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Sixteen novel lineages of SARS-CoV-2 in South Africa
No full textThe first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in South Africa was identified on 5 March 2020, and by 26 March the country was in full lockdown (Oxford stringency index of 90)1. Despite the early response, by November 2020, over 785,000 people in South Africa were infected, which accounted for approximately 50% of all known African infections2. In this study, we analyzed 1,365 near whole genomes and report the identification of 16 new lineages of SARS-CoV-2 isolated between 6 March and 26 August 2020. Most of these lineages have unique mutations that have not been identified elsewhere. We also show that three lineages (B.1.1.54, B.1.1.56 and C.1) spread widely in South Africa during the first wave, comprising ~42% of all infections in the country at the time. The newly identified C lineage of SARS-CoV-2, C.1, which has 16 nucleotide mutations as compared with the original Wuhan sequence, including one amino acid change on the spike protein, D614G (ref. 3), was the most geographically widespread lineage in South Africa by the end of August 2020. An early South African-specific lineage, B.1.106, which was identified in April 2020 (ref. 4), became extinct after nosocomial outbreaks were controlled in KwaZulu-Natal Province. Our findings show that genomic surveillance can be implemented on a large scale in Africa to identify new lineages and inform measures to control the spread of SARS-CoV-2. Such genomic surveillance presented in this study has been shown to be crucial in the identification of the 501Y.V2 variant in South Africa in December 2020
Candida glabrata produces a melanin-like pigment that protects against stress conditions encountered during parasitism
No full textAim: Melanin has been linked to pathogenesis in several fungi. They often produce melanin-like pigments in the presence of L-dihydroxyphenylalanine (L-DOPA), but this is poorly studied in Candida glabrata. Methods & materials: C. glabrata was grown in minimal medium with or without L-DOPA supplementation and submitted to a chemical treatment with denaturant and hot acid. Results: C. glabrata turned black when grown in the presence of L-DOPA, whereas cells grown without L-DOPA supplementation remained white. Biophysical properties demonstrated that the pigment was melanin. Melanized C. glabrata cells were effectively protected from azoles and amphotericin B, incubation at 42°C and macrophage killing. Conclusion: In the presence of L-DOPA, C. glabrata produces melanin, increases antifungal resistance and enhances host survival
Building the capacity of community health workers to support health and social care for dependent older people in Latin America: a pilot study in Fortaleza, Brazil
No full textBackground: Brazil is seeing rapid population ageing, which is leading to new demands on primary health care services. There is a need to develop and assess the effectiveness of new interventions to build the capacity of staff, including community health workers, to meet the needs of groups such as care-dependent older people and their care-givers. This study examines the feasibility of a small training intervention piloted in the Brazilian city of Fortaleza.
Methods: The study evaluated participants' own assessments of key knowledge and skills related to the needs of care-dependent older people, both before and after the training intervention. It also assessed their capacity to implement a simple screening tool of geriatric risk factors.
Results: The participant self-assessments indicate significant improvements in their perceived knowledge and capacity in responding to the health needs of care-dependent older people. Additionally, participants were able to successfully conduct the home visits and screening for risk factors.
Conclusions: The study demonstrates the feasibility of developing interventions to enhance the capacity of community health workers to meet the needs of dependent older people in countries like Brazil. The evidence of effectiveness, though limited and subjective, provides justification for a larger, formally evaluated intervention. The experience of Fortaleza provides valuable lessons for other cities and countries in the region which are facing similar challenges
HAV infection in Brazilian men who have sex with men: The importance of surveillance to avoid outbreaks
No full textBackground
Hepatitis A is a fecal-oral infection caused by hepatitis A virus (HAV). Men who have sex
with men (MSM) and transgender women (TW) have been reported as target groups for
HAV infection. This study aimed to determine the seroprevalence, risk factors, and circulating
strains associated with HAV infection among MSM and TW in Central Brazil.
Methods
A cross-sectional study was conducted from November 2011 to September 2013. Serum
samples were collected from 425 individuals for anti-HAV antibody testing and HAV molecular
characterization. Of them, 149 (35.1%) participants were self-identified as transgender
women. Statistical analysis was performed to evaluate the risk factors of HAV seropositivity.
