Impact of Pneumococcal Conjugate Vaccines on Pneumonia Hospitalizations in High- and Low-Income Subpopulations in Brazil.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations

Control of telomere length by a trimming mechanism that involves generation of t-circles

Telomere lengths are maintained in many cancer cells by the ribonucleoprotein enzyme telomerase but can be further elongated by increasing telomerase activity through the overexpression of telomerase components. We report here that increased telomerase activity results in increased telomere length that eventually reaches a plateau, accompanied by the generation of telomere length heterogeneity and the accumulation of extrachromosomal telomeric repeat DNA, principally in the form of telomeric circles (t-circles). Telomeric DNA was observed in promyelocytic leukemia bodies, but no intertelomeric copying or telomere exchange events were identified, and there was no increase in telomere dysfunction-induced foci. These data indicate that human cells possess a mechanism to negatively regulate telomere length by trimming telomeric DNA from the chromosome ends, most likely by t-loop resolution to form t-circles. Additionally, these results indicate that some phenotypic characteristics attributed to alternative lengthening of telomeres (ALT) result from increased mean telomere length, rather than from the ALT mechanism itself

Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Specialist laboratory networks as preparedness and response tool - The emerging viral diseases-expert laboratory network and the chikungunya outbreak, Thailand, 2019

We illustrate the potential for specialist laboratory networks to be used as preparedness and response tool through rapid collection and sharing of data. Here, the Emerging Viral Diseases-Expert Laboratory Network (EVD-LabNet) and a laboratory assessment of chikungunya virus (CHIKV) in returning European travellers related to an ongoing outbreak in Thailand was used for this purpose. EVD-LabNet rapidly collected data on laboratory requests, diagnosed CHIKV imported cases and sequences generated, and shared among its members and with the European Centre for Disease Prevention and Control. Data across the network showed an increase in CHIKV imported cases during 1 October 2018-30 April 2019 vs the same period in 2018 (172 vs 50), particularly an increase in cases known to be related to travel to Thailand (72 vs 1). Moreover, EVD-LabNet showed that strains were imported from Thailand that cluster with strains of the ECSA-IOL E1 A226 variant emerging in Pakistan in 2016 and involved in the 2017 outbreaks in Italy. CHIKV diagnostic requests increased by 23.6% between the two periods. The impact of using EVD-LabNet or similar networks as preparedness and response tool could be improved by standardisation of the collection, quality and mining of data in routine laboratory management systems

Model estimates of the burden of outpatient visits attributable to influenza in the United States

Abstract Background Although many studies have modelled the national burdens of hospitalizations and deaths due to influenza, few studies have considered the outpatient burden. To fill this gap for the United States (US), we applied traditional statistical modelling approaches to time series derived from large medical claims databases held in the private sector. Methods We accessed ICD-9-coded office visit data extracted from Truven Health Analytics’ MarketScan Commercial database covering about one third of the US population <65 years during 2001–2009, and Medicare Supplemental data covering about one fifth of US seniors 65+ during 2006–2009. We extracted weekly time series of visits due to respiratory diagnoses, otitis media (OM), and urinary tract infections (UTI), a “negative control”. We used multiple linear regression modelling to estimate age-specific influenza-related excess in office visits. Results In the <65 year age group, in the 8 pre-pandemic seasons studied and for the broadest defined respiratory outcome, the model attributed an average of ~14.5 M (Standard deviation [SD] across seasons 3.9 million) office visits to influenza (rate of 5,581/100,000 population). Of these, ~80 % of visits occurred in the 5–17 and 18–49 age group. In school children aged 5–17 year olds and adult 18–64 year age groups the majority of visits were due to influenza B, while A/H3N2 explained most visits in children <5 year olds. The model further attributed ~2.2 M OM visits (SD across seasons 790,000) annually to influenza, of which 86 % of these occurred in children <18 years; this indicates that 6.4 % of all infants <2 years and 4.9 % of all toddlers aged 2–4 years in the US have an influenza-attributable outpatient visit with an OM diagnosis. In seniors 65 years and older, our model attributed ~0.7 M (SD across seasons 351,000) respiratory visits to influenza (rate of 1,887/100,000 population). The model identified no significant excess UTI (negative control) visits in most seasons. Conclusions This is to our knowledge a first study of the outpatient burden of influenza in the US in a large database. The model estimated that 10 % of all children <18 years and 4 % of the entire population <65 years seek outpatient care for respiratory illness attributable to influenza annually. Trial registration ClinicalTrial.gov, NCT02019732