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\"\"Believing that she is a carrier of the deadly disease they are calling the \"Aberdeen flu,\" Shay has surrendered herself to the authorities and along with other survivors becomes an unwilling test subject in the effort to find a cure; but when the lab is attacked she and a few of the others with the strongest supernatural abilities escape, and her boyfriend Kai is determined to find her, while ghostly Callie, the true carrier, will atone for her deception\"--Provided by publisher.

Pneumococcal conjugate vaccines are an important but costly part of childhood vaccination. This trial assessed immunogenicity of fractional-dose regimens — a key consideration as countries transition out of Gavi support.

Background. The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed to replace the 7-valent pneumococcal conjugate vaccine (PCV7) based on serological noninferiority criteria. To date no randomized PCV13 pediatric trial has included clinical endpoints. Methods. This randomized double-blind trial compared the impact of PCV13 versus PCV7 on nasopharyngeal (NP) colonization and immunogenicity. Healthy infants were randomized (1:1) to receive PCV7 or PCV13 at ages 2, 4, 6, and 12 months; NP swabs were collected at 2, 4, 6, 7, 12, 13, 18, and 24 months, and blood was drawn at 7 and 13 months. Rates of NP acquisition and prevalence, and serotype-specific immunoglobulin G (IgG) concentrations were assessed. Results. The per protocol analysis population included 881 PCV13 and 873 PCV7 recipients. PCV13 significantly reduced NP acquisition of the additional PCV13 serotypes 1, 6A, 7F, and 19A; the cross-reacting serotype 6C; and the common PCV7 serotype 19F. For serotype 3, and the other PCV7 serotypes, there were no significant differences between the vaccine groups. There were too few serotype 5 events to draw inference. The impact on prevalence at predefined time points was similar to that observed with NP acquisition. PCV13 elicited significantly higher IgG responses for PCV13 additional serotypes and serotype 19F, and similar or lower responses for 6/7 PCV7 serotypes. Conclusions. PCV13 resulted in lower acquisition and prevalence of NP colonization than PCV7 did for 4 additional PCV13 serotypes, and serotypes 6C and 19F. It was comparable with PCV7 for all other common serotypes. These findings predict vaccine effectiveness through both direct and indirect protection. Clinical Trials Registration. NCT00508742.

Recently, a meningococcal vaccine for group B was approved and deployed into clinical practice. In this trial, the effect of widespread use of this vaccine on the nasopharyngeal carriage of meningococcus group B was assessed in more than 24,000 adolescents in Australia.

In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1–9 years in Niger. In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than –7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484). Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of –16·2% (95% CI –28·6 to –3·0) between the full-dose group and control group (p=0·002 for superiority), and –3·8% (–6·1 to –1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination. Multi-age cohort campaigns had a marked effect on vaccine-type carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection. EDCTP2 programme supported by the EU. For the French translation of the abstract see Supplementary Materials section.

We analyze data from the fall 2020 pandemic response efforts at the University of Colorado Boulder, where more than 72,500 saliva samples were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using qRT-PCR. All samples were collected from individuals who reported no symptoms associated with COVID-19 on the day of collection. From these, 1,405 positive cases were identified. The distribution of viral loads within these asymptomatic individuals was indistinguishable from what has been previously observed in symptomatic individuals. Regardless of symptomatic status, ∼50% of individuals who test positive for SARS-CoV-2 seem to be in noninfectious phases of the disease, based on having low viral loads in a range from which live virus has rarely been isolated. We find that, at any given time, just 2% of individuals carry 90% of the virions circulating within communities, serving as viral “supercarriers” and possibly also superspreaders.

Mass drug administration (MDA) programmes with the macrolide antibiotic azithromycin to reduce childhood mortality are expanding in Africa; however, concerns remain about the long-term effects of these programmes on antimicrobial resistance (AMR). We aimed to evaluate the persistence and spread of Streptococcus pneumoniae AMR following a community-randomised MDA trial. This population-based, cross-sectional, pneumococcal carriage survey was conducted in Mangochi, Malawi, 3·5 years after the MORDOR trial, in which communities received twice-yearly azithromycin or placebo for 2 years. Eligible participants in this carriage survey were children aged 4–9 years who lived in an azithromycin-treated or placebo-treated cluster during the MORDOR trial, and children aged 1–3 years who were resident in a cluster but born after the MORDOR trial ended. Nasopharyngeal swabs were collected from participants and analysed by whole genome sequencing; pneumococcal genomes obtained from a distant site in Malawi, in which MDA had not been conducted, were used as reference genomes. The primary outcome was the prevalence of S pneumoniae macrolide resistance, comparing placebo-treated and azithromycin-treated clusters at baseline, 6 months post-MDA, and 3·5 years post-MDA. Between April 8 and May 14, 2021, 924 children aged 1–9 years were screened, of whom 19 were excluded and 905 were recruited to the follow-up carriage survey: 452 from azithromycin-treated clusters and 453 from placebo-treated clusters of the MORDOR trial. We assessed 426 isolates from these participants (190 from azithromycin-treated clusters and 236 from placebo-treated clusters), as well as samples from the baseline of the MORDOR trial (164 isolates; 83 from azithromycin-treated clusters and 81 from placebo-treated clusters) and from 6 months post-MDA (223 isolates; 119 from azithromycin-treated clusters and 104 from placebo-treated clusters). In azithromycin-treated clusters, macrolide resistance increased from 21·7% (95% CI 14·2–31·7; 18 of 83 isolates) at baseline to 31·9% (24·2–40·8; 38 of 119 isolates) 6 months post-MDA and to 32·1% (25·9–39·0; 61 of 190 isolates) 3·5 years post-MDA. In placebo-treated clusters, resistance increased from 21·0% (13·5–31·1; 17 of 81 isolates) at baseline to 25·0% (17·7–34·1; 26 of 104 isolates) 6 months post-MDA and to 30·9% (25·4–37·1; 73 of 236 isolates) 3·5 years post-MDA. No significant differences were observed in odds ratios between treatment groups across the survey timepoints: 0·97 (95% CI 0·36–2·55) at baseline, 1·46 (0·67–3·17) at 6 months post-MDA, and 1·12 (0·66–1·91) at 3·5 years post-MDA. Macrolide resistance in the non-MDA site remained stable: 16·9% (95% CI 12·8–21·8; 45 of 267 isolates) at baseline, 16·5% (13·3–20·3; 70 of 424 isolates) at 6 months, and 16·5% (12·5–21·4; 44 of 267 isolates) at 2·5 years. Among children born into azithromycin-treated clusters after MDA, macrolide resistance was 36·0% (27·7–45·1; 41 of 114 children). Multidrug resistance to at least three antibiotic classes was significantly higher in azithromycin-treated (p=0·0015) and placebo-treated (p<0·0001) clusters than in the comparator population at 3·5 years post-MDA and was associated with integrative conjugative elements. Azithromycin MDA is associated with macrolide resistance that persists and potentially spreads to untreated populations. The co-existence of multidrug resistance and transmissible resistance on integrative conjugative elements in these populations is a public health concern. Careful monitoring of AMR is essential in areas where MDA is implemented. The Gates Foundation, the National Institute for Health and Care Research, and the Wellcome Trust.

