People living with HIV (PLH) suffer disproportionately from the chronic diseases exacerbated by smoking tobacco. We performed a systematic review and meta-analysis to establish the relative ...prevalence of smoking among PLH.
We included observational studies reporting current smoking rates among PLH and comparators without HIV. We searched Medline, EMBASE, LILACS and SciELO from inception to 31 August 2019. We excluded studies that recruited participants with smoking related illness. We used a random effects model to estimate the odds ratio for current smoking in PLH and people without HIV. We used the Newcastle--Ottawa scale to assess methodological bias. We performed subgroup analysis based on sex and WHO region. We quantified heterogeneity with meta-regression and predictive distributions. PROSPERO registration:CRD42016052608.
We identified 6116 studies and included 37. Of 111 258 PLH compared with 10 961 217 HIV-negative participants pooled odds of smoking were 1.64 (95% confidence interval, 95% CI: 1.45-1.85) (95% prediction interval: 0.66-4.10, I2 = 98.1%). Odds for men and women living with HIV were 1.68 (95% CI: 1.44-1.95) (95% prediction interval: 0.71-3.98, I2 = 91.1%) and 2.16 (95% CI: 1.77-2.63) (95% prediction interval: 0.92-5.07, I2 = 81.7%) respectively.
PLH are more likely to be smokers than people without HIV. This finding was true in subgroup analyses of men, women and in four of five WHO regions from which data were available. Meta-regression did not explain heterogeneity, which we attribute to the diversity of PLH populations worldwide. Smoking is a barrier to PLH achieving parity in life expectancy and an important covariate in studies of HIV-associated multimorbidity.
People living with HIV are at significantly increased risk of invasive pneumococcal disease, despite long-term antiretroviral therapy (ART). The mechanism explaining this observation remains ...undefined.
To determine if apoptosis-associated microbicidal mechanisms, required to clear intracellular pneumococci that survive initial phagolysosomal killing, are perturbed.
Alveolar macrophages (AM) were obtained by BAL from healthy donors or HIV-1-seropositive donors on long-term ART with undetectable plasma viral load. Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected with HIV-1
or treated with gp120. Macrophages were challenged with opsonized serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal activity, protein expression, and mitochondrial reactive oxygen species (mROS). AM phenotyping, ultrasensitive HIV-1 RNA quantification, and gp120 measurement were also performed in BAL.
HIV-1
infection impaired apoptosis, induction of mROS, and pneumococcal killing by MDM. Apoptosis-associated pneumococcal killing was also reduced in AM from ART-treated HIV-1-seropositive donors. BAL fluid from these individuals demonstrated persistent lung CD8
T lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite this, transcriptional activity in AM freshly isolated from people living with HIV was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect in pneumococcal killing in healthy MDM through post-translational modification of Mcl-1, preventing apoptosis induction, caspase activation, and increased mROS generation. Moreover, gp120 also inhibited mROS-dependent pneumococcal killing in MDM.
Despite ART, HIV-1, via gp120, drives persisting innate immune defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal disease.
•OPAT serves to avert inpatient costs of IV antimicrobial therapy for complicated urinary tract infections (UTIs).•OPAT outcomes for UTI are poorer in patients with urolithiasis and those ...hospitalized immediately before OPAT induction.•Prospective studies and service evaluations of OPAT for UTI treatment are needed to corroborate these findings.
Outpatient parenteral antimicrobial therapy (OPAT) is widely used to safely administer intravenous antibiotics in the outpatient setting. However, there are risks of treatment failure and clinical complications. We evaluate the outcomes of episodes of urinary tract infection (UTI) treated through OPAT at a large tertiary referral center in the UK.
We retrospectively reviewed patient records of episodes of UTI treated for ≥ 2 days at the Sheffield Teaching Hospitals OPAT unit from 2017 to 2021. We defined OPAT and infection failure as unplanned 30-day hospital readmissions and symptomatic non-improvement, respectively. Univariate and multivariate logistic regression analyses were performed to analyze predictors of these outcomes.
