Gogtay NJ

Bioline International

5J Postgrad Med March 2004 Vol 50 Issue 1 CMYK 5Editorial www.jpgmonline.comalaria is a major international public health problem, and the disease affects more than500 million people and causes 2-3 million deaths each year. Despite its already enormoustoll of suffering, deaths due to malaria are increasing as a consequence of drug resistance.1 Theglobal resurgence of malaria can be attributed to a variety of factors- insecticide resistance in theAnopheles mosquito, resistance of Plasmodium falciparum to affordable first line anti malarials,deterioration of national control programs and increased movement of populations secondary toincrease in international travel and tourism. South-east Asia as a region has been particularly hardhit by the development of parasites initially resistant to chloroquine, then to sulfadoxine-pyrimeth-amine, then to mefloquine and to a certain extent quinine.2 The Roll Back Malaria (RBM) cam-paign launched in 1998, with the stated goal to halve malaria deaths worldwide by 2010 is beingMalaria- hope on the horizonGogtay NJDepartment of ClinicalPharmacologySeth G. S. MedicalCollege and K. E. M.Hospital, Parel, Mumbai -400012, India.Correspondence:Nithya Gogtay, MDE-mail:nithyagogtay@gsmc.educonfounded by the problem of drug resistance.3 However, de-spite the grim scenario, there is reason to be optimistic.Considerable impetus to the management of malaria todayhas been given by the artemisinin (qinghaosu) derivatives firstisolated in 1971 by Chinese chemists. These drugs have a rapidonset of action, and resistance of Plasmodium falciparum tothese compounds has not yet been reported.4 An additionaladvantage is their ability to reduce gametocyte carriage andtherefore infectivity. The International Artemisinin study groupin a recent meta-analysis studied individual patients’ data(N=5948) from 16 randomized trials of acute, uncomplicatedPlasmodium falciparum malaria where artesunate had beenadded to the standard treatment. They showed that the addi-tion of 3 days of artesunate substantially reduced treatmentfailure, recrudescence and gametocyte carriage without an in-crease in serious adverse events. 5 The rationale for treatingmalaria with combination therapy is the same as for diseasessuch as AIDS, and tuberculosis where patients given two ormore robust and highly effective drugs are less likely to en-counter drug resistance and fail treatment which brings bothclinical and public health benefits. The advantages of theartemisinin combination treatments (ACT) makes it likely thatmany countries will now look at ACT as a viable treatmentoption.A parasite of perhaps equal importance is Plasmodium vivax,the causative agent of benign tertian malaria. Plasmodium vivaxhas the widest global distribution and is responsible for morethan 50% of malaria cases in Central and South America, Asiaand the Indian subcontinent.6 However, research into the biol-ogy and management of P vivax has been limited perhaps dueto greater emphasis on Plasmodium falciparum and also in partdue to the lack of a continuous in vitro culture system for theparasite. The clinical management of vivax malaria today hasassumed greater importance for two reasons- the emergenceof chloroquine resistant Plasmodium vivax and the decliningefficacy of primaquine as an anti-relapse agent.7-10  Althoughthe incidence of both remains low, the number of anti-relapsedrugs for vivax is limited. Of the 8-aminoquinolines, pri-maquine is likely to remain an important anti-relapse drug forsometime, but other drugs in this class such as tafenoquineand bulaquine hold promise as potential anti-relapse thera-pies.11,12Although challenges for the effective control and treatment ofmalaria are great, so are the current opportunities. Our under-standing of the biology of the malarial parasite is growing at arapid pace. A landmark in the fight against malaria was passedrecently with the publication of the complete genome sequenceof Plasmodium falciparum in combination with that of themalaria vector Anopheles gambiae.13,14 Analysis of the genomesequence data of the malarial parasite led to the identificationof the DOXP (1-deoxy-xylulose 5 phosphate) pathway, a path-way present in bacteria and plants but not in humans. A drugtargeting the pathway fosmidomycin originally developed forthe treatment for urinary tract infections has shown cure ratesof 88-89% in falciparum malaria after 4-5 days of treatment.15,16Aproject to sequence the complete genome of P vivax is inprogress and is expected to be completed shortly. It is hopedthat the vivax genome sequence will prove to be as valuable asthe Plasmodium falciparum genome sequence. 