Many national guidelines recommend annual influenza vaccination of immunocompromised patients, although the decision to vaccinate is usually at clinical discretion. We conducted a systematic review and meta-analyses to assess the evidence for influenza vaccination in this group, and we report our results by etiology. Meta-analyses showed significantly lower odds of influenza-like illness after vaccination in patients with human immunodeficiency virus (HIV) infection, patients with cancer, and transplant recipients and of laboratory-confirmed influenza in HIV-positive patients, compared with patients receiving placebo or no vaccination. Pooled odds of seroconversion and seroprotection were typically lower in HIV-positive patients, patients with cancer, and transplant recipients, compared with immunocompetent controls. Vaccination was generally well tolerated, with variation in mild adverse events between etiological groups. Limited evidence of a transient increase in viremia and a decrease in the percentage of CD4⁺ cells in HIV-positive patients was found although not accompanied by worsening of clinical symptoms. Clinical judgment remains important when discussing the benefits and safety profile with immunocompromised patients.

Vibrio cholerae transitions between aquatic environmental reservoirs and infection in the gastrointestinal tracts of human hosts. The second-messenger molecule cyclic di-GMP (c-di-GMP) and quorum sensing (QS) are important signaling systems that enable V. cholerae to alternate between these distinct environments by controlling biofilm formation and virulence factor expression. Here we identify a conserved regulatory mechanism in V. cholerae that integrates c-di-GMP and QS to control the expression of two transcriptional regulators: aphA , an activator of virulence gene expression and an important regulator of the quorum-sensing pathway, and vpsT , a transcriptional activator that induces biofilm formation. Surprisingly, aphA expression was induced by c-di-GMP. Activation of both aphA and vpsT by c-di-GMP requires the transcriptional activator VpsR, which binds to c-di-GMP. The VpsR binding site at each of these promoters overlaps with the binding site of HapR, the master QS regulator at high cell densities. Our results suggest that V. cholerae combines information conveyed by QS and c-di-GMP to appropriately respond and adapt to divergent environments by modulating the expression of key transcriptional regulators.

Mathematical models are useful for assessing the potential epidemiological impact of future tuberculosis (TB) vaccines. We conducted a systematic review of mathematical models estimating the epidemiological impact of future human TB vaccines. PubMed, Embase and WHO Global Health Library were searched, 3-stage manual sifted, and citation- and reference-tracked, identifying 23 papers. An adapted quality assessment tool was developed, with a resulting median study quality score of 20/28. The literature remains divided as to whether vaccines effective pre- or post-infection would provide greatest epidemiological impact. However, all-age or adolescent/adult targeted prevention of disease vaccines achieve greater and more rapid impact than neonatal vaccines. Mass campaigns alongside routine neonatal vaccination can have profound additional impact. Economic evaluations found TB vaccines overwhelmingly cost-effective, particularly when targeted to adolescents/adults. The variability of impact by setting, age group and vaccine characteristics must be accounted for in the development and delivery of future TB vaccines.

Tuberculosis is the leading single-pathogen cause of death worldwide, and China has the third largest number of cases worldwide. New tools, such as new vaccines, are needed to meet WHO tuberculosis goals. Tuberculosis vaccine development strategies mostly target infants or adolescents, but given China's ageing epidemic, vaccinating older people might be important. We modelled the potential impact of new tuberculosis vaccines in China targeting adolescents (15-19 years) or older adults (60-64 years) with varying vaccine characteristics to inform strategic vaccine development. A Mycobacterium tuberculosis transmission model was calibrated to age-stratified demographic and epidemiological data from China. Varying scenarios of vaccine implementation (age targeting [adolescents or older adults] and coverage [30% or 70%]) and characteristics (efficacy [40%, 60%, or 80%], duration of protection [10 years or 20 years], and host infection status required for efficacy [pre-infection, post-infection in latency, post-infection in latency or recovered, or pre-infection and post-infection]) were assessed. Primary outcomes were tuberculosis incidence and mortality rate reduction in 2050 in each vaccine scenario compared with the baseline (no new vaccine) scenario and cumulative number needed to vaccinate (NNV) per case or death averted, 2025-50. By 2050, results suggest that 74·5% (uncertainty interval [UI] 70·2-78·6) of incident tuberculosis cases in China would occur in people aged 65 years or older, and 75·1% (66·8-80·7) of all cases would be due to reactivation, rather than new infection. All vaccine profiles delivered to older adults had higher population-level impact (reduction of incidence and mortality rates) and lower NNV per case and per death averted than if delivered to adolescents. For an intermediate vaccine scenario of 60% efficacy, 10-year protection, and 70% coverage, the reduction of tuberculosis incidence rates with older adult vaccination was 1·9 times (UI 1·5-2·6) to 157·5 times (119·3-225·6) greater than with adolescent vaccination, and the NNV was 0·011 times (0·008-0·014) to 0·796 times (0·632-0·970) lower. Furthermore, with older adult vaccination, post-infection vaccines provided substantially greater mortality and incidence rate reductions than pre-infection vaccines. Adolescent-targeted tuberculosis vaccines, the focus of many development plans, would have only a small impact in ageing, reactivation-driven epidemics such as those in China. Instead, an efficacious post-infection vaccine delivered to older adults will be crucial to maximise population-level impact in this setting and would provide an important contribution towards achieving WHO goals. Older adults should be included in tuberculosis vaccine clinical development and implementation planning. Aeras and UK MRC.

Tuberculosis vaccines should aim to protect infected populations against disease, but other vaccine types may be of use in high-transmission settings.

Data on COVID-19-induced disruption to routine vaccinations in the South-East Asia and Western Pacific regions (SEAR/WPR) have been sparse. This study aimed to quantify the impact of COVID-19 on routine vaccinations by country, antigen, and sector (public or private), up to 1 June 2020, and to identify the reasons for disruption and possible solutions. Sanofi Pasteur teams from 19 countries in SEAR/WPR completed a structured questionnaire reporting on COVID-19 disruptions for 13–19 routinely delivered antigens per country, based on sales data, government reports, and regular physician interactions. Data were analysed descriptively, disruption causes ranked, and solutions evaluated using a modified public health best practices framework. 95% (18/19) of countries reported vaccination disruption. When stratified by country, a median of 91% (interquartile range 77–94) of antigens were impacted. Infancy and school-entry age vaccinations were most impacted. Both public and private sector healthcare providers experienced disruptions. Vaccination rates had not recovered for 39% of impacted antigens by 1 June 2020. Fear of infection, movement/travel restrictions, and limited healthcare access were the highest-ranked reasons for disruption. Highest-scoring solutions were separating vaccination groups from unwell patients, non-traditional vaccination venues, virtual engagement, and social media campaigns. Many of these solutions were under-utilised. COVID-19-induced disruption of routine vaccination was more widespread than previously reported. Adaptable solutions were identified which could be implemented in SEAR/WPR and elsewhere. Governments and private providers need to act urgently to improve coverage rates and plan for future waves of the pandemic, to avoid a resurgence of vaccine-preventable diseases. Sanofi Pasteur.