After pneumococcal disease and colonization have been controlled through vaccination campaigns, a reduced pneumococcal conjugate vaccine (PCV) schedule may be sufficient to sustain that control at reduced costs. We investigated whether a single primary dose and booster dose (1p+1) of the 10-valent PCV (PCV10) would be noninferior to alternative dose schedules in sustaining control of carriage of pneumococcal serotypes included in the vaccine. In Nha Trang, Vietnam, an area in which PCV had not been used previously, a PCV10 catch-up campaign was conducted in which the vaccine was offered to children younger than 3 years of age, after which a cluster-randomized trial was conducted in which children received PCV10 at 2, 3, and 4 months of age (3p+0 group); at 2, 4, and 12 months of age (2p+1 group); at 2 and 12 months of age (1p+1 group); or at 12 months of age (0p+1 group). Annual carriage surveys in infants (4 to 11 months of age) and toddlers (14 to 24 months of age) were conducted from 2016 through 2020. The primary end point was protection against carriage of vaccine serotypes, evaluated in a noninferiority analysis in the 1p+1 group as compared with the 2p+1 and 3p+0 groups, 3.5 years after vaccine introduction (noninferiority margin, 5 percentage points). Noninferiority of the 0p+1 schedule was also evaluated. In 2016, before the introduction of PCV10, vaccine-serotype carriage was found in 160 of 1363 infants (11.7%); in 2020, vaccine-serotype carriage was found in 6 of 333 (1.8%), 5 of 340 (1.5%), and 4 of 313 (1.3%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively, indicating noninferiority of 1p+1 to 2p+1 (difference, 0.3 percentage points; 95% confidence interval [CI], -1.6 to 2.2) and to 3p+0 (difference, 0.5 percentage points; 95% CI, -1.4 to 2.4). Similarly, 1p+1 was noninferior to 2p+1 and 3p+0 for protection against vaccine-serotype carriage among toddlers. In 2016, carriage of serotype 6A was found in 99 of 1363 infants (7.3%); in 2020, it was found in 12 of 333 (3.6%), 10 of 340 (2.9%), and 3 of 313 (1.0%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively. The 0p+1 schedule was also noninferior to the other three dose schedules among infants and toddlers, although cross-protection against serotype 6A was less common than with the other vaccination schedules. No PCV10-associated severe adverse effects were observed. A reduced vaccination schedule involving a single primary dose and booster dose of PCV10 was noninferior to alternative schedules in protecting against vaccine-serotype carriage in infants and toddlers. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02961231.).

As countries in Europe gradually relaxed lockdown restrictions after the first wave, test–trace–isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels 1 , 2 . Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological 3 and participatory syndromic 4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations 2 . Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO) 5 . The median detection rate increased from 7% (95% confidence interval, 6–8%) to 38% (35–44%) over time, with large regional variations, owing to a strengthening of the system as well as a decrease in epidemic activity. According to participatory surveillance data, only 31% of individuals with COVID-19-like symptoms consulted a doctor in the study period. This suggests that large numbers of symptomatic cases of COVID-19 did not seek medical advice despite recommendations, as confirmed by serological studies 6 , 7 . Encouraging awareness and same-day healthcare-seeking behaviour of suspected cases of COVID-19 is critical to improve detection. However, the capacity of the system remained insufficient even at the low epidemic activity achieved after lockdown, and was predicted to deteriorate rapidly with increasing incidence of COVID-19 cases. Substantially more aggressive, targeted and efficient testing with easier access is required to act as a tool to control the COVID-19 pandemic. The testing strategy will be critical to enable partial lifting of the current restrictive measures in Europe and to avoid a third wave. Analyses of virological and surveillance data in France show that a substantial proportion of symptomatic cases of COVID-19 have remained undetected and that easily accessible and efficient testing is required to control the pandemic.

Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units. The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered with ClinicalTrials.gov, number NCT02063867. There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures (figure 2), the HR for the intervention period versus the baseline period was 0·79 (0·73–0·87) in the decolonisation group versus 0·87 (95% CI 0·79–0·95) in the routine care group. No difference was seen in the relative HRs (p=0·17). There were 25 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin. Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients. National Institutes of Health.