Round 2, 2022
- Hybrid genome assembly and annotation of Plasmodium vivax from the Asia-Pacific region
Paolo Bareng, Deakin University
- Determining the degree of infant exposure to primaquine through colostrum and transitional breast milk – opening the gateway to early postpartum radical cure to curb maternal Plasmodium vivax relapse
Dr Brioni Moore, Curtin University
- Predicting malaria transmissibility in a near elimination setting and identifying key drivers for malaria elimination
Dr Kinley Wangdi, Australian National University
- Genomic surveillance for emerging Plasmodium knowlesi malaria
Dr Jacob Westaway, Menzies School of Health Research
The long-term goal of our project is to develop a cost-effective genomic surveillance tool for Plasmodium knowlesi. This involves the in-silico development of a microhaplotype panel using an appropriately geographically diverse dataset of P. knowlesi whole genomes. With support from our regional partners in Indonesia, we have obtained an additional 59 P. knowlesi isolates from outside the geographic distribution of our current dataset. However, given the difficulties in collecting high quality field-isolates and in sequencing low-parasitemia samples, we plan to sequence a high-quality subset and are in the process of testing several methods that will improve parasite DNA yield. We plan to send isolates for whole genome sequencing by the end of 2023, with in-silico development of the microhaplotype panel to commence in early 2024.
Round 1, 2022
- Defining the antigenic diversity of Plasmodium vivax apical membrane antigen-1 to inform vaccine development
Dr Lee Yeoh, Burnet Institute
Since the project initiation, the team has successfully completed a comprehensive meta-population analysis of Plasmodium vivax AMA1 genetic diversity. Using whole genome sequences obtained from MalariaGen, we have identified AMA1 variants circulating in various populations and provided insights into the selection pressure in different AMA1 domains. These findings will be used to select and express alleles to measure antibody responses in different serum samples. This will enable us to develop an effective vaccine against the parasite diversity in high-burden countries.
- A statistical framework for identifying sufficient data to infer a total parasite biomass
Dr David Price, Doherty Institute, University of Melbourne
- Feasibility assessment of the use of Optical Mark Recognition around Vivax Malaria surveillance
Dr Mary Malai, Papua New Guinea Institute of Medical Research
With the seed funding provided by ACREME, data collected in this surveillance will be a valuable resource in helping ACREME researchers and other relevant stakeholders understand the current data surveillance methods and also identify areas that will need improving. As of October 2023, 9 qualitative interviews were conducted with a diverse range of stakeholders (including health facility staff, implementation managers and members of Provincial Health Authorities). We are currently analysing the data and hope to share the findings upon completion.
- Utilising community malaria volunteers to expand molecular and serological surveillance of malaria in pre-elimination settings
Dr Win Han Oo, Burnet Institute
Current tools widely available to diagnose malaria in the field miss the majority of cases due to a huge proportion of low-density, subclinical Plasmodium spp. infections in many malaria-endemic regions. Molecular and serological assays can determine residual malaria transmission missed through routine detection and can be performed using samples derived from used RDTs. Using seed funding provided by ACREME, we optimised procedures for molecular and serological detection of malaria in laboratory and field-performed RDT. Protocols will be transferred to in-country partners to determine their feasibility and utility in pre-elimination settings to detect residual malaria transmission.
- Web-based interactive tool to improve decision-making for malaria elimination in Vietnam
Dr Yalemzewod Gelaw, Curtin University and Telethon Kids Institute
We employed the network diffusion model to estimate the transmission risk, represented by the case reproduction number (𝑅𝑐), for both P. falciparum and P. vivax in Vietnam. The dynamics of transmission for these parasites exhibited variations between 2019 and 2022. Specifically, P. falciparum transmission displayed a seasonal pattern, with forest cases playing a significant role in driving this seasonality. Geographically, transmission of both P. falciparum and P. vivax was clustered in the central and Northwest regions and showed a decreasing trend over time. Since the start of 2020, the fraction of total cases that were imported was much lower than those that were indigenous. The spikes in observed cases during this time can be attributed to indigenous cases.
