IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial

Kielmann, Karina - ORCID 0000-0001-5519-1658 https://orcid.org/0000-0001-5519-1658Introduction Compared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease.Methods and analysis This study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis.Ethics and dissemination This study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders.Trial registration number ISRCTN95243114Secondary identifying numbers University College London/University College London Hospitals Joint Research Office 17/0726. National Institute for Health Research, UK 16/88/06.https://doi.org/10.1136/bmjopen-2019-032760http://bmjopen.bmj.com/cgi/content/full/bmjopen-2019-0327609pubpub1

Incidence and risk factors of surgical site infections and related antibiotic resistance in Freetown, Sierra Leone: a prospective cohort study

BACKGROUND: There is limited information on surgical site infections (SSI) and the related antibiotic resistance needed to guide their management and prevention in Sierra Leone. In this study, we aimed to establish the incidence and risk factors of SSI and the related antibiotic resistance among adults attending a tertiary hospital, and a secondary health facility in Freetown, Sierra Leone. METHODS: This is a prospective cohort study designed to collect data from adult (18 years or older) patients who attended elective and emergency surgeries at two hospitals in Freetown between February and July, 2021. Data analysis was done using STATA version 16. RESULTS: Of 338 patients, 245 (72.5%) and 93 (27.5%) had their surgeries at the tertiary and secondary hospitals, respectively. Many were males 192 (56.8%), less than 35 years 164 (48.5%), and 39 (11.5%) developed an SSI. Of the 39 patients who acquired an SSI, 7 (17.9%) and 32 (82.1%) had their surgeries at the secondary and tertiary hospitals, respectively. The incidence of SSI is higher in contaminated 17 (43.6%) than in clean-contaminated 12 (30.8%) and clean 10 (25.6%) wounds. Wound swabs were collected in 29 (74.4%) patients, of which 18 (62.1%) had bacterial growth. In total, 49 isolates of 14 different bacteria including gram-negative 41 (83.7%) and gram-positive 8 (16.3%) isolates were identified. Of these, 32 (65.3%) were Enterobacteriaceae, 9 (18.4%) were Non-fermenting gram-negative bacilli and 10 (12.2%) were Enterococci. The most common isolates were Escherichia coli (12, 24.5%), Klebsiella pneumoniae (10, 20.4%), Acinetobacter baumannii (5, 10.2%), Klebsiella oxytoca (4, 8.2%) and Enterococcus faecalis (4, 8.2%). The Enterobacteriaceae were either resistance to carbapenems (4, 8.2%) or were extended-spectrum beta-lactamase (ESBL) producing organisms (29, 59.2%). Male sex [p = 0.031], an ASA score >/= 2 [p = 0.020), administration of general anaesthesia [p = 0.018] and elevated fasting glucose [p = 0.033] were predictive of SSI. CONCLUSION: The incidence of SSI in this study is comparable to other low- and middle-income countries, but a substantial proportion of these postoperative wounds have an ESBL-producing Enterobacteriaceae. Therefore, routine surveillance of SSI and related antibiotic resistance is required in resource-limited settings

Hospital readmission among people experiencing homelessness in England: a cohort study of 2772 matched homeless and housed inpatients

BackgroundInpatients experiencing homelessness are often discharged to unstable accommodation or the street, which may increase the risk of readmission.MethodsWe conducted a cohort study of 2772 homeless patients discharged after an emergency admission at 78 hospitals across England between November 2013 and November 2016. For each individual, we selected a housed patient who lived in a socioeconomically deprived area, matched on age, sex, hospital, and year of discharge. Counts of emergency readmissions, planned readmissions, and Accident and Emergency (A&amp;E) visits post-discharge were derived from national hospital databases, with a median of 2.8 years of follow-up. We estimated the cumulative incidence of readmission over 12 months, and used negative binomial regression to estimate rate ratios.ResultsAfter adjusting for health measured at the index admission, homeless patients had 2.49 (95% CI 2.29 to 2.70) times the rate of emergency readmission, 0.60 (95% CI 0.53 to 0.68) times the rate of planned readmission and 2.57 (95% CI 2.41 to 2.73) times the rate of A&amp;E visits compared with housed patients. The 12-month risk of emergency readmission was higher for homeless patients (61%, 95% CI 59% to 64%) than housed patients (33%, 95% CI 30% to 36%); and the risk of planned readmission was lower for homeless patients (17%, 95% CI 14% to 19%) than for housed patients (30%, 95% CI 28% to 32%). While the risk of emergency readmission varied with the reason for admission for housed patients, for example being higher for admissions due to cancers than for those due to accidents, the risk was high across all causes for homeless patients.ConclusionsHospital patients experiencing homelessness have high rates of emergency readmission that are not explained by health. This highlights the need for discharge arrangements that address their health, housing and social care needs.</jats:sec

The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Are health systems interventions gender blind? examining health system reconstruction in conflict affected states

Background Global health policy prioritizes improving the health of women and girls, as evident in the Sustainable Development Goals (SDGs), multiple women’s health initiatives, and the billions of dollars spent by international donors and national governments to improve health service delivery in low-income countries. Countries recovering from fragility and conflict often engage in wide-ranging institutional reforms, including within the health system, to address inequities. Research and policy do not sufficiently explore how health system interventions contribute to the broader goal of gender equity. Methods This paper utilizes a framework synthesis approach to examine if and how rebuilding health systems affected gender equity in the post-conflict contexts of Mozambique, Timor Leste, Sierra Leone, and Northern Uganda. To undertake this analysis, we utilized the WHO health systems building blocks to establish benchmarks of gender equity. We then identified and evaluated a broad range of available evidence on these building blocks within these four contexts. We reviewed the evidence to assess if and how health interventions during the post-conflict reconstruction period met these gender equity benchmarks. Findings Our analysis shows that the four countries did not meet gender equitable benchmarks in their health systems. Across all four contexts, health interventions did not adequately reflect on how gender norms are replicated by the health system, and conversely, how the health system can transform these gender norms and promote gender equity. Gender inequity undermined the ability of health systems to effectively improve health outcomes for women and girls. From our findings, we suggest the key attributes of gender equitable health systems to guide further research and policy. Conclusion The use of gender equitable benchmarks provides important insights into how health system interventions in the post-conflict period neglected the role of the health system in addressing or perpetuating gender inequities. Given the frequent contact made by individuals with health services, and the important role of the health system within societies, this gender blind nature of health system engagement missed an important opportunity to contribute to more equitable and peaceful societies

New filovirus disease classification and nomenclature

Filoviruses, the members of the family Filoviridae, are currently classified into one proposed and five established genera (Supplementary Table 1). Of the twelve described filoviruses, six have been identified as aetiological agents of naturally occurring human disease outbreaks

New filovirus disease classification and nomenclature.

The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children

Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial

Background The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. Methods The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5×1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1×108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant’s last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. Findings Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736–6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312–4383]) at 21 days after the second vaccination. Interpretation The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults