Trauma Program Value Assessment at an Academic Health Network System Over 12 Years.

BACKGROUND: Trauma is a leading cause of global death, with 200 000 deaths and over 3 million non-fatal injuries/year in the United States. We aim to assess trauma care value for patients who underwent urgent laparotomies (LAP) and thoracotomies (THO) in our Health Network System. METHODS: Clinical variables (v = 84) from trauma patients (>18 yo) were retrieved retrospectively (Jan-2010 to July-2016) and prospectively (Aug-2016 to Sept-2021) from a Health System warehouse under IRB-approved protocols. Patients were divided according to their Injury Severity Score (ISS) into mild/moderate cases (ISS <15) and severe cases (ISS >15). Value was assessed using quality and cost domains. Quality surrogates included graded postoperative complications (PCs), length of stay (LOS), 30-day readmission (RA), patient satisfaction (PS), and textbook (TB) cases. Total charges (TCs) and reimbursement index (RI) were included as surrogates for cost. Value domains were displayed in scorecards comparing Observed (O) with Expected (E) (using the ACS risk calculator) outcomes. Uni-/multivariate analyses were performed using SPSS. RESULTS: 41,927 trauma evaluations were performed, leading to 16 044 admissions, with 528 (3.2%) patients requiring urgent surgical procedures (LAP = 413 and THO = 115). Although the M:F ratio (7:3) was similar in LAP vs THO groups, age and BMI were significantly different (41.8 ± 19.1 vs 51.8 ± 19.9 years, 28.6 ± 9.9 vs 27.4 ± 7 Kg/m2, respectively, P < .05). Blunt trauma was involved in 68.8/77.3% of the LAP/THO procedures, respectively (P < .05). Multivariate analyses showed ISS, age, ASA class, and medical center as factors significantly predicting PC (P < .05). Postoperative complication grades from the LAP/THO groups showed above-average outcomes; nonetheless, LOS was higher than the national averages. CONCLUSIONS: The Trauma Program holds high value in our Health Network System. Protocols for decreasing LOS are being implemented.

Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants.

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.

Passively Acquired Constant Region 5-Specific Antibodies Associated With Improved Survival in Infants Who Acquire Human Immunodeficiency Virus.

Studying vertical human immunodeficiency virus (HIV) transmission enables the impact of passively transferred antibodies on HIV transmission and pathogenesis to be examined. Using phage display of HIV envelope peptides and peptide enzyme-linked immunosorbent assay (ELISA), we found that, in infants who acquired HIV, passive antibody responses to constant region 5 (C5) were associated with improved survival in 2 cohorts. In a combined analysis, C5 peptide ELISA activity was correlated directly with survival and estimated infection time and inversely with set point viral load. These results suggest that preexisting C5-specific antibodies may be correlated with the survival of infants living with HIV, motivating additional research into their protective potential.

Measuring the destruction and recuperation of the natural gas pipeline system at Oregon's Critical Energy Infrastructure Hub.

Portland has become a hot spot for geological discussions over the last few years. The event that has everyone talking, and preparing for, is the Cascadia Subduction Zone earthquake. Cascadia is categorized as a catastrophic natural, seismic event, where the Juan De Fuca plate and the North American plate subduct off the Northwest coast, causing a violent response in the zone between the two plates. Geological history has shown us that every 200-300 years, a major seismic event occurs in this area of the Pacific; in current disaster discussions in the emergency management industry, where this author has resided for the last 6 years, it is not a matter of if, but a matter of when. The Cascadia event will cause a massive earthquake, affecting millions of lives and costing just as much if not more. Currently, there is no model that exists to equate for all of the following: damages to pipes, restoration, and disruption, and maximum thresholds for utility usage. The models and plans discussed in this paper will cast a needed spotlight for establishing a new model combining these elements and more. It is vital that efforts be made to calculate, beyond a base percentage rate of recovery, what Oregon and the region will lose and what it will take regain a "back to business" level of operations, economically, structurally, and environmentally. Many calls were placed with nonprofit energy stewards to determine these statistics, but no current information was available, or easy to attain, further emphasizing a need for real-time utility data.

