Disease Severity and Effective Parasite Multiplication Rate in Falciparum Malaria.

Hugh W Kingston,Aniruddha Ghose,Benjamas Intharabut,Stije J Leopold,Nicholas P J Day,Amir Hossain,Arjen M Dondorp,Kamorat Silamut,Nicholas M Anstey,Kesinee Chotivanich,Katherine Plewes,Charles Woodrow,Richard J Maude,Haruhiko Ishioka,Nicholas J White,Sanjib Paul

doi:10.1093/ofid/ofx169

Abstract

Patients presenting with severe falciparum malaria in a Bangladeshi tertiary hospital had higher total parasite burden, estimated by parasitemia and plasma PfHRP2, than uncomplicated malaria patients despite shorter fever duration. This suggests that higher parasite multiplication rates (PMR) contribute to causing the higher biomass found in severe disease. Compared with patients without a history of previous malaria, patients with previous malaria carried a lower parasite biomass with similar fever duration at presentation, suggesting that host immunity reduces the PMR.

Highlights

Why some patients develop severe falciparum malaria and others do not is poorly understood [1, 2]
The odds of severe malaria decreased with longer fever duration, and in patients with severe malaria there was a borderline trend for the odds of death to decrease with longer fever duration (OR, 0.92; 95% CI, 0.84– 1.01)
The relationship between plasma PfHRP2 and fever duration appeared nonlinear in uncomplicated malaria, and a first-degree fractional polynomial (–2) provided the best fit (P < .01 vs constant only or linear untransformed model), indicating an increase followed by a plateau of PfHRP2 with fever duration (Figure 1B)

Summary

Introduction

Why some patients develop severe falciparum malaria and others do not is poorly understood [1, 2]. The parasite biomass is determined by the number of merozoites emerging from the liver at the end of preerythrocytic development (around 105), the effective parasite multiplication rate (PMR) (the average number of schizont progeny that complete the 48-hour asexual cycle), and the duration of blood stage infection [2]. CHMI studies in people with previous malaria found that PMRs are lower (2 vs 8), indicating that immunity reduces parasite multiplication [5]. Either variation in PMR or duration of blood stage infection before treatment may result in a higher parasite biomass at presentation, and an increased risk of developing severe disease. While it is well established that delayed antimalarial treatment may result in severe disease, the role of variation in effective PMR has been uncertain

Methods

Results

Conclusion