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The Lancet. Infectious Diseases May 2024Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether...
Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design.
BACKGROUND
Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population.
METHODS
ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing).
FINDINGS
Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9-18). The median age was 40 years (34-48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12-0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60-1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events.
INTERPRETATION
Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored.
FUNDING
ANRS Maladies Infectieuses Emergentes.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
PubMed: 38797183
DOI: 10.1016/S1473-3099(24)00236-6 -
The Journal of Infection Aug 2023To evaluate persistence of vaccine effectiveness (VE) and vaccine impact (VI) on invasive meningococcal B (MenB) disease and gonorrhoea at three years after...
OBJECTIVES
To evaluate persistence of vaccine effectiveness (VE) and vaccine impact (VI) on invasive meningococcal B (MenB) disease and gonorrhoea at three years after implementation of a state funded 4CMenB programme for infants, children, adolescents and young people in South Australia.
METHODS
VI was assessed using a Poisson or negative binomial regression model, and VE was estimated using screening and case-control methods. Chlamydia controls were used to estimate VE in the primary analysis to control potential confounding effects such as high-risk sexual behaviour associated with sexually transmitted infections.
RESULTS
During the three-year programme, reductions of 63.1% (95%CI 29.0-80.9%) and 78.5% (95%CI 33.0-93.1%) in incidence of MenB disease were observed in infants and adolescents, respectively. There were no cases in infants who had received three doses of 4CMenB. Two-dose VE against MenB disease was 90.7% (95%CI 6.9-99.1%) for the childhood programme and 83.5% (95%CI 0-98.2%) for the adolescent programme. Two-dose VE against gonorrhoea in adolescents was 33.2% (95%CI 15.9-47.0%). Lower VE estimates were demonstrated after 36 months post-vaccination (23.2% (95%CI 0-47.5%)> 36 months post-vaccination compared to 34.9% (95%CI 15.0-50.1%) within 6-36 months). Higher VE estimates were found after excluding patients with repeat gonorrhoea infections (37.3%, 95%CI 19.8-51.0%). For gonorrhoea cases co-infected with chlamydia VE was maintained (44.7% (95%CI 17.1-63.1%).
CONCLUSION
The third-year evaluation results show persistent vaccine effectiveness of 4CMenB against MenB disease in infants and adolescents. As this is the first ongoing programme for adolescents, moderate vaccine protection against gonorrhoea with waning effectiveness three years post-vaccination was demonstrated in adolescents and young adults. The additional protection of 4CMenB vaccine against gonorrhoea, likely through cross-protection should be considered in cost-effectiveness analyses. A booster dose may need to be further evaluated and considered in adolescents due to waning protection against gonorrhoea demonstrated after 36 months post-vaccination.
Topics: Child; Infant; Adolescent; Young Adult; Humans; Meningococcal Infections; Gonorrhea; Vaccine Efficacy; Meningococcal Vaccines; Immunization Schedule; Neisseria meningitidis, Serogroup B
PubMed: 37268223
DOI: 10.1016/j.jinf.2023.05.021 -
Current Opinion in Infectious Diseases Feb 2024While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria... (Review)
Review
PURPOSE OF REVIEW
While effective vaccines to prevent invasive infections by Neisseria meningitidis have been deployed around the world, development of a vaccine to prevent Neisseria gonorrhoeae has lagged. After multiple failed vaccine candidates, vaccine development for N. gonorrhoeae is showing promise for the first time in several decades. This review highlights recent progress in the field.
RECENT FINDINGS
Vaccines containing outer-membrane vesicles (OMV) have been used to manage outbreaks of the serogroup B N. meningitidis in a number of countries. Epidemiologic studies indicate these vaccination campaigns were associated with reductions in reported N. gonorrhoeae infections. Recently, a serogroup B N. meningitidis vaccine containing both recombinant antigens and OMV has been licensed through much of the world. Epidemiologic studies also demonstrate associations between 4CMenB immunization and reduced N. gonorrhoeae infections. Additionally, mathematical modeling studies have begun to identify potential strategies for vaccine deployment to maximize reduction of infections.
SUMMARY
After several decades with little progress towards an effective gonococcal vaccine, large observational studies have provided evidence that a new generation of group B N. meningitidis vaccines containing OMV have serendipitously restarted the field. Ongoing clinical trials will soon provide definitive evidence regarding the efficacy of these vaccines in preventing N. gonorrhoeae infection.