162 episodes of UTI in 115 patients were analyzed. OPAT failure was observed in 16.0 % (n = 26) of episodes, while infection remained unresolved in 8.0 % (n = 13) of episodes. Urolithiasis was an independent risk factor of both OPAT (odds ratio OR, 4.3; 95 % confidence interval CI, 1.2–16.1; p = 0.03) and infection failure (OR, 5.9; 95 % CI, 1.2–29.9; p = 0.03). Prior hospitalization also increased the risk of both OPAT (OR, 4.4; 95 % CI, 1.1–18.7; p = 0.04) and infection failure (OR, 8.0, 95 % CI, 1.3–78.4; p = 0.04).
These results can assist clinicians at commencement of OPAT to identify patients at high risk of treatment failure. Wider network studies are required to further elicit the role of urolithiasis and its treatment to improve outcomes of UTI management in OPAT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Immunocompromise is a commonly cited risk factor for Clostridium difficile infection (CDI). We reviewed the experimental and epidemiological literature on CDI in three immunocompromised ...groups, HIV-seropositive individuals, haematopoietic stem cell or bone marrow transplant recipients and solid organ transplant recipients. All three groups have varying degrees of impairment of humoral immunity, a major factor influencing the outcome of CDI. Soluble HIV proteins such as nef and immunosuppressive agents such as cyclosporin, azathioprine and mycophenalate mofetil modify signalling from the key cellular pathways triggered by C. difficile toxin A, although there is a paucity of data on how these factors may interact with pathways activated by toxin B. Despite this, there has been little direct investigation into the effect of immunosuppression on the pathogenesis of CDI. Epidemiological studies consistently show increased rates of CDI in these populations, which are higher in those with greater degrees of immunocompromise such as individuals with advanced AIDS not receiving combination antiretroviral therapy or allogeneic haematopoietic stem cell transplant recipients. Less consistently data suggests immunocompromise in each group also impacts rates of severe, recurrent or complicated CDI. However all these conditions are characterised by high levels of antibiotic use and prolonged hospital stay, both powerful drivers of CDI risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Microvascular abnormalities and impaired gas transfer have been observed in patients with COVID-19. The progression of pulmonary changes in these patients remains unclear.
Do patients hospitalized ...with COVID-19 without evidence of architectural distortion on structural imaging exhibit longitudinal improvements in lung function measured by using 1H and 129Xe MRI between 6 and 52 weeks following hospitalization?
Patients who were hospitalized with COVID-19 pneumonia underwent a pulmonary 1H and 129Xe MRI protocol at 6, 12, 25, and 51 weeks following hospital admission in a prospective cohort study between November 2020 and February 2022. The imaging protocol was as follows: 1H ultra-short echo time, contrast-enhanced lung perfusion, 129Xe ventilation, 129Xe diffusion-weighted, and 129Xe spectroscopic imaging of gas exchange.
Nine patients were recruited (age 57 ± 14 median ± interquartile range years; six of nine patients were male). Patients underwent MRI at 6 (n = 9), 12 (n = 9), 25 (n = 6), and 51 (n = 8) weeks following hospital admission. Patients with signs of interstitial lung damage were excluded. At 6 weeks, patients exhibited impaired 129Xe gas transfer (RBC to membrane fraction), but lung microstructure was not increased (apparent diffusion coefficient and mean acinar airway dimensions). Minor ventilation abnormalities present in four patients were largely resolved in the 6- to 25-week period. At 12 weeks, all patients with lung perfusion data (n = 6) showed an increase in both pulmonary blood volume and flow compared with 6 weeks, although this was not statistically significant. At 12 weeks, significant improvements in 129Xe gas transfer were observed compared with 6-week examinations; however, 129Xe gas transfer remained abnormally low at weeks 12, 25, and 51.
129Xe gas transfer was impaired up to 1 year following hospitalization in patients who were hospitalized with COVID-19 pneumonia, without evidence of architectural distortion on structural imaging, whereas lung ventilation was normal at 52 weeks.
Chronic lung disease (CLD) is common in individuals living with perinatally acquired HIV (PA-HIV) in southern/eastern Africa. Most of the UK PA-HIV population are African. We conducted a case-note ...review of CLD in 3 UK PA-HIV cohorts (n = 98). Bronchiectasis or obliterative bronchiolitis occurred in 8.1% of patients and ring/tramline opacities occurred in 19.2% of patients on chest radiograph. There may be unrecognized and underdiagnosed CLD among PA-HIV in the UK.
