The relevance of ultradeep sequencing for low HIV-1 viral loads and proviruses in the clinical setting.

Improving the therapeutic management of HIV-positive persons is a major public health issue and includes better detection of drug resistance mutations (DRMs). The aim of this study was (i) to explore DRMs in HIV-1-positive persons presenting a blood viral load (VL) < 1000 genomes copies (gc)/mL, including the analyze of cerebrospinal fluid (CSF) and HIV-DNA from peripheral blood mononuclear cells using ultradeep sequencing (UDS) and (ii), to evaluate how these DRMs could influence the clinical practices. For each patient (n = 12), including five low-VL patients (i.e., <1000 gc/mL), HIV-1 UDS targeting the protease, reverse transcriptase and integrase genes was performed on plasma, proviral DNA, and CSF when available. Sequencing discordances or failures were mostly found in samples from low-VL patients. A 5% UDS cut-off allowed to increase the sensitivity to detect DRMs in different compartments, excepted in CSF. Patients with the highest viral quasispecies heterogeneity were naïve of treatment or presented a medical history suggesting low selection pressure or virological failures. When analyzing compartmentalization and following-up patients: low-frequency variants (LFVs) were responsible for 47% (n = 8) and 76% (n = 13) of changes in drug resistance interpretation, respectively. In such cases, we conclude that UDS is a robust technique, which still could be improved by increase the RNA and/or DNA extraction in low-VL samples to detect LFVs. Further studies are needed to define the impact of LFVs on antiretroviral treatments. At last, when considering a DRM, the use of mutational load would probably be more suitable than frequencies.

High anti-SARS-CoV-2 seroprevalence among unvaccinated mother-child pairs from a rural setting in north-eastern Tanzania during the second wave of COVID-19.

Background: The reported infection rates and burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in low- and middle-income countries, including those in sub-Saharan Africa, are relatively low compared to the rates and burden in Europe and America, partly due to limited testing capability. Unlike many countries, Tanzania has implemented neither mass screening nor restrictive measures such as lockdowns to date. The prevalence of SARS-CoV-2 infection in rural mainland Tanzania is largely unknown. Methods: A cross-sectional study was conducted between April and October 2021 to assess the anti-SARS-CoV-2 seroprevalence among mother-child pairs (n = 634 children, n = 518 mothers) in a rural setting in north-eastern Tanzania. Results: A very high prevalence of anti-SARS-CoV-2 antibody titres was found, with seroprevalence rates ranging from 29% among mothers and 40% among children, with a dynamic peak in seropositivity incidence at the end of July/early August being revealed. Significant differences in age, socioeconomic status, and body composition were associated with seropositivity in mothers and children. No significant associations were observed between seropositivity and comorbidities, including anaemia, diabetes, malaria, and HIV. Conclusions: The transmission of SARS-CoV-2 in a rural region of Tanzania during 2021 was high, indicating a much higher infection rate in rural Tanzania compared to that reported in the UK and USA during the same period. Ongoing immune surveillance may be vital to monitoring the burden of viral infection in rural settings without access to molecular genotyping, where the load of communicable diseases may mask COVID-19. Surveillance could be implemented in tandem with the intensification of vaccination strategies.

Survey of delivery of parenteral antimicrobials in non-inpatient settings across Europe.

Delivery of parenteral antimicrobials in non-inpatient settings (DPANS) may be through a dedicated outpatient parenteral antimicrobial therapy (OPAT) service, co-ordinated by hospital- or community-based specialised teams, or via an infusion service involving community-based health professionals (nurses, general practitioners) without centralised hospital oversight, or through ad hoc arrangements. DPANS varies among countries. Our objective was to describe how DPANS is organised at a national level in European countries. A survey (65-item self-administered questionnaire) was conducted from February-June 2019 among infection specialists in 34 European countries on behalf of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) and the British Society for Antimicrobial Chemotherapy (BSAC) OPAT initiative. Most countries (28/34; 82.4%) participated in the survey. DPANS was available in almost all (27/28; 96.4%) responding countries. DPANS was predominantly provided either via specialised OPAT services (17/28; 60.7%) or via infusion services (16/28; 57.1%), with 11 countries (39.3%) providing both services. A formal OPAT team structure with specifically trained staff was reported in only six countries (6/17; 35.3%). Some countries (4/28; 14.3%) had no structured services but practiced DPANS via ad hoc arrangements. The costs of all stages of the process were covered for patients managed by specialised OPAT/infusion services, either completely, partially or for specific patient groups in the majority (20/28; 71.4%) of countries. The main barriers to implement OPAT/infusion services were lack of organisational structure or guidelines. In conclusion, DPANS with respect to availability and organisation is highly heterogeneous in Europe. National/European guidelines may help improve and standardise DPANS.