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Treatment of Severe Malaria: How will countries cope with changes in national malaria treatment policies?


Treatment of Severe Malaria: How will countries cope with ... Hypoglycaemia, CVS, CNS toxicity. Artemether IM. PCT more rapid, but clinically equivalent. ... – PowerPoint PPT presentation

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Title: Treatment of Severe Malaria: How will countries cope with changes in national malaria treatment policies?

Treatment of Severe Malaria How will countries
cope with changes in national malaria treatment
  • Karen I Barnes
  • Division of Pharmacology
  • University of Cape Town

Problem statement
  • Malaria infects approximately 250 million people
    and results in 1- 2 million deaths each year, the
    majority among children lt 5 years.
  • Malaria morbidity and mortality in Africa is
    rising, and this is principally a result of
    increasing chloroquine and sulfadoxine-pyrimethami
    ne (SP) resistance in Plasmodium falciparum and
    delays in access to effective therapy.
  • Many patients who cannot tolerate oral treatment
    do not have ready access to health facilities
    able to provide injectable treatment. Delay in
    access to prompt therapy can be fatal.

Treatment of Severe Malaria How will countries
cope with NO change in national malaria treatment
Malaria Epidemiology in KZN
High level SP treatment failure (together with
insecticide resistance in the vector), resulted
in the urgent need for replacement of first line
therapy. Similar levels of SP failure reported
in Malawi, Tanzania, Burundi. Temporal
association between increased antimarial
resistance and increased malaria deaths in KZN,
Senegal, Kenya.
Malaria Case Fatality Rates
  • Severe malaria 10-40
  • Moderately severe malaria 3
  • Uncomplicated malaria lt1
  • How would it be most feasible and cost-effective
    to intervene, to reduce malaria mortality?

Reduce malaria mortality by
  • Early access to effective parenteral Rx and
    modern intensive care, particularly
    haemofiltration and ventilation for patients with
    severe malaria1.
  • Rectal formulations for patients unable to
    tolerate oral treatment and who do not have
    access to parenteral treatment
  • Early access to effective treatment for
    uncomplicated malaria
  • Community IEC
  • Effective durable treatment policy
  • Delay resistance through combinations,
    particularly artemisinin-based combinations.
  • Reduce malaria transmission
  • Mosquito Vector control
  • Artemisinin-based combination therapy
  • 1White NJ (2003). The management of severe
    falciparum malaria. Am J Resp Crit Care Med 167

Reducing malaria mortalityEvidence for and
implementation of rational malaria treatment
Severe malaria meta-analysis2653 patients in
16 trialsOlliaro P, Cochrane review 2002
  • Artemether IM
  • PCT more rapid, but clinically equivalent.
  • Coma recovery time and neurological sequelae
  • Better survival than quinine (mortality odds
    ratio 0.61 0.46 0.82)
  • Quinine IV/IM
  • Constant rate infusion / painful IM injection
  • Narrow therapeutic range
  • Hypoglycaemia, CVS, CNS toxicity

But IV / IM artesunte is likely to be
significantly better than IM artemether.
Severe malaria
  • Randomized comparison of artesunate and quinine
    in the treatment of severe falciparum malaria.
  • Newton PN, Angus BJ, Chierakul W, Dondorp A,
    Ruangveerayuth R, Silamut K, Teerapong P,
    Suputtamongkol Y, Looareesuwan S, White NJ.
  • 113 adults with clinically severe falciparum
    malaria in western Thailand.
  • Mortality was 12 with artesunate and 22 with
    quinine treatment
  • (relative risk, 0.53 95 confidence interval,
    0.23-1.26 P.22).
  • Parasite clearance time was much shorter among
    artesunate-treated patients (P.019).
  • Fewer patients became hypoglycemic during
    artesunate therapy (10) than during quinine
    therapy (28) (P.03).
  • Artesunate is at least as effective as quinine in
    the treatment of adults with severe malaria.
    Larger trials are required to determine whether
    mortality is reduced among patients treated with

  • Patients with greater than 4 parasitaemia, but
    with no other features of severe malaria, are at
    an increased risk of developing severe malaria
    and have a 3 mortality rate.
  • Oral artesunate was found to be clinically and
    parasitologically superior to intravenous
  • Luxemborger C, Thwai KL, Raimond SD,
    Chongsuphajaisiddhi T, White NJ (1995). Oral
    artesunate in the treatment of uncomplicated
    hyperparasitaemic falciparum malaria. Am J Trop
    Med Hyg, 53 522-525.

Efficacy of rectal artesunate
  • SA Adults (n35) Malawian children (n109)
  • Percentage of baseline parasitaemia during
    initial 24 hours following rectal artesunate vs
    IM quinine, in patients with moderately severe
  • Rectal artesunate resulted in more rapid parasite
    clearance, and clinically equivalent to IM
  • Pharmacokinetic and or pharmacodynamic evidence
    of adequate absorption of rectal artesunate shown
    in all patients with moderately severe malaria.
  • Barnes KI, Mwenechanya J, Tembo M, McIlleron H,
    Folb PI, Ribeiro I, Little F, Gomes M, Molyneux
    ME Efficacy of rectal artesunate in the initial
    treatment of moderately severe malaria in African
    children and adults. Lancet 2004 (In press)

Artemisinin-based combination therapy in
uncomplicated malaria
Improve clinical cure rates Delay emergence of
resistance Reduce transmission
Widespread use of 1st line Rx with Artemisinin-ba
sed Combination Therapy
Cost effective
ACT delays resistance in NW Thailand
Nosten F, et al (2000). Effects of artesunate
mefloquine combination on incidence of Plasmodium
falciparum malaria and mefloquine resistance in
western Thailand a prospective study. Lancet
356 297-302.
ACT acts synergistically with vector control to
decrease malaria transmission in KwaZulu Natal,
South Africa
A DDT reintroduced
B IRS southern Mozambique
C Artemether-lumefantrine implemented
How did ACT decrease malaria case load in KZN?
  • Significantly Improved Cure rates
  • Significantly Decreased Gametocyte Carriage

Hospital admissions for malaria in 3 sentinel
rural district hospitals in KwaZulu Natal in 2000
Overcoming Challenges in Implementation
  • Drug regulation and registration.
  • Pricing and sustainable funding.
  • Strengthening the healthcare system.
  • Ongoing training and supervision.
  • Monitoring and evaluation and FEEDBACK.

Future research questionsin severe malaria
  • Efficacy and effectiveness of rectal artesunate
    in severe malaria.
  • Large scale multi-centre study of intravenous
    artesunate vs. quinine in severe malaria.
  • Feasible methods for enhancing referral systems
    in resource poor settings.
  • Effect of widespread use of ACTs on hospital
    malaria admissions in areas of higher intensity
    malaria transmission.
  • Outcome studies of interventions to promote early
    treatment seeking in malaria, particularly in
    more severe malaria.

Key Lessons Learnt Policy Implications
  • Artemisinins can play an important role in
    decreasing malaria mortality in children (and
  • Potential to decrease mortality from more severe
    malaria when artesunate is administered
    intravenously (and possibly rectally).
  • Rectal artesunate in moderately severe malaria
    allows earlier access to effective treatment in
    patients unable to tolerate oral treatment.
  • Artemisinin-based combination therapy for
    uncomplicated malaria should lead to a decrease
    the inpatient malaria burden by improving cure
    rates, delaying antimalaial resistance, and
    decreasing malaria transmission.

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