Abstract Background In the era of highly active antiretroviral therapy, incidence of bacterial pneumonia and invasive pneumococcal disease among HIV-1 seropositive individuals is still more than 30 ...times higher than for seronegative individuals. Risk remains elevated in those with CD4 cell counts in the normal range. A programme of host-mediated macrophage (M) apoptosis ensures killing of Streptococcus pneumoniae when canonical phagolysosomal killing capacity is exhausted. HIV-1 infection is associated with resistance of M to apoptosis. We hypothesised that HIV-1-mediated M apoptotic resistance impairs S pneumoniae killing. Methods The following M models were used: healthy donor monocyte derived M (MDM) infected with HIV-1BaL (HMDM) or sham infected (SMDM), with infection confirmed with anti-p24 immunohistochemistry; and MDM treated with gp120 10–100 ng/mL (gpMDM) or vehicle (cMDM). M were challenged with opsonised type 2 S pneumonia multiplicity of infection=10 or mock-infected and apoptosis up to 20 h by observing morphological changes (counting condensed or fragmented nuclei), counting rates of positivity with the TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay, measuring cells with hypodiploid DNA, and measuring caspase-3/7 activity. Bacterial internalisation and killing were measured by gentamicin protection assay. Data are mean and SD, and analysed by paired t test, or are median and IQR with Wilcoxon matched pairs signed rank test or Kruskal-Wallis test if non parametric. Findings After S pneumoniae challenge, rates of initial S pneumoniae internalisation were similar for all MDM conditions. HMDM showed fewer apoptotic nuclei than did SMDM (19% IQR 18–21 vs 33% 26–43, n=7, p<0·05), and smaller increases in caspase-3/7 activity and higher Mcl-1 expression on western blot after S pneumoniae challenge. Compared with cMDM, fewer gpMDM developed apoptotic nuclei after S pneumoniae challenge, which was dose dependent (cMDM 36% IQR 30–48 vs gpMDM 20% 12–28 at 10 ng/mL and 18% 14–22 at 100 ng/mL, n=12, p<0·01, confirmed with TUNEL), and gpMDM exhibited significantly less caspase 3/7 activity (p<0·05). In gpMDM, reduced apoptosis was associated with bacterial survival. Interpretation HIV-1 infection reduces M apoptosis in response to S pneumoniae , and gp120 may be sufficient to mediate this. Apoptosis resistance may impair killing of S pneumoniae after phagocytosis and increase susceptibility to invasive pneumococcal disease in HIV-1 seropositive individuals. Funding UK Medical Research Council.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains ...underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens.
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•HCM can detect SARS-CoV-2 N and S IgG responses with high specificity and sensitivity•SARS-CoV-2 M antibodies are a third high seroprevalence marker (85% of patients with COVID-19)•Anti-M IgG often displays a shallower time-dependent decline than N IgG post infection•Screening for SARS-CoV-2 M antibodies alongside N can boost serological sensitivity
Biological sciences; Immunology; Microbiology; Cell biology
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Records were reviewed (n=1052) for patients admitted to a large general intensive care unit (GICU) and examined for HIV testing criteria published in UK national testing guidelines (UKNG). All actual ...tests sent from GICU were also examined for comparison. Strict application of the UKNG revealed 30% of patients met criteria for HIV testing on admission to GICU. With pragmatic application, 18% of admissions met criteria for testing. Less than 5% of admissions were actually tested when no testing guideline was adopted.
The UKNG can be adopted in a representative GICU to increase HIV testing rate by 4-6-fold.
Clostridium difficile infection (CDI) affects significant numbers of hospitalized patients and is an increasing problem in the community. It is also among the most commonly isolated pathogens in HIV ...patients with diarrheal illness and is ≥2 fold more common in HIV-seropositive individuals. This association is stronger in those with low absolute CD4 T cell counts or meeting clinical criteria for an AIDS diagnosis, and was most pronounced before the wide availability of highly active antiretroviral therapy. The presentation and outcome of CDI in HIV appears similar to the general population. The increased risk can in part be attributed to increased hospitalization and antimicrobial use, but HIV related alterations in fecal microbiota, gut mucosal integrity, and humoral and cell mediated immunity are also likely to play a role. Here we review the evidence for these observations and the relevance of recent advances in the diagnosis and management of CDI for the HIV clinician.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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