Skip to main content
Top
Published in: Malaria Journal 1/2012

Open Access 01-12-2012 | Research

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

Authors: Ana C Santelli, Isabela Ribeiro, André Daher, Marcos Boulos, Paola B Marchesini, Roseli La Corte dos Santos, Marize BF Lucena, Izanelda Magalhães, Antonio P Leon, Washington Junger, José LB Ladislau

Published in: Malaria Journal | Issue 1/2012

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference WHO: Guidelines for the treatment of malaria. 2010, Geneva, Switzerland: World Health Organization WHO: Guidelines for the treatment of malaria. 2010, Geneva, Switzerland: World Health Organization
2.
go back to reference Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, Brockman A, Anderson T, McGready R, Phaiphun L, Proux S, van Vugt M, Hutagalung R, Lwin KM, Phyo AP, Preechapornkul P, Imwong M, Pukrittayakamee S, Singhasivanon P, White NJ, Nosten F: Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS ONE. 2009, 4: e4551-10.1371/journal.pone.0004551.PubMedCentralCrossRefPubMed Carrara VI, Zwang J, Ashley EA, Price RN, Stepniewska K, Barends M, Brockman A, Anderson T, McGready R, Phaiphun L, Proux S, van Vugt M, Hutagalung R, Lwin KM, Phyo AP, Preechapornkul P, Imwong M, Pukrittayakamee S, Singhasivanon P, White NJ, Nosten F: Changes in the treatment responses to artesunate-mefloquine on the northwestern border of Thailand during 13 years of continuous deployment. PLoS ONE. 2009, 4: e4551-10.1371/journal.pone.0004551.PubMedCentralCrossRefPubMed
3.
go back to reference Nosten F, Luxemburger C, ter Kuile FO, Woodrow C, Eh JP, Chongsuphajaisiddhi T, White NJ: Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis. 1994, 170: 971-977. 10.1093/infdis/170.4.971.CrossRefPubMed Nosten F, Luxemburger C, ter Kuile FO, Woodrow C, Eh JP, Chongsuphajaisiddhi T, White NJ: Treatment of multidrug-resistant Plasmodium falciparum malaria with 3-day artesunate-mefloquine combination. J Infect Dis. 1994, 170: 971-977. 10.1093/infdis/170.4.971.CrossRefPubMed
4.
go back to reference Nosten F, White NJ: Artemisinin-based combination treatment of falciparum malaria. Am J Trop Med Hyg. 2007, 77: 181-192.PubMed Nosten F, White NJ: Artemisinin-based combination treatment of falciparum malaria. Am J Trop Med Hyg. 2007, 77: 181-192.PubMed
5.
go back to reference Denis MB, Tsuyuoka R, Poravuth Y, Narann TS, Seila S, Lim C, Incardona S, Lim P, Sem R, Socheat D, Christophel EM, Ringwald P: Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia. Trop Med Int Health. 2006, 11: 1360-1366. 10.1111/j.1365-3156.2006.01690.x.CrossRefPubMed Denis MB, Tsuyuoka R, Poravuth Y, Narann TS, Seila S, Lim C, Incardona S, Lim P, Sem R, Socheat D, Christophel EM, Ringwald P: Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia. Trop Med Int Health. 2006, 11: 1360-1366. 10.1111/j.1365-3156.2006.01690.x.CrossRefPubMed
6.
go back to reference Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White NJ: Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet. 2000, 356: 297-302. 10.1016/S0140-6736(00)02505-8.CrossRefPubMed Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Brockman A, McGready R, ter Kuile F, Looareesuwan S, White NJ: Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study. Lancet. 2000, 356: 297-302. 10.1016/S0140-6736(00)02505-8.CrossRefPubMed
7.
go back to reference van den Broek IV, Maung UA, Peters A, Liem L, Kamal M, Rahman M, Rahman MR, Bangali AM, Das S, Barends M, Faiz AM: Efficacy of chloroquine + sulfadoxine–pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh. Trans R Soc Trop Med Hyg. 2005, 99: 727-735. 10.1016/j.trstmh.2005.02.007.CrossRefPubMed van den Broek IV, Maung UA, Peters A, Liem L, Kamal M, Rahman M, Rahman MR, Bangali AM, Das S, Barends M, Faiz AM: Efficacy of chloroquine + sulfadoxine–pyrimethamine, mefloquine + artesunate and artemether + lumefantrine combination therapies to treat Plasmodium falciparum malaria in the Chittagong Hill Tracts, Bangladesh. Trans R Soc Trop Med Hyg. 2005, 99: 727-735. 10.1016/j.trstmh.2005.02.007.CrossRefPubMed
8.
