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Quadrivalent HPV vaccine effectiveness against cervical intraepithelial lesion grade 2 or worse in Norway: A registry-based study of 0,9 million Norwegian women. 四价 HPV 疫苗对挪威 2 级或更严重宫颈上皮内瘤变的预防效果:一项针对 90 万挪威妇女的登记研究。
Pub Date : 2024-04-25 DOI: 10.1093/infdis/jiae209
Madleen Orumaa, Elen Johanne Lahlum, Marie Gulla, Joseph Tota, M. Nygård, Ståle Nygård
In Norway, single cohort vaccination with quadrivalent HPV (qHPV) vaccine targeting 12-year-old girls took place from 2009-2016. In 2020, the oldest vaccinated cohort was 23 years old and had approached the age where risk of being diagnosed with cervical intraepithelial lesion grade 2 or worse (CIN2+) increases rapidly. The aim of this cohort study was to assess direct qHPV vaccine effectiveness (VE) against CIN2+ among Norwegian women aged 16-30 in 2007-2020. By using population-based health registries and individual-level data on vaccination status and potential subsequent CIN2+ incidence, we found 82% qHPV VE among women vaccinated before the age of 17.
在挪威,2009 年至 2016 年期间,针对 12 岁女孩接种了四价人乳头瘤病毒 (qHPV) 疫苗。到 2020 年,接种疫苗年龄最大的组群为 23 岁,已接近被诊断为宫颈上皮内病变 2 级或更差(CIN2+)的风险迅速增加的年龄。这项队列研究旨在评估qHPV疫苗对2007-2020年16-30岁挪威女性CIN2+的直接有效性(VE)。通过使用基于人口的健康登记和有关疫苗接种情况及随后潜在的CIN2+发病率的个人水平数据,我们发现在17岁之前接种过疫苗的女性中,qHPV VE的接种率为82%。
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引用次数: 0
A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention 评估用于直肠给药预防艾滋病的替诺福韦-阿拉非那胺/依维曲韦插入物的安全性和药代动力学的 1 期临床试验
Pub Date : 2024-04-24 DOI: 10.1093/infdis/jiae211
Sharon A Riddler, Clifton W Kelly, Craig J Hoesley, Ken S Ho, Jeanna M Piper, Stacey Edick, Faye Heard, Gustavo F Doncel, Sherri Johnson, Peter L Anderson, Rhonda M Brand, Ratiya Pamela Kunjara Na Ayudhya, José A Bauermeister, Sharon L Hillier, Craig W Hendrix
Background On-demand topical products could be an important tool for HIV prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG; 16 mg/20 mg) insert administered rectally. Methods MTN-039 was a Phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid (RF), and rectal tissue (RT) were collected over 72 hours (hr) following rectal administration of one and two TAF/EVG inserts for each participant. ClinicalTrials.gov Identifier: NCT04047420 Results TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4 ng/mL and TFV 4.4 ng/mL. RT EVG peaked at 2-hr (median 2 inserts= 9 ng/mg) but declined to BLQ in the majority of samples at 24-hr, whereas TFV-DP remained high >2,000 fmol/million cells for 72-hr with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each timepoint for both 1 and 2 inserts (p<0.065 and p<0.039, respectively). Discussion Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72 hours.
背景 按需外用产品可能是预防艾滋病的重要工具。我们评估了直肠给药替诺福韦阿拉芬胺/埃替拉韦(TAF/EVG;16 毫克/20 毫克)插入物的安全性、药代动力学和体内外药效学。方法 MTN-039 是一项 1 期、开放标签、单臂、2 剂量研究。在每位受试者直肠给药1个和2个TAF/EVG插入物后的72小时(hr)内收集血液、直肠液(RF)和直肠组织(RT)。ClinicalTrials.gov Identifier:NCT04047420 结果 TAF/EVG插入物安全且耐受性良好。血浆中检测到的EVG和替诺福韦(TFV)浓度较低:插入2次后的中位峰值浓度为EVG 2.4纳克/毫升,TFV 4.4纳克/毫升。RT EVG 在 2 小时后达到峰值(2 次插入的中位数= 9 纳克/毫克),但在 24 小时后的大多数样本中下降到 BLQ,而 TFV-DP 在 2 次插入 72 小时后仍保持高浓度>2,000 fmol/百万细胞。与基线相比,插入 1 个和 2 个样本时,直肠组织外 HIV 感染的累积 log10 HIV p24 抗原中位数在每个时间点都有所降低(分别为 p<0.065 和 p<0.039)。讨论 通过直肠给药 TAF/EVG 嵌体,直肠组织中的 EVG 和 TFV-DP 浓度较高,全身药物暴露量较低,72 小时内可明显抑制体内外 HIV 感染。
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引用次数: 0
What Contributes to the MIC? Beyond β-Lactamase Gene Detection in Klebsiella pneumoniae 是什么导致了 MIC?肺炎克雷伯菌中β-内酰胺酶基因检测之外的问题
Pub Date : 2024-04-24 DOI: 10.1093/infdis/jiae204
Alyssa K W Maclean, Stacey Morrow, Fang Niu, Nancy D Hanson
Background K. pneumoniae is capable of resistance to β-lactam antibiotics through expression of β-lactamases (both chromosomal and plasmid-encoded) and downregulation of outer membrane porins. However, the extent to which these mechanisms interplay in a resistant phenotype is not well understood. The purpose of this study was to determine the extent to which β-lactamases and outer membrane porins affected β-lactam resistance. Methods MICs to β-lactams and inhibitor combinations were determined by agar dilution or E-test. Outer membrane porin production was evaluated by western blot of outer membrane fractions. β-lactamase carriage was determined by whole genome sequencing and expression evaluated by RT-qPCR. Results Plasmid-encoded β­-lactamases were important for cefotaxime and ceftazidime resistance. Elevated expression of chromosomal SHV was important for ceftolozane/tazobactam resistance. Loss of outer membrane porins was predictive of meropenem resistance. ESβLs and pAmpCs in addition to porin loss were sufficient to confer resistance to the third generation cephalosporins, pipercillin/tazobactam, ceftolozane/tazobactam, and meropenem. pAmpCs (CMY-2 and DHA) alone conferred resistance to pipercillin/tazobactam. Discussion Detection of a resistance gene by whole genome sequencing was not sufficient to predict resistance to all antibiotics tested. some β-lactam resistance was dependent on the expression of both plasmid-encoded and chromosomal β-lactamases and loss of porins.
背景肺炎双球菌能够通过表达β-内酰胺酶(染色体和质粒编码)和下调外膜孔蛋白对β-内酰胺类抗生素产生耐药性。然而,这些机制在多大程度上相互作用产生耐药表型还不十分清楚。本研究旨在确定β-内酰胺酶和外膜孔蛋白对β-内酰胺耐药性的影响程度。方法 通过琼脂稀释法或 E 测试法确定β-内酰胺类药物和抑制剂组合的 MIC。外膜孔蛋白的生成通过外膜分馏物的 Western 印迹进行评估。通过全基因组测序确定β-内酰胺酶的携带情况,并通过 RT-qPCR 评估其表达情况。结果 质粒编码的β-内酰胺酶对头孢他啶和头孢唑肟的耐药性非常重要。染色体 SHV 的高表达对头孢羟氨苄/他唑巴坦的耐药性很重要。外膜孔蛋白的缺失可预测美罗培南的耐药性。ESβLs和pAmpCs以及孔蛋白缺失足以产生对第三代头孢菌素、哌西林/他唑巴坦、头孢唑烷/他唑巴坦和美罗培南的耐药性。讨论 通过全基因组测序检测耐药基因并不足以预测对所有测试抗生素的耐药性。某些 β-内酰胺耐药性取决于质粒编码和染色体 β-内酰胺酶的表达以及孔蛋白的缺失。
