Time-to-infection by Plasmodium falciparum is largely determined by random factors

BMC Medicine

Miles P Davenport³  Ann M Moormann¹  James W Kazura⁴  John Vulule²  Kiprotich Chelimo²  Mykola Pinkevych³ 

[1] University of Massachusetts Medical School, 373 Plantation Street, Room 318, Worcester 01605, MA, USA;Kenya Medical Research Institute, Centre for Global Health Research, Kisumu 40100, Kenya;Centre for Vascular Research, University of New South Wales Australia, Kensington NSW 2052, Sydney, Australia;Case Western Reserve University, Biomedical Research Building Suite 431, 2109 Adelbert Road, Cleveland 44106, OH, USA

关键词: Time-to-infection;    Plasmodium falciparum;    Mathematical modelling;    Malaria;    Blood-stage immunity;   

Others  :  1109702
DOI  :  10.1186/s12916-014-0252-9

 received in 2014-08-07, accepted in 2014-12-10,  发布年份 2015

【 摘 要 】

Background

The identification of protective immune responses to P. falciparum infection is an important goal for the development of a vaccine for malaria. This requires the identification of susceptible and resistant individuals, so that their immune responses may be studied. Time-to-infection studies are one method for identifying putative susceptible individuals (infected early) versus resistant individuals (infected late). However, the timing of infection is dependent on random factors, such as whether the subject was bitten by an infected mosquito, as well as individual factors, such as their level of immunity. It is important to understand how much of the observed variation in infection is simply due to chance.

Methods

We analyse previously published data from a treatment-time-to-infection study of 201 individuals aged 0.5 to 78 years living in Western Kenya. We use a mathematical modelling approach to investigate the role of immunity versus random factors in determining time-to-infection in this cohort. We extend this analysis using a modelling approach to understand what factors might increase or decrease the utility of these studies for identifying susceptible and resistant individuals.

Results

We find that, under most circumstances, the observed distribution of time-to-infection is consistent with this simply being a random process. We find that age, method for detection of infection (PCR versus microscopy), and underlying force of infection are all factors in determining whether time-to-infection is a useful correlate of immunity.

Conclusions

Many epidemiological studies of P. falciparum infection assume that the observed variation in infection outcomes, such as time-to-infection or presence or absence of infection, is determined by host resistance or susceptibility. However, under most circumstances, this distribution appears largely due to the random timing of infection, particularly in children. More direct measurements, such as parasite growth rate, may be more useful than time-to-infection in segregating patients based on their level of immunity.

【 授权许可】

   
2015 Pinkevych et al.; licensee BioMed Central.

【 图 表 】

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