Differential Patterns of Infection and Disease with P. falciparum and P. vivax in Young Papua New Guinean Children

Enmoore Lin,Peter Zimmerman,Leanne Robinson,Danielle Stanisic,Laurie Gray,Ivo Mueller,Peter Siba,Louis Schofield,Benson Kiniboro,Melinda Blood-Zikursh,Annemarie Laumaea,Inoni Betuela,Stuart Dobbie,Sonja Schöpflin,Ingrid Felger

doi:10.1371/journal.pone.0009047

Abstract

BackgroundWhere P. vivax and P. falciparum occur in the same population, the peak burden of P. vivax infection and illness is often concentrated in younger age groups. Experiences from malaria therapy patients indicate that immunity is acquired faster to P. vivax than to P. falciparum challenge. There is however little prospective data on the comparative risk of infection and disease from both species in young children living in co-endemic areas.Methodology/Principal FindingsA cohort of 264 Papua New Guinean children aged 1-3 years (at enrolment) were actively followed-up for Plasmodium infection and febrile illness for 16 months. Infection status was determined by light microscopy and PCR every 8 weeks and at each febrile episode. A generalised estimating equation (GEE) approach was used to analyse both prevalence of infection and incidence of clinical episodes. A more pronounced rise in prevalence of P. falciparum compared to P. vivax infection was evident with increasing age. Although the overall incidence of clinical episodes was comparable (P. falciparum: 2.56, P. vivax 2.46 episodes / child / yr), P. falciparum and P. vivax infectious episodes showed strong but opposing age trends: P. falciparum incidence increased until the age of 30 months with little change thereafter, but incidence of P. vivax decreased significantly with age throughout the entire age range. For P. falciparum, both prevalence and incidence of P. falciparum showed marked seasonality, whereas only P. vivax incidence but not prevalence decreased in the dry season.Conclusions/SignificanceUnder high, perennial exposure, children in PNG begin acquiring significant clinical immunity, characterized by an increasing ability to control parasite densities below the pyrogenic threshold to P. vivax, but not to P. falciparum, in the 2nd and 3rd year of life. The ability to relapse from long-lasting liver-stages restricts the seasonal variation in prevalence of P. vivax infections.

Highlights

The epidemiology of P. falciparum malaria suggests immunity might be acquired in ‘stages’, with children first acquiring immunity against severe disease after relatively few episodes/ infections [1,2]
In highly endemic areas, such as New Guinea, the risk of severe P. vivax disease is highest among children less than 2 yrs of age [6,7], while uncomplicated P. vivax illness is rare among children over 5 yrs [5,6] even though infections are commonly found even in adolescents and adults [3,8,9,10]
Children were between 0.91–3.21 yrs of age (median 1.70, Inter-quartile range (IQR): [1.27, 2.43] and 118 (43.9%) were female

Summary

Introduction

The epidemiology of P. falciparum malaria suggests immunity might be acquired in ‘stages’, with children first acquiring immunity against severe disease after relatively few episodes/ infections [1,2]. A recent study in Papua New Guinean children 5–14 yrs of age found that despite acquiring a similar number of new blood stage infections with P. falciparum and P. vivax, children had attained very high levels of clinical immunity to P. vivax but remained at significant risk of uncomplicated P. falciparum illness [5]. This was linked to a greater ability to control P. vivax parasitaemia at levels well below the pyrogenic threshold than for P. falciparum. The study design combined repeated blood sampling and molecular detection of parasitemia with a large array of classical and functional immune assays and provided an excellent opportunity to examine epidemiological evidence of different rates of acquisition of immunity to P. falciparum and P. vivax and investigate possible mechanisms of immune protection

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