Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00038-7
Annika Saukkoriipi PhD , Natalie C Silmon de Monerri PhD , Maija Toropainen PhD , Laura Lindholm MSc , Riitta Veijola MD PhD , Jorma Toppari MD PhD , Mikael Knip MD PhD , David Radley MSc , Emily Gomme PhD , Babalwa Jongihlati MD , Annaliesa S Anderson PhD , Arto A Palmu MD PhD , Raphael Simon PhD
Background
Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants.
Methods
In this retrospective case–control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia–V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk–concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data.
Findings
Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120–0·266 μg/mL serotype III-specific IgG was estimated to confer 75–90% risk reduction against serotype III disease. A universal risk–concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease.
Interpretation
Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious.
Funding
Pfizer.
背景:B 组链球菌是新生儿疾病的主要病因。自然史研究将母体转移的抗 B 群链球菌荚膜多糖抗体与预防婴儿 B 群链球菌疾病联系起来。以往对欧洲人群中囊多糖抗体浓度的研究使用的是母体(而非婴儿)血清和非标准化的检测方法。本研究旨在评估抗囊多糖 IgG 浓度与芬兰婴儿预防侵袭性 B 群链球菌疾病的相关性:在这项回顾性病例对照研究中,我们使用了来自芬兰 DIPP 研究资料库的脐带血清,这些血清是在 1995 年 1 月 1 日至 2017 年 12 月 31 日期间获得的。我们纳入了6个月或6个月以下的B组链球菌感染婴儿(病例)和健康婴儿(对照)。我们从芬兰健康登记册中登记了患有侵袭性新生儿 B 组链球菌感染的婴儿(55 例)和年龄在 6 个月或 6 个月以下的匹配对照组(229 例)。我们使用标准化免疫测定法测定了抗囊多糖 IgG(血清型 Ia-V)的浓度,并使用贝叶斯模型估算了其与疾病风险的关系。根据之前报告的免疫原性数据,我们利用得出的风险-浓度曲线预测了六价乙型链球菌荚膜多糖疫苗(GBS6)的潜在疗效:大多数(55 例病例中的 32 例[58%])B 组链球菌病例是由血清 III 型引起的,血清 III 型匹配对照组的抗血清 III 型链球菌荚膜 IgG 浓度高于病例(p解释:血清 III 型匹配对照组的抗荚膜 IgG 浓度高于病例(p解释:血清 III 型匹配对照组的抗荚膜 IgG 浓度高于病例):在芬兰,新生儿出生时抗囊多糖血清 IgG 浓度较高与婴儿患 B 群链球菌疾病的风险降低有关。根据这些结果,预计目前正在开发的母体 B 群链球菌荚膜结合疫苗具有疗效:辉瑞公司。
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Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00095-8
Leonardo Pereira de Araújo , Evandro Neves Silva , Patrícia Paiva Corsetti , Leonardo Augusto de Almeida
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Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00133-2
Priya Venkatesan
{"title":"New measures to tackle the global cholera surge","authors":"Priya Venkatesan","doi":"10.1016/S2666-5247(24)00133-2","DOIUrl":"10.1016/S2666-5247(24)00133-2","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724001332/pdfft?md5=02dae21d80f83fb901e8fbda6ea458d6&pid=1-s2.0-S2666524724001332-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00041-7
Lucrèce Ahovègbé PharmD , Rajiv Shah MD , Prof Aboudou Raïmi Kpossou MD , Chris Davis PhD , Marc Niebel PhD , Ana Filipe PhD , Emily Goldstein PhD , Khadidjatou S Alassan MD , René Keke MD , Prof Jean Sehonou MD , Prof Nicolas Kodjoh MD , Sossa Edmond Gbedo MD , Prof Surajit Ray PhD , Craig Wilkie PhD , Sreenu Vattipally PhD , Lily Tong PhD , Pakoyo F Kamba PhD , S Judith Gbenoudon PhD , Prof Rory Gunson PhD , Prof Patrick Ogwang PhD , Prof Emma C Thomson PhD FRCP
Background
10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%.
Methods
This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir–velpatasvir or sofosbuvir–ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay.
Findings
Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the NS5A gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful.
Interpretation
This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir–velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated.
Funding
Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.