go back to reference Price RN, Nosten F, Luxemburger C, van Vugt M, Phaipun L, Chongsuphajaisiddhi T, White NJ: Artesunate/mefloquine treatment of multi-drug resistant falciparum malaria. Trans R Soc Trop Med Hyg. 1997, 91: 574-577. 10.1016/S0035-9203(97)90032-8.CrossRefPubMed Price RN, Nosten F, Luxemburger C, van Vugt M, Phaipun L, Chongsuphajaisiddhi T, White NJ: Artesunate/mefloquine treatment of multi-drug resistant falciparum malaria. Trans R Soc Trop Med Hyg. 1997, 91: 574-577. 10.1016/S0035-9203(97)90032-8.CrossRefPubMed
9.
go back to reference Ashley EA, Lwin KM, McGready R, Simon WH, Phaiphun L, Proux S, Wangseang N, Taylor W, Stepniewska K, Nawamaneerat W, Thwai KL, Barends M, Leowattana W, Olliaro P, Singhasivanon P, White NJ, Nosten F: An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. Trop Med Int Health. 2006, 11: 1653-1660. 10.1111/j.1365-3156.2006.01724.x.CrossRefPubMed Ashley EA, Lwin KM, McGready R, Simon WH, Phaiphun L, Proux S, Wangseang N, Taylor W, Stepniewska K, Nawamaneerat W, Thwai KL, Barends M, Leowattana W, Olliaro P, Singhasivanon P, White NJ, Nosten F: An open label randomized comparison of mefloquine-artesunate as separate tablets vs. a new co-formulated combination for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand. Trop Med Int Health. 2006, 11: 1653-1660. 10.1111/j.1365-3156.2006.01724.x.CrossRefPubMed
10.
go back to reference Krudsood S, Looareesuwan S, Tangpukdee N, Wilairatana P, Phumratanaprapin W, Leowattana W, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WR: New fixed-dose artesunate-mefloquine formulation against multidrug-resistant Plasmodium falciparum in adults: a comparative phase IIb safety and pharmacokinetic study with standard-dose nonfixed artesunate plus mefloquine. Antimicrob Agents Chemother. 2010, 54: 3730-3737. 10.1128/AAC.01187-09.PubMedCentralCrossRefPubMed Krudsood S, Looareesuwan S, Tangpukdee N, Wilairatana P, Phumratanaprapin W, Leowattana W, Chalermrut K, Ramanathan S, Navaratnam V, Olliaro P, Vaillant M, Kiechel JR, Taylor WR: New fixed-dose artesunate-mefloquine formulation against multidrug-resistant Plasmodium falciparum in adults: a comparative phase IIb safety and pharmacokinetic study with standard-dose nonfixed artesunate plus mefloquine. Antimicrob Agents Chemother. 2010, 54: 3730-3737. 10.1128/AAC.01187-09.PubMedCentralCrossRefPubMed
11.
go back to reference WHO: World Health Organization. 2009, Geneva, Switzerland: World malaria report WHO: World Health Organization. 2009, Geneva, Switzerland: World malaria report
12.
go back to reference Oliveira-Ferreira J, Lacerda MV, Brasil P, Ladislau JL, Tauil PL, Daniel-Ribeiro CT: Malaria in Brazil: an overview. Malar J. 2010, 9: 115-10.1186/1475-2875-9-115.PubMedCentralCrossRefPubMed Oliveira-Ferreira J, Lacerda MV, Brasil P, Ladislau JL, Tauil PL, Daniel-Ribeiro CT: Malaria in Brazil: an overview. Malar J. 2010, 9: 115-10.1186/1475-2875-9-115.PubMedCentralCrossRefPubMed
13.
go back to reference Manual de Terapêutica da Malária: Manual de Terapêutica da Malária. 2003, Ministério da Saúde: Manual de Terapêutica da Malária Manual de Terapêutica da Malária: Manual de Terapêutica da Malária. 2003, Ministério da Saúde: Manual de Terapêutica da Malária
14.
