Age-dependent sex bias in clinical malarial disease in hypoendemic regions.

Sulabha Pathak,Gyan Bhanot,Surya Kant Sharma,Nithya J Gogtay,Shobhona Sharma,Nilima A Kshirsagar,Umesh Aigal,Mayuri Rege,Neena Valecha,Georges Snounou

doi:10.1371/journal.pone.0035592

Abstract

Background and ObjectivesExperimental models show a male bias in murine malaria; however, extant literature on biases in human clinical malaria is inconclusive. Studies in hyperendemic areas document an absence of sexual dimorphism in clinical malaria. Data on sex bias in clinical malaria in hypoendemic areas is ambiguous—some reports note a male bias but do not investigate the role of differential mosquito exposure in that bias. Moreover, these studies do not examine whether the bias is age related. This study investigates whether clinical malaria in hypoendemic regions exhibits a sex bias and whether this bias is age-dependent. We also consider the role of vector exposure in this bias.MethodsRetrospective passive clinical malaria datasets (2002–2007) and active surveillance datasets (2000–2009) were captured for the hypoendemic Mumbai region in Western India. To validate findings, passive retrospective data was captured from a primary malaria clinic (2006–2007) in hypoendemic Rourkela (Eastern India). Data was normalized by determining percent slide-positivity rates (SPRs) for males and females, and parasite-positivity distributions were established across age groups. The Mann–Whitney test, Wilcoxon Signed Rank test, and Chi-square analysis were used to determine statistical significances.ResultsIn both the Mumbai and Rourkela regions, clinical malaria exhibited an adult male bias (p<0.01). A sex bias was not observed in children aged ≤10. Post-puberty, male SPRs were significantly greater than females SPRs (p<0.01). This adult male bias was observed for both vivax and falciparum clinical disease. Analysis of active surveillance data did not reveal an age or sex bias in the frequency of parasite positivity.ConclusionThis study demonstrates an age-dependent sex bias in clinical malaria in hypoendemic regions and enhanced incidence of clinical malaria in males following puberty. Possible roles of sex hormones, vector exposure, co-infections, and other factors in this enhanced susceptibility are discussed.

Highlights

Malaria accounts for a major portion of the global disease burden [1]
This adult male bias was observed for both vivax and falciparum clinical disease
Our study indicates the existence of an adult male bias in clinical malaria in hypoendemic regions of India

Summary

Introduction

Malaria accounts for a major portion of the global disease burden [1]. A male bias in malarial infections has been noted in host species as diverse as lizards and great tits [2,3]. Studies in the murine model clearly establish a male bias in malaria and show that testosterone increases susceptibility to the disease [4,5]. Sexual dimorphism does not exist in hyperendemic regions for both Plasmodium falciparum and P. vivax infections, some reports note an increased parasite density in pubertal and post-pubertal males [7,12]. Data on sex bias in clinical malaria in hypoendemic areas is ambiguous—some reports note a male bias but do not investigate the role of differential mosquito exposure in that bias. These studies do not examine whether the bias is age related. We consider the role of vector exposure in this bias

Methods

Results

Discussion

Conclusion