Dataset Information

Severe childhood malaria syndromes defined by plasma proteome profiles.

ABSTRACT:

Background

Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes.

Methods and findings

Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children.

Conclusions

We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.

SUBMITTER: Burte F

PROVIDER: S-EPMC3514223 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Severe childhood malaria syndromes defined by plasma proteome profiles.

Burté Florence F Brown Biobele J BJ Orimadegun Adebola E AE Ajetunmobi Wasiu A WA Battaglia Francesca F Ely Barry K BK Afolabi Nathaniel K NK Athanasakis Dimitrios D Akinkunmi Francis F Kowobari Olayinka O Omokhodion Samuel S Osinusi Kikelomo K Akinbami Felix O FO Shokunbi Wuraola A WA Sodeinde Olugbemiro O Fernandez-Reyes Delmiro D

PloS one 20121204 12

<h4>Background</h4>Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis ...[more]

PMID: 23226502

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Project description:BackgroundThe RTS,S/AS01 vaccine for Plasmodium falciparum malaria demonstrated moderate efficacy in 5-17-month-old children in phase 3 trials, and from 2018, the vaccine will be evaluated through a large-scale pilot implementation program. Work is ongoing to optimise this vaccine, with higher efficacy for a different schedule demonstrated in a phase 2a challenge study. The objective of our study was to investigate the population-level impact of a modified RTS,S/AS01 schedule and dose amount in order to inform the target product profile for a second-generation malaria vaccine.MethodsWe used a mathematical modelling approach as the basis for our study. We simulated the changing anti-circumsporozoite antibody titre following vaccination and related the titre to vaccine efficacy. We then implemented this efficacy profile within an individual-based model of malaria transmission. We compared initial efficacy, duration and dose timing, and evaluated the potential public health impact of a modified vaccine in children aged 5-17 months, measuring clinical cases averted in children younger than 5 years.ResultsIn the first decade of delivery, initial efficacy was associated with a higher reduction in childhood clinical cases compared to vaccine duration. This effect was more pronounced in high transmission settings and was due to the efficacy benefit occurring in younger ages where disease burden is highest. However, the low initial efficacy and long duration schedule averted more cases across all age cohorts if a longer time horizon was considered. We observed an age-shifting effect due to the changing immunological profile in higher transmission settings, in scenarios where initial efficacy was higher, and the fourth dose administered earlier.ConclusionsOur findings indicate that, for an imperfect childhood malaria vaccine with suboptimal efficacy, it may be advantageous to prioritise initial efficacy over duration. We predict that a modified vaccine could outperform the current RTS,S/AS01, although fourth dose timing will affect the age group that derives the greatest benefit. Further, the outcome measure and timeframe over which a vaccine is assessed are important when prioritising vaccine elements. This study provides insight into the most important characteristics of a malaria vaccine for at-risk groups and shows how distinct vaccine properties translate to public health outcomes. These findings may be used to prioritise target product profile elements for second-generation childhood malaria vaccines.

Dataset Information

Severe childhood malaria syndromes defined by plasma proteome profiles.

Background

Methods and findings

Conclusions

Publications

Severe childhood malaria syndromes defined by plasma proteome profiles.

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