We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

A survey of diagnosis and treatment of invasive aspergillosis was conducted in eight University Medical Centers (UMCs) and eight non-academic teaching hospitals in the Netherlands. Against a background of emerging azole resistance in Aspergillus fumigatus routine resistance screening of clinical isolates was performed primarily in the UMCs. Azole resistance rates at the hospital level varied between 5% and 10%, although rates up to 30% were reported in high-risk wards. Voriconazole remained first choice for invasive aspergillosis in 13 out of 16 hospitals. In documented azole resistance 14 out of 16 centres treated patients with liposomal amphotericin B.

Staphylococcus aureus is a versatile pathogen of medical significance, using multiple virulence factors to cause disease. A prophylactic S. aureus 4-antigen (SA4Ag) vaccine comprising capsular polysaccharide (types 5 and 8) conjugates, clumping factor A (ClfA) and manganese transporter C (MntC) is under development. This study was designed to characterize S. aureus isolates recovered from infected patients and also to investigate approaches for examining expression of S. aureus vaccine candidates and the host response during human infection. Confirmation of antigen expression in different disease states is important to support the inclusion of these antigens in a prophylactic vaccine. Hospitalized patients with diagnosed S. aureus wound (27) or bloodstream (24) infections were enrolled. Invasive and nasal carriage S. aureus isolates were recovered and characterized for genotypic diversity. S. aureus antigen expression was evaluated directly by real-time, quantitative, reverse-transcriptase PCR (qRT-PCR) analysis and indirectly by serology using a competitive Luminex immunoassay. Study isolates were genotypically diverse and all had the genes encoding the antigens present in the SA4Ag vaccine. S. aureus nasal carriage was detected in 55% of patients, and in those subjects 64% of the carriage isolates matched the invasive strain. In swab samples with detectable S. aureus triosephosphate isomerase housekeeping gene expression, RNA transcripts encoding the S. aureus virulence factors ClfA, MntC, and capsule polysaccharide were detected by qRT-PCR. Antigen expression was indirectly confirmed by increases in antibody titer during the course of infection from acute to convalescent phase. Demonstration of bacterial transcript expression together with immunological response to the SA4Ag antigens in a clinically relevant patient population provides support for inclusion of these antigens in a prophylactic vaccine.

Background Staphylococcus aureus bacteremia (SAB) is in 10% to 20% of cases complicated by infective endocarditis (SA-IE). Clinical prediction scores may select SAB patients at highest risk for endocarditis, improving the diagnostic process of endocarditis. We compared the accuracy of the POSITIVE, PREDICT and VIRSTA scores for classifying the likelihood of endocarditis in SAB patients. Methods Between August 2017 and September 2019 we enrolled consecutive adult patients with SAB in a prospective cohort study in seven hospitals in the Netherlands. Using the modified Duke Criteria for definite endocarditis as reference standard, sensitivity, specificity, negative predictive (NPV) and positive predictive values (PPV) were determined for the POSITIVE, PREDICT and VIRSTA scores. A NPV of at least 98% was considered safe for excluding endocarditis. Results Of 477 SAB patients enrolled, 33% had community-acquired SAB, 8% had a prosthetic valve and 11% a cardiac implantable electronic device. Echocardiography was performed in 87% of patients, and 42% received a TEE. 87 (18.2%) had definite endocarditis. Sensitivity was 77.6% (65.8 – 86.9), 85.1% (75.8 – 91.8) and 98.9% (95.7 – 100) for the POSITIVE (n=362), PREDICT and VIRSTA scores, respectively. NPVs were 92.5% (87.9 – 95.8), 94.5% (90.7 – 97.0), and 99.3% (94.9 – 100).) For the POSITIVE, PREDICT and VIRSTA scores, 44.5%, 50.7% and 70.9% of SAB patients, respectively were classified as high-risk for endocarditis. Conclusions Only the VIRSTA score had a NPV of at least 98%, but at the expense of a high number of patients classified as high risk and thus requiring TEE.