Medical Research: Bench to Bedside Department of Medicine (RMH)

Malaria

Go to: Current Projects | Publications | Techniques | Links

Areas of Research Interest

Importance of Malaria

More than 2 million children die each year from malaria. Fatal infection in children and low birth weight associated with malaria in pregnancy both contribute. We aim to understand how malaria causes its massive mortality, to improve its treatment and prevention.

Malaria in Pregnancy

Malaria Laboratory staff and students

We focus on the pathogenesis of malaria in pregnancy and childhood. We use clinical samples from Malawi (Africa) and Papua New Guinea to understand how pregnant women become susceptible to malaria, and how this impairs the growth of the unborn child. We have developed assays to quantitate antibodies, important in protection against malaria, using live parasites and ELISAs. Var genes encode Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on the surface of red cells and responsible for parasite adhesion to cells lining blood vessels. We are studying the expression of var genes associated with malaria in pregnancy. We are planning to follow pregnant women through pregnancy, using ultrasound examinations to determine how episodes of malaria affect fetal growth.

Malaria and HIV Infection

We are working on a study in Malawi to investigate the interaction between malaria and human immunodeficiency virus (HIV) in pregnant women. Each infection may make the other worse, HIV increasing susceptibility to malaria and malaria increasing the risk of the mother passing HIV to her child. In this study, we have shown microtransfusions—passage of small amounts of blood across the placenta—and untreated syphilis infection are especially important mechanisms by which babies may acquire HIV infection.

In related laboratory studies, we showed that HIV decreases antibody immunity to malaria, and affects the ability of white blood cells such as macrophages to clear malaria infected red cells. We are presently examining the effects of HIV on white blood cell function in malaria.

Fatal Malaria in Young Children

Using autopsy samples from Malawi we are studying why some children die from malaria. Malaria-infected red blood cells accumulate in large numbers in the brain. We are studying expression of PfEMP1 and encoding var genes in association with fatal disease. We are also studying immune responses to malaria in the brain and other organs.

Better Treatment and Prevention of Malaria

Funded by the Bill and Melinda Gates Foundation, Dr Nicolas Senn from our department is working in Papua New Guinea to see whether giving children antimalarial treatment when they come for immunisations prevents malaria and anaemia.

In a new grant from the Gates Foundation, we will study preventive malaria treatment in pregnant women. The drug combination we are using may also help sexually transmitted infections such as chlamydia and gonorrhoea.

Current Projects

Title: Regulation of var gene transcription and PfEMP1 expression

Project Leader(s): Dr Michael Duffy & Professor Graham Brown
Students: Ee-Ken Choong
Start Date: 02/2001
Proposed Completion Date: 01/2009
For More Information: Dr Michael Duffy, T: +61 3 8344 3263; E: mduffy@unimelb.edu.au

Title: Mechanisms of malaria parasite adhesion and of immunity to malaria

Project Leader(s): A/Professor Stephen Rogerson & Professor Graham Brown with Dr James Beeson, The Walter and Eliza Hall Institute of Medical Research
Students: Elizabeth Aitken, Gaoqian Feng
Start Date: 02/2001
Proposed Completion Date: 01/2009
For More Information: A/Professor Stephen Rogerson, T: +61 3 8344 3259; E: sroger@unimelb.edu.au

Title: Malaria and HIV in pregnant Malawian women

Project Leader(s): A/Professor Stephen Rogerson & Professor Steven Meshnick (University of North Carolina, USA)
Start Date: 02/2001
Proposed Completion Date: 01/2009
For More Information: A/Professor Stephen Rogerson, T: 61 3 8344 3259; E: sroger@unimelb.edu.au

Title: HIV and immunity to malaria

Project Leader(s): A/Professor Stephen Rogerson & Dr Anthony Jaworowski, Burnet Institute Melbourne

Students: Ricardo Ataide
Start Date: 01/2006
Proposed Completion Date: 12/2011
For More Information: A/Professor Stephen Rogerson, T: 61 3 8344 3259; E: sroger@unimelb.edu.au

