Abstract

BackgroundThe duration of untreated Plasmodium falciparum infections is a defining characteristic of the parasite’s biology. It is not clear whether naturally acquired immunity (NAI) can shorten infections, despite the potential implications for malaria control and elimination as well as for basic research.MethodsData on the presence of P. falciparum msp2 genotypes in six blood samples collected over one year was analysed, together with four samples collected over 1 week, from a cohort in Navrongo (Ghana). Mathematical models assuming either exponential, Weibull, gamma, or log-normal infection durations were estimated separately for six age-groups. The method allowed for varying clonal acquisition and detection rates.ResultsThe best fitting (Weibull) mean durations were 124 days (children <5years old), 179 days (5–9 years), and 70–90 days (>10 years). This non-monotonic age pattern is not suggestive of an infection-clearing effect of NAI since immunity increases with exposure, and thus, age. Age-related differences in innate immunity are a more plausible explanation. 21% of blood-stage infections terminated within 1 week, in stark contrast to months of persistence in infections induced in neuro-syphilis patients (malariatherapy data). Age independence in this percentage raises the possibility that this clearance may result from innate mechanisms or genetic incompatibility between hosts and parasites, rather than from NAI.ConclusionIn all ages of hosts a substantial proportion of infections are cleared in the first days or weeks of appearance in the blood, while others persist for many months. Although cumulative exposure and NAI increase with age, this does apparently not translate into an increased rate of termination of infections.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0813-1) contains supplementary material, which is available to authorized users.

Highlights

  • The duration of untreated Plasmodium falciparum infections is a defining characteristic of the parasite’s biology

  • The term “detectability” is used to describe the probability of detecting a particular infecting clone conditional on it being present in the host. This is similar to “sensitivity” but emphasizes host and parasite factors rather than the quality of a diagnostic test. The consequences of this detectability-reducing effect of naturally acquired immunity (NAI) for the interpretation of epidemiological data are profound: it leads to uncertainty about whether exposure-related trends in malaria prevalence are due to reduction in acquisition of new infections, shorter infection durations, or merely due to lower detectability

  • Obtaining information on the effect of immunity on infection durations from epidemiological data is not straightforward. This led to false confidence that an important effect of NAI is to significantly shorten P. falciparum infections[7]

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Summary

Introduction

The duration of untreated Plasmodium falciparum infections is a defining characteristic of the parasite’s biology. Cumulative exposure (the total number of Bretscher et al Malar J (2015) 14:294 infections experienced by an individual) is proportional to host age for a given transmission intensity. This is similar to “sensitivity” but emphasizes host and parasite factors rather than the quality of a diagnostic test The consequences of this detectability-reducing effect of NAI for the interpretation of epidemiological data are profound: it leads to uncertainty about whether exposure-related trends in malaria prevalence are due to reduction in acquisition of new infections, shorter infection durations, or merely due to lower detectability. Obtaining information on the effect of immunity on infection durations from epidemiological data is not straightforward This led to false confidence that an important effect of NAI is to significantly shorten P. falciparum infections[7]. It is important to fill this knowledge gap by analyzing infection clearance in naturally exposed populations

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