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Early parasitological response following artemisinin-containing regimens: a critical review of the literature.

Das D, Price RN, Bethell D, Guerin PJ, Stepniewska K - Malar. J. (2013)

Bottom Line: Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076).These results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity.Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

View Article: PubMed Central - HTML - PubMed

Affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK.

ABSTRACT

Background: Parasitaemia on Day 3 has been proposed as a useful alert of potential artemisinin resistance, however, the normal variation of parasite clearance observed in artemisinin-based combination therapy clinical trials is poorly documented.

Methods: The trends in early parasitological response following treatment with an artemisinin anti-malarial regimen were reviewed. A PubMed literature search identified all studies using an artemisinin regimen for uncomplicated falciparum malaria published between January 2000 and December 2011. Data from clinical studies were extracted for analysis using a standardized questionnaire.

Results: In total 65,078 patients were enrolled into 213 clinical trials with 413 treatment arms containing either an artemisinin derivative alone (n=26) or in combination with a partner drug (n=387). The proportion of patients remaining parasitaemic at 24, 48 and 72 hours was documented in 115 (28%), 167 (40%) and 153 (37%) treatment arms, respectively. Excluding resistance studies in Cambodia, the median proportion of patients still parasitaemic was 53.8% [range 3-95, IQR=30.5-69.2] on Day 1, 6% [range 0-65.9, IQR=2-11.5] on Day 2 and 0 [range 0-12.6, IQR=0-2] on Day 3. Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076). In 95% of studies the proportion of patients with peripheral parasitaemia was less than 6% at 72 hours.

Conclusions: These results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity. Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

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Forest plots of Day 3 parasite positivity rates in Asia. Estimates and 95% CI are shown by treatment, sorted by year in descending order (most recent first). Heterogeneity between studies I2: AL = 0.0%; AS+AQ = 93.0%; AS+MQ = 88.0%; AS+SP = NA; PIP+DHA = 44.9%.
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Figure 7: Forest plots of Day 3 parasite positivity rates in Asia. Estimates and 95% CI are shown by treatment, sorted by year in descending order (most recent first). Heterogeneity between studies I2: AL = 0.0%; AS+AQ = 93.0%; AS+MQ = 88.0%; AS+SP = NA; PIP+DHA = 44.9%.

Mentions: The parasite prevalence rates and 95% confidence intervals are presented in the forest plots at Day 3 (Figures 6 and 7) and at Day 2 (Additional files 6 and 7). Overall the median proportion of patients remaining parasitaemic after three-day regimens was 53.8% [range 3–95, IQR=30.5-69.2] at Day 1, 6.7% [range 0–73, IQR=2-12.9] at Day 2 and 0.5% [range 0–55, IQR=0-2.2] at Day 3. When studies from Cambodia were excluded, the corresponding proportions were 53.8% [range 3–95, IQR=30.5-69.2], 6.0% [range 0–65.9, IQR=2-11.5] and 0 [range 0–12.6, IQR=0-2]. In 95% of studies the proportion of patients with peripheral parasitaemia was <84% at Day 1, <34.5% at Day 2 and <6% at Day 3. In comparison, the studies from Western Cambodia reported median parasite positivity rates of 60% [range 48–73] at Day 2 and 48% [range 22–55] at Day 3.


Early parasitological response following artemisinin-containing regimens: a critical review of the literature.

Das D, Price RN, Bethell D, Guerin PJ, Stepniewska K - Malar. J. (2013)

Forest plots of Day 3 parasite positivity rates in Asia. Estimates and 95% CI are shown by treatment, sorted by year in descending order (most recent first). Heterogeneity between studies I2: AL = 0.0%; AS+AQ = 93.0%; AS+MQ = 88.0%; AS+SP = NA; PIP+DHA = 44.9%.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3649884&req=5

Figure 7: Forest plots of Day 3 parasite positivity rates in Asia. Estimates and 95% CI are shown by treatment, sorted by year in descending order (most recent first). Heterogeneity between studies I2: AL = 0.0%; AS+AQ = 93.0%; AS+MQ = 88.0%; AS+SP = NA; PIP+DHA = 44.9%.
Mentions: The parasite prevalence rates and 95% confidence intervals are presented in the forest plots at Day 3 (Figures 6 and 7) and at Day 2 (Additional files 6 and 7). Overall the median proportion of patients remaining parasitaemic after three-day regimens was 53.8% [range 3–95, IQR=30.5-69.2] at Day 1, 6.7% [range 0–73, IQR=2-12.9] at Day 2 and 0.5% [range 0–55, IQR=0-2.2] at Day 3. When studies from Cambodia were excluded, the corresponding proportions were 53.8% [range 3–95, IQR=30.5-69.2], 6.0% [range 0–65.9, IQR=2-11.5] and 0 [range 0–12.6, IQR=0-2]. In 95% of studies the proportion of patients with peripheral parasitaemia was <84% at Day 1, <34.5% at Day 2 and <6% at Day 3. In comparison, the studies from Western Cambodia reported median parasite positivity rates of 60% [range 48–73] at Day 2 and 48% [range 22–55] at Day 3.

Bottom Line: Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076).These results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity.Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

View Article: PubMed Central - HTML - PubMed

Affiliation: WorldWide Antimalarial Resistance Network, Oxford, UK.

ABSTRACT

Background: Parasitaemia on Day 3 has been proposed as a useful alert of potential artemisinin resistance, however, the normal variation of parasite clearance observed in artemisinin-based combination therapy clinical trials is poorly documented.

Methods: The trends in early parasitological response following treatment with an artemisinin anti-malarial regimen were reviewed. A PubMed literature search identified all studies using an artemisinin regimen for uncomplicated falciparum malaria published between January 2000 and December 2011. Data from clinical studies were extracted for analysis using a standardized questionnaire.

Results: In total 65,078 patients were enrolled into 213 clinical trials with 413 treatment arms containing either an artemisinin derivative alone (n=26) or in combination with a partner drug (n=387). The proportion of patients remaining parasitaemic at 24, 48 and 72 hours was documented in 115 (28%), 167 (40%) and 153 (37%) treatment arms, respectively. Excluding resistance studies in Cambodia, the median proportion of patients still parasitaemic was 53.8% [range 3-95, IQR=30.5-69.2] on Day 1, 6% [range 0-65.9, IQR=2-11.5] on Day 2 and 0 [range 0-12.6, IQR=0-2] on Day 3. Comparing studies from 2000 to 2005 and 2006 to 2011, the median proportion of patients reported to remain parasitaemic at 72 hours decreased in Africa (1.2% vs 0%, p=0.007), but increased in Asia (0.4% vs 3.9%, p=0.076). In 95% of studies the proportion of patients with peripheral parasitaemia was less than 6% at 72 hours.

Conclusions: These results highlight the normal distribution of early parasitological responses following ACT, and the influence that heterogeneity in study design, host and parasite factors have in confounding a surveillance system based on Day 3 parasite positivity. Greater understanding of factors influencing parasite clearance is crucial, but will require analysis of pooled data from individual patient records.

Show MeSH
Related in: MedlinePlus