Clinical Screening of Cytomegalovirus Infection beyond 21 Days in the Absence of its Routine Screening in Resource Limited Settings: A Cross-sectional Study

Introduction: Testing for congenital Cytomegalovirus (cCMV) infection is not part of routine care in resource-limited settings. Consequently, the diagnosis is often missed because most infections are asymptomatic and when present, symptoms are non specific. Diagnosis is required to prevent long-term sequelae. Aim: To introduce a clinical screening strategy for detecting possible CMV infections, including both congenital and postnatal infections among symptomatic neonates/infants presenting after 21 days. Materials and Methods: In this cross-sectional study, 387 subjects with clinical signs or symptoms compatible with congenital or postnatal CMV infection from birth to 365 days of life were included from three metropolitan hospitals in Kolkata, West Bengal, India, from January 2018 to March 2020. CMV infection was determined by Polymerase Chain Reaction (PCR) analysis of the urine. The Constellation of Symptoms (COS) was employed as a clinical screening tool for subjects older than 21 days. The Chi-square test was used to compare categorical variables, while the Mann-Whitney U test assessed differences in numerical data. Results: Of the 387 subjects with compatible signs or symptoms, 126 (32.6%) tested positive for CMV. Among the CMV-infected group, 8 (6.3%) presented within 21 days, while 118 (93.7%) presented after 21 days. CMV-infected infants had slightly lower birth weight and younger age at presentation compared with CMV-negative infants, though the differences were not statistically significant. The presence of individual symptoms of CMV infection did not differ significantly between CMV-positive and CMV-negative groups (p-value>0.05). However, the COS was significantly associated with CMV positivity (p-value<0.001). The sensitivity and specificity of COS were in the ranges of 77%-81% and 40%-44%, respectively. The Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were in the ranges of 38%-44% and 75%-82%, respectively. Conclusion: The COS-based strategy will be a valuable tool for screening symptomatic CMV infections in individuals up to one year of age in resource-limited settings where routine CMV screening is unavailable.