A genome-wide association study for rheumatoid arthritis replicates previous HLA and non-HLA associations in a cohort from South Africa.

The complex pathogenesis of rheumatoid arthritis (RA) is not fully understood, with few studies exploring the genomic contribution to RA in patients from Africa. We report a genome-wide association study (GWAS) of South-Eastern Bantu-Speaking South Africans (SEBSSAs) with seropositive RA (n = 531) and population controls (n = 2653). Association testing was performed using PLINK (logistic regression assuming an additive model) with sex, age, smoking and the first three principal components as covariates. The strong association with the Human Leukocyte Antigen (HLA) region, indexed by rs602457 (near HLA-DRB1), was replicated. An additional independent signal in the HLA region represented by the lead SNP rs2523593 (near the HLA-B gene; Conditional P-value = 6.4 × 10-10) was detected. Although none of the non-HLA signals reached genome-wide significance (P < 5 × 10-8), 17 genomic regions showed suggestive association (P < 5 × 10-6). The GWAS replicated two known non-HLA associations with MMEL1 (rs2843401) and ANKRD55 (rs7731626) at a threshold of P < 5 × 10-3 providing, for the first time, evidence for replication of non-HLA signals for RA in sub-Saharan African populations. Meta-analysis with summary statistics from an African-American cohort (CLEAR study) replicated three additional non-HLA signals (rs11571302, rs2558210 and rs2422345 around KRT18P39-NPM1P33, CTLA4-ICOS and AL645568.1, respectively). Analysis based on genomic regions (200 kb windows) further replicated previously reported non-HLA signals around PADI4, CD28 and LIMK1. Although allele frequencies were overall strongly correlated between the SEBSSA and the CLEAR cohort, we observed some differences in effect size estimates for associated loci. The study highlights the need for conducting larger association studies across diverse African populations to inform precision medicine-based approaches for RA in Africa.

Barriers and enablers for implementation of digital-linked diagnostics models at point-of-care in South Africa: stakeholder engagement.

The integration of digital technologies holds significant promise in enhancing accessibility to disease diagnosis and treatment at point-of-care (POC) settings. Effective implementation of such interventions necessitates comprehensive stakeholder engagements. This study presents the outcomes of a workshop conducted with key stakeholders, aiming to discern barriers and enablers in implementing digital-connected POC diagnostic models in South Africa. The workshop, a component of the 2022 REASSURED Diagnostics symposium, employed the nominal group technique (NGT) and comprised two phases: Phase 1 focused on identifying barriers, while Phase 2 centered on enablers for the implementation of digital-linked POC diagnostic models. Stakeholders identified limited connectivity, restricted offline functionality, and challenges related to load shedding or rolling electricity blackouts as primary barriers. Conversely, ease of use, subsidies provided by the National Health Insurance, and 24-h assistance emerged as crucial enablers for the implementation of digital-linked POC diagnostic models. The NGT workshop proved to be an effective platform for elucidating key barriers and enablers in implementing digital-linked POC diagnostic models. Subsequent research endeavors should concentrate on identifying optimal strategies for implementing these advanced diagnostic models in underserved populations.

Diagnostic performance of NxTek™ Eliminate Malaria-Pf test for the detection of Plasmodium falciparum in school children with asymptomatic malaria.

BACKGROUND: One of the major roadblocks to the falciparum malaria elimination programme is the presence of a portion of the population, such as school children, with asymptomatic malaria infection. Targeting such reservoirs of infections is critical to interrupting transmission and enhancing elimination efforts. The NxTek™ Eliminate Malaria Pf test is a highly sensitive rapid diagnostic test (hsRDT) for the detection of HRP-2. However, knowledge gaps exist in Ethiopia on the diagnostic performance of hsRDT for the detection of Plasmodium falciparum in school children with asymptomatic malaria. METHODS: A school-based cross-sectional study was conducted from September 2021 to January 2022 on 994 healthy school children (aged 6-15 years). Finger-pricked whole blood samples were collected for microscopy, hsRDT, conventional RDT (cRDT or SD Bioline Malaria Ag Pf/P.v), and QuantStudio™ 3 Real-Time PCR system (qPCR). The hsRDT was compared to cRDT and microscopy. qPCR and microscopy were used as reference methods. RESULTS: The prevalence of Plasmodium falciparum was 1.51%, 2.2%. 2.2% and 4.52%, by microscopy, hsRDT, cRDT and qPCR, respectively. Using qPCR as reference, the sensitivity of hsRDT was higher (48.89%) than the microscopy (33.3%), and showed 100% specificity and a positive predictive value (PPV). Microscopy showed similar specificity and PPV as hsRDT. Using microscopy as a reference, the diagnostic perforrmances of both hsRDT and cRDT were similar. Both RDTs demonstrated identical diagnostic performances in both comparison methods. CONCLUSIONS: hsRDT has the same diagnostic performance as cRDT but improved diagnostic characteristics than microscopy for detection of P. falciparum in school children with asymptomatic malaria. It can be a useful tool for the national malaria elimination plan of Ethiopia.

m-PIMA™ HIV1/2 VL: A suitable tool for HIV-1 and HIV-2 viral load quantification in West Africa.