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引用次数: 0
SARS-CoV-2 RNA and nucleocapsid antigen are blood biomarkers associated with severe disease outcomes that improve in response to remdesivir. SARS-CoV-2 RNA 和核壳抗原是与严重疾病后果相关的血液生物标志物,对雷米替韦的反应有所改善。
Pub Date : 2024-04-24 DOI: 10.1093/infdis/jiae198
Kanal Singh, Kevin Rubenstein, Viviane Callier, K. Shaw-Saliba, Adam W. Rupert, Robin L. Dewar, S. Laverdure, Helene Highbarger, P. Lallemand, Meei-Li W Huang, Keith R Jerome, R. Sampoleo, Margaret G. Mills, Alexander L. Greninger, K. Juneja, D. Porter, Constance A Benson, Walla Dempsey, Hana M. El Sahly, Chris Focht, N. Jilg, Catharine I. Paules, Rekha R Rapaka, T. Uyeki, H. C. Lane, J. Beigel, Lori E Dodd, Aneesh K Mehta, Nadine G Rouphael, Jessica J. Traenkner, V. Cantos, Ghina Alaaeddine, Barry S. Zingman, R. Grossberg, Paul F. Riska, Elizabeth Hohmann, Mariam Torres-Soto, N. Jilg, Helen Y Chu, Anna Wald, Margaret Green, Anne Luetkemeyer, Pierre-Cedric B. Crouch, Hannah Jang, Susan Kline, Joanne Billings, B. Noren, Diego López de Castilla, Jason W. Van Winkle, Francis X. Riedo, Robert W. Finberg, Jennifer P. Wang, Mireya Wessolossky, Kerry Dierberg, Benjamin Eckhardt, Henry J. Neumann, Victor F. Tapson, Jonathan Grein, F. Sutterwala, L. Hsieh, Alpesh N Amin, Thomas F. Patterson, H. Javeri, Trung Vu, R
BACKGROUNDAlthough antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo.METHODSLongitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed.RESULTSHigher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive.CONCLUSIONSReductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.
背景尽管抗病毒药物对于治疗COVID-19仍很重要,但却缺乏评估疗效的方法。在此,我们研究了雷米替韦对病毒动态的影响及其对了解多中心 ACTT-1 临床试验中抗病毒疗效的贡献,该试验将患者随机分配给雷米替韦或安慰剂。结果较高的基线血浆病毒载量与较差的临床结果相关,而血液中病毒 RNA 和抗原的降低与雷米替韦治疗效果的增强相关,但上呼吸道病毒 RNA 和抗原的降低与雷米替韦治疗效果的增强无关。雷米替韦的治疗效果在基线核苷酸抗原水平升高的患者中最为明显:水平>245 pg/ml的康复率比为1.95(95%CI 1.40-2.71),而水平<245 pg/ml的康复率比为1.04(95%CI 0.76-1.42)。结论血液中 SARS-CoV-2 RNA 和抗原水平的降低与抗病毒治疗的临床获益相关。
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引用次数: 0
Rotavirus hospitalization in early childhood: fine motor skills and cognition at six years old—Population-based cohort study 幼儿期轮状病毒住院治疗:六岁时的精细动作技能和认知能力--基于人群的队列研究
Pub Date : 2024-04-24 DOI: 10.1093/infdis/jiae218
Eun Kyo Ha, Ju Hee Kim, Bo Eun Han, Jeewon Shin, Eun Lee, Seonkyeong Rhie, Won Seok Lee, Soonchul Lee, Man Yong Han
Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4–6 months of age, head circumference at 4–6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds.
