Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 26
Filter
1.
Nat Commun ; 14(1): 5948, 2023 Sep 23.
Article in English | MEDLINE | ID: mdl-37741831

ABSTRACT

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.


Subject(s)
Sexual and Gender Minorities , Smallpox Vaccine , Smallpox , Male , Humans , Monkeypox virus/genetics , Smallpox/prevention & control , Immunity, Humoral , Homosexuality, Male
2.
Sex Transm Infect ; 99(4): 261-267, 2023 06.
Article in English | MEDLINE | ID: mdl-35981863

ABSTRACT

OBJECTIVES: To investigate how differential access to key interventions to reduce STIs, HIV and their sequelae changed during the COVID-19 pandemic. METHODS: British participants (18-59 years) completed a cross-sectional web survey 1 year (March-April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16-74 years) conducted in 2010-2012. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually experienced participants (18-44 years) (n=3869, Natsal-COVID; n=8551, Natsal-3). ORs adjusted for age and other potential confounders describe associations with demographic and behavioural factors. RESULTS: In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18-24 years, of black or black British ethnicity, and reporting same-sex sex (past 5 years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners and with cervical screening among smokers. CONCLUSIONS: Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, there was not strong evidence that differential access has changed during the pandemic when compared with 2010-2012. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , Chlamydia , HIV Infections , Sexually Transmitted Diseases , Uterine Cervical Neoplasms , Male , Humans , Female , Condoms , Early Detection of Cancer , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Pandemics/prevention & control , United Kingdom/epidemiology , Cross-Sectional Studies , COVID-19/epidemiology , COVID-19/prevention & control , Communicable Disease Control , Sexual Behavior , Sexual Partners , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/prevention & control , Acquired Immunodeficiency Syndrome/epidemiology , HIV Testing , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control
4.
Lancet Infect Dis ; 20(10): e251-e260, 2020 10.
Article in English | MEDLINE | ID: mdl-32768390

ABSTRACT

The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving.


Subject(s)
Metagenomics/methods , Metagenomics/statistics & numerical data , Computational Biology , Humans , Molecular Epidemiology , Research Design/standards
5.
PLoS One ; 15(1): e0226817, 2020.
Article in English | MEDLINE | ID: mdl-31978082

ABSTRACT

BACKGROUND: A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS: Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS: Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION: Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.


Subject(s)
Bacteria/isolation & purification , Bacterial Infections/diagnosis , Candida/isolation & purification , Candidiasis/diagnosis , Neonatal Sepsis/microbiology , RNA, Ribosomal, 16S/genetics , Age of Onset , Bacteria/genetics , Candida/genetics , DNA, Ribosomal/genetics , Early Diagnosis , Enterobacteriaceae/genetics , Enterobacteriaceae/isolation & purification , Enterococcus/genetics , Enterococcus/isolation & purification , Humans , Infant, Extremely Premature , Infant, Newborn , Infant, Premature , Multiplex Polymerase Chain Reaction , Mycoplasma/genetics , Mycoplasma/isolation & purification , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Streptococcus/genetics , Streptococcus/isolation & purification , Ureaplasma/genetics , Ureaplasma/isolation & purification
6.
J Infect Dis ; 220(5): 802-810, 2019 07 31.
Article in English | MEDLINE | ID: mdl-31107958

ABSTRACT

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.


Subject(s)
Hepatitis E virus/pathogenicity , Hepatitis E/epidemiology , Adult , Aged , Animals , Databases, Factual , England/epidemiology , Female , Genotype , Hepatitis E virus/genetics , Humans , Logistic Models , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Swine , Wales , Young Adult
13.
J Infect ; 71(1): 43-52, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25709085

