Abstract
Introducion: The impact of malaria scourge has been characterized by daunting challenges including antimalarial drug resistance. This necessitates the search for newer antimalaria drugs using approaches including drug repurposing. This study assessed whether Tinidazole (T) can be repurposed as antimalaria in combination with artemether/lumefantrine (A/L) in Plasmodium berghei infected mice. Materials and Methods: Plasmodium berghei infected mice were grouped and orally treated with A/L (2.3/13.7mg/kg), T (28.6 mg/kg), and A/L/T daily in curative, suppressive and prophylactic studies. The negative control (NC) and positive control (MC) were orally treated with 0.9% normal saline (0.2mL) and chloroquine (CQ) (10mg/kg) daily for 4 days, respectively. After drug administration, blood samples were collected and evaluated for parasitemia level, lipid and hematological parameters. Results: Significant decreases in parasitemia levels in the curative, suppressive and prophylactic groups were observed in mice treated with T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7 mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Mean survival times were significantly increased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. Red blood cells, hemoglobin, packed cell volume, high density lipoprotein, cholesterol levels were significantly (p<0.001) increased whereas white blood cells, total cholesterol, triglyceride and low density lipoprotein cholesterol levels were significantly decreased at T (28.6 mg/kg) (p<0.05), A/L (2.3/13.7mg/kg) (p<0.01) and A/L/T (p<0.001) when compared to negative control. The antiplasmodial effect of A/L/T differ significantly (p<0.05) when compared to positive control. Conclusion: This study recommends the repurposing of tinidazole in combination with artemether/lumefantrine for malaria treatment and further studies in humans.
Highlights
Malaria is one of the protozoan parasites that have caused significant health challenge to man
In the suppression and curative tests, treatment with individual doses of T and A/L produced significant reductions in percentage parasitemia levels at p
The reduction in percentage parasitemia level in mice treated with A/L/T differ at p
Summary
Malaria is one of the protozoan parasites that have caused significant health challenge to man. It is primarily endemic in sub-tropical and tropical parts of the world. Malaria affects about 3.3 billion people and causes 0.6–1.1 million mortality annually [1]. African countries have the heaviest malaria burden; globally it records 90% of all malaria infections and 92% of malaria associated mortality which significantly impairs economic growth and development [2]. Most deaths associated with malaria are caused by Plasmodium falciparum (P. falciparum) and occurred in sub-Saharan Africa whereas malaria death in Asia Pacific region and South America is caused by P. vivax [3]
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