Persistent Immune Activation in Human Immunodeficiency Virus-Infected Pregnant Women Starting Combination Antiretroviral Therapy After Conception.

This study evaluated the impact of human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV-exposed but uninfected children followed up from birth. Activated CD8+ T cells (CD38+ and HLA-DR+) were compared among HIV-uninfected (n = 95), cART experienced HIV-infected (n = 111), and cART-naive HIV-infected (n = 21) pregnant women. Immune activation was highest among HIV-infected/cART-naive women but decreased during pregnancy. Immune activation HIV-infected women who started cART during pregnancy was reduced but not to levels similar to those in HIV-uninfected women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.

Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants.

Maternal human immunodeficiency virus (HIV) infection has been shown to leave profound and lasting impacts on the HIV-exposed uninfected (HEU) infant, including increased mortality and morbidity, immunological changes, and developmental delays compared to their HIV-unexposed (HU) counterparts. Exposure to HIV or antiretroviral therapy may influence immune development, which could increase morbidity and mortality. However, a direct link between the increased mortality and morbidity and the infant's immune system has not been identified. To provide a global picture of the neonatal T cell repertoire in HEU versus HU infants, the diversity of the T cell receptor beta chain (TRB) expressed in cord blood samples from HEU infants was determined using next-generation sequencing and compared to healthy (HU) infants collected from the same community. While the TRB repertoire of HU infants was broadly diverse, in line with the expected idea of a naïve T cell repertoire, samples of HEU infants showed a significantly reduced TRB diversity. This study is the first to demonstrate differences in TRB diversity between HEU and HU cord blood samples and provides evidence that maternal HIV, in the absence of transmission, influences the adaptive immune system of the unborn child.

HIV-exposed uninfected infants: elevated cord blood Interleukin 8 (IL-8) is significantly associated with maternal HIV infection and systemic IL-8 in a Kenyan cohort.

BACKGROUND: In low and middle income countries, human immunodeficiency virus (HIV) exposed, uninfected (HEU) infants demonstrate higher morbidity and mortality than their unexposed counterparts. To determine possible immune correlates of this effect, we investigated the impact of in utero HIV exposure on the uninfected neonatal immune milieu and maternal factors mediating these abnormalities in a cohort of vaginally delivered mother-infants. Samples of delivery and cord blood plasma were selected from 22 Kenyan HIV-infected women and their HIV exposed uninfected (HEU) infants drawn from the pre-ARV era, while 19 Kenyan HIV-uninfected (HU) women and their infants were selected from a control cohort. RESULTS: Compared to HU cord plasma, HEU cord plasma contained significantly higher levels of pro-inflammatory cytokines interleukins (IL)-6 and -8 (both p < 0.001) and significantly lower levels of CXC motif chemokine 11 (CXC11) (p < 0.001). Mediation analysis demonstrated that maternal HIV infection status was a significant determinant of infant IL-8 responses: HEU status was associated with a ninefold higher infant:mother (cord:delivery) plasma levels of IL-8 (p < 0.005), whereas maternal viral load was negatively associated with HEU IL-8 levels (p = 0.04) and not associated with HEU IL-6 levels. CONCLUSIONS: Exposure to maternal HIV infection drives an increase in prenatal IL-8 that is partially mediated by maternal cytokine levels. Differences between maternal and infant cytokine levels strongly suggest independent modulation in utero, consistent with prenatal immune activation. Elevated pro-inflammatory signals at birth may interfere with T cell responses at birth and subsequently influence immune maturation and the risk of morbidity and mortality in HEU infants.

High background in ELISpot assays is associated with elevated levels of immune activation in HIV-1-seronegative individuals in Nairobi.

