Making the digital markets act more resilient and effective

Aiming to improve the European Commission’s Digital Markets Act proposal as it continues to be scrutinised and refined, CERRE has prepared four issue papers and a subsequent set of recommendations for the Digital Markets Act

Enduring pathogenicity of African strains of Salmonella on plastics and glass in simulated peri-urban environmental waste piles

In low- and middle-income countries, plastic has become a major constituent of landfills and urban dump sites. Environmental plastic pollution can also provide a novel surface for the formation of microbial biofilm, which often includes pathogenic bacteria and viruses. Here, under conditions simulating a peri-urban waste pile typical of an African informal settlement, we aimed to determine if pathogenic Salmonella spp. can retain their virulence following a prolonged period of desiccation on the surfaces of environmental plastic and glass. We show that clinically (and environmentally) relevant strains of Salmonella including S. Enteritidis, S. Typhimurium and S. Typhi can persist on plastic and glass for at least 28-days and that temperature (which increases with the depth of an urban waste pile) is a key determinant of this survival. All three strains of Salmonella retained their pathogenicity (determined by using a Galleria mellonella model of infection) following their recovery from the plastisphere indicating that plastics in the environment can act as reservoirs for human pathogens and could facilitate their persistence for extended periods of time. Pathogens colonising environmental plastic waste therefore pose a heightened public health risk, particularly in areas where people are frequently exposed to plastic pollution

Open defecation by proxy : tackling the increase of disposable diapers in waste piles in informal settlements

Disposable diapers are becoming increasingly popular and present an emerging challenge for global waste management, particularly within LMICs. They offer a cheap and convenient way for caregivers to manage child excreta; however, insufficient understanding of safe disposal methods, combined with limited access to waste management services results in hazardous disposal. Used diapers are being increasingly found dumped in the open environment, including in water bodies and in open fields, leading to faecal contamination of the environment and an enhanced risk of transmission of faecal-oral diseases such as cholera and typhoid. United Nations SDG 6 aims to end open defaecation globally by 2030; however, improper disposal of used diapers will hamper progress towards reaching this goal. In this review, we identify current trends in use and subsequent disposal of single use disposable diapers in LMICs, and critically discuss the environmental and public health impacts of current practices, and potential solutions to address these challenges. Contemporary methods for managing the disposal of single use diapers for communities in LMICs tend to be cost prohibitive with few alternative options other than dumping in the environment. Modern cloth diapers offer a low waste alternative to disposable diapers but often carry an unaffordable high upfront cost. Here, in addition to advocating improved efforts by governments to upgrade access and quality of waste management services, we recommend the design and implementation of intervention schemes aimed to increase awareness of safe and hygienic disposal practices for disposable diapers

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A

Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.

BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid

An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid.

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations