Background Cases of reported tick-borne diseases in humans have increased over the past decades. ... more Background Cases of reported tick-borne diseases in humans have increased over the past decades. Strategies informing the public about ticks, their associated diseases, and preventive measures are often highlighted as important in limiting pathogen transfer and disease. However, knowledge about the motivation for people to apply preventative measures is sparse. The aim was to examine if Protection Motivation Theory, a model of disease prevention and health promotion, can predict the use of protective measures against ticks. Ordinal logistic regression and Chi-square tests were used on data from a cross-sectional survey with respondents from Denmark, Norway, and Sweden (n = 2658). We examined the effect of (1) the perceived seriousness of tick bites, Lyme borreliosis (LB), and tick-borne encephalitis (TBE), and (2) the perceived probability of getting a tick bite, Lyme borreliosis, and tick-borne encephalitis on protection against ticks. Finally, we examined if there was an association between the use of a protective measure and the perceived efficacy of that measure. The perceived seriousness of a tick bite and LB significantly predict who is more likely to apply protective measures for all three countries combined. The perceived seriousness of TBE did not significantly predict the level of adoption of protective measures applied by respondents. The perceived likelihood of getting a tick bite within the next 12 months and the perceived likelihood of getting LB if bitten by a tick significantly predicted the application of protective measures. However, the increases in the likelihood of protection were very small. The application of a certain type of protection was always correlated with the perceived efficacy of the same protective measure. Conclusion Some variables of PMT may be used to predict the level of adoption of protection applied against ticks and tick-borne diseases. We found that the perceived seriousness of a tick bite and LB significantly predict the level of adoption protection. The perceived likelihood of getting a tick bite or LB also significantly predicted the level of adoption of protection, although the change was very small. The results regarding TBE were less clear. Lastly, there was an association between applying a protective measure and the perceived efficacy of the same measure.
Frontiers in Cellular and Infection Microbiology, Feb 13, 2023
Leptospirosis is a zoonotic bacterial infection that can cause influenza-like symptoms and severe... more Leptospirosis is a zoonotic bacterial infection that can cause influenza-like symptoms and severe disease. In Denmark, leptospirosis is rare, non-endemic, and most commonly transferred to humans from mice and rats. Cases of human leptospirosis in Denmark are by law notifiable to Statens Serum Institut. This study aimed to describe trends in incidence of leptospirosis in Denmark from 2012 to 2021. Descriptive analyses were used to calculate the incidence, geographical distribution and possible routes of infection, as well as testing capacity and serological trends. The overall incidence rate was 0.23 per 100,000 inhabitants, with the highest annual incidence of 24 cases in 2017. Men between 40-49 years old were the demographic group most commonly diagnosed with leptospirosis. August and September were the months with highest incidence over the entire study period. The most common serovar observed was Icterohaemorrhagiae, although over a third of cases were diagnosed via polymerase chain reaction alone. The most common sources of exposure reported were travel abroad, farming, and recreational contact with fresh water, the latter being a new exposure compared to previous studies. Overall, a One Health approach would ensure better detection of outbreaks and milder disease. Additionally, preventative measures should be expanded to include recreational water sports.
The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently ident... more The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5 -(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL).
Hyldig conceived and planned the study, organized the intervention and collection of samples and ... more Hyldig conceived and planned the study, organized the intervention and collection of samples and critically revised the manuscript Dr. Krogfelt and DMSc Greisen conceived and planned the study and critically revised the manuscript. MSc Kamal performed all laboratory analysis, performed bioinformatics and data analysis and drafted the initial manuscript Dr. Krych performed bioinformatics and data analysis. Dr. Nielsen conceived and planned the study, did data analysis and drafted the initial manuscript
Annals of Clinical Microbiology and Antimicrobials, Mar 20, 2023
Background The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe feb... more Background The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher's exact test. Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 -3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8-11.5%) and 11/192 (5.7%, 95%: CI 3.2-10.0%). In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.
