EFFECTS OF ARTEMISININ-BASED COMBINATION THERAPY ON HAEMATOLOGICAL PARAMETERS AND HISTOPATHOLOGY OF PLASMODIUM BERGHEI INFECTED MICE (MUS MUSULUS).

SOURCE:

Faculty: Biosences
Department: Zoology

CONTRIBUTORS:

Okafor, U. E.
Njoku, O. O.
Ufele, A. N.

ABSTRACT:

Indiscriminate uses of antimalaria drugs remained a significant common practice in Africa due to the burden of malaria infection which is caused by Plasmodium parasite. Repeated infection is a common feature of the disease. Artemisinin-based combination therapy had been the current drug of choice in the management of Plasmodium infection. This study therefore, evaluated the effects of oral administration of artesunate+ amodiaquine (A/A) and dihydroartemisinin+piperaquine (D/P) on the haematological parameters and histopathology of the liver, spleen, kidney and lung of Plasmodium berghei infected mice. One hundred and eighty mice were divided into three replicates; each replicate contained 60 mice of both sexes which were randomly distributed into six groups (A, B, C, D, E, F) of ten animals each. Plasmodium berghei (0.2ml) was inoculated intraperitoneally to the animals in groups A, B, C, D, and E, and observed for 7 days, followed by 3 days antimalaria drug administration. Group A was infected but untreated, group B was treated with 10/14mg/kg body weight of A/A for 3 days, group C was treated with 10/18mg/kg body weight of D/P for 3 days, group D was treated with 10/14mg/kg body weight of A/A for 3 days and allowed 28 days recovery, group E was treated with 10/18mg/kg body weight of D/P for 3 days and allowed 28 days recovery, group F was uninfected and untreated (normal control). Haematological investigations revealed a significant (p < 0.05) increase in total white blood cell count in the infected untreated group (16.54± 0.54), artesunate+amodiaquine treated group (12.87± 0.38) and dihydroartemisinin+piperaquine treated group (10.65±0.07) compared to normal control (7.42 ± 0.23). Lymphocyte count increased significantly (p<0.05) in infected untreated group (77.13±1.02), artesunate+amodiaquine treated group (77.53±0.55), dihydroartemisinin+piperaquine treated group (82.47±1.11) compared to normal control (65.47± 7.09). Neutrophil count decreased significantly (p<0.05) in infected untreated group (16.13± 0.88), artesunate+amodiaquine treated group (17.27±0.65) and dihydroartemisinin+piperaquine treated group (15.93±1.12) compared to normal control (33.33±1.73). A significant (p < 0.05) increase in basophil count (1.07± 0.18), eosinophil count (1.40 ± 0.13), and monocyte count (4.40±0.21) was observed in infected untreated group compared to the uninfected untreated group (0.60 ± 0.13, 0.40 ± 0.13, 0.73±0.11). A significant (p<0.05) decrease in red blood cell count was observed in infected untreated group (4.60 ± 0.48), artesunate+amodiaquine treated group (6.10±0.15) and dihydroartemisinin+piperaquine treated group (6.16±0.09) compared to normal control (7.82±0.84). Packed cell volume was significantly (p<0.05) decreased in infected untreated group (21.27 ± 1.22), artesunate+amodiaquine treated group (34.47±1.00) and dihydroartemisinin+piperaquine treated group (37.00±0.62) compared to normal control (41.33 ± 0 .61). There was a significant (p<0.05) decrease in haemoglobin concentration of the infected untreated group (4.56±0.20), artesunate+amodiaquine treated group (7.72 ±0.14) dihydroartemisinin+piperaquine treated group (7. 80±0. 97) compared to normal control (10.93±0.13). Signs of recovery were observed after 28 days. Histopathology results revealed; periportal inflammatory cells, haemopoietic precursor cells, haemozoin pigmentation in the liver of the infected untreated and treated groups. The spleen showed haemozoin pigments, loss of the typical structure of the germinal centre, apoptotic lymphocytes with tinged macrophages, megakaryocytes and haemopoietic precursor cells in the infected untreated and treated groups. Inflammation of the renal pelvis was found in the kidney of the infected groups. Degeneration of hepatocytes was found in the liver while mild tubular degeneration was observed in the kidney after 28 days post treatment. Pigment accumulation in the parenchymal and pulmonary emphysema was found in lungs of the infected but untreated and treated groups. Plasmodium infection and treatment with artesunate+amodiaquine and dihydroartemisinin+piperaquine caused reversible alterations on haematological parameters and reversible damages to the liver, kidney and spleen.