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Cytomegalovirus Infections in Ugandan Infants:Newborns, Neonates with Sepsis and Infants with Hydrocephalus

30 Pages Posted: 20 Jul 2021

See all articles by Christine Hehnly

Christine Hehnly

Pennsylvania State University - Institute of Personalized Medicine

Paddy Ssentongo

Pennsylvania State University - Center for Neural Engineering

Lisa Bebell

Harvard University - Division of Infectious Diseases

Kathy Burgoine

University of Liverpool; Mbale Regional Referral Hospital - Neonatal Unit

Joel Bazira

Mbarara University of Science and Technology

Claudio Fronterre

Lancaster University - Centre for Health Informatics, Computing, and Statistics

Elias Kumbakumba

Mbarara University of Science and Technology - Department of Pediatrics

Ronald Mulondo

CURE Children's Hospital of Uganda

Edith Mbabazi-Kabachelor

CURE Children's Hospital of Uganda

Sarah U. Morton

Harvard University - Harvard Medical School; Harvard University - Division of Newborn Medicine

Joseph Ngonzi

Mbarara University of Science and Technology - Department of Obstetrics and Gynaecology

Moses Ochora

Mbarara University of Science and Technology - Department of Pediatrics

Peter Olupot Oluput

Mbale Regional Referral Hospital - Neonatal Unit; Busitema University - Mbale Clinical Research Institute

Justin Onen

Mbarara University of Science and Technology - Department of Pediatrics; CURE Children's Hospital of Uganda

Drucilla J. Roberts

Harvard University - Department of Pathology

Kathryn Sheldon

Pennsylvania State University - Institute of Personalized Medicine

Shamim A. Sinnar

Pennsylvania State University - Penn State College of Medicine

Jasmine Smith

Pennsylvania State University - Institute of Personalized Medicine

Peter Ssenyonga

Mbarara University of Science and Technology - Department of Pediatrics; CURE Children's Hospital of Uganda

Joseph N. Paulson

Genentech, Inc. - San Francisco - Department of Biostatistics

Frederick A. Meier

Henry Ford Health System - Henry Ford Hospital; Wayne State University - School of Medicine

Jessica E. Ericson

Pennsylvania State University - Division of Pediatric Infectious Disease

James R. Broach

Pennsylvania State University - Institute of Personalized Medicine

Steven Schiff

Pennsylvania State University - Center for Neural Engineering; Pennsylvania State University - Department of Engineering Science and Mechanics; Pennsylvania State University - Center for Infection Disease Dynamics; Pennsylvania State University - Department of Neurosurgery; Pennsylvania State University - Department of Physics

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Abstract

Background: Congenital and postnatal cytomegalovirus (CMV) infections in Uganda is prevalent and may compromise the health of Ugandan children. The objective of this study is to estimate the prevalence of CMV infections in newborns, neonates with sepsis, and infants with hydrocephalus in Uganda.

Methods: Three populations: (1) newborn-mother pairs, (2) neonates with sepsis, and (3) infants (≤ 3 months) with non-postinfectious (NPIH) or postinfectious (PIH) hydrocephalus, were evaluated over four years (2016-2019) for CMV infection at three medical centers – two in the Eastern (Mbale) and one in Western (Mbarara) Uganda. To characterize the prevalence of CMV we used quantitative PCR (qPCR) analysis. In newborn-mother pairs maternal blood (n=99) and a subset of matching cord blood (n=92), placental tissue (n=99), and vaginal specimens (n=99) were tested for CMV. In neonates and infants aged 3 months or less, peripheral blood (751 with sepsis, 399 with hydrocephalus) and cerebrospinal fluid samples (560 with sepsis, 399 with hydrocephalus (205 PIH, 194 NPIH) were also tested for CMV.

Findings: The overall CMV prevalence across all groups was 9%. In newborn-mother pairs, a 3% (n=3/92; 95% CI, 1-9%) prevalence of cord blood positivity and 33% (n=33/99; 95% CI, 24-44%) prevalence of maternal vaginal shedding of CMV was estimated. In neonates with clinical sepsis, a 2% (n=17/751; 95% CI, 1-4%) CMV prevalence was estimated. Maternal HIV seropositivity (adjusted odds ratio [aOR], 21.09; 95% CI, 4-109; p= 0.0002), residence in Eastern Uganda (aOR, 11.10; 95% CI, 3-77; p=0 .003), maternal age < 25 years (aOR, 4.91; 95% CI, 2-20; p=0.012), and older neonatal age (9 days vs. 5 days; p= 0.006) were associated with CMV in neonates with clinical sepsis. In infants with PIH, the prevalence in blood was 24% (n=50/205; 95% CI, 19-31%) and in infants with NPIH it was 20% (n=39/194; 95% CI, 15-26%; p=0.34). CMV was present in the CSF of 13% (n=26/205; 95% CI, 8-18%) of infants with PIH compared to 0.5% of infants with NPIH (n=1/194; 95% CI, 0-3%, p<0.0001).

Interpretation: Our findings highlight that congenital and postnatal CMV prevalence is high in this African setting and the associated complications may be significant. Universal testing and longitudinal studies are critical to understand the burden infant CMV has in sub-Saharan African countries.

Funding Statement: U.S. National Institutes of Health (N.I.H) Director’s Pioneer Award 5DP1HD086071 and NIH Director’s Transformative Award 1R01AI145057.