African Journal of Microbiology Research, Feb 21, 2017
Poultry meat and products are major transmission routes of human campylobacteriosis. The aim of t... more Poultry meat and products are major transmission routes of human campylobacteriosis. The aim of this study was to determine the numbers and antibiogram profile of Campylobacter isolates from slaughtered broiler and layer birds. One hundred and sixty caecal and one hundred and thirty two carcasses were randomly sampled at the Kejetia poultry slaughter, isolated on charcoal-cefoperazonedeoxycholate agar (CCDA) and confirmed by API CAMPY and their resistance profiles assessed by Kirby-Bauer disk diffusion. Prevalence was 22.5 and 21.9% in the faecal and carcasses, respectively with no significant differences. Species identified among faecal isolates were Campylobacter jejuni (42%), Campylobacter coli (28%), Campylobacter lari (22%) and Campylobacter hyo-intestinalis (8%) while 79% C. jejuni, 14% C. coli, 4% C. jejuni sub sp. doylei, and 3% C. lari were obtained from the carcasses. Resistance to the β-lactams ranged from 75 to 100%, 41 to 86% to the quinolones, 14 to 36% to the aminoglycosides, 100% to erythromycin, 97 to 100% to tetracycline, 72 to 83% to chloramphenicol and 90 to 94% to trimethoprim sulfamethoxazole. All species were sensitive to imipenem, but 100% of isolates were multidrug resistant. Contamination of carcasses with multidrug resistant strains of Campylobacter is a threat to handlers and consumers and of major public health issue.
nature publishing group Background: Preterm infants are vulnerable to pathogens and at risk of de... more nature publishing group Background: Preterm infants are vulnerable to pathogens and at risk of developing necrotizing enterocolitis (NEC) or sepsis. Nasogastric feeding tubes (NG-tubes) might contaminate feeds given through them due to biofilm formation. We wanted to determine if there is a rationale in replacing NG-tubes more often to reduce contamination. Methods: We conducted an observational study of used NG-tubes from a tertiary neonatal department. After removal, we flushed a 1-ml saline solution through the tube, determined the density of bacteria by culture, and related it to the duration of use and any probiotic administration through the tube. results: Out of the 94 NG-tubes, 89% yielded more than 1,000 colony-forming units (CFU)/ml bacteria, and 55% yielded the potentially pathogenic Enterobacteriaceae and/or Staphylococcus aureus. The mean concentration in the yield was 5.3 (SD: 2.1, maximum 9.4) log 10 CFU/ml. Neither the presence of contamination nor the density was associated with the time the NG-tube had been in use. Probiotic administration did not protect against contamination. conclusion: NG-tubes yielded high densities of bacteria even within the first day of use. Further studies are needed to determine if changing the NG-tubes between meals or once a day will make a positive impact on tube contamination and clinical parameters.
In vitro and in vivo models were used to investigate the role of capsule on the virulence of Kleb... more In vitro and in vivo models were used to investigate the role of capsule on the virulence of Klebsiella pneumoniae. We showed that capsule expression reduces dramatically the ability of the K. pneumoniae to bind to epithelial cells when compared to its non-capsulated variant. The presence/absence of capsule had no effect on the colonization of the gastrointestinal tract, while in the urinary tract we established that capsule is an important virulence factor. Our study demonstrates the caution needed when extrapolating from results of in vitro studies and emphasizes the necessity of in vivo models in studies of bacterial virulence.
Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had se... more Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had serious economic and social consequences. COVID-19 manifests differently in children than adults, as children usually have a milder course of disease, mild symptoms if any, and lower fatality rates are recorded among children. SARS-CoV-2 transmission also seems to be different between children and adults. Many factors are proposed to explain the milder outcome in children, e.g., a more appropriate immune response (especially active innate response), trained immunity, a lack of immunosenescence, and the reduced prevalence of comorbidities. A better understanding of the differences in susceptibility and outcome in children compared with adults could lead to greater knowledge of risk factors for complicated COVID-19 cases and potential treatment targets. We highlight proposed reasons as to why children are less affected by COVID-19 than adults.