go back to reference Kremsner PG, Zotter GM, Feldmeier H, Graninger W, Kollaritsch M, Wiedermann G, Rocha RM, Wernsdorfer WH: In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil. Bull World Health Organ. 1989, 67: 289-293.PubMedCentralPubMed Kremsner PG, Zotter GM, Feldmeier H, Graninger W, Kollaritsch M, Wiedermann G, Rocha RM, Wernsdorfer WH: In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil. Bull World Health Organ. 1989, 67: 289-293.PubMedCentralPubMed
15.
go back to reference Neifer S, Kremsner PG: Drug susceptibility of Plasmodium falciparum in the western Amazon region, State of Acre, Brazil. Rev Inst Med Trop Sao Paulo. 1991, 33: 205-211.CrossRefPubMed Neifer S, Kremsner PG: Drug susceptibility of Plasmodium falciparum in the western Amazon region, State of Acre, Brazil. Rev Inst Med Trop Sao Paulo. 1991, 33: 205-211.CrossRefPubMed
16.
go back to reference Ferreira MU, Da Silva-Nunes M: Evidence-based public health and prospects for malaria control in Brazil. J Infect Dev Ctries. 2010, 4: 533-545.CrossRefPubMed Ferreira MU, Da Silva-Nunes M: Evidence-based public health and prospects for malaria control in Brazil. J Infect Dev Ctries. 2010, 4: 533-545.CrossRefPubMed
17.
go back to reference Ruebush TK: Marquino W, Zegarra J, Neyra D, Villaroel R, Avila JC, Diaz C, Beltran E: Practical aspects of in vivo antimalarial drug efficacy testing in the Americas. Am J Trop Med Hyg. 2003, 68: 391-397.PubMed Ruebush TK: Marquino W, Zegarra J, Neyra D, Villaroel R, Avila JC, Diaz C, Beltran E: Practical aspects of in vivo antimalarial drug efficacy testing in the Americas. Am J Trop Med Hyg. 2003, 68: 391-397.PubMed
18.
go back to reference Ferreira Goncalves MJ, Alecrim WD: Non-planed urbanization as a contributing factor for malaria incidence in Manaus-Amazonas, Brazil. Rev Salud Publica (Bogota). 2004, 6: 156- Ferreira Goncalves MJ, Alecrim WD: Non-planed urbanization as a contributing factor for malaria incidence in Manaus-Amazonas, Brazil. Rev Salud Publica (Bogota). 2004, 6: 156-
19.
go back to reference Implementation of Artemisinin Combination Therapies (ACTs): Role of ASMQ: Implementation of Artemisinin Combination Therapies (ACTs): Role of ASMQ:
20.
go back to reference de Andrade AL, Martelli CM, Oliveira RM, Arias JR, Zicker F, Pang L: High prevalence of asymptomatic malaria in gold mining areas in Brazil. Clin Infect Dis. 1995, 20: 475-10.1093/clinids/20.2.475.CrossRefPubMed de Andrade AL, Martelli CM, Oliveira RM, Arias JR, Zicker F, Pang L: High prevalence of asymptomatic malaria in gold mining areas in Brazil. Clin Infect Dis. 1995, 20: 475-10.1093/clinids/20.2.475.CrossRefPubMed
21.
go back to reference Duarte EC, Gyorkos TW, Pang L, Abrahamowicz M: Epidemiology of malaria in a hypoendemic Brazilian Amazon migrant population: a cohort study. Am J Trop Med Hyg. 2004, 70: 229-237.PubMed Duarte EC, Gyorkos TW, Pang L, Abrahamowicz M: Epidemiology of malaria in a hypoendemic Brazilian Amazon migrant population: a cohort study. Am J Trop Med Hyg. 2004, 70: 229-237.PubMed
22.
go back to reference Tadei WP, Thatcher BD, Santos JM, Scarpassa VM, Rodrigues IB, Rafael MS: Ecologic observations on anopheline vectors of malaria in the Brazilian Amazon. Am J Trop Med Hyg. 1998, 59: 325-335.PubMed Tadei WP, Thatcher BD, Santos JM, Scarpassa VM, Rodrigues IB, Rafael MS: Ecologic observations on anopheline vectors of malaria in the Brazilian Amazon. Am J Trop Med Hyg. 1998, 59: 325-335.PubMed
23.
