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1.
BMC Womens Health ; 23(1): 660, 2023 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-38066506

RESUMO

BACKGROUND: Cervical cancer is the most common cancer and the leading cause of cancer-related death in Gambian women. The Gambian Ministry of Health is striving to improve access to screening, diagnostic, and treatment services for cervical cancer, but comprehensive data on currently available services is limited making it challenging to appropriately prioritize the ideal next steps for expanding care. This study aims to describe the current services available for the prevention, screening, and treatment of cervical cancer in The Gambia and provide suggestions for expanding geographic access to care. METHODS: A survey aimed at assessing the availability of key cervical cancer-related services was developed and then administered in person by research assistants to all secondary and tertiary health facilities (HFs) in The Gambia. ArcGIS Pro Software and 2020 LandScan population density raster were used to visualize and quantify geographic access to care. Survey results were compared with published targets outlined by the Gambian Ministry of Health in the "Strategic Plan for the Prevention and Control of Cervical Cancer in The Gambia: 2016-2020." RESULTS: One hundred and two HFs were surveyed including 12 hospitals, 3 major health centers, 56 minor health centers, and 31 medical centers/clinics. Seventy-eight of these HFs provided some form of cervical cancer-related service. HPV vaccination was available in all health regions. Two-thirds of the population lived within 10 km of a HF that offered screening for cervical cancer and half lived within 10 km of a HF that offered treatment for precancerous lesions. Ten HFs offered hysterectomy, but nine were located in the same region. Two HFs offered limited chemotherapy. Radiotherapy was not available. If all major health centers and hospitals started offering visual inspection with acetic acid and cryotherapy, 86.1% of the population would live within 25 km of a HF with both services. CONCLUSIONS: Geographic access to cervical cancer screening, and precancer treatment is relatively widespread across The Gambia, but targeted expansion in line with the country's "Strategic Plan" would improve access for central and eastern Gambia. The availability of treatment services for invasive cancer is limited, and establishing radiotherapy in the country should continue to be prioritized.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Gâmbia , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer/métodos , Densidade Demográfica , Análise Espacial
2.
PLoS One ; 16(9): e0256980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495988

RESUMO

BACKGROUND: A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection. METHODOLOGY: This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method. RESULTS: In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection. CONCLUSIONS: This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.


Assuntos
Vacinas contra Adenovirus/imunologia , Adenovirus dos Símios/imunologia , Antígenos de Protozoários/imunologia , DNA de Protozoário/imunologia , DNA Recombinante/imunologia , Imunização Secundária/métodos , Vacinas Antimaláricas/imunologia , Malária Falciparum/prevenção & controle , Proteínas de Membrana/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Vacinas de DNA/imunologia , Vacinas contra Adenovirus/administração & dosagem , Vacinas contra Adenovirus/efeitos adversos , Adenovirus dos Símios/genética , Adulto , Antígenos de Protozoários/genética , Linfócitos T CD8-Positivos/imunologia , DNA de Protozoário/genética , Epitopos/genética , Epitopos/imunologia , Feminino , Vetores Genéticos/administração & dosagem , Vetores Genéticos/imunologia , Voluntários Saudáveis , Humanos , Imunogenicidade da Vacina/imunologia , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/efeitos adversos , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Masculino , Proteínas de Membrana/genética , Proteínas de Protozoários/genética , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Adulto Jovem
3.
BMC Health Serv Res ; 21(1): 943, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503503

RESUMO

BACKGROUND: The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care. METHODS: A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care. RESULTS: All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%. CONCLUSIONS: Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Gâmbia/epidemiologia , Acessibilidade aos Serviços de Saúde , Humanos , Programas de Rastreamento
4.
Nat Commun ; 12(1): 4636, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330906

RESUMO

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Vacinas Virais/imunologia , Adolescente , Adulto , Febre de Chikungunya/prevenção & controle , Febre de Chikungunya/virologia , Vírus Chikungunya/classificação , Vírus Chikungunya/fisiologia , Citocinas/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Fadiga/induzido quimicamente , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/imunologia , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinação/métodos , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Adulto Jovem
5.
Nat Med ; 27(2): 270-278, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33335323

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.


