Use of polymerase chain reaction and antibody tests in the diagnosis of vertically transmitted hepatitis C virus infection.
Data on patterns of polymerase chain reaction (PCR) and antibody test results in infants born to hepatitis C virus (HCV)-infected mothers were systematically reviewed to aid development of optimum testing schedules and diagnostic criteria for vertically exposed infants and to facilitate early identification of infected infants. Survival and cross-sectional analyses were used to estimate the timing of initial PCR positivity and subsequent PCR negativity in infected infants, and maternal antibody loss in uninfected infants was estimated as a weighted average of individual study findings. Of 74 eligible infants with strong evidence of HCV infection, an estimated 89% (90% confidence interval, 80-95%) were first PCR positive by 3 months of age, and less than 10% had subsequent PCR negativity attributable to intermittent viraemia or resolved infection in the first 18 months of life. The negative predictive value of PCR at 3 months of age was greater than 98% at an assumed rate of 5% vertical transmission, but as low as 88% at 25% transmission. The inclusion of 22 infants, each with a single PCR-positive result, increased the estimated frequency of resolved infections but made little difference to other estimates. A minority of PCR-positive infants had periods of antibody negativity by second- or third-generation assays, and among 297 uninfected infants, maternal antibody was not detected beyond 18 months. Thus, the majority of infected infants may be persistently PCR positive from 3 months of age, and the negative predictive value of PCR at 3 months is generally high. However, poor repeatability of PCR, inadequate infant follow-up, and inclusion of postnatally infected infants limits interpretation of the pooled data. Further studies using standardised PCR methodologies are needed.
Thomas
S L
SL
Infectious Disease Epidemiology Unit, London School of Hygiene & Tropical Medicine, UK.
Newell
M L
ML
Peckham
C S
CS
Ades
A E
AE
Hall
A J
AJ
D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006526:Hepatitis C / Q000175:diagnosis* / Q000453:epidemiology / Q000635:transmission*; D018937:Hepatitis C Antibodies / Q000032:analysis; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis / Q000302:isolation & purification; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D013997:Time Factors; D014766:Viremia / Q000175:diagnosis
D018937:Hepatitis C Antibodies; D012367:RNA, Viral