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Focuses on a study which determined the influence of human lymphocyte antigen supertype A2/6802 on HIV type 1 transmission in HIV positive mothers and children in Kenya. Methods; Results; Discussion.

Unlabelled: OBJECTIVES To compare sociodemographic profiles, child care, child feeding practices and growth indices of children born to HIV-1 seropositive and seronegative mothers.Methods: A cohort study of 234 children (seropositive and seronegative) born to HIV-1 seropositive mothers and 139 children born to seronegative mothers in Pumwani Maternity Hospital which serves a low-income population in Nairobi, Kenya from December 1991 and January 1994.Results: With few exceptions, at the time of their birth children in all three cohorts had parents with similar characteristics, lived in similar housing in similar geographical areas, had their mothers as their primary care givers, had similar feeding practices and similar growth status and patterns. However, the HIV-1 seropositive mothers were slightly younger (23.8 years vs. 25.0 years, P < 0.01), if married they were less likely to be their husband's first wife (79% vs. 91%, P = 0.02) and more likely to have a one-room house (75% vs. 63%, P = 0.04). All three cohorts had mean Z-scores in length-for-age and in weight-for-height within the normal range (>/= 2.0 Z-scores) from birth to 21 months with the exception of the length-for-age of the seropositive children at the 18-month visit. In all cohorts length-for-age became more compromised than weight-for-length, dropping to about -1.45 Z-score by 21 months; in contrast, weight-for-length dropped to about -0.5 Z-score by this age. The only statistically significant differences in growth indices among the three cohorts were between the two cohorts of seronegative children: those with seronegative mothers were less compromised in length-for-age at 1.5 months (mean Z-score = -0.19 vs. -0.48, P < 0.05) and more compromised in weight-for-length at 6 months (mean Z-score = 0.10 vs. 0.45, P < 0.05) and at 18 months (mean Z-score = -0.73 vs. -0.16, P < 0.05). 27-34% were exclusively breastfed at 1.5 months; 52-61% consumed solid foods in addition to breast milk by 2.5 months.Conclusions: Low-income HIV-1 seropositive- and seronegative-born children were from families with similar characteristics and similar housing environments. Similar growth patterns in the cohorts suggest that the challenging environment and the choice of weaning foods had an impact on all three cohorts. The aggressive care given the children with HIV-1 seropositive mothers and their children may have reduced the progression and impact of HIV-1 disease on the growth of the seropositive children. Further research is needed to corroborate our findings to be certain that our results are not affected by loss to follow-up bias: we lost the same proportion in all three cohorts but cannot verify that the children we lost had the same growth patterns as those who remained in the study. [ABSTRACT FROM AUTHOR]

Examines the effect of human immunodeficiency virus (HIV) type 1 viral genotype on mother-to-child transmission of HIV-1. Distribution of the HIV-1 clades among different transmitting groups of mothers in Nairobi, Kenya; Identification of recombinant, mixed and clade B isolates in Nairobi; Factors known to be associated with mother-to-child HIV transmission.

Résumé: Contexte: Les facteurs de risque de complications graves de l'infection par le SRAS-CoV-2 n'ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. Méthodes: Nous avons procédé à une étude prospective nationale en utilisant l'infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d'enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés. Résultats: Sur les 264 hospitalisations d'enfants ayant contracté le SRAS-CoV-2 au cours de la période de l'étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d'autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d'une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d'une forme d'assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d'obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l'exclusion de l'asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19. Interprétation: Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l'obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue. [ABSTRACT FROM AUTHOR]

Background: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease.Methods: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital.Results: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19.Interpretation: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease. [ABSTRACT FROM AUTHOR]

Whereas the infant gut microbiome is the subject of intense study, relatively little is known regarding the nares microbiome in newborns and during early life. This study aimed to survey the typical composition and diversity of human anterior nare microflora for developing infants over time, and to explore how these correlate to their primary caregivers. Single nare swabs were collected at five time points over a one-year period for each subject from infant-caregiver pairs. Our study comprised of 50 infants (recruited at 2 weeks, post delivery) and their 50 primary caregivers. Applying the chaperonin-60 (cpn60) universal target (UT) amplicon as our molecular barcoding marker to census survey the microbial communities, we longitudinally surveyed infant nares microbiota at 5 time points over the course of the first year of life. The inter- and intra-subject diversity was catalogued and compared, both longitudinally and relative to their adult primary caregivers. Although within-subject variability over time and inter-subject variability were both observed, the assessment detected only one or two predominant genera for individual infant samples, belonging mainly to phyla Actinobacteria, Firmicutes, and Proteobacteria. Consistent with previously observed microbial population dynamics in other body sites, the diversity of nares microflora increased over the first year of life and infants showed differential operational taxonomic units (OTUs) relative to their matched primary caregiver. The collected evidence also support that both temporal and seasonal changes occur with respect to carriage of potentially pathogenic bacteria (PPBs), which may influence host predisposition to infection. This pilot study surveying paired infant/caregiver nare microbiomes provides novel longitudinal diversity information that is pertinent to better understanding nare microbiome development in infants. [ABSTRACT FROM AUTHOR]