ABSTRACT

OBJECTIVES: Recent development of serogroup B meningococcal (MenB) vaccines highlights the importance of pharyngeal carriage data, particularly in adolescents and young adults, to inform implementation strategies. We describe current UK carriage prevalence in this high risk population and compare methods of carriage detection. METHODS: In this multisite study, pharyngeal swabs were collected on 3-4 occasions over 6-12 months, from 1040 school and university students, aged 10-25 years. Meningococcal carriage was detected by standard culture combined with seroagglutination or PCR of cultured isolates, or by direct PCR from swab. The factor H binding protein (fHBP) variants present in meningococcal isolates were determined. RESULTS: Meningococcal serogroups B and Y were most common, with carriage up to 6.5% and 5.5% respectively, increasing throughout adolescence. Identification by seroagglutination was often unreliable, and the sensitivity of direct PCR detection was 66% compared to culture combined with PCR. Of MenB isolates, 89.1% had subfamily A variants of fHBP. The acquisition rate of MenB carriage was estimated at 2.8 per 1000 person-months. CONCLUSIONS: If vaccination is to precede the adolescent rise in MenB carriage, these data suggest it should take place in early adolescence. Studies assessing vaccine impact should use molecular methods to detect carriage.


Subject(s)
Carrier State/epidemiology , Meningococcal Infections/epidemiology , Adolescent , Adult , Agglutination Tests , Antigens, Bacterial/genetics , Bacterial Proteins/genetics , Child , Epidemiologic Studies , Humans , Longitudinal Studies , Male , Neisseria meningitidis/classification , Neisseria meningitidis/isolation & purification , Pharynx/microbiology , Polymerase Chain Reaction , Serogroup , United Kingdom/epidemiology , Vaccination , Young Adult
14.
J Antimicrob Chemother ; 68(12): 2733-45, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23904558

ABSTRACT

Antibiotic licensing studies remain a problem in neonates. The classical adult clinical syndrome-based licensing studies do not apply to neonates, where sepsis is the most common infection. The main obstacle to conducting neonatal antibiotic trials is a lack of consensus on the definition of neonatal sepsis itself and the selection of appropriate endpoints. This article describes the difficulties of the clinical and laboratory definitions of neonatal sepsis and reviews the varying designs of previous neonatal sepsis trials. The optimal design of future trials of new antibiotics will need to be based on pharmacokinetic/pharmacodynamic parameters, combined with adequately powered clinical studies to determine safety and efficacy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Clinical Trials as Topic/standards , Sepsis/diagnosis , Sepsis/drug therapy , Endpoint Determination/standards , Humans , Infant, Newborn , Terminology as Topic , Treatment Outcome
15.
Pediatr Infect Dis J ; 32(6): 675-81, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23348809

ABSTRACT

AIM: To test for immunologic noninferiority of antibody responses to Hib and MenC using a 6-in-1 combination vaccine (DTPa-IPV/Hib-MenC-TT) compared with DTPa-IPV-Hib plus MenC-CRM197, before and after a 12-month Hib-MenC-TT booster. METHODS: Pragmatic open-label, randomized, multicenter, UK study. "6-in-1" group received DTPa-IPV/Hib-MenC-TT at 2, 3 and 4 months; control group received DTPa-IPV-Hib at 2, 3 and 4 months and MenC-CRM197 at 3 and 4 months. Both groups received Hib-MenC-TT at 12 months. Concomitant vaccines: pneumococcal conjugate vaccine at 2, 4 and 13 months, and measles, mumps and rubella vaccine at 13 months. RESULTS: One hundred forty-two children were randomized to each group. One hundred children in the "6-in-1" group and 112 control group children completed the study according-to-protocol. One month postprimary immunizations: 100% of "6-in-1" group and 93.3% of control children had anti-polyribosylribitol phosphate (PRP) IgG ≥0.15 µg/mL; 96.2% and 100%, respectively, had rSBA-MenC titers ≥1:8. One month after booster all children met these thresholds, with anti-PRP geometric mean concentrations of 66.7 (53.3; 83.5) in "6-in-1" recipients and 26.9 (20.9; 34.6) in control children (4.4 [3.5; 5.4] and 3.0 [2.2-4.2] postprimary immunizations, respectively,). rSBA-MenC geometric mean titers were 3062.9 (2421.2; 3874.6) and 954.0 (761.3; 1195.5), respectively, postbooster and 393.2 (292.5; 528.7) and 3110.5 (2612; 3704.2) postprimary. CONCLUSION: Noninferiority of DTPa-IPV/Hib-MenC-TT compared with DTPa-IPV/Hib plus MenC-CRM197 was demonstrated. In the "6-in-1" group, lower postprimary and greater postbooster rSBA-MenC geometric mean titers suggest memory B-cell priming may be favored by this vaccine over plasma cell induction. Furthermore, greater immunogenicity of TT conjugates used in both primary and booster vaccines in this group may be important.


