Do anti-malarials in Africa meet quality standards? The market penetration of non quality-assured artemisinin combination therapy in eight African countries

BACKGROUND: Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. RESULTS: In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. CONCLUSIONS: Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance

Development of a simple and specific direct competitive ELISA for the determination of artesunate using an anti-artesunate polyclonal antiserum

Background: Since artesunate (ART) became a vital component of artemisinin (ARM)-based combination therapies for the treatment for malaria,counterfeit ART drugs have spread in regions of Southeast Asia and Africa. The consumption of counterfeit ART drugs has resulted in the death of many patients. Thus,evaluating the quality of ART drugs is needed. There are several methods for quantitating the ART content in tablets,the most common being a high-performance liquid chromatography. However,that method is hampered by the need for expensive equipment and a rather time-consuming process of extraction. By contrast,enzyme-linked immunosorbent assays (ELISAs) are faster and much less expensive,and they require less sample preparation than the above method. The objective of the present study was to establish a simple and specific direct competitive ELISA for the determination of ART concentrations using an anti-ART polyclonal antibody (pAb). Results: Anti-ART pAb was raised in mice,and ART-horseradish peroxidase (HRP) conjugate was produced. A direct competitive ELISA was performed by simultaneously incubating ART and the ART-HRP conjugate with the anti-ART pAb over a second antibody. Subsequently,the enzyme activity of the remaining ART-HRP conjugate was measured. The intra-and inter-assay coefficients of variation of the ELISA were less than 10 % in the range of 0.3 to 30 ng/ml with a detection limit of 0.1 ng/ml. The cross-reactivities of the anti-ART pAb with ARM and dihydroartemisinin were 0.12 and 0.04 %,respectively,and those with other antimalarial drugs were negligible. Furthermore,the recovery of 10 or 50 ng/ml ART added to the drug tablet solutions containing an expected amount of 10 ng/ml was estimated by the ELISA. The recovery of the ART amount ranged between 98 and 106 %,with coefficient variations of less than 7.0 %. Conclusions: The present ELISA is a simple and specific method for the determination of ART concentrations. Thus,this ELISA can be used to identify ART counterfeits and substandard drugs and to quantify the ART drugs

Scope for non-crop plants to promote conservation biological control of crop pests and serve as sources of botanical insecticides

Besides providing food and shelter to natural enemies of crop pests, plants used in conservation biological control interventions potentially provide additional ecosystem services including providing botanical insecticides. Here we concurrently tested the strength of these two services from six non-crop plants in managing cabbage pests in Ghana over three successive field seasons. Crop margin plantings of Ageratum conyzoides, Tridax procumbens, Crotalaria juncea, Cymbopogon citratus, Lantana camara and Talinum triangulare were compared with a bare earth control in a three-way split plot design such that the crop in each plot was sprayed with either a 10% (w/v) aqueous extract from the border plant species, a negative control (water) and a positive control (emamectin benzoate ‘Attack’ insecticide). Pests were significantly less numerous in all unsprayed treatments with non-crop plant margins and in corresponding sprayed treatments (with botanical or synthetic insecticide positive control) while treatments with bare earth margin or sprayed with water (negative controls) had the highest pest densities. Numbers of predators were significantly depressed by synthetic insecticide but higher in other treatments whether unsprayed or sprayed with botanical insecticide. We conclude that some plant species have utility in both conservation biological control and as source of botanical insecticides that are relatively benign to natural enemies. In this crop system, however, the additional cost associated with using botanical insecticides was not justified by greater levels of pest suppression than achieved from border plants alone