Safety-Constrained Cascade Inference for Robust Malaria Cell Classification Under Field Corruptions

Automated malaria diagnosis from blood smear microscopy is a critical challenge in global health AI; in resource-limited settings, the scarcity of expert microscopists remains the primary bottleneck to timely and accurate diagnosis. Three compounding failure modes prevent reliable clinical deployment of existing deep learning systems. First, end-to-end detectors treat unannotated cells as background during training, producing recall figures that are strongly influenced by annotation completeness rather than reflecting true cell recovery. Second, Non-Maximum Suppression tends to suppress valid detections in dense smear regions where infection counts matter most. Third, existing whole-slide detection pipelines lack per-cell spatial evidence for clinical audit, despite image-level explainability methods such as Grad-CAM having been applied to malaria image classification tasks. We present MalariAI, a two-stage decoupled framework that addresses all three failure modes in a unified pipeline. Stage 1 applies an annotation-agnostic distance-transform guided watershed algorithm to isolate every cell in a full 1600x1200 blood smear image, recovering 75.95% of ground-truth cells by centroid localisation across the 120-image NIH BBBC041 test set without any ground-truth input. Stage 2 fine-tunes EfficientNet-B0 with Focal Loss (gamma = 2.0, per-class inverse-frequency weights) on 64x64 crops, achieving 98.36% overall classification accuracy with 87.5% and 75.0% per-class accuracy on the rare schizont and gametocyte stages, compared to only 24.57% and 25.95% AP for a Faster R-CNN baseline on the same classes. Grad-CAM++ heatmaps generated per detected cell provide instance-level spatial evidence for clinical audit, enabling microscopists to verify model predictions at the individual parasite level without sacrificing classification performance.

Automated malaria diagnosis from stained blood-smear microscopy is dominated by deep convolutional neural networks that are accurate but computationally expensive, poorly interpretable, and rarely validated with patient-level rigor. We present EMFE (Efficient Mathematical Feature Extraction), a five-feature framework for classifying single red-blood-cell images as parasitized or uninfected using Gray World color normalization, adaptive green-channel thresholding, morphological spot detection, and classical machine learning. Using the NIH LHNCBC malaria dataset (27,558 images from 200 patients), we evaluate Random Forest, Histogram Gradient Boosting, and Support Vector Machine classifiers under patient-grouped nested cross-validation (K_outer=20, K_inner=3), ensuring that cells from each patient remain within a single fold. The optimized Random Forest achieves 94.6% pooled out-of-fold accuracy (95% CI [93.6, 95.7]), corroborated by an untouched 40-patient holdout test (94.3%) and a patient-level permutation test (p<0.001, 1,000 permutations). Ablation experiments quantify the contribution of individual features and pipeline stages. Hardware-matched comparisons with retrained DenseNet121, ResNet50, and MobileNetV2 models assess the accuracy-efficiency trade-off. Synthetic perturbations characterize three failure modes, while explainability analysis identifies spot saturation as the dominant discriminative feature. Patient-level aggregation further quantifies sensitivity-specificity trade-offs and false-positive accumulation. These results demonstrate a statistically rigorous, interpretable, and computationally lightweight alternative to deep learning, while explicitly quantifying its limitations.

Malaria remains a leading cause of mortality in resource-limited settings, where expert microscopists are scarce. Automated diagnosis based on microscopy images thus has strong potential to improve care delivery. But for an algorithm to deploy, a necessary requirement is that it meet a suite of non-obvious (from a machine learning (ML) perspective) clinical constraints. Therefore, in close consultation with a national health center we developed a malaria diagnosis pipeline which addresses key requirements listed by the health care center but typically ignored in the ML malaria literature. In particular, it includes: (i) stopping criteria (to reduce image acquisition and time-to-result); (ii) human-in-the-loop functionality (for review and accountability); (iii) multi-species discrimination (since treatment varies by species); (iv) thick film detection (standard for microscopy); (v) computationally-efficient uncertainty calculations (to aid clinician review); and (vi) an edge device platform (since internet can be spotty in this catchment area). The mobile system performs all inference on-device using YOLOv13n deployed via TensorFlow Lite. It detects four species and white blood cells from Giemsa-stained thick blood smear images, aggregating per-image detections into slide-level parasitemia with World Health Organization (WHO)-standard quantification. This paper highlights these various clinical constraints and offers methods to address them. Evaluated on 2,739 annotated images across all four species, the system achieves [email protected] of 0.863, per-image parasite count correlation of r = 0.812, slide-level r = 0.951 (soft counting, 10 images/slide), and runs entirely offline with a pipeline time of 10.27 +- 1.65 s per image.