title: Age-dependent sex bias in clinical malarial disease in hypoendemic regions.
abstract: OBJECTIVE
  Experimental 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.
  
  
  METHODS
  Retrospective 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India. suepathak@tifr.res.in
authors.forename: Sulabha
authors.initials: S
authors.lastname: Pathak
authors.forename: Mayuri
authors.initials: M
authors.lastname: Rege
authors.forename: Nithya J
authors.initials: NJ
authors.lastname: Gogtay
authors.forename: Umesh
authors.initials: U
authors.lastname: Aigal
authors.forename: Surya Kant
authors.initials: SK
authors.lastname: Sharma
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
authors.forename: Gyan
authors.initials: G
authors.lastname: Bhanot
authors.forename: Nilima A
authors.initials: NA
authors.lastname: Kshirsagar
authors.forename: Shobhona
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000852:Anopheles / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004199:Disease Vectors; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D058974:Phylogeography; D010963:Plasmodium falciparum / Q000502:physiology; D010966:Plasmodium vivax / Q000502:physiology; D011159:Population Surveillance; D012189:Retrospective Studies; D012737:Sex Factors