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Background: Epidemic forms of hepatitis E cause high mortality among pregnant people, with case fatality risks over 30% and adverse fetal outcomes. In 2022, the first mass reactive vaccination campaign against hepatitis E was conducted in South Sudan with the HEV239 vaccine. We aimed to assess whether vaccination against hepatitis E in pregnancy increases the risk of fetal loss in a cohort of vaccinated and unvaccinated pregnant people., Methods: In this emulated target trial, an exhaustive pregnancy census was conducted in Bentiu internally displaced persons camp after the second of three vaccination rounds. Women and girls aged 14-45 years with no current jaundice or acute illness were eligible for participation. Individuals who consented were revisited 28 days after their delivery date to document the pregnancy outcome. We used an emulated target trial framework to address biases inherent in observational studies. We matched vaccinated to unvaccinated participants on age, gestational age, and vaccination propensity score and estimated cumulative incidence functions for fetal loss in vaccinated compared to unvaccinated women in a competing risks framework using the Aalen-Johansen estimator., Findings: Between May 16 and June 30, 2022, 3421 participants were enrolled and followed up for inclusion in analysis. Among 2741 women who had a pregnancy outcome after the start of the vaccination campaign, 67 (2·4%) were vaccinated before conception, 2036 (74·3%) were vaccinated during pregnancy, and 638 (23·2%) were not vaccinated. Among the 2407 women retained in the matched analyses, the cumulative risk of fetal loss among individuals vaccinated during pregnancy was 7·2% (95% CI 5·6-8·7) compared with 6·1% (3·7-9·2) among unvaccinated individuals, implying a risk ratio of 1·2 (95% CI 0·7-1·9)., Interpretation: No evidence of increased risk of fetal loss was found among individuals vaccinated during pregnancy., Funding: Médecins Sans Frontières., Competing Interests: Declaration of interests Médecins Sans Frontières provided support in the form of salaries for ASA, VKA, PGi, PN, JD, MH, PGa, NS, MA, MR, and IC and indirectly provided salary support for Epicentre employees RCN and EG. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Improving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini., Methods: Between April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo., Results: Four themes emerged that reflected participants' experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones., Conclusions: vDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences., (© 2024. The Author(s).)

Background: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic., Methods: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis., Results: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis., Conclusions: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes., (© 2024. The Author(s).)

Objectives: Despite declining TB notifications in Southern Africa, TB-related deaths remain high. We describe patient- and population-level trends in TB-related deaths in Eswatini over a period of 11 years., Methods: Patient-level (retrospective cohort, from 2009 to 2019) and population-level (ecological analysis, 2009-2017) predictors and rates of TB-related deaths were analysed in HIV-negative and HIV-coinfected first-line TB treatment cases and the population of the Shiselweni region. Patient-level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient-level and population-level predictors of deaths., Results: Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV-negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV-status. The treatment case fatality ratio remained above 10% in most years. At patient-level, fatality risk was higher in PLHIV (aRR 1.74, 1.51-2.02), and for older age and extra-pulmonary TB irrespective of HIV-status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18-1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47-1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB-LAM testing (aRR 0.65, 0.35-0.90). At population-level, mortality rates decreased 6.4-fold (-147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (-826/100,000 vs. HIV-negative: -23/100,000), the relative population-level mortality risk remained higher in PLHIV (aRR 4.68, 3.25-6.72) compared to the HIV-negative population., Conclusions: TB-related mortality rapidly decreased at population-level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted., (© 2023 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Acute and early HIV infection (AEHI) is rarely diagnosed in sub-Saharan Africa, despite its potential contribution to incidence reduction. This qualitative study in Eswatini explored the experiences of health workers, people diagnosed with AEHI, and their partners towards AEHI diagnosis, to inform its scale-up. In-depth interviews were undertaken with 11 women and four men diagnosed with AEHI. Three patients' partners were interviewed about their understanding of AEHI and six health workers were interviewed about experiences of delivering AEHI services. Data were coded inductively and analysed iteratively following the principles of grounded theory. Experiences with AEHI diagnoses were shaped by (i) understanding the nature and consequences of AEHI, and (ii) social norms that influence disclosure and sexual behaviour. AEHI was a new concept for health workers who struggled to explain it to patients, leading to some confusion over their HIV status and misunderstandings around its high transmissibility and prognosis. Disclosure tended to occur to primary partners, if at all, limiting the ability to provide partner services, and one relationship breakdown was reported. If AEHI diagnosis and care interventions are to realise their full potential, it will be essential to reinforce the accompanying counselling sessions and closely monitor for potential social harms.

