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Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities

Ana C Santelli1, Isabela Ribeiro3*, André Daher23, Marcos Boulos4, Paola B Marchesini5, Roseli La Corte dos Santos6, Marize BF Lucena7, Izanelda Magalhães7, Antonio P Leon8, Washington Junger8 and José LB Ladislau1

Author Affiliations

1 Programa Nacional de Controle da Malária, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil

2 Drugs for Neglected Diseases initiative, Rio de Janeiro, Brazil

3 Instituto de Tecnologia em Fármacos - Farmanguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

4 Universidade de São Paulo, São Paulo, Brazil

5 Pan American Health Organization, Brasília, Brazil

6 Universidade Federal de Sergipe, Sergipe, Brazil

7 Secretaria Estadual de Saúde, Acre, Brazil

8 Universidade do Estado do Rio de Janeiro – UERJ, Rio de Janeiro, Brazil

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Malaria Journal 2012, 11:286  doi:10.1186/1475-2875-11-286

Published: 20 August 2012

Abstract

Background

Studies in South-East Asia have suggested that early diagnosis and treatment with artesunate (AS) and mefloquine (MQ) combination therapy may reduce the transmission of Plasmodium falciparum malaria and the progression of MQ resistance.

Methods

The effectiveness of a fixed-dose combination of AS and MQ (ASMQ) in reducing malaria transmission was tested in isolated communities of the Juruá valley in the Amazon region.

Priority municipalities within the Brazilian Legal Amazon area were selected according to pre-specified criteria. Routine national malaria control programmatic procedures were followed. Existing health structures were reinforced and health care workers were trained to treat with ASMQ all confirmed falciparum malaria cases that match inclusion criteria. A local pharmacovigilance structure was implemented. Incidence of malaria and hospitalizations were recorded two years before, during, and after the fixed-dose ASMQ intervention. In total, between July 2006 and December 2008, 23,845 patients received ASMQ. Two statistical modelling approaches were applied to monthly time series of P. falciparum malaria incidence rates, P. falciparum/Plasmodium vivax infection ratio, and malaria hospital admissions rates. All the time series ranged from January 2004 to December 2008, whilst the intervention period span from July 2006 to December 2008.

Results

The ASMQ intervention had a highly significant impact on the mean level of each time series, adjusted for trend and season, of 0.34 (95%CI 0.20 – 0.58) for the P. falciparum malaria incidence rates, 0.67 (95%CI 0.50 – 0.89) for the P. falciparum/P. vivax infection ratio, and 0.53 (95%CI 0.41 – 0.69) for the hospital admission rates. There was also a significant change in the seasonal (or monthly) pattern of the time series before and after intervention, with the elimination of the malaria seasonal peak in the rainy months of the years following the introduction of ASMQ. No serious adverse events relating to the use of fixed-dose ASMQ were reported.

Conclusions

In the remote region of the Juruá valley, the early detection of malaria by health care workers and treatment with fixed-dose ASMQ was feasible and efficacious, and significantly reduced the incidence and morbidity of P. falciparum malaria.

Keywords:
Malaria; ACT; artesunate; mefloquine; Fixed-dose combination; P. falciparum; Brazil; Amazon