Molecular approaches to malaria: MAM 2004 and beyond

This special issue of Trends in Parasitology comprises a collection of timely reviews arising from the 2nd Molecular Approaches to Malaria meeting held 1-5 February 2004 in Lorne, Australia, four years after the successful inaugural meeting. As the name suggests, Molecular Approaches to Malaria focused on the latest molecular developments in malaria research, and their biological and clinical implications. By no means is this special issue intended to represent a comprehensive recapitulation of all of the presentations at the meeting. Rather, the articles address, in more general terms, recent advances on broader themes that were prominent at Molecular Approaches to Malaria meeting 2004.     

Variant surface antigens, virulence genes and the pathogenesis of malaria

The first Molecular Approaches to Malaria meeting was held 2-5 February 2000 in Lorne, Australia. Following the meeting, Brian Cooke, Mats Wahlgren and Ross Coppel predicted that research into the molecular details of the mechanisms behind sequestration of parasitized erythrocytes would "become increasingly more complicated, with further interactions, receptors, ligands and functional domains". Furthermore, they cautioned that "the challenge will be not to lose ourselves in the molecular detail, but remain focused on the role of [the var genes and other multigene families] in pathogenesis of malaria". We contemplate on these statements, following the recent second Molecular Approaches to Malaria meeting, which was held at the same venue on 2-5 February 2004.     

Malaria vaccines: if at first you don't succeed..

The Roll Back Malaria campaign vowed to halve the global burden of malaria in ten years but, midway into that campaign, few new malaria control tools have been introduced, and many established methods appear to be failing with effective chemotherapy being perhaps the most problematic. It has been repeatedly argued that the discovery and implementation of a safe and effective vaccine against malaria is a major priority in the control of the disease. Indeed, many malaria control experts believe that sustainable reductions in malaria control will be nigh on impossible in the absence of such a vaccine. While most would agree that we are still some way from being able to introduce a vaccine, steady progress is being made. We review here some new approaches and developments in vaccine research that were discussed at the Molecular Approaches to Malaria conference held 1-5 February 2004 in Lorne, Australia.     

Molecular approaches to malaria: seeking the whole picture

This year, Australia hosted its first major international conference on malaria - Molecular Approaches to Malaria in Lorne, Victoria, 2-5 February 2000 (MAM2000). The worldwide research effort toward a better understanding of the pathogenesis and control of malaria in the post-genomic era was discussed and debated by over 250 researchers from 18 countries during four days packed with molecular biology, cell biology, genomics, vaccines and pathogenic mechanisms. This special malaria edition of Parasitology Today is an attempt to capture and summarize the quality and breadth of work presented at the conference and place this in the context of the current global malaria research effort; eight of the nine Reviews in this issue have been written by session chairs or presenters at MAM2000.     

Molecular approaches to malaria: on the way to integration

A report on the Molecular Approaches to Malaria meeting, Lome, Australia, 4-8 February 2004.     

Malaria parasite transmission stages: an update

The Molecular Approaches to Malaria 2004 meeting provided an opportunity to see the impressive progress in all research fields and in the four years since the previous Molecular Approaches to Malaria meeting, when much of the Plasmodium falciparum genome sequence was already available. Study of the part of the Plasmodium life cycle associated with transmission through the vector, which begins with the commitment of blood-stage forms to sexual development, has been especially fruitful. This success is a result of several reasons including: (i) the availability of the genome sequence; (ii) the availability of good animal models that allow parasite culture and facile in vivo studies of many of the life cycle stages involved in transmission; (iii) the availability of genetic manipulation technologies for the animal models of malaria, as well as P. falciparum; and (iv) the ability to study lethal gene knockouts at this stage of the life cycle.     

