Seroprotection rates of vaccine-preventable diseases among newly arrived Eritrean asylum seekers in Switzerland: a cross-sectional study.

BACKGROUND According to 2016 WHO/UNICEF country estimates Eritrea has overall high vaccination coverage with immunisation rates for 3 doses of diphtheria/tetanus/pertussis and polio vaccine of 95%, for 2 doses measles vaccine of 85%, and for 3 doses Hepatitis B vaccine of 85%. If confirmed, this could imply that routine basic vaccination of newly arrived Eritreans could be safely omitted. METHODS We used stored serum samples from two cross-sectional studies that screened newly arrived Eritrean refugees for infectious diseases. Consenting refugees aged 16 years and older who registered in one of three neighbouring cantons in northwestern Switzerland were enrolled between January 2016 and December 2017. Antibody titers against the following vaccine-preventable diseases were measured (applied thresholds for seroprotection in brackets): diphtheria (> 0.1 IU/ml), tetanus (> 0.1 IU/ml), measles (> 150 mIU/ml), rubella (only for women,> 11 IU/ml), varicella (> 50 mIU/ml), hepatitis B (HbsAg Index > 0.9, antiHBc Index > 0.9 and antiHBs > 10 IE/L). Differences between sex and age groups (≤ 25 and >25 years) were measured by Fisher's exact test. RESULTS We analysed samples of 133 study participants (20 women, 15%) with a median age of 25 years (range 16-61). Rates of sero-positivity were as follow for women / men respectively: diphtheria 57.9% / 74.8% (difference non significant), tetanus 94.8% / 41.1% (p<0.001), measles 73.7% / 76.6% (non sig.), rubella in women 78.9%, varicella 89.5% / 95.3% (non sig.), anti-HBc 15.8% / 26.2% (non sig.), and anti-HBs 15.8% / 17.8% (non sig.). CONCLUSIONS Sero-prevalence for vaccine-preventable infections did not meet levels required to confer herd-immunity in any of the human-to-human transmissible diseases that were studied. In general, the strategy proposed by the Federal Office of Public Health to offer basic immunization to all newly arrived refugees, including newly arriving Eritrean refugees, is justified

Population pharmacokinetics of dolutegravir: influence of drug-drug interactions in a real-life setting.

Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir's pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition. A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug-drug interactions. A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h-1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively. Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases