Pre-exposure prophylaxis against HIV infection.

Pre-exposure prophylaxis (PrEP) decreases the risk for HIV transmission in high-risk populations. PrEP has been available in Denmark since 2019 and consists of antiretroviral drugs in a combination tablet taken daily or on demand. The effect of this prophylaxis in Denmark is summarized in the review. PrEP is indicated in men and transgender persons with unprotected anal intercourse with multiple male partners in the latest 12 weeks or recent diagnoses of syphilis, chlamydia, or gonorrhoea. PrEP is provided by infectious disease specialists. Continued implementation could significantly reduce HIV transmission and potentially end the epidemic in Denmark.

Prospective screening for monkeypox infection among users of HIV pre-exposure prophylaxis in Denmark.

INTRODUCTION: During the 2022 outbreak of mpox (previously called monkeypox), which primarily affected Gay, Bisexual, and other Men who have Sex with Men (GBMSM), testing was mainly limited to individuals with symptoms of infection. Although sporadic cases of mpox continue to be diagnosed in Denmark, the feasibility of screening asymptomatic high-risk populations, such as those using HIV pre-exposure prophylaxis (PrEP), is still unknown. METHODS: During the autumn of 2022, a rectal swab test for mpox PCR was included in the routine sexually transmitted infections (STI) screening for PrEP users. RESULTS: The screening included 224 asymptomatic men with a median age of 36.5 years. One patient (0.4%) tested positive for mpox. Ten (4.5%) and nine (4.0%) had chlamydia and gonorrhea, respectively. DISCUSSION: Our study demonstrates that screening for mpox is feasible in two Danish PrEP clinics.

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.

[Atypical mycocutaneous manifestation of Leishmania tropica in a refugee].

In this case report a male 19-year-old Syrian refugee presented with a sore throat. A biopsy from larynx detected Leishmania tropica compatible with leishmaniasis, although L. tropica does not normally cause mucosal leishmaniasis (CL). An immunodeficiency was detected, and the patient was treated for hypogammaglobulinaemia and CL three times, before the symptoms disappeared. Leishmaniasis is a disease, which should be taken into consideration, when refugees present with atypical clinical manifestations, especially in immunosuppressed patients.

Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era. METHODS: A nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995-2014 was included in this study. RESULTS: Among 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05-0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00-4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10-50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity. CONCLUSION: The incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.

Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era.

BACKGROUND: HIV-associated incidence and prognosis of cerebral toxoplasmosis (CTX) is not well established during later years. METHODS: From the Danish HIV Cohort Study, we identified 6325 HIV-infected individuals. We assessed incidence, mortality, predictive and prognostic factors of CTX during the pre-combination antiretroviral therapy (pre-cART; 1995-1996) and cART-era (1997-2014). Adjusted incidence rate ratios (aIRR), mortality rate ratios (aMRR) and 95% confidence intervals (CI) were assessed using Poisson regression analysis. RESULTS: CTX IR was 1.17/1000 PYR (95% CI 0.93-1.47). We observed no change in CTX-risk in the first year after HIV-diagnosis, but a substantial reduction in mortality in the first 3 months after CTX diagnosis when comparing the cART-era to the pre-cART-era; {(aIRR: 0.79; 95% CI: 0.37-1.72) (aMRR: 0.15; 95% CI: 0.06-0.38)}. For individuals surviving the first year after HIV-diagnosis or the first 3 months after CTX-diagnosis, IRR and MRR had declined to minimal levels {(aIRR: 0.06; 95% CI: 0.03-0.10); (aMRR: 0.02; 95% CI: 0.01-0.05)}. Three years after CTX-diagnosis 30% of the patients still had neurological deficits. CONCLUSION: Although, CTX remains an important cause of morbidity and mortality in the cART-era, with high prevalence of neurological sequelae, incidence and mortality has largely declined, especially among those surviving the first year after diagnosis.

[Progressive multifocal leukoencephalopathy in a patient with multiple myeloma].

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease in the central nervous system. It is caused by reactivation of John Cunningham-virus and has a grave prognosis. PML occurs most frequently in HIV-patients, but can also be seen in patients with iatrogenic immunodeficiency. Here, we present a patient with multiple myeloma and cardiac amyloidosis who developed PML after receiving treatment with several chemotherapeutics. This case report underlines the importance of bearing PML in mind when immunocompromised patients develop diffuse neurological symptoms.

Mumps resurgence in Denmark.

BACKGROUND: The past decade has witnessed a resurgence of parotitisvirus (mumps) in several countries where seemingly good mumps control otherwise had been achieved through vaccination. Recently detection of mumps has increased in Denmark. OBJECTIVES: To describe the age-specific changes and time trends of parotitisvirus detection in Denmark over a 10 year period. STUDY DESIGN: Retrospective cohort study based on national laboratory data for parotitisvirus typing surveillance and national epidemiology data for mumps reporting. RESULTS: The parotitisvirus detection rate has increased almost 10 times during the past 10 years from an incidence <0.1 per 100,000 in 2003 to 0.96 per 100,000 in 2013. The age distribution has shifted from children to young adults, and most cases are unvaccinated (54%) or vaccinated once (41%). The increase is due mainly to the existence of cohorts with low MMR vaccine coverage. CONCLUSION: Analysis of mumps surveillance data from Denmark documents that the incidence of mumps is increasing, and that the resurgence of parotitisvirus is primarily occurring among young Danish adults. Almost half of the infected clinical mumps cases had received the first dose of MMR.

