Is ultraviolet light disinfection fit to be the future standard for the disinfection of flexible endoscopes without a working channel?

OBJECTIVE: To investigate colony-forming unit (CFU) reduction on contaminated flexible endoscopes (FEs) without a working channel after UV-C light disinfection, compared to the current disinfection method with the endoscope washer disinfector (EWD). DESIGN, SETTING AND PARTICIPANTS: After pharyngolaryngoscopy, a manual pre-cleaning with tap water was performed. A culture was then collected by rolling the distal 8-10 cm of the FE over an Agar plate. The FE was disinfected using the D60 (60-s disinfection process with UV-C light) or the EWD (gold standard reprocessing process with water and chemicals). Another culture was then taken. After incubation, a CFU count was performed. RESULTS: A total of 200 FEs without a working channel were divided equally between the two disinfection groups. After clinical use and manual pre-cleaning, 84 of the 100 (84.0%) (UV-C light group) and 79 of the 100 (79.0%) (EWD) FEs were contaminated with at least 1 CFU. FEs that showed no contamination after use were excluded from further analysis. After disinfection with UV-C light, 72 (85.7%) FEs showed no contamination (i.e., 0 CFUs) versus 66 (83.5%) FEs after reprocessing with the EWD. CONCLUSION: There is no difference in CFUs reduction on contaminated FEs without a working channel between UV-C light disinfection and the current gold standard, the EWD.

Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020.

Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies.

Correction: Early warning for healthcare acquired infections in neonatal care units in a low-resource setting using routinely collected hospital data: The experience from Haiti, 2014-2018.

[This corrects the article DOI: 10.1371/journal.pone.0269385.].

Screening for Clostridioides difficile colonization at admission to the hospital: a multi-centre study.

OBJECTIVES: To assess the value of screening for Clostridioides difficile colonization (CDC) at hospital admission in an endemic setting. METHODS: A multi-centre study was conducted at four hospitals located across the Netherlands. Newly admitted patients were screened for CDC. The risk of development of Clostridioides difficile infection (CDI) during admission and 1-year follow-up was assessed in patients with and without colonization. C. difficile isolates from patients with colonization were compared with isolates from incident CDI cases using core genome multi-locus sequence typing to determine whether onwards transmission had occurred. RESULTS: CDC was present in 108 of 2211 admissions (4.9%), whereas colonization with a toxigenic strain (toxigenic Clostridoides difficile colonization [tCDC]) was present in 68 of 2211 admissions (3.1%). Among these 108 patients with colonization, diverse PCR ribotypes were found and no 'hypervirulent' PCR ribotype 027 (RT027) was detected (95% CI, 0-0.028). None of the patients with colonization developed CDI during admission (0/49; 95% CI, 0-0.073) or 1-year follow-up (0/38; 95% CI, 0-0.93). Core genome multi-locus sequence typing identified six clusters with genetically related isolates from patients with tCDC and CDI; however, in these clusters, only one possible transmission event from a patient with tCDC to a patient with CDI was identified based on epidemiological data. CONCLUSION: In this endemic setting with a low prevalence of 'hypervirulent' strains, screening for CDC at admission did not detect any patients with CDC who progressed to symptomatic CDI and detected only one possible transmission event from a patient with colonization to a patient with CDI. Thus, screening for CDC at admission is not useful in this setting.

Protection against a malaria challenge by sporozoite inoculation.

BACKGROUND: An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites. METHODS: We exposed 15 healthy volunteers--with 10 assigned to a vaccine group and 5 assigned to a control group--to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection. RESULTS: All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-gamma, tumor necrosis factor alpha, and interleukin-2 as a promising immunologic marker of protection. CONCLUSIONS: Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.)

Reply to Viner, A.; Ayrey, S. Comment on "Scheepers et al. Comparative Performance Testing of Respirator versus Surgical Mask Using a Water Droplet Spray Model. Int. J. Environ. Res. Public Health 2021, 18, 1599".

The response to our publication by Andrew Viner and Stewart Ayrey is much appreciated [...].

Early warning for healthcare acquired infections in neonatal care units in a low-resource setting using routinely collected hospital data: The experience from Haiti, 2014-2018.

