Anstey, NM

Barber, BE

Boyle, M

Grigg, MJ

Miningo, G

Piera, K

Price, Richard

William, T

Yeo, TW

American Journal of Tropical Medicine and Hygiene

English

Oxford University Research Archive

81astmh.orgthat the disruption of PfPuf2 gene, a translational repressor increases the number of male gametocytes generated. In addition, the majority of the male-specific proteins are expressed early from stage II onwards. Therefore we hypothesized that gametocytes are predestined to be male but actively switch to female gametocyte maturation during the stage III-IV transition phase. To establish a list of putative early sex-specific gametocyte markers, we used Click-Chemistry to profile de novo protein synthesis over 5 days; spanning the gametocyte transition period from stage III-IV. We compared the protein list for each 24 period to our predicted male- and female-specific gametocyte proteome to identify proteins and pathways that are putatively involved in gender switching.262ANTI-PHOSPHATIDYLSERINE IGM AND IGG ANTIBODIES ARE INCREASED IN FALCIPARUM AND VIVAX MALARIA AND CORRELATE WITH ANAEMIABridget E. Barber1, Matthew J. Grigg1, Kim Piera1, Tim William2, Michelle Boyle1, Gabriella Miningo1, Ric N. Price1, Tsin W. Yeo3, Nicholas M. Anstey11Menzies School of Health Research, Darwin, Northern Territory, Australia, 2Jesselton Medical Centre, Kota Kinabalu, Malaysia, 3Nanyang Technological University, Singapore, SingaporeMalarial anaemia results primarily from the loss of uninfected erythrocytes, although its aetiology is incompletely understood. Phosphatidylserine (PS) is a membrane phospholipid normally located on the internal leaflet of the lipid bilayer, which in malaria becomes exposed on the surface of infected and uninfected erythrocytes. In a mouse model anti-PS antibodies have been shown to contribute to anaemia by binding to the surface of uninfected erythrocytes and mediating their phagocytosis. To investigate the role of anti-PS antibodies in malarial anaemia in humans, we measured anti-PS IgG and IgM antibodies in Malaysian adults hospitalised with falciparum and vivax malaria, and correlated with day 0 and nadir haemoglobin. Compared to controls, anti-PS IgM and IgG in patients with falciparum malaria were increased at baseline: 129 (80 - 205) U/ml vs. 27 (19 - 41) U/ml for IgM (p<0.0001), and 81 (65 - 116) U/ml vs 17 (14 - 21) U/ml for IgG (p<0.0001). The corresponding values for P. vivax were 117 (75 - 215) U/ml vs. 27 (19 - 41) U/ml (p<0.0001) and 65 (54 - 172) U/ml vs 17 (14 - 21) U/ml (p=0.0001). In falciparum malaria, anti-PS IgG correlated inversely with day 0 haemoglobin (r=-0.37, p=0.041) and haemoglobin nadir (r=-0.41, p=0.025). In vivax malaria, anti-PS IgM correlated inversely with baseline haemoglobin (r=-0.72, p=0.029) and haemoglobin nadir (r=-0.81, p=0.008). In vivax malaria, anti-PS IgM antibodies also correlated inversely with the percentage loss of haemoglobin, from baseline to nadir (r=0.70, p=0.036). No correlation was detected between anti-PS antibodies and parasitemia. In adults with vivax and falciparum malaria, anti-PS antibodies are increased and correlate inversely with haemoglobin. This may have implications for development of therapeutic strategies for malarial anaemia.263ELEVATED CEREBROSPINAL FLUID TAU PROTEIN LEVELS ARE ASSOCIATED WITH LONG-TERM NEURODEVELOPMENTAL IMPAIRMENT IN UGANDAN CHILDREN WITH CEREBRAL MALARIADibyadyuti Datta1, Robert O. Opoka2, Paul Bangirana3, Kathleen F. Ireland4, Chandy C. John11Ryan White Center for Pediatric Infectious Disease and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States, 2Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda, 3Department of Psychiatry, Makerere University, Kampala, Uganda, 4University of Minnesota School of Medicine, Minneapolis, MN, United StatesMicrotubule associated protein (MAP) tau is a known marker of brain parenchymal damage. Elevated levels of total tau protein in cerebrospinal fluid (CSF) has been linked with neurodegeneration and cognitive impairment in several forms of dementia and Alzheimer’s disease. Studies