Plasmodium Falciparum-Induced Kidney and Liver Dysfunction in Malaria Patients in Freetown, Sierra Leone

This study was undertaken to investigate the effect of Plasmodium falciparum infection on kidney and liver function parameters in malaria patients in Freetown, Sierra Leone. Blood samples taken from 64 malaria patients and 64 non-malaria volunteers at Abanita and Blue Shield Hospitals, Freetown Sierra Leone between January to April, 2009 were examined. Changes in serum biochemical parameters were analysed using normal range values as baseline. Serum bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations were significantly elevated in falciparum malaria patients compared to their non-malaria counterparts which is an indication of defective liver function. Most of patients with falciparum malaria also have significantly high serum concentrations of urea, creatinine, sodium and potassium showing alteration in kidney function. This study suggests that malaria parasites could be responsible for derangement of kidney and liver functions in patients and could therefore contribute to organ damage in affected individuals if not treated. Keywords: Kidney function, Liver function, Malaria, Plasmodium falciparu

Research Involving People of a Refugee Background:Considerations for Ethical Engagement

This paper is of relevance to both those considering carrying out research and those participating in it. It is based on discussions between three researchers of a non-refugee background and a small group of nine people of a refugee background living in Ireland and Scotland, all of whom have been involved in research in some way. The paper is divided into three sections outlining what should be considered before, during and after data has been collected from people of a refugee background.Irish Research CouncilUniversity College DublinFunded by the Irish Research Council and the Scottish Irish Migration Initiativ

Complicity and contestation in the gentrifying urban primary school.

The transformation of primary schools in gentrifying localities has sometimes been referred to as a form of ‘class colonisation’. This article draws on ethnographic research with teachers, teaching assistants, and parents in two inner-London primary schools to explore the largely unexamined role of school leaders (headteachers) in mediating gentrification processes within urban schools. It argues that institutional history, contexts of headship and leadership style all play an important role in negotiating and recontextualising middle-class mobilisation and power to re-shape primary schools. Headteachers’ relationship to gentrification is therefore not simply one of complicity, but often of contestation and conflict. This article therefore challenges understandings of gentrification as a hegemonic process, and contributes to a more nuanced picture of the educational consequences of gentrification, particularly the institutional realities and experiences of urban social change

The impact of the COVID-19 pandemic on the provision & utilisation of primary health care services in Goma, Democratic Republic of the Congo, Kambia district, Sierra Leone & Masaka district, Uganda.

INTRODUCTION: This study aimed to determine whether the COVID-19 pandemic had an impact on essential primary healthcare services at public primary healthcare facilities. METHODS: The number of weekly consultations for antenatal care (ANC), outpatient (OPD), immunisations (EPI), family planning (FP) and HIV services, between January 2018 and December 2020, were collected from 25 facilities in Masaka district, Uganda, 21 in Goma, and 29 in Kambia district, Sierra Leone. Negative binomial regression models accounting for clustering and season were used to analyse changes in activity levels between 2018, 2019 and 2020. RESULTS: In Goma, we found no change in OPD, EPI or ANC consultations, FP was 17% lower in March-July 2020 compared to 2019, but this recovered by December 2020. New diagnoses of HIV were 34% lower throughout 2020 compared to 2019. In Sierra Leone, compared to the same periods in 2019, facilities had 18-29% fewer OPD consultations throughout 2020, and 27% fewer DTP3 doses in March-July 2020. There was no evidence of differences in other services. In Uganda there were 20-35% fewer under-5 OPD consultations, 21-66% fewer MCV1 doses, and 48-51% fewer new diagnoses of HIV throughout 2020, compared to 2019. There was no difference in the number of HPV doses delivered. CONCLUSIONS: The level of disruption varied across the different settings and qualitatively appeared to correlate with the strength of lockdown measures and reported attitudes towards the risk posed by COVID-19. Mitigation strategies such as health communications campaigns and outreach services may be important to limit the impact of lockdowns on primary healthcare services

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

Tuning main group redox chemistry through steric loading: subvalent Group 13 metal complexes of carbazolyl ligands.

The ability of substituted carbazol-9-yl systems to ligate in σ fashion through the amido N-donor, or to adopt alternative coordination modes through the π system of the central five-membered ring, can be tuned by systematic variation in the steric demands of substituents in the 1- and 8-positions. The differing affinities of the two modes of coordination for hard and soft metal centres can be shown to influence not only cation selectivity, but also the redox properties of the metal centre. Thus, the highly sterically sterically demanding 1,3,6,8-tetra-tert-butylcarbazolyl ligand can be used to generate the structurally characterised amido-indium(I) complex, [{(tBu(4)carb)In}(n)], (together with its isostructural thallium counterpart) in which the metal centre interacts with the central pyrrolyl ring in η(3) fashion [d(In-N)=2.679(3) Å; d(In-C)=2.819(3), 2.899(3) Å]. By contrast, the smaller 3,6-di-tert-butylcarbazolyl system is less able to restrict the metal centre from binding at the anionic nitrogen donor in the plane of the carbazolyl ligand (i.e. in σ fashion). Analogous chemistry with In(I) precursors therefore leads to disproportionation to the much harder In(II) [and In(0)], and the formation of the mixed-valence product, [In(2){In(2)(tBu(2)carb)(6)}], a homoleptic molecular [In(4)(NR(2))(6)] system. This chemistry reveals a flexibility of ligation for carbazolyl systems that contrasts markedly with that of the similarly sterically encumbered terphenyl ligand family