In low-resource settings, detection of healthcare-acquired outbreaks in neonatal units relies on astute clinical staff to observe unusual morbidity or mortality from sepsis as microbiological diagnostics are often absent. We aimed to generate reliable (and automated) early warnings for potential clusters of neonatal late onset sepsis using retrospective data that could signal the start of an outbreak in an NCU in Port au Prince, Haiti, using routinely collected data on neonatal admissions. We constructed smoothed time series for late onset sepsis cases, late onset sepsis rates, neonatal care unit (NCU) mortality, maternal admissions, neonatal admissions and neonatal antibiotic consumption. An outbreak was defined as a statistical increase in any of these time series indicators. We created three outbreak alarm classes: 1) thresholds: weeks in which the late onset sepsis cases exceeded four, the late onset sepsis rates exceeded 10% of total NCU admissions and the NCU mortality exceeded 15%; 2) differential: late onset sepsis rates and NCU mortality were double the previous week; and 3) aberration: using the improved Farrington model for late onset sepsis rates and NCU mortality. We validated pairs of alarms by calculating the sensitivity and specificity of the weeks in which each alarm was launched and comparing each alarm to the weeks in which a single GNB positive blood culture was reported from a neonate. The threshold and aberration alarms were the strongest predictors for current and future NCU mortality and current LOS rates (p<0.0002). The aberration alarms were also those with the highest sensitivity, specificity, negative predictive value, and positive predictive value. Without microbiological diagnostics in NCUs in low-resource settings, applying these simple algorithms to routinely collected data show great potential to facilitate early warning for possible healthcare-acquired outbreaks of LOS in neonates. The methods used in this study require validation across other low-resource settings.

Memory-like IFN-γ response by NK cells following malaria infection reveals the crucial role of T cells in NK cell activation by P. falciparum.

NK cells are rapid IFN-γ responders to Plasmodium falciparum-infected erythrocytes (PfRBC) in vitro and are involved in controlling early parasitaemia in murine models, yet little is known about their contribution to immune responses following malaria infection in humans. Here, we studied the dynamics of and requirements for in vitro NK responses to PfRBC in malaria-naïve volunteers undergoing a single experimental malaria infection under highly controlled circumstances, and in naturally exposed individuals. NK-specific IFN-γ responses to PfRBC following exposure resembled an immunological recall pattern and were tightly correlated with T-cell responses. However, although PBMC depleted of CD56(+) cells retained 20-55% of their total IFN-γ response to PfRBC, depletion of CD3(+) cells completely abrogated the ability of remaining PBMC, including NK cells, to produce IFN-γ. Although NK responses to PfRBC were partially dependent on endogenous IL-2 signaling and could be augmented by exogenous IL-2 in whole PBMC populations, this factor alone was insufficient to rescue NK responses in the absence of T cells. Thus, NK cells make a significant contribution to total IFN-γ production in response to PfRBC as a consequence of their dependency on (memory) T-cell help, with likely positive implications for malaria vaccine development.

Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali.

INTRODUCTION: Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood. METHODS AND RESULTS: Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection. CONCLUSIONS: These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses.

Acute Endophthalmitis after Cataract Surgery: Clinical Characteristics and the Role of Intracameral Antibiotic Prophylaxis.

PURPOSE: To evaluate the clinical characteristics and investigate the role of surgical antibiotic prophylaxis (SAP) in acute endophthalmitis cases after cataract surgery. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: A total of 126 patients referred to a tertiary center from 2007 to 2015 for acute endophthalmitis after unilateral cataract surgery. METHODS: All patients who underwent a vitreous biopsy were included. Clinical and microbiology data were reviewed, and associations with visual outcome were analyzed using multivariate logistic regression. Data regarding SAP via intracameral injection were also retrieved. MAIN OUTCOME MEASURES: Bacterial culture results and visual acuity outcome. RESULTS: Bacterial growth was observed in 92 of 126 cases (73%). Among these positive cultures, 49 (53.3%), 29 (31.5%), and 13 (14.1%) were coagulase-negative staphylococci, other gram-positive, and gram-negative bacteria, respectively. Among the 77 gram-positive strains tested, 76 (98.7%) were vancomycin-sensitive; among the 12 gram-negative strains tested, all 12 (100%) were ceftazidime-sensitive. Best achieved visual acuity outcome was ≥20/40 Snellen in 77 of 114 cases (67.5%). On multivariate analysis, we found an association between visual outcome of worse than 20/40 Snellen and a positive culture of more virulent bacteria (gram-negative and other gram-positive groups) and presentation with light perception or worse, with an odds ratio of 3.3 and 3.0, respectively. A subgroup of 25 cases (19.8%) developed endophthalmitis despite receiving a SAP by cefuroxime at the end of cataract surgery. CONCLUSIONS: Two-thirds of the patients in this endophthalmitis cohort experienced a visual outcome of ≥20/40 Snellen. Efficacy of primary treatment with vancomycin combined with ceftazidime is supported by this study. A subgroup treated prophylactically with cefuroxime demonstrated that SAP alone does not prevent endophthalmitis. This highlights the importance of surgical factors in the prevention of postoperative endophthalmitis.

Disinfecting handheld electronic devices with UV-C in a healthcare setting.

Handheld Electronic Devices (HEDs) play a central role in the hospital environment. However, they can be a vehicle for transmitting (pathogenic) microorganisms. We studied whether disinfection with UV-C light is successful in disinfecting three different HEDs in a clinical setting. Disinfection with UV-C light was performed with the UV-Smart® D25. We took a total of 800 samples on two departments and counted colony forming units. More than half of the baseline measurements were moderately (>10CFU) or highly (>50 CFU) contaminated. Post-disinfection the CFU was 0 in 87% of measurements. We conclude that the UV-Smart® D25 can be used to disinfect non-critical HEDs in clinical healthcare.

Identifying the priority infection prevention and control gaps contributing to neonatal healthcare-associated infections in low-and middle-income countries: results from a modified Delphi process.

Background: In low- and middle-income countries (LMIC), neonatal healthcare-associated infections (HAI) are associated with increased morbidity, mortality, hospital stay, and costs. When resources are limited, addressing HAI through infection prevention and control (IPC) requires prioritizing interventions to maximize impact. However, little is known about the gaps in LMIC that contribute most to HAI. Methods: A literature review was conducted to identify the leading IPC gaps contributing to neonatal HAIs in intensive care units and specialty care wards in LMIC. Additionally, a panel of 21 global experts in neonatology and IPC participated in an in-person modified Delphi process to achieve consensus on the relative importance of these gaps as contributors to HAI. Results: Thirteen IPC gaps were identified and summarized into four main categories: facility policies such as prioritizing a patient safety culture and maintaining facility capacity, general healthcare worker behaviors such as hand hygiene and proper device insertion and maintenance, specialty healthcare worker behaviors such as cleaning and reprocessing of medical equipment, and infrastructural considerations such as adequate medical equipment and hand hygiene supplies. Conclusions: Through a modified Delphi process, we identified the leading IPC gaps contributing to neonatal HAIs; this information can assist policymakers, public health officials, researchers, and clinicians to prioritize areas for further study or intervention.

Comparative Performance Testing of Respirator versus Surgical Mask Using a Water Droplet Spray Model.

BACKGROUND: During the SARS-CoV-2 pandemic, there was shortage of the standard respiratory protective equipment (RPE). The aim of this study was to develop a procedure to test the performance of alternative RPEs used in the care of COVID-19 patients. METHODS: A laboratory-based test was developed to compare RPEs by total inward leakage (TIL). We used a crossflow nebulizer to produce a jet spray of 1-100 µm water droplets with a fluorescent marker. The RPEs were placed on a dummy head and sprayed at distances of 30 and 60 cm. The outcome was determined as the recovery of the fluorescent marker on a membrane filter placed on the mouth of the dummy head. RESULTS: At 30 cm, a type IIR surgical mask gave a 17.7% lower TIL compared with an FFP2 respirator. At 60 cm, this difference was similar, with a 21.7% lower TIL for the surgical mask compared to the respirator. When adding a face shield, the TIL at 30 cm was further reduced by 9.5% for the respirator and 16.6% in the case of the surgical mask. CONCLUSIONS: A safe, fast and very sensitive test method was developed to assess the effectiveness of RPE by comparison under controlled conditions.