conducted in Vietnamese adults and in Kenyan children with severe malaria (SM) have shown that levels of tau proteins were increased in patients with SM and associated with poor acute neurologic outcomes. To assess the association of total tau with mortality and long-term neurodevelopmental outcomes, we measured CSF tau levels in a prospective study of 145 Ugandan children 18 months-12 years of age with cerebral malaria (CM). CSF tau levels did not differ significantly between those who died (n=8) and those who survived (n=137, P=0.27). However, CSF tau levels were significantly higher in children with retinopathy positive CM (n=100) compared to retinopathy negative CM (n=45. P=0.03). CSF tau levels also associated with duration of coma (β= 0.2, P=<0.0001) but not with number of seizures, and CSF tau levels were higher at discharge and 6, 12 and 24 months after discharge in children with neurologic deficits than children without deficits (all P<0.05). Finally, higher CSF tau levels were associated with worse scores for overall cognition (β=-0.8, P=0.03) and working memory (β=-0.9, P=0.05) 12 months after discharge, but only in children over 5 years of age. Higher CSF tau levels also correlated with higher plasma levels of the endothelial function markers soluble P-selectin (Spearman’s rho=0.22, P=0.007) and angiotensin-2 (Spearman’s rho=0.47, P=<0.0001). Thus, in children with CM, CSF tau levels are associated with endothelial damage and predict acute and long-term neurologic and cognitive impairment.264RETICULOCYTE DISCONTINUOUS ENRICHMENT USING PERCOLL GRADIENT HAS A NEGATIVE IMPACT ON IN VITRO GROWTH OF PLASMODIUM VIVAX D’Arbra Blankenship, Sebastien Dechavanne, Brenden Jenks, Peter A. Zimmerman, Brian T. GrimbergCase Western Reserve University, Cleveland, OH, United StatesIn vitro cultures of Plasmodium parasites have provided important insights into malaria research. Unfortunately, culturing P. vivax (Pv) in adult human peripheral blood has presented significant challenges. Recent improvements have made short-term culturing possible with the addition of reticulocyte-enriched human blood. Reticulocyte enrichment is considered an essential process to increase invasion events by providing numerous preferable target cells for the parasites to invade. However, the process of isolating reticulocytes, based on density properties requires further optimization to justify efforts, and results in small quantities. In this study, we tested the invasion efficiency of cryopreserved Pv Vietnam/Palo Alto strain in human adult peripheral blood that was reticulocyte enriched using 40%, 70%, and 80% Percoll gradients, with reticulocytes harvested from the 70% layer. Initial flow cytometry of Pv invasion events after 48 hours of in vitro culture was higher in reticulocyte enriched blood (41.0±10) compared to unenriched blood (13.5±3.5). However, continued parasite maturation with subsequent invasion cycles is more successful at 72 hours in unenriched blood (92±1) when compared to enriched blood (51±1). After repeated observation of improved parasite propagation in unenriched human blood and the obligate binding of Pv Duffy Binding Protein (PvDBP) to host cell Duffy antigens we further investigated, by flow cytometry, the impact of discontinuous gradient Percoll selection of reticulocytes on the red blood cells from three adult donors expressing three different Duffy blood groups FY*A/*A, FY*A/*B, and FY*B/*B. All three donors showed decreased binding of PvDBP to their RBCs after Percoll treatment FY*A/*A (45.3 Unenriched, 36.2 Enriched), FY*A/*B (67.1 Unenriched, 41.3 Enriched), and FY*B/*B 981.9 Unenriched, 62.9 Enriched). Our data illustrates that the use of Percoll to isolate reticulocytes 

Anti-phosphatidylserine IGM and IGG antibodies are increased in falciparum and vivax malaria and correlate with anaemia

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Anti-phosphatidylserine IGM and IGG antibodies are increased in falciparum and vivax malaria and correlate with anaemia

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