Key questions in COVID-19 are the duration and determinants of infectious virus shedding. Here, we report that infectious virus shedding is detected by virus cultures in 23 of the 129 patients ...(17.8%) hospitalized with COVID-19. The median duration of shedding infectious virus is 8 days post onset of symptoms (IQR 5-11) and drops below 5% after 15.2 days post onset of symptoms (95% confidence interval (CI) 13.4-17.2). Multivariate analyses identify viral loads above 7 log
RNA copies/mL (odds ratio OR of 14.7 (CI 3.57-58.1; p < 0.001) as independently associated with isolation of infectious SARS-CoV-2 from the respiratory tract. A serum neutralizing antibody titre of at least 1:20 (OR of 0.01 (CI 0.003-0.08; p < 0.001) is independently associated with non-infectious SARS-CoV-2. We conclude that quantitative viral RNA load assays and serological assays could be used in test-based strategies to discontinue or de-escalate infection prevention and control precautions.
To assess predictors and reported treatment strategies of HIV-related fatigue in the combined antiretroviral (cART) era.
Five databases were searched and reference lists of pertinent articles were ...checked. Studies published since 1996 on predictors or therapy of HIV-related fatigue measured by a validated instrument were selected.
A total of 42 studies met the inclusion criteria. The reported HIV-related fatigue prevalence in the selected studies varied from 33 to 88%. The strongest predictors for sociodemographic variables were unemployment and inadequate income. Concerning HIV-associated factors, the use of cART was the strongest predictor. Comorbidity and sleeping difficulties were important factors when assessing physiological influences. Laboratory parameters were not predictive of fatigue. The strongest and most uniform associations were observed between fatigue and psychological factors such as depression and anxiety. Reported therapeutic interventions for HIV-related fatigue include testosterone, psycho-stimulants (dextroamphetamine, methylphenidate hydrochloride, pemoline, modafinil), dehydroepiandrosterone, fluoxetine and cognitive behavioural or relaxation therapy.
HIV-related fatigue has a high prevalence and is strongly associated with psychological factors such as depression and anxiety. A validated instrument should be used to measure intensity and consequences of fatigue in HIV-infected individuals. In the case of fatigue, clinicians should not only search for physical mechanisms, but should question depression and anxiety in detail. There is a need for intervention studies comparing the effect of medication (antidepressants, anxiolytics) and behavioural interventions (cognitive-behavioural therapy, relaxation therapy, graded exercise therapy) to direct the best treatment strategy. Treatment of HIV-related fatigue is important in the care for HIV-infected patients and requires a multidisciplinary approach.
We assessed the value of screening for cognitive abnormalities in a chronically infected HIV population (N = 388) and investigated the association with clinical correlates. The mean age was 48 years ...(±11), the majority of the patients were male (89%), the median duration of infection was 6 years interquartile range (IQR) = 2-12, the median CD count was 600 (IQR = 450-780), and 326 (84%) had a viral load below 200 copies/mL. Screening for cognitive complaints was applied using the three Simioni questions and the international HIV dementia scale (iHDS). Neuropsychological assessment (NPA) included 13 well-validated tests assessing motor speed, concentration, and memory. A total of 69 patients completed the NPA. CD4 (nadir), viral load, combination antiretroviral therapy (cART) duration, and the presence of comorbidities were evaluated for associations with NPA result. A total of 127 (33%) reported cognitive complaints during screening. The sensitivity and specificity of the Simioni questions were 82% and 24%, respectively. Adding the iHDS resulted in a sensitivity of 50% and a specificity of 73%. A CD4 nadir count <50 cells/m
was associated with an abnormal NPA (p = 0.01). Comorbidities were more prevalent in patients with an abnormal NPA, although not statistically significant (p = 0.276). Age, current CD4, viral load, and cART duration were not associated with abnormal NPA. The authors conclude that current screening strategies are insufficient in detecting HIV-associated neurocognitive disorder. A low CD4 nadir is associated with poor neurocognitive outcome in HIV.
