Herpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis.

Jacob Bodilsen, Trine Mogensen og Christian Brandt's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Neurotropic herpesviruses may be implicated in the development of dementia. Moreover, vaccines may have important off-target immunological effects. Here we aim to determine the effect of live-attenuated herpes zoster vaccination on the occurrence of dementia diagnoses. To provide causal as opposed to correlational evidence, we take advantage of the fact that, in Wales, eligibility for the zoster vaccine was determined on the basis of an individual's exact date of birth. Those born before 2 September 1933 were ineligible and remained ineligible for life, whereas those born on or after 2 September 1933 were eligible for at least 1 year to receive the vaccine. Using large-scale electronic health record data, we first show that the percentage of adults who received the vaccine increased from 0.01% among patients who were merely 1 week too old to be eligible, to 47.2% among those who were just 1 week younger. Apart from this large difference in the probability of ever receiving the zoster vaccine, individuals born just 1 week before 2 September 1933 are unlikely to differ systematically from those born 1 week later. Using these comparison groups in a regression discontinuity design, we show that receiving the zoster vaccine reduced the probability of a new dementia diagnosis over a follow-up period of 7 years by 3.5 percentage points (95% confidence interval (CI) = 0.6-7.1, P = 0.019), corresponding to a 20.0% (95% CI = 6.5-33.4) relative reduction. This protective effect was stronger among women than men. We successfully confirm our findings in a different population (England and Wales's combined population), with a different type of data (death certificates) and using an outcome (deaths with dementia as primary cause) that is closely related to dementia, but less reliant on a timely diagnosis of dementia by the healthcare system. Through the use of a unique natural experiment, this study provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence.

Professor Lars Østergaard's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Refugees and asylum seekers might have an increased risk of antimicrobial resistance (AMR) carriage or infection due to several factors, with conflict and war known to accelerate the spread of AMR. However, data are scarce on prevalence and risk factors for AMR among refugees and asylum seekers and how they are affected globally; in addition, how their risk compares to that of the host-country population is unclear. We aimed to explore and assess global AMR data among refugees and asylum seekers. Ovid (MEDLINE and Embase) and PubMed were searched for peer-reviewed primary research articles from Jan 1, 2015, to Oct 23, 2023, and articles were included if they reported carriage or infection with laboratory-confirmed drug-resistant organisms in refugees or asylum seekers from any country. Of 884 articles identified, 41 reported prevalence of AMR among 16 970 refugees and asylum seekers and were included in the study. The most common phenotypes reported were multidrug-resistant Gram-negative bacteria (n=26; prevalence ranged from 4·2% to 60·8%), methicillin-resistant Staphylococcus aureus (n=24; 0·92% to 73%), and extended-spectrum β-lactamase-producing Gram-negative bacteria (n=20; 1·6% to 61·1%). Refugees and asylum seekers had a higher likelihood of carriage or infection with any AMR than the host-country population (n=7849 vs n=81 283, respectively; odds ratio 2·88, 95% CI 2·61-3·18; I=94%). Refugees and asylum seekers are at an increased risk of AMR carriage and infection, with our data suggesting that refugees and asylum seekers might be exposed to conditions that support the emergence of drug resistance (including living in overcrowded camps and facing barriers to health and vaccine systems). Hence, more global and regional data on AMR are needed through strengthened surveillance programmes and health-care facilities, especially in low-income and middle-income countries. Increased efforts are needed to drive improvements in infection prevention and control (including vaccination), antimicrobial stewardship, treatment strategies tailored to groups at high risk, accessiblity to quality health care in these populations at risk globally, and address risk factors such as poor living and transit conditions.

Professor Marie Nørredam's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

Professor Isik Somuncu Johansen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Professor Lars Østergaard's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

To determine the yield of screening for latent tuberculosis infection (LTBI) among people with HIV (PWH) in low tuberculosis (TB) incidence countries (<10 TB cases per 100 000 persons).