INTRODUCTION: Spontaneous interferon-γ (IFNγ) released detected by enzyme-linked immunospot (ELISpot) assays may be a biological phenomenon. Markers of immune activation levels were assessed as correlates of high background among individuals in Kenya. METHODS: Couples concordantly seronegative for HIV-1 were enrolled. IFN-γ ELISpot assays were conducted and negative control wells were categorized as having either high or low background (≥50 and <50 SFU/106 peripheral blood mononuclear cells [PBMC], respectively). PBMC were stained for CD4, CD8, and immune activation markers (CD38 and HLA-DR) and analyzed using flow cytometry. Proportions of activated T-cells were compared between those with low and high background by Mann-Whitney U test. Correlates of background SFU and immune activation were assessed using regression models. RESULTS: Among 58 individuals, 14 (24%) had high background. Frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ cells were higher in individuals with high background compared to those with low background (P = 0.02). Higher background SFU was associated with history of sexually transmitted infections (P = 0.03), and illness in the past 3 months (P = 0.005), in addition to increased levels of activated CD4+ and CD8+ cells (P range = 0.008-0.03). Female gender and male circumcision decreased levels of CD4+ and CD8+ immune activation (P range = 0.002-0.03). Additionally, higher background SFU and activated CD4+ and CD8+ cells were individually associated with positive ELISpot responses to HIV-1 peptide pools (P range = 0.01-0.03). CONCLUSIONS: These findings suggest that increased basal immune responses may be a biological mechanism contributing to higher background ELISpot SFU. Systematic exclusion of data from individuals with increased background in IFN-γ release assays may bias results in population-based studies.

The impact of dairy cows' bedding material and its microbial content on the quality and safety of milk - A cross sectional study of UK farms.

The introduction of bedding dairy cows on recycled manure solids (RMS) in the UK led to concern by competent authorities that there could be an increased, unacceptable risk to animal and human health. A cross-sectional study was designed to evaluate the microbial content of different bedding materials, when used by dairy cows, and its impact on the microbial content of milk. Data were collected from farms bedding lactating cows on sand (n=41), sawdust (n=44) and RMS (n=40). The mean duration of RMS use prior to sampling was 13months. Total bacterial count, and counts of Streptococcus/Enterococcus spp., Staphylococcus spp., Bacillus cereus, thermophilic, thermoduric and psychrotrophic bacteria were determined in used bedding and milk. Samples were evaluated for the presence/absence of Listeria monocytogenes, Salmonella spp. and Yersinia enterocolitica. Data on milking practices were collected to investigate their potential to reduce microbial transfer from bedding to milk. There were substantial differences in bacterial counts both within and between bedding materials. However, there were no significant differences between bedding groups in counts in milk for any of the organisms studied, and no significant correlations between bacterial load in used bedding and milk. Fore-milking was associated with a reduced total bacterial count in milk. Dipping teats with disinfectant and drying, prior to milking, was associated with lower numbers of Streptococcus/Enterococcus spp. in milk. Disinfecting clusters between milking different cows was associated with a reduction in thermophilic and psychrotrophic counts in milk. This study did not provide evidence that use of RMS bedding increased the risk of presence of Y. enterocolitica, Salmonella spp. or L. monocytogenes in milk. However, the strength of this conclusion should be tempered by the relatively small number of farms on which Y. enterocolitica and Salmonella spp. were isolated. It is concluded that, despite the higher bacterial load of RMS, its use as bedding for lactating dairy cows need not be associated with a higher bacterial load in milk than the use of sand or sawdust. However, this finding must be interpreted in the light of the relatively recent introduction of RMS as a bedding material on the farms studied. Teat preparation provides a control point for the potential transfer of microorganisms from bedding to milk. The detection of zoonotic pathogens in a small proportion of milk samples, independent of bedding type, indicates that pasteurisation of milk prior to human consumption remains an important control measure.

Higher Transplacental Pathogen-Specific Antibody Transfer Among Pregnant Women Randomized to Triple Antiretroviral Treatment Versus Short Course Zidovudine.

