High Prevalence of <i>Plasmodium falciparum</i> HRP2/3 Gene Deletions in Ethiopia: Implications for Malaria Diagnosis and Treatment—A Systematic Review and Meta‐Analysis
Bibliographic record
Abstract
Introduction Plasmodium parasite species are the causative agents of malaria, which affects populations worldwide. Rapid diagnostic tests (RDTs), microscopy, and molecular methods have been used to diagnose the disease. HRP2 antigens are unique to P. falciparum , while RDTs can detect lactate dehydrogenase, aldolase, and HRP3. Nevertheless, PfHRP2‐based RDTs may produce false‐negative results if the parasite’s PfHRP2/3 genes are deleted. This study is necessary because there is currently no compiled evidence‐based information regarding PfHRP2/3 gene deletion in Ethiopia. Methods Primary research articles on PfHRP2/3 gene deletions (2000–2025) were retrieved from PubMed, Science Direct, and Google Scholar. Eligible studies were systematically searched between May 3 2025, and June 2, 2025. The quality of the included studies was assessed using the Newcastle–Ottawa Scale. Data analysis was performed using STATA Version 17, employing a random effects model. Heterogeneity among studies was evaluated using the I 2 test. To assess publication bias, Begg’s and Egger’s tests were conducted along with funnel plot symmetry analysis. Results A total of 932 studies were initially identified, among these 18 studies were selected for full‐text review. After excluding 7 studies, 11 articles were included in the meta‐analysis. The overall pooled prevalence of PfHRP2/3 gene deletions was 35.64% (95% CI: 21.43, 49.85). Specifically, the pooled prevalence of PfHRP2 and PfHRP3 gene deletions was 8.48% (95% CI: 0.96, 16.01) and 23.74% (95% CI: 12.16, 35.32), respectively, while concurrent deletions of both genes account for 8.14% (95% CI: 0.67, 15.61). Conclusion This systematic review and meta‐analysis revealed a high prevalence of PfHRP2 /3 gene deletions, highlighting significant challenges to the continued use of PfHRP2/3‐based RDTs in malaria control programs in Ethiopia. Further nationwide surveillance using standardized methodologies is recommended to better understand the extent of these gene deletions and to guide the immediate phasing out of PfHRP2/3‐based RDTs from the national malaria diagnostic algorithm. We also recommend that PCR be considered an essential diagnostic tool in in‐vitro diagnosis (IVD).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.024 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.031 |
| Bibliometrics | 0.010 | 0.011 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".