OBJECTIVE. The goal was to determine incidence, determinants, and morbidity and mortality rates of neonatal herpes simplex virus infections in Canada. METHODS. From October 1, 2000, to September 30, 2003, reports of neonatal herpes simplex virus infection were solicited actively from all Canadian pediatricians and pediatric subspecialists on a monthly basis. RESULTS. Fifty-eight cases of neonatal herpes simplex virus were reported (5.9 cases per 100 000 live births). Cesarean section was performed in 24.6% of cases, 28.1% of patients were born prematurely, 28.6% had birth weights of <2500 g, and 7.5% had Apgar scores of <7 at 5 minutes of life. Mothers <20 years of age and those reporting Aboriginal ethnicity were affected disproportionately; 40% of mothers had no history of genital herpes before delivery, and intrapartum genital lesions were present in only 1 of 58 cases. Of cases with known herpes simplex virus type, 62.5% were herpes simplex virus-1. Localized infections accounted for 59.6% of cases, whereas disseminated disease and central nervous system disease were reported for 17.5% and 22.8%, respectively. Localized infections were more likely to be herpes simplex virus-1 and disseminated and central nervous system infections herpes simplex virus-2. Nine of 58 cases were fatal. All cases with known treatment information (n = 55) were treated with intravenously administered acyclovir. CONCLUSIONS. This is the first study to examine the national incidence of neonatal herpes simplex virus in Canada. Many women had no genital herpes simplex virus history before delivery, and the majority of cases were herpes simplex virus-l, which has implications for prenatal screening and vaccine/drug development. Follow-up monitoring of case subjects is being performed annually for 3 years, to be completed in October 2006. [ABSTRACT FROM AUTHOR]

The initial site of exposure to human immunodeficiency virus (HIV)-1 during heterosexual transmission occurs in the genital tract. Although the majority of immunological studies have focused on the immune response to HIV-1 at the systemic level, our understanding of tissue-specific immunity is deficient. The goal of the present study was to characterize T cell populations found in the cervix of women shown to be resistant to infection by HIV-1. Levels of both systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant, HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV-1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1-resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was also determined, and cytokine and beta chemokine levels in the genital mucosa were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES expression, compared with the HIV-1-uninfected CSWs. This is the first study to show elevated levels of beta chemokines and CD4+ T cells in the genital tracts of women who are exposed to HIV-1 and yet are uninfected. [ABSTRACT FROM AUTHOR]

The initial site of exposure to human immunodeficiency virus (HIV)-1 during heterosexual transmission occurs in the genital tract. Although the majority of immunological studies have focused on the immune response to HIV-1 at the systemic level, our understanding of tissue-specific immunity is deficient. The goal of the present study was to characterize T cell populations found in the cervix of women shown to be resistant to infection by HIV-1. Levels of both systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant, HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV-1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1-resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was also determined, and cytokine and β chemokine levels in the genital mucosa were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES expression, compared with the HIV-1-uninfected CSWs. This is the first study to show elevated levels of β chemokines and CD4+ T cells in the genital tracts of women who are exposed to HIV-1 and yet are uninfected. [ABSTRACT FROM AUTHOR]

APOBEC3G is an important innate immune molecule that causes human immunodeficiency virus type 1 (HIV-1) hypermutation, which can result in detrimental viral genome mutations. The Vif protein of wild-type HIV-1 counteracts APOBEC3G activity by targeting it for degradation and inhibiting its incorporation into viral particles. Additional APOBEC cytidine deaminases have been identified, such as APOBEC3F, which has a similar mode of action but different sequence specificity. A relationship between APOBEC3F/G and HIV disease progression has been proposed. During HIV-1 sequence analysis of the vpu/env region of 240 HIV-infected subjects from Nairobi, Kenya, 13 drastically hypermutated proviral sequences were identified. Sequences derived from plasma virus, however, lacked hypermutation, as did proviral vif. When correlates of disease progression were examined, subjects with hypermutated provirus were found to have significantly higher CD4 counts than the other subjects. Furthermore, hypermutation as estimated by elevated adenine content positively correlated with CD4 count for all 240 study subjects. The sequence context of the observed hypermutation was statistically associated with APOBEC3F/G activity. In contrast to previous studies, this study demonstrates that higher CD4 counts correlate with increased hypermutation in the absence of obvious mutations in the APOBEC inhibiting Vif protein. This strongly suggests that host factors, such as APOBEC3F/G, are playing a protective role in these patients, modulating viral hypermutation and host disease progression. These findings support the potential of targeting APOBEC3F/G for therapeutic purposes. [ABSTRACT FROM AUTHOR]