medRxiv (Cold Spring Harbor Laboratory), Apr 10, 2020
Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... more Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays are rapidly being developed and placed on the market with limited validation on clinical samples. Thorough validation of serological tests are required to facilitate their use in the accurate diagnosis of SARS-CoV-2 infection, confirmation of molecular results, contact tracing, and epidemiological studies. This study evaluated the sensitivity and specificity of nine commercially available serological tests. These included three enzyme-linked immunosorbent assays (ELISAs) and six point-of-care (POC) lateral flow tests. The assays were validated using serum samples from: i) SARS-CoV-2 PCR-positive patients with a documented first day of disease; ii) archived sera obtained from healthy individuals before the emergence of SARS-CoV-2 in China; iii) sera from patients with acute viral respiratory tract infections caused by other coronaviruses or noncoronaviruses; and iv) sera from patients positive for dengue virus, cytomegalovirus and Epstein Barr virus. The results showed 100% specificity for the Wantai SARS-CoV-2 Total Antibody ELISA, 93% for the Euroimmun IgA ELISA, and 96% for the Euroimmun IgG ELISA with sensitivities of 90%, 90%, and 65%, respectively. The overall performance of the POC tests according to manufacturer were in the rank order of AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech ≥ Hangzhou Alltest Biotech. Overall, these findings will facilitate selection of serological assays for the detection SARS-CoV-2-specific antibodies towards diagnosis as well as sero-epidemiological and vaccine development studies.
The ideal vaccine against viral infections should elicit antibody responses that protect against ... more The ideal vaccine against viral infections should elicit antibody responses that protect against divergent strains. Designing broadly protective vaccines against SARS-CoV-2 and other divergent viruses requires insight into the specific targets of cross-protective antibodies on the viral surface protein(s). However, unlike therapeutic monoclonal antibodies, the B-cell epitopes of vaccine-induced polyclonal antibody responses remain poorly defined. Here we show that, through the combination of neutralizing antibody functional responses with B-cell epitope mapping, it is possible to identify unique antibody targets associated with neutralization breadth. The polyclonal antibody profiles of SARS-CoV-2 index-strain-vaccinated rabbits that demonstrated a low, intermediate, or high neutralization efficiency of different SARS-CoV-2 variants of concern (VOCs) were distinctly different. Animals with an intermediate and high cross-neutralization of VOCs targeted fewer antigenic sites on the sp...
Reactive case detection (RACD) is the screening of household members and neighbors of index cases... more Reactive case detection (RACD) is the screening of household members and neighbors of index cases reported in passive surveillance. This strategy seeks asymptomatic infections and provides treatment to break transmission without testing or treating the entire population. This review discusses and highlights RACD as a recommended strategy for the detection and elimination of asymptomatic malaria as it pertains in different countries. Relevant studies published between January 2010 and September 2022 were identified mainly through PubMed and Google Scholar. Search terms included “malaria and reactive case detection”, “contact tracing”, “focal screening”, “case investigation”, “focal screen and treat”. MedCalc Software was used for data analysis, and the findings from the pooled studies were analyzed using a fixed-effect model. Summary outcomes were then presented using forest plots and tables. Fifty-four (54) studies were systematically reviewed. Of these studies, 7 met the eligibilit...
Coronavirus disease 2019 (COVID-19) contact tracing and malaria reactive case detection (RACD) ar... more Coronavirus disease 2019 (COVID-19) contact tracing and malaria reactive case detection (RACD) are effective strategies for disease control. The emergence of the COVID-19 pandemic and the global attention COVID-19 has received in the recent past and present has hampered malaria control efforts. Among these are difficulties in finding and treating malaria-infected individuals in hypoendemic settings in the community, due to lockdown restrictions by countries. It is common knowledge that malaria cases that cannot be identified remain untreated. To sustain the gains made in malaria control, we proposed a two-pronged hybrid approach for COVID-19 contact tracing and malaria RACD in communities with COVID-19 and malaria coinfections. Such an approach would equally factor the burden of malaria cases and COVID-19 to support an effective strategy for responding to current and future pandemics.
Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has... more Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore might have lifelong effects on disease risk. To understand maternal vaginal microbiota’s role in seeding the child’s microbiota and the extent of delivery mode-dependent transmission, we studied 665 mother–child dyads from the COPSAC2010 cohort. The maternal vaginal microbiota was evaluated twice in the third trimester and compared with the children’s fecal (at 1 week, 1 month, and 1 year of age) and airway microbiota (at 1 week, 1 month, and 3 months). Based on the concept of weighted transfer ratios (WTRs), we have identified bacterial orders for which the WTR displays patterns indicate persistent or transient transfer from the maternal vaginal microbiome, as well as orders that are shared at later time points independent of delivery mode, indicating a common reservoir.
