This clinical trial study was conducted during the malaria transmission seasons from September 25, 2021 to December 2, 2021 (for 8 weeks) in the Lirdaf area of Jask county, Hormozgan province, south of Iran. MDA with primaquine (15 mg base once a week) was studied, in asymptomatic and low parasitemia cases, on 168 Pakistani cases who had illegally moved from malaria-endemic spots in Pakistan to the given region. This target population mostly lived in countryside near gardens and farms. The distance of the Pakistani cases' residence to the indigenous peoples was varied from 50 meters to 7 kilometers. They were distributed into five villages named Askani Kach, Sohroki, Kormi, Ranaz, and Taratekan in the age range of 17–50 years. The two peaks of malaria transmission were from April to June and the fall season, respectively. Before initiating the MDA, active case detection was accomplished every three days in the spring and fall seasons, and their results were recorded. The criteria for carrying out our research was to reach a prevalence of more than 2% based on the outcome of the intensified case detection in accordance with the national program. For this purpose, Microscopy and malaria rapid diagnostic tests (RDTs) were used to detect active cases. Glucose-6-phosphate dehydrogenase (G6PD) was measured in all 168 cases; in addition, severe anemia, active rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), favism, and patients treated with quinacrine during the previous 3 months were assessed. It should be noted that the test results were archived for at least 18 months. Due to the primaquine contraindication, pregnant, lactating mothers, and children under 4 years were excluded from the study. Individuals with moderate and severe G6PD deficiency; some patients with severe anemia, active rheumatoid arthritis, lupus, favism, and also cases treated with quinacrine in the past three months, were excluded. Regular check-ups were done every two weeks to prevent side effects caused by medications such as pallor, dizziness, hypotension, dark urine, abdominal cramps, epigastric pain, mild hemolytic anemia, methemoglobinemia (MetHb), cyanosis, leukocytosis, and leukopenia. Symptoms such as a change in urine color, which is a sign of hemolysis of red blood cells after taking the drug, were also observed; in that case, the drug use was stopped. People were advised to refer to the physicians in the Lirdaf health center in case of bruised fingers, cyanosis of lips and skin, difficulty in breathing, and vertigo. To minimize any possible digestive disorders, the drug was taken with food or an antacid medicine. Side effects were followed up and the results were reported. Patients were referred to the physician, in the available health center, after stopping the use of primaquine. Notably, the treatment process was carried out under the direct supervision of the health providers. Interventions such as the distribution of 332 ITNs (insecticide-treated nets), indoor residual spraying (IRS) of 345,360 m2, larvicide in the amount of 3000 m3 with Bacillus thuringiensis (Bt), and thermal fogging around the dwellings of the patients were carried out once every three days before sunrise and sunset to prevent local transmission in the zone after identifying positive malaria cases. This work was approved by the research ethics committee of Hormozgan University of Medical Sciences (HUMS).