Long-term mortality in patients diagnosed with Listeria monocytogenes meningitis: a Danish nationwide cohort study.

OBJECTIVES: To determine the long-term mortality, the causes of death and the incidence of cancer in listeria meningitis patients. METHODS: Nationwide, population-based cohort study including all adult patients diagnosed with listeria meningitis from 1977 to 2006 and alive 1 year after diagnosis, and an age-and gender-matched, population control cohort. Kaplan-Meier tables, Cox regression analysis and cumulative incidence function were used as outcome analyses. RESULTS: We identified 114 listeria meningitis patients and 1026 population controls. The adjusted mortality rate ratio (MRR) for listeria meningitis patients the first 5 years of follow-up was 2.35(95% confidence interval (CI) 1.60-3.45) thereafter the MRR was 0.93(95% CI: 0.56-1.55). Listeria meningitis patients had an increased risk of death due to cancer the first 5 years of follow-up, and in the same period patients above 50 years of age had a 2-fold increased risk of being diagnosed with cancer, thereafter the risks declined to that of the background population. CONCLUSIONS: The long-term mortality in adult patients diagnosed with listeria meningitis was increased the first 5 years of follow-up, mainly due to death from cancer, thereafter the mortality did not differ from the background population. To improve survival this patient population should be meticulously screened for predisposing conditions, mainly underlying malignant diseases.

Long-term mortality in children diagnosed with Haemophilus influenzae meningitis: a Danish nationwide cohort study.

BACKGROUND: The long-term mortality in children diagnosed with Haemophilus influenzae meningitis is poorly documented. METHODS: We performed a nationwide, population-based cohort study including all Danish children diagnosed at the age between 0 and <5 years with H. influenzae meningitis from 1977 through 1996 and who were alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. For each H. influenzae meningitis patient, 6 age- and gender-matched population controls were indentified. We constructed Kaplan-Meier survival curves and used Cox regression analysis to estimate mortality rate ratios (MRR) and analyze causes of death. The risk of inpatient admission and of requiring hospital outpatient services during follow-up was calculated. RESULTS: We identified 1242 H. influenzae meningitis patients and 7452 population controls, with a median follow-up time of 21.3 years. The MRR for patients with H. influenzae meningitis was 1.08 (95% confidence interval, 0.57-2.05), adjusted MRR was 0.97 (95% confidence interval, 0.50-1.89). No increased mortality due to infections, respiratory diseases, or cancer was observed. The overall risk of inpatient admission and of requiring hospital outpatient services for the H. influenzae meningitis patients was increased the first 15 years of follow-up, mainly due to the nervous system diseases and ear diseases, thereafter the risk decreased to that of the population controls. CONCLUSIONS: In a developed country, children younger than 5 years surviving the acute phase of H. influenzae meningitis have no increased long-term mortality and only moderately increased morbidity.

Incidence and impact on mortality of severe neurocognitive disorders in persons with and without HIV infection: a Danish nationwide cohort study.

OBJECTIVE: The risk of neurocognitive disorders in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART) is controversial. We aimed to compare the incidence and impact on mortality of severe neurocognitive disorders (SNCDs) in HIV-infected patients with that of the background population. METHODS: The method used was a nationwide, population-based cohort study using Danish registries. We calculated incidence rates, incidence rate ratios, mortality rate ratios, and Kaplan-Meier tables to estimate the incidence of and survival after SNCD in HIV-infected patients, compared with a general population control cohort matched by age and sex. RESULTS: We observed 32 cases of SNCDs among 4452 HIV-infected patients and 120 cases of SNCDs among 62 328 population control subjects. The overall risk of SNCD among HIV-infected patients was 1.0 case per 1000 person-years (PYR), compared with 0.23 cases per 1000 PYR for population control subjects but became 0.35 cases/1000 PYR after 2004, compared with 0.27 cases/1000 PYR in population control subjects. The absence of HAART and a low CD4 lymphocyte count increased the risk of SNCD. The mortality among HIV-infected patients with SNCD was higher than that among population controls with SNCD (median survival, 4.3 years vs 9.7 years [P = .02]). CONCLUSION: HIV-infected patients have an increased risk of SNCD, but the risk is low and has, in recent years, become comparable to that seen in the background population. In contrast, the mortality remains high among HIV-infected patients diagnosed with SNCD.

Long-term mortality in patients diagnosed with pneumococcal meningitis: a Danish nationwide cohort study.

