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.

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.

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.

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.

Incident HSV-2 infections are common among HIV-1-discordant couples.

BACKGROUND: The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. METHODS: HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner. CONCLUSIONS: The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

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.

Acute cytomegalovirus infection is associated with increased frequencies of activated and apoptosis-vulnerable T cells in HIV-1-infected infants.

Cytomegalovirus (CMV) coinfection is associated with infant HIV-1 disease progression and mortality. In a cohort of Kenyan HIV-infected infants, the frequencies of activated (CD38(+) HLA-DR(+)) and apoptosis-vulnerable (CD95(+) Bcl-2(-)) CD4(+) and CD8(+) T cells increased substantially during acute CMV infection. The frequency of activated CD4(+) T cells was strongly associated with both concurrent CMV coinfection (P = 0.001) and HIV-1 viral load (P = 0.05). The frequency of apoptosis-vulnerable cells was also associated with CMV coinfection in the CD4 (P = 0.02) and CD8 (P < 0.001) T cell subsets. Similar observations were made in HIV-exposed uninfected infants. CMV-induced increases in T cell activation and apoptosis may contribute to the rapid disease progression in coinfected infants.

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.

Diagnostic performance of dual-energy CT for the detection of traumatic bone marrow lesions in the ankle: comparison with MR imaging.

PURPOSE: To evaluate prospectively the performance of noncalcium images reconstructed from dual-energy (DE) computed tomography (CT) for the diagnosis of bone marrow lesions in patients with acute ankle joint trauma in comparison with magnetic resonance (MR) images. MATERIALS AND METHODS: The study had local ethics board approval, and written informed consent was obtained. Thirty consecutive patients (15 women; mean age, 34 years±11.8 [standard deviation]) underwent dual-source DE CT (80 kVp and 140 kVp with tin filter) and MR imaging within 1 day following acute ankle trauma. DE CT data were postprocessed by using a three-material decomposition algorithm for generating noncalcium images. MR and noncalcium images were graded by two blinded, independent readers using a four-point system (1=distinct bone marrow lesion, 4=no lesion); CT numbers in noncalcium images were calculated by a third reader. MR imaging interpretations served as the reference standard. RESULTS: Interreader agreement for qualitative grading of DE CT images was substantial (κ=0.66). The respective sensitivity, specificity, positive predictive value, and negative predictive value of DE CT for depicting distinct bone marrow lesions for both readers were 90.0% each, 80.5% and 81.6%, 25.4% and 26.5%, and 99.1% each. In regions without abnormality, CT numbers in noncalcium images gradually increased from proximal to distal location (P<.001). Significant differences in CT numbers were found in regions positive for bone marrow lesions compared with those that were negative (P<.001). CT numbers for the diagnosis of distinct bone marrow lesions according to MR imaging revealed areas under the receiver operating characteristic curve of 0.973, 0.813, and 0.758 for ankle mortise, talar dome, and talar body/head, respectively. CONCLUSION: Compared with MR images, distinct traumatic bone marrow lesions of the ankle joint can be diagnosed on noncalcium images reconstructed from DE CT with high sensitivity and excellent negative predictive value, but with moderate specificity and low positive predictive value.

Consistency of Mycobacterium tuberculosis-specific interferon-gamma responses in HIV-1-infected women during pregnancy and postpartum.

BACKGROUND: We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women. METHODS: Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models. RESULTS: Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8 spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9-117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: -1.5-21.8 SFCs/well). CONCLUSION: Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum.

Breast milk HIV-1 RNA levels and female sex are associated with HIV-1-specific CD8+ T-cell responses in HIV-1-exposed, uninfected infants in Kenya.

BACKGROUND: Although evidence supports a relationship between human immunodeficiency virus (HIV)-1 exposure and HIV-1-specific CD8(+) T cell responses, studies have not demonstrated a direct association between the quantity of HIV-1 to which a person is exposed and the presence or absence of a response. METHODS: From 1999 to 2005, maternal HIV-1 RNA levels were measured in blood, cervical secretions, and breast milk at delivery and 1 month after delivery. HIV-1-specific interferon (IFN)-γ Elispot assays were conducted to determine infant CD8(+) T-cell responses at 3 months of age. RESULTS: Among 161 infants tested with Elispot assays, 23 (14%) had positive results. Mothers whose infants had a positive assay had higher breast milk HIV-1 RNA levels at month 1 compared with mothers whose infants had negative Elispot assays (3.1 vs 2.5 log(10) copies/mL; P = .017). Female infants were also more likely to have positive Elispot assays than male infants (P = .046), and in multivariate analyses, both female sex and high breast milk HIV-1 levels remained important predictors of a positive response (P = .022 and P = .015, respectively). CONCLUSIONS: Exposure to breast milk HIV-1 and sex were associated with development of HIV-1-specific CD8(+) T-cell responses in infants. These data support a role for mucosal exposure via the oral route in induction of systemic HIV-1-specific cellular immunity.

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.

Latent tuberculosis detection by interferon γ release assay during pregnancy predicts active tuberculosis and mortality in human immunodeficiency virus type 1-infected women and their children.

