Accuracy and operational feasibility of point-of-care (PoC) viral load monitoring of HIV-positives mothers at delivery in the context of HIV vertical transmission reduction in Mozambique

Background: Many resource-limited countries face challenges in implementing HIV viral load testing within their public health programs due to suboptimal laboratory infrastructure and limited human resources. HIV point-of-care viral load (PoC VL) testing in pregnant and breastfeeding women could provide an opportunity for faster identification and management of virologic failure in mothers, which in turn may contribute to higher effectiveness in preventing mother-to-child transmission. The objective of this research project was to describe the diagnostic accuracy, feasi-bility and usability of PoC VL for pregnant and breastfeeding women in primary health care clinics in southern and central region of Mozambique. Methods: HIV-infected pregnant and postpartum women were included in the first cross-sectional study. Each participant was tested using both on-site m-PIMA PoC VL and referral la-boratory-based VL assays. In the second study, mother/child pairs were recruited in maternity wards in 14 primary health facilities. Half of those mothers were tested with PoC VL at delivery (Intervention Arm). The other half (Control Arm) saw samples collected and sent to the central laboratory for referral viral load testing. Three months post-delivery, all mothers had a viral load performed (laboratory based or PoC). Linear regression analysis and Bland-Altman plots were used to describe diagnostic accuracy in the first study and generalized linear mixed-effects models were used for to account for clustered data in the second study. Results: The sensitivity and specificity of the m-PIMA PoC VL assay were 95.0% (95% CI: 91.6-97.3%) and 96.5% (95% CI: 94.2-98.0%), respectively at a threshold of 1,000 copies/mL. In the intervention arm, 1906 (92.7%) of women had a viral load processed via PoC VL on site by nurses and of which 1891 (99.2%) results were communicated to the patients on the same day. There was no effect of PoC VL (intervention arm) in terms of viral suppression at week 12 [OR 1.25 (95% CI: 0.86-1.82); p=0.235] nor in transmission rate at by week 12 in the intervention arm compared to the control arm [1.69 (95% CI: 1.11-2.26) versus 1.49 (95% CI: 0.92 -2.05)]. Conclusions: M-PIMA PoC VL is accurate and operationally feasible in maternity wards of pri-mary healthcare settings in Mozambique. Nevertheless, having the viral load result available might not be sufficient to have an impact on maternal viral suppression rate or in transmission rates at 12 weeks post-delivery. Other operational aspects should be considered such as quality of adherence counselling and social support for improved adherence and early second line regimen switches to see a greater impact of PoC viral load monitoring at delivery

Study of pathogenicity, virulence, and antimicrobial resistance in Acinetobacter baumannii clinical isolates from Norway and India using whole-genome sequence data

Acinetobacter baumannii er et fremvoksende patogen over hele verden som hovedsakelig forårsaker sykehusinfeksjoner og har blitt en trussel for helsevesenet på grunn av dets multimedikamentresistens (MDR). Fremskrittene innen rimelige og raske DNA-sekvenseringsteknologier og bioinformatiske verktøy har gjort det lettere å studere patogenisitet, virulens og antimikrobiell resistens. I denne studien ble data fra hele genomsekvensen (WGS) hentet fra A. baumannii kliniske isolater fra Norge og India brukt til å studere de viktige faktorene knyttet til dens patogenisitet, virulens og antimikrobiell resistens ved bruk av bioinformatiske verktøy. Totalt ble WGS-data fra Illumina-sekvensering av 96 A. baumannii kliniske isolater gitt. For å oppfylle formålet med studien ble det først opprettet genomsamling av WGS-data etter å ha valgt den best egnede trimmeren og montøren. Senere ble de sammensatte genomene som ikke var A. baumannii, ekskludert ved bruk av Multilocus-sekvenstyping (MLST) og Whole genome alignment (WGA). Deretter ble de sammensatte genomene kommentert ved å bruke Prokka for å identifisere CDS, rRNA og tRNA. Plasmidene, AMR-genene og virulensfaktorene ble forutsagt ved bruk av forskjellige bioinformatiske verktøy og databaser inkludert PLSDB, CARD og VFDB. Til slutt ble de genotypiske (oppdagede AMR-gener) og fenotypiske (AST-resultater) resistensdata sammenlignet for å finne sammenhengen mellom dem. I denne studien var Trimmomatic og Unicycler den valgte trimmeren og montøren. QUAST, BUSCO og Bandage-resultatene viste at genomene satt sammen ved hjelp av disse verktøyene var kompatible med referansegenomet. MLST og WGA indikerte at 8 av 96 isolater ikke var A. baumannii. Antallet CDS, rRNA og tRNA oppnådd var sammenlignbart med referansegenomet. Plasmidet pVB11737_6, AMR-genet AdeK, effluxpumpe-resistensmekanisme og acinetobactin-virulensgenklynge ble funnet i flertallet av både norske og indiske A. baumannii kliniske isolater. Sammenligningen mellom genotypiske og fenotypiske resistensdata viste mindre samsvar i indiske isolater. AST-resultatene viste MDR-naturen til A. baumannii. Forekomsten av antibiotikaresistens hos A. baumannii ble funnet å være mer i India enn i Norge. Avslutningsvis er valg av verktøy for å utføre genomsamling og for å studere de andre faktorene knyttet til patogenisiteten, en forutsetning. Totalt sett presenterte denne studien potensialet til WGS for å undersøke bakteriell patogenisitet, virulens og antimikrobiell resistens til forskjellige populasjoner.Acinetobacter baumannii is an emerging pathogen worldwide that mainly causes nosocomial infections and has become a threat for healthcare systems due to its multidrug resistance (MDR) nature. The advancements in affordable and fast DNA sequencing technologies and bioinformatic tools have made it easier to study pathogenicity, virulence, and antimicrobial resistance. In this study whole genome sequence (WGS) data obtained from A. baumannii clinical isolates from Norway and India were used to study the important factors related to its pathogenicity, virulence and antimicrobial resistance using bioinformatic tools. In total, WGS data from Illumina sequencing of 96 A. baumannii clinical isolates were provided. To fulfil the objective of the study, first, genome assembly of the WGS data was created after choosing the best suited trimmer and assembler. Later, the assembled genomes which were not A. baumannii, were excluded using Multilocus sequence typing (MLST) and Whole genome alignment (WGA). Then, the assembled genomes were annotated using Prokka to identify the CDS, rRNA and tRNA. The plasmids, AMR genes and virulence factors were predicted using different bioinformatic tools and databases including PLSDB, CARD and VFDB. Finally, the genotypic (detected AMR genes) and phenotypic (AST results) resistance data were compared to find the correlation between them. In this study, the Trimmomatic and Unicycler were the chosen trimmer and assembler. The QUAST, BUSCO and Bandage results showed that the genomes assembled using these tools were compatible with the reference genome. MLST and WGA indicated that 8 out of 96 isolates were not A. baumannii. The number of CDS, rRNA and tRNA obtained were comparable to the reference genome. The plasmid pVB11737_6, AMR gene AdeK, efflux pump resistance mechanism and acinetobactin virulence gene cluster were found in majority of both Norwegian and Indian A. baumannii clinical isolates. The comparison between genotypic and phenotypic resistance data showed less concordance in Indian isolates. The AST results showed the MDR nature of A. baumannii. The occurrence of antibiotic resistance in A. baumannii was found to be more in India than in Norway. In conclusion, the selection of tools for performing genome assembly and to study the other factors related to the pathogenicity, is a prerequisite. Overall, this study presented the potential of WGS to investigate the bacterial pathogenicity, virulence, and antimicrobial resistance of different population