The Effect of Early Postnatal Nutrition on Human T Cell Leukemia Virus Type 1 Mother-to-Child Transmission: A Systematic Review and Meta-Analysis.

The main route of mother-to-child transmission (MTCT) of human T cell leukemia virus type 1 is vertical transmission via breastfeeding. Although the most reliable method for preventing MCTC is exclusive formula feeding (ExFF), short-term breastfeeding (STBF) or frozen-thawed breast milk feeding (FTBMF) has been offered as an alternative method if breastfeeding is strongly desired. The aim of this review was to clarify the pooled risk ratio of MCTC of STBF and FTBMF compared with ExFF. This study was registered with PROSPERO (number 42018087317). A literature search of PubMed, CINAHL, the Cochrane Database, EMBASE, and Japanese databases through September 2018 identified 1979 articles, 10 of which met the inclusion criteria. Finally, 11 articles, including these 10 studies and the report of a recent Japanese national cohort study, were included in the meta-analysis. The pooled relative risks of STBF ≤3 months, STBF ≤6 months, and FTBMF compared with ExFF were 0.72 (95% confidence interval (CI): 0.30-1.77; p = 0.48), 2.91 (95% CI: 1.69-5.03; p = 0.0001), and 1.14 (95% CI: 0.20-6.50; p = 0.88), respectively. This meta-analysis showed no statistical difference in the risk of MTCT between STBF ≤3 months and ExFF, but the risk of MTCT significantly increased in STBF ≤6 months.

Lactancia materna y COVID-19 / Breastfeeding and COVID-19

Resumen La pandemia de enfermedad por coronavirus 2019 (COVID-19) ha afectado a todas las dimensiones de la atención en salud, entre ellas el aseguramiento de la lactancia materna exclusiva y su promoción. El riesgo de contagio y las consecuencias de la pandemia han provocado preocupación entre las futuras madres o las que se ya encuentran lactando debido al riesgo de una posible transmisión del virus a través de la leche materna. Aunque aún no se ha detectado el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) activo en la leche materna. El miedo al contagio ha favorecido las políticas de aislamiento madre-hijo. Hasta el momento no existe evidencia de transmisión vertical y el riesgo de transmisión horizontal en el lactante es similar al de la población general. En lactantes con COVID-19 la lactancia materna incluso puede cambiar favorablemente el curso clínico de la enfermedad.

Abstract The COVID-19 pandemic has affected the health attention in all dimensions, one of them, the exclusive breastfeeding assurance and her promotion. The high risk of contagion and the pandemic consequences have raised a number of concerns in future mothers or those who are breastfeeding because of the risk of a possible transmission of the virus through breast milk. Although SARS-CoV2 has no evidence of being active on breast milk, the fear of contagion has favored mother-child isolation policies. At this point, there are no evidence of vertical transmission and the risk of horizontal transmission in the infant is similar to the general population. Breastfeeding in newborn with COVID-19, can even favorably change the clinical course of the disease.

High Levels of Interferon-Alpha Expressing Macrophages in Human Breast Milk During SARS-CoV-2 Infection: A Case Report.

Introduction: In addition to hand washing and wearing masks, social distancing and reducing exposure time to <15 minutes are the most effective measures against the spread of COVID-19. Unfortunately, three of these guidelines are very difficult, if not impossible, for nursing babies: they cannot wear masks, stay six feet away from the lactating breasts, nor consistently finish within 15 minutes while nursing. We report a case of a nursing mother with SARS-CoV-2 infection, documenting changes of immune cells and cytokines in breast milk with and without the infection. Case Description: With Institutional Review Board (IRB) approval, we obtained expressed breast milk samples from a lactating mother before and during SARS-CoV-2 infection as documented by reverse transcription-PCR. Using flow cytometry analysis, we measured the immune cell profiles and expression of cytokines such as interferon alpha (IFNα) in milk leukocytes before and during infection. Results: There was an eightfold increase in IFNα+ milk leukocytes, from 1% before SARS-CoV-2 infection to 8% when actively infected. The milk macrophages showed the highest increase in IFNα expression. Both T and B lymphocytes showed mild increase. Innate lymphoid cells, neutrophils, and natural killer cells showed no increase in IFNα expression and the dendritic cells actually showed a reduction. Conclusion: We document the presence and high expression of IFNα in the breast milk macrophages of a lactating mother with confirmed COVID-19, compared with her milk before the infection.