{"title":"Hepatitis C virus diversity and treatment outcomes in Benin: a prospective cohort study","authors":"Lucrèce Ahovègbé PharmD , Rajiv Shah MD , Prof Aboudou Raïmi Kpossou MD , Chris Davis PhD , Marc Niebel PhD , Ana Filipe PhD , Emily Goldstein PhD , Khadidjatou S Alassan MD , René Keke MD , Prof Jean Sehonou MD , Prof Nicolas Kodjoh MD , Sossa Edmond Gbedo MD , Prof Surajit Ray PhD , Craig Wilkie PhD , Sreenu Vattipally PhD , Lily Tong PhD , Pakoyo F Kamba PhD , S Judith Gbenoudon PhD , Prof Rory Gunson PhD , Prof Patrick Ogwang PhD , Prof Emma C Thomson PhD FRCP","doi":"10.1016/S2666-5247(24)00041-7","DOIUrl":"10.1016/S2666-5247(24)00041-7","url":null,"abstract":"<div><h3>Background</h3><p>10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%.</p></div><div><h3>Methods</h3><p>This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir–velpatasvir or sofosbuvir–ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay.</p></div><div><h3>Findings</h3><p>Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the <em>NS5A</em> gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful.</p></div><div><h3>Interpretation</h3><p>This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir–velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated.</p></div><div><h3>Funding</h3><p>Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000417/pdfft?md5=d6f397699411d57249844adb520a903c&pid=1-s2.0-S2666524724000417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141411145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00046-6
Edwin P Armitage BMBS , Gabrielle de Crombrugghe MD , Alexander J Keeley BMBS , Elina Senghore BSc , Fatoumata E Camara MSc , Musukoi Jammeh , Amat Bittaye ADN , Haddy Ceesay CHN , Isatou Ceesay RN , Bunja Samateh BSN , Muhammed Manneh TNA , Prof Beate Kampmann , Claire E Turner PhD , Prof Adam Kucharski , Anne Botteaux PhD , Prof Pierre R Smeesters , Prof Thushan I de Silva , Prof Michael Marks
Background
Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting.
Methods
We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for S pyogenes culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent emm genotyping. The primary outcome measures were incidence of S pyogenes carriage and disease. Additional outcomes were prevalence of S pyogenes skin and pharyngeal carriage, S pyogenes skin and pharyngeal clearance time, S pyogenes emm type, risk factors for carriage and disease events, household secondary attack rate, and emm-linked household transmission events. The study is registered on ClinicalTrials.gov, NCT05117528.
Findings
Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6–28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin S pyogenes carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1–1·9) for S pyogenes pharyngeal carriage and 1·2% (0·9–1·6) for S pyogenes skin carriage. Incidence was 120 per 1000 person-years (95% CI 87–166) for S pyogenes pharyngeal carriage, 124 per 1000 person-years (90–170) for S pyogenes skin carriage, 51 per 1000 person-years (31–84) for S pyogenes pharyngitis, and 263 per 1000 person-years (212–327) for S pyogenes pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19–14·69) and in larger households (per additional person: 1·03, 1·00–1·05), as was pharyngitis risk (rainy season: 3·00, 1·10–8·22; household size: 1·04, 1·02–1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22–0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08–167·21), with similar findings for pyoderma (female sex: 0·34, 0·19–0·61; age <5 years: 7
{"title":"Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study","authors":"Edwin P Armitage BMBS , Gabrielle de Crombrugghe MD , Alexander J Keeley BMBS , Elina Senghore BSc , Fatoumata E Camara MSc , Musukoi Jammeh , Amat Bittaye ADN , Haddy Ceesay CHN , Isatou Ceesay RN , Bunja Samateh BSN , Muhammed Manneh TNA , Prof Beate Kampmann , Claire E Turner PhD , Prof Adam Kucharski , Anne Botteaux PhD , Prof Pierre R Smeesters , Prof Thushan I de Silva , Prof Michael Marks","doi":"10.1016/S2666-5247(24)00046-6","DOIUrl":"10.1016/S2666-5247(24)00046-6","url":null,"abstract":"<div><h3>Background</h3><p><em>Streptococcus pyogenes</em> causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of <em>S pyogenes</em> skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both <em>S pyogenes</em> asymptomatic carriage and infection in a high-burden setting.</p></div><div><h3>Methods</h3><p>We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for <em>S pyogenes</em> culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent <em>emm</em> genotyping. The primary outcome measures were incidence of <em>S pyogenes</em> carriage and disease. Additional outcomes were prevalence of <em>S pyogenes</em> skin and pharyngeal carriage, <em>S pyogenes</em> skin and pharyngeal clearance time, <em>S pyogenes emm</em> type, risk factors for carriage and disease events, household secondary attack rate, and <em>emm</em>-linked household transmission events. The study is registered on ClinicalTrials.gov, <span>NCT05117528</span><svg><path></path></svg>.