Implementation of basic quality control tests for malaria medicines in Amazon Basin countries: results for the 2005-2010 period.

BACKGROUND: Ensuring the quality of malaria medicines is crucial in working toward malaria control and eventual elimination. Unlike other validated tests that can assess all critical quality attributes, which is the standard for determining the quality of medicines, basic tests are significantly less expensive, faster, and require less skilled labour; yet, these tests provide reproducible data and information on several critical quality attributes, such as identity, purity, content, and disintegration. Visual and physical inspection also provides valuable information about the manufacturing and the labelling of medicines, and in many cases this inspection is sufficient to detect counterfeit medicines. The Promoting the Quality of Medicines (PQM) programme has provided technical assistance to Amazon Malaria Initiative (AMI) countries to implement the use of basic tests as a key screening mechanism to assess the quality of malaria medicines available to patients in decentralized regions. METHODS: Trained personnel from the National Malaria Control Programmes (NMCPs), often in collaboration with country's Official Medicine Control Laboratory (OMCL), developed country- specific protocols that encompassed sampling methods, sample analysis, and data reporting. Sampling sites were selected based on malaria burden, accessibility, and geographical location. Convenience sampling was performed and countries were recommended to store the sampled medicines under conditions that did not compromise their quality. Basic analytical tests, such as disintegration and thin layer chromatography (TLC), were performed utilizing a portable mini-laboratory. RESULTS: Results were originally presented at regional meetings in a non-standardized format that lacked relevant medicines information. However, since 2008 information has been submitted utilizing a template specifically developed by PQM for that purpose. From 2005 to 2010, the quality of 1,663 malaria medicines from seven AMI countries was evaluated, mostly collected from the public sector, 1,445/1,663 (86.9%). Results indicate that 193/1,663 (11.6%) were found not to meet quality specifications. Most failures were reported during visual and physical inspection, 142/1663 (8.5%), and most of these were due to expired medicines, 118/142 (83.1%). Samples failing TLC accounted for 27/1,663 (1.6%) and those failing disintegration accounted for 24/1,663 (1.4%). Medicines quality failures decreased significantly during the last two years. CONCLUSIONS: Basic tests revealed that the quality of medicines in the public sector improved over the years, since the implementation of this type of quality monitoring programme in 2005. However, the lack of consistent confirmatory tests in the quality control (QC) laboratory, utilizing methods that can also evaluate additional quality attributes, could still mask quality issues. In the future, AMI countries should improve coordination with their health authorities and their QC lab consistently, to provide a more complete picture of malaria medicines quality and support the implementation of corrective actions. Facilities in the private and informal sectors also should be included when these sectors constitute an important source of medicines used by malaria patients.

[Therapeutic response of Plasmodium vivax to chloroquine in Bolivia]. / Respuesta terapéutica de Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia.

INTRODUCTION: Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. OBJECTIVE: The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. MATERIALS AND METHODS: An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. RESULTS: The mean parasitemias (asexual) on day 0 were 6,147 parasites/µl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. CONCLUSION: Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

Respuesta terapéutica de Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia / Therapeutic response of Plasmodium vivax to chloroquine in Bolivia

Introducción. La determinación de la eficacia de la cloroquina contra Plasmodium vivax permite mejorar la capacidad de vigilancia de la resistencia a los antipalúdicos. Objetivo. Evaluar la eficacia terapéutica de la cloroquina como tratamiento de malaria no complicadapor P. vivax en Riberalta, Guayaramerín y Yacuiba, Bolivia. Materiales y métodos. Se llevó a cabo un estudio de la eficacia in vivo en pacientes mayores de cinco años; se suministró cloroquina (25 mg/kg en tres días) y se hizo seguimiento por 28 días, midiendo los niveles de cloroquina en sangre y desetilcloroquina, el día dos y el día de registro de reaparición de parasitemia. Para la evaluación de la incidencia acumulada de falla del tratamiento, se usó el análisis de supervivencia de Kaplan-Meier. Resultados. Se estudiaron 223 pacientes (Riberalta, 84; Guayaramerín, 80; Yacuiba, 59). Las medias de densidad parasitaria (formas asexuadas) del día 0 en Riberalta fueron de 6.147, en Guayaramerín, 4.251, y en Yacuiba, 5.214 parásitos/μl de sangre. En el mismo orden, los promedios de concentraciones sanguíneas de cloroquina-desetilcloroquina del día 2 fueron de 783, 817 y 815 ng/ml. Mientras en Yacuiba no se presentaron fracasos terapéuticos, en Riberalta ocurrieron con frecuencia de 6,2 % y en Guayaramerín de 10 %. Los valores de cloroquina y desetilcloroquina en sangre de pacientes con fracaso terapéutico fueron menores de 70 ng/ml en el día de reaparición de parasitemia. Conclusión. No se evidenció resistencia de P. vivax a la cloroquina en las tres regiones de evaluación en Bolivia. Se requieren mayores estudios de la concentración de la cloroquina en sangre.

Introduction. Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. Objective. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. Materials and methods. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. Results. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Conclusion. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.