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Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis.

Okell LC, Cairns M, Griffin JT, Ferguson NM, Tarning J, Jagoe G, Hugo P, Baker M, D'Alessandro U, Bousema T, Ubben D, Ghani AC - Nat Commun (2014)

Bottom Line: DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk.Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large.We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK.

ABSTRACT
There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on disease burden. Two major antimalarial policy options are artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQP). Clinical trial data show that DHA-PQP provides longer protection against reinfection, while AL is better at reducing patient infectiousness. Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducing effects and cost into a mathematical model and simulate malaria transmission and treatment in Africa, using geographically explicit data on transmission intensity and seasonality, population density, treatment access and outpatient costs. DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk. Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large. We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden.

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Related in: MedlinePlus

Generic model simulations.Model-simulated impact in all age groups on clinical episodes and parasite prevalence of having DHA–PQP as first-line treatment versus AL over 5 years in low, medium and high transmission settings with (red) and without (orange) seasonal variation in transmission, assuming high treatment access (80% of cases are treated), but no other interventions. Low, medium and high indicate baseline slide prevalence levels before treatment change of 5, 15 and 50%, respectively, in children aged 2–10 years in the non-seasonal setting. Seasonal settings have the same baseline clinical incidence as the non-seasonal settings. Absolute reductions (a,c) and percentage reductions (b,d) in the DHA–PQP versus AL scenarios are shown.
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f3: Generic model simulations.Model-simulated impact in all age groups on clinical episodes and parasite prevalence of having DHA–PQP as first-line treatment versus AL over 5 years in low, medium and high transmission settings with (red) and without (orange) seasonal variation in transmission, assuming high treatment access (80% of cases are treated), but no other interventions. Low, medium and high indicate baseline slide prevalence levels before treatment change of 5, 15 and 50%, respectively, in children aged 2–10 years in the non-seasonal setting. Seasonal settings have the same baseline clinical incidence as the non-seasonal settings. Absolute reductions (a,c) and percentage reductions (b,d) in the DHA–PQP versus AL scenarios are shown.

Mentions: Generalized simulations of switching treatment policy from AL to DHA–PQP were run to explore the impact in areas with different initial transmission intensity (50, 15 and 5% baseline slide prevalence of malaria in 2–10 year olds) and seasonality in transmission (uniform over the year or strongly seasonal with ~90% of infectious bites occurring within 4 months). Here we assumed that 80% of clinical cases would be treated with AL, switching all treatment to DHA–PQP at a given time point. Outcomes of cumulative number of clinical episodes prevented and reductions in slide prevalence were assessed 5 years after the change in treatment policy in all age groups, comparing this with a continuation of the AL policy. In the scenarios considered, DHA–PQP reduced transmission compared with AL, indicating that its longer post-treatment prophylactic period was more important than the higher gametocytocidal effect of AL (Fig. 3). Reductions in transmission were higher in areas with high initial transmission intensity due to the greater chance of receiving an infectious bite during periods of post-treatment prophylaxis. For example, in non-seasonal settings, an estimated 0.03 and 0.19 clinical episodes were prevented per person when initial slide prevalence was 5 and 50%, respectively (Fig. 3a). Approximately 82 and 26% of this impact is due to the direct protection by the drug in the highest and lowest transmission settings, respectively, the remainder being due to a community-wide effect on transmission. Estimated impacts were always higher in areas with seasonal variation in transmission. For example, an estimated 0.19 episodes were prevented per person in a non-seasonal setting with baseline slide prevalence of 50% versus 0.56 episodes in a seasonal setting with the same total annual clinical incidence.


Contrasting benefits of different artemisinin combination therapies as first-line malaria treatments using model-based cost-effectiveness analysis.