17 Considerableadvances have also been made in vaccine technology and im-munology. The rate of clinical assessment of candidate ma-laria vaccines is increasing; in the past 5 years, the number ofgroups doing such research has increased from three to 11.Worldwide, funding for malaria vaccines has increased recentlyfrom USD 50 million to around USD 60-70 million.18 How-ever, much remains to be accomplished. While the ACT isattractive, additional research into their comparisons with othercombinations, cost-effectiveness and the issue of safety in preg-nancy still need to be addressed. Traditionally, implementa-tion of national malaria policies is done by public health de-partments.2 However, it is important to remember that provi-M6 J Postgrad Med March 2004 Vol 50 Issue 16 CMYKGogtay: Malariasion of malaria care by private practitioners can be vastly dif-ferent and their involvement in policy making is crucial. Fi-nally, for a disease where millions of lives are at stake each year,the value of working in partnership at all levels, cannot be over-emphasized.References1. Breman JG, Egan A, Keusch GT. The intolerable burden of malaria-a new look atthe numbers. Am Jr Trop Med Hyg 2001;64:4-7i.2. Bloland PB, Ettling M. Making malaria-treatment policy in the face of drug resist-ance. Ann Trop Med Parasitol 1999;93:5-23.3. Nabarro DN, Taylor EM. The Roll Back Malaria Campaign. Science 1998;280:2067-8.4. Price RN , Nosten F. Drug resistant falciparum malaria: clinical consequences andstrategies for prevention. Drug Resist Updat 2001;4:187-96.5. International Artemisinin study group. Artesunate combinations for the treatmentof malaria: meta analysis. Lancet 2004;363:9-17.6. Mendis K, Sina BJ, Marchesini P, Carter R. The neglected burden of Plasmodiumvivax malaria. Am J Trop Med Hyg 2001;64:97-106.7. Garg M, Gopinathan N, Bodhe P, Kshirsagar NA. Vivax malaria resistant to chloro-quine: case reports from Bombay. Trans Roy Soc Trop Med Hyg 1995;89:656-57.8. Murphy GS, Purnomo HB, Andersen EM, Bangs MJ, Mount DL, Gorden J, et al.Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet1993;341:96-100.9. Smoak BL , Defraites RF, Magill AJ, Kain KC, Wellde BT. Plasmodium vivax infec-tions in US. Army troops: failure of primaquine to prevent relapse in studies fromSomalia. Am Jr Trop Med Hyg 1997;56:231-34.10. Gogtay NJ, Desai S, Kamtekar KD, Kadam VS, Dalvi SS, Kshirsagar NA. Efficaciesof 5- and 14-day primaquine regimens in the prevention of relapses in Plasmodiumvivax infections. Ann Trop Med Parasitol 1999;93:809-12.11. Walsh DS, Looaresuwan S, Wilairatana P, Hopner DG, Jr,Tnag DB, Brewer TG.Randomized dose ranging study of the safety and efficacy of WR 238605(tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.J Infect Dis 1999;180:1282-7.12. Dutta GP, P uri SK, Bhaduri AP, Seth M. Radical curative activity of a new 8-aminoquinoline derivative (CDRI 80/53) against Plasmodium cynomolgi B in mon-keys. Am Jr Trop med Hyg 1989;41:635-7.13. Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, et al. Genomesequence of the human malaria parasite Plasmodium falciparum. Nature2002;419:498-511.14. Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, et al.The genome sequence of the malaria mosquito Anopheles gambiae. Science2002;298:129-49.15. Pang T. Impact of pharmacogenomics on neglected diseases of the developingworld. Am J Pharmacogenomics 2003;3:393-98.16. Missinou MA, Borrmann S, Schindler A, Issifou S, Adegnika AA, Matsiegui PB, etal. Fosmidomycin for malaria. Lancet 2002;360:1941-2.17. Carlton J. The Plasmodium vivax genome sequencing project. Trends Parasitol2003;19:227-231.18. Moorthy VS, Good MF, Hill AVS. Malaria vaccine developments. Lancet 2004;363:150-6.AnnouncementNew Website for the journalThe Journal of Postgraduate Medicine is pleased to announce the launch of a new version of its website. The siteaddress would remain same [www.jpgmonline.com]. The features of the new site include:• Free full text availability of articles form 1980• Direct link to abstracts and full text from the cited references• Link from text of articles to various databases and search engines• Facility to submit comments on articles• Search across multiple journals• Email notifications on new issue release• Statistics of articles download and visits• Better user interface• New structure based on OpenURL, DC Metadata and other international standards

Malaria- hope on the horizon

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