IgA binds to the AD-2 epitope of glycoprotein B and neutralizes human cytomegalovirus.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that is potentially pathogenic in immunosuppressed individuals and pregnant females during primary infection. The HCMV envelope glycoprotein B (gB) facilitates viral entry into all cell types and induces a potent immune response. AD-2 epitope is a highly conserved linear neutralizing epitope of gB and a critical target for antibodies; however, only 50% of sero-positive individuals make IgG antibodies to this site and IgA responses have not been fully investigated. This study aimed to compare IgG and IgA responses against gB and the AD-2 epitope in naturally exposed individuals and those receiving a recombinant gB/MF59 adjuvant vaccine. Thus, vaccination of sero-positive individuals improved pre-existing gB-specific IgA and IgG levels and induced de novo gB-specific IgA and IgG responses in sero-negative recipients. Pre-existing AD-2 IgG and IgA responses were boosted with vaccination, but de novo AD-2 responses were not detected. Naturally exposed individuals had dominant IgG responses towards gB and AD-2 compared with weaker and variable IgA responses, although a significant IgA binding response to AD-2 was observed within human breastmilk samples. All antibodies binding AD-2 contained kappa light chains, whereas balanced kappa/lambda light chain usage was found for those binding to gB. V region-matched AD-2-specific recombinant IgG and IgA bound both to gB and to AD-2 and neutralized HCMV infection in vitro. Overall, these results indicate that although human IgG responses dominate, IgA class antibodies against AD-2 are a significant component of human milk, which may function to protect neonates from HCMV.

The nucleic acid positive rate and genotype distribution of human cytomegalovirus in human milk banks in China.

To determine the status of human cytomegalovirus (HCMV) infection in human milk in China, a total of 510 human milk samples obtained from three provinces, including 211 donor human milk samples from human milk banks and 299 milk samples obtained from the mothers of premature infants, were tested to detect HCMV DNA. Overall, 46.4% of the donated milk samples and 59.2% of the samples obtained from mothers of premature infants were positive for HCMV DNA. The concentration of HCMV DNA was approximately 103 -104 copies/ml in the HCMV-DNA-positive human milk samples. Based on the nucleotide sequence of a 299- to 305-bp fragment of the glycoprotein B (gB) gene, three HCMV genotypes (gB1, gB2 and gB3) were identified in human milk samples. Mixed infection with genotypes gB1 and gB3 was also found in four milk samples from mothers. Genotype gB1 was the predominant genotype in the HCMV-DNA-positive human milk samples, and it could be subdivided into three lineages. There were also some characteristic nucleotides and amino acids in the three HCMV genotypes, which were helpful for distinguishing the genotypes. This is the first study to clarify the HCMV infection status and genetic characteristics of human milk obtained from banks in China, which will be helpful in preventing postnatal HCMV infections and ensuring the safety of human milk banks.

To breastfeed or not to breastfeed? Lack of evidence on the presence of SARS-CoV-2 in breastmilk of pregnant women with COVID-19 / Lactancia materna en mujeres con COVID-19: falta de evidencia sobre la presencia de SARS-CoV-2 en la leche materna / Aleitamento materno em mulheres com COVID-19: falta de evidência da presença da SARS-CoV-2 no leite materno

A rapid systematic review was carried out to evaluate the current evidence related to the presence of SARS-CoV-2 in breast milk from pregnant women with COVID-19. Eight studies analyzing the presence of SARS-CoV-2 RNA in the breast milk of 24 pregnant women with COVID-19 during the third trimester of pregnancy were found. All patients had fever and/or symptoms of acute respiratory illness and chest computed tomography images indicative of COVID-19 pneumonia. Most pregnant women had cesarean delivery (91.7%) and two neonates had low birthweight (< 2 500 g). Biological samples collected immediately after birth from upper respiratory tract (throat or nasopharyngeal) of neonates and placental tissues showed negative results for the presence SARS-CoV-2 by RT-PCR test. No breast milk samples were positive for SARS-CoV-2 and, to date, there is no evidence on the presence of SARS-CoV-2 in breast milk of pregnant women with COVID-19. However, data are still limited and breastfeeding of women with COVID-19 remains a controversial issue. There are no restrictions on the use of milk from a human breast milk bank.(AU)

