Antimalarial drug resistance, artemisinin-based combination therapy, and the contribution of modeling to elucidating policy choices.

Increasing resistance of Plasmodium falciparum malaria to antimalarial drugs is posing a major threat to the global effort to "Roll Back Malaria". Chloroquine and sulfadoxine-pyrimethamine (SP) are being rendered increasingly ineffective, resulting in increasing morbidity, mortality, and economic and social costs. One strategy advocated for delaying the development of resistance to the remaining armory of effective drugs is the wide-scale deployment of artemisinin-based combination therapy. However, the cost of these combinations are higher than most of the currently used monotherapies and alternative non-artemisinin-based combinations. In addition, uncertainty about the actual impact in real-life settings has made them a controversial choice for first-line treatment. The difficulties in measuring the burden of drug resistance and predicting the impact of strategies aimed at its reduction are outlined, and a mathematical model is introduced that is being designed to address these issues and to clarify policy options.

[1]  J. Aron Malaria epidemiology and detectability. , 1982, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[2]  B. Sharp,et al.  Antifolate antimalarial resistance in southeast Africa: a population-based analysis , 2003, The Lancet.

[3]  J. Sachs,et al.  The economic and social burden of malaria , 2002, Nature.

[4]  A. Fleming,et al.  Cost-effectiveness of malaria control in sub-Saharan Africa , 1999, The Lancet.

[5]  A. Taylor-Robinson,et al.  A model of development of acquired immunity to malaria in humans living under endemic conditions. , 2002, Medical hypotheses.

[6]  S. McCombie Treatment seeking for malaria: a review of recent research. , 1996, Social science & medicine.

[7]  R. Snow,et al.  The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. , 2001, The American journal of tropical medicine and hygiene.

[8]  I. Hastings Modelling parasite drug resistance: lessons for management and control strategies , 2001, Tropical medicine & international health : TM & IH.

[9]  J. Botella de Maglia,et al.  [Prevention of malaria]. , 1999, Revista clinica espanola.

[10]  C. Dolecek,et al.  Dihydroartemisinin-piperaquine against multidrug-resistant Plasmodium falciparum malaria in Vietnam: randomised clinical trial , 2004, The Lancet.

[11]  Introduction. Antimalarial drug resistance: ramifications, explanations and challenges. , 2002, Microbes and infection.

[12]  N. White,et al.  The evolution of drug-resistant malaria: the role of drug elimination half-life. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[13]  N. White Why is it that antimalarial drug treatments do not always work? , 1998, Annals of tropical medicine and parasitology.

[14]  M. Gatton,et al.  Mutations in Cytochrome b Resulting in Atovaquone Resistance Are Associated with Loss of Fitness in Plasmodium falciparum , 2002, Antimicrobial Agents and Chemotherapy.

[15]  R. Price,et al.  Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. , 2000, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  B. Karoumi,et al.  Vitamin therapy and prevention of neural tube defects , 2001 .

[17]  Anne Mills,et al.  The economic impact of malaria in Africa: a critical review of the evidence. , 2003, Health policy.

[18]  R. Price,et al.  Effects of artemisinin derivatives on malaria transmissibility , 1996, The Lancet.

[19]  U. d’Alessandro,et al.  Modelling a predictable disaster: the rise and spread of drug-resistantmalaria. , 2000, Parasitology today.

[20]  R. Snow,et al.  The past, present and future of childhood malaria mortality in Africa. , 2001, Trends in parasitology.

[21]  F Reed Johnson,et al.  Modeling for health care and other policy decisions: uses, roles, and validity. , 2002, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[22]  O. Traoré,et al.  Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. , 2003, The American journal of tropical medicine and hygiene.

[23]  N. White,et al.  Antimalarial drug resistance and combination chemotherapy. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[24]  K. Marsh Malaria disaster in Africa , 1998, The Lancet.

[25]  R. Baltussen,et al.  Real world designs in economic evaluation. Bridging the gap between clinical research and policy-making. , 1999, PharmacoEconomics.

[26]  R. Snow,et al.  Estimating mortality, morbidity and disability due to malaria among Africa's non-pregnant population. , 1999, Bulletin of the World Health Organization.