Topics: Humans; Meningococcal Infections; Meningococcal Vaccines; Bacterial Vaccines; Neisseria meningitidis; Neisseria gonorrhoeae; Gonorrhea
PubMed: 38050729
DOI: 10.1097/QCO.0000000000000992 -
The New England Journal of Medicine Aug 2023
Topics: Humans; Meningococcal Vaccines; Gambia; Mali; Vaccines, Conjugate
PubMed: 37590459
DOI: 10.1056/NEJMc2307375 -
Human Vaccines & Immunotherapeutics Dec 2023The Advisory Committee on Immunization Practices (ACIP) has recommended human papillomavirus (HPV) vaccination for adolescents in the United States since 2006. Though... (Review)
Review
The Advisory Committee on Immunization Practices (ACIP) has recommended human papillomavirus (HPV) vaccination for adolescents in the United States since 2006. Though recommended at a similar time to the routine recommendations for adolescent tetanus, diphtheria, and acellular pertussis vaccination (Tdap) and quadrivalent meningococcal vaccination (MCV4), HPV vaccine uptake has consistently lagged behind these other adolescent vaccines. The ACIP recommends HPV vaccination at 11-12 y, with vaccination starting at 9 y of age included as an option that is routinely encouraged by the American Academy of Pediatrics and American Cancer Society. To support efforts to increase HPV vaccination at the first opportunity, this commentary summarizes the current HPV vaccination recommendations and available evidence regarding HPV vaccination starting at 9 y - including recent studies and trials documenting the effectiveness of HPV vaccination at 9 in supporting vaccine series completion, while providing future directions for research and implementation to improve HPV vaccination.
Topics: Adolescent; Humans; United States; Child; Human Papillomavirus Viruses; Papillomavirus Infections; Diphtheria-Tetanus-acellular Pertussis Vaccines; Vaccines, Conjugate; Immunization Schedule; Papillomavirus Vaccines; Vaccination; Meningococcal Vaccines
PubMed: 37218520
DOI: 10.1080/21645515.2023.2213603 -
Pediatrics Jun 2024The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention,...
The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The Advisory Committee on Immunization Practices met February 28 to 29, 2024, to discuss coronavirus disease 2019 vaccines, chikungunya vaccines, diphtheria-tetanus vaccine, influenza vaccines, polio vaccines, respiratory syncytial virus vaccines, meningococcal vaccines, pneumococcal vaccines, and Vaxelis (Diphtheria, Tetanus, Pertussis, Inactivated Poliovirus, Haemophilus influenzae b Conjugate, and Hepatitis B Vaccine). This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information about changes on influenza vaccine composition, meningococcal vaccination considerations, updated guidance for children with a contraindication to pertussis-containing vaccines, and recommendations of the world's first chikungunya vaccine for certain populations.
Topics: Humans; Child; Advisory Committees; COVID-19 Vaccines; Meningococcal Vaccines; United States; Respiratory Syncytial Virus Vaccines; Centers for Disease Control and Prevention, U.S.; COVID-19
PubMed: 38548682
DOI: 10.1542/peds.2024-066653 -
The Lancet. Infectious Diseases Dec 2023Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Meningococcal serogroups A, B, C, W, and Y cause nearly all meningococcal disease, and comprehensive protection requires vaccination against all five serogroups. We aimed to assess the immunogenicity and safety of a pentavalent MenABCWY vaccine comprising two licensed vaccines-meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) and a quadrivalent meningococcal serogroup ACWY tetanus toxoid conjugate vaccine (MenACWY-TT)-compared with two doses of MenB-FHbp and a single dose of quadrivalent meningococcal serogroup ACWY CRM-conjugate vaccine (MenACWY-CRM) as the active control. We previously reported the primary safety and immunogenicity data relating to the two-dose MenB-FHbp schedule. Here we report secondary outcomes and ad-hoc analyses relating to MenABCWY immunogenicity and safety.