Results
The seroprevalence of HAV exposure was 69.7% (95% Confidence Interval: 65.3–74.0%).
Serological evidence of HAV was significantly higher in participants who self-identified as
transgender women (83.2%) than MSM (62.3%). Increasing age, non-white race, and lower
monthly household income were independently associated with HAV exposure among
MSM. Only lower monthly household income was independently associated with HAV exposure
among TW. One anti-HAV IgM positive sample, from a transgender woman (0.2%),
was detected and classified as subgenotype IA. Conclusions
High HAV prevalence was observed, markedly among TW. Considering the risky
sexual behaviors this population is exposed to, HAV vaccination and prevention programs targeting this population should be considered to prevent outbreaks and the burden of the
disease
The Leishmania antigen-specific pro-inflammatory response in cutaneous leishmaniasis 3 is linked to disease progression but not to the therapeutic failure of pentavalent 4 antimonials
No full textNational Institutes of Health [AI136862.High levels of pro-inflammatory cytokines in cutaneous leishmaniasis patients are associated
with tissue damage and ulcer development. We found higher levels of TNF and IL-1in
peripheral blood mononuclear cell supernatants in response to soluble Leishmania antigen in
individuals with a longer duration of disease. In addition, L. braziliensis-infected patients
with a longer disease progression before treatment presented a shorter time to cure after
treatment onset. No associations were found between the levels of the pro-inflammatory
cytokines IL-6, TNF and IL-1- and patients’ response to pentavalent antimony treatment.
Our data suggest that while the Leishmania antigen-specific pro-inflammatory cytokines
investigated may lead to ulcer development, they do not influence therapeutic failure in
cutaneous leishmaniasis patients
Virus-related neurological lower urinary tract dysfunction: lessons learned during 4-year follow-up of patients with Congenital Zika Syndrome
No full textIntroduction: We have previously reported on neurogenic bladder dysfunction among Congenital Zika Vírus Syndrome (CZS) patients, but it is unknown how they will respond to treatment. Objective: To assess whether children with neurological lower urinary tract dysfunction and CZS will respond to Standard therapies. Methodology: A prospective observational cohort study of children with CZS referred for urological assessment between 2016 and 2020 to our quaternary center in Brazil. Urological protocol included clinical history, urinalysis and culture, renal and bladder ultrasonography and urodynamic study. Patients were treated based on findings from the first evaluation, with oxybutynin chloride for overactive bladder and low bladder compliance, clean intermittent catheterization for ineffective bladder emptying, or dual therapy when both were observed. Urological outcomes were evaluated between the first and second visits considering patient’s adherence. Outcomes measured included clinical, imaging, and urodynamic variables. Data was analyzed using the IBM SPSS 22 software. Results: From the cohort of 90 patients, 56 completed the second urodynamic assessment and were included. One presented underactive bladder and 55 overactive bladder. Among these 55, 39 were adherent and 16 non-adherents to the prescribed treatment. Among the 39 adherents, 8 adhered regularly to oxybutynin and clean intermittent catheterization (CIC), 29 to oxybutynin alone, and two to catheterization alone. During follow-up, the number of patients with urinary tract infection and postvoid residual increased, but all other parameters had improved. Renal and bladder ultrasonography improved in 10, maximum bladder pressure decreased in 22 and maximum cystometric capacity and compliance increased in 14 patients. Sixteen patients did not adhere regularly to the prescribed treatment and although the number of patients with urinary tract infection reduced with antibiotic therapy, their bladder capacity and compliance did not improve during follow-up. Discussion: Ultrasonographic and urodynamic improvements were observed after 10.8 ± 7.5 months of treatment, including one patient with ureterohydronephrosis