Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan.

Ghulam Mujtaba,Muhammad Suleman Rana,Mehar Angez,Muhammad Masroor Alam,Aamer Ali Shah,Uzma Bashir Aamir,Salmaan Sharif,Massab Umair,Shahzad Shaukat,Syed Sohail Zahoor Zaidi,Adnan Khurshid

doi:10.1371/journal.pone.0156049

Ghulam Mujtaba, Muhammad Suleman Rana + Show 9 more

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https://doi.org/10.1371/journal.pone.0156049

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Journal: PloS one	Publication Date: Jul 1, 2016
Citations: 18	License type: CC BY 4.0

Affiliation: Quaid-i-Azam University, National Institute of Health

Abstract

BackgroundCongenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined. The objective of this study was to find the impact of active CMV infection during pregnancy and the clinical significance of genotypes in neonates with congenital cytomegalovirus infections in Pakistan.MethodsA total of 409 blood samples from pregnant women seeking health care services at the two antenatal hospitals of Islamabad during January to December 2012 were tested by ELISA and nested-PCR. Pregnant women with active infection (detected as IgM positive, PCR positive or positive on both assays) were followed until delivery, to detect the outcome of overt cCMV infection in neonates. Genetic characterization of CMV strains was performed by sequence analysis of envelope glycoproteins: gB, gN and gH to detect the contributing CMV genotypes.ResultsThe seroprevalence of anti-CMV IgG and IgM was 97.5% (399 out of 409) and 12.7% (52 out of 409), respectively, while 20% (82/409) pregnant women were found positive for CMV DNA by PCR. Logistic regression analysis showed a significant association of active infection with parity [OR = 2.56, 95% CI = 1.82–2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76–3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53–85.02, p = 0.002]. We were able to isolate virus in 41 out of 70 neonates; 36.6% (15 out of 41) of them were symptomatic at birth while 63.4% (26 out of 41) were asymptomatic. The most prominent clinical feature observed in symptomatic neonates was hepatosplenomegaly (26.6%; 4 out of 15). All three genotypes gB, gN and gH were found with the highest frequency of gB1 genotype, found in 75% infants with hepatic damage. Phylogenetic analysis of Pakistani strains showed 96%-100% homology to their prototype strains.ConclusionsActive CMV infection during pregnancy is a major cause of congenital CMV infection with comparable distribution of all three genotypes: gB, gN and gH in symptomatic and asymptomatic neonates. Our findings emphasize to conduct a comprehensive large scale survey and introduction of country wide routine screening at maternity clinics for early diagnosis of CMV to reduce its associated devastating outcomes.

Highlights

Human cytomegalovirus (HCMV) belongs to the beta herpesvirinae family, and humans are its only natural hosts
Logistic regression analysis showed a significant association of active infection with parity [odds ratio (OR) = 2.56, 95% confidence intervals (CI) = 1.82–2.62, p = 0.04], febrile illness [OR = 1.84, 95% CI = 1.76–3.65, p = 0.01] and jaundice [OR = 22.5, 95% CI = 4.53–85.02, p = 0.002]
Active CMV infection during pregnancy is a major cause of congenital CMV infection with comparable distribution of all three genotypes: gB, gN and gH in symptomatic and asymptomatic neonates

Summary

Introduction

Human cytomegalovirus (HCMV) belongs to the beta herpesvirinae family, and humans are its only natural hosts. HCMV is a common cause of congenital cytomegalovirus (cCMV) infections in developed as well as developing countries. Cytomegalovirus (CMV) infection may be acquired prenatally (congenital) through transplacental acquisition of either a primary or a recurrent maternal infection or during the perinatal/postnatal phase—at the time of birth or immediately after, due to exposure to infected cervical secretions, breast milk, or blood products [1]. Mostly congenitally infected neonates born to women with recurrent infections are clinically asymptomatic [2]. Congenital cytomegalovirus (cCMV) infection contributes to considerable long-term sequelae in neonates and children all over the world. The association between viral genotypes and severity of clinical cytomegalovirus (CMV) infection is yet to be defined.

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