Se llevó a cabo una revisión sistemática rápida para evaluar la evidencia disponible sobre la presencia de SARS-CoV-2 en la leche materna de mujeres embarazadas afectadas con COVID-19. Se encontraron ocho estudios que analizaron la presencia de ARN de SARS-CoV-2 en la leche materna de 24 mujeres embarazadas con COVID-19 durante el tercer trimestre del embarazo. Todas las pacientes tenían fiebre o síntomas de enfermedad respiratoria aguda e imágenes de tomografía computarizada de tórax indicativas de neumonía por COVID-19. La mayoría de las mujeres embarazadas (91,7%) tuvieron un parto por cesárea y dos neonatos presentaron bajo peso al nacer (< 2 500 g). Las muestras biológicas recogidas inmediatamente después del parto de las vías respiratorias superiores (faringe o nasofaringe) de los neonatos y los tejidos placentarios mostraron resultados negativos para SARS-CoV-2 mediante RT-PCR. Ninguna muestra de leche materna fue positiva para SARS-CoV-2 y, hasta la fecha, no hay evidencia de la presencia de SARS-CoV-2 en la leche materna de las mujeres embarazadas con COVID-19. Sin embargo, los datos disponibles todavía son limitados y la lactancia materna en las mujeres con COVID-19 sigue siendo un tema controvertido. No hay restricciones para el uso de leche materna de banco.(AU)

Foi realizada uma revisão sistemática rápida para avaliar as evidências atuais relacionadas à presença da SARS-CoV-2 no leite materno de mulheres grávidas com COVID-19. Foram encontrados oito estudos analisando a presença de RNA do SARS-CoV-2 no leite materno de 24 gestantes com COVID-19 durante o terceiro trimestre de gravidez. Todas as pacientes apresentavam febre ou sintomas de doença respiratória aguda e imagens de tomografia computadorizada do tórax indicativas de pneumonia pela COVID-19. A maioria das gestantes teve parto cesáreo (91,7%) e dois recém-nascidos tiveram baixo peso ao nascer (< 2 500 g). As amostras biológicas coletadas imediatamente após o nascimento do trato respiratório superior (faringe ou nasofaringe) de neonatos e tecidos placentários apresentaram resultados negativos para a presença do SARS-CoV-2 pelo teste RT-PCR. Nenhuma amostra de leite materno foi positiva para o SARS-CoV-2 e, até à data, não há evidências da presença do SARS-CoV-2 no leite materno de mulheres grávidas com COVID-19. No entanto, os dados ainda são limitados e a amamentação de mulheres com COVID-19 continua a ser uma questão controversa. Não há restrições ao uso de leite de um banco de leite materno humano.(AU)

Productive Infection of Mouse Mammary Glands and Human Mammary Epithelial Cells by Zika Virus.

Zika virus (ZIKV) belongs to the large category of arboviruses. Surprisingly, several human-to-human transmissions of ZIKV have been notified, either following sexual intercourse or from the mother to fetus during pregnancy. Importantly, high viral loads have been detected in the human breast milk of infected mothers, and the existence of breastfeeding as a new mode of mother-to-child transmission of ZIKV was recently hypothesized. However, the maternal origin of infectious particles in breast milk is currently unknown. Here, we show that ZIKV disseminates to the mammary glands of infected mice after both systemic and local exposure with differential kinetics. Ex vivo, we demonstrate that primary human mammary epithelial cells were sensitive and permissive to ZIKV infection in this study. Moreover, by using in vitro models, we prove that mammary luminal- and myoepithelial-phenotype cell lines are both able to produce important virus progeny after ZIKV exposure. Our data suggest that the dissemination of ZIKV to the mammary glands and subsequent infection of the mammary epithelium could be one mechanism of viral excretion in human breast milk.

Microwave treatment of breast milk for prevention of cytomegalovirus infection.

BACKGROUND: Breast milk (BM) is the best nutrition for very preterm infants (VPI), except when provided by human cytomegalovirus (HCMV)-seropositive mothers. Given that VPI are at high risk of developing a sepsis-like syndrome or cholestasis, methods for prevention of HCMV infection via BM have been investigated. Although Holder pasteurization (HP) is the gold standard, HP needs special instruments. Microwave (MW) is available anywhere, therefore, we performed this study to determine whether MW can be used for HCMV prevention. METHODS: Human cytomegalovirus Towne strain was added to formula, followed by heating procedure using HP or MW (at 500 W for 20, 30, 40, or 60 s). HFL-III cells were seeded in culture dishes. Aliquots of HCMV-milk samples after heating were inoculated onto susceptible cell monolayers. The number of plaques was counted to determine the viral titer. The determination of HCMV-DNA copies was also performed. RESULTS: Addition of HCMV for a viral load of 5.0 × 103 plaque-forming units (p.f.u.)/mL achieved 772 p.f.u./mL at baseline, with a decrease to 257 p.f.u./mL after MW radiation for 20 s. No plaque was detected after HP or MW for 30, 40, and 60 s. The temperature of the breast milk reached 60°C after MW radiation for 40 s. The number of HCMV-DNA copies did not change with MW. CONCLUSIONS: Microwave at 500 W for 40 s can be used as a prevention strategy for HCMV transmission. Further research including the loss of bioactive properties in BM is required prior to clinical application.

