Viral Load, Clinical Disease Severity and Cellular Immune Responses in Primary Varicella Zoster Virus Infection in Sri Lanka

Gathsaurie Neelika Malavige,Antony P Black,A Wijewickrama,Louise Jones,S D Kamaladasa,Graham S Ogg,S L Seneviratne,Jacques Zimmer

doi:10.1371/journal.pone.0003789

Abstract

BackgroundIn Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. T cells are believed to be important in the control of VZV replication and in the prevention of reactivation. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied.MethodologyWe used IFNγ ELISpot assays and MHC class II tetramers based on VZV gE and IE63 epitopes, together with quantitative real time PCR assays to compare the frequency and phenotype of specific T cells with virological and clinical outcomes in 34 adult Sri Lankan individuals with primary VZV infection.Principal FindingsViral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p<0.001) and were significantly higher in those over 25 years of age (P<0.01). A significant inverse correlation was seen between the viral loads and the ex vivo IFNγ ELISpot responses of patients (P<0.001, r = −0.85). VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation.ConclusionsOverall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses.

Highlights

Primary infection with varicella zoster virus (VZV) results in chickenpox, which is usually a benign self-limiting illness, characterized by fever and a generalized pruritic vesicular rash
VZV-specific CD4+ T cells expressed markers of intermediate differentiation and activation. Overall, these data show that increased clinical severity in Sri Lankan adults with primary VZV infection associates with higher viral load and reduced viral specific T cell responses
1000 patients with VZV infections are admitted to just one infectious diseases hospital in Colombo in Sri Lanka each year [14] and many patients develop complications with an overall mortality rate of 4.2% [14]

Summary

Introduction

Primary infection with varicella zoster virus (VZV) results in chickenpox, which is usually a benign self-limiting illness, characterized by fever and a generalized pruritic vesicular rash. Adults are 9 to 15 times more likely to be hospitalized [1] and 25 times more likely than children to die from varicella [2]. In the tropics, due to the lower incidence of VZV infection among children, it more commonly affects adults [10,11,12], resulting in significant morbidity and mortality. 1000 patients with VZV infections are admitted to just one infectious diseases hospital in Colombo in Sri Lanka each year [14] and many patients develop complications with an overall mortality rate of 4.2% [14]. In Sri Lanka, varicella zoster virus (VZV) is typically acquired during adulthood with significant associated disease morbidity and mortality. The relationship between viral load, disease severity and cellular immune responses in primary VZV infection has not been well studied

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Results

Conclusion