title: Distribution of Cytomegalovirus Genotypes among Neonates Born to Infected Mothers in Islamabad, Pakistan.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  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. 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.
authors.affiliation: Department of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mujtaba
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Adnan
authors.initials: A
authors.lastname: Khurshid
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Salmaan
authors.initials: S
authors.lastname: Sharif
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Muhammad Masroor
authors.initials: MM
authors.lastname: Alam
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Uzma Bashir
authors.initials: UB
authors.lastname: Aamir
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Shahzad
authors.initials: S
authors.lastname: Shaukat
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Mehar
authors.initials: M
authors.lastname: Angez
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Muhammad Suleman
authors.initials: MS
authors.lastname: Rana
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Massab
authors.initials: M
authors.lastname: Umair
authors.affiliation: Department of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Aamer Ali
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Department of Virology, National Institute of Health, Islamabad, Pakistan.
authors.forename: Syed Sohail Zahoor
authors.initials: SS
authors.lastname: Zaidi
mesh_terms: D000293:Adolescent; D000328:Adult; D003587:Cytomegalovirus / Q000235:genetics* / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000151:congenital*; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D009035:Mothers; D010154:Pakistan; D010802:Phylogeny; D011247:Pregnancy; D055815:Young Adult