An increased incidence of venous thromboembolism (VTE) is observed in human immunodeficiency virus (HIV)-infected patients. Only a limited number of studies described the effect of combined ...antiretroviral therapy (cART) on coagulation markers. In a prospective cohort study in cART-naive South African HIV-infected individuals the effect of initiating cART on markers of endothelial cell activation, coagulation and natural anticoagulation was studied. These markers were compared to the reference ranges for an HIV-uninfected control population recruited from hospital staff. A venous ultrasound of both legs was performed to detect asymptomatic deep venous thrombosis (DVT). A total number of 123 HIV-infected participants were included. The patients were predominantly black and severely immuno-compromised. The CD4 cell count increased and the HIV viral load decreased significantly after the initiation of cART (p<0.001). The median follow-up period was 7.2 (± 1.6) months. Laboratory testing before and after initiation of cART was completed by 86 patients. Before initiating cART significantly elevated von Willebrand factor and D-dimer levels, increased activated protein C sensitivity ratio (APCsr) and decreased total and free protein S and protein C levels were observed compared to HIV-negative controls. At follow-up all markers, except APCsr, improved towards the normal range for controls without showing complete normalisation. In a subgroup of 57 patients no asymptomatic DVT was found. Compared to the controls, abnormal levels of coagulation markers were observed in HIV-infected individuals before and after the initiation of cART. Most markers improved after starting cART, but remained significantly different from the controls, indicating a persistent disturbed haemostatic balance.
Healthy eyes and good vision are important determinants of populations' health across the globe. Sub‐Saharan Africa is affected by simultaneous epidemics of ocular infections and human ...immunodeficiency virus (HIV). Ocular infection and its complications, along with cataract and ocular trauma, are common conditions in this region with great impact on daily life. In this review, we discuss the epidemiology, clinical manifestations and microbial aetiology of the most important infectious ocular conditions in sub‐Saharan Africa: conjunctivitis, keratitis and uveitis. We focus specifically on the potential association of these infections with HIV infection, including immune recovery uveitis. Finally, challenges and opportunities for clinical management are discussed, and recommendations made to improve care in this neglected but very important clinical field.
La santé des yeux et une bonne vision sont des déterminants importants de la santé des populations à travers le monde. L'Afrique subsaharienne est affectée par des épidémies simultanées d'infections oculaires et du virus de l'immunodéficience humaine (VIH). L'infection oculaire et de ses complications, ainsi que la cataracte et le traumatisme oculaire sont des affections courantes dans cette région avec un grand impact sur la vie quotidienne. Dans cette revue, nous discutons de l’épidémiologie, des manifestations cliniques et de l’étiologie microbienne des plus importantes maladies oculaires infectieuses en Afrique subsaharienne: la conjonctivite, la kératite et l'uvéite. Nous nous focalisons particulièrement sur l'association potentielle entre ces infections et l'infection à VIH, y compris l'uvéite de reconstitution immunitaire. Enfin, les défis et les opportunités pour la prise en charge clinique sont discutés et des recommandations sont formulées pour améliorer les soins dans ce domaine clinique négligé et pourtant très important.
Unos ojos sanos y una buena visión son determinantes importantes de la salud de la población mundial. África subsahariana está afectada por una epidemia simultánea de infecciones oculares y del virus de inmunodeficiencia humana (VIH). La infección ocular y sus complicaciones, junto con las cataratas y el trauma ocular son condiciones comunes en esta región, y tienen un gran impacto en la vida diaria. En esta revisión, discutimos la epidemiología, manifestaciones clínicas y etiología microbiológica de las principales condiciones infecciosas en África subsahariana: conjuntivitis, queratitis y uveítis. Se enfatiza especialmente sobre la posible asociación entre estas infecciones y la infección por VIH, incluyendo la uveítis por reconstitución inmune. Finalmente, se discuten los retos y las oportunidades para su manejo clínico, y se hacen recomendaciones para mejorar los cuidados en esta área clínica desatendida, pero tan importante.
Background: In 2015–2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid ...waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. Methods: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. Results: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. Conclusions: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.
Several case reports have described hypopituitarism following orthohantavirus infection, mostly following Puumala virus. The pathogenesis of this seemingly rare complication of orthohantavirus ...infection remains unknown. This review explores the possible pathophysiological mechanisms of pituitary damage due to orthohantavirus infection. In only three out of the 28 reported cases, hypopituitarism was detected during active infection. In the remaining cases, detection of pituitary damage was delayed, varying from two months up to thirteen months post-infection. In these cases, hypopituitarism remained undetected during the acute phase of infection or only occurred weeks to months post infection. Both ischemic and hemorrhagic damage of the pituitary gland have been detected in radiographic imaging and post-mortem studies in the studied case reports series. Ischemic damage could be caused by hypotension and/or vasospasms during the acute phase of hemorrhagic fever with renal syndrome (HFRS) while hemorrhage could be caused by thrombocytopenia, thrombopathy, and other known causes of coagulation disorders during orthohantavirus infection. Also, hypophysitis due to the presence of auto-antibodies have been suggested in the literature. In conclusion, a significant number of case reports and series describe hypopituitarism after orthohantavirus infection. In most cases hypopituitarism was diagnosed with a delay and therefore could very well be underreported. Clinicians should be aware of this potential endocrine complication, with substantial morbidity, and if unrecognized, significant mortality.
