Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa

Hearing Loss Clinical Trial

Official title:

Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03722615
• Other study ID #: M151161
• Status: Completed
• Start date: May 6, 2016
• Est. completion date: April 1, 2019

Study information

• Verified date: August 2019
• Source: University of Witwatersrand, South Africa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this project is to determine the epidemiology of congenital cytomegalovirus (CMV) infection and incidence of subsequent permanent neurological sequelae in a high HIV prevalent setting in Soweto, Johannesburg. A cross-sectional study will be conducted on mother-infant pairs, screening mothers for CMV infection and newborns for congenital CMV infection. Maternal CMV prevalence will be determined by testing for CMV specific antibodies in blood. Newborn congenital infection will be determined by polymerase chain reaction (PCR) tests on newborn saliva and urine within 3 weeks of birth. Various risk factors associated with congenital CMV such as HIV exposure, and gestational age will be assessed. The association between maternal vaginal CMV shedding postnatally with congenital CMV infection will be explored by swabbing maternal vaginal fluid and conducting quantitative CMV PCR analysis. Newborns confirmed with congenital CMV and a control group of uninfected newborns will form a cohort to be followed up until 12 months of age monitoring for various neurological sequelae such as hearing loss, neurodevelopmental impairment, ocular damage, cerebral damage and seizures.

A comparison of vaccine immune responses between cases of congenital CMV and the CMV uninfected infants to the primary series of vaccines in the National Expanded Programme on Immunisation will be compared. The contribution of CMV infection to neonatal death and stillbirths will be described by minimally invasive tissue sampling (MITS) for CMV on babies that die during the neonatal period and stillbirths.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Est. completion date: April 1, 2019
• Est. primary completion date: April 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 48 Hours

Eligibility

Inclusion Criteria:

• Mother's age =18y

• Residing in Soweto and would be available for study follow-up

• Consents to enrol self and baby in study

Exclusion Criteria:

• Mother not enrolled in V98_28OBTP (NCT02215226)

Related Conditions & MeSH terms

• Cytomegalovirus Congenital
• Cytomegalovirus Infections
• Hearing Loss
• Immunogenicity
• Neonatal Death
• Neurodevelopmental Disorders
• Perinatal Death
• Stillbirth

Locations

Country	Name	City	State
South Africa	Respiratory and Meningeal Pathogen Research Unit, Soweto	Johannesburg

Sponsors (1)

Lead Sponsor	Collaborator
University of Witwatersrand, South Africa

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of congenital cytomegalovirus infection in HIV exposed and HIV unexposed newborns	Prevalence will be determined by testing a saliva sample collected at birth for CMV DNA by polymerase chain reaction (PCR) assay. Newborns that test positive for CMV at birth will have confirmatory testing done within 3 weeks of birth by testing a repeat saliva and urine sample for CMV DNA by PCR. Confirmed cases will be divided by the total number of newborns screened, stratified by HIV exposure status to determine CMV prevalence.	May 2016 - December 2016
Primary	Incidence of sensorineural hearing loss in congenital CMV infected and uninfected infants, assessed by visual reinforced audiometry	Screening for sensorineural hearing loss is initially conducted by acoustic reflex testing (ART) and distortion product otoacoustic emissions (DPOAE). To pass ART testing, the infant will have to obtain at least two reflexes at either 0.5, 1, 2 and/or 4kHz in both ears. To pass DPOAE testing, the infant will have to pass at least 3 frequencies (2,3,4 and/or 5kHz) in both ears, which is an overall pass. If any of ART or DPOAE has not been passed, the child will have diagnostic visual reinforced audiometry. Hearing thresholds will be defined as: 0 to 20 dB for normal hearing, 21 to 45 dB for mild hearing loss, 46 to 70 dB for moderate hearing loss, and 71 dB or higher for severe hearing loss.	May 2016 - May 2019
Primary	Incidence of neurodevelopmental delay in congenital CMV infected and uninfected children at one year of age assessed by scores obtained in the Bayley III developmental assessment tool.	The Bayley III scales of infant and toddler development assess the neurodevelopmental domains based on observed responses to a set of tasks presented to the child which are scored directly on the following subscales: cognitive scale, language summed scale of receptive and expressive language subscales and motor summed scale of fine and gross-motor subscales. Composite scores are derived from raw scores for cognitive, language, and motor development and scaled to a metric, with a mean of 100, standard deviation of 15, and range of 40 to 160. Performance that is 2.0 or more standard deviations below the mean score for each group will be used to define neurodevelopmental delay at 6 and 12 months.	May 2017 to March 2018
Secondary	Prevalence of CMV infection in stillbirths and neonatal deaths	Prevalence of in-utero CMV infection in stillbirths and neonatal deaths (occurring before 3 weeks age) and sites of infection. Minimally invasive tissue sampling of the major organs (lungs, brain, liver) and cerebrospinal fluid and blood samples will be tested for CMV by PCR assay.	July 2015 to August 2016
Secondary	Immunogenicity to primary series of childhood vaccinations in congenital CMV infected and uninfected children	When infants are aged 6 months a venous blood sample will be collected. Antibody to diphtheria toxoid, tetanus-toxoid, pertussis toxoid, filamentous hemagglutinin (FHA) and hepatitis B surface antigen (HBsAg) will be measured by an in-house Luminex multiplex immunoassay. Immune responses to the primary series of PCV will be measured by a standardized enzyme immunoassay (EIA) to test for vaccine serotype-specific capsular immunoglobulin (Ig) G antibody concentrations and opsonophagocytic assay.	October 2016 to February 2018