Ebola Virus Isolation Using Huh-7 Cells has Methodological Advantages and Similar Sensitivity to Isolation Using Other Cell Types and Suckling BALB/c Laboratory Mice.

Following the largest Ebola virus disease outbreak from 2013 to 2016, viral RNA has been detected in survivors from semen and breast milk long after disease recovery. However, as there have been few cases of sexual transmission, it is unclear whether every RNA positive fluid sample contains infectious virus. Virus isolation, typically using cell culture or animal models, can serve as a tool to determine the infectivity of patient samples. However, the sensitivity of these methods has not been assessed for the Ebola virus isolate, Makona. Described here is an efficiency comparison of Ebola virus Makona isolation using Vero E6, Huh-7, monocyte-derived macrophage cells, and suckling laboratory mice. Isolation sensitivity was similar in all methods tested. Laboratory mice and Huh-7 cells were less affected by toxicity from breast milk than Vero E6 and MDM cells. However, the advantages associated with isolation in Huh-7 cells over laboratory mice, including cost effectiveness, sample volume preservation, and a reduction in animal use, make Huh-7 cells the preferred substrate tested for Ebola virus Makona isolation.

Human papillomavirus (HPV) shedding in breast milk from African women living with HIV.

BACKGROUND: Little is known about human papillomavirus (HPV) shedding in human breast milk. OBJECTIVE: To investigate HPV shedding in mature breast milk specimens collected from breastfeeding African women living with HIV-1 and not receiving antiretroviral treatment. DESIGN: 62 African women enrolled in the ANRS 12174 trial participated in this study. 79 lactoserum specimens obtained from right and/or left breasts from 42 Zambian women as well as lactosera and cell pellets from 40 milk samples collected from right and left breasts among 20 Ugandan women were tested for HPV using the INNO-LiPA HPV Genotyping Extra II assay. RESULTS: HPV DNA was detected in 9 (11.4%) lactoserum specimens collected from 8 (19.0%) Zambian women. Fourteen (17.5%) samples from 5 (25%) Ugandan women were positive for HPV detection. Differences in HPV type identification between the two breasts as well as between lactoserum and cell pellet were oberved. Overall, 13 (21.0%) of the 62 women included in this study had detectable HPV DNA in their breast milk, representing 11 HPV types, including high-risk, probable high-risk and low-risk types. CONCLUSION: This study confirms that HPV can be frequently detected in breast milk in HIV-infected women. Further studies are needed to understand the way by which maternal milk can shed HPV.

[Xenobiotics and pathogens in breast milk : A risk for the child?] / Fremdstoffe und Krankheitserreger in der Muttermilch : Ein Risiko für das Kind?

Although breast milk is the best diet in the first few months of life, risks can arise for the breast-fed infant. The article gives a comprehensive overview of possible risks regarding xenobiotics and pathogens in mother's milk, including medications, smoking, alcohol consumption, coffee consumption, persistent environmental contaminants and residues as well as infections.Where drug therapy is indicated, suitable medications are available for most conditions nowadays, so that prolonged nursing breaks or even weaning is not required. Long-term treatment, especially under combination therapy, needs to be examined on a case-by-case basis, however. Smoking and alcohol consumption should be avoided during the breastfeeding period, while moderate coffee consumption (up to 2 cups daily) is not of concern. The current levels of environmental contaminants and residues in breast milk are considered to be harmless to health; indeed, the body burden of dioxins considered to be critically high more than 20 years ago has been reduced by a factor of 10 to date. Among maternal infections, an human deficiency virus (HIV) infection is one of the few medical indications for weaning in countries with adequate hygiene standards.All in all, the risks of xenobiotics and pathogens in mother's milk are generally low in exclusively breastfed infants, so that there is usually no need for prolonged nursing breaks or even weaning. In only a small number of maternal conditions (certain medications, HIV infection), the infant should not be breastfed.

