The World Health Organization estimates that yearly 300-500 million cases of malaria occur and more than 1 million people die of malaria. About 1,200 cases of malaria are diagnosed in the United States each year, most cases of them in immigrants and travelers returning from malaria-risk areas, mostly from sub-Saharan Africa and the Indian subcontinent. (WHO, 2000)
After World War II many countries tried to eradicate malaria by using the insecticide DDT to kill off the vector, draining stagnant water and using cheap and effective drugs like chloroquine. However, the disease was not eradicated completely, the support for massive eradication operations waned in 1970s, and the situation deteriorated. Drug resistant malaria has become one of the most important problems in malaria control in recent years. Resistance in vivo has been reported to all antimalarial drugs except artemisnin and its derivatives. (Bradley, 2001)
�Several mechanisms can account for changes in drug sensitivity in the malaria parasites, for example, physiological adaptations due to non genetic changes, selection of previously existing drug resistant cells from a mixed population under drug pressure, spontaneous mutation, mutation of extranuclear genes, or the existence of plasmid-like factors. (Bradley, 2001) The recent studies have proven that the chroroquine resistance in P. falciparum was due to a mutation in a single gene (NIH 2002), and the continued drug mediated elimination of intraspecific competition from the non resistant forms has allowed the resistant forms to attain numerical superiority - to the point that drugs such as chloroquine are officially considered useless.� (Bradley, 2001) One of the major factors is the incorrect use of prophylaxis and the use of subcurative doses of drugs, likely for economical reasons.
To illustrate the seriousness and the extent of the problem, in Southeast Asia, notably Cambodia, Myanmar and Thailand, P. falciparum infections do not respond to treatment with chloroquine or sulfadoxine�pyrimethamine, and sensitivity to quinine is reduced. Treatment failures in excess of 50% with mefloquine are also being reported. (WHO, 2000) In man, the problem of resistance to the common antimalarial drugs such as chloroquine and pyrimethamine, and the decreasing effectiveness of quinine is mainly limited to P.falciparum infection; chloroquine remains the treatment of choice for P.vivax. (Bradley, 2001)
Of the current antimalarials on the market, Primaquine is widely used for relapse prevention, but resistance arises rapidly in schizonts, though there is no evidence that gametocyte resistance exists, so stages of parasite development have to be monitored closely during primaquine treatment to prevent the resistance development. Resistance to sulfonamides have been recorded on all stages of parasite development. Resistance to proguanil and pyrimethamine has developed recently and is spreading rapidly, affecting all stages of parasite life cycle. Resistance to one of the oldest antimalarials, quinine, is stable and readily transmissible in many areas. While resistance to tetracycline antibiotics, such as doxycycline, has not been reported as a potential problem, these drugs cannot be used by themselves, as they only potentiate the effect of chloroquine. Resistance to recently developed artemisnin derivatives hasn�t been reported in the wild yet, but lab strains of P. falciparum with artemisnin resistance have arisen. (Bradley, 2001)
The common prophylactic drugs are, for many areas, obsolete and the use of advanced drugs such as artemisnin derivatives for uncontrolled prophylaxis would be downright irresponsible given the obvious ability of Plasmodium falciparum to attain a high degree of resistance in a short period. It has already been suggested that strains resistant to Artemisnins will appear by the end of the decade, and this does seem inevitable. (Bradley, 2001) The best way to limit the development and spread of drug resistance in Plasmodium species is to monitor drug resistance patterns in the area where malaria has been acquired to make the best choice of empiric therapy; test the parasite for susceptibility and change the therapy based on the lab results; closely monitor the patient for the stages of parasite development and for drug effectiveness.
http://www-micro.msb.le.ac.uk/224/Bradley/Bradley.html
Last accessed April 1, 2004
2. National Institute of Health News Release, October 2, 2002
http://www.nih.gov.library1.unmc.edu:2048/news/pr/oct2002/niaid-02.htm
Last accessed April 1, 2004
3. Virtual Naval Hospital, Navy Environmental Health Center, September 2000
http://www.vnh.org/Malaria/Malaria.html
Last accessed April 1, 2004
4. World Health Organization, 2004
http://www.who.int/ith/chapter07_04.html
Last accessed April 1, 2004