- Collection of cells to isolate monoclonal antibodies to placental malaria antigens
Dr Elizabeth Aitken, Doherty Institute, University of Melbourne
Using funding from the seed grant and in collaboration with researchers at the PNG IMR we identified women in the Madang region who were likely to have B-cells which make anti-VAR2CSA antibodies and then collected cells from 11 of these women. These samples should be sufficient to make monoclonal antibodies to placental binding parasite antigen VAR2SCA which is responsible for placental malaria. Further funding to continue the work from this seed grant has been acquired via a NHMRC Idea’s grant scheme and we will be making monoclonal antibodies to VAR2CSA and then characterising them in the coming months. We aim to find functional monoclonal antibodies that recognise heterologous parasite strains as they can assist in vaccine design and be potential therapeutics against placental malaria.
Round 2, 2021
- MinION sequencing for rapid detection of imported P. vivax cases
Dr Mariana Kleinecke, Menzies School of Health Research
We have successfully established a 33 SNP short amplicon assay on the MinION to rapidly determine the country of origin in P.vivax infections. We are currently validating the assay on a diverse sample set from a range of malaria endemic sites with the plan of completion by the end of the year.
- Estimating disease prevalence in a sentinel site catchment population to complement case-based surveillance and develop decision-making tools
Dr Diana Timbi, Papua New Guinea Institute of Medical Research
Estimating disease prevalence in a sentinel site catchment population to complement case-based surveillance and develop decision-making tools’ will start in July 2023. Staff recruitment begins in July and training of the new staff in August. Data collection will begin in September and end in mid-October.
- Characterizing the longitudinal immune response to salivary antigens of Southeast Asian mosquito vectors of malaria, with a human challenge model
Ms Ellen Kearney, Burnet Institute, Melbourne School of Population and Global Health
Using samples collected as part of a world-first human challenge trial of controlled exposure to mosquito bites, we have measured antibodies against proteins from the saliva-dominant vectors of malaria in the Greater Mekong Subregion and quantified the changes over time in response to mosquito biting exposure. We determined that antibody levels against all salivary proteins decayed overall but were boosted with and following biting exposure. These findings provide evidence of a causal relationship between biting exposure and antibodies against salivary antigens and highlight a role for these antibodies to serve as species-specific biomarkers of exposure to mosquito bites in Southeast Asia. This salivary antibody approach may help to overcome the sensitivity and feasibility limitations of traditional entomological methods to measure mosquito biting exposure.
- Understanding cross-reactive antibodies in children without documented exposure to malaria
Dr Rhea Longley, Walter and Eliza Hall Institute of Medical Research
- Artificial Intelligence-based drug resistance screening of malaria parasites using ‘Read Until’
Dr Kirsty McCann, Deakin University
- Methodological comparison of P. vivax genotyping approaches for molecular surveillance within the ACREME network
Dr Caitlin Bourke, Walter and Eliza Hall Institute of Medical Research
- Identification of antibody targets and mechanisms associated with duration and spontaneous clearance of subclinical Plasmodium vivax infection
Dr Katherine O’Flaherty, Burnet Institute
In this study, we sought to identify the specific antibody targets and mechanisms associated with the clearance of P. vivax parasites. Using novel bead-based immunological assays, specific targets anti-P. vivax IgG antibodies were determined in a unique cohort of participants residing in malaria-endemic regions of Cambodia and Laos with rich follow-up data and ultra-sensitive detection of P. vivax infection with defined parasite clearance end points. Using this data, we will identify and prioritise targets of combinations thereof, to investigate the role of antibody function associated with antibody-mediated clearance of P. vivax parasitemia and quantify their effect on the duration and clearance of P. vivax infection. Findings from this research will further our understanding of the acquired immune response to P. vivax and deepen our understanding of the role of acquired immunity in the maintenance and clearance of P. vivax infection, and will inform novel vaccine candidates and strategies.