Early life microbiota has been linked to the development of chronic inflammatory diseases. It has... more Early life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore can have lifelong effects on disease risk. To understand maternal vaginal microbiota’s role in seeding the child’s microbiota and the extent of delivery mode-dependent transmission, we studied 700 mother-child dyads from the COPSAC2010 cohort.The maternal vaginal microbiota was evaluated in the third trimester and compared with the children’s fecal and airway microbiota.The vaginal samples displayed known stable community state types and only 1:6 changed over time. Only one OTU was significantly transferred to children’s fecal compartment, but an inflated number had positive transfer odds. A few taxonomic families showed early transfer enrichment to vaginally-born children, indicating vertical transfer, while half of the observed transfer effects were delivery mode independent enrichm...
Francisella tularensis is a zoonotic bacterium that causes the infection tularemia. It colonises ... more Francisella tularensis is a zoonotic bacterium that causes the infection tularemia. It colonises invertebrates and vertebrates, counting wildlife animals and rodents. Humans can become infected through several pathways including contaminated food, water, handling animals and due to bites from vectors. Ticks are known to cause tularemia in humans, though their role as a disease transferring vector is not well understood. We describe two case reports of tularemia transferred by ticks on Southern Zealand, Denmark.
Background Cases of reported tick-borne diseases in humans have increased over the past decades. ... more Background Cases of reported tick-borne diseases in humans have increased over the past decades. Strategies informing the public about ticks, their associated diseases, and preventive measures are often highlighted as important in limiting pathogen transfer and disease. However, knowledge about the motivation for people to apply preventative measures is sparse. The aim was to examine if Protection Motivation Theory, a model of disease prevention and health promotion, can predict the use of protective measures against ticks. Ordinal logistic regression and Chi-square tests were used on data from a cross-sectional survey with respondents from Denmark, Norway, and Sweden (n = 2658). We examined the effect of (1) the perceived seriousness of tick bites, Lyme borreliosis (LB), and tick-borne encephalitis (TBE), and (2) the perceived probability of getting a tick bite, Lyme borreliosis, and tick-borne encephalitis on protection against ticks. Finally, we examined if there was an association between the use of a protective measure and the perceived efficacy of that measure. The perceived seriousness of a tick bite and LB significantly predict who is more likely to apply protective measures for all three countries combined. The perceived seriousness of TBE did not significantly predict the level of adoption of protective measures applied by respondents. The perceived likelihood of getting a tick bite within the next 12 months and the perceived likelihood of getting LB if bitten by a tick significantly predicted the application of protective measures. However, the increases in the likelihood of protection were very small. The application of a certain type of protection was always correlated with the perceived efficacy of the same protective measure. Conclusion Some variables of PMT may be used to predict the level of adoption of protection applied against ticks and tick-borne diseases. We found that the perceived seriousness of a tick bite and LB significantly predict the level of adoption protection. The perceived likelihood of getting a tick bite or LB also significantly predicted the level of adoption of protection, although the change was very small. The results regarding TBE were less clear. Lastly, there was an association between applying a protective measure and the perceived efficacy of the same measure.
Frontiers in Cellular and Infection Microbiology, Feb 13, 2023
Leptospirosis is a zoonotic bacterial infection that can cause influenza-like symptoms and severe... more Leptospirosis is a zoonotic bacterial infection that can cause influenza-like symptoms and severe disease. In Denmark, leptospirosis is rare, non-endemic, and most commonly transferred to humans from mice and rats. Cases of human leptospirosis in Denmark are by law notifiable to Statens Serum Institut. This study aimed to describe trends in incidence of leptospirosis in Denmark from 2012 to 2021. Descriptive analyses were used to calculate the incidence, geographical distribution and possible routes of infection, as well as testing capacity and serological trends. The overall incidence rate was 0.23 per 100,000 inhabitants, with the highest annual incidence of 24 cases in 2017. Men between 40-49 years old were the demographic group most commonly diagnosed with leptospirosis. August and September were the months with highest incidence over the entire study period. The most common serovar observed was Icterohaemorrhagiae, although over a third of cases were diagnosed via polymerase chain reaction alone. The most common sources of exposure reported were travel abroad, farming, and recreational contact with fresh water, the latter being a new exposure compared to previous studies. Overall, a One Health approach would ensure better detection of outbreaks and milder disease. Additionally, preventative measures should be expanded to include recreational water sports.