Declaration of Interests: No conflict of interest reported.

Ethics Approval Statement: For all participants, mothers had to be at least 18 years of age and able to give informed written consent in either English, Lumasaba, Lugwere, Luganda, Ateso or Runyankole. The study was performed with approval from the CCHU Institutional Review Board, the Mbarara University of Science and Technology Research Ethics Committee, the Pennsylvania State University Institutional Review Board, and with oversight from the Ugandan National Council on Science and Technology. Material Transfer Agreements and a US Centers for Disease Control permit were obtained for the proper transfer and importation of samples to the Pennsylvania State University.

Suggested Citation

Hehnly, Christine and Ssentongo, Paddy and Bebell, Lisa and Burgoine, Kathy and Bazira, Joel and Fronterre, Claudio and Kumbakumba, Elias and Mulondo, Ronald and Mbabazi-Kabachelor, Edith and Morton, Sarah U. and Ngonzi, Joseph and Ochora, Moses and Olupot Oluput, Peter and Onen, Justin and Roberts, Drucilla J. and Sheldon, Kathryn and Sinnar, Shamim A. and Smith, Jasmine and Ssenyonga, Peter and Paulson, Joseph N. and Meier, Frederick A. and Ericson, Jessica E. and Broach, James R. and Schiff, Steven, Cytomegalovirus Infections in Ugandan Infants:Newborns, Neonates with Sepsis and Infants with Hydrocephalus. Available at SSRN: https://ssrn.com/abstract=3889999 or http://dx.doi.org/10.2139/ssrn.3889999

Christine Hehnly

Pennsylvania State University - Institute of Personalized Medicine ( email )

University Park
State College, PA 16802
United States

Paddy Ssentongo

Pennsylvania State University - Center for Neural Engineering ( email )

212 Earth and Engineering Sciences Building
University Park, PA 16802
United States

Lisa Bebell

Harvard University - Division of Infectious Diseases ( email )

Boston, MA
United States

Kathy Burgoine

University of Liverpool

Chatham Street
Brownlow Hill
Liverpool, L69 7ZA
United Kingdom

Mbale Regional Referral Hospital - Neonatal Unit ( email )

Mbale
Uganda

Joel Bazira

Mbarara University of Science and Technology

Uganda

Claudio Fronterre

Lancaster University - Centre for Health Informatics, Computing, and Statistics ( email )

Lancaster
United Kingdom

Elias Kumbakumba

Mbarara University of Science and Technology - Department of Pediatrics ( email )

Uganda

Ronald Mulondo

CURE Children's Hospital of Uganda ( email )

Uganda

Edith Mbabazi-Kabachelor

CURE Children's Hospital of Uganda ( email )

Uganda

Sarah U. Morton

Harvard University - Harvard Medical School

25 Shattuck St
Boston, MA 02115
United States

Harvard University - Division of Newborn Medicine ( email )

Boston, MA
United States

Joseph Ngonzi

Mbarara University of Science and Technology - Department of Obstetrics and Gynaecology ( email )

Mbarara
Uganda

Moses Ochora

Mbarara University of Science and Technology - Department of Pediatrics ( email )

Uganda

Peter Olupot Oluput

Mbale Regional Referral Hospital - Neonatal Unit ( email )

Mbale
Uganda

Busitema University - Mbale Clinical Research Institute ( email )

P.O Box 236
Tororo, 236
Uganda

Justin Onen

Mbarara University of Science and Technology - Department of Pediatrics ( email )

Uganda

CURE Children's Hospital of Uganda ( email )

Uganda

Drucilla J. Roberts

Harvard University - Department of Pathology ( email )

Boston, MA
United States

Kathryn Sheldon

Pennsylvania State University - Institute of Personalized Medicine ( email )

University Park
State College, PA 16802
United States

Shamim A. Sinnar

Pennsylvania State University - Penn State College of Medicine

700 HMC Crescent Road Hershey
Hershey, PA 17033
United States

Jasmine Smith

Pennsylvania State University - Institute of Personalized Medicine

University Park
State College, PA 16802
United States

Peter Ssenyonga

Mbarara University of Science and Technology - Department of Pediatrics ( email )

Uganda

CURE Children's Hospital of Uganda ( email )

Uganda

Joseph N. Paulson

Genentech, Inc. - San Francisco - Department of Biostatistics ( email )

United States

Frederick A. Meier

Henry Ford Health System - Henry Ford Hospital

Detroit
United States

Wayne State University - School of Medicine ( email )

Detroit, MI 48201
United States

Jessica E. Ericson

Pennsylvania State University - Division of Pediatric Infectious Disease ( email )

Hershey, PA
United States

James R. Broach

Pennsylvania State University - Institute of Personalized Medicine ( email )

University Park
State College, PA 16802
United States

Steven Schiff (Contact Author)

Pennsylvania State University - Center for Neural Engineering ( email )

212 Earth and Engineering Sciences Building
University Park, PA 16802
United States

Pennsylvania State University - Department of Engineering Science and Mechanics ( email )

101 Hammond Building
University Park
PA 16802
United States

Pennsylvania State University - Center for Infection Disease Dynamics ( email )

PA
United States

Pennsylvania State University - Department of Neurosurgery ( email )

PA
United States

Pennsylvania State University - Department of Physics ( email )

104 Davey Lab
University Park, PA 16802
United States