that resolved. Adherence to CIC remains a challenge and reflected in the number of patients presenting urinary tract infection and postvoid residual. The immediate clinical relevance is the major study strength, given the previously uncharacterized therapy options for this patient population. The number of patients remains one of the study limitations, reducing our ability to perform more advanced statistical analyses. Conclusion: Patients with Zika-related neurological lower urinary tract dysfunction may benefit from conventional therapies. Results confirmed ultrasonographic and urodynamic improvements after treatment, although not statically significant. Adherence to treatment, specifically to CIC, remains a challenge
Estudo da eficácia pré-clínica de combinações binárias envolvendo miltefosina, anfotericina B lipossomal e infiltração intralesional de antimoniato de meglumina para tratamento de leishmaniose cutânea causada por Leishmania (Viannia) braziliensis
No full textLeishmanioses integram o grupo de doenças infecciosas negligenciadas, sendo o tratamento uma das principais estratégias para o seu controle. O arsenal terapêutico disponível é limitado e marcado por reconhecida toxicidade, aliado a uma insuficiência persistente no desenvolvimento de novos fármacos. Neste contexto, o reposicionamento de drogas e avaliação de novos esquemas posológicos de medicamentos existentes, incluindo as combinações, despontam como estratégias potencialmente úteis para ampliar as opções terapêuticas. Objetivo: avaliar a eficácia e a toxicidade de esquemas terapêuticos constituídos por combinações binárias dos medicamentos: miltefosina, anfotericina B lipossomal e antimoniato de meglumina para o tratamento de leishmaniose cutânea causada por Leishmania (Viannia) braziliensis, em modelo animal. Metodologia: modelo experimental animal de leishmaniose cutânea utilizando hamsters (Mesocricetus auratus) machos infectados por cepa de referência L. (V.) braziliensis (MHOM/BR/75/M2903). Inicialmente definiu-se a dose da miltefosina a ser utilizada na combinação. As combinações binárias foram comparadas como os medicamentos em monoterapia, nomeadamente miltefosina na dose de 25mg/kg, via oral, por 20 dias consecutivos, anfotericina B lipossomal 10mg/kg, dose única, via intraperitoneal e antimoniado de meglumina por via intralesional em infiltração única. Para controle do experimento, foram constituídos grupos de animais mantidos sem tratamento. A eficácia clínica foi avaliada comparando-se o maior diâmetro da úlcera entre os grupos de animais no 23º dia após início do tratamento e, a eficácia parasitológica, pela comparação da carga parasitária na lesão e no baço. A toxicidade foi avaliada por meio da inspeção do comportamento dos animais e pela mensuração da massa corpórea. Resultados: redução significativa do tamanho da lesão em relação ao controle foi observada em animais tratados com antimoniato de meglumina, anfotericina B lipossomal associada com miltefosina e com antimoniato de meglumina. Na comparação entre as intervenções, apresentaram maior redução na lesão em relação ao grupo tratado com miltefosina, grupos de animais tratados com as combinações de anfotericina B com antimoniato de meglumina e com miltefosina. As combinações de anfotericina B lipossomal com antimoniato de meglumina e com miltefosina produziram significativa redução nas lesões dos animais tratados em comparação com o grupo controle, diferentemente do observado com o tratamento em monoterapia. Em relação ao parâmetro parasitológico, animais tratados com anfotericina B lipossomal associada a antimoniato de meglumina apresentaram a maior redução na carga parasitária na lesão. Por sua vez, os tratamentos com miltefosina, seja em monoterapia ou em associação com antimoniato de meglumina, também se relacionaram com redução significativa da carga parasitária em relação aos grupos de animais tratados com anfotericina B lipossomal e antimoniato de meglumina, ambos em monoterapia. No baço, verificou-se que todos os grupos de animais tratados com combinação, assim como o grupo tratado com miltefosina, apresentaram redução significativa da carga parasitária em comparação com animais sem tratamento. Conclusão: Os esquemas baseados em anfotericina