Mujtaba Ghulam, Khurshid Adnan, Sharif Salmaan, Alam Muhammad Masroor, Aamir Uzma Bashir, Shaukat Shahzad, Angez Mehar, Rana Muhammad Suleman, Umair Massab, Shah Aamer Ali, Zaidi Syed Sohail Zahoor
Department of Microbiology, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Virology, National Institute of Health, Islamabad, Pakistan.
PLoS One. 2016 Jul 1;11(7):e0156049. doi: 10.1371/journal.pone.0156049. eCollection 2016.
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.
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.
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.
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.
先天性巨细胞病毒（cCMV）感染在全球范围内导致新生儿和儿童出现相当多的长期后遗症。病毒基因型与临床巨细胞病毒（CMV）感染严重程度之间的关联尚待明确。本研究的目的是探讨巴基斯坦孕期活动性CMV感染的影响以及先天性CMV感染新生儿中基因型的临床意义。
2012年1月至12月期间，在伊斯兰堡两家产前医院寻求医疗服务的孕妇共409份血样，通过酶联免疫吸附测定（ELISA）和巢式聚合酶链反应（PCR）进行检测。对活动性感染（检测为IgM阳性、PCR阳性或两种检测均为阳性）的孕妇进行随访直至分娩，以检测新生儿显性cCMV感染的结局。通过包膜糖蛋白gB、gN和gH的序列分析对CMV毒株进行基因特征分析，以检测相关的CMV基因型。
抗CMV IgG和IgM的血清阳性率分别为97.5%（409例中的399例）和12.7%（409例中的52例），而通过PCR发现20%（82/409）的孕妇CMV DNA呈阳性。逻辑回归分析显示，活动性感染与产次[比值比（OR）=2.56，95%置信区间（CI）=1.82 - 2.62，p = 0.04]、发热性疾病[OR = 1.84，95% CI = 1.76 - 3.65，p = 0.01]和黄疸[OR = 22.5，95% CI = 4.53 - 85.02，p = 0.002]之间存在显著关联。我们在70例新生儿中的41例中分离出病毒；其中36.6%（41例中的15例）出生时出现症状，63.4%（41例中的26例）无症状。有症状新生儿中观察到的最突出临床特征是肝脾肿大（26.6%；15例中的4例）。发现gB、gN和gH三种基因型，其中gB1基因型频率最高，在75%有肝损伤的婴儿中发现。巴基斯坦毒株的系统发育分析显示与其原型毒株有96% - 100%的同源性。
孕期活动性CMV感染是先天性CMV感染的主要原因，gB、gN和gH三种基因型在有症状和无症状新生儿中的分布相当。我们的研究结果强调应进行全面的大规模调查，并在产科诊所引入全国范围的常规筛查，以早期诊断CMV，减少其相关的严重后果。
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