Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1.

UNLABELLED: Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

The ecocultural context and child behavior problems: A qualitative analysis in rural Nepal.

Commonly used paradigms for studying child psychopathology emphasize individual-level factors and often neglect the role of context in shaping risk and protective factors among children, families, and communities. To address this gap, we evaluated influences of ecocultural contextual factors on definitions, development of, and responses to child behavior problems and examined how contextual knowledge can inform culturally responsive interventions. We drew on Super and Harkness' "developmental niche" framework to evaluate the influences of physical and social settings, childcare customs and practices, and parental ethnotheories on the definitions, development of, and responses to child behavior problems in a community in rural Nepal. Data were collected between February and October 2014 through in-depth interviews with a purposive sampling strategy targeting parents (N = 10), teachers (N = 6), and community leaders (N = 8) familiar with child-rearing. Results were supplemented by focus group discussions with children (N = 9) and teachers (N = 8), pile-sort interviews with mothers (N = 8) of school-aged children, and direct observations in homes, schools, and community spaces. Behavior problems were largely defined in light of parents' socialization goals and role expectations for children. Certain physical settings and times were seen to carry greater risk for problematic behavior when children were unsupervised. Parents and other adults attempted to mitigate behavior problems by supervising them and their social interactions, providing for their physical needs, educating them, and through a shared verbal reminding strategy (samjhaune). The findings of our study illustrate the transactional nature of behavior problem development that involves context-specific goals, roles, and concerns that are likely to affect adults' interpretations and responses to children's behavior. Ultimately, employing a developmental niche framework will elucidate setting-specific risk and protective factors for culturally compelling intervention strategies.

HomeBank: An Online Repository of Daylong Child-Centered Audio Recordings.

HomeBank is introduced here. It is a public, permanent, extensible, online database of daylong audio recorded in naturalistic environments. HomeBank serves two primary purposes. First, it is a repository for raw audio and associated files: one database requires special permissions, and another redacted database allows unrestricted public access. Associated files include metadata such as participant demographics and clinical diagnostics, automated annotations, and human-generated transcriptions and annotations. Many recordings use the child-perspective LENA recorders (LENA Research Foundation, Boulder, Colorado, United States), but various recordings and metadata can be accommodated. The HomeBank database can have both vetted and unvetted recordings, with different levels of accessibility. Additionally, HomeBank is an open repository for processing and analysis tools for HomeBank or similar data sets. HomeBank is flexible for users and contributors, making primary data available to researchers, especially those in child development, linguistics, and audio engineering. HomeBank facilitates researchers' access to large-scale data and tools, linking the acoustic, auditory, and linguistic characteristics of children's environments with a variety of variables including socioeconomic status, family characteristics, language trajectories, and disorders. Automated processing applied to daylong home audio recordings is now becoming widely used in early intervention initiatives, helping parents to provide richer speech input to at-risk children.