New Treatments for Malaria: Whats all the fuss about

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New Treatments for Malaria Whats all the fuss
about?
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Malaria Treatment - Overview

• Goal prevent mortality and reduce morbidity
  through prompt therapy with a safe and effective
  drug
• Traditionally, treatment for malaria has
  consisted of single drug therapy, e.g., quinine,
  chloroquine, amodiaquine, (sulfadoxine-pyrimethami
  ne SP)

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• Antimalarial Resistance, 2003
• South America and Southeast Asia

CQ, SP
CQ, SP, Mefloquine, Quinine
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• Intensification of Chloroquine
• Resistance in Africa (1980-2003)

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Current Status of Malaria Therapy

• Spread and intensification of resistance
• Limited number of efficacious antimalarial drugs
  still available
• Very few new drugs in the pipeline
• Cost of discovering and bringing new antimalarial
  drug to market US500 million 10-12 years
• Little economic incentive for investment in new
  drug discovery and development - malaria affects
  worlds poorest nations

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Response to Spread of Drug Resistance

• Critically important that we use drugs that are
  currently available in rational fashion to
• achieve maximum impact on malaria
  morbidity/mortality
• prolong their useful therapeutic lifetimes
• WHO has recommended that countries experiencing
  resistance to current first-line single drug
  therapy change to combination therapy
• Preferred combination therapy regimens consist of
  artemisinin drug plus a second drug, i.e.,
  artemisinin-based combination therapy, or ACT

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USAID Position on Malaria Therapy

• USAID strongly supports WHO position on change to
  ACT and has been instrumental in laying
  groundwork for implementation of ACT
• assessing drug efficacy
• evaluating new combination therapy regimens
• preparing for widespread implementation

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Rationale for Combination Therapy for Malaria

• Similar to the treatment of tuberculosis, cancer,
  HIV
• Objective Prevent the selection of mutations
  conferring drug resistance by the simultaneous
  use of two or more antimalarial drugs with
  different modes of action
• Probability of encountering parasites with
  mutations conferring resistance to both drugs is
  significantly lower than one with resistance to a
  single drug

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Artemisinin-based Combination Therapy (ACT)

• Artemisinin natural product used in China for
  gt1000 years for fever treatment
• Artemisinin and its derivatives most
  efficacious of all known antimalarial drugs
  against P. falciparum
• rapid reduction of parasite density and symptoms
• may reduce/interrupt transmission
• Less susceptible to development of resistance
• Relatively inexpensive
• Few side effects

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ACT - Advantages

• Reduce the possibility of selecting resistant
  parasites
• Protect both components from development of
  resistance and prolongs their useful therapeutic
  lifetimes
• Produce a very rapid reduction of parasite
  density in the blood and malaria symptoms
• Have potential for reducing transmission

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Combination Therapy Options Recommended by WHO

• ACT
• Artemether-lumefantrine (Coartem)
• Amodiaquine-artesunate
• SP-artesunate (areas where SP efficacy high)
• Mefloquine-artesunate (not for high transmission
  areas, e.g., Africa)
• Others
• SP-amodiaquine (areas where both SP and AQ
  efficacy high)

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Potential Obstacles to the Introduction of ACT

• Cost ACT costs 10 times more than CQ or SP
• Demand may well outstrip supply for next several
  years
• Impact of these problems has been greater in
  Africa than in Asia or the Americas

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What is process of change to ACT in Africa?

• Ideally, MOH would move directly from CQ (or
  existing first-line drug) to ACT
• Realistically, likely to be a 2-step process
• Stop using CQ (or existing first-line drug) and
  change to a more efficacious interim treatment
  regimen while preparations for implementation of
  ACT are being made
• Change in national treatment policy to ACT and
  then implement that new policy

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Interim Malaria Treatment Regimens

• Dont have to be 100 efficacious
• Dont have to be combination therapies
• Aim is to rapidly replace CQ with a more
  efficacious drug until ACT can be implemented
• SP
• AQ
• SP CQ or SP AQ

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Preparation for Implementation of ACT

• In vivo drug efficacy studies of candidate ACT
  regimens using standardized WHO protocol
• Consensus meeting to review drug resistance
  in-country, discuss results of ACT studies,
  experiences from other countries with malaria
  treatment policy and ACT
• Recommendation to change policy to ACT
• Official approval of policy change by Minister of
  Health

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Challenges of Implementing ACT

• Improve recognition of symptoms of malaria and
  treatment-seeking behavior at household level
• Improve case management in health facilities
• Improve ability of caretakers to follow treatment
  guidelines
• Develop effective strategies for delivering
  treatment to vulnerable groups
• Establish routine monitoring of drug efficacy

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Challenges of Implementing ACTProcurement

• Supply limited number of sources of artemisinin
  drugs availability of those drugs
• Drug quality counterfeit and sub-standard drugs
  - drug assays and prequalification
• Presentation and packaging for the more
  complicated treatment regimens
• Increased cost of new treatment regimens -
  financing

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Challenges of Implementing ACTDistribution

• Distribution within public sector
• Role of private vendors
• Home-based management

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Preparing the Way for More Widespread Use of ACT

• Support to IOM Expert Committee on Economics of
  Antimalarial Drugs to address issues of financing
• Activities related to improved implementation of
  IMCI
• Development and field testing of improved malaria
  diagnostics rapid diagnostic tests
• Evaluation of different approaches to home-based
  treatment of malaria

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Discovery and Development of New Antimalarial
Drugs

• USAID has supported drug development through
  WHO-TDR for several years
• USAID support to the Medicines for Malaria
  Venture
• Non-profit, public-private partnership that
  manages large RD portfolio of 22 candidate
  malaria drugs
• Goal is registration of at least one new and
  affordable antimalarial drug every 5 years

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Future Options for Malaria Therapy

• Piperaquine plus dihydroartemisinin
• Chlorproguanil-dapsone plus artesunate
• Pyronaridine plus artesunate

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Summary

• Spread of drug resistance is major challenge to
  malaria control worldwide
• Must use antimalarial drugs in a way that will
  slow development of resistance and prolong their
  useful therapeutic lifetimes
• WHO recommends use of combination therapy,
  ideally with artemisinin drug (ACT)
• USAID strongly supports that recommendation and
  is working at many different levels to facilitate
  implementation of ACT