Our understanding of the burden and drivers of cholera mortality is hampered by limited surveillance and confirmation capacity. Leveraging enhanced clinical and laboratory surveillance in the cholera-endemic community of Uvira, eastern Democratic Republic of Congo, we describe cholera deaths across 3 epidemics between September 2021 and September 2023 following mass vaccination., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Hepatitis E (HEV) genotypes 1 and 2 are the common cause of jaundice and acute viral hepatitis that can cause large-scale outbreaks. HEV infection is associated with adverse fetal outcomes and case fatality risks up to 31% among pregnant women. An efficacious three-dose recombinant vaccine (Hecolin) has been licensed in China since 2011 but until 2022, had not been used for outbreak response despite a 2015 WHO recommendation. The first ever mass vaccination campaign against hepatitis E in response to an outbreak was implemented in 2022 in Bentiu internally displaced persons camp in South Sudan targeting 27,000 residents 16-40 years old, including pregnant women., Methods: We conducted a vaccination coverage survey using simple random sampling from a sampling frame of all camp shelters following the third round of vaccination. For survey participants vaccinated in the third round in October, we asked about the onset of symptoms experienced within 72 hours of vaccination. During each of the three vaccination rounds, passive surveillance of adverse events following immunisation (AEFI) was put in place at vaccination sites and health facilities in Bentiu IDP camp., Results: We surveyed 1,599 individuals and found that self-reported coverage with one or more dose was 86% (95% CI 84-88%), 73% (95% CI 70-75%) with two or more doses and 58% (95% CI 55-61%) with three doses. Vaccination coverage did not differ significantly by sex or age group. We found no significant difference in coverage of at least one dose between pregnant and non-pregnant women, although coverage of at least two and three doses was 8 and 14 percentage points lower in pregnant women. The most common reasons for non-vaccination were temporary absence or unavailability, reported by 60% of unvaccinated people. Passive AEFI surveillance captured few mild AEFI, and through the survey we found that 91 (7.6%) of the 1,195 individuals reporting to have been vaccinated in October 2022 reported new symptoms starting within 72 hours after vaccination, most commonly fever, headache or fatigue., Conclusions: We found a high coverage of at least one dose of the Hecolin vaccine following three rounds of vaccination, and no severe AEFI. The vaccine was well accepted and well tolerated in the Bentiu IDP camp community and should be considered for use in future outbreak response., Competing Interests: The authors have no competing interests to disclose., (Copyright: © 2024 Nesbitt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Literature reviews (LRs) identify, evaluate, and synthesize relevant papers to a particular research question to advance understanding and support decision-making. However, LRs, especially traditional systematic reviews, are slow, resource-intensive, and become outdated quickly., Objective: LiteRev is an advanced and enhanced version of an existing automation tool designed to assist researchers in conducting LRs through the implementation of cutting-edge technologies such as natural language processing and machine learning techniques. In this paper, we present a comprehensive explanation of LiteRev's capabilities, its methodology, and an evaluation of its accuracy and efficiency to a manual LR, highlighting the benefits of using LiteRev., Methods: Based on the user's query, LiteRev performs an automated search on a wide range of open-access databases and retrieves relevant metadata on the resulting papers, including abstracts or full texts when available. These abstracts (or full texts) are text processed and represented as a term frequency-inverse document frequency matrix. Using dimensionality reduction (pairwise controlled manifold approximation) and clustering (hierarchical density-based spatial clustering of applications with noise) techniques, the corpus is divided into different topics described by a list of the most important keywords. The user can then select one or several topics of interest, enter additional keywords to refine its search, or provide key papers to the research question. Based on these inputs, LiteRev performs a k-nearest neighbor (k-NN) search and suggests a list of potentially interesting papers. By tagging the relevant ones, the user triggers new k-NN searches until no additional paper is suggested for screening. To assess the performance of LiteRev, we ran it in parallel to a manual LR on the burden and care for acute and early HIV infection in sub-Saharan Africa. We assessed the performance of LiteRev using true and false predictive values, recall, and work saved over sampling., Results: LiteRev extracted, processed, and transformed text into a term frequency-inverse document frequency matrix of 631 unique papers from PubMed. The topic modeling module identified 16 topics and highlighted 2 topics of interest to the research question. Based on 18 key papers, the k-NNs module suggested 193 papers for screening out of 613 papers in total (31.5% of the whole corpus) and correctly identified 64 relevant papers out of the 87 papers found by the manual abstract screening (recall rate of 73.6%). Compared to the manual full text screening, LiteRev identified 42 relevant papers out of the 48 papers found manually (recall rate of 87.5%). This represents a total work saved over sampling of 56%., Conclusions: We presented the features and functionalities of LiteRev, an automation tool that uses natural language processing and machine learning methods to streamline and accelerate LRs and support researchers in getting quick and in-depth overviews on any topic of interest., (©Erol Orel, Iza Ciglenecki, Amaury Thiabaud, Alexander Temerev, Alexandra Calmy, Olivia Keiser, Aziza Merzouki. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 15.09.2023.)