Antimalarial drug development and new targets

The Molecular Approaches to Malaria (MAM2000) conference, Lorne, Australia, 2-5 February 2000, brought together world-class malaria research scientists. The development of new tools and technologies - transfection, DNA microarrays and proteomic analysis - and the availability of DNA sequences generated by the Malaria Genome Project, along with more classic approaches, have facilitated the identification of novel drug targets, the development of new antimalarials and the generation of a deeper understanding of the molecular mechanism(s) of drug resistance in malaria. It is hoped that combinations of these technologies could lead to strategies that enable the development of effective, efficient and affordable new drugs to overcome drug-resistant malaria, as discussed at MAM2000 and outlined here by Ian Macreadie and colleagues.     

Comparative evolutionary genomics of human malaria parasites

The parasites Plasmodium falciparum and Plasmodium vivax are responsible for the majority of human malaria cases worldwide. Despite many similarities in their biology, they frequently are studied in isolation. With the completion of the P. vivax genome and the generation of an initial P. falciparum genetic diversity map, attempts are being made to infer inter- and intra-species genome evolution. Here, we briefly review our current knowledge of comparative evolutionary genomics of the two species in the light of several presentations at the Molecular Approaches to Malaria 2008 meeting in Lorne, Australia and ask the question: can evolutionary genomics of one species inform the other?     

Recent highlights in antimalarial drug resistance and chemotherapy research

This review summarizes recent investigations into antimalarial drug resistance and chemotherapy, including reports of some of the many exciting talks and posters on this topic that were presented at the third Molecular Approaches to Malaria meeting held in Lorne, Australia, in February 2008 (MAM 2008). After surveying this area of research, we focus on two important questions: what is the molecular contribution of pfcrt to chloroquine resistance, and what is the mechanism of action of artemisinin? We conclude with thoughts about the current state of antimalarial chemotherapy and priorities moving forward.     

Malaria vaccines

Although the possibility of a live attenuated malaria vaccine has been considered, current malaria vaccine development activities are dominated by attempts to develop a subunit vaccine. Hence, it is entirely appropriate that a session of the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, was devoted to vaccine development. The oral presentations in this session and the relevant poster presentations are outlined here by Robin Anders and Allan Saul.     

Molecular approaches to epidemiology and clinical aspects of malaria

Malaria is a problem of global importance, responsible for 1-2 million deaths per year, mainly in African children, as well as considerable morbidity manifested as severe anaemia and encephalopathy in young children. Fundamental to the development of new tools for malaria control in humans is an increased understanding of key features of malaria infection, such as the diversity of outcome in different individuals, the understanding of different manifestations of the disease and of the mechanisms of immunity that allow clinical protection in the face of ongoing low-grade infection (concomitant immunity or premunition). Here, Graham Brown and colleagues review some of the ways in which molecular approaches might be used to increase our understanding of the epidemiology and clinical manifestations of malaria, as discussed at the Molecular Approaches to Malaria conference (MAM2000), Lorne, Australia, 2-5 February 2000.     

Pathogenesis of malaria

As the mortality rate of 20-30% for severe falciparum malaria under even the best clinical conditions testifies, access to antimalarial drugs is not sufficient to prevent an appreciable mortality from this disease. Understanding the cause of death at a cellular level is essential if additional rational treatments are to be developed. Here, Ian Clark and Louis Schofield discuss recent work presented at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, that updates the cytokine-based concept of malarial disease.     

Host cell invasion by malaria parasites

The complex life cycle of the malaria parasite includes three specialized invasive stages, distinct both in terms of their cellular architecture and in their choice of target host cell. Despite the dissimilarities between these forms, there are clear parallels in the manner by which they enter their respective host cells. Advances in the area of erythrocyte invasion by the malaria merozoite, outlined here by Chetan Chitnis and Mike Blackman and discussed at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000, will undoubtedly impact on our understanding of mechanisms of cell entry by the other invasive forms. Similarly, recent progress in dissecting the functional role of surface proteins expressed by sporozoite and ookinete stages has provided fascinating insights into general aspects of invasion by all invasive stages of apicomplexan parasites.     

