The August 2014 issue [109(5)] of Memórias do Instituto Oswaldo Cruz is dedicated to advances in malaria research, with special attention directed toward vector control, epidemiology and the use of new technologies (e.g., proteomics and metabolomics) (Lacerda et al. 2014). This issue represents the fourth time that Memórias do Instituto Oswaldo Cruz has published a special malaria issue. When reviewing these special issues, we cannot avoid thinking of how the knowledge of malaria and related technology have changed since the first special issue was published in 1986. At that time, the technologies available for diagnosis and molecular epidemiological analysis were limited in scope and power. The heroic Sanger sequencing was being used then; however, it was entirely manual and dependent upon radioactive labelling and polyacrylamide gel electrophoresis, with an output of no more than one hundred bases per run. Likewise, Southern blotting (for DNA) and Northern blotting (for RNA) were among the workhorses of the typical molecular biology laboratory. The concept of high throughput at that time referred to the maximum number of graduate students, postdocs and technicians a laboratory could gather to work on a specific project. Polymerase chain reaction had just been invented (1985) and a few dozen labs were testing the potential of this technique, which was manually performed in reaction tubes, without a thermostable polymerase. Taq polymerase was not yet available; therefore, the Klenow fragment of the Escherichia coli DNA polymerase I was used instead to replicate DNA. The first machines were large and costly and real-time methods or fluorescent chemistry, such as those we routinely use today, were not available. Plasmodium spp resistance was already a concern of researchers, but the involvement of single nucleotide polymorphisms in key genes had not yet been recognised as a primary mechanism. In addition, the spread of resistance mutations in the population was unclear at that time and remains poorly understood. Randomised clinical trials of artemisinin-based combination therapy (ACT) were a “future objective” for malaria researchers and no synthetic routes to its complex chemical structure had been described. Despite the global movement of persons and goods, the frontiers for the Anopheles mosquito have remained unaltered and the real threat is the rapid resistance that Plasmodium populations develop immediately after a new therapeutic is deployed in the field.
These are the problems and challenges that malaria researchers have been facing thus far. However, what are the solutions? The malaria special issues that were published in Memórias do Instituto Oswaldo Cruz in 1986, 2007 and 2011 recount a history of not only intelligent analysis and questioning, but also failed expectations. Most of the proposed solutions or technical approaches to make malaria challenges more tractable (from both scientific and public health perspectives) have been hampered by the double complexity of Plasmodium-human interactions. Human population behaviour and biology might be viewed as a multi-agent system that is inherently unpredictable in terms of the interactions between these agents and these interactions become increasingly complex when a unicellular organism, such as Plasmodium, adds an additional layer after human exposure to the parasite. Instead of two single parameters on the right side of the parasitism equation, the entry of Plasmodium into the human body leads to a series of events that are the result of genome content asymmetry: three billion nucleotide bases for humans and one hundred million nucleotide bases for Plasmodium result in a series of biochemical reactions that ultimately leads to debilitation for one and survival and gene transmission for the other.
This amazing genome interaction mobilises multidisciplinary teams of biochemists, molecular biologists, parasitologists, immunologists, epidemiologists, chemists, policy makers, drug companies, non-governmental organisations, patients, activists and physicians. An impressive amount of brainpower is being deployed today to study and control the much smaller Plasmodium genome and the results are somewhat frustrating. Malaria is still a great burden in several developing countries and future prospects are not promising; no effective vaccine exists and there is a constant threat of resistance to the latest generation of drugs (e.g., ACT). Climate change provides new frontiers to Plasmodium species and their Anopheles vectors and poverty and economic issues limit the success of public health policies.
These facts remind us of the metaphoric words of Prof Leonard Jan Bruce-Chwatt that appeared in the first malaria issue in 1986: "Like Hydra, the monster of the Lernean marshes in Greek Argolis that had nine heads, malaria has not yet encountered its final Heraclean conqueror. Like Hydra, which grew two new heads as soon as one was cut off, malaria remains one of the main health problems of the developing tropical world”.
While we wait for scientific investigation to one day provide us with affordable solutions to the challenges of malaria, Memórias do Instituto Oswaldo Cruz opens its pages to record all of the milestones in this relatively recent evolutionary race between humans and Plasmodium species.
Adeilton Alves Brandão | Publisher Editor
Bruce-Chwatt LJ 1986. Malaria control at the cross-roads! Where do we go from here? Mem Inst Oswaldo Cruz 81(Suppl. II):1-4.
Lacerda MVG, Costa FTM, Lourenço-de-Oliveira R 2014. Malaria research in Brazil: we are doing well. Mem Inst Oswaldo Cruz 5: 515-516.