Epstein-Barr Virus Type 2 Infects T Cells in Healthy Kenyan Children.

Background: The 2 strains of Epstein-Barr virus (EBV), EBV type 1 (EBV-1) and EBV-2, differ in latency genes, suggesting that they use distinct mechanisms to establish latency. We previously reported that EBV-2 infects T cells in vitro. In this study, we tested the possibility that EBV-2 infects T cells in vivo. Methods: Purified T-cell fractions isolated from children positive for EBV-1 or EBV-2 and their mothers were examined for the presence of EBV and for EBV type. Results: We detected EBV-2 in all T-cell samples obtained from EBV-2-infected children at 12 months of age, with some children retaining EBV-2-positive T cells through 24 months of age, suggesting that EBV-2 persists in T cells. We were unable to detect EBV-2 in T-cell samples from mothers but could detect EBV-2 in samples of their breast milk and saliva. Conclusions: These data suggest that EBV-2 uses T cells as an additional latency reservoir but that, over time, the frequency of infected T cells may drop below detectable levels. Alternatively, EBV-2 may establish a prolonged transient infection in the T-cell compartment. Collectively, these novel findings demonstrate that EBV-2 infects T cells in vivo and suggest EBV-2 may use the T-cell compartment to establish latency.

Breast Milk Is a Potential Vehicle for Human Papillomavirus Transmission to Oral Mucosa of the Spouse.

BACKGROUND: Human papillomavirus (HPV) DNA has been detected in breast milk, but its origin has remained obscure. The aim of the study was to analyze the prevalence and persistence of HPV in breast milk in the Finnish Family HPV cohort study. The association of breast milk HPV positivity with the family members' oral HPV status was evaluated. METHODS: We included 308 families to the study where the mother was breast feeding her offspring. Mothers collected the milk samples manually at day 3, and at months 2, 6 and 12. Cervical and/or oral samples were collected from all family members. HPV testing was performed using nested polymerase chain reaction and Luminex-based Multimetrix kit. RESULTS: Breast milk HPV DNA was found in 10.1% (31/308), 20.1% (39/194) and 28.8% (17/59) of samples at day 3, months 2 and 6, respectively. The following HPV genotypes were detected: 6, 16, 18, 33, 45, 53, 56, 59, 66 and 82. Breast milk HPV persisted among 5.5% (9/164) of the lactating mothers. No significant associations were detected between the persistent breast milk HPV and the offspring's oral incident HPV infection. Breast milk HPV positivity showed a strong association with the fathers' oral HPV positivity at baseline, as well as at 6- and 12-month follow-up visits, with odds ratio (OR) = 3.24 [95% confidence interval (CI): 1.04-10.12], OR = 6.34 (95% CI: 1.84-21.89) and OR = 14.25 (95% CI: 1.16-174.80), respectively. CONCLUSIONS: HPV in breast milk is prevalent among the lactating mothers and HPV can also persist in breast milk. The breast milk is a potential vehicle for HPV transmission to oral mucosa of the spouse but not of the offspring.

Secondary haemophagocytic lymphohistiocytosis triggered by postnatally acquired cytomegalovirus infection in a late preterm infant.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory condition with impairment of cytotoxic T-cells and natural killer cells. Causes in infants are mostly hereditary immune defects as well as various infectious triggering factors, amongst these cytomegalovirus (CMV). Vertical CMV transmission may occur in utero, during birth, and by breast feeding. Usually, a CMV infection transmitted via breast milk is symptomatic only in very immature preterm infants. We report on a late preterm infant born after 35 + 5 weeks of gestation with a birth weight of 1840 g, being admitted to our intensive care unit at the age of 9 weeks with acute enteritis and severe dehydration. After a prolonged recovery, the infant developed a sepsis-like condition with hyperpyrexia, hepatosplenomegaly, and pancytopenia. Combination with high ferritin levels (2809 µg/l), hypertriglyceridaemia (481 mg/dl), elevated soluble IL-2 receptor (sCD25, 9120 U/ml), and reduced perforin expression allowed diagnosis of HLH, caused by an acute CMV infection. Since connatal CMV infection had been ruled out earlier, we report the rare case of secondary HLH triggered by a postnatally acquired symptomatic CMV infection in an immunocompetent infant, most likely transmitted via breast milk. The infant was successfully treated with ganciclovir without need for immunosuppressive therapy.