Point-of-Care for HIV viral RNA quantification seems to be a complementary strategy to the existing conventional systems. This study evaluated the performance of the m-PIMA™ HIV1/2 Viral Load for the quantification of both HIV-1 and HIV-2 RNA viral load. A total of 555 HIV-1 and 90 HIV-2 samples previously tested by Abbott RealTime HIV-1 (Abbott, Chicago, USA) and Generic HIV-2® Charge virale (Biocentric, France) were tested using the m-PIMA™ HIV1/2 Viral Load at the HIV National Reference lab in Senegal. For HIV-1, Pearson correlation and Bland-Altman plots showed a coefficient r = 0.97 and a bias of -0.11 log10 copies/ml (95% confidence interval [CI]: -0.086 to -0.133 log10 copies/ml) for the m-PIMA™ HIV1/2 Viral Load, respectively. Sensitivity and specificity at 3 log10 copies/ml (threshold of virological failure) were 93.6% (95%[CI]: 91.5% to 95.6%) and 99.1% (95%[CI]: 98.3% to 99.9%), respectively. For HIV-2, a correlation of r = 0.95 was also noted with a bias of - 0.229 log10 copies/ml (95%[CI]: -0.161 to -0.297 log10 copies/ml). Sensitivity and specificity at 3 log10 copies/ml were 97.6% (95%[CI]: 94.3% to 100%) and 93.9% (95%[CI]: 88.9% to 98.8%), respectively. These results confirmed that m-PIMA™ HIV1/2 VL could be a good alternative for HIV-1 and HIV-2 viral load testing in decentralized settings in Senegal.

Quality Assurance for Hepatitis C Virus Point-of-Care Diagnostics in Sub-Saharan Africa.

As part of a multinational study to evaluate the Bioline Hepatitis C virus (HCV) point-of-care (POC) testing in sub-Saharan Africa (SSA), this narrative review summarises regulatory standards and quality indicators for validating and approving HCV clinical diagnostics. In addition, this review also provides a summary of their diagnostic evaluations using the REASSURED criteria as the benchmark and its implications on the WHO HCV elimination goals 2030.

REASSURED diagnostics at point-of-care in sub-Saharan Africa: A scoping review.

Point-of-care (POC) diagnostics that meet the REASSURED criteria are essential in combating the rapid increase and severity of global health emergencies caused by infectious diseases. However, little is known about whether the REASSURED criteria are implemented in regions known to have a high burden of infectious diseases such as sub-Saharan Africa (SSA). This scoping review maps evidence of the use of REASSURED POC diagnostic tests in SSA. The scoping review was guided by the advanced methodological framework of Arksey and O'Malley, and Levac et al. We searched the following electronic databases for relevant literature: Scopus, Dimensions, ProQuest Central, Google Scholar, and EBSCOhost (MEDLINE, CINAHL, as well as AFRICA-WIDE). Two reviewers independently screened abstracts and full-text articles using the inclusion criteria as reference. We appraised the quality of the included studies using the mixed-method appraisal tool (MMAT) version 2018. We retrieved 138 publications, comprising 134 articles and four grey literature articles. Of these, only five articles were included following abstract and full-text screening. The five included studies were all conducted in SSA. The following themes emerged from the eligible articles: quality assurance on accuracy of REASSURED POC diagnostic tests, sustainability of REASSURED POC diagnostic tests, and local infrastructure capability for delivering REASSURED POC diagnostic tests to end users. All five articles had MMAT scores between 90% and 100%. In conclusion, our scoping review revealed limited published research on REASSURED diagnostics at POC in SSA. We recommend primary studies aimed at investigating the implementation of REASSURED POC diagnostic tests in SSA.

B-cell epitopes of African horse sickness virus serotype 4 recognised by immune horse sera.

Identifying antigenic proteins and mapping their epitopes is important for the development of diagnostic reagents and recombinant vaccines. B-cell epitopes of African horse sickness virus (AHSV) have previously been mapped on VP2, VP5, VP7 and NS1, using mouse, rabbit and chicken monoclonal antibodies. A comprehensive study of the humoral immune response of five vaccinated horses to AHSV-4 antigenic peptides was undertaken. A fragmented-genome phage display library expressing a repertoire of AHSV-4 peptides spanning the entire genome was constructed. The library was affinity selected for binders on immobilised polyclonal immunoglobulin G (IgG) isolated from horse sera collected pre- and post-immunisation with an attenuated AHSV-4 monovalent vaccine. The DNA inserts of binding phages were sequenced with Illumina high-throughput sequencing. The data were normalised using preimmune IgG-selected sequences. More sequences mapped to the genes coding for NS3, VP6 and VP5 than to the other genes. However, VP2 and VP5 each had more antigenic regions than each of the other proteins. This study identified a number of epitopes to which the horse's humoral immune system responds during immunisation with AHSV-4.