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Aim of the studyThe in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five Congolese plants were evaluated. The plants were selected following an ethnobotanical survey conducted in D.R. Congo and focusing on plants used traditionally to treat malaria. The in vivo antimalarial activity of aqueous and methanolic extracts active in vitro was also determined in mice infected by Plasmodium berghei berghei. Materials and methodsThe growth inhibition of Plasmodium falciparum strains was evaluated using the measurement of lactate dehydrogenase activity. The extracts (aqueous, CH 3 OH, EtOH and CH 2 Cl 2 ) were prepared by maceration and tested in vitro against the 3D7 (chloroquine sensitive) and W2 (chloroquine resistant) strains of Plasmodium falciparum and against the human normal fetal lung fibroblasts WI-38 to determine the selectivity index. Some extracts were also used at the dose of 300mg/kg to evaluate their activity in mice infected since 4 days by Plasmodium berghei. ResultsTwo plants presented a very high activity (IC 50 < 3µg/ml). These plants were Strychnos icaja roots bark (MeOH and CH 2 Cl 2 ) and Physalis angulata leaves (MeOH and CH 2 Cl 2 ). One plant (Anisopappus chinensis whole plant, MeOH and CH 2 Cl 2 ) presented a high activity (IC50 < 15µg/ml).The extracts of Anisopappus chinensis and Physalis angulata showed also a good inhibition of parasitemia in vivo. Flavonoids, phenolic acids and terpenes were identified in these plants by a general phytochemical screening method. ConclusionThree plants showed a very interesting antiplasmodial activity (Anisopappus chinensis, Physalis angulata, Strychnos icaja) and one of them showed a good selectivity index ( >10, Anisopappus chinensis). Anisopappus chinensis and Physalis angulata were also active in vivo.

The antimalarial activities of crude extracts and 17 fractions from the partition of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as antimalarial remedies in the Democratic Republic of Congo were studied both in vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei berghei. The toxic effects of dried aqueous extracts of the plants were also investigated, in uninfected mice. The most active crude extracts in vitro, with median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the methanolic and dichloromethane extracts of C. mubango, and the dichloromethane extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml), followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py. staudii (IC(50) = 15.2 microg/ml). Results from the in-vivo tests of antimalarial activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water-soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n-butanolic fractions from Py. staudtii produced >80% chemosuppression of the parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii produced a slightly lower but still significant inhibition of parasitaemia (60%-80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%. The dried aqueous extract of the stem bark of C. mubango showed some signs of toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female mice and 900 mg/kg in the male. The extract significantly increased the serum concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood levels of creatinine or urea. No significant toxic effect was observed for the dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg). Neither of these extracts affected the serum concentrations of GPT or the blood concentrations of creatinine and urea, although the N. pobeguinii extract did increase the serum concentration of GOT.

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a ‘best practice’ that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries. In response to the WHO request, a best practices and bottlenecks analysis was conducted in 2015. This analysis was updated in 2018 in the light of the minimum requirements of the WHO to set up a PV system taking into account other guidance for PV systems. The following themes were retained for analysis: (1) creation of the national PV center; (2) implementation of PV in the health system; (3) data collection and analysis; (4) collaboration with public health programs; (5) collaboration with the National Regulatory Authority. Lessons learnt from the DRC experience show that it is possible to implement PV systems in order to promote patients’ safety in resource limited sub-Saharan African countries with no guaranteed funding. The ability of national PV centers to collaborate with Public health stakeholders, including public health authorities at all levels as well as public health programs, and to use existing health information systems are considered the main key to success and may substantially reduce the cost of PV activities.