The objective of the study was to determine the long-term mortality and the causes of death in patients diagnosed with pneumococcal meningitis. The authors performed a nationwide, population-based cohort study including all Danish patients diagnosed with pneumococcal meningitis from 1977 through 2006 and alive 1 year after diagnosis. Data were retrieved from medical databases in Denmark. The absolute and relative risks of all-cause and cause-specific death were analyzed by using Kaplan-Meier survival curves, Poisson regression analysis, Cox regression analysis, and cumulative incidence functions. The authors identified 2,131 pneumococcal meningitis patients and an age- and gender-matched, population-based cohort of 8,524 individuals. Compared with the background population, the pneumococcal meningitis patients had an increased long-term mortality varying from an 8-fold increased mortality in the age category 0-<20 years to a 1.5-fold increased mortality in those aged 60-<80 years. The increased risk of death stemmed from neoplasms, liver diseases, and nervous system diseases. The excess mortality due to neoplasms stemmed mainly from a 5-fold increased risk of death due to hematologic neoplasms. To improve survival in patients surviving the acute phase of pneumococcal meningitis, physicians should meticulously screen this patient population for neurologic sequelae and comorbidity predisposing to the disease.

Long-term mortality in patients diagnosed with meningococcal disease: a Danish nationwide cohort study.

BACKGROUND: In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented. METHODOLOGY/PRINCIPAL FINDINGS: We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95% confidence interval (CI), 1.12-1.45), adjusted MRR, 1.21 (95% CI, 1.06-1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95% CI, 1.82-7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95% CI, 0.92-1.48). CONCLUSIONS: Patients surviving the acute phase of MD have increased long-term mortality, but the excess risk of death is small and stems mainly from nervous system diseases.

Inpatient admissions and outpatient visits in persons with and without HIV infection in Denmark, 1995-2007.

OBJECTIVE: HAART has changed morbidity and mortality in the HIV-infected population dramatically. We aimed to estimate the use of healthcare facilities in HIV-infected patients after the introduction of HAART. DESIGN: This is a prospective nationwide cohort study. METHODS: We identified all Danish HIV patients and a cohort of population controls matched on sex and date of birth. The study period was 1995-2007. We calculated inpatient admission rates and outpatient visit rates stratified by medical speciality and International Classification of Diseases-10 diagnose categories. Relative risks were computed. RESULTS: Four thousand, seven hundred and sixty HIV-infected patients and 23 800 population controls were identified. Overall inpatient admission rates [95% confidence interval (CI)] for HIV-infected patients decreased from 90 (88-93) to 57 (56-58)/100 person-years in the study period. The risk ratio (95% CI) fell from 6.2 (6.0-6.5) to 3.1 (3.1-3.2) predominantly due to reduced inpatient admission rates to departments of infectious diseases. The overall outpatient visit rates (95% CI) for the HIV-infected patients increased from 744 (737-751) to 877 (872-882)/100 person-years, mainly due to visits at departments other than infectious diseases. A marked increase in outpatient visit rates (95% CI) in the background population decreased the risk ratio from 16.5 (16.2-16.8) to 7.1 (7.0-7.2). We observed a decreased relative risk of inpatient admissions and outpatient visits due to cancers and a small increase in relative risk due to cardiovascular disease. CONCLUSION: After the introduction of HAART, the inpatient treatment of HIV-infected patients has decreased, especially at departments of infectious disease. In contrast, this population's use of outpatient facilities has increased in noninfectious disease specialities.

Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995-1996) and during the early HAART (1997-1999) and late HAART (2000-2006) periods. METHODS: Patients from a nationwide population-based cohort of adult HIV-1-infected individuals were included. We calculated incidence rates of PML and median survival times after diagnosis. We also described neurological symptoms at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence interval [CI], 0.0-0.7) in 1995-1996 and 1.8 years (95% CI, 0.6-3.0) in both 1997-1999 and 2000-2006. CD4(+) cell count >50 cells/microL at diagnosis of PML was significantly associated with reduced mortality. CONCLUSIONS: The incidence of PML in HIV-infected patients decreased after the introduction of HAART. Survival after PML remains poor. In the management of PML, the main focus should be on prophylactic measures to avoid immunodeficiency.

Extreme neutrophil granulocytosis in a patient with anaplastic large cell lymphoma of T-cell lineage.

We describe a 47-year-old male admitted with fever and extreme neutrophil granulocytosis (up to 80 x 10(9)/L). All microbiology tests and test for autoimmune disease were negative. CT scan showed pulmonary infiltrates bilaterally, mediastinal lymphadenopathy and splenomegaly. Conventional pathological examination of bone marrow and lymph node biopsies did not demonstrate malignant cells and inflammatory disease was suspected. The patient died of multiorgan failure 23 days after admission. Autopsy showed neutrophil infiltration of several organs. Immunohistochemistry and cytogenetics postmortem led to a diagnosis of anaplastic large cell lymphoma (ALCL) of T-cell lineage. Involvement of peripheral blood with leukemoid reaction is a rare manifestation of ALCL. This case emphasizes the importance of immunophenotyping in unexplained extreme granulocytosis.