Multi-drug resistance and high mortality associated with community-acquired bloodstream infections in children in conflict-affected northwest Nigeria.

Pediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.

SARS-CoV-2 whole-genome sequencing using reverse complement PCR: For easy, fast and accurate outbreak and variant analysis.

During the course of the SARS-CoV-2 pandemic reports of mutations with effects on spreading and vaccine effectiveness emerged. Large scale mutation analysis using rapid SARS-CoV-2 Whole Genome Sequencing (WGS) is often unavailable but could support public health organizations and hospitals in monitoring transmission and rising levels of mutant strains. Here we report a novel WGS technique for SARS-CoV-2, the EasySeq™ RC-PCR SARS-CoV-2 WGS kit. By applying a reverse complement polymerase chain reaction (RC-PCR), an Illumina library preparation is obtained in a single PCR, thereby saving time, resources and facilitating high-throughput screening. Using this WGS technique, we evaluated SARS-CoV-2 diversity and possible transmission within a group of 173 patients and healthcare workers (HCW) of the Radboud university medical center during 2020. Due to the emergence of variants of concern, we screened SARS-CoV-2 positive samples in 2021 for identification of mutations and lineages. With use of EasySeq™ RC-PCR SARS-CoV-2 WGS kit we were able to obtain reliable results to confirm outbreak clusters and additionally identify new previously unassociated links in a considerably easier workaround compared to current methods. Furthermore, various SARS-CoV-2 variants of interest were detected among samples and validated against an Oxford Nanopore sequencing amplicon strategy which illustrates this technique is suitable for surveillance and monitoring current circulating variants.

[Rational use of respiratory protective equipment: advice for health care professionals in time of COVID-19]. / Rationeel gebruik van ademhalingsbeschermingsmaskers.

The current COVID-19 pandemic has led to a worldwide shortage of respiratory protective equipment. In order to offer maximum protection against infection for all healthcare workers, we need to optimise our use of the available equipment. This article provides practical advice on which type of mask is indicated in what specific situation, what requirements the mask should meet and how to optimise the local workflow, including the re-use of masks after decontamination.

Rectal screening displays high negative predictive value for bloodstream infection with (ESBL-producing) Gram-negative bacteria in neonates with suspected sepsis in a low-resource setting neonatal care unit.

OBJECTIVES: We analysed the concordance of rectal swab isolates and blood culture for Gram-negative bacteria (GNB) isolates in neonates with a suspicion of neonatal sepsis admitted to a neonatal care unit in Haiti. METHODS: We matched pairs of blood and rectal samples taken on the date of suspected sepsis onset in the same neonate. We calculated the proportion of rectal isolates in concordance with the blood isolates by species and genus. We calculated the negative predictive value (NPV) for GNB and extended-spectrum ß-lactamase (ESBL)-producing GNB for all rectal and blood isolate pairs in neonates with suspected sepsis. RESULTS: We identified 238 blood and rectal samples pairs, with 238 blood isolate results and 309 rectal isolate results. The overall concordance in genus and species between blood and rectal isolates was 22.3% [95% confidence interval (CI) 17.4-28.0%] and 20.6% (95% CI 16.0-26.2%), respectively. The highest concordance between blood and rectal isolates was observed for samples with no bacterial growth (65%), followed byKlebsiella pneumoniae (18%) and Klebsiella oxytoca (12%). The NPV of detecting GNB bacterial isolates in rectal samples compared with those in blood samples was 81.6% and the NPV for ESBL-positive GNB was 92.6%. CONCLUSIONS: The NPV of rectal swab GNB isolates was high in all patient groups and was even higher for ESBL-positive GNB. Clinicians can use the results from rectal swabs when taken simultaneously with blood samples during outbreaks to inform the (de-)escalation of antibiotic therapy in those neonates that have an ongoing sepsis profile.