Round 1, 2021
- Spatial imaging and transcriptomic analysis of immune cells and malaria parasites in Plasmodium-infected human spleens
Dr Steven Kho, Menzies School of Health Research
Using the ACREME seed grant, we have established a framework for multiplex spatial profiling of immune cells in human splenic tissue. Analytical pipelines are now being established and optimization of further multiplex panels is underway to enable spatial profiling of all major cell types, their activation status, and their interactions with malaria parasites. We have also identified important steps in the preparation and storage of spleen samples for high-quality downstream spatial transcriptomics studies. Together, these frameworks will be applied to spleen samples from a unique cohort of splenectomy patients with current and past malaria infections in Indonesia, to understand a) how malaria parasites and host immune cells co-exist in the splenic environment, b) the mechanisms of malaria immunity, and c) how parasites have adapted to survive and replicate in splenic tissue.
- Assessing the early development of functional antibody responses and target antigens in controlled human malaria infection to inform vaccine development
Dr Linda Reiling, Burnet Institute
We have used serum samples from a Controlled Human Malaria Infection (CHMI) trial to assess the immunogenicity and antigenicity of a panel of merozoite antigens in malaria infections of naïve adults. We found that the magnitude of antibody responses against different antigens varied and followed different kinetics. Amongst the most reactive antigens were leading malaria vaccine targets and targets that had been associated with protective antibody responses previously. The results so far give us important insights into the development of antibody responses in malaria-naïve participants, and the boosting effect of vaccine-induced antibody responses by natural infection. We will extend our study to assess functional antibody responses such as complement fixation and FcR interactions in this cohort. This study will help to characterize efficacious antibody responses after first malaria infection.
- Investigating asymptomatic transmission of malaria parasites in the Madang province of Papua New Guinea
Dr Lincoln Timinao, Papua New Guinea Institute of Medical Research and Burnet Institute
Several studies have identified asymptomatic individuals with submicroscopic levels of parasitemia but to date there has been no study confirming the proportion of asymptomatic infections that can potentially contribute to ongoing malaria transmission in Papua New Guinea (PNG). In this study we exposed asymptomatic individuals from a village along the north coast in the Madang province of PNG to lab-reared Anopheles farauti mosquitoes. Our aim was to investigate the proportion of asymptomatic individuals that can potentially transmit malaria parasites to mosquitoes. Our findings reveal that 31% (83/269) of the individuals screened were diagnosed as having malaria infection by either, the malaria rapid diagnostic test or by qPCR. Among these infected individuals, 57% (47/83) were asymptomatic carriers. Among the asymptomatic individuals who agreed to participate in the mosquito feeding experiments, only 5% (2/40) were able to successfully transmit Plasmodium vivax parasites to our lab-reared mosquitoes. These results highlight the need for further investigation, as these cases remain untreated, contribute to the malaria reservoir and perpetuate ongoing transmission within the community.
Round 1, 2020
- Validating molecular and serological tools for detecting hidden reservoirs of Plasmodium infections in Papua New Guinea
Dr Fiona Angrisano, Burnet Institute
In this study, we sought to identify novel screening tools that are superior to standard diagnostics tools for detecting foci of ongoing malaria transmission. Serological indicators of recent exposure to P. falciparum and P. vivax were compared to ultra-sensitive qPCR (usqPCR) parasite prevalence indicator for surveillance using samples from a 2013 East Sepik Province longitudinal child cohort. Using this data, we will discover the best combination of screening tools to identify ‘hidden’ reservoirs of and develop evidence-based surveillance strategies to take forward into novel implementation trials. Understanding the usefulness of these new strategies is critical if we are to transform surveillance as an intervention that accelerates malaria elimination.