Professor Troels Lillebæk's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear.

Professor Lars Østergaard's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

The bacille Calmette-Guérin (BCG) vaccine has immunomodulatory "off-target" effects that have been hypothesized to protect against coronavirus disease 2019 (Covid-19).

Professor Niels Obel's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis.

Professor Troels Lillebæk's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Professor Nina Weis's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Given the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces 'adjuvant-imprinted' qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.

Professor Troels Lillebæk's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

The bedaquiline-pretomanid-linezolid regimen has been reported to have 90% efficacy against highly drug-resistant tuberculosis, but the incidence of adverse events with 1200 mg of linezolid daily has been high. The appropriate dose of linezolid and duration of treatment with this agent to minimize toxic effects while maintaining efficacy against highly drug-resistant tuberculosis are unclear.

Professor Troels Lillebæk's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Nirmatrelvir is an orally administered severe acute respiratory syndrome coronavirus 2 main protease (M) inhibitor with potent pan-human-coronavirus activity in vitro.

Professor Jens Lundgren's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing future zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports, but later this conclusion became controversial. We show here that the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2-susceptible mammals were sold at the market in late 2019 and that within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. Although there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred through the live wildlife trade in China and show that the Huanan market was the epicenter of the COVID-19 pandemic.

Professor Jens Lundgren's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.

Professor Henrik Nielsen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries.

Professor Jens Lundgren's kommentar til artiklen:

In 1999, the World Health Organization (WHO) estimated that one-third of the world's population had latent tuberculosis infection (LTBI), which was recently updated to one-fourth. However, this is still based on controversial assumptions in combination with tuberculin skin test (TST) surveys. Interferon-γ release assays (IGRAs) with a higher specificity than TST have since been widely implemented, but never used to estimate the global LTBI prevalence.We conducted a systematic review and meta-analysis of LTBI estimates based on both IGRA and TST results published between 2005 and 2018. Regional and global estimates of LTBI prevalence were calculated. Stratification was performed for low, intermediate and high TB incidence countries and a pooled estimate for each area was calculated using a random effects model.Among 3280 studies screened, we included 88 studies from 36 countries with 41 IGRA (n=67 167) and 67 TST estimates (n=284 644). The global prevalence of LTBI was 24.8% (95% CI 19.7-30.0%) and 21.2% (95% CI 17.9-24.4%), based on IGRA and a 10-mm TST cut-off, respectively. The prevalence estimates correlated well to WHO incidence rates (Rs=0.70, p<0.001).In the first study of the global prevalence of LTBI derived from both IGRA and TST surveys, we found that one-fourth of the world's population is infected. This is of relevance, as both tests, although imperfect, are used to identify individuals eligible for preventive therapy. Enhanced efforts are needed targeting the large pool of latently infected individuals, as this constitutes an enormous source of potential active tuberculosis.

Professor Troels Lillebæk's kommentar til artiklen:

To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes).

Professor Lars Østergaard's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication.

Professor Thomas Benfield's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.

Professor Niels Obel's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

The optimal duration of antibiotic treatment for community-acquired pneumonia (CAP) has not been well established.

Professor Thomas Benfield's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Professor Morten Sodemann's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Previous studies have shown that statins use is associated with a lower mortality risk or occurrence of non-Hodgkin's lymphoma or non-AIDS-defining malignancies (NADMs) in HIV-positive patients. We evaluated the effect of statin therapy on the occurrence of all AIDS-defining malignancy (ADM) and NADM among HIV-positive patients.

Professor Niels Obel's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Tuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.

