Nikolai Kirkby - Academia.edu (original) (raw)

Papers by Nikolai Kirkby

Journal of Antimicrobial Chemotherapy, 2021

Pediatric Infectious Disease Journal, 2022

We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bac... more We reviewed all cases of Panton-Valentine leukocidin-producing Staphylococcus aureus (PVL-SA) bacteremia in Danish children between 2016 and 2021. We found 2 fatal cases with preceding viral prodrome due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the usual benign course of SARS-CoV-2 infection in children, awareness of possible superinfection with PVL-SA in a child with rapid deterioration is crucial to ensure adequate treatment, including antimicrobial drugs with antitoxin effect.

Nature Communications, 2021

New lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of sever... more New lineages of SARS-CoV-2 are of potential concern due to higher transmissibility, risk of severe outcomes, and/or escape from neutralizing antibodies. Lineage B.1.1.7 (the Alpha variant) became dominant in early 2021, but the association between transmissibility and risk factors, such as age of primary case and viral load remains poorly understood. Here, we used comprehensive administrative data from Denmark, comprising the full population (January 11 to February 7, 2021), to estimate household transmissibility. This study included 5,241 households with primary cases; 808 were infected with lineage B.1.1.7 and 4,433 with other lineages. Here, we report an attack rate of 38% in households with a primary case infected with B.1.1.7 and 27% in households with other lineages. Primary cases infected with B.1.1.7 had an increased transmissibility of 1.5–1.7 times that of primary cases infected with other lineages. The increased transmissibility of B.1.1.7 was multiplicative across age an...

Acta Paediatrica, 2021

We thank Chu and Hale for their important comments on the findings of our study investigating the... more We thank Chu and Hale for their important comments on the findings of our study investigating the use of saliva for detecting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children.1 Our study followed 20 children and found that in week one and two after diagnosis SARS-CoV-2 was detected in 29% and 11% of saliva samples, 86% and 50% of nasal swabs and 58% and 40% of throat swabs, respectively.2 Chu and Hale got the impression that all saliva samples were taken by a parent, except for the first sample.

The Lancet Infectious Diseases, 2021

Leukemia & Lymphoma, 2013

In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludar... more In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.

Background and objective: The bacterial profile of saliva is composed of bacteria from different ... more Background and objective: The bacterial profile of saliva is composed of bacteria from different oral surfaces. The objective of this study was to determine whether different diet intake, lifestyle, or socioeconomic status is associated with characteristic bacterial saliva profiles. Design: Stimulated saliva samples from 292 participants with low levels of dental caries and periodontitis, enrolled in the Danish Health Examination Survey (DANHES), were analyzed for the presence of approx-imately 300 bacterial species by means of the Human Oral Microbe Identification Microarray (HOMIM). Using presence and levels (mean HOMIM-value) of bacterial probes as endpoints, the influence of diet intake, lifestyle, and socioeconomic status on the bacterial saliva profile was analyzed by MannWhitney tests with BenjaminiHochberg’s correction for multiple comparisons and principal component analysis. Results: Targets for 131 different probes were identified in 292 samples, with Streptococcus and Ve...

<b>Copyright information:</b>Taken from "Recombinant human erythropoietin increa... more <b>Copyright information:</b>Taken from "Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria"http://www.malariajournal.com/content/7/1/3Malaria Journal 2008;7():3-3.Published online 7 Jan 2008PMCID:PMC2257967.eated with recombinant human Erythropoietin 200 U daily on day 4–7 show a similar drop on day 9–10, but recover afterwards (right graph). The data shown are representative for repeated experiments. The data presented are from one single experiment. Data for the treatment group is representative for mice that received rhEpo 50–200 U daily on day 4–5.