[27]  M. Rauner,et al.  Using Simulation for AIDS Policy Modeling: Benefits for HIV/AIDS Prevention Policy Makers in Vienna, Austria , 2002, Health care management science.

[28]  A. Zwi,et al.  Viewpoint: Management of malaria – working with the private sector , 1999, Tropical medicine & international health : TM & IH.

[29]  K Dietz,et al.  A malaria model tested in the African savannah. , 1974, Bulletin of the World Health Organization.

[30]  A. Mills,et al.  Economic analysis of malaria control in Sub-Saharan Africa , 2000 .

[31]  E. Fèvre,et al.  Malaria-treatment policies: when and how should they be changed? , 1999, Annals of tropical medicine and parasitology.

[32]  P. Bloland,et al.  Chloroquine in Africa: critical assessment and recommendations for monitoring and evaluating chloroquine therapy efficacy in sub‐Saharan Africa , 1998, Tropical medicine & international health : TM & IH.

[33]  B. Singer,et al.  Modelling the development of resistance of Plasmodium falciparum to anti-malarial drugs. , 1991, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[34]  N. White,et al.  Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. , 1994, The Journal of infectious diseases.

[35]  G. Macdonald,et al.  The analysis of infection rates in diseases in which superinfection occurs. , 1950, Tropical diseases bulletin.

[36]  C. Ziba,et al.  Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine‐pyremethamine and other antimalarial drugs in Malawian children , 2001, Tropical medicine & international health : TM & IH.

[37]  W. Hawley,et al.  Longitudinal cohort study of the epidemiology of malaria infections in an area of intense malaria transmission II. Descriptive epidemiology of malaria infection and disease among children. , 1999, The American journal of tropical medicine and hygiene.

[38]  P. Rees Chloroquine resistant malaria. , 1984, East African medical journal.

[39]  J. Trape The public health impact of chloroquine resistance in Africa. , 2001, The American journal of tropical medicine and hygiene.

[40]  C. Curtis,et al.  A simple model of the build-up of resistance to mixtures of anti-malarial drugs. , 1986, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[41]  J. Baird Host age as a determinant of naturally acquired immunity to Plasmodium falciparum. , 1995, Parasitology today.

[42]  Richard N. Price,et al.  Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study , 2000, The Lancet.

[43]  R. Snow,et al.  Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence. , 2001, The American journal of tropical medicine and hygiene.

[44]  J. Breman,et al.  The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. , 2001, The American journal of tropical medicine and hygiene.

[45]  J. Breman,et al.  Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. , 2001, The American journal of tropical medicine and hygiene.

[46]  P. Bloland,et al.  Making malaria-treatment policy in the face of drug resistance. , 1999, Annals of tropical medicine and parasitology.

[47]  B. Karoumi,et al.  Monitoring antimalarial drug resistance within National Malaria Control Programmes: the EANMAT experience , 2001, Tropical medicine & international health : TM & IH.

[48]  A. Brennan,et al.  Modelling in health economic evaluation. What is its place? What is its value? , 2000, PharmacoEconomics.

[49]  P. Newton,et al.  Contribution of humoral immunity to the therapeutic response in falciparum malaria. , 2001, The American journal of tropical medicine and hygiene.

[50]  M. Lwin,et al.  Influence of blister packaging on the efficacy of artesunate + mefloquine over artesunate alone in community-based treatment of non-severe falciparum malaria in Myanmar. , 1998, Bulletin of the World Health Organization.

[51]  P. Olliaro,et al.  Averting a malaria disaster , 1999, The Lancet.

[52]  P. Bloland,et al.  Combination therapy for malaria in Africa: hype or hope? , 2000, Bulletin of the World Health Organization.

[53]  A. Buckling,et al.  The effect of partial host immunity on the transmission of malaria parasites , 2001, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[54]  C. Menéndez,et al.  The burden of malaria in pregnancy in malaria-endemic areas. , 2001, The American journal of tropical medicine and hygiene.

[55]  M. Enserink Malaria Researchers Wait for Industry to Join Fight , 2000, Science.

[56]  Joan L. Aron,et al.  Mathematical modelling of immunity to malaria , 1988 .

[57]  N. White The assessment of antimalarial drug efficacy. , 2002, Trends in parasitology.