Title: Malaria and fetal growth restriction

Project Leader(s): A/Professor Stephen Rogerson and Dr Philippe Boeuf
Students: Elizabeth Aitken, Alex Umbers, Caroline Chua
Start Date: 01/2008
Proposed Completion Date: 12/2010
For More Information: A/Professor Stephen Rogerson, T:+61 3 8344 3259; E: sroger@unimelb.edu.au or Dr Philippe Boeuf, T +61 3 8344 3263; E: pboeuf@unimelb.edu.au

Title: Intermittent presumptive treatment to prevent malaria and anaemia in infants in Papua New Guinea

Project Leader(s): Professor John Reeder & Dr Ivo Mueller, Papua New Guinea Institute of Medical Research, Drs Louis Schofield & James Beeson, The Walter and Eliza Hall Institute of Medical Research, and A/Professor Stephen Rogerson
Start Date: 12/2005
Proposed Completion Date: 12/2009
For More Information: A/Professor Stephen Rogerson, T: +61 3 8344 3259; E: sroger@unimelb.edu.au

Title: Placental pathology of malaria

Project Leaders: A/Professor Stephen Rogerson & Dr Philippe Boeuf
Students: Caroline Clapham, Ainunnadiah Darus
Start Date: 04/2001
Proposed Completion Date: 03/2009
For More Information: A/Professor Stephen Rogerson, T: +61 3 8344 3259; E: sroger@unimelb.edu.au

Title: Intermittent preventive treatment for malaria in Papua New Guinea

Project Leader(s): A/Professor Stephen Rogerson
Start Date: 02/2008
Proposed Completion Date: 01/2013
For More Information: A/Professor Stephen Rogerson, T: 61 3 8344 3259; E: sroger@unimelb.edu.au

Most Significant Publications

  1. Montgomery J, Milner, DA Jr, Tse MT, Njobvu A, Kayira K, Dzamalala CP, Taylor TE, Rogerson SJ & Craig AG & Molyneux ME (2006). Genetic analysis of circulating and sequestered populations of Plasmodium falciparum in fatal paediatric malaria. J Infect Dis, (in press).

  2. Beeson JG, Mann EJ, Byrne TJ, Caragounis A, Elliott SR, Brown GV & Rogerson SJ (2006). Antigenic differences and conservation among placental type Plasmodium falciparum-infected erythrocytes and acquisition of variant-specific and cross-reactive antibodies. J Infect Dis., 1 March, 193(5):721–30.

  3. Kwiek JJ, Mwapasa V, Milner DA Jr, Alker AP, Miller WC, Tadesse E, Molyneux ME, Rogerson SJ & Meshnick SR (2005). Maternal-fetal microtransfusions and HIV-1 mother-to-child transmission in Malawi. PLoS Med, 22 November, 3(1):e10.

  4. Alker AP, Mwapasa V, Purfield A, Rogerson SJ, Molyneux ME, Kamwendo DD, Tadesse E, Chaluluka E & Meshnick SR (2005). Mutations Associated with Sulfadoxine-Pyrimethamine and Chlorproguanil Resistance in Plasmodium falciparum isolates from Blantyre, Malawi. Antimicrob Agents Chemother September, 49(9):3919–21.

  5. Elliott SR, Brennan AK, Beeson JG, Tadesse E, Molyneux ME, Brown GV & Rogerson SJ (2005). Placental malaria induces variant specific antibodies of the cytophilic subtypes, G1 (IgG1) and IgG3, that correlate with adhesion inhibitory activity. Infect Immun, September, 73(9):5903–07.

  6. Abrams ET, Kwiek JJ, Mwapasa V, Kamwendo DD, Tadesse E, Lema VM, Molyneux ME, Rogerson SJ & Meshnick SR (2005). Malaria during pregnancy and foetal haematological status in Blantyre, Malawi. Malar J, 25 August, 4(1):39.

