Editorial [Hot Topic: New Drugs and Drug Targets for Human Diseases Caused by Apicomplexan Parasites (Guest Editor: Frank Seeber)]

This theme issue of CDT brings together a number of leading experts in the field of drug (target) discovery against human apicomplexan parasites and highlights major current concepts in this field. Although parasites of the phylum Apicomplexa (single-celled intracellular protozoa) are less well appreciated in public to cause potentially deadly and widespread infectious diseases (like AIDS or influenza), the recently published World malaria report draws a different picture [1]. It states that currently 3.2 billion people are affected by malaria worldwide, killing at least one million people a year, mostly children. Malaria is caused by several species of the apicomplexan parasite Plasmodium able to infect humans, with P. falciparum the most widespread but also the most dangerous species. The fight against malaria has been a top priority of the World Health Organization (WHO) already since its creation in 1948 [2]. In the 1950's there was strong hope that malaria could be eventually eradicated through the widespread use of chloroquine to kill the parasite and DTT to do the same with the Anopheles mosquitos (responsible for malaria transmission). Some malariologists even expressed their concerns that they might have nothing to do in the near future [3]. Now, more than 50 years later, there is no worry that scientists around the world working on malaria or other diseases caused by apicomplexan parasites would be without a job anytime soon. In 107 countries or territories individuals are at risk to contract the disease. In the last 25 years, the burden of malaria has mainly risen because of the general deterioration of primary health services in developing countries, the interruption of eradication measures or due to insecticide-resistant mosquitoes [1]. Moreover, HIV infection also increases the incidence of severe malaria in adults where both diseases are endemic [4]. However, the most important factor responsible for the current malaria situation is the ongoing development of drug resistance in the parasite population [5, 6]. The consequences are that cheap and effective drugs like chloroquine no longer work in most parts of the world. This is a vicious circle since more infected individuals lead to higher transmission rates. All this led to the launch of the Roll Back Malaria (RBM) initiative by WHO, the World Bank, UNICEF and the United Nations Development Program (UNDP) in 1998, with the aim to reduce the global malaria burden by halve by 2010. The time seems right to achieve this goal, since all three genomes of the players involved (Homo sapiens, Plasmodium and Anopheles) are known, and public awareness of the problem seems to have risen, positively affecting also private funding for research on malaria [7]. In addition, combination therapy with drugs having different targets is now a promising approach to treat malaria in areas with widespread resistance to monotherapy [6, 8]. The artemisinin-based combinations are the most promising ones. However, they are very expensive which almost prohibits their widespread use in endemic areas until the plant-derived compounds can be obtained in large amounts and at reasonable prices from precursor molecules [9]. This special issue of CDT is not only about Plasmodium and malaria, however. A number of other Apicomplexa are also important pathogens of humans and livestock. Toxoplasma gondii (causative agent of toxoplasmosis) and Cryptosporidium parvum (causative agent of cryptosporidiosis) are opportunistic pathogens of immunocompromised patients, especially with AIDS, and can lead to either fatal encephalomyelitis (T. gondii) or severe and chronic life-threatening gastroenteritis (C. parvum) if not treated [10, 11]. In addition, T. gondii is also a major cause of congenital infection leading to severe clinical symptoms. Although an acute infection with T. gondii in an immunocompetent person is usually mild and can be controlled by effective drugs if necessary, no proven therapy exists which would be able to eradicate the persistent form of the parasite. Therefore, all currently infected individuals (an estimated 30% worldwide) are at risk should they ever become immune suppressed in the future. In the case of C. parvum no satisfactory medication exists to date, although recent data suggest that highly active antiretroviral therapy (HAART) in HIV-infected individuals also leads to substantially reduced prevalence rates of C. parvum [12]. These and other data might give hints to novel therapies and drug targets [13, 14]. Again, the genomes of both organisms are now known.....