Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants

Gantt, Soren; Orem, Jackson; Krantz, Elizabeth M; Morrow, Rhoda Ashley; Selke, Stacy; Huang, Meei Li; Schiffer, Joshua T.; Jerome, Keith R.; Nakaganda, Annet; Wald, Anna; Casper, Corey; Corey, Lawrence

doi:10.1093/infdis/jiw076

Cited by 53 publications

(86 citation statements)

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“…We present a detailed description of oral shedding during primary CMV infection in a cohort of healthy Ugandan infants [10]. While primary CMV infection in infants is notable for protracted shedding with high viral load [3,5], we were able to identify 3 distinct phases of oral CMV shedding in this cohort of infants, using their known time of infection.…”

Section: Discussionmentioning

confidence: 97%

“…As previously described [10], pregnant women in Kampala were enrolled, and oral swabs were collected in a standardized manner [11] from the mother and all children for quantitative polymerase chain reaction (qPCR) analysis of CMV [12]. Blood samples were collected from the infants at 6 weeks of age and every 4 months thereafter.…”

Section: Study Cohort and Datamentioning

confidence: 99%

“…Among 32 Ugandan infants followed prospectively from birth, 20 postnatal primary CMV infections were captured over 30 months [10]. We excluded 6 infants following acquisition, owing to limited data (Supplementary Methods and Figure S1).…”

Section: Primary CMV Infectionmentioning

confidence: 99%

“…All newborns were healthy and had normal growth and development during the study period. None had symptoms of CMV infection [10].…”

Section: Primary CMV Infectionmentioning

confidence: 99%

“…Oral swabs and plasma samples were tested for CMV, using real-time qPCR. Primary infection was defined virologically and serologically as described elsewhere [10]. Additional information about subject selection is provided in the Supplementary Materials.…”

mentioning

confidence: 99%

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Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

Mayer¹,

Matrajt²,

Casper³

et al. 2016

J Infect Dis.

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Cytomegalovirus (CMV) infection occurs frequently in young children, who, when infected, are then a major source of transmission. Oral CMV shedding by 14 infants with primary infection was comprehensively characterized using quantitative polymerase chain reaction weekly for ≥9 months. Three phases of oral shedding were identified: expansion, transition, and clearance. Viral expansion occurred over a median of 7 weeks, with a median doubling time of 3 days. During the transition phase, expansion slowed over a median of 6 weeks before peak viral load was reached. Clearance was slow (22-day median half-life), and shedding did not resolve during observation for any infant. Mathematical modeling demonstrated that prolonged oral CMV expansion is explained by a low within-host reproduction number (median, 1.63) and a delayed immune response that only decreases the infected cell half-life by 44%. Thus, the prolonged oral CMV shedding observed during primary infection can be explained by slow viral expansion and inefficient immunologic control.Keywords. epidemiology; cytomegalovirus; transmission; mathematical model; immunology; theoretical biology.Worldwide, most primary cytomegalovirus (CMV) infections occur during early childhood, through the oral route [1]. Infected infants shed CMV orally at high, persistent levels [2-6] and are a major source of transmission, including to pregnant women, which contributes to congenital infection [3,[7][8][9]. Viral dynamics during primary infection are governed by properties of viral infectivity and the immune response. A detailed study of these processes could identify immunologic thresholds necessary for effective vaccination. Here, we use mathematical models to describe oral shedding dynamics during primary CMV infection in a cohort of Ugandan infants. MATERIALS AND METHODS Study Cohort and DataAs previously described [10], pregnant women in Kampala were enrolled, and oral swabs were collected in a standardized manner [11] from the mother and all children for quantitative polymerase chain reaction (qPCR) analysis of CMV [12]. Blood samples were collected from the infants at 6 weeks of age and every 4 months thereafter. Oral swabs and plasma samples were tested for CMV, using real-time qPCR. Primary infection was defined virologically and serologically as described elsewhere [10]. Additional information about subject selection is provided in the Supplementary Materials. This study was approved by all relevant institutional review boards in Uganda, the United States, and Canada. Written informed consent was obtained from all study participants or their guardians. Statistical Analysis and Classification of EpisodesEpisode duration was defined as the interval from the start of oral shedding until the end of observation. Correlations between same-day log 10 copies of CMV in plasma and oral swabs were calculated using Pearson correlation for all values and for positive values only. To see whether positive plasma samples were associated with higher oral log 10 CMV levels, we performed ...

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Section: Discussionmentioning

confidence: 97%

Section: Study Cohort and Datamentioning

confidence: 99%

Section: Primary CMV Infectionmentioning

confidence: 99%

“…All newborns were healthy and had normal growth and development during the study period. None had symptoms of CMV infection [10].…”

Section: Primary CMV Infectionmentioning

confidence: 99%

mentioning

confidence: 99%

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Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

Mayer¹,

Matrajt²,

Casper³

et al. 2016

J Infect Dis.

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Attenuation of human herpesvirus 6B reactivation by aging

Kobayashi

Nishiyama

Yamauchi

et al. 2019

Journal of Medical Virology

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Objective: There has been little research on human herpesvirus 6B (HHV-6B) in healthy adults and prevalences in different age groups have been unclear. Therefore, the major objective of this study was to evaluate seroprevalence to HHV-6 antibodies in ordinary working people and examine the effect of aging on seroprevalence. Also, as HHV-6B is reactivated in saliva, another objective was to investigate an association between age and HHV-6B reactivation based on measured salivary HHV-6 DNA levels.Methods: Our subjects were 77 ordinary office workers who underwent a health checkup. In this population, we measured anti-HHV-6 antibody titers using enzyme-linked immunosorbent assay and salivary HHV-6 DNA levels. In addition to examining an association with age, we examined associations with body mass index, smoking habit, and alcohol consumption as confounding factors.Results: There was a significant decrease in the seropositivity of HHV-6 antibodies in subjects of 50 years and older, and age was significantly negatively correlated with anti-HHV-6 antibody titers. Age and salivary HHV-6 DNA levels were also significantly negatively correlated but there were no significant correlations with other factors. Conclusions:Our results suggest that HHV-6B reactivation is attenuated by aging.Thus, HHV-6 antibodies steadily decrease in the body with aging. K E Y W O R D S human herpesvirus 6 (HHV-6), immune system, latent infection, reactivation J Med Virol. 2019;91:1335-1341.wileyonlinelibrary.com/journal/jmv

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Tuberculosis and Other Opportunistic Infections in HIV-Infected Children

Rabie

Marais

2017

Viral Infections in Children, Volume I

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Prospective Characterization of the Risk Factors for Transmission and Symptoms of Primary Human Herpesvirus Infections Among Ugandan Infants

Abstract: By capturing exposures and acquisition events, we found that the incidence and risk factors of infection vary by HHV type. HSV-1 infection, unlike other HHV infections, caused acute clinical illness in these infants.

Cited by 53 publications

References 40 publications

Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

Dynamics of Persistent Oral Cytomegalovirus Shedding During Primary Infection in Ugandan Infants

Attenuation of human herpesvirus 6B reactivation by aging

Tuberculosis and Other Opportunistic Infections in HIV-Infected Children

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