METHODS
We did an observer-blind, active-controlled trial at 68 sites in the USA, Czech Republic, Finland, and Poland. Healthy individuals (aged 10-25 years) who had or had not previously received a MenACWY vaccine were randomly assigned (1:2) using an interactive voice or web-based response system, stratified by previous receipt of a MenACWY vaccine, to receive 0·5 mL of MenABCWY (months 0 and 6) and placebo (month 0) or MenB-FHbp (months 0 and 6) and MenACWY-CRM (month 0) via intramuscular injection into the upper deltoid. All individuals were masked to group allocation, except staff involved in vaccine dispensation, preparation, and administration; and protocol adherence. Endpoints for serogroups A, C, W, and Y included the proportion of participants who achieved at least a four-fold increase in serum bactericidal antibody using human complement (hSBA) titres between baseline and 1 month after each vaccination. For serogroup B, secondary endpoints included the proportion of participants who achieved at least a four-fold increase in hSBA titres from baseline for each of four primary test strains and the proportion of participants who achieved titres of at least the lower limit of quantitation against all four test strains combined at 1 month after the second dose. Endpoints for serogroups A, C, W, and Y were assessed in the modified intent-to-treat (mITT) population, which included all randomly assigned participants who received at least one vaccine dose and had at least one valid and determinate MenB or serogroup A, C, W, or Y assay result before vaccination up to 1 month after the second dose, assessed in ACWY-experienced and ACWY-naive participants separately. Secondary endpoints for serogroup B were analysed in the evaluable immunogenicity population, which included all participants in the mITT population who were randomly assigned to the group of interest, received all investigational products as randomly assigned, had blood drawn for assay testing within the required time frames, had at least one valid and determinate MenB assay result after the second vaccination, and had no important protocol deviations; outcomes were assessed in both ACWY-experienced and ACWY-naive populations combined. Non-inferiority of MenABCWY to MenACWY-CRM and MenB-FHbp was determined using a -10% non-inferiority margin for these endpoints. Reactogenicity and adverse events were assessed among all participants who received at least one vaccine dose and who had available safety data. This trial is registered with Clinicaltrials.gov, NCT03135834, and is complete.
FINDINGS
Between April 24 and November 10, 2017, 1610 participants (809 MenACWY-naive; 801 MenACWY-experienced) were randomly assigned: 544 to receive MenABCWY and placebo (n=272 MenACWY-naive; n=272 MenACWY-experienced) and 1066 to receive MenB-FHbp and MenACWY-CRM (n=537 MenACWY-naive; n=529 MenACWY-experienced). Among MenACWY-naive or MenACWY-experienced MenABCWY recipients, 75·5% (95% CI 69·8-80·6; 194 of 257; serogroup C) to 96·9% (94·1-98·7; 254 of 262; serogroup A) and 93·0% (88·4-96·2; 174 of 187; serogroup Y) to 97·4% (94·4-99·0; 224 of 230; serogroup W) achieved at least four-fold increases in hSBA titres against serogroups ACWY after dose 1 or 2, respectively, in ad-hoc analyses. Additionally, 75·8% (71·5-79·8; 320 of 422) to 94·7% (92·1-96·7; 396 of 418) of MenABCWY and 67·4% (64·1-70·6; 563 of 835) to 95·0% (93·3-96·4; 782 of 823) of MenB-FHbp recipients achieved at least four-fold increases in hSBA titres against MenB strains after dose 2 in secondary analyses; 79·9% (334 of 418; 75·7-83·6) and 74·3% (71·2-77·3; 605 of 814), respectively, achieved composite responses. MenABCWY was non-inferior to MenACWY-CRM (single dose) and to MenB-FHbp in ad-hoc analyses based on the proportion of participants with at least a four-fold increase in hSBA titres from baseline and (for MenB-FHbp only) composite responses. Reactogenicity events after vaccination were similarly frequent across groups, were mostly mild or moderate, and were unaffected by MenACWY experience. No adverse events causing withdrawals were related to the investigational product. Serious adverse events were reported in four (1·5%; 0·4-3·7) MenACWY-naive individuals in the MenABCWY group versus six (2·2%; 0·8-4·8) among MenACWY-experienced individuals in the MenABCWY group and 14 (1·3%; 0·7-2·2) in the active control group (MenACWY-experienced and MenACWY-naive individuals combined); none of these were considered related to the investigational product.
INTERPRETATION
MenABCWY immune responses were robust and non-inferior to MenACWY-CRM and MenB-FHbp administered separately, and MenABCWY was well tolerated. The favourable benefit-risk profile supports further MenABCWY evaluation as a simplified schedule compared with current adolescent meningococcal vaccination programmes.
FUNDING
Pfizer.