B lipossomal associada a miltefosina por via oral ou a antimoniato de meglumina em infiltração intralesional se mostraram clinicamente mais efetivos que os medicamentos usados individualmente, em modelo experimental de hamsters infectados por L. braziliensis, sugerindo a viabilidade da estratégia combinada também no tratamento da forma cutânea da leishmaniose.Leishmaniasis is a neglected infectious disease for which treatment is still the main control strategy. The available therapeutic arsenal is limited and marked by recognized toxicity, a situation aggravated by the lack of interest of governments and industry in the development of new drugs. In this context, drug repositioning and evaluation of new dosage regimens for existing drugs, including combinations, emerge as potentially useful strategies to expand therapeutic options. Objective: To evaluate the efficacy and toxicity of regimens based on combinations of the miltefosine, liposomal amphotericin B and meglumine antimoniate for the treatment of cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis. Methodology: experimental animal model of cutaneous leishmaniasis using male hamsters (Mesocricetus auratus) infected by the reference strain L. braziliensis (MHOM/BR/75/M2903). Initially, the dose of miltefosine to be used in the combination was defined as 25mg/kg. Binary combinations were compared with drugs in monotherapy, namely miltefosine at 25mg/kg, orally, for 20 consecutive days; liposomal amphotericin B 10mg/kg, single dose, intraperitoneally and meglumine antimony, intralesional route in a single infiltration. To control the experiment, one group of animals were kept untreated. The clinical efficacy was evaluated by comparing the largest ulcer diameter between the groups of animals on the 23rd day after the start of treatment and, the parasitological efficacy, by comparing the parasite load in the lesion and in the spleen. Toxicity was assessed by inspecting the behavior of animals and measuring body mass. Results: Significant lesion size reduction compared to control group was observed in animals treated with intralesional infiltration of meglumine antimoniate monotherapy, liposomal amphotericin B associated with miltefosine and liposomal amphotericin B associated with infiltration of meglumine antimoniate. Animals treated with the combinations of amphotericin B and meglumine antimoniate and amphotericin B and miltefosine exhibited higher reduction in the lesion compared to animals treated with miltefosine monotherapy. The combinations of liposomal amphotericin B with intralesional infiltration of meglumine antimoniate and liposomal amphotericin B with miltefosine produced a significant reduction in the lesions compared to the control group, differently from what was observed with the monotherapy treatment. Regarding the parasitological parameter, animals treated with liposomal amphotericin B associated with intralesional infiltration of meglumine antimoniate showed the highest reduction in the parasite load in the skin lesion. In turn, treatments with miltefosine, either in monotherapy or in association with intralesional infiltration of meglumine antimoniate were also related to a significant reduction in the parasite load compared to animals treated with liposomal amphotericin B and meglumine antimoniate, both in monotherapy. In the spleen, we observed that all animals treated with combination of drugs, as well as the group treated with miltefosine, showed a significant reduction in the parasite load compared to animals without treatment. Conclusion: in an experimental model of hamsters infected by L. braziliensis, the regimens based on liposomal amphotericin B associated with oral miltefosine or intralesional infiltration of meglumine antimoniate were clinically more effective than the drugs used individually, suggesting the viability of the strategy also in the treatment of the cutaneous form of leishmaniasis
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
No full textSOUZA, Bruno Solano Freitas Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. O autor consta da lista Oxford COVID Vaccine Trial Group.Clare L Cutland, Thomas C Darton, Keertan Dheda, Christina Dold, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Amy Flaxman, Lee Fairlie,
Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Eva Galiza, Anna L Goodman, Catherine M Green, Christopher A Green,
Melanie Greenland, Catherine Hill, Helen C Hill, Ian Hirsch, Alane Izu, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra,
Rajeka Lazarus, Vincenzo Libri, Patrick J Lillie, Natalie G Marchevsky, Richard P Marshall, Ana V A Mendes, Eveline P Milan, Angela M Minassian,
Alastair McGregor, Yama F Mujadidi, Anusha Nana, Sherman D Padayachee, Daniel J Phillips, Ana Pittella, Emma Plested, Katrina M Pollock,
Maheshi N Ramasamy, Adam J Ritchie, Hannah Robinson, Alexandre V Schwarzbold, Andrew Smith, Rinn Song, Matthew D Snape,
Eduardo Sprinz, Rebecca K Sutherland, Emma C Thomson, M Estée Török, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana,
Thomas White, Christopher J Williams, Alexander D Douglas*, Adrian V S Hill*, Teresa Lambe*, Sarah C Gilbert*, Andrew J Pollard*, on behalf of
the Oxford COVID Vaccine Trial Group†. Oxford Vaccine Group,
Department of Paediatrics,
University of Oxford, Oxford,
UK (M Voysey DPhil,
P K Aley DPhil, S Bibi PhD,
E A Clutterbuck PhD, C Dold PhD,
K R W Emary FRCPath,
S Feng PhD, M Greenland MSc,
S Kerridge MSc,
N G Marchevsky MSc,
Y F Mujadidi MSc,
D J Phillips MMath, E Plested,
M N Ramasamy DPhil,
H Robinson RN, M D Snape MD,
R Song MD,
Prof A J Pollard FMedSci); Jenner
Institute, Nuffield Department
of Medicine, University of
Oxford, Oxford, UK
(A D Douglas DPhil,
A Flaxman DPhil, S C Gilbert PhD,
T Lambe PhD, A V S Hill FMedSci,
P M Folegatti MD, B Angus MD,
P Cicconi MD, K J Ewer PhD,
D Jenkin MRCP, C C D Joe PhD,
A M Minassian DPhil,
A J Ritchie PhD); Institute of
Global Health, University of
Siena, Siena, Italy
(S A Costa Clemens MD); Department of Paediatrics
(S A Costa Clemens) and Clinical
BioManufacturing Facility
(C M Green PhD), University of
Oxford, Oxford, UK;
South African Medical Research
Council Vaccines and Infectious
Diseases Analytics Research
Unit, Faculty of Health Sciences
(S A Madhi PhD, V L Baillie PhD,
C L Cutland MD, C Hill BA,
A Izu PhD, A Koen MBChB,
G Kwatra PhD), Department of
Science and Innovation/
National Research Foundation
South African Research Chair
Initiative in Vaccine
Preventable Diseases Unit
(S A Madhi, V L Baillie,
C L Cutland, C Hill, A Izu, A Koen,
G Kwatra), Wits Reproductive
Health and HIV Institute,
Faculty of Health Sciences
(L Fairlie FCPaeds), and Perinatal
HIV Research Unit, Faculty of
Health Sciences (C Briner MBBCh,
A Nana BPharm), University of
the Witwatersrand,
Johannesburg, South Africa;
Department of Pediatrics,
Universidade Federal de
São Paulo, São Paulo, Brazil
(L Y Weckx MD); AstraZeneca
BioPharmaceuticals,
Cambridge, UK (I Hirsch PhD,
R P Marshall MD,
J Vekemans MD PhD,
T L Villafana PhD, T White PhD);
Family Centre for Research
with Ubuntu, Department of
Paediatrics, University of
Stellenbosch, Cape Town,
South Africa (S L Barnabas PhD);
Soweto Clinical Trials Centre,
Soweto, South Africa
(Q E Bhorat MSc); Department
of Clinical Sciences, Liverpool
School of Tropical Medicine and
Liverpool University Hospitals
NHS Foundation Trust,
Liverpool, UK (A M Collins PhD,
D M Ferreira PhD, H C Hill PhD);
Department of Infection,
Immunity and Cardiovascular
Disease, University of Sheffield,
Sheffield, UK (T C Darton DPhil);
Department of Infection and
Tropical Medicine, Sheffield
Teaching Hospitals NHS
Foundation Trust, Sheffield, UK
(T C Darton); Escola Bahiana de
Medicina e Saúde Pública,
Salvador, Braziland Hospital
São Rafael, Salvador, Brazil
(A V A Mendes MD); Instituto
D’Or, Salvador, Brazil
(A V A Mendes); Division of
Pulmonology, Groote Schuur
Hospital and the University of
Cape Town, Cape Town,
South Africa (K Dheda FRCPCH, Faculty of Infectious and
Tropical Diseases, Department
of Immunology and Infection,
London School of Hygiene &
Tropical Medicine, London, UK
(K Dheda); Department of
Infection and Tropical
Medicine, Newcastle upon Tyne
Hospitals NHS Foundation
Trust, Newcastle upon Tyne, UK
(C J A Duncan DPhil);
Translational and Clinical
Research Institute, Immunity
and Inflammation Theme,
Newcastle University,
Newcastle upon Tyne, UK
(C J A Duncan); NIHR
Southampton Clinical Research
Facility and Biomedical
Research Centre, University
