TITLE:
Therapeutic and Biochemical Effects of Chloroquine-Based Combination Therapies in Murine Plasmodium berghei Infection
AUTHORS:
Segun Afolabi Olomu, Jane-Rose Ifunanyachi Oche, Yusuf Samuel Gazuwa, Titilayo Omolara Johnson
KEYWORDS:
Malaria, Plasmodium berghei, Chloroquine, Combination Therapy, Oxidative Stress, Hematology, Liver Function
JOURNAL NAME:
Advances in Infectious Diseases,
Vol.15 No.4,
December
24,
2025
ABSTRACT: Background: Malaria remains a major global health burden, with increasing concerns about resistance to artemisinin-based combination therapies (ACTs). Chloroquine (CQ), once the mainstay of treatment, was abandoned due to widespread resistance but is regaining interest following reports of re-sensitivity in some endemic regions. This study evaluated the efficacy of CQ in combination with other standard antimalarials against Plasmodium berghei infection in mice. Methods: Wistar albino mice were inoculated intraperitoneally with P. berghei and randomly divided into groups treated with CQ, artemether-lumefantrine (AL), sulphadoxine-pyrimethamine (SP), dihydroartemisinin-piperaquine (DHAP), amodiaquine (AA), or CQ combined with each of these agents. Treatment was administered orally for four days, and parasitemia was monitored microscopically. On Day 4, blood samples were analyzed for oxidative stress markers (lipid peroxidation, nitric oxide), liver function tests (ALT, AST, ALP, total protein, albumin, bilirubin), and hematological parameters (RBC, Hb, PCV, WBC, platelets, leukocyte differentials). Results: CQ monotherapy produced moderate parasite suppression, whereas combinations—especially CQ + AL and CQ + DHAP—significantly reduced parasitemia compared to single-drug regimens (p 6/µL), reversing malaria-induced anemia. Platelet counts and lymphocyte levels were also improved in most CQ-based regimens. Conclusion: Chloroquine, when combined with other antimalarials, enhanced parasite clearance and improved biochemical and hematological outcomes in murine malaria. These findings highlight the potential of CQ-based combinations as viable alternatives or adjuncts to ACTs, particularly in regions where CQ sensitivity has re-emerged. Further clinical validation is recommended.