Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants

Boucoiran, Isabelle; Mayer, Bryan T.; Krantz, Elizabeth Em; Marchant, Arnaud; Pati, Sunil; Boppana, Suresh; Wald, Anna; Corey, Lawrence; Casper, Corey; Schiffer, Joshua Jt; Gantt, Soren

doi:10.1097/inf.0000000000001877

Cited by 32 publications

(38 citation statements)

References 39 publications

(41 reference statements)

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“…Although oral shedding by household contacts did not appear to be relevant for infant acquisition of CMV in this setting, we posit that there is a relationship between the CMV viral load of an exposure and transmission. We did not collect breast milk from mothers in this cohort, but others have reported a positive correlation between the viral load in breast milk and the risk of infant CMV acquisition [22,43,44], and we have shown a dose-response between oral CMV viral load shedding by young children and transmission to their mothers [45]. Breast milk does not appear to be a route of HHV-6 transmission [24]; rather, saliva has been thought to be the major source of HHV-6 transmission based on the frequency of viral detection in saliva [3], which our data strongly support.…”

Section: Discussionmentioning

confidence: 90%

Estimating the Risk of Human Herpesvirus 6 and Cytomegalovirus Transmission to Ugandan Infants from Viral Shedding in Saliva by Household Contacts

Mayer

Krantz

Wald

et al. 2020

Viruses

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Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) infections are common in early childhood. In a prospective Ugandan birth cohort study, most infants acquired HHV-6 (24/31; 77%) and CMV (20/30; 67%) during follow-up. To assess the transmission risk, we modeled a dose–response relationship between infant HHV-6 and CMV infections and weekly oral viral shedding by mothers and all other (“secondary”) children in the home. Oral viral loads that were shed by mothers and secondary children were significantly associated with HHV-6 but not CMV transmission. While secondary children had higher and more frequent HHV-6 shedding than their mothers, they had a lower per-exposure transmission risk, suggesting that transmission to maternal contacts may be more efficient. HHV-6 transmission was relatively inefficient, occurring after <25% of all weekly exposures. Although HHV-6 transmission often occurs following repeated, low dose exposures, we found a non-linear dose–response relationship in which infection risk markedly increases when exposures reached a threshold of > 5 log10 DNA copies/mL. The lack of association between oral CMV shedding and transmission is consistent with breastfeeding being the dominant route of infant infection for that virus. These affirm saliva as the route of HHV-6 transmission and provide benchmarks for developing strategies to reduce the risk of infection and its related morbidity.

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Section: Discussionmentioning

confidence: 90%

Estimating the Risk of Human Herpesvirus 6 and Cytomegalovirus Transmission to Ugandan Infants from Viral Shedding in Saliva by Household Contacts

Mayer

Krantz

Wald

et al. 2020

Viruses

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“…Leukocyte infiltrates have been characterised during this period [36], and may be the source of reactivated virus. A study conducted in Uganda has shown that mothers can be infected with strains from children [37]. However, even though multiple-strain infections were common in the cohort, there was limited evidence for reinfection or reactivation during the 4-16 week period postpartum.…”

Section: Discussionmentioning

confidence: 99%

Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia

Suárez

Musonda

Escriva

et al. 2018

Preprint

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BackgroundIn developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, in whom multiple-strain infection is linked to disease severity. The situation is less documente in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in HIV-positive women. We investigated HCMV strain diversity.MethodsHigh-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-positive and seven HIV-negative) at 4 or 16 weeks (or both) postpartum and analysed by genotyping 12 hypervariable HCMV genes.ResultsAmong the 20 samples from 14 donors (13 HIV-positive and one HIV-negative) that yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to five strains per person were apparent in nine HIV-positive women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within the hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus-entry and immunomodulation, but not between genes more distant from each other.ConclusionsBreast milk from HIV-positive women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.

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“…Mothers with earlier excretion of infectious virus, higher CMV milk viral loads and longer duration of excretion, are more likely to transmit CMV 26--28 . An intriguing recent study from Uganda suggested that infant--to--mother transmission of CMV can also occur, such that infants first acquire primary CMV, either from another child in the house or from their mother through breastfeeding, and then transmit the infection to their mother 29 .…”

Section: CMVmentioning

confidence: 99%

Transmission of CMV, HTLV-1, and HIV through breastmilk

Prendergast

Goga

Waitt

et al. 2019

The Lancet Child & Adolescent Health

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Breastfeeding is a critical child survival intervention. The potential for transmission of some viral infections from mother-to-child, however, presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. Here, we compare the transmission dynamics, risk factors and outcomes of infection with three chronic viruses transmitted through breast milk: cytomegalovirus (CMV), human T-cell lymphotropic virus type 1 (HTLV-1), and human immunodeficiency virus (HIV). We provide an overview of current intervention approaches and discuss scientific, policy and programming gaps in our understanding of these major global infections. Key messages: • Three viruses are known to be transmitted through breastfeeding and to result in chronic infection: CMV, HTLV-1 and HIV. • CMV transmission through breast milk mostly leads to subclinical infection, except in preterm infants in whom severe clinical disease can occur; the best preventive and treatment approaches in this group remain unclear and more data are needed on long-term sequelae. • HTLV-1 is restricted to specific geographic foci and can be transmitted from mother-to-child through breastfeeding in 10-25% of cases; the best preventive strategy is avoidance or shortening of breastfeeding where safe alternatives are available. • The absolute transmission risk of HIV through breastfeeding in the context of suppressive maternal antiretroviral therapy is now low, even over extended periods. • Guidance for infant feeding for women living with HIV varies by setting: in low-and middle-income countries, breastfeeding with suppressive ART and adherence support is recommended, while in high-income settings formula feeding is advised.

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Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants

Cited by 32 publications

References 39 publications

Estimating the Risk of Human Herpesvirus 6 and Cytomegalovirus Transmission to Ugandan Infants from Viral Shedding in Saliva by Household Contacts

Estimating the Risk of Human Herpesvirus 6 and Cytomegalovirus Transmission to Ugandan Infants from Viral Shedding in Saliva by Household Contacts

Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia

Transmission of CMV, HTLV-1, and HIV through breastmilk

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