Malaria is a major and growing threat to economic development and public health in developing countries. There are about 2.7 million malaria deaths annually. Plasmodium knowlesi, the fifth human malaria parasite, is an attractive model for malaria research and is also phylogenetically close to human malaria parasite P. vivax.

Background Senna occidentalis (L.) Link has been used worldwide in traditional treatment of many diseases and conditions including snakebite. In Kenya, a decoction from the plant roots taken orally, is used as a cure for malaria. Several studies have demonstrated that extracts from the plant possess antiplasmodial activity, in vitro. However, the safety and curative potency of the plant root against established malaria infection is yet to be scientifically validated, in vivo. On the other hand, there are reports on variation in bioactivity of extracts obtained from this plant species, depending on the plant part used and place of origin among other factors. In this study, we demonstrated the antiplasmodial activity of Senna occidentalis roots extract in vitro, and in mice. Methods Methanol, ethyl acetate, chloroform, hexane and water extracts of S. occidentalis root were tested for in vitro antiplasmodial activity against Plasmodium falciparum, strain 3D7. Cytotoxicity of the most active solvent extracts was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the curative potency in Plasmodium berghei infected mice evaluated by Rane’s test. Results All of the solvent extracts tested in this study inhibited the propagation of P. falciparum, strain 3D7, in vitro, with polar extracts being more active than non-polar ones. Methanolic extracts had the highest activity (IC50 = 1.76) while hexane extract displayed the lowest activity (IC50 = 18.47). At the tested concentrations, methanolic and aqueous extracts exhibited high selectivity index against P. falciparum strain 3D7 (SI > 10) in the cytotoxicity assay. Further, the extracts significantly suppressed the propagation of P. berghei parasites (P < 0.05) in vivo and increased the survival time of the infected mice (P < 0.0001). Conclusions Senna occidentalis (L.) Link root extract inhibits the propagation of malaria parasites in vitro and in BALB/c mice.

Aims: To determine the toxicity of astemizole-methylene blue combination therapy as effective candidates for therapeutic repurposing against malaria. Study Design: Randomized block study design. Place and Duration of Study: Department of Tropical and Infectious Diseases, Institute of Primate Research, between July and December, 2019. Methodology: The Lorke’s technique was used to evaluate the toxicity of the drug combinations in Balb/c mice (N=25). The mice were monitored for clinical signs at 2-hour intervals. After 48 hours, the mice were euthanized, and their tissues collected, weighed and grossly examined. Biochemistry and hematological tests were performed after blood samples were collected. Analysis of Variance and the t-test were used for statistical analysis; differences were considered significant if P values were less than 0.05 (p˂ 0.05). Results: The findings revealed that mice treated with methylene blue alone experienced a decrease of appetite, while mice treated with astemizole alone experienced slight tremors, which were not observed in the medication combined groups. When compared to the negative controls, the astemizole-methylene blue 3:1 combination group exhibited reduced heart (p=0.007) and liver (p=0.0001) mean weights. Platelet levels in the astemizole-methylene blue 3:1 group were lower in comparison to the other groups (p=0.005), according to the hematological data collected. Conclusion: When delivered in ratios with less astamizole, astemizole-methylene blue combination therapy showed better results in terms of safety than monotherapy with either drug alone.

Malaria parasites are known to mediate the induction of inflammatory immune responses at the maternal-foetal interface during placental malaria (PM) leading to adverse consequences like pre-term deliveries and abortions. Immunological events that take place within the malaria-infected placental micro-environment leading to retarded foetal growth and disruption of pregnancies are among the critical parameters that are still in need of further elucidation. The establishment of more animal models for studying placental malaria can provide novel ways of circumventing problems experienced during placental malaria research in humans such as inaccurate estimation of gestational ages. Using the newly established olive baboon (Papio anubis)-Plasmodium knowlesi (P. knowlesi) H strain model of placental malaria, experiments were carried out to determine placental cytokine profiles underlying the immunopathogenesis of placental malaria. Four pregnant olive baboons were infected with blood stage P. knowlesi H strain parasites on the one fiftieth day of gestation while four other uninfected pregnant olive baboons were maintained as uninfected controls. After nine days of infection, placentas were extracted from all the eight baboons through cesarean surgery and used for the processing of placental plasma and sera samples for cytokine sandwich enzyme linked immunosorbent assays (ELISA). Results indicated that the occurrence of placental malaria was associated with elevated concentrations of tumour necrosis factor alpha (TNF-a) and interleukin 12 (IL-12). Increased levels of IL-4, IL-6 and IL-10 and interferon gamma (IFN-?) levels were detected in uninfected placentas. These findings match previous reports regarding immunity during PM thereby demonstrating the reliability of the olive baboon-P. knowlesi model for use in further studies.

Background: Senna occidentalis (L.) Link has been used worldwide in traditional treatment of many diseases and conditions including snakebite. In Kenya, a decoction from the plant roots taken orally, is used as a cure for malaria. Leaf extracts from the plant have been shown to possess antiplasmodial activity, in vitro. However, the curative potency of the plant root against established malaria infection is yet to be scientifically validated, in vivo. On the other hand, there are reports on variation in bioactivity of extracts obtained from this plant species, depending on the plant part used and place of origin among other factors. In this study, we demonstrated the antiplasmodial potency of Senna occidentalis roots extract in vitro, and in mice.Methods: Methanol, ethyl acetate, chloroform, hexane and water extracts of S. occidentalis root were tested for in vitro antiplasmodial activity against Plasmodium falciparum, strain 3D7. Cytotoxicity of the most active solvent extracts was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the curative potency in Plasmodium berghei infected mice evaluated by Rane’s test. Results: All the solvent extracts showed suppressive activity against P. falciparum, in vitro, in a concentration dependent manner. The suppression was also dependent on polarity of solvents used with the methanolic extract (most polar) being 10-fold more active than hexane extract (least polar). The extracts showed no toxicity to Vero cells at the tested concentrations and significantly suppressed P. berghei parasitemia in Rane’s test. Similarly, the extracts prolonged the survival time the infected animals significantly. Conclusions: Senna occidentalis (L.) Link root extract suppresses malaria parasites growth in vitro and in BALB/c mice. The plant root, therefore, is a potential source of antimalarial principles. This study has scientifically validated the ethnomedical usage of S. occidentalis roots in management of malaria among some Kenyan communities.