The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently ident... more The natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5 -(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 µg/mL).
Hyldig conceived and planned the study, organized the intervention and collection of samples and ... more Hyldig conceived and planned the study, organized the intervention and collection of samples and critically revised the manuscript Dr. Krogfelt and DMSc Greisen conceived and planned the study and critically revised the manuscript. MSc Kamal performed all laboratory analysis, performed bioinformatics and data analysis and drafted the initial manuscript Dr. Krych performed bioinformatics and data analysis. Dr. Nielsen conceived and planned the study, did data analysis and drafted the initial manuscript
Annals of Clinical Microbiology and Antimicrobials, Mar 20, 2023
Background The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe feb... more Background The tick-borne bacterium, Neoehrlichia mikurensis (N. mikurensis) can cause severe febrile illness and thromboembolic complications in immunocompromised individuals. We investigated the presence of N. mikurensis DNA in retrospectively collected plasma from a well-characterized cohort of Danish immunocompromised patients. Methods Plasma samples from 239 patients with immune dysfunction related to hematological or rheumatological disease or due to immunosuppressive therapy, were retrieved from a transdisciplinary biobank (PERSIMUNE) at Rigshospitalet, Copenhagen, Denmark. Serving as immunocompetent controls, plasma samples from 192 blood donors were included. All samples were collected between 2015 and 2019. Real-time PCR targeting the groEL gene was used to detect N. mikurensis DNA. Sequencing was used for confirmation. Borrelia burgdorferi sensu lato IgG antibodies were detected by ELISA as a proxy of tick exposure. Prevalence was compared using Fisher's exact test. Neoehrlichia mikurensis DNA was detected in 3/239 (1.3%, 95% confidence interval (CI): 0.3 -3.6%) patients, all of whom primarily had a hematological disease. Follow-up samples of these patients were negative. N. mikurensis DNA was not detected in any of the blood donor samples. IgG antibodies against B. burgdorferi s.l. were detected with similar prevalence in immunocompromised patients and blood donors, i.e., 18/239 (7.5%, 95% CI: 4.8-11.5%) and 11/192 (5.7%, 95%: CI 3.2-10.0%). In this study, patients with N. mikurensis were not identified by clinical indication and N. mikurensis may therefore be underdiagnosed in Danish patients. Further investigations are needed to explore the clinical significance and implications of this infection.
African Journal of Microbiology Research, Feb 21, 2017
Poultry meat and products are major transmission routes of human campylobacteriosis. The aim of t... more Poultry meat and products are major transmission routes of human campylobacteriosis. The aim of this study was to determine the numbers and antibiogram profile of Campylobacter isolates from slaughtered broiler and layer birds. One hundred and sixty caecal and one hundred and thirty two carcasses were randomly sampled at the Kejetia poultry slaughter, isolated on charcoal-cefoperazonedeoxycholate agar (CCDA) and confirmed by API CAMPY and their resistance profiles assessed by Kirby-Bauer disk diffusion. Prevalence was 22.5 and 21.9% in the faecal and carcasses, respectively with no significant differences. Species identified among faecal isolates were Campylobacter jejuni (42%), Campylobacter coli (28%), Campylobacter lari (22%) and Campylobacter hyo-intestinalis (8%) while 79% C. jejuni, 14% C. coli, 4% C. jejuni sub sp. doylei, and 3% C. lari were obtained from the carcasses. Resistance to the β-lactams ranged from 75 to 100%, 41 to 86% to the quinolones, 14 to 36% to the aminoglycosides, 100% to erythromycin, 97 to 100% to tetracycline, 72 to 83% to chloramphenicol and 90 to 94% to trimethoprim sulfamethoxazole. All species were sensitive to imipenem, but 100% of isolates were multidrug resistant. Contamination of carcasses with multidrug resistant strains of Campylobacter is a threat to handlers and consumers and of major public health issue.