- Investigating antibody responses to mosquito salivary antigens across the Asia Pacific to advance novel malaria surveillance strategies
Dr Julia Cutts, Burnet Institute
Developing new tools, such as antibody markers of malaria and vector exposure,is important for identifying communities where malaria is being transmitted, to enable rapid deployment of resources, such as vector control interventions. Archival human sera collected by ACREME investigators across seven malaria endemic sites in the Asia-Pacific and Africa were screened for antibodies specific to novel salivary gland antigens of known dominant vectors. Findings suggest region-specific Anopheles serological markers could be used as a tool to monitor vector exposure and augment current malaria surveillance strategies.
- Understanding the role of polymorphisms in vaccine escape to guide malaria vaccine development and implementation
Dr Liriye Kurtovic, Burnet Institute
- Optimal geospatial design of malaria surveillance programs
Dr Freya Shearer, University of Melbourne
- Serological exposure markers for P. vivax in pregnant women
Dr Holger Unger, Menzies School of Health Research
- Characterizing antibody responses to PfEMP1 as biomarkers of severe and uncomplicated malaria in Papua New Guinea
Dr Isobel Walker, University of Melbourne
Round 2, 2019
- How best can we detect the hidden splenic parasite biomass in human Plasmodium infection? Part 1: peripheral blood
Dr Steven Kho, Menzies School of Health Research
- Age-dependent diversity of innate immune responses in malaria
Dr Jessica Loughland, QIMR Berghofer Medical Research Institute
- Use of proteomics as a platform for evaluating new biomarkers for improving diagnosis of Plasmodium vivax for the purpose of malaria elimination
Dr Sumudu Britton, QIMR Berghofer Medical Research Institute
- Investigating the transmissibility of artemisinin-resistant P. falciparum and the effect of artesunate on gametocyte production
Dr Zuleima Pava, QIMR Berghofer Medical Research Institute
Round 1, 2019
- Field evaluation of a Point-of-Contact device for P. falciparum malaria serosurveillance
Dr Aung Pyae Phyo, Burnet Institute
- Functional human antibodies that target P. falciparum gametocytes to reduce malaria transmission
Dr Jo-Anne Chan, Burnet Institute
- The impact of a malaria infection on G6PD activity (MAGY)
Dr Benedikt Ley, Menzies School of Health Research
- Building capacity for an innovative amplicon deep sequencing tool to genotype Plasmodium infections for improved surveillance
Dr Shazia Ruybal Pesántez, Walter and Eliza Hall Institute of Medical Research
- Development of a high-sensitivity reader for improving use of malaria RDTs
Dr Leanna Surrao, Burnet Institute
Round 2, 2018
- Enhanced geospatial surveillance for identifying malaria transmission hotspots using antenatal screening in PNG
Dr Ricardo Ataide, Burnet Institute
- Development of a novel mouse model of artemisinin-resistant malaria to screen and prioritize antimalarial drugs effective against artemisinin-resistant parasites
Dr Maria Rebelo, QIMR Berghofer Medical Research Institute
- Paving the way for universal radical cure
Dr Kamala Thriemer, Menzies School of Health Research
Round 1, 2018
- The cost-effectiveness of molecular epidemiology to inform malaria control program decision-making: a scoping exercise.
Dr Angela Devine, Burnet Institute
A big question is how much it costs to do molecular epidemiology for malaria. Our seed grant funded the collection of this cost data in Papua New Guinea, setting up a new collaboration and providing the data needed to write a report for decision makers. We leveraged this work to successfully apply for a larger seed grant that will collect further cost data in Indonesia. We are currently collecting that cost data and writing a manuscript that includes costs from both countries, enabling comparisons. We hope that this will enable us to secure larger grant funding to do a cost-effectiveness analysis.
- Understanding RTS,S immunity to inform vaccine implementation and design an improved pre-erythrocyte stage vaccine to facilitate malaria elimination
Dr Gaoqian Feng, Burnet Institute
- Novel serological markers for surveillance of both P. vivax malaria exposure and immunity
Dr Rhea Longley, Walter and Eliza Hall Institute of Medical Research
- Developing a multiscale model combining both within-host and population level information to predict the emergence and spread of antimalarial resistance
Dr Pengxing Cao, University of Melbourne