Professorerne Åse Bengaard Andersen og Isik Somuncu Johansen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Animal sociality facilitates the transmission of pathogenic microorganisms among hosts, but the extent to which sociality enables animals' beneficial microbial associations is poorly understood. The question is critical because microbial communities, particularly those in the gut, are key regulators of host health. We show evidence that chimpanzee social interactions propagate microbial diversity in the gut microbiome both within and between host generations. Frequent social interaction promotes species richness within individual microbiomes as well as homogeneity among the gut community memberships of different chimpanzees. Sampling successive generations across multiple chimpanzee families suggests that infants inherited gut microorganisms primarily through social transmission. These results indicate that social behavior generates a pan-microbiome, preserving microbial diversity across evolutionary time scales and contributing to the evolution of host species-specific gut microbial communities.

Professor Lars Østergaard's kommentar til artiklen:

There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

Professor Jens Lundgren's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.

Professor Henrik Nielsen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Duration of treatment for patients with vertebral osteomyelitis is mainly based on expert recommendation rather than evidence. We aimed to establish whether 6 weeks of antibiotic treatment is non-inferior to 12 weeks in patients with pyogenic vertebral osteomyelitis.

Professor Thomas Benfield's kommentar til artiklen:

Activating the expression of latent virus is an approach that might form part of an HIV cure. We assessed the ability of the histone deacetylase inhibitor panobinostat to disrupt HIV-1 latency and the safety of this strategy.

Professor Lars Østergaard's kommentar til artiklen:

We conducted a retrospective cohort study of patients with MRC grade II/III tuberculous meningitis (TBM) who accepted a background antitubercular regimen (BR) with or without linezolid (LZD). At the 4th week, the LZD-BR group achieved a faster and higher percentage of Glasgow coma scale recovery and temperature recovery, a higher cerebrospinal fluid (CSF)/blood glucose ratio, and lower CSF white blood cell counts than did the BR group. Short-term linezolid supplementation may be a more effective treatment for life-threatening TBM.

Professor Åse Bengaard Andersen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

Professor Jens Lundgren's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.

Professor Henrik Nielsen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Interferon-based treatment is not suitable for many patients with hepatitis C virus (HCV) infection because of contraindications such as psychiatric illness, and a high burden of adverse events. We assessed the efficacy and safety of an interferon-free regimen--a fixed-dose combination of the nucleotide polymerase inhibitor sofosbuvir (400 mg) and the HCV NS5A inhibitor ledipasvir (90 mg), with and without ribavirin--in patients with genotype-1 hepatitis C infection who were treatment-naive or previously treated with a protease-inhibitor regimen.

Professor Henrik Nielsen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Professor Court Petersen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy.

Professor Peter Skinhøj's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Antiretroviral drugs that inhibit viral replication were expected to reduce transmission of HIV by lowering the concentration of HIV in the genital tract. In 11 of 13 observational studies, antiretroviral therapy (ART) provided to an HIV-infected index case led to greatly reduced transmission of HIV to a sexual partner. In the HPTN 052 randomised controlled trial, ART used in combination with condoms and counselling reduced HIV transmission by 96·4%. Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV. However, the full benefits of this strategy will probably need universal access to very early ART and excellent adherence to treatment. Challenges to this approach are substantial. First, not all HIV-infected individuals can be located, especially people with acute and early infection who are most contagious. Second, the ability of ART to prevent HIV transmission in men who have sex with men (MSM) and people who use intravenous drugs has not been shown. Indeed, the stable or increased incidence of HIV in MSM in some communities where widespread use of ART has been established emphasises the concern that not enough is known about treatment as prevention for this crucial population. Third, although US guidelines call for immediate use of ART, such guidelines have not been embraced worldwide. Some experts do not believe that immediate or early ART is justified by present evidence, or that health-care infrastructure for this approach is sufficient. These concerns are very difficult to resolve. Ongoing community-based prospective trials of early ART are likely to help to establish the population-level benefit of ART, and-if successful-to galvanise treatment as prevention.

Professor Jens Lundgren's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.

Professor Åse Bengaard Andersen's kommentar til artiklen:

Login og få direkte adgang til hele artiklen!
Endnu ikke oprettet? Klik her.
Glemt password? Klik her.