轮状病毒与严重的儿童肠胃炎和神经系统并发症有关,但其对神经发育的影响仍不确定。我们利用韩国国民健康保险系统研究了1,420,941名2009年至2011年间出生的韩国儿童的数据。6 岁时,我们使用经过验证的韩国发育测试评估了神经发育结果,该测试涵盖六个主要领域。利用基于倾向得分的反概率加权法确保协变量包括性别、出生体重、出生至 4-6 个月期间体重的变化、4-6 个月时的头围、出生时的居住地、经济状况、婴儿喂养类型和出生年份。主要分析包括 5,451 名轮状病毒住院患儿和 310,874 名未接触过轮状病毒的患儿,结果显示,接触过轮状病毒的患儿疑似精细动作技能和认知能力迟缓的几率增加。我们的研究结果表明,婴儿期与轮状病毒相关的住院治疗与 6 岁儿童的精细动作功能和认知能力疑似发育迟缓之间存在关联。
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引用次数: 0
Antibody titers and the risk of infection during the SARS-CoV-2 Omicron phase in Bizen City, Japan 日本备前市 SARS-CoV-2 Omicron 阶段的抗体滴度和感染风险
Pub Date : 2024-04-21 DOI: 10.1093/infdis/jiae207
Tomoka Kadowaki, Ayako Sasaki, Naomi Matsumoto, Toshiharu Mitsuhashi, Hideharu Hagiya, Soshi Takao, Takashi Yorifuji
Background Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. Methods This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1,899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. Results Compared with the &lt;2,500 arbitrary unit (AU)/mL category, the 2,500–5,000, 5,000–10,000, and ≥10,000 AU/mL categories had adjusted RRs (95% CI) of 0.81 (0.61–1.08), 0.51 (0.36–0.72), and 0.41 (0.31–0.54), respectively. The spline function showed a non-linear relationship between antibody titer and risk. Conclusions Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future vaccination.
背景 了解免疫反应与严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)感染风险之间的关系对即将实施的预防策略具有重要意义。我们评估了抗体滴度与普通人群在 Omicron 主导阶段的感染风险之间的关系。方法 这是一项前瞻性队列研究,研究对象为备前市的居民或机构附属人员,共包括 1,899 名参与者。从 2022 年 6 月到 2023 年 3 月,我们每两个月重复测量一次 SARS-CoV-2 抗体滴度。感染状况通过自我报告问卷和官方登记册获得。我们根据抗体滴度类别和样条函数估算了每次抗体测定后 2 个月内感染的风险比 (RRs),以及 95% 的置信区间 (CIs)。结果 与&lt;2,500任意单位(AU)/毫升类别相比,2,500-5,000、5,000-10,000和≥10,000 AU/毫升类别的调整RR(95% CI)分别为0.81(0.61-1.08)、0.51(0.36-0.72)和0.41(0.31-0.54)。曲线函数显示抗体滴度与风险之间存在非线性关系。结论 抗体滴度越高风险越低。我们证明了测量抗体滴度对于确定未来接种疫苗的适当时机非常有用。
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引用次数: 0
Hepatitis B virus and hepatitis C virus affect mitochondrial function through different metabolic pathways, explaining virus-specific clinical features of chronic hepatitis 乙型肝炎病毒和丙型肝炎病毒通过不同的代谢途径影响线粒体功能,从而解释了慢性肝炎的病毒特异性临床特征
Pub Date : 2024-04-20 DOI: 10.1093/infdis/jiae210
Sakthi Priya Selvamani, Anis Khan, Enoch S E Tay, Matthew Garvey, Harout Ajoyan, Eve Diefenbach, Brian S Gloss, Thomas Tu, Jacob George, Mark W Douglas
Background Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause chronic hepatitis with important clinical differences. HCV causes hepatic steatosis and insulin resistance, while HBV confers increased risk of liver cancer. We hypothesised these differences may be due to virus-specific effects on mitochondrial function. Methods Seahorse technology was utilised to investigate effects of virus infection on mitochondrial function. Cell based assays were used to measure mitochondrial membrane potential and quantify pyruvate and lactate. Mass spectrometry was performed on mitochondria isolated from HBV expressing, HCV infected and control cells cultured with isotope-labelled amino acids, to identify proteins with different abundance. Altered expression of key mitochondrial proteins was confirmed by real time PCR and western blot. Results Reduced mitochondrial function and ATP production were observed with HCV infection and HBV expression. HCV impairs glycolysis and reduces expression of genes regulating fatty acid oxidation, promoting lipid accumulation. HBV causes lactate accumulation by increasing expression of lactate dehydrogenase A, which converts pyruvate to lactate. In HBV expressing cells there was marked enrichment of pyruvate dehydrogenase kinase, inhibiting conversion of pyruvate to acetyl-CoA and thereby reducing its availability for mitochondrial oxidative phosphorylation. Conclusions HCV and HBV impair mitochondrial function and reduce ATP production. HCV reduces acetyl-CoA availability for energy production by impairing fatty acid oxidation, causing lipid accumulation and hepatic steatosis. HBV has no effect on fatty oxidation but reduces acetyl-CoA availability by disrupting pyruvate metabolism. This promotes lactic acidosis and oxidative stress, increasing the risk of disease progression and liver cancer.
