A qualitative study of the feasibility and community perception on the effectiveness of artemether-lumefantrine use in the context of home management of malaria in south-west Nigeria

<p>Abstract</p> <p>Background</p> <p>In Nigeria ACT use at the community level has not been evaluated and the use of antimalarial drugs (commonly chloroquine (CQ)) at home has been shown to be largely incorrect. The treatment regimen of ACT is however more complicated than that of CQ. There is thus a need to determine the feasibility of using ACT at the home level and determine community perception on its use.</p> <p>Methods</p> <p>A before and after qualitative study using key informant interviews (KII) and focus group discussions (FGDs) was conducted in selected villages in Ona-Ara local government area. At baseline, 14 FGDs and 14 KIIs were conducted. Thereafter, community medicine distributors (CMDs) were trained in each village to dispense artemeter-lumenfantrine (AL) to febrile children aged 6–59 months presumed to have uncomplicated malaria. After one year of drug distribution, nine KIIs and 10 FGDs were conducted. Participants and key informants were mothers and fathers with children under five years, traditional heads of communities, opinion leaders and health workers.</p> <p>Results</p> <p>None of the participants have heard of AL prior to study. Participants were favourably disposed to introduction of AL into the community. Mothers/caregivers were said to have used AL in place of the orthodox drugs and herbs reported commonly used prior to study after commencement of AL distribution. The use of CMDs for drug distribution was acceptable to the participants and they were judged to be efficient as they were readily available, distributed correct dose of AL and mobilised the community effectively. AL was perceived to be very effective and no significant adverse event was reported. Major concerns to the sustainability of the program were the negative attitudes of health workers towards discharge of their duties, support to the CMDs and the need to provide CMDs incentives. In addition regular supply of drugs and adequate supervision of CMDs were advised.</p> <p>Conclusion</p> <p>Our findings showed that the use of AL at home and community level is feasible with adequate training of community medicine distributors and caregivers. Community members perceived AL to be effective thus fostering acceptability. The negative attitudes of the health workers and issue of incentives to CMDs need to be addressed for successful scaling-up of ACT use at community level.</p

Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa

BACKGROUND: In vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa. METHODS: The prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing. RESULTS: 295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site. CONCLUSION: No Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers

Antitrypanosomal activity of some medicinal plants from Nigerian ethnomedicine

Human African trypanosomiasis is a neglected tropical disease with complex clinical presentation, diagnosis, and difficult treatment. The available drugs for the treatment of trypanosomiasis are old, expensive, and less effective, associated with severe adverse reactions and face the problem of drug resistance. This situation underlines the urgent need for the development of new, effective, cheap, and safe drugs for the treatment of trypanosomiasis. The search for new antitrypanosomal agents in this study is based on ethnomedicine. In vitro antitrypanosomal activity of 36 plant extracts from 10 plant species from Nigerian ethnomedicine was evaluated against bloodstream forms of Trypanosoma brucei rhodesiense STIB 900. Cytotoxic activity was determined against mammalian L6 cells. Alamar blue assay was used to measure the endpoint of both antitrypanosomal and toxicity assays. The ethyl acetate extract of leaves of Ocimum gratissimum Linn. (Labiatae) showed the highest antitrypanosomal activity (IC(50) of 2.08 +/- 0.01 mug/ml) and a high selective index of 29. Furthermore, the hexane, ethyl acetate, or methanol extracts of Trema orientalis (L.) Blume (Ulmaceae), Pericopsis laxiflora (Benth. ex Baker) Meeuwen, Jatropha curcas Linn. (Euphorbiaceae), Terminalia catappa Linn. (Combretaceae), and Vitex doniana Sweet (Verbenaceae) displayed remarkable antitrypanosomal activity (IC(50) 2.1-17.2 mug/ml) with high selectivity indices (20-80) for trypanosomes. The antitrypanosomal activity of T. catappa and T. orientalis against T. brucei rhodesiense (STIB 900) is being reported for the first time in Nigerian ethnomedicine, and these plants could be a potential source of antitrypanosomal agent

In Vitro and In Vivo Antimalarial Activity of Ficus thonningii Blume (Moraceae) and Lophira alata Banks (Ochnaceae), Identified from the Ethnomedicine of the Nigerian Middle Belt

Drug resistance in Plasmodium falciparum requires that new drugs must be developed. Plants are a potential source for drug discovery and development. Two plants that used to treat febrile illnesses in Nigeria were tested for in vitro and in vivo antimalarial activity and cytotoxicity in cancer cell lines. Methanol, hexane, and ethyl acetate leaf extracts of Ficus thonningii and Lophira alata were active in in vitro assays against P. falciparum NF54 (sensitive) and K1 (multiresistant) strains. Hexane extracts of F. thonningii and L. alata were the most effective extracts in in vitro assays with IC50 of 2.7±1.6 μg/mL and 2.5±0.3 μg/mL for NF54 and 10.4±1.6 μg/mL and 2.5±2.1 μg/mL for K1 strain. All extracts were nontoxic in cytotoxicity assays against KB human cell line with IC50 of over 20 μg/mL, demonstrating selectivity against P. falciparum. In vivo analysis shows that hexane extracts of both plants reduced parasitaemia. At the maximum dose tested, L. alata had a 74.4% reduction of parasitaemia while F. thonningii had a reduction of 84.5%, both extracts prolonged animal survival in mice infected with P. berghei NK65 when compared with vehicle treated controls. The antiplasmodial activity observed justifies the use of both plants in treating febrile conditions

Comparison of SYBR Green I-, PicoGreen-, and [H-3]-hypoxanthine-based assays for in vitro antimalarial screening of plants from Nigerian ethnomedicine

The standard method for in vitro antimalarial drug screening is based on the isotopic assay which is expensive and utilizes radioactive materials with limited availability, safety, and disposal problems in developing countries. The use of non-radioactive DNA stains SYBR Green I (SG) and PICO greenA (R) (PG) for antimalarial screening had been reported. However, the use of the two DNA stains for antimalarial screening of medicinal plants has not been compared. Thus, this study compared SG, PG with the [H-3]-hypoxanthine (HP) incorporation assays for in vitro antimalarial screening of medicinal plants. The 50% inhibitory concentration (IC50) values obtained using the three methods for antimalarial activity of medicinal plants and standard antimalarial drugs were similar. Data generated from this study suggests that the non-radioactive microflourimetric assay is sufficiently sensitive to reproducibly identify plant extracts with antimalarial activity from those lacking activity. The HP-based assay exhibited the most robust signal-to-noise ratio of 100, compared with signal-to-noise ratios of 7 for SG and 8 for PG. The SG-based assay is less expensive than the PG- and HP-based assays. SG appears to be a cost-effective alternative for antimalarial drug screening and a viable technique that may facilitate antimalarial drug discovery process especially in developing countrie