Background and Aims: Hepatitis C (HCV) programs face challenges, especially linked to key populations to achieve World Health Organization (WHO) goals of eliminating hepatitis. Médecins Sans Frontières and Mozambique's Ministry of Health first implemented HCV treatment in Maputo, in 2016 and harm reduction activities in 2017., Methods: We retrospectively analyzed routine data of patients enrolled between December 2016 and July 2021. Genotyping was systematically requested up to 2018 and subsequently in cases of treatment failure. Sustainable virological response was assessed 12 weeks after the end of treatment by sofosbuvir-daclatasvir or sofosbuvir-velpatasvir., Results: Two hundred and two patients were enrolled, with 159 (78.71%) males (median age: 41 years [interquartile range (IQR): 37.10, 47.00]). Risk factors included drug use (142/202; 70.29%). One hundred and eleven genotyping results indicated genotype 1 predominant (87/111; 78.37%). Sixteen patients presented genotype 4, with various subtypes. The people who used drugs and HIV coinfected patients were found more likely to present a genotype 1. Intention-to-treat analysis showed 68.99% (89/129) cure rate among the patients initiated and per-protocol analysis, 88.12% (89/101) cure rate. Nineteen patients received treatment integrated with opioid substitution therapy, with a 100% cure rate versus 59.37% (38/64) for initiated ones without substitution therapy ( p  < 0.001). Among the resistance testing performed, NS5A resistance-associated substitutions were found in seven patients among the nine tested patients and NS5B ones in one patient., Conclusion: We found varied genotypes, including some identified as difficult-to-treat subtypes. People who used drugs were more likely to present genotype 1. In addition, opioid substitution therapy was key for these patients to achieve cure. Access to second-generation direct-acting antivirals (DAAs) and integration of HCV care with harm reduction are crucial to program effectiveness., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objective: To describe the implementation of case-area targeted interventions to reduce cholera transmission using a rapid, localized response in Kribi district, Cameroon., Methods: We used a cross-sectional design to study the implementation of case-area targeted interventions. We initiated interventions after rapid diagnostic test confirmation of a case of cholera. We targeted households within a 100-250 metre perimeter around the index case (spatial targeting). The interventions package included: health promotion, oral cholera vaccination, antibiotic chemoprophylaxis for nonimmunized direct contacts, point-of-use water treatment and active case-finding., Findings: We implemented eight targeted intervention packages in four health areas of Kribi between 17 September 2020 and 16 October 2020. We visited 1533 households (range: 7-544 per case-area) hosting 5877 individuals (range: 7-1687 per case-area). The average time from detection of the index case to implementation of interventions was 3.4 days (range: 1-7). Oral cholera vaccination increased overall immunization coverage in Kribi from 49.2% (2771/5621 people) to 79.3% (4456/5621 people). Interventions also led to the detection and prompt management of eight suspected cases of cholera, five of whom had severe dehydration. Stool culture was positive for Vibrio cholerae O1 in four cases. The average time from onset of symptoms to admission of a person with cholera to a health facility was 1.2 days., Conclusion: Despite challenges, we successfully implemented targeted interventions at the tail-end of a cholera epidemic, after which no further cases were reported in Kribi up until week 49 of 2021. The effectiveness of case-area targeted interventions in stopping or reducing cholera transmission needs further investigation., ((c) 2023 The authors; licensee World Health Organization.)