背景丙型肝炎病毒(HCV)和乙型肝炎病毒(HBV)引起的慢性肝炎在临床上有很大的不同。丙型肝炎病毒(HCV)会导致肝脂肪变性和胰岛素抵抗,而乙型肝炎病毒(HBV)则会增加罹患肝癌的风险。我们假设这些差异可能是由于病毒对线粒体功能的特异性影响。方法 利用海马技术研究病毒感染对线粒体功能的影响。采用基于细胞的检测方法测量线粒体膜电位,并对丙酮酸和乳酸进行量化。对从表达 HBV、感染 HCV 和用同位素标记氨基酸培养的对照细胞中分离出来的线粒体进行了质谱分析,以确定不同丰度的蛋白质。通过实时 PCR 和 Western 印迹证实了关键线粒体蛋白表达的改变。结果 观察到线粒体功能和 ATP 生成随着 HCV 感染和 HBV 表达而降低。HCV 会损害糖酵解,减少调节脂肪酸氧化基因的表达,促进脂质积累。HBV 通过增加将丙酮酸转化为乳酸的乳酸脱氢酶 A 的表达,导致乳酸积累。在表达 HBV 的细胞中,丙酮酸脱氢酶激酶的表达明显增加,抑制了丙酮酸向乙酰-CoA 的转化,从而减少了乙酰-CoA 在线粒体氧化磷酸化中的可用性。结论 HCV 和 HBV 会损害线粒体功能并减少 ATP 的产生。HCV 通过损害脂肪酸氧化减少了乙酰-CoA 在能量生成中的可用性,导致脂质积累和肝脏脂肪变性。HBV 不影响脂肪氧化,但会通过破坏丙酮酸代谢减少乙酰-CoA 的供应。这会促进乳酸酸中毒和氧化应激,增加疾病恶化和肝癌的风险。
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引用次数: 0
Clonal hematopoiesis in patients with HIV and cancer 艾滋病毒和癌症患者的克隆性造血
Pub Date : 2024-04-20 DOI: 10.1093/infdis/jiae212
Nancy Gillis, Brittney L Dickey, Christelle Colin-Leitzinger, Yi-Han Tang, Ryan M Putney, Tania E Mesa, Sean J Yoder, Gita Suneja, Adam M Spivak, Ami B Patel, Martine Extermann, Anna R Giuliano, Mingxiang Teng, Jacob Kresovich, Anders Berglund, Anna E Coghill
Background Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. Methods We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. Results In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). Conclusion This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.