Hospital Southampton NHS
Foundation Trust
(S N Faust PhD); Faculty of
Medicine and Institute for Life
Sciences, University of
Southampton, Southampton,
UK (S N Faust); School of
Population Health Sciences,
University of Bristol and
University Hospitals Bristol and
Weston NHS Foundation Trust,
UK (A Finn FRCPCH);
Department of Infection, Guy’s
and St Thomas’ NHS
Foundation Trust, St Thomas’
Hospital, London, UK
(A L Goodman FRCP);
MRC Clinical Trials Unit,
University College London,
London, UK (A L Goodman);
NIHR/Wellcome Trust Clinical
Research Facility, University
Hospitals Birmingham NHS
Foundation Trust, Birmingham,
UK (C A Green DPhil); St George’s
Vaccine Institute, St George’s,
University of London, London,
UK (E Galiza MBBS); Severn
Pathology, North Bristol NHS
Trust, Bristol, UK
(R Lazarus DPhil); NIHR UCLH
Clinical Research Facility and
NIHR UCLH Biomedical
Research Centre, London, UK
(V Libri FRCP); Department of
Infection, Hull University
Teaching Hospitals NHS Trust,
Hull, UK (P J Lillie PhD); London
Northwest University
Healthcare, Harrow, UK
(A C McGregor FRCPath);
Setshaba Research Centre,
Pretoria, South Africa
(S D Payadachee MBChB);
Universidade Federal do
Rio Grande do Norte, Natal,
Brazil (E P Milan PhD); Hospital
Quinta D’Or, Rede D’Or,
Rio De Janeiro, Brazil
(A Pittella MD); NIHR Imperial
Clinical Research Facility and NIHR Imperial Biomedical
Research Centre, London, UK
(K M Pollock PhD); College of
Medical, Veterinary & Life
Sciences, Glasgow Dental
Hospital & School, University of
Glasgow, Glasgow, UK
(A Smith FRCPath); Infectious
Diseases Service, Hospital de
Clinicas de Porto Alegre,
Universidade Federal do
Rio Grande do Sul,
Porto Alegre, Brazil
(E Sprinz MD); Clinical Research
Unit, Department of Clinical
Medicine, Universidade Federal
de Santa Maria, Santa Maria,
Brazil (A V Schwarzbold PhD);
Clinical Infection Research
Group, Regional Infectious
Diseases Unit, Western General
Hospital, Edinburgh, UK
(R K Sutherland FRCP);
MRC-University of Glasgow
Centre for Virus Research &
Department of Infectious
Diseases, Queen Elizabeth
University Hospital, Glasgow,
UK (E C Thomson FRCP PhD);
Department of Medicine,
University of Cambridge, UK
(M E Török FRCP); Cambridge
University Hospitals NHS
Foundation Trust, Cambridge,
UK (M E Török); Heart Lung
Research Institute, Dept of
Medicine, University of
Cambridge and NIHR
Cambridge Clinical Research
Facility, Cambridge University
Hospital and Royal Papworth
NHS Foundation Trusts,
Cambridge, UK (M Toshner MD);
University of Nottingham and
Nottingham University
Hospitals NHS Trust,
Nottingham, UK
(D P J Turner PhD); Public Health
Wales, Cardiff, Wales
(C J Williams FFPH); Aneurin
Bevan University Health Board,
Newport, Wales (C J Williams).UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic
Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’Or, the Brava and
Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical
Research Network, and AstraZenecaBackground The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5×10¹⁰ viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2×10¹⁰ viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAATpositive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24422 participants were recruited and vaccinated across the four studies, of whom 17178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68])
Leprosy incidence and risk estimates in a 33-year contact cohort of leprosy patients
No full textProdução científica do Laboratório de Hanseníase.This work was supported by FIOCRUZ.Coordination for the Improvement of Higher Education Personnel (CAPES).National Council for Scientific and Technological Development (CNPq).Novartis Foundation Leprosy Research Initiative.Turing Foundation.Reduction in incidence has been associated with the introduction of novel approaches, like chemo/immune-prophylaxis. Incidence determined through follow-up cohort studies can evaluate the implementation of these innovative policies towards control and prevention. We have assessed the incidence in our contacts cohort over past 33 years, considering the effect of demographic and clinical variables. Survival analysis was used to estimate the risk of leprosy. A total of 9024 contacts were