Assuntos
Formação de Anticorpos/imunologia , Vacinas contra COVID-19/imunologia , Linfócitos T/imunologia , Adolescente , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/virologia , ChAdOx1 nCoV-19 , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Subunidades Proteicas/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto Jovem
6.
Lancet ; 396(10267): 1979-1993, 2021 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-33220855

RESUMO

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Imunogenicidade da Vacina , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/farmacologia , ChAdOx1 nCoV-19 , Feminino , Humanos , Imunização Secundária/efeitos adversos , Imunoglobulina G/sangue , Imunoglobulina G/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , Método Simples-Cego , Adulto Jovem
7.
Lancet ; 396(10249): 467-478, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702298

RESUMO

BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Imunogenicidade da Vacina , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia , Acetaminofen/uso terapêutico , Adenovirus dos Símios/genética , Adulto , Analgésicos não Narcóticos/uso terapêutico , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Feminino , Vetores Genéticos/administração & dosagem , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Masculino , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Método Simples-Cego , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia , Reino Unido , Vacinas Virais/administração & dosagem
8.
Lancet Infect Dis ; 20(7): 816-826, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32325038

RESUMO

BACKGROUND: Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans. METHODS: This dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial was done at the Centre for Clinical Vaccinology and Tropical Medicine (Oxford, UK) and included healthy people aged 18-50 years with negative pre-vaccination tests for HIV antibodies, hepatitis B surface antigen, and hepatitis C antibodies (and a negative urinary pregnancy test for women). Participants received a single intramuscular injection of ChAdOx1 MERS at three different doses: the low-dose group received 5 × 109 viral particles, the intermediate-dose group received 2·5 × 1010 viral particles, and the high-dose group received 5 × 1010 viral particles. The primary objective was to assess safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited, unsolicited, and serious adverse events after vaccination. The secondary objective was to assess the cellular and humoral immunogenicity of ChAdOx1 MERS, measured by interferon-γ-linked enzyme-linked immunospot, ELISA, and virus neutralising assays after vaccination. Participants were followed up for up to 12 months. This study is registered with ClinicalTrials.gov, NCT03399578. FINDINGS: Between March 14 and Aug 15, 2018, 24 participants were enrolled: six were assigned to the low-dose group, nine to the intermediate-dose group, and nine to the high-dose group. All participants were available for follow-up at 6 months, but five (one in the low-dose group, one in the intermediate-dose group, and three in the high-dose group) were lost to follow-up at 12 months. A single dose of ChAdOx1 MERS was safe at doses up to 5 × 1010 viral particles with no vaccine-related serious adverse events reported by 12 months. One serious adverse event reported was deemed to be not related to ChAdOx1 MERS. 92 (74% [95% CI 66-81]) of 124 solicited adverse events were mild, 31 (25% [18-33]) were moderate, and all were self-limiting. Unsolicited adverse events in the 28 days following vaccination considered to be possibly, probably, or definitely related to ChAdOx1 MERS were predominantly mild in nature and resolved within the follow-up period of 12 months. The proportion of moderate and severe adverse events was significantly higher in the high-dose group than in the intermediate-dose group (relative risk 5·83 [95% CI 2·11-17·42], p<0·0001) Laboratory adverse events considered to be at least possibly related to the study intervention were self-limiting and predominantly mild in severity. A significant increase from baseline in T-cell (p<0·003) and IgG (p<0·0001) responses to the MERS-CoV spike antigen was observed at all doses. Neutralising antibodies against live MERS-CoV were observed in four (44% [95% CI 19-73]) of nine participants in the high-dose group 28 days after vaccination, and 19 (79% [58-93]) of 24 participants had antibodies capable of neutralisation in a pseudotyped virus neutralisation assay. INTERPRETATION: ChAdOx1 MERS was safe and well tolerated at all tested doses. A single dose was able to elicit both humoral and cellular responses against MERS-CoV. The results of this first-in-human clinical trial support clinical development progression into field phase 1b and 2 trials. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research.


