Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses

Abstract

BackgroundIn malaria endemic populations, complex patterns of Plasmodium vivax and Plasmodium falciparum blood-stage infection dynamics may be observed. Genotyping samples from longitudinal cohort studies for merozoite surface protein (msp) variants increases the information available in the data, allowing multiple infecting parasite clones in a single individual to be identified. msp genotyped samples from two longitudinal cohorts in Papua New Guinea (PNG) and Thailand were analysed using a statistical model where the times of acquisition and clearance of each clone in every individual were estimated using a process of data augmentation.ResultsFor the populations analysed, the duration of blood-stage P. falciparum infection was estimated as 36 (95% Credible Interval (CrI): 29, 44) days in PNG, and 135 (95% CrI 94, 191) days in Thailand. Experiments on simulated data indicated that it was not possible to accurately estimate the duration of blood-stage P. vivax infections due to the lack of identifiability between a single blood-stage infection and multiple, sequential blood-stage infections caused by relapses. Despite this limitation, the method and data point towards short duration of blood-stage P. vivax infection with a lower bound of 24 days in PNG, and 29 days in Thailand. On an individual level, P. vivax recurrences cannot be definitively classified into re-infections, recrudescences or relapses, but a probabilistic relapse phenotype can be assigned to each P. vivax sample, allowing investigation of the association between epidemiological covariates and the incidence of relapses.ConclusionThe statistical model developed here provides a useful new tool for in-depth analysis of malaria data from longitudinal cohort studies, and future application to data sets with multi-locus genotyping will allow more detailed investigation of infection dynamics.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2318-1) contains supplementary material, which is available to authorized users.

Plasmodium malariae and Plasmodium ovale infections and their association with common red blood cell polymorphisms in a highly endemic area of Uganda

“…falciparum co-infection dynamics showed that even when this type of data is available, there is limited statistical power to classify a given infection as a re-infection, recrudescence or relapse with a high probability. 36 The prevalence of all Plasmodium species was highest among children 6-10 y of age, as reported elsewhere. 14,37 This result is likely related to the development of immunity that limits clinical symptoms but does not reduce the chance of being infected.…”

The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density

“…However in these infections, low-density periods also occurred early in infection, with more than 60% of untreated patients experiencing a subpatent period lasting for 1–34 days directly after the initial peak in parasitaemia 16 . In naturally acquired infections, changes in detectability in relation to duration of infection are extremely difficult to measure due to superinfection, where individuals may be repeatedly infected over time with different parasite strains 17 . This makes it difficult to measure the relative densities or durations of different parasite clones without longitudinal genetic studies.…”

Estimating the probable cause of recurrence in Plasmodium vivax malaria: relapse, reinfection or recrudescence?

“…Various statistical and mathematical models of P. vivax exist, ranging from models of within host dynamics to global geostatistical descriptions of prevalence [7,27,33-35,37-54]. However, only two publications to our knowledge have formally considered recurrence states on an individual basis [37,55]. Ross et al .…”

“…White et al . combined genetic (from a single polyallelic locus) and time-to-event data using a statistical model of parasite clone acquisition and clearance using samples from cohorts in Papua New Guinea and Thailand [37]. The majority of recurrent episodes were asymptomatic and not treated, and the main target of inference was the duration of asymptomatic infection.…”

“…The majority of P. vivax endemic areas are consistent with the low transmission settings studied here on the Thailand-Myanmar border [1], where over 99% of the single recurrences fit these stipulations (the median COI in both VHX and BPD is 1). However, the method would require modification before application to data from high transmission settings such as Papua New Guinea, where the estimated complexity of a single infection is often greater than 6 [37,55].…”