Effects of anti-protozoal drugs and histopathological studies on trypanosome species.

The trypanosomostatic and trypanosomicidal effects of four anti-protozoal drugs, namely halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine, on species of trypanosomes, viz. Trypanosoma brucei brucei (MBOS/NG/94/NITR) Bassa strain, T. congolense (MBOS/NG/93/NVRI) Zaria strain and T. brucei gambiense (MHOM/NG/92/NITR) Abraka strain, were investigated. In vitro and in vivo studies on these drugs vis-a-vis the parasites were carried out. The histopathological changes in organs and tissues of experimentally infected rats were also studied. Results from the in vitro studies indicated that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine appeared to be effective trypanosomicidal agents against T. brucei brucei (Bassa strain), T. congolense (Zaria strain) and T. brucei gambiense (Abraka strain). The in vivo studies showed that these drugs were sub-curative by prolonging the survival period of the trypanosome-infected rats, but not necessarily curing the infection. Histopathological findings indicated inflammatory reactions characterised by infiltration to variable degrees in the majority of tissues, mostly in the lungs and liver. The most consistent lesions were interstitial pneumonia, multifocal necrosis and oedema. Pathological findings showed the T. brucei brucei and T. brucei gambiense strains studied to be both intravascular and extravascular parasites. These results suggest that halofantrine hydrochloride, chloroquine phosphate, benzoylmetronidazole and pyrimethamine could be used as supportive, suppressive and/or synergistic/additive drugs in the treatment of African trypanosomiasis. Their effects on species of trypanosomes have been studied and are reported for the first time.

Effect of chlorpheniramine on the pharmacokinetics of and response to chloroquine of Nigerian children with falciparum malaria.

Chlorpheniramine (CP), a histamine H1-receptor antagonist, enhances the efficacy of chloroquine (CQ) in acute uncomplicated falciparum malaria. The effects of this combination therapy on the pharmacokinetic disposition of CQ is, however, unpredictable. A standard treatment with 25 mg CQ base per kg bodyweight was orally administered over 3 days, alone or in combination with CP, to 17 semi-immune Nigerian children with Plasmodium falciparum parasitaemia attending hospital in Lagos, Nigeria, and observed for 28 days. Whole-blood CQ concentrations were monitored 14 times during the follow-up by high-performance liquid chromatography analysis of blood dried on filter paper. Parasitaemia was determined on thick blood films stained with Giemsa, and treatment failures were established following the WHO classification for CQ resistance. Our pharmacokinetic data showed that the peak whole-blood CQ concentration was significantly increased (P < 0.05) by CP administration, and the time to achieve the peak was reduced in the presence of CP. The area under the first-moment drug-concentration-time curve was also significantly increased (P < 0.05) by CP administration. Treatment with CQ-CP combination resulted in a shorter parasite clearance time (2.0 +/- 0.5 days) and a higher cure rate (87.5%) compared to treatment with CQ alone (3.5 +/- 0.5 days; 66.7%). Our data suggest that CP enhanced the efficacy of CQ against resistant P. falciparum in acute uncomplicated malaria by increasing the uptake/concentration of CQ in resistant parasites.