</p></div><div><h3>Findings</h3><p>Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6–28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin <em>S pyogenes</em> carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1–1·9) for <em>S pyogenes</em> pharyngeal carriage and 1·2% (0·9–1·6) for <em>S pyogenes</em> skin carriage. Incidence was 120 per 1000 person-years (95% CI 87–166) for <em>S pyogenes</em> pharyngeal carriage, 124 per 1000 person-years (90–170) for <em>S pyogenes</em> skin carriage, 51 per 1000 person-years (31–84) for <em>S pyogenes</em> pharyngitis, and 263 per 1000 person-years (212–327) for <em>S pyogenes</em> pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19–14·69) and in larger households (per additional person: 1·03, 1·00–1·05), as was pharyngitis risk (rainy season: 3·00, 1·10–8·22; household size: 1·04, 1·02–1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22–0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08–167·21), with similar findings for pyoderma (female sex: 0·34, 0·19–0·61; age <5 years: 7","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000466/pdfft?md5=bc8389712029b740af2e4fb87875e5e4&pid=1-s2.0-S2666524724000466-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In October, 2022, WHO published the first fungal priority pathogen list, which categorised 19 fungal entities into three priority groups (critical, high, and medium), for prioritisation of research efforts. The final ranking was determined via multiple criteria decision analysis, considering both research and development needs and perceived public health importance. In this Personal View, we discuss the positioning of the fungal pathogens, namely, Mucorales, Candida spp, Histoplasma spp, Coccidioides and Paracoccidioides spp, Fusarium spp, eumycetoma causative agents, Talaromyces marneffei, and Pneumocystis jirovecii, while expressing concerns about potential disparities between the WHO fungal priority pathogen list ranking and the actual disease burden associated with these pathogens. Finally, we propose a revised prioritisation list that also considers the regional disparities in the burden of fungal diseases.
{"title":"The WHO fungal priority pathogens list: a crucial reappraisal to review the prioritisation","authors":"Giacomo Casalini MD , Andrea Giacomelli MD , Prof Spinello Antinori PhD","doi":"10.1016/S2666-5247(24)00042-9","DOIUrl":"10.1016/S2666-5247(24)00042-9","url":null,"abstract":"<div><p>In October, 2022, WHO published the first fungal priority pathogen list, which categorised 19 fungal entities into three priority groups (critical, high, and medium), for prioritisation of research efforts. The final ranking was determined via multiple criteria decision analysis, considering both research and development needs and perceived public health importance. In this Personal View, we discuss the positioning of the fungal pathogens, namely, Mucorales, <em>Candida</em> spp, <em>Histoplasma</em> spp, <em>Coccidioides</em> and <em>Paracoccidioides</em> spp, <em>Fusarium</em> spp, eumycetoma causative agents, <em>Talaromyces marneffei</em>, and <em>Pneumocystis jirovecii</em>, while expressing concerns about potential disparities between the WHO fungal priority pathogen list ranking and the actual disease burden associated with these pathogens. Finally, we propose a revised prioritisation list that also considers the regional disparities in the burden of fungal diseases.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000429/pdfft?md5=0c9f8fbc91e25678c968c4dbe0f721a0&pid=1-s2.0-S2666524724000429-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140792248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00044-2
Lucia Molinengo MSc , Theodore Estrin-Serlui MBBS , Brian Hanley FRCPath , Prof Michael Osborn FRCPath , Prof Robert Goldin FRCPath
Post-mortem examinations continue to play a crucial role in understanding the epidemiology and pathogenesis of infectious diseases. However, the perceived infection risk can preclude traditional, invasive, complete diagnostic autopsy. Post-mortem examination is especially important in emerging infectious diseases with potentially unknown infection risks, but rapid acquisition of good quality tissue samples is needed as part of the scientific and public health response. Needle biopsy post-mortem is a minimally invasive, rapid, closed-body autopsy technique that was originally developed to minimise the infection risk to practitioners. Since its inception, needle biopsy post-mortem has also been used as a technique to support complete diagnostic autopsy provision in poorly resourced regions and to facilitate post-mortem examinations in communities that might have religious or cultural objections to an invasive autopsy. This Review analyses the evolution and applicability of needle biopsy post-mortem in investigating endemic and emerging infectious diseases.
