Perceptions about controlled human infection model (CHIM) studies among members of ethics committees of Indian medical institutions: A qualitative exploration
by Abhishek Sharma, Aditi Apte, Medha Rajappa, Manjulika Vaz, Vina Vaswani, Shifalika Goenka, Samir Malhotra, Rashmi Sangoram, Sabitha Lakshminarayanan, Suganya Jayaram, Jayanthi Mathaiyan, Knadeejath Farseena, Prarthna Mukerjee, Surinder Jaswal, Amol Dongre, Olinda Timms, Nusrat Shafiq, Rakesh Aggarwal, Manmeet Kaur, Sanjay Juvekar, Amrita Sekhar, Gagandeep KangPractical considerations for a TB controlled human infection model; the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi
by Stephen B. Gordon, Simon Sichone, Anthony E. Chirwa, Phoebe Hazenberg, Zacharia Kafuko, Daniela M. Ferreira, Joanne Flynn, Sarah Fortune, Shobana Balasingam, Giancarlo A. Biagini, Helen McShane, Henry Mwandumba, Kondwani Jambo, Keertan Dedha, Nimisha Raj Sharma, Brian D. Roberston, Naomi Walker, Ben MortonSame-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP)
by Valdiléa G Veloso et al.Summary Background Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. Methods Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. Findings From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18–24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20–2·14), participants aged 18–24 years (1·80, 1·49–2·18), and participants with primary education (2·18, 1·29–3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46–0·70), participants aged 18–24 years (0·52, 0·46–0·58), and those with primary education (0·60, 0·40–0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45–0·71), participants aged 18–24 years (0·56, 0·49–0·64), and those with secondary education (0·74, 0·68–0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70–1·03) and was higher for transgender women, participants from Peru, those aged 18–24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. Interpretation Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. Funding Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. Translations For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.
Ambulatory and hospitalized patients with suspected and confirmed mpox: an observational cohort study from Brazil
by Mayara Secco Torres Silva et al.Summary Background By October 30, 2022, 76,871 cases of mpox were reported worldwide, with 20,614 cases in Latin America. This study reports characteristics of a case series of suspected and confirmed mpox cases at a referral infectious diseases center in Rio de Janeiro, Brazil. Methods This was a single-center, prospective, observational cohort study that enrolled all patients with suspected mpox between June 12 and August 19, 2022. Mpox was confirmed by a PCR test. We compared characteristics of confirmed and non-confirmed cases, and among confirmed cases according to HIV status using distribution tests. Kernel estimation was used for exploratory spatial analysis. Findings Of 342 individuals with suspected mpox, 208 (60.8%) were confirmed cases. Compared to non-confirmed cases, confirmed cases were more frequent among individuals aged 30–39 years, cisgender men (96.2% vs. 66.4%; p < 0.0001), reporting recent sexual intercourse (95.0% vs. 69.4%; p < 0.0001) and using PrEP (31.6% vs. 10.1%; p < 0.0001). HIV (53.2% vs. 20.2%; p < 0.0001), HCV (9.8% vs. 1.1%; p = 0.0046), syphilis (21.2% vs. 16.3%; p = 0.43) and other STIs (33.0% vs. 21.6%; p = 0.042) were more frequent among confirmed mpox cases. Confirmed cases presented more genital (77.3% vs. 39.8%; p < 0.0001) and anal lesions (33.1% vs. 11.5%; p < 0.0001), proctitis (37.1% vs. 13.3%; p < 0.0001) and systemic signs and symptoms (83.2% vs. 64.5%; p = 0.0003) than non-confirmed cases. Compared to confirmed mpox HIV-negative, HIV-positive individuals were older, had more HCV coinfection (15.2% vs. 3.7%; p = 0.011), anal lesions (45.7% vs. 20.5%; p < 0.001) and clinical features of proctitis (45.2% vs. 29.3%; p = 0.058). Interpretation Mpox transmission in Rio de Janeiro, Brazil, rapidly evolved into a local epidemic, with sexual contact playing a crucial role in its dynamics and high rates of coinfections with other STI. Preventive measures must address stigma and social vulnerabilities. Funding Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz).
Human infection studies: Key considerations for challenge agent development and production
by Emma SmithViewpoint of a WHO Advisory Group Tasked to Consider Establishing COVID Human Infection Studies
by Levine MHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely?monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coro?navirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a “rescue treatment” to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.
This article discusses the science behind herd immunity and the important role that vaccinations play in ensuring that herd immunity can be achieved.
Request for proposals : Regulatory support consultancy for the use of human infection studies to accelerate coronavirus vaccine licensure
by Editorial teamThis article, published in The Lancet Infectious Diseases, presents the ethical issues associated with human challenge studies and COVID-19.
Reports from IABS Covid-19 webinars
by Editorial teamAccelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models
by The Editorial TeamThe third coronavirus outbreak in the past 20 years, the SARS-CoV-2 pandemic has caused unprecedented morbidity, mortality, and economic disruption. Safe, effective, and deployable SARS-CoV-2 vaccines are urgently needed to mitigate the consequences of the pandemic and protect from future outbreaks. The accelerated response to Covid-19 includes investments in preclinical and clinical testing and manu- facture of multiple vaccine candidates, with efficacy trials in the United States anticipated to start in July 2020.