Assuntos
Relação Dose-Resposta Imunológica , Imunogenicidade da Vacina , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vacinas Virais/administração & dosagem , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais , Infecções por Coronavirus/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Reino Unido , Vacinas de DNA , Adulto Jovem
9.
BMC Infect Dis ; 19(1): 259, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30876397

RESUMO

BACKGROUND: Infection with Hepatitis B virus (HBV) is a serious public health problem worldwide, with over 360 million carriers. Sixty million of these are resident in Sub-saharan Africa. Hepatitis B infection is the cause of Hepatocellular carcinoma (HCC), which is the second commonest cause of death from cancers among women in The Gambia. Vertical transmission is the commonest route of spread of Hepatitis B Virus in many endemic areas. The main aim of the study was to determine the sero-prevalence of Hepatitis B surface antigen (HBsAg) among pregnant women attending antenatal clinic at the Edward Francis Small Teaching Hospital, Banjul, The Gambia. METHODS: Four hundred and twenty six pregnant women were recruited from our antenatal clinics and tested for HBsAg. Serum Hepatitis B surface antigen (HBsAg) was tested using commercial rapid diagnostic Elisa kits at the point of care. RESULTS: A prevalence rate of 9.20% among all pregnant women studied was found. Women who were likely to have been vaccinated had a prevalence rate of 2.30% whiles those unlikely to have been vaccinated had a prevalence of 13.71%. There was a statistically significant difference between those likely to have been vaccinated and those unlikely to have been vaccinated. CONCLUSION: The prevalence of hepatitis B infection is very high among pregnant women at EFSTH as in the high endemic zone that is more than 8%. However the prevalence rate is lower than the national average of 15%. The prevalence is of moderate endemicity among the women who likely received vaccination during childhood. More interventions during pregnancy need to be undertaken if more successes are to be registered.


Assuntos
Vírus da Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adolescente , Adulto , Feminino , Gâmbia/epidemiologia , Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Soroepidemiológicos , Adulto Jovem
10.
BMC Med Educ ; 12: 72, 2012 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-22873698

RESUMO

BACKGROUND: Understanding preferences for specialties by medical students and the factors driving choices assists policy makers in ensuring optimal spread of personnel across disciplines. METHODS: This cross-sectional survey using self-administered structured questionnaires was conducted on consenting students of the first medical school in The Gambia, established in 1999. Data collection was in June/July 2011. Questions were on sociodemographic characteristics of students, their parents, factors related to career preferences and opinions about counseling services. Data were analysed using JMP 8.0 software. RESULTS: Respondents were 52.4% of 202 eligible students. Mean age was 24.1 ± 5.0 years. Females constituted 54.7%. Muslims were 72.7% while Gambians formed 77.0%. Commonest specialties chosen by females were Obstetrics/Gynaecology, Paediatrics and Surgery in that order, while males preferred Internal Medicine, Surgery and Obstetrics/Gynaecology. Commonest factors influencing choices by females were 'focus on urgent care' (65.5%) and 'intellectual content of specialty' (56.9%). For males, these were 'intellectual content of specialty' (60.4%) and 'focus on urgent care' / 'individual's competence' (50.0% each). More females (30.0%) than males (23.0%) had ever received career counseling, but all students desired it. CONCLUSIONS: Significant gender differences exist in specialty choices and factors influencing these choices amongst these students. All want career counseling.


Assuntos
Escolha da Profissão , Especialização , Estudantes de Medicina/psicologia , Orientação Vocacional , Adulto , Estudos Transversais , Educação de Graduação em Medicina , Feminino , Gâmbia , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
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