When are we going to celebrate the centenary of the discovery of efficient treatment for congenital toxoplasmosis?

In 2008, we have celebrated the centenary of the discovery of Toxoplasma gondii.Although this ubiquitous protozoan can generate devastating damage in foetuses and newborns, its treatment is the only field in which we have made little progress, despite a huge body of research, and has not yet been validated. Pregnant women who seroconvert are generally given spiramycine in order to reduce the risk of vertical transmission. However, to date, we have no evidence of the efficacy of this treatment because no randomized controlled trials have as yet been conducted. When foetal contamination is demonstrated, pyrimethamine, in association with sulfadoxine or sulfadiazine, is normally prescribed, but the effectiveness of this treatment remains to be shown. With regard to postnatal treatment, opinions vary considerably in terms of drugs, regimens and length of therapy. Similarly, we do not have clear evidence to support routine antibiotic treatment of acute ocular toxoplasmosis. We must be aware that pregnant women and newborns are currently being given empirically potentially toxic drugs that have no proven benefit. We must make progress in this field through well-designed collaborative studies and by drawing the attention of policy makers to this disastrous and unsustainable situation.

A new approach for potential drug target discovery through in silico metabolic pathway analysis using Trypanosoma cruzi genome information

The current drug options for the treatment of chronic Chagas disease have not been sufficient and high hopes have been placed on the use of genomic data from the human parasite Trypanosoma cruzi to identify new drug targets and develop appropriate treatments for both acute and chronic Chagas disease. However, the lack of a complete assembly of the genomic sequence and the presence of many predicted proteins with unknown or unsure functions has hampered our complete view of the parasite's metabolic pathways. Moreover, pinpointing new drug targets has proven to be more complex than anticipated and has revealed large holes in our understanding of metabolic pathways and their integrated regulation, not only for this parasite, but for many other similar pathogens. Using an in silicocomparative study on pathway annotation and searching for analogous and specific enzymes, we have been able to predict a considerable number of additional enzymatic functions in T. cruzi. Here we focus on the energetic pathways, such as glycolysis, the pentose phosphate shunt, the Krebs cycle and lipid metabolism. We point out many enzymes that are analogous to those of the human host, which could be potential new therapeutic targets.

Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery

Chagas disease originated millions of years ago as an enzootic infection of wild animals and began to be transmitted to humans as an anthropozoonosis when man invaded wild ecotopes. While evidence of human infection has been found in mummies up to 9,000 years old, endemic Chagas disease became established as a zoonosis only in the last 200-300 years, as triatomines adapted to domestic environments. It is estimated that 15-16 million people are infected with Trypanosoma cruzi in Latin America, and 75-90 million are exposed to infection. Control of Chagas disease must be undertaken by interrupting its transmission by vectors and blood transfusions, improving housing and areas surrounding dwellings, providing sanitation education for exposed populations and treating acute and recently infected chronic cases. These measures should be complemented by surveillance and primary, secondary and tertiary care.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

Platform for Plasmodium vivax vaccine discovery and development

Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development.

New approaches in antimalarial drug discovery and development: a review

Malaria remains a major world health problem following the emergence and spread of Plasmodium falciparum that is resistant to the majority of antimalarial drugs. This problem has since been aggravated by a decreased sensitivity of Plasmodium vivax to chloroquine. This review discusses strategies for evaluating the antimalarial activity of new compounds in vitro and in animal models ranging from conventional tests to the latest high-throughput screening technologies. Antimalarial discovery approaches include the following: the discovery of antimalarials from natural sources, chemical modifications of existing antimalarials, the development of hybrid compounds, testing of commercially available drugs that have been approved for human use for other diseases and molecular modelling using virtual screening technology and docking. Using these approaches, thousands of new drugs with known molecular specificity and active against P. falciparum have been selected. The inhibition of haemozoin formation in vitro, an indirect test that does not require P. falciparum cultures, has been described and this test is believed to improve antimalarial drug discovery. Clinical trials conducted with new funds from international agencies and the participation of several industries committed to the eradication of malaria should accelerate the discovery of drugs that are as effective as artemisinin derivatives, thus providing new hope for the control of malaria.

Drug discovery for Chagas disease should consider Trypanosoma cruzi strain diversity

This opinion piece presents an approach to standardisation of an important aspect of Chagas disease drug discovery and development: selecting Trypanosoma cruzi strains for in vitro screening. We discuss the rationale for strain selection representing T. cruzi diversity and provide recommendations on the preferred parasite stage for drug discovery, T. cruzi discrete typing units to include in the panel of strains and the number of strains/clones for primary screens and lead compounds. We also consider experimental approaches for in vitro drug assays. The Figure illustrates the current Chagas disease drug-discovery and development landscape.

A process for mining science & technology documents databases, illustrated for the case of "knowledge discovery and data mining"

This paper presents a process of mining research & development abstract databases to profile current status and to project potential developments for target technologies, The process is called "technology opportunities analysis." This article steps through the process using a sample data set of abstracts from the INSPEC database on the topic o "knowledge discovery and data mining." The paper offers a set of specific indicators suitable for mining such databases to understand innovation prospects. In illustrating the uses of such indicators, it offers some insights into the status of knowledge discovery research*.

What about Th1/Th2 in cutaneous leishmaniasis vaccine discovery?

The T helper cell type 1 (Th1) response is essential to resist leishmaniasis, whereas the Th2 response favors the disease. However, many leishmanial antigens, which stimulate a Th1 immune response during the disease or even after the disease is cured, have been shown to have no protective action. Paradoxically, antigens associated with an early Th2 response have been found to be highly protective if the Th1 response to them is generated before infection. Therefore, finding disease-associated Th2 antigens and inducing a Th1 immune response to them using defined vaccination protocols is an interesting unorthodox alternative approach to the discovery of a leishmania vaccine.