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Malaria continues to be a major barrier to socioeconomic development in Africa, where its death rate is over 90%. The predictive power of many machine learning models—such as multi-linear regression (MLR), artificial neural networks (ANN), adaptive neuro-fuzzy inference systems (ANFISs) and Random Forest classifier—is investigated in this study using data from 2207 patients. The dataset was reduced from the initial dataset of thirty-two criteria samples to fifteen. Assessment measures such as the root mean square error (RMSE), mean square error (MSE), coefficient of determination (R2), and adjusted correlation coefficient R were used. ANFIS, Random Forest, MLR, and ANN are among the models. After training, ANN outperforms ANFIS (97%), MLR (92%), and Random Forest (68%) with the greatest R (99%) and R2 (99%), respectively. The testing stage confirms the superiority of ANN. The paper also presents a statistical forecasting sheet with few errors and excellent accuracy for MLR models. When the models are assessed with Random Forest, the latter shows the least results, thus broadening the modeling techniques and offering significant insights into the prediction of malaria and healthcare decision making. The outcomes of using machine learning models for precise and efficient illness prediction add to an expanding body of knowledge, assisting healthcare systems in making better decisions and allocating resources more effectively. [ABSTRACT FROM AUTHOR]