Objectives
Since HIV has become a manageable chronic disease, employment is of increasing importance for people living with HIV (PLWH). This study aimed to investigate the level of work participation ...among PLWH in the Netherlands, and the associated determinants of employment.
Methods
For this study the baseline measurements of a longitudinal cohort study with a 2-year follow-up, the TREVI project, were used. The TREVI project aims to study cognitive function disorders among PLWH in relation to their employment, productivity, and social functioning. From December 2012 until December 2013, data on cognitive functioning, measured by the HIV Dementia Scale, and medical data derived from patient records were collected. Employment status and possible determinants of employment were assessed by a digital survey. Chi square analysis and multivariate logistic regression analysis were conducted in order to investigate the level of employment and associated determinants of employment.
Results
This cross-sectional study revealed significant differences in the level of employment compared with Dutch reference data: i.e. in the age group 40–54 years PLWH had a significantly lower employment rate than the general Dutch population. Multivariate analysis showed that employment was negatively associated with a lower or higher age (reference: 40–54 years), a longer period since diagnosis, problems with physical functioning, and a higher score on the HADS Depression. Having paid work at diagnosis was positively associated with employment.
Conclusion
PLWH, particularly in the age of 40–54, in the Netherlands have a significant lower level of employment compared to the general population. Counseling should address reduced psychological and physical functioning in order to improve the position of PLWH on the labor market.
Leptospirosis is a global zoonotic disease. Although important for the assessment of the burden of leptospirosis, data on the duration of the illness and the occurrence of post-leptospirosis ...complaints are not well documented. Hence the main objective of this study was to estimate the occurrence of persistent complaints and duration of hospital stay in laboratory confirmed leptospirosis patients in the Netherlands during 1985 to 2010. Additionally, several risk factors potentially impacting on the occurrence of post-leptospirosis complaints were investigated.
The duration of the acute phase of leptospirosis was 16 days (IQR 12-23); 10 days (IQR 7-16) were spent hospitalized. Eighteen fatal cases were excluded from this analysis. Complaints of leptospirosis patients by passive case investigations (CPC) derived from files on ambulant consultations occurring one month after hospital discharge, revealed persistent complaints in 108 of 236 (45.8%) laboratory confirmed cases. Data on persistent complaints after acute leptospirosis (PCAC), assessed in 225 laboratory confirmed leptospirosis cases collected through questionnaires during 1985-1993, indicated 68 (30.2%) PCAC cases. Frequently reported complaints included (extreme) fatigue, myalgia, malaise, headache, and a weak physical condition. These complaints prolonged in 21.1% of the cases beyond 24 months after onset of disease. There was no association between post-leptospirosis complaints and hospitalization. However, individuals admitted at the intensive care unit (ICU) were twice as likely to have continuing complaints after discharge adjusting for age and dialysis (OR 2.0 95% CI 0.8-4.8). No significant association could be found between prolongation of complaints and infecting serogroup, although subgroup analysis suggest that infection with serogroups Sejroe (OR 4.8, 95%CI 0.9-27.0) and icterohaemorrhagiae (OR 2.0, 95%CI 0.9-4.3 CI) are more likely to result in CPC than infections with serogroup Grippotyphosa.
In addition to the acute disease, persistent complaints have an impact on the burden of leptospirosis.
The incidence of venous thrombosis, mostly pulmonary embolism (PE), ranging from local immunothrombosis to central emboli, but also deep vein thrombosis (DVT) in people with coronavirus disease 2019 ...(COVID‐19) is reported to be remarkably high. The relevance of better understanding, predicting, treating, and preventing COVID‐19–associated venous thrombosis meets broad support, as can be concluded from the high number of research, review, and guideline papers that have been published on this topic. The Dutch COVID & Thrombosis Coalition (DCTC) is a multidisciplinary team involving a large number of Dutch experts in the broad area of venous thrombosis and hemostasis research, combined with experts on virology, critically ill patients, pulmonary diseases, and community medicine, across all university hospitals and many community hospitals in the Netherlands. Within the consortium, clinical data of at least 5000 admitted COVID‐19–infected individuals are available, including substantial collections of biobanked materials in an estimated 3000 people. In addition to considerable experience in preclinical and clinical thrombosis research, the consortium embeds virology‐hemostasis research models within unique biosafety facilities to address fundamental questions on the interaction of virus with epithelial and vascular cells, in relation to the coagulation and inflammatory system. The DCTC has initiated a comprehensive research program to answer many of the current questions on the pathophysiology and best anticoagulant treatment of COVID‐19–associated thrombotic complications. The research program was funded by grants of the Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development. Here, we summarize the design and main aims of the research program.
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