BACKGROUND: HIV-1 infection may impair transplacental antibody transfer to infants. The impact of highly active antiretroviral treatment (ART) given during pregnancy on transplacental antibody transport is unknown. METHODS: HIV-1 infected pregnant women with CD4 counts between 200 - 500 were randomized to short-course zidovudine (ZDV) or triple ART at 32 weeks gestation for prevention of mother-to-child HIV-1 transmission. Levels of maternal antibody against measles, pneumococcus and rotavirus at delivery, and antibody transfer to the baby through cord blood, were compared between trial arms. RESULTS: Overall, 141 and 148 women were randomized to triple ART and ZDV, respectively; cord blood was available for a subset (n = 20 in triple ART and n = 22 in ZDV). Maternal antibody levels to all pathogens during pregnancy and at delivery were not significantly different between arms. Within each arm, antibody levels at delivery were lower than at enrolment. For all antibodies, a woman's levels before delivery were an important predictor of amount transferred to her infant. Women on triple ART transferred higher levels of pathogen-specific antibodies when compared with women on short course ZDV. CONCLUSIONS: Women on triple ART transferred higher levels of pathogen-specific antibodies compared with women on ZDV alone.

What the FLOQ? A quality improvement project to reduce unnecessary paediatric respiratory viral swabs in a peripheral metropolitan hospital.

AIM: To reduce the number of paediatric respiratory viral swabs (locally referred to as a FLOQ) performed across the authors clinical centre from a baseline of over 800 ($38 000) per year by 25% over 4 months from 6 February 2017 to 31 May 2017. METHODS: A quality improvement project 'What the FLOQ?' (WTF) was instigated from 6 February 2017 to complement the Emergency Department (ED) 'Sensible Test Ordering Process' project from 1 April 2017. Stakeholder engagement across ED and general paediatric staff was sought. Alterations in practice included education of staff, targeted feedback to groups frequently ordering a FLOQ and rationalising patients appropriate for testing. Monthly requests were tallied on a run chart for FLOQs ordered in ED and the paediatric ward. A monthly audit of FLOQs performed on ED-discharged patients was conducted with feedback. RESULTS: Total FLOQ swabs decreased by 55% from 336 (February to May 2016) to 151 (February to May 2017). ED performed 66% less FLOQs from 237 (February to May 2016) to 82 (February to May 2017). There was no increase in the number of FLOQs performed on the paediatric ward February to May 2017. Monthly auditing of ED discharged patients under 2 years with a FLOQ went from 40 to 3%. CONCLUSION: Rationalising patient groups appropriate for testing with targeted feedback and broad stakeholder engagement successfully reduced FLOQs performed by 55%. This has projected savings of over $21 000 by 12 months. WTF has reduced the number of invasive patient procedures performed, benefitting staff and patients. Sustaining this change will be achieved through ongoing staff education on rationalisation criteria and consultant only requests outside of these parameters.

Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection.

Antiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines.

High Rates of Exclusive Breastfeeding in Both Arms of a Peer Counseling Study Promoting EBF Among HIV-Infected Kenyan Women.

BACKGROUND: Exclusive breastfeeding (EBF) is recommended for 6 months after delivery as the optimal infant feeding method and is especially important for prevention of mother-to-child HIV transmission (PMTCT). However, EBF promotion efforts among HIV-infected mothers in sub-Saharan Africa have achieved mixed success and require context-specific interventions. METHODS: HIV-positive, pregnant women from six clinics in Nairobi were enrolled into a clinic-level, before-after counseling intervention study. All women received standard perinatal and HIV care. Women in the intervention arm were offered three counseling sessions that promoted EBF, described its benefits, and explained breastfeeding techniques. Mother-infant pairs were followed until 14 weeks postpartum, with infant HIV testing at 6 weeks. EBF prevalence at 14 weeks postpartum was compared between study arms using log-binomial regression. Proportions of 6-week HIV-free survival and 14-week infant survival were assessed using Cox regression. Risk estimates were adjusted for clinic, relationship status, and antiretroviral therapy. RESULTS: Between 2009 and 2013, 833 women were enrolled of whom 94% planned to practice EBF for 6 months and 95% were taking therapeutic or prophylactic antiretrovirals. Median age was 27 years; median CD4 count was 403 cells/µL. EBF prevalence at 14 weeks postpartum was 86% in the control and 81% in the intervention group (p = 0.19). No differences were observed between groups for 6-week HIV-free survival and 14-week infant survival. CONCLUSION: Women who received breastfeeding counseling were not more likely to breastfeed exclusively, in part due to high overall EBF prevalence in this study population. The high EBF prevalence is an important finding, given recent efforts to promote EBF in Kenya.

