or representative of the broader Plasmodium reservoir circulating in the community. Further characterization and comparability of the hidden asymptomatic parasite reservoir are needed to inform on the potenti...
Submicroscopic Plasmodium infections are an important parasite reservoir, but their clinical relevance is poorly defined. A cross-sectional household survey was conducted in southern Papua, Indonesia, using cluster random sampling. Data were recorded using a standardized questionnaire. Blood samples were collected for haemoglobin measurement. Plasm...
Characteristics of household individuals present and sampled during the survey and those absent from the household.
(DOCX)
Adjusted odds ratios for severe or moderate anaemia in symptomatic and asymptomatic malaria.
(DOCX)
Adjusted odds ratios for severe or moderate anaemia in asymptomatic malaria stratified by age group.
(DOCX)
The distribution and severity of anaemia.
(DOCX)
Background
Plasmodium falciparum and Plasmodium vivax infections compromise dendritic cell (DC) function and expand regulatory T (Treg) cells in both clinical disease (malaria) and experimental human sub-microscopic infection. Conversely, in asymptomatic microscopy-positive (patent) P. falciparum or P. vivax infection in endemic areas, blood DC inc...
Background:
The emergence and spread of multidrug-resistant Plasmodium falciparum and Plasmodium vivax highlights the need for objective measures of ex vivo drug susceptibility. Flow cytometry (FC) has potential to provide a robust and rapid quantification of ex vivo parasite growth.
Methods:
Field isolates from Papua, Indonesia, underwent ex vi...
Clinical illness with P. falciparum or P. vivax compromises dendritic cell (DC) function and expands regulatory T (Treg) cells. Individuals with asymptomatic parasitemia have clinical immunity restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomatic Plasmodium infection is unclear. During a c...