背景 艾滋病毒感染者(PWH)与癌症相关的死亡人数正在增加,原因是他们的预期寿命更长,而与癌症相关的结果却不尽相同。我们假设,晚期生物衰老会导致艾滋病病毒感染者和癌症患者的癌症相关发病率和死亡率。我们试图确定克隆性造血(CH)对威尔士人癌症差异的影响。方法 我们进行了一项回顾性研究,以比较克隆性造血在感染艾滋病病毒(PWH)和未感染艾滋病病毒(PWoH)的人群中的发病率和临床结果。根据肿瘤部位、年龄、肿瘤序列和癌症治疗状况,研究对象包括艾滋病感染者和类似的艾滋病感染者。此外,还使用表观遗传甲基化钟测量了生物老化。结果 在136名癌症患者中,PWH的CH发生率是相似PWoH的两倍(23% vs 11%,P=0.07)。在对患者特征进行调整后,PWH 患 CH 的几率是 PWoH 的四倍(OR 4.1,95% CI 1.3-13.9,P=0.02)。CH对存活率的影响在PWH中最为明显,与PWoH相比,如果患有CH,PWH的5年存活率为38%(如果没有CH,则为59%),而如果患有CH,PWoH的5年存活率为75%(如果没有CH,则为83%)。结论 本研究首次证明,与罹患相同癌症的 PWoH 相比,PWH 的 CH 患病率可能更高。CH可能是导致威尔士族癌症患者生存率较低的一个独立的生物老化风险因素。
{"title":"Clonal hematopoiesis in patients with HIV and cancer","authors":"Nancy Gillis, Brittney L Dickey, Christelle Colin-Leitzinger, Yi-Han Tang, Ryan M Putney, Tania E Mesa, Sean J Yoder, Gita Suneja, Adam M Spivak, Ami B Patel, Martine Extermann, Anna R Giuliano, Mingxiang Teng, Jacob Kresovich, Anders Berglund, Anna E Coghill","doi":"10.1093/infdis/jiae212","DOIUrl":"https://doi.org/10.1093/infdis/jiae212","url":null,"abstract":"Background Cancer-related deaths for people living with HIV (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH. Methods We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks. Results In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, p=0.07). After adjusting for patient characteristics, PWH were four-times more likely to have CH than PWoH (OR 4.1, 95% CI 1.3-13.9, p=0.02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH). Conclusion This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140642629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chlamydia trachomatis seroassays used in epidemiologic research: a narrative review and practical considerations 流行病学研究中使用的沙眼衣原体血清测定法:叙述性综述和实际考虑因素
Pub Date : 2024-04-19 DOI: 10.1093/infdis/jiae199
Mary Bridget Waters, Kevin Hybiske, Ren Ikeda, Bernhard Kaltenboeck, Lisa E Manhart, Kristen M Kreisel, Christine M Khosropour
Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the “state of the science” for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.
沙眼衣原体(CT)是一种可导致不良生殖健康后果的性传播感染。沙眼衣原体感染率的估计值主要来自使用核酸扩增检测(NAATs)进行的筛查。然而,美国的筛查指南只包括特定的亚人群,而且核酸扩增检测只能检测当前的感染情况。与此相反,血清分析可确定过去的 CT 感染情况,这对于了解 CT 对公共卫生的影响(包括盆腔炎和输卵管因素导致的不孕症)非常重要。较早的血清分析法一直受到灵敏度和特异性较低的困扰,而且没有使用统一的参考标准进行验证,因此在比较研究结果、确定 CT 的流行病学以及确定控制计划的有效性方面具有挑战性。较新的血清分析法具有更好的性能特征。这篇叙述性综述总结了已应用于流行病学研究的 CT 血清分析的 "科学现状",并为解读文献和在未来研究中使用血清分析提供了实用的注意事项。
{"title":"Chlamydia trachomatis seroassays used in epidemiologic research: a narrative review and practical considerations","authors":"Mary Bridget Waters, Kevin Hybiske, Ren Ikeda, Bernhard Kaltenboeck, Lisa E Manhart, Kristen M Kreisel, Christine M Khosropour","doi":"10.1093/infdis/jiae199","DOIUrl":"https://doi.org/10.1093/infdis/jiae199","url":null,"abstract":"Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the “state of the science” for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment for Antibodies to Rifapentine and Isoniazid in Persons Developing Flu-like Reactions During Treatment of Latent Tuberculosis Infection 在治疗潜伏肺结核感染期间出现流感样反应者的利福喷丁和异烟肼抗体评估
