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Open Access 01-12-2013 | Research article

Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data

Authors: George M Warimwe, Helen A Fletcher, Ally Olotu, Selidji T Agnandji, Adrian VS Hill, Kevin Marsh, Philip Bejon

Published in: BMC Medicine | Issue 1/2013

Abstract

Background

RTS,S is the most advanced candidate malaria vaccine but it is only partially protective and the causes of inter-individual variation in efficacy are poorly understood. Here, we investigated whether peripheral blood monocyte-to-lymphocyte ratios (ML ratio), previously shown to correlate with clinical malaria risk, could account for differences in RTS,S efficacy among phase II trial participants in Africa.

Methods

Of 11 geographical sites where RTS,S has been evaluated, pre-vaccination ML ratios were only available for trial participants in Kilifi, Kenya (N = 421) and Lambarene, Gabon (N = 189). Using time to first clinical malaria episode as the primary endpoint we evaluated the effect of accounting for ML ratio on RTS,S vaccine efficacy against clinical malaria by Cox regression modeling.

Results

The unadjusted efficacy of RTS,S in this combined dataset was 47% (95% confidence interval (CI) 26% to 62%, P <0.001). However, RTS,S efficacy decreased with increasing ML ratio, ranging from 67% (95% CI 64% to 70%) at an ML ratio of 0.1 to 5% (95% CI -3% to 13%) at an ML ratio of 0.6. The statistical interaction between RTS,S vaccination and ML ratio was still evident after adjustment for covariates associated with clinical malaria risk in this dataset.

Conclusion

The results suggest that stratification of study participants by ML ratio, easily measured from full differential blood counts before vaccination, might help identify children who are highly protected and those that are refractory to protection with the RTS,S vaccine. Identifying causes of low vaccine efficacy among individuals with high ML ratio could inform strategies to improve overall RTS,S vaccine efficacy.

Trial registration

ClinicalTrials.Gov numbers NCT00380393 and NCT00436007

Available only for authorised users

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/184/prepub

Title: Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data
Authors: George M Warimwe
Helen A Fletcher
Ally Olotu
Selidji T Agnandji
Adrian VS Hill
Kevin Marsh
Philip Bejon
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Medicine / Issue 1/2013
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/1741-7015-11-184

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Springer Medicine

Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data

Abstract

Background

Methods

Results

Conclusion

Trial registration

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Trial registration

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