Phase 3 evaluation of an innovative simple molecular test for the diagnosis of malaria in different endemic and health settings in sub-Saharan Africa (DIAGMAL).

BACKGROUND: Rapid Diagnostic Tests (RDTs) have become the cornerstone for the management of malaria in many endemic settings, but their use is constrained for several reasons: (i) persistent malaria antigen (histidine-rich protein 2; HRP2) leading to false positive test results; (ii) hrp2 deletions leading to false negative PfHRP2 results; and (iii) limited sensitivity with a detection threshold of around 100 parasites/µl blood (pLDH- and HRP2-based) leading to false negative tests. Microscopy is still the gold standard for malaria diagnosis, and allows for species determination and quantitation, but requires trained microscopists, maintained microscopes and has detection limit issues. Consequently, there is a pressing need to develop and evaluate more sensitive and accurate diagnostic tests. To address this need we have developed a direct on blood mini PCR-NALFIA test that combines the benefits of molecular biology with low infrastructural requirements and extensive training. METHODS: This is a Phase 3 diagnostic evaluation in 5 African countries. Study sites (Sudan, Ethiopia, Burkina, Kenya and Namibia) were selected to ensure wide geographical coverage of Africa and to address various malaria epidemiological contexts ranging from high transmission to near elimination settings with different clinical scenarios and diagnostic challenges. Study participants will be enrolled at the study health facilities after obtaining written informed consent. Diagnostic accuracy will be assessed following the WHO/TDR guidelines for the evaluation of diagnostics and reported according to STARD principles. Due to the lack of a 100% specific and sensitive standard diagnostic test for malaria, the sensitivity and specificity of the new test will be compared to the available diagnostic practices in place at the selected sites and to quantitative PCR as the reference test. DISCUSSION: This phase 3 study is designed to validate the clinical performance and feasibility of implementing a new diagnostic tool for the detection of malaria in real clinical settings. If successful, the proposed technology will improve the diagnosis of malaria. Enrolment started in November 2022 (Kenya) with assessment of long term outcome to be completed by 2023 at all recruitment sites. TRIAL REGISTRATION: Pan African Clinical Trial Registry (www.pactr.org) PACTR202202766889963 on 01/02/2022 and ISCRTN (www.isrctn.com/) ISRCTN13334317 on 22/02/2022.

Implementing a regional integrated laboratory proficiency testing scheme for peripheral health facilities in East Africa.

INTRODUCTION: Regular participation in external quality assessment (EQA) is critical for maintaining laboratory performance and is required for laboratory accreditation. Proficiency testing (PT) is effective for providing EQA, but available schemes rarely address the range of tests performed by peripheral laboratories in resource-limited settings. The East African Regional External Quality Assessment Scheme (EA-REQAS) was established in 2004 to address this need. MATERIALS AND METHODS: Surveys were distributed biannually comprising seven different panel materials and questions addressing laboratory, clinical and public health topics. Preserved materials were prepared using standard procedures and validated by accredited laboratories to establish target values. Survey materials were shipped by courier and results returned by paper copy, email or online. Immediate feedback reports included advice for addressing errors. Composite reports addressing participants' performance were provided to national quality assurance offices. RESULTS: Sixteen surveys were distributed between 2008 and 2015; enrolment increased from 195 to 560 facilities. Mean response rate remained static (56-59%), but overall number of participating facilities increased. Mean performance scores increased from 51% to 68% but remained below the accepted score of 80%; individual facilities achieving 80% or more increased from 0 to 25%. Facilities participating in 10 or more surveys performed better than facilities participating in 5 or less surveys. CONCLUSION: PT can be applied at peripheral level in resource-limited settings and identifies poorly performing areas. PT can also be used to assess performance of equipment and test kits as part of post-market surveillance. Smaller health facilities require additional support to address deficiencies.