Browsing by Subject "malaria"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Open Access
    Modeling the relationship between precipitation and malaria incidence in Mpumalanga, South Africa
    (BioMed Central Ltd, 2012) Silal, Sheetal
    Climatic or weather-driven factors such as rainfall have considerable impact on vector abundance and the extrinsic cycles that parasites undergo in mosquitoes. Climate models therefore allow for a better understanding of the dynamics of malaria transmission. While malaria seasons occur regularly between October and May in Mpumalanga, there is considerable variation in the starting point, peak and magnitude of the season. The relationship between rainfall and malaria incidence may be used to better model the variation in the malaria season. As a first step, this study seeks to explore the complex association between rainfall and malaria incidence through time series methods.
  • Thumbnail Image
    Item
    Open Access
    Mutation of GGMP Repeat Segments of Plasmodium falciparum Hsp70-1 Compromises Chaperone Function and Hop Co-Chaperone Binding
    (2021-02-23) Makumire, Stanley; Dongola, Tendamudzimu Harmfree; Chakafana, Graham; Tshikonwane, Lufuno; Chauke, Cecilia Tshikani; Maharaj, Tarushai; Zininga, Tawanda; Shonhai, Addmore
    Parasitic organisms especially those of the Apicomplexan phylum, harbour a cytosol localised canonical Hsp70 chaperone. One of the defining features of this protein is the presence of GGMP repeat residues sandwiched between α-helical lid and C-terminal EEVD motif. The role of the GGMP repeats of Hsp70s remains unknown. In the current study, we introduced GGMP mutations in the cytosol localised Hsp70-1 of Plasmodium falciparum (PfHsp70-1) and a chimeric protein (KPf), constituted by the ATPase domain of E. coli DnaK fused to the C-terminal substrate binding domain of PfHsp70-1. A complementation assay conducted using E. coli dnaK756 cells demonstrated that the GGMP motif was essential for chaperone function of the chimeric protein, KPf. Interestingly, insertion of GGMP motif of PfHsp70-1 into DnaK led to a lethal phenotype in E. coli dnaK756 cells exposed to elevated growth temperature. Using biochemical and biophysical assays, we established that the GGMP motif accounts for the elevated basal ATPase activity of PfHsp70-1. Furthermore, we demonstrated that this motif is important for interaction of the chaperone with peptide substrate and a co-chaperone, PfHop. Our findings suggest that the GGMP may account for both the specialised chaperone function and reportedly high catalytic efficiency of PfHsp70-1.
  • Thumbnail Image
    Item
    Open Access
    A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers
    (BioMed Central Ltd, 2011) Chilengi, Roma; Juma, Rashid; Abdallah, Ahmed; Bashraheil, Mahfudh; Lodenyo, Hudson; Nyakundi, Priscilla; Anabwani, Evelyn; Salim, Amina; Mwambingu, Gabriel; Wenwa, Ednah; Jemutai, Julie; Kipkeu, Chemtai; Oyoo, George; Muchohi, Simon; Kokwaro, Gilber
    BACKGROUND: Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. METHODS: Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. RESULTS: The mean age of participants was 23.9 +/- 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product) were reported. The maximum concentration (Cmax) was 160-200 nM and after 6 hours, the effective concentration (Ceff) was <150 nM. CONCLUSION: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.
  • Thumbnail Image
    Item
    Open Access
    Studies on in vitro antiplasmodial activity of cleome rutidosperma
    (2010) Bose, Anindya; Lategan, Carmen Abriette; Smith, Peter J; Gupta, Jayanta Kumar
    Malaria is a protozoal disease transmitted by the Anopheles mosquito, caused by minute parasitic protozoa of the genus Plasmodium, which infect human and insect hosts alternatively. It affects over 40% of the worldís population, with 120 million cases reported, and about 2 million deaths annually (1). The P. falciparum variety of the parasite accounts for 80% of cases and 90% of deaths caused by malaria. The declining efficacy of classical medication in relation to the rapid increase of parasite resistant strains, mainly of Plasmodium falciparum, as well as the greater resistance of vectors to insecticides, and the difficulty of creating efficient vaccines have led to an urgent need for new efficient antimalarial drugs (2, 3). Natural molecules may provide innovative strategies towards malarial control, hence active research groups are now working to develop new active compounds as an alternative to chloroquine, especially from artemisinin (4, 5), a plant-based antimalaria drug isolated from the Chinese plant Artemisia annua (6). Plants may well, therefore, prove to be the sources of new antimalarial in view of the success with the two important chemotherapeutic agents, quinine and artemisinin, both of which are derived from plants. Cleome rutidosperma (Capparidaceae) is a low-growing herb, up to 70 cm tall, found in waste grounds and grassy places with trifoliate leaves and small, violet-blue flowers, which turn pink as they age. The elongated capsules display the asymmetrical, dull black seeds. The plant is native to West Africa, although it has become naturalized in various parts of tropical America as well as Southeast Asia (7, 8). The diuretic, laxative, anthelmintic, antimicrobial, analgesic, anti-inflammatory, antipyretic, antioxidant and free radical scavenging activities of Cleome rutidosperma were reported earlier by the authors (9-13). The plant is used as antimalarial by the traditional healers in Cameroon and mild antiplasmodial activity of chloroform/methanol (1:1) extract of leaves of Cleome rutidosperma against chloroquine-sensitive (F32) laboratory strain of P. falciparum was reported earlier in Cameroon (14). The present study investigates the in vitro antiplasmodial activity of ethanolic extract and its fractions of aerial parts of Cleome rutidosperma against the chloroquine sensitive (CQS) D10 strain of the parasite, as well as their toxicity against a mammalian cell lines.
  • Thumbnail Image
    Item
    Open Access
    Synthesis of triazole-linked 2-trichloromethylquinazolines and exploration of their efficacy against P. falciparum
    (South African Chemical Institute, 2013) Hamann, A R; de Kock, C; Smith, P J; van Otterlo, W A; Blackie, M A
    Using 2-trichloromethylquinazoline as scaffold, seven novel triazole-linked compounds have been synthesized using CuAAC chemistry. The in vitrobiological activity of four of the compounds on the Plasmodium falciparumchloroquine-sensitive strain NF54 was then determined. The compounds which were tested showed moderate activity with 1.45 /iM as the lowest inhibitory concentration.