nature publishing group Background: Preterm infants are vulnerable to pathogens and at risk of de... more nature publishing group Background: Preterm infants are vulnerable to pathogens and at risk of developing necrotizing enterocolitis (NEC) or sepsis. Nasogastric feeding tubes (NG-tubes) might contaminate feeds given through them due to biofilm formation. We wanted to determine if there is a rationale in replacing NG-tubes more often to reduce contamination. Methods: We conducted an observational study of used NG-tubes from a tertiary neonatal department. After removal, we flushed a 1-ml saline solution through the tube, determined the density of bacteria by culture, and related it to the duration of use and any probiotic administration through the tube. results: Out of the 94 NG-tubes, 89% yielded more than 1,000 colony-forming units (CFU)/ml bacteria, and 55% yielded the potentially pathogenic Enterobacteriaceae and/or Staphylococcus aureus. The mean concentration in the yield was 5.3 (SD: 2.1, maximum 9.4) log 10 CFU/ml. Neither the presence of contamination nor the density was associated with the time the NG-tube had been in use. Probiotic administration did not protect against contamination. conclusion: NG-tubes yielded high densities of bacteria even within the first day of use. Further studies are needed to determine if changing the NG-tubes between meals or once a day will make a positive impact on tube contamination and clinical parameters.
In vitro and in vivo models were used to investigate the role of capsule on the virulence of Kleb... more In vitro and in vivo models were used to investigate the role of capsule on the virulence of Klebsiella pneumoniae. We showed that capsule expression reduces dramatically the ability of the K. pneumoniae to bind to epithelial cells when compared to its non-capsulated variant. The presence/absence of capsule had no effect on the colonization of the gastrointestinal tract, while in the urinary tract we established that capsule is an important virulence factor. Our study demonstrates the caution needed when extrapolating from results of in vitro studies and emphasizes the necessity of in vivo models in studies of bacterial virulence.
Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had se... more Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had serious economic and social consequences. COVID-19 manifests differently in children than adults, as children usually have a milder course of disease, mild symptoms if any, and lower fatality rates are recorded among children. SARS-CoV-2 transmission also seems to be different between children and adults. Many factors are proposed to explain the milder outcome in children, e.g., a more appropriate immune response (especially active innate response), trained immunity, a lack of immunosenescence, and the reduced prevalence of comorbidities. A better understanding of the differences in susceptibility and outcome in children compared with adults could lead to greater knowledge of risk factors for complicated COVID-19 cases and potential treatment targets. We highlight proposed reasons as to why children are less affected by COVID-19 than adults.
medRxiv (Cold Spring Harbor Laboratory), Apr 10, 2020
Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ... more Due to urgency and demand, numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoassays are rapidly being developed and placed on the market with limited validation on clinical samples. Thorough validation of serological tests are required to facilitate their use in the accurate diagnosis of SARS-CoV-2 infection, confirmation of molecular results, contact tracing, and epidemiological studies. This study evaluated the sensitivity and specificity of nine commercially available serological tests. These included three enzyme-linked immunosorbent assays (ELISAs) and six point-of-care (POC) lateral flow tests. The assays were validated using serum samples from: i) SARS-CoV-2 PCR-positive patients with a documented first day of disease; ii) archived sera obtained from healthy individuals before the emergence of SARS-CoV-2 in China; iii) sera from patients with acute viral respiratory tract infections caused by other coronaviruses or noncoronaviruses; and iv) sera from patients positive for dengue virus, cytomegalovirus and Epstein Barr virus. The results showed 100% specificity for the Wantai SARS-CoV-2 Total Antibody ELISA, 93% for the Euroimmun IgA ELISA, and 96% for the Euroimmun IgG ELISA with sensitivities of 90%, 90%, and 65%, respectively. The overall performance of the POC tests according to manufacturer were in the rank order of AutoBio Diagnostics > Dynamiker Biotechnology = CTK Biotech > Artron Laboratories > Acro Biotech ≥ Hangzhou Alltest Biotech. Overall, these findings will facilitate selection of serological assays for the detection SARS-CoV-2-specific antibodies towards diagnosis as well as sero-epidemiological and vaccine development studies.
The ideal vaccine against viral infections should elicit antibody responses that protect against ... more The ideal vaccine against viral infections should elicit antibody responses that protect against divergent strains. Designing broadly protective vaccines against SARS-CoV-2 and other divergent viruses requires insight into the specific targets of cross-protective antibodies on the viral surface protein(s). However, unlike therapeutic monoclonal antibodies, the B-cell epitopes of vaccine-induced polyclonal antibody responses remain poorly defined. Here we show that, through the combination of neutralizing antibody functional responses with B-cell epitope mapping, it is possible to identify unique antibody targets associated with neutralization breadth. The polyclonal antibody profiles of SARS-CoV-2 index-strain-vaccinated rabbits that demonstrated a low, intermediate, or high neutralization efficiency of different SARS-CoV-2 variants of concern (VOCs) were distinctly different. Animals with an intermediate and high cross-neutralization of VOCs targeted fewer antigenic sites on the sp...