Open Forum Infectious Diseases, 2017

BackgroundManagement of CMV infection in solid organ transplantation (SOT) and haematopoietic ste... more BackgroundManagement of CMV infection in solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) recipients mainly relies on screening of emerging CMV DNA in plasma or whole blood by PCR. However, a first positive CMV PCR may not be reproducible, but constitute a CMV blip (single positive CMV PCR measurements). Such blips are known from monitoring of other viral infections using PCR technology, and may either constitute a false positive read due to assay variability or reflect transient low-level viral replication. We investigated the impact of CMV blips in a cohort of SOT and HSCT recipients.MethodsSOT and HSCT recipients transplanted between 2010 and 2015, who had a known donor (D)/recipient (R) CMV IgG serostatus (D+/R+, D+/R- or D-/R+), and with ≥3 CMV PCRs fulfilling the CMV PCR triplicate criteria (Figure 1) were included (N = 851). Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model.Results851 transplant recipients generated 3883 CMV PCR triplicates (104 blips, 307 infections, 3472 negatives, Figure 1). In the 411 positive triplicates, the OR of a triplicate being a blip decreased with increasing CMV viral load of the second measurement ([vs. = 273 IU/mL]; >273–910 IU/mL: OR 0.2 [95% CI 0.1–0.4], >910 IU/mL: OR 0.07 [95% CI 0.03–0.2], P < 0.0001) and was elevated in recipients with intermediary/low-risk CMV IgG serostatus ([vs. those with high] OR 2.2 [95% CI 1.3–3.6] P = 0.003). If the cumulative exposure to viremia in the CMV blips was >910 IU/mL, there was a higher risk of subsequent CMV infection (HR 4.6 [95% CI 1.2–17.2] P = 0.02) (Figure 2).ConclusionCMV blips are frequent while screening transplant recipients with CMV PCR. CMV blips >910 IU/mL is a risk factor for subsequent infection, indicating that CMV blips at least partly reflect transient low-level CMV infection in transplant recipients. These observations suggest that first positive CMV PCR results should be confirmed before initiation of anti-CMV treatment, especially if the viral load of the first positive PCR is <910 IU/mL, or if the patient has intermediary/low-risk serostatus.Open in a separate windowOpen in a separate windowDisclosures All authors: No reported disclosures.

Open Forum Infectious Diseases, 2015

Transplant Infectious Disease

Cytomegalovirus (CMV) infection is common among solid organ transplant (SOT) recipients and may c... more Cytomegalovirus (CMV) infection is common among solid organ transplant (SOT) recipients and may cause CMV disease. To optimize the implementation of existing prevention strategies, the Management of Post‐transplant Infections in Collaborating Hospitals (MATCH) program was developed. Two key performances of MATCH (diagnosing CMV infection at low viral load (VL) and before the onset of CMV disease) were assessed prior to, during and after the implementation of MATCH.

INTRODUCTION The reference test to evaluate patients with suspected respiratory virus infection i... more INTRODUCTION The reference test to evaluate patients with suspected respiratory virus infection is a real-time reverse transcription-polymerase chain reaction (RT-PCR) from a nasopharyngeal swab (NPS). However, other specimen collection methods such as an oropharyngeal swab (OPS) or saliva specimen are also used for SARS-CoV-2 testing during the ongoing COVID-19 pandemic. However, it remains unclear if rates of SARS-CoV-2 detection differ between sampling methods. This study will compare the rates of SARS-CoV-2 detection by saliva, OPS, and NPS sampling in a public setting. METHODS Individuals referred for outpatient SARS-CoV-2 testing will be invited to participate in a prospective clinical study. They will have saliva, OPS and NPS specimens collected that will be analysed separately for SARS-CoV-2 RNA by RT-PCR. The rate of SARS-CoV-2 detection in saliva, OPS and NPS will be compared using a logistic regression mixed-effect model analysis. A sample of 19,110 participants is requir...

Background Healthcare workers (HCW) have been identified as index cases in disease outbreaks of v... more Background Healthcare workers (HCW) have been identified as index cases in disease outbreaks of vaccine-preventable diseases (VPD) in hospitals. Aim We investigated whether Danish paediatric HCW were protected against selected serious VPD. Methods We included 90% of staff members from two paediatric departments. All 555 HCW (496 women) supplied a blood sample for serology and filled in a questionnaire. Antibodies were measured with enzyme immunoassay against measles, mumps, rubella (MMR), varicella zoster, pertussis toxin and diphtheria toxin. Results Protective levels of IgG were found for measles (90.3%), mumps (86.5%), rubella (92.3%), varicella (98.6%) and diphtheria (80.5%). We found seropositivity for all three MMR components in 421 (75.9%) HCW, lowest in those younger than 36 years (63.3%). Only 28 (5%) HCW had measurable IgG to pertussis. HCW with self-reported immunity defined as previous infection or vaccination, had protective levels of IgG against measles, mumps, rubella...

Diagnostics

Proper specimen collection is the most important step to ensure accurate testing for the coronavi... more Proper specimen collection is the most important step to ensure accurate testing for the coronavirus disease 2019 (COVID-19) and other infectious diseases. Assessment of healthcare workers’ upper respiratory tract specimen collection skills is needed to ensure samples of high-quality clinical specimens for COVID-19 testing. This study explored the validity evidence for a theoretical MCQ-test and checklists developed for nasopharyngeal (NPS) and oropharyngeal (OPS) specimen collection skills assessment. We found good inter-item reliability (Cronbach’s alpha = 0.76) for the items of the MCQ-test and high inter-rater reliability using the checklist for the assessment of OPS and NPS skills on 0.86 and 0.87, respectively. The MCQ scores were significantly different between experts (mean 98%) and novices (mean 66%), p < 0.001, and a pass/fail score of 91% was established. We found a significant discrimination between checklist scores of experts (mean 95% score for OPS and 89% for NPS) ...

Blood Advances

Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated wi... more Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumpti...