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1.
Biologicals ; 85: 101747, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38350825

RESUMEN

Earlier meetings laid the foundations for Controlled Human Infection Models (CHIMs), also known as human challenge studies and human infection studies, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on CHIM studies being conducted in endemic countries. Over the last ten years we have seen a vast expansion of the number of countries in Africa performing CHIM studies, as well as a growing number of different challenge organisms being used. Community and public engagement with assiduous ethical and regulatory oversight has been central to successful introductions and should be continued, in more community-led or community-driven models. Valuable initiatives for regulation of CHIMs have been undertaken but further capacity building remains essential.

2.
Am J Transplant ; 20(7): 1885-1890, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32330356

RESUMEN

With the rapidly expanding pandemic of SARS-CoV-2, there is concern that solid organ transplant recipients will be particularly vulnerable to infection and may experience a more severe clinical course. We report four cases of COVID-19 in solid organ transplant recipients including recipients of kidney, liver, lung, and heart transplants. We describe each patient's medical history including transplantation history, their clinical presentation and workup, and their course from diagnosis to either hospital discharge or to improvement in symptoms. These reports demonstrate a range of symptoms, clinical severity, and disease course in solid organ transplant recipients with COVID-19, including two hospitalized patients and two patients managed entirely in the outpatient setting.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Terapia de Inmunosupresión/métodos , Neumonía Viral/complicaciones , Receptores de Trasplantes , Anciano , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Enfermedad Hepática en Estado Terminal/complicaciones , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón , Hospitalización , Humanos , Terapia de Inmunosupresión/efectos adversos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Trasplante de Hígado , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Estados Unidos/epidemiología , Poblaciones Vulnerables , Washingtón
3.
Lancet Glob Health ; 12(1): e45-e54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38097297

RESUMEN

BACKGROUND: Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising non-sputum alternative sample type for the diagnosis of pulmonary tuberculosis. We aimed to assess the diagnostic accuracy of oral swabs to detect pulmonary tuberculosis in adults and children and suggest research implications. METHODS: In this systematic review, we searched published and preprint studies from Jan 1, 2000, to July 5, 2022, from eight databases (MEDLINE, Embase, Scopus, Science Citation Index, medRxiv, bioRxiv, Global Index Medicus, and Google Scholar). We included diagnostic accuracy studies including cross-sectional, cohort, and case-control studies in adults and children from which we could extract or derive sensitivity and specificity of oral swabs as a sample type for the diagnosis of pulmonary tuberculosis against a sputum microbiological (nucleic acid amplification test [NAAT] on sputum or culture) or composite reference standard. FINDINGS: Of 550 reports identified by the search, we included 16 eligible reports (including 20 studies and 3083 participants) that reported diagnostic accuracy estimates on oral swabs for pulmonary tuberculosis. Sensitivity on oral swabs ranged from 36% (95% CI 26-48) to 91% (80-98) in adults and 5% (1-14) to 42% (23-63) in children. Across all studies, specificity ranged from 66% (95% CI 52-78) to 100% (97-100), with most studies reporting specificity of more than 90%. Meta-analysis was not performed because of sampling and testing heterogeneity. INTERPRETATION: Sensitivity varies in both adults and children when diverse methods are used. Variability in sampling location, swab type, and type of NAAT used in accuracy studies limits comparison. Although data are suggestive that high accuracy is achievable using oral swabs with molecular testing, more research is needed to define optimal methods for using oral swabs as a specimen for tuberculosis detection. The current data suggest that tongue swabs and swab types that collect increased biomass might have increased sensitivity. We would recommend that future studies use these established methods to continue to refine sample processing to maximise sensitivity. FUNDING: Bill and Melinda Gates foundation (INV-045721) and FIND (Netherlands Enterprise Agency on behalf of the Minister for Foreign Trade and Development Cooperation [NL-GRNT05] and KfW Development Bank, German Federal Ministry of Education and Research [KFW-TBBU01/02]).