Reactive case detection (RACD) is the screening of household members and neighbors of index cases... more Reactive case detection (RACD) is the screening of household members and neighbors of index cases reported in passive surveillance. This strategy seeks asymptomatic infections and provides treatment to break transmission without testing or treating the entire population. This review discusses and highlights RACD as a recommended strategy for the detection and elimination of asymptomatic malaria as it pertains in different countries. Relevant studies published between January 2010 and September 2022 were identified mainly through PubMed and Google Scholar. Search terms included “malaria and reactive case detection”, “contact tracing”, “focal screening”, “case investigation”, “focal screen and treat”. MedCalc Software was used for data analysis, and the findings from the pooled studies were analyzed using a fixed-effect model. Summary outcomes were then presented using forest plots and tables. Fifty-four (54) studies were systematically reviewed. Of these studies, 7 met the eligibilit...
Coronavirus disease 2019 (COVID-19) contact tracing and malaria reactive case detection (RACD) ar... more Coronavirus disease 2019 (COVID-19) contact tracing and malaria reactive case detection (RACD) are effective strategies for disease control. The emergence of the COVID-19 pandemic and the global attention COVID-19 has received in the recent past and present has hampered malaria control efforts. Among these are difficulties in finding and treating malaria-infected individuals in hypoendemic settings in the community, due to lockdown restrictions by countries. It is common knowledge that malaria cases that cannot be identified remain untreated. To sustain the gains made in malaria control, we proposed a two-pronged hybrid approach for COVID-19 contact tracing and malaria RACD in communities with COVID-19 and malaria coinfections. Such an approach would equally factor the burden of malaria cases and COVID-19 to support an effective strategy for responding to current and future pandemics.
Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has... more Early-life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore might have lifelong effects on disease risk. To understand maternal vaginal microbiota’s role in seeding the child’s microbiota and the extent of delivery mode-dependent transmission, we studied 665 mother–child dyads from the COPSAC2010 cohort. The maternal vaginal microbiota was evaluated twice in the third trimester and compared with the children’s fecal (at 1 week, 1 month, and 1 year of age) and airway microbiota (at 1 week, 1 month, and 3 months). Based on the concept of weighted transfer ratios (WTRs), we have identified bacterial orders for which the WTR displays patterns indicate persistent or transient transfer from the maternal vaginal microbiome, as well as orders that are shared at later time points independent of delivery mode, indicating a common reservoir.
Early life microbiota has been linked to the development of chronic inflammatory diseases. It has... more Early life microbiota has been linked to the development of chronic inflammatory diseases. It has been hypothesized that maternal vaginal microbiota is an important initial seeding source and therefore can have lifelong effects on disease risk. To understand maternal vaginal microbiota’s role in seeding the child’s microbiota and the extent of delivery mode-dependent transmission, we studied 700 mother-child dyads from the COPSAC2010 cohort.The maternal vaginal microbiota was evaluated in the third trimester and compared with the children’s fecal and airway microbiota.The vaginal samples displayed known stable community state types and only 1:6 changed over time. Only one OTU was significantly transferred to children’s fecal compartment, but an inflated number had positive transfer odds. A few taxonomic families showed early transfer enrichment to vaginally-born children, indicating vertical transfer, while half of the observed transfer effects were delivery mode independent enrichm...
Francisella tularensis is a zoonotic bacterium that causes the infection tularemia. It colonises ... more Francisella tularensis is a zoonotic bacterium that causes the infection tularemia. It colonises invertebrates and vertebrates, counting wildlife animals and rodents. Humans can become infected through several pathways including contaminated food, water, handling animals and due to bites from vectors. Ticks are known to cause tularemia in humans, though their role as a disease transferring vector is not well understood. We describe two case reports of tularemia transferred by ticks on Southern Zealand, Denmark.
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Papers by karen krogfelt