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1.
Emerg Infect Dis ; 23(4): 611-615, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27997333

RESUMO

Zika virus RNA has been detected in semen collected several months after onset of symptoms of infection. Given the potential for sexual transmission of Zika virus and for serious fetal abnormalities resulting from infection during pregnancy, information regarding the persistence of Zika virus in semen is critical for advancing our understanding of potential risks. We tested serial semen samples from symptomatic male patients in the United Kingdom who had a diagnosis of imported Zika virus infection. Among the initial semen samples from 23 patients, Zika virus RNA was detected at high levels in 13 (56.5%) and was not detected in 9 (39.1%); detection was indeterminate in 1 sample (4.4%). After symptomatic infection, a substantial proportion of men have detectable Zika virus RNA at high copy numbers in semen during early convalescence, suggesting high risk for sexual transmission. Viral RNA clearance times are not consistent and can be prolonged.


Assuntos
RNA Viral/isolamento & purificação , Sêmen/virologia , Infecção por Zika virus/transmissão , Zika virus/isolamento & purificação , Adulto , Humanos , Masculino , Reino Unido/epidemiologia , Infecção por Zika virus/virologia
2.
PLoS Med ; 13(4): e1001997, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27093560

RESUMO

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.


Assuntos
Antivirais/uso terapêutico , Ebolavirus/genética , Doença pelo Vírus Ebola/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , RNA Viral/genética , Terapêutica com RNAi/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ebolavirus/patogenicidade , Feminino , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/genética , Doença pelo Vírus Ebola/mortalidade , Doença pelo Vírus Ebola/virologia , Interações Hospedeiro-Patógeno , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Nanopartículas , RNA Interferente Pequeno/administração & dosagem , RNA Viral/sangue , Terapêutica com RNAi/efeitos adversos , Serra Leoa , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Carga Viral/genética , Adulto Jovem
3.
Emerg Infect Dis ; 21(2)2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25626057

RESUMO

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.


Assuntos
Melioidose/diagnóstico , Humanos , Guias de Prática Clínica como Assunto
4.
J Travel Med ; 30(2)2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36708032

RESUMO

BACKGROUND: Every year, many thousands of travellers return to the United Kingdom (UK) from visits to other countries and some will become unwell due to infections acquired abroad. Many imported infections have similar clinical presentations, such as fever and myalgia, so diagnostic testing is an important tool to improve patient management and outcomes. The aim of this study was to examine the demographics, travel history, presenting symptoms and diagnostic outcomes of referrals to the UK's specialist diagnostic Rare & Imported Pathogens Laboratory (RIPL) for the period 2015-2020. METHODS: Anonymised clinical and laboratory data were extracted from RIPL's Laboratory Information Management System and cleaned prior to descriptive analysis of the data. Travel history data were mapped to one of eight world regions, whereas symptom data were categorised into presenting syndromes. Diagnostic data were categorised as either positive, equivocal or negative. RESULTS: During the period 2015-2020, RIPL received 73 951 samples from 53 432 patients suspected of having infections that are rare in the UK. The most common age group for unwell returning travellers was 30-39 years and the most commonly reported travel destination was Southern and SE Asia. Dengue virus was the most diagnosed infection overall, followed by chikungunya, Zika, leptospirosis and spotted fever group Rickettsia. Dengue virus was among the top three most frequent diagnoses for all world regions except Europe and represented 62.5% of all confirmed/probable diagnoses. CONCLUSIONS: None of the top five infections diagnosed by RIPL in travellers are vaccine-preventable, therefore understanding traveller demographics, destination-specific risk factors and encouraging preventative behaviours is the best available strategy to reduce the number of returning travellers who become infected. Prompt referral of acute samples with a detailed travel history, including purpose of travel and activities undertaken as well as dates and destinations can be a valuable tool in designing public health interventions and diagnostic algorithms.


Assuntos
Febre de Chikungunya , Infecção por Zika virus , Zika virus , Humanos , Adulto , Estudos Retrospectivos , Viagem , Febre de Chikungunya/diagnóstico , Reino Unido
5.
J Infect ; 86(5): 446-452, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36948252

RESUMO

OBJECTIVE: The burden of imported rickettsial infection in the UK is not previously described. This retrospective review identifies rickettsial cases diagnosed at the national reference laboratory between 2015 and 2022. METHODS: Samples testing positive for spotted fever group, typhus group, and scrub typhus IgG/IgM on acute and convalescent blood samples, and/or PCR on tissue/blood were categorized as suspected, confirmed or past infection. RESULTS: 220 patients had rickettsioses, and the commonest import was acute spotted fever group infection (61%, 125/205), 54% (62/114) from South Africa. In acute typhus group cases, 60% (40/67) were from Southeast Asia. One patient with Rickettsia typhi bacteremia died. Scrub typhus group infections (5%, 10/205) were exclusively from Asia and the Western Pacific regions. Overall, 43% of confirmed cases (39/91) had not received doxycycline prior to results. CONCLUSIONS: Rickettsial infections are important and under-recognized causes of imported fever in the UK. Thorough history, examination, and timely treatment with doxycycline should be considered if there is suspicion of Rickettsia infection before testing.


