Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Artemisinin-based combination therapy (ACT) is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ) have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS) combination therapy was adopted as the first-line treatment for uncomplicated <it>Plasmodium falciparum </it>malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the <it>in vivo </it>efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam^®, Mephaquin^®, and Mefloquina-AC^®Farma) given in combination with artesunate.</p> <p>Methods</p> <p>Thirty-nine non-pregnant adults with <it>P. falciparum </it>mono-infection were randomly assigned to receive artesunate in combination with either (1) Lariam, (2) Mephaquin, or (3) Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours), 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol.</p> <p>Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data.</p> <p>Results</p> <p>By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (C_max) and interquartile range was 2,820 ng/ml (2,614–3,108) for Lariam, 2,500 ng/ml (2,363–2,713) for Mephaquin, and 2,750 ng/ml (2,550–3,000) for Mefloquina AC Farma. The pharmacokinetics of the three formulations were generally similar, with the exception of the C_maxof Mephaquin which was significantly different to that of Lariam (<it>p </it>= 0.04).</p> <p>Conclusion</p> <p>All three formulations had similar pharmacokinetics; in addition, the pharmacokinetics seen in this Peruvian population were similar to reports from other ethnic groups. All patients rapidly cleared their parasitaemia with no evidence of recrudescence by Day 56. Continued surveillance is needed to ensure that patients continue to receive optimal therapy.</p

El proceso de adecuación y cambio en la política del tratamiento de la malaria por Plasmodium falciparum en el Perú, 1990-2001

Durante la década de 1990 el Perú experimentó la reemergencia de la malaria en la cuenca amazónica y la costa norte de su territorio; observándose simultáneamente la aparición y extensión de resistencia del Plasmodium falciparun a los medicamentos antimaláricos en ambas áreas geográficas. El Ministerio de Salud respondió al problema fortaleciendo las medidas de control disponibles y llevando a cabo una serie de estudios para precisar mejor la extensión geográfica y intensidad de la resistencia a los antimaláricos, con el objetivo de revisar y adecuar la política de tratamiento para enfrentar esta situación sanitaria emergente en el país. Se presenta una revisión del proceso de cambio de la política de tratamiento de la malaria entre 1990 y 2001 por el Ministerio de Salud del Perú, cuando decidió implementar una nueva terapia de combinación que incluye un medicamento de la familia de las artemisininas para el tratamiento de P. falciparum. Con este cambio en la política del tratamiento antimalárico, el Perú es actualmente el primer país en las Américas en utilizar la terapia de combinación con artemisininas como tratamiento de primera línea para P. falciparum no complicado. La experiencia peruana es mostrada como un modelo para otros países en la región que también están enfrentando la emergencia de malaria por P. Falciparum farmacoresistente

Qualities of an ideal volunteer community malaria worker: A comparison of the opinions of community residents and national malaria service staff

Since the late 1950s, most malaria surveillance and treatment in rural areas of Latin America has been carried out by networks of unpaid community malaria workers, known as Volunteer Collaborators, who are selected and supervised by staff of the national malaria services (NMSs) in each country. In spite of the free and readily accessible antimalarial treatment available at these Volunteer Collaborator posts, many residents continue to seek treatment elsewhere and in most cases take doses of antimalarials that are insufficient to cure their infections. To identify ways in which the Volunteer Collaborator Network could be made more attractive to residents and to improve the process of selection of new workers, we asked community residents and Guatemalan NMS workers to rank order, according to their importance, 11 qualities or characteristics of an 'ideal' volunteer malaria worker. Community residents preferred someone who is available to take care of patients at all times of the day, is a responsible person, and has a general knowledge of medicine. No significant differences were noted in the rank orders of male and female residents or literate and illiterate residents. National Malaria Service workers also preferred someone who takes care of patients at all times of the day, even when busy. In addition, they wanted individuals who recognize the importance of their work as a Volunteer Collaborator, but choosing volunteers who had a general knowledge of medicine was not inportant. By modifying the procedures used to select Volunteer Collaborators so as identify candidates with the qualities preferred by residents, it should be possible to increase acceptance and improve the performance of these volunteer workers.malaria volunteer community health worker Latin America