Topics: Humans; Adolescent; Young Adult; Vaccines, Conjugate; Meningococcal Infections; Neisseria meningitidis; Vaccination; Neisseria meningitidis, Serogroup B; Meningococcal Vaccines; Vaccines, Combined; Antibodies, Bacterial; Immunogenicity, Vaccine
PubMed: 37579773
DOI: 10.1016/S1473-3099(23)00191-3 -
Human Vaccines & Immunotherapeutics Dec 2023Invasive meningococcal disease (IMD) is a life-threatening disease caused by and has high mortality rates. Survivors often exhibit long-term sequelae and reduced life...
Invasive meningococcal disease (IMD) is a life-threatening disease caused by and has high mortality rates. Survivors often exhibit long-term sequelae and reduced life expectancy. Disease incidence is highest in infants and toddlers, with a resurgence of cases in adolescents and older adults (>50 years of age). Substantial heterogeneity exists in the recommendations of meningococcal vaccines included in National Immunization Programs (NIPs) across countries. Recommendations are usually based on infant/toddler immunization, with some countries recommending immunization only for toddlers. While existing recommendations have led to a reduced incidence of IMD in children <5 years of age, there has been an increase in cases among adolescents and older adults. Currently, older adults are not included in the recommendations. The higher healthcare burden and the economic costs associated with IMD in these age groups suggest that it is time to consider including adolescents and older adults in NIPs to protect against IMD caused by the five most prevalent serogroups. Currently, the lack of equity of access to vaccines in the immunization programs is a glaring gap in the betterment of public health, and a broader meningococcal strategy is recommended to provide optimal protection for all age groups.
Topics: Infant; Adolescent; Humans; Aged; Meningococcal Infections; Neisseria meningitidis; Vaccination; Meningococcal Vaccines; Incidence; Immunization Programs
PubMed: 37017273
DOI: 10.1080/21645515.2023.2186111 -
Human Vaccines & Immunotherapeutics Dec 2023This review reports on the recent epidemiology of invasive meningococcal disease (IMD) within the Gulf Cooperation Council (GCC) Countries (focusing from 2012 onwards),... (Review)
Review
This review reports on the recent epidemiology of invasive meningococcal disease (IMD) within the Gulf Cooperation Council (GCC) Countries (focusing from 2012 onwards), the existing immunization strategies and the potential for IMD resurgence. MenACWY vaccination is now established in infant or adolescent immunization programs in Saudi Arabia, Bahrain, Kuwait, and the United Arab Emirates. At present, GCC Countries do not include MenB immunization. National health surveillance reports indicate a total of 156 IMD cases reported across the GCC Countries between 2012 and 2021; between 30% and 80% of cases were reported in individuals aged ≥15 years. Lack of serogroup data hinders the assessment of vaccine impact and decision-making on additional vaccine introductions (e.g. MenB immunization). Hajj/Umrah pilgrimage and the increasing number of large-scale commercial and social events held in the GCC Countries pose a potential risk for future IMD outbreaks. Immunization policies for such events could be strengthened.
Topics: Infant; Adolescent; Humans; Meningococcal Infections; Saudi Arabia; Disease Outbreaks; United Arab Emirates; Vaccination; Meningococcal Vaccines
PubMed: 37051899
DOI: 10.1080/21645515.2023.2193120 -
The Journal of Infection Dec 2023Few data outside of individual case reports are available on non-meningococcal, non-gonococcal species of Neisseria as causative agents of invasive disease. This review... (Review)
Review
OBJECTIVE
Few data outside of individual case reports are available on non-meningococcal, non-gonococcal species of Neisseria as causative agents of invasive disease. This review collates disease, organism and patient information from case reports on the topic.
METHODS
A literature search was performed examining articles describing diseases caused by non-meningococcal and non-gonococcal Neisseria.
FINDINGS
Neisseria present as opportunistic pathogens causing a wide variety of diseases including serious presentations, endocarditis being the most common condition described and N. mucosa the most commonly presenting pathogen overall. Disease may occur in otherwise healthy patients, although risk factors for infection include recent surgery, an immunocompromised state, poor oral health, and intravenous drug use.
CONCLUSIONS
Commensal Neisseria infections are rare but can present serious invasive diseases. Further research is required to determine why some species cause disease more than others or why some are inclined towards particular manifestations.
Topics: Humans; Neisseria; Endocarditis; Symbiosis; Immunocompromised Host; Neisseria meningitidis
PubMed: 37797844
DOI: 10.1016/j.jinf.2023.09.007