Subject(s)
Diphtheria-Tetanus-Pertussis Vaccine/immunology , Haemophilus Vaccines/immunology , Meningococcal Vaccines/immunology , Poliovirus Vaccine, Inactivated/immunology , Vaccination/methods , Antibodies, Bacterial/blood , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Female , Haemophilus Vaccines/administration & dosage , Humans , Immunoglobulin G/blood , Immunologic Memory , Infant , Male , Meningococcal Vaccines/administration & dosage , Poliovirus Vaccine, Inactivated/administration & dosage , United Kingdom , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunology
16.
Pediatr Infect Dis J ; 32(1): 23-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23241987

ABSTRACT

BACKGROUND: There are few population-based studies on the epidemiology of neonatal and pediatric invasive Candida infections, despite their significant clinical impact on patients. This study aimed to describe the epidemiology of pediatric candidemia in England and Wales during a 10-year period as a means of quantifying the changing burden of infection and identifying emerging trends. METHODS: National Health Service hospital microbiology laboratories in England and Wales routinely report clinically significant invasive infections electronically to the Health Protection Agency. Records of all positive blood cultures for Candida species in children aged <15 years between 2000 and 2009 inclusive were extracted for analysis. RESULTS: During 2000 to 2009, 1473 childhood candidemia cases were reported in England and Wales (annual incidence, 1.52/100,000 person-years), with the highest rate in <1 year olds (n = 706; 11.0/100,000), followed by 1-4 year olds (n = 440; 1.77/100,000), 5-9 year olds (n = 168; 0.53/100,000) and 10-14 year olds (n = 159; 0.47/100,000). Incidence increased from 1.04 per 100,000 in 2000 to 2.09 per 100,000 in 2007 (P < 0.001) before falling to 1.53 per 100,000 in 2009 (P < 0.001). Candida species was reported in 89.6% (1320/1473) cases, with Candida albicans and Candida parapsilosis accounting for most infections in all age groups. There were no significant differences in species distribution by season or year of study and the proportion of non-albicans cases did not increase with time. CONCLUSIONS: Pediatric candidemia rates are beginning to fall in England and Wales. C. albicans continues to account for most Candida bloodstream infections in all age groups with no evidence of increases in non-albicans species.


Subject(s)
Candida/isolation & purification , Candidemia/epidemiology , Infant, Newborn, Diseases/epidemiology , Adolescent , Candida/classification , Candidemia/microbiology , Child , Child, Preschool , England/epidemiology , Female , Humans , Infant , Infant, Newborn , Infant, Newborn, Diseases/microbiology , Male , Wales/epidemiology
17.
PLoS One ; 7(3): e33736, 2012.
Article in English | MEDLINE | ID: mdl-22438987

ABSTRACT

UNLABELLED: The sublingual route has been proposed as a needle-free option to induce systemic and mucosal immune protection against viral infections. In a translational study of systemic and mucosal humoral immune responses to sublingual or systemically administered viral antigens, eighteen healthy female volunteers aged 19-31 years received three immunizations with a quadravalent Human Papilloma Virus vaccine at 0, 4 and 16 weeks as sublingual drops (SL, n = 12) or intramuscular injection (IM, n = 6). IM antigen delivery induced or boosted HPV-specific serum IgG and pseudovirus-neutralizing antibodies, HPV-specific cervical and vaginal IgG, and elicited circulating IgG and IgA antibody secreting cells. SL antigens induced ~38-fold lower serum and ~2-fold lower cervical/vaginal IgG than IM delivery, and induced or boosted serum virus neutralizing antibody in only 3/12 subjects. Neither route reproducibly induced HPV-specific mucosal IgA. Alternative delivery systems and adjuvants will be required to enhance and evaluate immune responses following sublingual immunization in humans. TRIAL REGISTRATION: ClinicalTrials.govNCT00949572.


