Summary Background In survivors of Ebola virus disease, clinical sequelae including uveitis, arthralgia, and fatigue are common and necessitate systematic follow-up. However, the infection risk to ...health-care providers is poorly defined. Here we report Ebola virus RT-PCR data for body site and fluid samples from a large cohort of Ebola virus survivors at clinic follow-up. Methods In this cross-sectional cohort study, consecutive survivors of Ebola virus disease attending Kerry Town survivor clinic (Freetown, Sierra Leone), who had been discharged from the Kerry Town Ebola treatment unit, were invited to participate. We collected and tested axillary, blood, conjunctival, forehead, mouth, rectal, semen, urine, and vaginal specimens for presence of Ebola virus using RT-PCR. We regarded samples to be positive for Ebola virus disease if the cycle threshold was 40 or lower. We collected demographic data from survivors of their age, sex, time since discharge from the treatment unit, and length of acute admission in the Ebola treatment unit using anonymised standard forms. Findings Between April 2, and June 16, 2015, of 151 survivors of Ebola virus disease invited to participate, 112 (74%) provided consent. The median age of participants was 21·5 years (IQR 14–31·5) with 34 (30%) participants younger than 16 years. 50 (45%) of 112 participants were male. We tested a total of 555 specimens: 103 from the axilla, 93 from blood, 92 from conjunctiva, 54 from forehead, 105 from mouth, 17 from the rectum, one from semen, 69 from urine, and 21 from the vagina. The median time from Ebola treatment unit discharge to specimen collection was 142 days (IQR 127–159). 15 participants had a total of 74 swabs taken less than 100 days from discharge. The semen sample from one participant tested positive for Ebola virus at 114 days after discharge from the treatment unit; specimens taken from the axilla, blood, conjunctiva, forehead, mouth, rectum, and urine of the same participant tested negative. All specimens from the other 111 participants tested negative. Interpretation Patients recovering from Ebola virus disease who do not meet the case definition for acute disease pose a low infection risk to health-care providers 6 weeks after clearance of viraemia. Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged. Funding Save the Children International, Public Health England.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background: Optimal management of intracranial infections relies on microbiological diagnosis and antimicrobial choice, but conventional culture-based testing is limited by pathogen viability and ...pre-sampling antimicrobial exposure. Broad-range 16S rRNA gene sequencing has been reported in the management of culture-negative infections but its utility in intracranial infection is not well-described. We studied the efficacy of 16S rRNA gene sequencing to inform microbiological diagnosis and antimicrobial choice in intracranial infections.
Methods: This was a retrospective study of all intraoperative neurosurgical specimens sent for 16S rRNA gene sequencing over an 8-year period at a regional neurosurgical centre in the UK. Specimen selection was performed using multidisciplinary approach, combining neurosurgical and infection specialist discussion.
Results: Twenty-five intraoperative specimens taken during neurosurgery from 24 patients were included in the study period. The most common reason for referral was pre-sampling antimicrobial exposure (68%). Bacterial rDNA was detected in 60% of specimens. 16S rRNA gene sequencing contributed to microbiological diagnosis in 15 patients and informed antimicrobial management in 10 of 24 patients with intracranial infection. These included targeted antibiotics after detection of a clinically-significant pathogen that had not been identified through other microbiological testing (3 cases), detection of commensal organisms in neurosurgical infection which justified continued broad cover (2 cases) and negative results from intracranial lesions with low clinical suspicion of bacterial infection which justified avoidance or cessation of antibiotics (5 cases).
Conclusion: Overall, 16S rRNA gene sequencing represented an incremental improvement in diagnostic testing and was most appropriately used to complement, rather than replace, conventional culture-based testing for intracranial infection.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a lack of consensus about which non-human immunodeficiency virus (HIV) patient groups would benefit from prophylaxis. Here, we analysed an enhanced Pneumocystis jirovecii database to ...describe the epidemiology of Pneumocystis pneumonia (PCP) and P. jirovecii colonizations in Northern Ireland (NI) with a view to identifying risk groups who may benefit from prophylaxis.
We prospectively collected information on demographics, clinical severity and clinical features for all hospital inpatients in NI aged ≥18 years with P. jirovecii confirmed in any respiratory tract sample. We defined P. jirovecii colonization or PCP according to clinical symptoms and radiological findings. We compared P. jirovecii colonization to PCP using exact logistic regression and presented the odds ratios (OR), 95 % confidence intervals (CI) and likelihood ratio test P-values.Results/Key findings. Overall, 36/49 (73 %) of P. jirovecii detections were categorized as PCP. A total of 28/36 (78 %) were in non-HIV patients, of which 18 (64 %) had cancer. The odds of PCP compared to P. jirovecii colonization were eight times higher in those with current exposure to chemotherapy (OR 8.73; 95 % CI 0.84, ∞), 16 times higher for those diagnosed with HIV (OR 16.2; 95 % CI 1.71, ∞) and 12 times higher for those ever exposed to another immunosuppressive drug (OR 12.1; 95 % CI 1.94, ∞).
The greatest burden of PCP is now in the non-HIV group, particularly cancer patients. We recommend increasing clinician awareness of PCP risk and strengthening prevention guidelines in non-HIV patients, and promoting the consideration of prophylaxis on a case-by-case basis.
Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical ...surveillance and the lack of predictable seasonal dynamics limits the public health response. Wastewater-based epidemiology (WBE) has recently been used globally as a key metric in determining prevalence of SARS-CoV-2 in the community but its application to other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, applying RT-qPCR and partial G-gene sequencing to track RSV levels and variants in the community. We report increasing detection of RSV in wastewater concomitant with increasing numbers of positive clinical cases. Analysis of wastewater-derived RSV sequences permitted identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance and aid the management of RSV by informing the timely deployment of pharmaceutical and non-pharmaceutical interventions.
Pneumocystis jirovecii causes pneumonia, a severe opportunistic infection in immunosuppressed patients that has both person-to-person airborne transmission and environmental transmission as important ...routes of infection. An increasing incidence of P. jirovecii in Northern Ireland prompted a detailed epidemiological and molecular review that included enhanced surveillance on all lower respiratory specimens. Genotyping of these P. jirovecii positive specimens was undertaken using multiple locus sequence typing (MLST) targeting known variable regions of the P. jirovecii genome. Multiple circulating types were found among all patient risk categories. However, a predominance of one MLST type was found in a P. jirovecii outbreak amongst the renal transplant population. Our results demonstrate the diversity of P. jirovecii strains amongst the local immunosuppressed cohort and highlight the importance of genotyping in the investigation of common sources of P. jirovecii amongst immunosuppressed patients.
Biofilms containing Candida albicans are responsible for a wide variety of clinical infections. The protective effects of the biofilm matrix, the low metabolic activity of microorganisms within a ...biofilm and their high mutation rate, significantly enhance the resistance of biofilms to conventional antimicrobial treatments. Peptoids are peptide‐mimics that share many features of host defence antimicrobial peptides but have increased resistance to proteases and therefore have better stability in vivo. The activity of a library of peptoids was tested against monospecies and polymicrobial bacterial/fungal biofilms. Selected peptoids showed significant bactericidal and fungicidal activity against the polymicrobial biofilms. This coupled with low cytotoxicity suggests that peptoids could offer a new option for the treatment of clinically relevant polymicrobial infections.
Peptoids can mimic host‐defence antimicrobial peptides but have increased resistance to proteases. We constructed a library of such peptoids and showed that they reduce the cell numbers of C. albicans, S. aureus and E. coli in polymicrobial biofilms, as quantified by a novel PMA‐qPCR assay.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the ...epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40–20) and inter‐seasonal periods (weeks 21–39) during the pandemic between October 2020 and September 2022.
Methods
Using data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country‐specific weekly RSV counts of sentinel, non‐sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 2021/22 seasons and inter‐seasons were compared with pre‐pandemic 2016/17 to 2019/20 seasons and inter‐seasons.
Results
Although more specimens were tested than in pre‐COVID‐19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter‐season, a gradual increase in detections was observed in all systems. In 2021/22, all systems saw early peaks of RSV infection, and during the 2022 inter‐seasonal period, patterns of detections were closer to those seen before the COVID‐19 pandemic.
Conclusion
RSV surveillance continued throughout the COVID‐19 pandemic, with an initial reduction in transmission, followed by very high and out‐of‐season RSV circulation (summer 2021) and then an early start of the 2021/22 season. As of the 2022/23 season, RSV circulation had not yet normalised.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
PURPOSEResearch has not convincingly demonstrated the utility of saliva secretory immunoglobulin-A (SIgA) as a biomarker of upper respiratory tract infection (URTI) risk, and disagreement exists ...about the influence of heavy exercise (“open-window theory”) and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study 1) and assessed the influence of exercise (study 2) and dehydration (study 3) using a repeated-measures crossover design.
METHODSIn study 1, 40 subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper respiratory symptoms (URS) daily for 3 wk. Real-time PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected during the week before URS. In study 2, 13 subjects performed a 2-h run at 65% V˙O2peak. In study 3, 13 subjects performed exercise heat stress to 3% body mass loss followed by overnight fluid restriction.
RESULTSTear SIgA concentration and secretion rate were 48% and 51% lower, respectively, during URTI and 34% and 46% lower the week before URS (P < 0.05), but saliva SIgA remained unchanged. The risk of URS the following week increased ninefold (95% confidence interval, 1.7–48) when the tear SIgA secretion rate was <5.5 μg·min and sixfold (95% confidence interval, 1.2–29) when the tear SIgA secretion rate decreased >30%. Tear SIgA secretion rate >5.5 μg·min or no decrease of >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased after exercise (−57%, P < 0.05) in line with the “open-window theory” but was unaffected by dehydration. Saliva flow rate decreased and saliva SIgA concentration increased after exercise and during dehydration (P < 0.05).
CONCLUSIONSTear SIgA has utility as a noninvasive biomarker of mucosal immunity and common-cold risk.
Against a background of point-source outbreaks of Pneumocystis pneumonia (PCP) in renal transplant units in Europe, we undertook a retrospective 3 year observational review of PCP in Northern ...Ireland. This showed an unexpected increase in incidence, with a mortality rate of 30 %. Fifty-one cases were confirmed compared to 10 cases confirmed in the preceding 7 years. Where undiagnosed HIV infection had previously been the main risk factor for PCP, this was now equally matched by chemotherapy for haematological and non-haematological malignancy and immune suppression for a range of autoimmune conditions. Congenital immunodeficiency and transplantation were less common predisposing factors, but renal grafts also showed a rising incidence. Asymptomatic carriage was uncommon. At presentation both upper and lower respiratory samples were of equal use in establishing the diagnosis, and treatment resulted in rapid clearance. These data suggest the need for considering PCP in at-risk patients, reviewing its mode of acquisition and whether iatrogenic colonization is a treatable pre-condition.