The African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents.

BACKGROUND: In sub-Saharan Africa, acute respiratory infections (ARI), acute gastrointestinal infections (GI) and acute febrile disease of unknown cause (AFDUC) have a large disease burden, especially among children, while respective aetiologies often remain unresolved. The need for robust infectious disease surveillance to detect emerging pathogens along with common human pathogens has been highlighted by the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA) is a sentinel surveillance study on the aetiology and clinical characteristics of ARI, GI and AFDUC in sub-Saharan Africa. METHODS: ANDEMIA includes 12 urban and rural health care facilities in four African countries (Côte d'Ivoire, Burkina Faso, Democratic Republic of the Congo and Republic of South Africa). It was piloted in 2018 in Côte d'Ivoire and the initial phase will run from 2019 to 2021. Case definitions for ARI, GI and AFDUC were established, as well as syndrome-specific sampling algorithms including the collection of blood, naso- and oropharyngeal swabs and stool. Samples are tested using comprehensive diagnostic protocols, ranging from classic bacteriology and antimicrobial resistance screening to multiplex real-time polymerase chain reaction (PCR) systems and High Throughput Sequencing. In March 2020, PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and analysis of full genomic information was included in the study. Standardised questionnaires collect relevant clinical, demographic, socio-economic and behavioural data for epidemiologic analyses. Controls are enrolled over a 12-month period for a nested case-control study. Data will be assessed descriptively and aetiologies will be evaluated using a latent class analysis among cases. Among cases and controls, an integrated analytic approach using logistic regression and Bayesian estimation will be employed to improve the assessment of aetiology and associated risk factors. DISCUSSION: ANDEMIA aims to expand our understanding of ARI, GI and AFDUC aetiologies in sub-Saharan Africa using a comprehensive laboratory diagnostics strategy. It will foster early detection of emerging threats and continued monitoring of important common pathogens. The network collaboration will be strengthened and site diagnostic capacities will be reinforced to improve quality management and patient care.

A Klebsiella pneumoniae ST307 outbreak clone from Germany demonstrates features of extensive drug resistance, hypermucoviscosity, and enhanced iron acquisition.

BACKGROUND: Antibiotic-resistant Klebsiella pneumoniae are a major cause of hospital- and community-acquired infections, including sepsis, liver abscess, and pneumonia, driven mainly by the emergence of successful high-risk clonal lineages. The K. pneumoniae sequence type (ST) 307 lineage has appeared in several different parts of the world after first being described in Europe in 2008. From June to October 2019, we recorded an outbreak of an extensively drug-resistant ST307 lineage in four medical facilities in north-eastern Germany. METHODS: Here, we investigated these isolates and those from subsequent cases in the same facilities. We performed whole-genome sequencing to study phylogenetics, microevolution, and plasmid transmission, as well as phenotypic experiments including growth curves, hypermucoviscosity, siderophore secretion, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance for an in-depth characterization of this outbreak clone. RESULTS: Phylogenetics suggest a homogenous phylogram with several sub-clades containing either isolates from only one patient or isolates originating from different patients, suggesting inter-patient transmission. We identified three large resistance plasmids, carrying either NDM-1, CTX-M-15, or OXA-48, which K. pneumoniae ST307 likely donated to other K. pneumoniae isolates of different STs and even other bacterial species (e.g., Enterobacter cloacae) within the clinical settings. Several chromosomally and plasmid-encoded, hypervirulence-associated virulence factors (e.g., yersiniabactin, metabolite transporter, aerobactin, and heavy metal resistance genes) were identified in addition. While growth, biofilm formation, desiccation resilience, serum survival, and heavy metal resistance were comparable to several control strains, results from siderophore secretion and hypermucoviscosity experiments revealed superiority of the ST307 clone, similar to an archetypical, hypervirulent K. pneumoniae strain (hvKP1). CONCLUSIONS: The combination of extensive drug resistance and virulence, partly conferred through a "mosaic" plasmid carrying both antibiotic resistance and hypervirulence-associated features, demonstrates serious public health implications.

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study.

BACKGROUND: Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. METHODS: We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. FINDINGS: Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. INTERPRETATION: HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. FUNDING: Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

Molecular phylogeny of a novel human adenovirus type 8 strain causing a prolonged, multi-state keratoconjunctivitis epidemic in Germany.

The German infectious disease surveillance system revealed an increase of epidemic keratoconjunctivitis (EKC) from an average of 320 cases/year (2001 to 2010) up to 2146 and 1986 cases in 2012 and 2013, respectively. From November 2011 until December 2013 (epidemic period) 85% of typed isolates were human adenovirus type 8 (HAdV-D8), whereas only low level circulation (19%) of HAdV-D8 was observed outside the epidemic period. In order to investigate whether a novel monophyletic HAdV-D8 strain prevailed during the epidemic period, complete genomic sequences of 23 HAdV-D8 isolates were generated by deep sequencing and analyzed phylogenetically. For comparison, eight HAdV-D8 isolates from outside the epidemic period were sequenced. HAdV-D8 isolates of the epidemic period had a very high sequence identity of at least 99.9% and formed a monophyletic cluster with two subclusters. A single outlier was closely related to HAdV-D8 strains isolated prior to the epidemic period. Circulation of the epidemic strain was detected as early as 2010 but not after the epidemic period in 2014. In conclusion, molecular phylogeny of complete genomic sequences proved a monophyletic HAdV-D8 epidemic. However, co-circulation of other HAdV types as well as better reporting may have contributed to the huge increase of reported cases.

Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016.

Invasive infections with Mycobacterium chimaera were reported in patients with previous open chest surgery and exposure to contaminated heater-cooler units (HCUs). We present results of the surveillance of clinical cases and of contaminated HCUs as well as environmental investigations in Germany up until February 2016. Clinical infections occurred in five male German cases over 50 years of age (range 53-80). Cases had been exposed to HCUs from one single manufacturer during open chest surgery up to five years prior to onset of symptoms. During environmental investigations, M. chimaera was detected in samples from used HCUs from three different countries and samples from new HCUs as well as in the environment at the manufacturing site of one manufacturer in Germany. Our investigation suggests that at least some of the M. chimaera infections may have been caused by contamination of HCUs at manufacturing site. We recommend that until sustainable measures for safe use of HCUs in operation theatres are implemented, users continue to adhere to instructions for use of HCUs and Field Safety Notices issued by the manufacturer, implement local monitoring for bacterial contamination and continuously check the websites of national and European authorities for current recommendations for the safe operation of HCUs.

A survey of outpatient antibiotic prescribing for cystitis.

BACKGROUND: In view of the currently increasing rates of antibiotic resistance, we studied the factors that affect the prescribing of specific antibiotics for uncomplicated cystitis in outpatient care. METHODS: A nationwide cross-sectional survey of physicians in private practice in various specialties (internal medicine, general medicine, surgery, obstetrics/gynecology, child and adolescent medicine, otorhinolaryngology, dermatology, urology) was carried out in 2008. The sample was derived from the German state directories of medical specialists. RESULTS: 1810 (60%) of the physicians surveyed reported that they made decisions about antibiotic treatment every day, with uncomplicated urinary tract infection as the most common diagnosis (715 physicians). The antibiotics that they prescribed most commonly for it were cotrimoxazole (61%) and fluoroquinolones (21%). The following factors were significantly associated with a preference for fluoroquinolones: being a gynecologist (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.27-0.80), location of practice in the former East Germany (OR 2.01, CI 1.16-3.46), a treatment strategy incorporating a switch from empirical to targeted treatment (OR 1.72, CI 1.02-2.90), and the stated intention of avoiding inconvenience to the patient (OR 2.14, CI 1.25-3.68). DISCUSSION: Fluoroquinolones are no longer recommended as the drug of first choice for uncomplicated urinary tract infections because of the development of resistance, but are still commonly prescribed for it. ARS (Antibiotic Resistance Surveillance in Germany) publishes current regional and patient-group-specific resistance rates to promote good clinical practice and improve prescribing behavior.

Under-reporting of measles: an evaluation based on data from north rhine-westphalia.

BACKGROUND: Eliminating measles in Europe by 2015 is a WHO health goal. In Germany, physicians are legally required to report measles cases, yet it seems likely that reporting is less than universal. The goal of this study is to compare the number of measles cases that are reflected by data from the statutory health insurance (SHI) carriers with the number of physician-reported cases during and after a recent outbreak in the German state of North Rhine-Westphalia (NRW). METHODS: We analyzed the billing data of SHI carriers relating to measles in 2006 and 2007, as well as the measles cases that were reported in NRW over this period as required by law. We calculated the incidence of measles as the number of measles cases per 100 000 insurees (SHI carrier data) or per 100 000 persons in the overall population (reporting data). RESULTS: The measles outbreak in the first half of 2006 comprised 1713 measles cases according to the SHI data and 1665 cases that were reported as required by law (ratio, 1.02:1). From mid-2006 to the end of 2007, the SHI data reflected 821 cases, but only 349 cases were reported (ratio, 2.35:1). Younger patients were more commonly found among the cases reflected in the SHI data than among the reported cases. CONCLUSION: Our study confirms that the system of legally mandated reporting underestimates the true number of measles cases, particularly in times when most cases are sporadic, and particularly in children who are less than 5 years old.

The influence of high-efficiency particulate air filtration on mortality and fungal infection among highly immunosuppressed patients: a systematic review.

BACKGROUND: Patients with hematological malignancies who are treated with intensive chemotherapy or who receive bone marrow transplants are exposed to an increased risk of developing nosocomial fungal infections. The aim of this systematic review was to compare the effectiveness of high-efficiency particulate air (HEPA) filtration with that of non-HEPA filtration in decreasing the rates of mortality and fungal infection among patients with diagnosed hematological malignancies and neutropenia or among patients with bone marrow transplants. METHODS: Articles identified in a Medline search, guidelines, and books, as well as the bibliographies of review articles, monographs, and the articles identified by Medline, were researched. Randomized trials and observational studies comparing HEPA filtration with conventional room ventilation were selected for inclusion in the present review. RESULTS: Sixteen trials (9 with death as an outcome and 10 with fungal infection as an outcome) that compared HEPA filtration with non-HEPA filtration were selected for meta-analyses. We discovered no significant advantages of HEPA filtration in the prevention of death among patients with hematological malignancies with severe neutropenia in randomized controlled trials (RCTs; relative risk [RR], 0.86 [95% confidence interval {CI}, 0.65-1.14]) and in studies of a lower standard (non-RCTs; RR, 0.87 [95% CI, 0.60-1.25]). CONCLUSIONS: The placement in protected areas of patients with hematological malignancies with severe neutropenia or patients with bone marrow transplants appears to be beneficial, but no definitive conclusion could be drawn from the data available.