{"title":"Infectious diseases and the role of needle biopsy post-mortem","authors":"Lucia Molinengo MSc , Theodore Estrin-Serlui MBBS , Brian Hanley FRCPath , Prof Michael Osborn FRCPath , Prof Robert Goldin FRCPath","doi":"10.1016/S2666-5247(24)00044-2","DOIUrl":"10.1016/S2666-5247(24)00044-2","url":null,"abstract":"<div><p>Post-mortem examinations continue to play a crucial role in understanding the epidemiology and pathogenesis of infectious diseases. However, the perceived infection risk can preclude traditional, invasive, complete diagnostic autopsy. Post-mortem examination is especially important in emerging infectious diseases with potentially unknown infection risks, but rapid acquisition of good quality tissue samples is needed as part of the scientific and public health response. Needle biopsy post-mortem is a minimally invasive, rapid, closed-body autopsy technique that was originally developed to minimise the infection risk to practitioners. Since its inception, needle biopsy post-mortem has also been used as a technique to support complete diagnostic autopsy provision in poorly resourced regions and to facilitate post-mortem examinations in communities that might have religious or cultural objections to an invasive autopsy. This Review analyses the evolution and applicability of needle biopsy post-mortem in investigating endemic and emerging infectious diseases.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000442/pdfft?md5=4a0cde4ea539d7e4504d1d4c1229f91b&pid=1-s2.0-S2666524724000442-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00025-9
Susan Jackson MRCP , Julia L Marshall DPhil , Andrew Mawer BMBCh , Raquel Lopez-Ramon MSc , Stephanie A Harris BSc , Iman Satti PhD , Eileen Hughes BSc , Hannah Preston-Jones MSc , Ingrid Cabrera Puig PhD , Stephanie Longet PhD , Tom Tipton PhD , Stephen Laidlaw PhD , Rebecca Powell Doherty PhD , Hazel Morrison MRCP , Robert Mitchell MSc , Rachel Tanner DPhil , Alberta Ateere MSc , Elena Stylianou PhD , Meng-San Wu MRCP , Timothy P W Fredsgaard-Jones MRCP , Gavindren Vuddamalay
Background
A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×101 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals.
Methods
Healthy, UK volunteers aged 18–30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×101, 1×102, 1×10³, 1×104, or 1×105 TCID50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal–nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete.
Findings
Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×101 to 1×105 TCID50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×105 TCID50, we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8+ T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events.
{"title":"Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study","authors":"Susan Jackson MRCP , Julia L Marshall DPhil , Andrew Mawer BMBCh , Raquel Lopez-Ramon MSc , Stephanie A Harris BSc , Iman Satti PhD , Eileen Hughes BSc , Hannah Preston-Jones MSc , Ingrid Cabrera Puig PhD , Stephanie Longet PhD , Tom Tipton PhD , Stephen Laidlaw PhD , Rebecca Powell Doherty PhD , Hazel Morrison MRCP , Robert Mitchell MSc , Rachel Tanner DPhil , Alberta Ateere MSc , Elena Stylianou PhD , Meng-San Wu MRCP , Timothy P W Fredsgaard-Jones MRCP , Gavindren Vuddamalay","doi":"10.1016/S2666-5247(24)00025-9","DOIUrl":"10.1016/S2666-5247(24)00025-9","url":null,"abstract":"<div><h3>Background</h3><p>A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10<sup>1</sup> 50% tissue culture infectious dose (TCID<sub>50</sub>) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals.</p></div><div><h3>Methods</h3><p>Healthy, UK volunteers aged 18–30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×10<sup>1</sup>, 1×10<sup>2</sup>, 1×10³, 1×10<sup>4</sup>, or 1×10<sup>5</sup> TCID<sub>50</sub> SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal–nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (<span>NCT04864548</span><svg><path></path></svg>); enrolment and follow-up to 12 months post-enrolment are complete.</p></div><div><h3>Findings</h3><p>Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×10<sup>1</sup> to 1×10<sup>5</sup> TCID<sub>50</sub> SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×10<sup>5</sup> TCID<sub>50</sub>, we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8<sup>+</sup> T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events.</p></div><div><h3>Interpretatio","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000259/pdfft?md5=8d64e946c4adedce34c02dfe630a7574&pid=1-s2.0-S2666524724000259-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}