Comparative assessment of Plasmodium falciparum sensitivity to chloroquine and amodiaquine in vitro

The in vitro sensitivity of Plasmodium falciparum isolates to chloroquine and amodiaquine were assessed in children with symptomatic uncomplicated malaria in Ibadan, Nigeria. The WHO standard in vitro micro-test method was employed for the study. A total of one hundred and two children were admitted into the study. Inhibition of schizont maturation at varying concentration of the study drugs was used as an index for drug activity. Effective concentrations by probit analysis of log dose/response for 50, 90 and 99% (EC50, EC90and EC99) inhibition were 0.37, 2.38 and 5.76 mol/l, respectively, for chloroquine and 0.06, 0.26 and 0.59 mol/l, respectively, for amodiaquine. Forty isolates of P. falciparum were tested for chloroquine sensitivity. Eighty percent (32/40) showed schizont maturation at 1.6 mol/l and were classified as resistant, while 39% (14/36) of isolates tested for amodiaquine matured at 0.4 mol/l and were also classified as resistant. This shows that amodiaquine is significantly more effective than chloroquine. While this data provides no absolute demonstration of chloroquine resistance, it underlies the need for continuous monitoring of the susceptibility of P. falciparum to chloroquine in southwest Nigeria

Serum biochemical parameters and cytokine profiles associated with natural African trypanosome infections in cattle.

BACKGROUND: Animal African trypanosomiasis (AAT) greatly affects livestock production in sub-Saharan Africa. In Ghana prevalence of AAT is estimated to range between 5 and 50%. Studies have reported serum biochemical aberrations and variability in cytokine profiles in animals during infection. However, information regarding the biochemical parameters and cytokine profiles associated with natural infections are limited. This study was therefore aimed at investigating changes in the levels of serum biochemical parameters and inflammatory cytokines during a natural infection. METHODS: Nested internal transcribed spacer (ITS)-based PCR and sequencing were used to characterise trypanosome infection in cattle at two areas in Ghana (Adidome and Accra) of different endemicities. The cattle were sampled at four to five-week intervals over a period of six months. Levels of serum biochemical parameters, including creatinine, cholesterol, alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bilirubin and total protein and cytokines (interleukin 10, interleukin 4, interleukin 12, interferon gamma and tumor necrosis factor alpha) were measured in serum samples and then compared between infected cattle and uninfected controls. RESULTS: The predominant trypanosome species detected in Accra (non-endemic) and Adidome (endemic) were Trypanosoma theileri and Trypanosoma vivax, respectively. Serum biochemical parameters were similar between infected and uninfected cattle in Accra. Infected cattle at Adidome however, had significantly higher levels of ALP, creatinine, total protein and total bilirubin (P < 0.05) and significantly lower levels of cholesterol (P < 0.05) at specific time points. At basal levels and during infection, significantly higher pro-inflammatory to anti-inflammatory (Th1/Th2) cytokine ratios were observed in cattle at Adidome compared to Accra (P < 0.05), indicating a shift towards Th1 immune response in Adidome. Levels of IL-10 were, however, significantly elevated in infected cattle in Accra (P < 0.05), suggesting high anti-inflammatory cytokine response in Accra. CONCLUSION: These results suggests that cattle in an endemic area repeatedly infected with trypanosomes of different species or different antigenic types demonstrate high pro-inflammatory (Th1) immune response and biochemical alterations whereas cattle in a non-endemic area with predominantly chronic T. theileri infections demonstrate high anti-inflammatory response and no biochemical alterations

Antitrypanosomal activity of Khaya senegalensis and Anogeissus leiocarpus stem bark on Trypanosoma brucei brucei infected rats

Trypanosoma brucei brucei, a haemo-protozoan parasite causes African Animal Trypanosomiasis (AAT). Khaya senegalensis (KS) and Anogeissus leiocarpus (AL) are medicinal plants used either individually or in combination by local farmers in Northern Nigeria in the treatment of many diseases including trypanosomiasis. There is however, no information on the efficacy of the plants used in combination. In this study, the antitrypanosomal activity of combined methanolic stem bark extracts of K. senegalensis and A. leiocarpus were determined in vivo using suppressive and repository tests. The combined extracts were administered at 250 mg/kg to T. b. brucei infected rats in ratios 1:4, 2:3, 1:1, 3:2 and 4:1 (K. senegalensis to A. leiocarpus). Diminor® (3.5 mg/kg) was positive control and Tween-80 the negative control. Trypanocidal activity was recorded in all four ratios with the highest in the 4:1 ratio for both tests. All ratios in repository test had varying levels of prophylactic activity which were significantly higher (p&lt;0.05) than the negative control group. Chemo-prophylactic activity in the 4:1 ratio compared (p&gt;0.05) favorably with the positive control. The extracts however had significantly lower (p&lt;0.05) parasite suppressive activity compared to Diminor® (100%). The 1:4 combinations had the lowest activity (4.35%). In the repository test, packed cell volume (PCV) levels varied in the groups with an increase as the quantity of K. senegalensis in the dose increased. The results therefore show that the antitrypanosomal activity and haemolytic effects of the extracts was dependent on the ratio of K. senegalensis to A. leiocarpus. A higher quantity of K. senegalensis provided a more effective prophylaxis and normal PCV. The use of a threefold quantity of K. senegalensis to A. leiocarpus in the local management of animal trypanosomiasis is therefore suggested. Key words: Antitrypanosoma, suppressive test, repository test, Khaya senegalensis, Anogeissus leiocarpus