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Adulto , Niño , Humanos , Mycobacterium tuberculosis/genética , Estudios Transversales , Patología Molecular , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Sensibilidad y Especificidad , Técnicas de Diagnóstico Molecular
4.
Immunohorizons ; 8(9): 695-711, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39283647

RESUMEN

Cutaneous mycobacterial infections cause substantial morbidity and are challenging to diagnose and treat. An improved understanding of the dermal immune response to mycobacteria may inspire new therapeutic approaches. We conducted a controlled human infection study with 10 participants who received 2 × 106 CFUs of Mycobacterium bovis bacillus Calmette-Guérin (Tice strain) intradermally and were randomized to receive isoniazid or no treatment. Peripheral blood was collected at multiple time points for flow cytometry, bulk RNA sequencing (RNA-seq), and serum Ab assessments. Systemic immune responses were detected as early as 8 d postchallenge in this M. bovis bacillus Calmette-Guérin-naive population. Injection-site skin biopsies were performed at days 3 and 15 postchallenge and underwent immune profiling using mass cytometry and single-cell RNA-seq, as well as quantitative assessments of bacterial viability and burden. Molecular viability testing and standard culture results correlated well, although no differences were observed between treatment arms. Single-cell RNA-seq revealed various immune and nonimmune cell types in the skin, and communication between them was inferred by ligand-receptor gene expression. Day 3 communication was predominantly directed toward monocytes from keratinocyte, muscle, epithelial, and endothelial cells, largely via the migration inhibitory factor pathway and HLA-E-KLRK1 interaction. At day 15, communication was more balanced between cell types. These data reveal the potential role of nonimmune cells in the dermal immune response to mycobacteria and the utility of human challenge studies to augment our understanding of mycobacterial infections.


Asunto(s)
Mycobacterium bovis , Piel , Humanos , Mycobacterium bovis/inmunología , Piel/inmunología , Piel/microbiología , Piel/patología , Masculino , Adulto , Isoniazida/uso terapéutico , Isoniazida/farmacología , Femenino , Tuberculosis/inmunología , Tuberculosis/microbiología , Adulto Joven , Antituberculosos/uso terapéutico
5.
J Acquir Immune Defic Syndr ; 96(4): 350-360, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-38916429

RESUMEN

BACKGROUND: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B. METHODS: HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination. RESULTS: From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose. CONCLUSIONS: The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016.


Asunto(s)
Vacunas contra el SIDA , Adyuvantes Inmunológicos , Anticuerpos Anti-VIH , Proteína gp120 de Envoltorio del VIH , Infecciones por VIH , VIH-1 , Polisorbatos , Escualeno , Vacunas de ADN , Humanos , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/efectos adversos , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/efectos adversos , Femenino , Masculino , Adulto , Escualeno/administración & dosificación , Polisorbatos/administración & dosificación , Proteína gp120 de Envoltorio del VIH/inmunología , Adyuvantes Inmunológicos/administración & dosificación , VIH-1/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/prevención & control , Anticuerpos Anti-VIH/sangre , Método Doble Ciego , Persona de Mediana Edad , Adulto Joven , Adyuvantes de Vacunas/administración & dosificación , Sudáfrica , Inmunogenicidad Vacunal , Adolescente , Estados Unidos
6.
F S Rep ; 3(3): 285-291, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36212574

RESUMEN

Objective: To report 2 cases of adverse pregnancy outcomes due to delayed diagnosis of urogenital tuberculosis and propose a screening algorithm for patients from tuberculosis-endemic countries. Design: Case report. Setting: Academic medical center. Patients: Two patients with delayed diagnosis of urogenital tuberculosis leading to a fetal loss and a preterm delivery of an infant with congenital tuberculosis. Interventions: Endometrial biopsy, acid-fast bacilli culture of urine, and endometrium. Main outcome measures: Pregnancy outcomes. Results: Fetal loss at 19 weeks and preterm delivery of an infant with congenital tuberculosis before urogenital tuberculosis treatment. Conclusions: Patients who are at risk of urogenital tuberculosis should be screened in advance of infertility treatment to potentially prevent adverse pregnancy outcomes.

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