Okell LC, Cairns M, Griffin JT, Ferguson NM, Tarning J, Jagoe G, Hugo P, Baker M, D'Alessandro U, Bousema T, Ubben D, Ghani AC - Nat Commun (2014)

Generic model simulations.Model-simulated impact in all age groups on clinical episodes and parasite prevalence of having DHA–PQP as first-line treatment versus AL over 5 years in low, medium and high transmission settings with (red) and without (orange) seasonal variation in transmission, assuming high treatment access (80% of cases are treated), but no other interventions. Low, medium and high indicate baseline slide prevalence levels before treatment change of 5, 15 and 50%, respectively, in children aged 2–10 years in the non-seasonal setting. Seasonal settings have the same baseline clinical incidence as the non-seasonal settings. Absolute reductions (a,c) and percentage reductions (b,d) in the DHA–PQP versus AL scenarios are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4263185&req=5

f3: Generic model simulations.Model-simulated impact in all age groups on clinical episodes and parasite prevalence of having DHA–PQP as first-line treatment versus AL over 5 years in low, medium and high transmission settings with (red) and without (orange) seasonal variation in transmission, assuming high treatment access (80% of cases are treated), but no other interventions. Low, medium and high indicate baseline slide prevalence levels before treatment change of 5, 15 and 50%, respectively, in children aged 2–10 years in the non-seasonal setting. Seasonal settings have the same baseline clinical incidence as the non-seasonal settings. Absolute reductions (a,c) and percentage reductions (b,d) in the DHA–PQP versus AL scenarios are shown.
Mentions: Generalized simulations of switching treatment policy from AL to DHA–PQP were run to explore the impact in areas with different initial transmission intensity (50, 15 and 5% baseline slide prevalence of malaria in 2–10 year olds) and seasonality in transmission (uniform over the year or strongly seasonal with ~90% of infectious bites occurring within 4 months). Here we assumed that 80% of clinical cases would be treated with AL, switching all treatment to DHA–PQP at a given time point. Outcomes of cumulative number of clinical episodes prevented and reductions in slide prevalence were assessed 5 years after the change in treatment policy in all age groups, comparing this with a continuation of the AL policy. In the scenarios considered, DHA–PQP reduced transmission compared with AL, indicating that its longer post-treatment prophylactic period was more important than the higher gametocytocidal effect of AL (Fig. 3). Reductions in transmission were higher in areas with high initial transmission intensity due to the greater chance of receiving an infectious bite during periods of post-treatment prophylaxis. For example, in non-seasonal settings, an estimated 0.03 and 0.19 clinical episodes were prevented per person when initial slide prevalence was 5 and 50%, respectively (Fig. 3a). Approximately 82 and 26% of this impact is due to the direct protection by the drug in the highest and lowest transmission settings, respectively, the remainder being due to a community-wide effect on transmission. Estimated impacts were always higher in areas with seasonal variation in transmission. For example, an estimated 0.19 episodes were prevented per person in a non-seasonal setting with baseline slide prevalence of 50% versus 0.56 episodes in a seasonal setting with the same total annual clinical incidence.

Bottom Line: DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk.Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large.We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK.

ABSTRACT
There are currently several recommended drug regimens for uncomplicated falciparum malaria in Africa. Each has different properties that determine its impact on disease burden. Two major antimalarial policy options are artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQP). Clinical trial data show that DHA-PQP provides longer protection against reinfection, while AL is better at reducing patient infectiousness. Here we incorporate pharmacokinetic-pharmacodynamic factors, transmission-reducing effects and cost into a mathematical model and simulate malaria transmission and treatment in Africa, using geographically explicit data on transmission intensity and seasonality, population density, treatment access and outpatient costs. DHA-PQP has a modestly higher estimated impact than AL in 64% of the population at risk. Given current higher cost estimates for DHA-PQP, there is a slightly greater cost per case averted, except in areas with high, seasonally varying transmission where the impact is particularly large. We find that a locally optimized treatment policy can be highly cost effective for reducing clinical malaria burden.

Show MeSH
Related in: MedlinePlus