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

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ClinicalTrials.gov Identifier: NCT03722615
Recruitment Status : Recruiting
First Posted : October 29, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Jayani Pathirana, University of Witwatersrand, South Africa

Brief 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.


Condition or disease
Cytomegalovirus Congenital Hearing Loss Neurodevelopmental Disorders Immunogenicity Neonatal Death Stillbirth

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Study Type : Observational
Estimated Enrollment : 3000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Epidemiology of Congenital Cytomegalovirus in a High HIV Prevalence Setting, South Africa
Actual Study Start Date : May 6, 2016
Estimated Primary Completion Date : April 1, 2019
Estimated Study Completion Date : April 1, 2019





Primary Outcome Measures :
  1. Prevalence of congenital cytomegalovirus infection in HIV exposed and HIV unexposed newborns [ Time Frame: May 2016 - December 2016 ]
    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.

  2. Incidence of sensorineural hearing loss in congenital CMV infected and uninfected infants, assessed by visual reinforced audiometry [ Time Frame: May 2016 - May 2019 ]
    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.

  3. 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. [ Time Frame: May 2017 to March 2018 ]
    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.


Secondary Outcome Measures :
  1. Prevalence of CMV infection in stillbirths and neonatal deaths [ Time Frame: July 2015 to August 2016 ]
    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.

  2. Immunogenicity to primary series of childhood vaccinations in congenital CMV infected and uninfected children [ Time Frame: October 2016 to February 2018 ]
    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.



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Ages Eligible for Study:   up to 48 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Newborns of women aged 18 years or older born at Chris Hani Baragwanath Academic hospital in the Johannesburg area enrolled in V98_28OBTP (NCT02215226).

Stillbirths and Neonatal deaths at Chris Hani Baragwanath Academic hospital in the Johannesburg area.

Criteria

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)


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722615


Contacts
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Contact: Jayani C Pathirana, MBBS, MSc +27119834283 pathiranaj@rmpru.co.za

Locations
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South Africa
Respiratory and Meningeal Pathogen Research Unit, Soweto Recruiting
Johannesburg, South Africa
Contact: Jayani C Pathirana, MBBS, MSc    +27119834283 ext +27711406911    pathiranaj@rmpru.co.za   
Principal Investigator: Jayani C Pathirana, MBBS, MSc         
Sponsors and Collaborators
University of Witwatersrand, South Africa
Investigators
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Study Director: Shabir A Madhi Univeristy of Witwatersrand, South Africa
  Study Documents (Full-Text)

Documents provided by Jayani Pathirana, University of Witwatersrand, South Africa:

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Responsible Party: Jayani Pathirana, PhD Fellow, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT03722615     History of Changes
Other Study ID Numbers: M151161
First Posted: October 29, 2018    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Hearing Loss
Hearing Disorders
Stillbirth
Neurodevelopmental Disorders
Perinatal Death
Cytomegalovirus Infections
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Fetal Death
Pregnancy Complications
Death
Pathologic Processes
Mental Disorders
Herpesviridae Infections
DNA Virus Infections
Virus Diseases