Anti-Cytomegalovirus Activity in Human Milk and Colostrum From Mothers of Preterm Infants.

OBJECTIVES: This study aimed to investigate the anti-human cytomegalovirus (CMV) activity of milk from seropositive and seronegative mothers of preterm infants and to analyze its changes throughout the different stages of lactation and after Holder pasteurization, a procedure adopted by donor human milk banks. METHODS: Eighteen mothers of preterm infants were enrolled in the study. Colostrum, transitional milk, and mature milk samples were collected and tested for anti-CMV activity. Depletion of immunoglobulins A from milk samples was carried out by jacalin resin. Pools of milk samples were pasteurized according to Holder technique. RESULTS: All samples were endowed with anti-CMV activity, although to a different extent. In CMV IgG-positive mothers, colostra were significantly more active than the transitional milk and mature milk samples. Moreover, they were more potent than colostra from seronegative mothers. Immunoglobulins A depletion in colostra from IgG-positive mothers resulted in a partial loss of anti-CMV activity. Holder pasteurization significantly reduced the antiviral activity. CONCLUSIONS: Human milk is endowed with anti-CMV activity and its potency may vary depending on the stage of lactation and the serological status of the mother. This biological property could partially neutralize CMV particles excreted in the milk of CMV IgG-positive mothers thus reducing the risk of transmitting infectious viruses to the infant.

Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa.

BACKGROUND: Breastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers. METHODS: Two cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration. RESULTS: Human cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs <12 months; 95% confidence interval [CI], 0.84-8.59; P = .03) and HIV-exposed infants (OR = 20.37 for >6 months vs never; 95% CI, 3.71-111.70; P < .001). CONCLUSIONS: Prolonged breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding.

An email survey of midwives knowledge about CytoMegaloVirus (CMV) in Hannover and a skeletal framework for a proposed teaching program.

At present there is lack of information about CMV transmission given to midwives, general practitioners, neonatal pediatricians and nurses, with intrauterine transmission having profound consequences in terms of outcomes for the infected neonate. To identify one particular group of midwives knowledge about CMV, the research question surveyed midwives' knowledge of CMV. A quantitative electronic survey was the research method utilized in this study. To assess midwives knowledge about CMV, the first author emailed colleagues in Hannover and was in receipt of 40 completed questionnaires. Results showed that midwives have gaps in their knowledge about CMV and that an educational program is necessary to enlarge their understandings. Given the catastrophic consequences to the neonate of contracting congenital CMV, it is imperative that both health care professionals and women receive the educational message about prevention. In response an education program for lecturers has been proposed, which consists of eleven learning objectives.

Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia.

BACKGROUND: Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. METHODS: Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. RESULTS: All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: -0.44 [95% confidence interval {CI}, -.72 to -.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: -0.72 [95% CI, -1.23 to -.22]; P = .01) and lower psychomotor development (Bayley test score difference: -4.1 [95% CI, -7.8 to -.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. CONCLUSION: HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region.

A population-based study of how children are exposed to saliva in KwaZulu-Natal Province, South Africa: implications for the spread of saliva-borne pathogens to children.

OBJECTIVES: In sub-Saharan Africa, many viral infections, including Epstein-Barr virus, cytomegalovirus, Kaposi's sarcoma-associated herpesvirus and hepatitis B are acquired in childhood. While saliva is an important transmission conduit for these viruses, little is known about how saliva is passed to African children. We endeavoured to identify the range and determinants of acts by which African children are exposed to saliva. METHODS: To identify the range of acts by which African children are exposed to saliva, we conducted focus groups, semi-structured interviews and participant observations in an urban and a rural community in South Africa. To measure the prevalence and determinants of the identified acts, we administered a questionnaire to a population-based sample of caregivers. RESULTS: We identified 12 caregiving practices that expose a child's oral-respiratory mucosa, cutaneous surfaces or anal-rectal mucosa to saliva. Several acts were heretofore not described in the contemporary literature (e.g., caregiver inserting finger lubricated with saliva into child's rectum to relieve constipation). Among 896 participants in the population-based survey, many of the acts were commonly practised by all respondent types (mothers, fathers, grandmothers and siblings). The most common were premastication of food, sharing sweets and premastication of medicinal plants that are spit onto a child's body. CONCLUSIONS: African children are exposed to saliva through a variety of acts, practised by a variety of caregivers, with no single predominant practice. This diversity poses challenges for epidemiologic work seeking to identify specific saliva-passing practices that transmit viruses. Most acts could be replaced by other actions and are theoretically preventable.

Human cytomegalovirus infection of breast milk.

Human cytomegalovirus is the most common cause of congenital and perinatal infections throughout the world. Primary infection with human cytomegalovirus usually follows a benign course, but the virus remains latent or persistent in the host cell thereafter. Understanding the epidemiology of human cytomegalovirus is a key element in the development of strategies for prevention of infection. Although the actual sites of latency or persistence of human cytomegalovirus infections are still controversial, peripheral blood mononuclear cells and endothelial cells appear to be major sites of infection. Persistent infections caused by human cytomegalovirus could be augmented by a decrease in major histocompatibility complex expression as well as by virus-mediated immune dysfunction. It is possible that specific cellular interactions as well as production of several cytokines are necessary for the reactivation of human cytomegalovirus. Breast-fed infants are susceptible to human cytomegalovirus infection from breast milk. Human cytomegalovirus was isolated more frequently from breast milk at more than 1 month after delivery than from colostrum or early breast milk. Human cytomegalovirus DNA was also not detected in colostrum, but was found in breast milk samples 1 month after delivery. To clarify the role of milk cells and whey in vertical infection by breast feeding, we separated breast milk into milk cells and whey and examined each fraction. Human cytomegalovirus was isolated more frequently from milk whey samples than from cell samples. Human cytomegalovirus particle shedding into whey may be more important in vertical infection by breast milk than cell-to-cell transmission. The supernatant of colostrum did not exert an inhibitory effect on human cytomegalovirus-infected cells. Serum levels of cell free soluble interleukin-2 receptor of mothers with DNA-positive milk at 1 month after delivery were significantly higher than those of mothers with DNA-negative milk. It is likely that levels of factors such as soluble interleukin-2 receptor in serum are related to the reactivation of human cytomegalovirus which occurs locally in the mammary gland of the lactating mother after delivery. This minireview focuses on recent advances in the study of human cytomegalovirus infection of breast milk.