Malaria and urbanization in sub-Saharan Africa

There are already 40 cities in Africa with over 1 million inhabitants and the United Nations Environmental Programme estimates that by 2025 over 800 million people will live in urban areas. Recognizing that malaria control can improve the health of the vulnerable and remove a major obstacle to their economic development, the Malaria Knowledge Programme of the Liverpool School of Tropical Medicine and the Systemwide Initiative on Malaria and Agriculture convened a multi-sectoral technical consultation on urban malaria in Pretoria, South Africa from 2nd to 4th December, 2004. The aim of the meeting was to identify strategies for the assessment and control of urban malaria. This commentary reflects the discussions held during the meeting and aims to inform researchers and policy makers of the potential for containing and reversing the emerging problem of urban malaria.     

Traffic jams: protein transport in Plasmodium falciparum

Protein targeting in malaria parasites is a complex process, involving several cellular compartments that distinguish these cells from more familiar systems, such as yeast or mammals. At least a dozen distinct protein destinations are known. The best studied of these is the vestigial chloroplast (the apicoplast), but new tools promise rapid progress in understanding how Plasmodium falciparum and related apicomplexan parasites traffic proteins to their invasion-related organelles, and how they modify the host by trafficking proteins into its cytoplasm and plasma membrane. Here, Giel van Dooren and colleagues discuss recent insights into protein targeting via the secretory pathway in this fascinating and important system. This topic emerged as a major theme at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000.     

Helminth-infected patients with malaria: a low profile transmission hub?

The scale-up of malaria control efforts in recent years, coupled with major investments in malaria research, has produced impressive public health impact in a number of countries and has led to the development of new tools and strategies aimed at further consolidating malaria control goals. As a result, there is a growing need for the malaria policy setting process to rapidly review increasing amounts of evidence. The World Health Organization Global Malaria Programme, in keeping with its mandate to set evidence-informed policies for malaria control, has convened the Malaria Policy Advisory Committee as a mechanism to increase the timeliness, transparency, independence and relevance of its recommendations to World Health Organization member states in relation to malaria control and elimination. The Malaria Policy Advisory Committee, composed of 15 world-renowned malaria experts, will meet in full twice a year, with the inaugural meeting scheduled for 31 January to 2 February 2012 in Geneva. Policy recommendations, and the evidence to support them, will be published within two months of every meeting as part of an open access Malaria Journal thematic series. This article is a prelude to that series and provides the global malaria community with the background and overview of the Committee and its terms of reference.     

Focus on Plasmodium vivax

In Bangkok, Thailand, 3-8 February 2002, the Multilateral Initiative on Malaria convened the first malaria conference, Vivax Malaria Research: 2002 and Beyond, devoted entirely to Plasmodium vivax research.     

Molecular approaches to malaria

Malaria is a serious health problem in developing countries. With the complete sequencing of the genomes of the parasite and of the mosquito vector, malaria research has entered the post-genome era. In this report we summarize the results and new research avenues presented at a recent meeting held with the aim of developing interdisciplinary approaches to combat this disease.     

Protein kinases of malaria parasites: an update

Protein kinases (PKs) play crucial roles in the control of proliferation and differentiation in eukaryotic cells. Research on protein phosphorylation has expanded tremendously in the past few years, in part as a consequence of the realization that PKs represent attractive drug targets in a variety of diseases. Activity in Plasmodium PK research has followed this trend, and several reports on various aspects of this subject were delivered at the Molecular Approaches to Malaria 2008 meeting (MAM2008), a sharp increase from the previous meeting. Here, the authors of most of these communications join to propose an integrated update of the development of the rapidly expanding field of Plasmodium kinomics.     

Parasites are GO

The Malaria Genome Sequencing Consortium Meeting was held on 5–6 June 2001 in Cambridge, UK, and was followed by a workshop discussing the generation of new parasite-specific gene ontology (GO) terms. Present at the meeting, which focused primarily on malaria, were representatives from the research community, the sequencing centres, including the Sanger Centre (Cambridge, UK) and The Institute for Genome Research (TIGR; Rockville, MD, USA), the European Bioinformatics Institute (EBI; Cambridge, UK), Plasmo DB and the GO consortium (Cambridge, UK).