  7. Elliott SR, Duffy MF, Byrne TJ, Beeson JG, Mann EJ, Wilson DW, Rogerson SJ & Brown GV (2005). Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium falciparum-infected erythrocytes are associated with transcription of var2csa. Infect Immun, 73(5):2848–56.

  8. Duffy MF, Byrne TJ, Elliott SR, Wilson DW, Rogerson SJ, Beeson JG, Noviyanti R & Brown GV (2005). Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype. Mol Microbiol, 56(3):774–88.

  9. Mwapasa V, Rogerson SJ, Molyneux ME, Abrams E, Kamwendo DD, Lema VM, Tadesse E, Chaluluka E, Wilson P & Meshnick SR (2004). The effect of Plasmodium falciparum malaria on peripheral and placental HIV-1 RNA concentrations in pregnant Malawian women. AIDS, 18:1051–9.

  10. Mount AM, Mwapasa V, Elliott SR, Beeson JG, Tadesse E, Lema VM, Molyneux ME, Meshnick SR & Rogerson SJ (2004). Impairment of humoral immunity to Plasmodium falciparum malaria in pregnancy by HIV infection. Lancet, 363:1860–7.

  11. Beeson JG, Mann EJ, Elliott SR, Lema VM, Tadesse E, Molyneux ME, Brown GV & Rogerson SJ (2004). Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes and adhesion inhibitory antibodies are associated with placental malaria and have overlapping and distinct targets. J Infect Dis, 189: 540–51.

  12. Rogerson SJ, Mkundika P & Kanjala MK (2003). Diagnosis of Plasmodium falciparum malaria at delivery: A comparison of blood film preparation methods and of blood films with histology. J Clin Micro, 41:1370–4.

  13. Abrams ET, Brown HC, Chensue S, Turner GDH, Tadesse E, Lema VM, Molyneux ME, Rochford R, Meshnick SR & Rogerson SJ (2003). Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression. J Immunol, 170:2759–64.

  14. Rogerson SJ, Brown HC, Pollina E, Abrams ET, Tadesse E, Lema VM & Molyneux ME (2003). Placental tumor necrosis factor alpha but not interferon gamma is associated with placental malaria and low birth weight in Malawian women. Infect Immun, 71:267–70.

  15. Rogerson SJ, Pollina E, Getachew A, Tadesse E, Lema VM & Molyneux ME (2003). Placental monocyte infiltrates in response to Plasmodium falciparum malaria infection and their association with adverse pregnancy outcomes. Am J Trop Med Hyg, 68: 115–19.

  16. Beeson JG, Amin N, Kanjala M & Rogerson SJ (2002). Selective accumulation of mature asexual stages of Plasmodium falciparum-infected erythrocytes in the placenta. Infect Immun, 70: 5412–15.

  17. MacDonald SM, Bhisutthibhan J, Shapiro TA, Rogerson SJ, Taylor TE, Tembo M, Langdon JM & Meshnick SR (2001). Immune mimicry in malaria: Plasmodium falciparum secretes a functional histamine-releasing factor homolog in vitro and in vivo. Proc Natl Acad Sci USA, 98:10829–32.

  18. Rogerson SJ, Chaluluka E, Kanjala M, Mkundika P, Mhango CG & Molyneux ME (2000). Intermittent sulphadoxine-pyrimethamine in pregnancy: Effectiveness against malaria morbidity in Blantyre, Malawi 1997–1999. Trans Roy Soc Trop Med Hyg, 94:549–53.

  19. Rowe JA, Rogerson SJ, Raza A, Kazatchkine MD, Marsh K, Newbold CI & Miller LH (2000). Mapping of the region of complement receptor 1 (CR1) required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates. J Immunol, 165: 6341–6.

  20. Beeson JG, Rogerson SJ, Cooke BM, Reeder JC, Chai W, Lawson AM, Molyneux ME & Brown GV (2000). Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nature Medicine, 6:86–90.

Techniques

Links

top of page