BACKGROUND: We evaluated the prognostic usefulness of interferon γ release assays (IGRAs) for active tuberculosis and mortality in Kenyan human immunodeficiency virus type 1 (HIV-1)-infected women and their infants. METHODS: Prevalence and correlates of Mycobacterium tuberculosis-specific T-SPOT.TB IGRA positivity were determined during pregnancy in a historical cohort of HIV-1-infected women. Hazard ratios, adjusted for baseline maternal CD4 cell count (aHR(CD4)), were calculated for associations between IGRA positivity and risk of active tuberculosis and mortality over 2-year postpartum follow-up among women and their infants. RESULTS: Of 333 women tested, 52 (15.6%) had indeterminate IGRA results. Of the remaining 281 women, 120 (42.7%) had positive IGRA results, which were associated with a 4.5-fold increased risk of active tuberculosis (aHR(CD4), 4.5; 95% confidence interval [CI], 1.1-18.0; P = .030). For immunosuppressed women (CD4 cell count, <250 cells/µL), positive IGRA results were associated with increased risk of maternal mortality (aHR(CD4), 3.5; 95% CI, 1.02-12.1;), maternal active tuberculosis or mortality (aHR(CD4), 5.2; 95% CI, 1.7-15.6; P = .004), and infant active tuberculosis or mortality overall (aHR(CD4), 3.0; 95% CI, 1.0-8.9; P = .05) and among HIV-1-exposed uninfected infants (aHR(CD4), 7.3; 95% CI, 1.6-33.5; P = .01). CONCLUSIONS: Positive IGRA results for HIV-1-infected pregnant women were associated with postpartum active tuberculosis and mortality among mothers and their infants.

Maternal human leukocyte antigen A*2301 is associated with increased mother-to-child HIV-1 transmission.

We examined associations between maternal human leukocyte antigen (HLA) and vertical human immunodeficiency virus type 1 (HIV-1) transmission in a perinatal cohort of 277 HIV-infected women in Nairobi. HLA class I genes were amplified by using sequence-specific oligonucleotide probes, and analyses were performed using logistic regression. Maternal HLA-A*2301 was associated with increased transmission risk before and after adjusting for maternal viral load (unadjusted: odds ratio [OR], 3.21; 95% confidence interval [CI], 1.42-7.27; P = .005; Pcorr = 0.04; adjusted: OR, 3.07; 95% CI, 1.26-7.51; P =.01; Pcorr is not significant). That maternal HLA-A*2301 was associated with transmission independent of plasma HIV-1 RNA levels suggests that HLA may alter infectivity through mechanisms other than influencing HIV-1 load.

Immune responses to measles and tetanus vaccines among Kenyan human immunodeficiency virus type 1 (HIV-1)-infected children pre- and post-highly active antiretroviral therapy and revaccination.

BACKGROUND: : HIV-1-infected children have lower response rates after measles and tetanus immunization than uninfected children. We determined the extent to which highly active antiretroviral therapy (HAART) augments vaccine immunity and promotes responses to revaccination. METHODS: : Previously immunized, antiretroviral-naive HIV-1-infected children were evaluated for immunity against measles and tetanus. After 6 months on HAART, children meeting CD4% criteria (>15%) who were persistently antibody negative were revaccinated and immunity was reassessed. RESULTS: : At enrollment, among 90 children with mean age of 4.9 years, 67% had negative measles IgG and 22% negative tetanus IgG. Among 62 children completing 6 months on HAART, 17 (40%) of 43 without protective measles IgG converted and 10 (53%) of 19 positive children lost measles responses (P = 0.3). Children who lost responses had significantly lower measles antibody concentrations than those who remained measles IgG positive during follow-up (7.1 vs. 20.3 mg/mL; P = 0.003). Three (23%) of 13 children negative for tetanus IgG spontaneously seroconverted on HAART, while 15 (31%) of 49 children lost tetanus antibody (P = 0.008). There was a nonsignificant trend for an association between spontaneous measles seroconversion and lower baseline HIV-1 viral load (P = 0.06). Tetanus seroconversion was associated with older age (P = 0.03). After revaccination, positive responses were observed in 78% and 75% of children reimmunized against measles and tetanus, respectively. CONCLUSIONS: : After 6 months of HAART, more than half of previously immunized children still lacked positive measles antibody. With increased use of HAART in pediatric populations, revaccination against measles and tetanus should be considered to boost response rates and immunization coverage.

The consistency of definitions of successful aging provided by older men: the Manitoba follow-up study.

ABSTRACTIn the absence of a universally agreed-upon definition of successful aging, researchers increasingly look to older adults for layperson views of aging and definitions of successful aging. To use lay definitions in studies of aging, however, researchers must address the definitions' consistency. In 2004, surviving members of the Manitoba Follow-up Study male cohort (mean age: 83 years) were asked twice for their definition of successful aging. A consistency category was assigned based on the similarity of themes in each of 654 pairs of definitions. At least half of the main themes were similar in 70 per cent of the definition pairs; 80 per cent of respondents repeated at least one theme. Positive or negative health events in the four-week interval between definitions and specific respondents' characteristics did not vary across consistency categories. This evidence for consistency supports our continued reliance on lay definitions of successful aging.

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.

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.

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.