Emergency nurses' perceptions of the role of confidence, self-efficacy and reflexivity in managing the cognitively impaired older person in pain.

AIMS AND OBJECTIVES: The study aimed to explore the practice of care among emergency nurses caring for older persons with cognitive impairment and who presented in pain from a long bone fracture, to highlight nurse confidence and self-efficacy in practice. BACKGROUND: Cognitive impairment is an issue increasingly facing emergency departments. Older persons with cognitive impairment have complex care needs, requiring effective clinical decision-making and provision of care. Nurse confidence and self-efficacy are critical to meeting the necessary standards of care for this vulnerable patient group. DESIGN: A multi-centre study. METHODS: The study was undertaken across four emergency departments in Sydney, Australia. Sixteen focus group discussions were conducted with 80 emergency departments of nurses. RESULTS: Four main themes emerged: confidence and self-efficacy through experience; confidence and self-efficacy as a balancing act; confidence and self-efficacy as practice; and confidence and self-efficacy and interpersonal relations. CONCLUSIONS: Our findings demonstrate that confidence, self-efficacy and reflexivity enabled the delivery of appropriate, timely and compassionate care. Further, confidence and self-efficacy within nursing praxis relied on clinical experience and reflective learning and was crucial to skill and knowledge acquisition. RELEVANCE TO CLINICAL PRACTICE: Our research suggests that confidence, self-efficacy and reflexivity need to be developed and valued in nurses' careers to better meet the needs of complex older persons encountered within everyday practice.

Depot Medroxyprogesterone Acetate Use Is Associated With Elevated Innate Immune Effector Molecules in Cervicovaginal Secretions of HIV-1-Uninfected Women.

OBJECTIVE: The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use. METHODS: HIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception. RESULTS: Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log10 ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log10 ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar. CONCLUSIONS: Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.

PedVacc 002: a phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi.

BACKGROUND: A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants. TRIAL DESIGN: A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya. METHODS: Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines. RESULTS: Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p=0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p=0.05). CONCLUSIONS: This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens.

Natural killer cell and T-cell subset distributions and activation influence susceptibility to perinatal HIV-1 infection.

OBJECTIVE: To determine neonatal immunologic factors that correlate with mother-to-child-transmission of HIV-1. DESIGN: This case-control study compared cord blood natural killer (NK) and T-cell populations of HIV-1 exposed infants who subsequently acquired infection by 1 month (cases) to those who remained uninfected by 1 year of life (controls). Control specimens were selected by proportional match on maternal viral load. METHODS: Cryopreserved cord blood mononuclear cells (CBMCs) were thawed and stained for multiparameter flow cytometry to detect NK and T-cell subsets and activation status. CBMCs were also used in a viral suppression assay to evaluate NK cell inhibition of HIV-1 replication in autologous CD4 T cells. RESULTS: Cord blood from cases contained a skewed NK cell repertoire characterized by an increased proportion of CD16CD56 NK cells. In addition, cases displayed less-activated CD16CD56 NK cells and CD8 T cells, based on HLA-DRCD38 costaining. NK cell suppression of HIV-1 replication ex vivo correlated with the proportion of acutely activated CD68CD16CD56 NK cells. Finally, we detected a higher proportion of CD27CD45RA effector memory CD4 and CD8 T cells in cord blood from cases compared with controls. CONCLUSION: When controlled for maternal viral load, cord blood from infants who acquired HIV-1 had a higher proportion of CD16CD56 NK cells, lower NK cell activation and higher levels of mature T cells (potential HIV-1 targets) than control infants who remained uninfected. Our data provide evidence that infant HIV-1 acquisition may be influenced by both innate and adaptive immune cell phenotypes and activation status.

Measles seropositivity in HIV-infected Kenyan children on antiretroviral therapy.

This article describes results from a cross-sectional study among HIV-infected children 15 months to 12 years of age who were receiving antiretroviral therapy. We found a low prevalence of measles IgG seropositivity (45.7%) and identified CD4% ≥ 25 as a predictor. Most HIV-infected children on ART were not measles seropositive and might benefit from revaccination.