Subject(s)
Alphapapillomavirus/immunology , Antigens, Viral/administration & dosage , Papillomavirus Vaccines/administration & dosage , Administration, Sublingual , Adult , Antibodies, Neutralizing/biosynthesis , Antibodies, Neutralizing/blood , Antibodies, Viral/biosynthesis , Antibodies, Viral/blood , Capsid Proteins/immunology , Cervix Uteri/immunology , Female , Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 , Human papillomavirus 11/immunology , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Human papillomavirus 6/immunology , Humans , Immunity, Mucosal , Immunoglobulin A, Secretory/biosynthesis , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Injections, Intramuscular , Oncogene Proteins, Viral/immunology , Vagina/immunology , Young Adult
18.
Clin Infect Dis ; 54(5): 661-9, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22267719

ABSTRACT

BACKGROUND: We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). METHODS: Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. RESULTS: Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. CONCLUSIONS: This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.


Subject(s)
Antibodies, Viral/blood , Influenza A Virus, H1N1 Subtype/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Adjuvants, Immunologic , Antibodies, Viral/immunology , Follow-Up Studies , Hemagglutination Inhibition Tests , Humans , Influenza Vaccines/administration & dosage , Influenza Vaccines/adverse effects , Neutralization Tests , Virion/immunology
20.
Trials ; 12: 215, 2011 Sep 30.
Article in English | MEDLINE | ID: mdl-21958494

ABSTRACT

BACKGROUND: Late onset neonatal sepsis (LOS) with the mortality of 17 to 27% is still a serious disease. Meropenem is an antibiotic with wide antibacterial coverage. The advantage of it over standard of care could be its wider antibacterial coverage and thus the use of mono-instead of combination therapy. METHODS: NeoMero-1, an open label, randomised, comparator controlled, superiority trial aims to compare the efficacy of meropenem with a predefined standard of care (ampicillin + gentamicin or cefotaxime + gentamicin) in the treatment of LOS in neonates and infants aged less than 90 days admitted to a neonatal intensive care unit.A total of 550 subjects will be recruited following a 1:1 randomisation scheme. The trial includes patients with culture confirmed (at least one positive culture from normally sterile site except coagulase negative staphylococci in addition to one clinical or laboratory criterion) or clinical sepsis (at least two laboratory and two clinical criteria suggestive of LOS in subjects with postmenstrual age < 44 weeks or fulfilment of criteria established by the International Pediatric Sepsis Consensus Conference in subjects with postmenstrual age ≥ 44 weeks). Meropenem will be given at a dose of 20 mg/kg q12h or q8h depending on the gestational- and postnatal age. Comparator agents are administered as indicated in British National Formulary for Children. The primary endpoint measured at the test of cure visit (2 days after end of study therapy) is graded to success (all baseline symptoms and laboratory parameters are resolved or improved with no need to continue antibiotics and the baseline microorganisms are eradicated and no new microorganisms are identified and the patient has received allocated treatment for 11 ± 3 days with no modification) or a failure (all remaining cases). Secondary outcome measures include comparison of survival, relapse rates or new infections by Day 28, clinical response at Day 3 and end of therapy, duration of hospitalisation, population pharmacokinetic analysis of meropenem and effect of antibiotics on mucosal colonisation and development of antibacterial resistance.The study will start recruitment in September 2011; the total duration is of 24 months. TRIAL REGISTRATION: EudraCT 2011-001515-31.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Clinical Protocols , Sepsis/drug therapy , Thienamycins/therapeutic use , Humans , Infant , Infant, Newborn , Length of Stay , Meropenem , Thienamycins/pharmacokinetics
SELECTION OF CITATIONS
SEARCH DETAIL
...