evaluated, of which 192 developed leprosy, resulting in an overall incidence of 1.4/1000 person-years. The multivariate analysis showed that the major risk factors were (i) contact from MB index cases and (ii) consanguinity (iii) intra household contact. Lower risk was detected for contacts with BCG scar who were revaccinated. There was a significant decrease in accumulated risk between the 2011–2019 period compared with 1987, probably linked to the improvement in laboratory tools to monitor contacts, thereby providing early diagnosis of contacts at intake and reduction of transmission. Our findings suggest that a combination of contact surveillance and tracing, adequate neurodermatological examination, and availability of molecular tools is highly effective in supporting early diagnosis, while a second dose of the BCG vaccination can exert extra protection
Artisanal fisherwomen and workers’ health: Brazilian Unified Health System unknown scenarios
No full textOs autores declaram que o trabalho contou com apoio do Programa Institucional de Bolsas de Iniciação Cientifica (PIBIC) ofertado pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) sob processo 117818/2019-4 e que não há conflitos de interesses. Os autores informam que o trabalho não foi apresentado em evento científico e não foi baseado em dissertação ou tese.Objetivo: compreender a percepção de trabalhadoras da pesca artesanal acerca dos riscos e agravos relacionados ao trabalho e das ações de promoção à saúde dirigidas a sua atividade produtiva. Métodos: pesquisa-ação com sete pescadoras e marisqueiras do rio Pacoti, em Eusébio, Ceará. A coleta de dados foi realizada no domicílio das trabalhadoras em 2019. As entrevistas foram gravadas, transcritas e seu conteúdo analisado por meio da análise de discurso. Resultados: as mulheres pescadoras têm baixa escolaridade e renda. Enfrentam condições de trabalho precárias em ambiente inóspito (manguezal). Relatam quedas, fraturas, ferimentos, afogamentos e sintomas de distúrbios musculoesqueléticos relacionados ao trabalho, porém não consideram que estejam expostas à riscos. Esses acidentes são vistos por elas como inerentes ao processo produtivo e os agravos à saúde não são percebidos como decorrentes do trabalho. Também não identificam ações de promoção de saúde dirigidas a elas. Conclusão: as situações relatadas e vivenciadas pelas trabalhadoras indicam que o serviço de saúde local ainda não atua a partir de uma visão de Saúde do Trabalhador. Há necessidade do Sistema Único de Saúde avançar na promoção da saúde, por meio de educação, vigilância e atenção em saúde com foco na prevenção de agravos relacionados à pesca artesanal.Programa Institucional de Bolsas de Iniciação Cientifica (PIBIC) ofertado pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) sob processo 117818/2019-4 .Objective: to understand the artisanal fisherwomen’s perception about the risks and health problems related to their work, as well as to the health promotion actions aimed at their activity. Methods: action research conducted with seven fisherwomen/shellfish gatherers of the Pacoti River, in Eusébio, state of Ceará, Brazil. Participants were interviewed at their home in 2019. The interviews were recorded, transcribed, and their content examined using discourse analysis. Results: our findings indicated that fisherwomen have low education and income levels, besides facing precarious working conditions in an inhospitable environment (mangrove). Although reporting falls, fractures, injuries, drownings, and symptoms of work-related musculoskeletal disorders, they do not consider that they are exposed to risks. They see these accidents as inherent to the production process and do not perceive their health problems as resulting from the working conditions to which they are subjected. They also do not identify the existence of health promotion actions aimed at fisherwomen and shellfish gatherers. Conclusion: the situations experienced and reported by the workers indicate that the local health service is not committed to occupational health yet. Brazilian Unified Health System (SUS) must advance in health promotion through education, surveillance, and healthcare, aimed at preventing artisanal fishing work-related diseases