Pub Date : 2024-04-19 DOI: 10.1093/infdis/jiae180
Ruth N Moro, Carolina Mehaffy, Prithwiraj De, Elizabeth Phillips, Andrey S Borisov, Timothy R Sterling, Karen M Dobos
Background Flu-like reactions can occur after exposure to rifampin, rifapentine, or isoniazid. Prior studies have reported the presence of antibodies to rifampin, but associations with underlying pathogenesis are unclear. Methods We evaluated PREVENT TB study participants who received weekly isoniazid + rifapentine for 3 months (3HP) or daily isoniazid for 9 months (9H) as treatment for M. tuberculosis infection. Flu-like reaction was defined as a grade ≥2 of any of flu-like symptoms. Controls (3HP or 9H) did not report flu-like reactions. We developed a competitive enzyme-linked immunosorbent assays (ELISA) to detect antibodies against rifapentine, isoniazid, rifampin, and rifapentine metabolite. Results Among 128 participants, 69 received 3HP (22 with flu-like reactions; 47 controls) and 59 received 9H (12 with flu-like reactions; 47 controls). In participants receiving 3HP, anti-rifapentine IgG was identified in 2/22 (9%) participants with flu-like reactions and 6/47 (13%) controls (P = 0.7), anti-isoniazid IgG in 2/22 (9%) participants with flu-like reactions and 4/47 (9%) controls (P = 0.9), and anti-rifapentine metabolite IgG in 2/47 (4%) controls (P = 0.9). Among participants receiving 9H, IgG and IgM anti-isoniazid antibodies were each present in 4/47 (9%) controls, respectively, but none among participants with flu-like reactions; anti-rifapentine IgG antibodies were not present in any participants with flu-like reactions or controls. Conclusions We detected anti-rifapentine, anti-isoniazid, and anti-rifapentine metabolite antibodies, but the proportions of participants with antibodies were low, and did not differ between participants with flu-like reactions and those without such reactions. This suggests that flu-like reactions associated with 3HP and 9H were not antibody-mediated.
背景接触利福平、利福喷汀或异烟肼后可出现流感样反应。之前的研究报告了利福平抗体的存在,但与潜在发病机制的关系尚不清楚。方法 我们对 PREVENT TB 研究的参与者进行了评估,他们每周接受异烟肼+利福喷丁治疗 3 个月(3HP)或每天接受异烟肼治疗 9 个月(9H),以治疗结核杆菌感染。流感样反应的定义是任何流感样症状≥2级。对照组(3HP 或 9H)未报告流感样反应。我们开发了一种竞争性酶联免疫吸附试验(ELISA)来检测针对利福喷丁、异烟肼、利福平和利福喷丁代谢物的抗体。结果 在128名参与者中,69人接受了3HP治疗(22人出现流感样反应;47人对照),59人接受了9H治疗(12人出现流感样反应;47人对照)。在接受3HP治疗的参试者中,有2/22(9%)人出现流感样反应,6/47(13%)人对照(P=0.7);有2/22(9%)人出现流感样反应,4/47(9%)人对照(P=0.9);有2/47(4%)人对照(P=0.9)。在接受9H治疗的参与者中,分别有4/47(9%)名对照者出现了IgG和IgM抗异烟肼抗体,但在出现流感样反应的参与者中却没有出现;在任何出现流感样反应的参与者或对照者中都没有出现抗利伐喷丁IgG抗体。结论 我们检测到了抗利伐喷丁、抗异烟肼和抗利伐喷丁代谢物抗体,但出现抗体的参与者比例较低,而且在出现流感样反应和未出现流感样反应的参与者之间没有差异。这表明与 3HP 和 9H 相关的流感样反应并非由抗体介导。
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The Journal of Infectious Diseases
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