Assuntos
Infecções por Rickettsia , Rickettsia , Tifo por Ácaros , Rickettsiose do Grupo da Febre Maculosa , Tifo Epidêmico Transmitido por Piolhos , Humanos , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/microbiologia , Doxiciclina/uso terapêutico , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/microbiologia , Rickettsiose do Grupo da Febre Maculosa/diagnóstico , Rickettsiose do Grupo da Febre Maculosa/epidemiologia
6.
J Infect ; 82(5): 162-169, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33766553

RESUMO

BACKGROUND: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England. METHODS: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression. FINDINGS: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S). INTERPRETATION: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Inglaterra , Pessoal de Saúde , Humanos , Estudos Prospectivos , Saúde Pública
8.
FEMS Immunol Med Microbiol ; 49(3): 410-4, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17316368

RESUMO

Incubation in the presence of structurally modified disaccharides altered the in vitro attachment of Yersinia pestis GB to three human respiratory epithelial cell lines. Each disaccharide resulted in decreased attachment to the alveolar epithelial (A549) cell line. The best inhibitor of attachment for each cell line was the benzylated derivative of Galbeta1-4GalNAc. Highly negatively charged saccharides were efficient inhibitors, particularly for the bronchial epithelial (BEAS2-B) cell line. The data indicate that targeted modification of receptor ligands could offer a novel therapeutic preventing Y. pestis attachment to host cells.


Assuntos
Antibacterianos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Dissacarídeos/química , Dissacarídeos/farmacologia , Células Epiteliais/microbiologia , Yersinia pestis/fisiologia , Linhagem Celular , Humanos , Estrutura Molecular , Yersinia pestis/efeitos dos fármacos
10.
Int J Antimicrob Agents ; 36(1): 87-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20462743

RESUMO

The efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of Burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. Trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. Overall, the data suggest that some fluoroquinolones may have potential utility in prophylaxis of melioidosis and suggest that azithromycin would not be effective in prophylaxis of B. pseudomallei infection.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Azitromicina/uso terapêutico , Burkholderia pseudomallei/efeitos dos fármacos , Fluoroquinolonas/uso terapêutico , Melioidose/prevenção & controle , Naftiridinas/uso terapêutico , Piperazinas/uso terapêutico , Animais , Burkholderia pseudomallei/isolamento & purificação , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Análise de Sobrevida
11.
Int J Antimicrob Agents ; 36(1): 66-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20022474

RESUMO

The prophylactic potential of the azalide azithromycin as well as the fluoroquinolones trovafloxacin and grepafloxacin was assessed for the control of infection with Brucella melitensis in an experimental mouse model, determined by reduction in splenic bacterial burden. Trovafloxacin showed limited protective efficacy when administered 2h following a low-dose B. melitensis challenge, whereas grepafloxacin was ineffective. In comparison, azithromycin provided significant control of infection both following low- and high-dose challenges. Overall, the data confirm the potential utility of azithromycin in the prophylaxis of brucellosis and suggest that neither trovafloxacin nor grepafloxacin would likely be valuable for post-exposure prophylaxis of Brucella infection.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Azitromicina/uso terapêutico , Brucella melitensis/efeitos dos fármacos , Brucelose/prevenção & controle , Fluoroquinolonas/uso terapêutico , Naftiridinas/uso terapêutico , Piperazinas/uso terapêutico , Animais , Brucella melitensis/isolamento & purificação , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Baço/microbiologia
13.
Int J Antimicrob Agents ; 34(5): 471-3, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19682862

RESUMO

The prophylactic potential of moxifloxacin and gatifloxacin was assessed in comparison with doxycycline, an established therapeutic antibiotic, to limit or control infection by Brucella melitensis in an experimental mouse model, determined by reduced bacterial burden in the spleen. Although moxifloxacin was found to have a small protective effect when administered 6 h following infection, neither moxifloxacin nor gatifloxacin showed significant efficacy in vivo. In comparison, doxycycline provided significant protection when prophylaxis was started at 6 h, 7 days or 14 days following infection. Overall, these results confirm the utility of doxycycline in the prophylaxis of brucellosis and suggest that neither moxifloxacin nor gatifloxacin are likely to be valuable for post-exposure prophylaxis of Brucella infection.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Compostos Aza/uso terapêutico , Brucelose/prevenção & controle , Fluoroquinolonas/uso terapêutico , Quinolinas/uso terapêutico , Animais , Brucella melitensis/efeitos dos fármacos , Brucelose/microbiologia , Contagem de Colônia Microbiana , Doxiciclina/uso terapêutico , Feminino , Gatifloxacina , Camundongos , Camundongos Endogâmicos BALB C , Moxifloxacina , Baço/microbiologia , Resultado do Tratamento
14.
Vaccine ; 23(17-18): 2090-4, 2005 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-15755577

RESUMO

This paper describes a proposed Strategic Vaccine Facility (SVF) to provide a capability to the UK to deal with new and emerging disease threats. It would underpin the vaccine manufacturing industry by developing expertise and technology to enable rapid manufacture of small batches of vaccines for emergency use against agents, such as bioterrorist agents and emerging diseases. It would have a rare ability to work with dangerous pathogens under containment, allowing the production of inactivated and live vaccines, which would be difficult in a conventional plant. The facility's output will include vaccine candidates and manufacturing protocols for transfer to industry, small vaccine batches for emergency use or clinical trials, and vaccine reference standards. It would also be available for manufacturing small batches of experimental and public health vaccines for the UK and the developing world, allowing clinical trials to be undertaken against key diseases.


Assuntos
Arquitetura de Instituições de Saúde , Vacinas/isolamento & purificação , Bioterrorismo/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis Emergentes/imunologia , Doenças Transmissíveis Emergentes/prevenção & controle , Humanos , Reino Unido , Vacinação
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