go back to reference World Health Organization, Communicable Diseases Cluster: Severe falciparum malaria. Trans R Soc Trop Med Hyg. 2000, 94 (1): 1-90. 10.1016/S0035-9203(00)90413-9.CrossRef World Health Organization, Communicable Diseases Cluster: Severe falciparum malaria. Trans R Soc Trop Med Hyg. 2000, 94 (1): 1-90. 10.1016/S0035-9203(00)90413-9.CrossRef
24.
go back to reference Fellegi IP, Sunter AB: A theory for record linkage. Journal of the American Statistical Association. 1969, 64: 1183-1210. 10.1080/01621459.1969.10501049.CrossRef Fellegi IP, Sunter AB: A theory for record linkage. Journal of the American Statistical Association. 1969, 64: 1183-1210. 10.1080/01621459.1969.10501049.CrossRef
25.
go back to reference Camargo KR: Coeili CM: Reclink: aplicativo para o relacionamento de bases de dados, implementando o método probabilistic record linkage. Cad Saúde Pública. 2000, 16: 439-447.CrossRefPubMed Camargo KR: Coeili CM: Reclink: aplicativo para o relacionamento de bases de dados, implementando o método probabilistic record linkage. Cad Saúde Pública. 2000, 16: 439-447.CrossRefPubMed
26.
go back to reference Barnes KI, Durrheim DN, Little F, Jackson A, Mehta U, Allen E, Dlamini SS, Tsoka J, Bredenkamp B, Mthembu DJ, White NJ, Sharp BL: Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal. South Africa. PLoS Med. 2005, 2: e330-PubMed Barnes KI, Durrheim DN, Little F, Jackson A, Mehta U, Allen E, Dlamini SS, Tsoka J, Bredenkamp B, Mthembu DJ, White NJ, Sharp BL: Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal. South Africa. PLoS Med. 2005, 2: e330-PubMed
27.
go back to reference Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, Naing AL, Nyo MY, Myint NZ, Imwong M, Ashley E, Lee SJ, White NJ: Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010, 10: 673-681. 10.1016/S1473-3099(10)70187-0.PubMedCentralCrossRefPubMed Smithuis F, Kyaw MK, Phe O, Win T, Aung PP, Oo AP, Naing AL, Nyo MY, Myint NZ, Imwong M, Ashley E, Lee SJ, White NJ: Effectiveness of five artemisinin combination regimens with or without primaquine in uncomplicated falciparum malaria: an open-label randomised trial. Lancet Infect Dis. 2010, 10: 673-681. 10.1016/S1473-3099(10)70187-0.PubMedCentralCrossRefPubMed
28.
go back to reference Carrara VI, Sirilak S, Thonglairuam J, Rojanawatsirivet C, Proux S, Gilbos V, Brockman A, Ashley EA, McGready R, Krudsood S, Leemingsawat S, Looareesuwan S, Singhasivanon P, White N, Nosten F: Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: the Tak Malaria Initiative. PLoS Med. 2006, 3: e183-10.1371/journal.pmed.0030183.PubMedCentralCrossRefPubMed Carrara VI, Sirilak S, Thonglairuam J, Rojanawatsirivet C, Proux S, Gilbos V, Brockman A, Ashley EA, McGready R, Krudsood S, Leemingsawat S, Looareesuwan S, Singhasivanon P, White N, Nosten F: Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: the Tak Malaria Initiative. PLoS Med. 2006, 3: e183-10.1371/journal.pmed.0030183.PubMedCentralCrossRefPubMed
29.
go back to reference Ashley EA, Stepniewska K, Lindegardh N, McGready R, Hutagalung R, Hae R, Singhasivanon P, White NJ, Nosten F: Population pharmacokinetic assessment of a new regimen of mefloquine used in combination treatment of uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2006, 50: 2281-2285. 10.1128/AAC.00040-06.PubMedCentralCrossRefPubMed Ashley EA, Stepniewska K, Lindegardh N, McGready R, Hutagalung R, Hae R, Singhasivanon P, White NJ, Nosten F: Population pharmacokinetic assessment of a new regimen of mefloquine used in combination treatment of uncomplicated falciparum malaria. Antimicrob Agents Chemother. 2006, 50: 2281-2285. 10.1128/AAC.00040-06.PubMedCentralCrossRefPubMed
30.
go back to reference Simpson JA, Watkins ER, Price RN, Aarons L, Kyle DE, White NJ: Mefloquine pharmacokinetic-pharmacodynamic models: implications for dosing and resistance. Antimicrob Agents Chemother. 2000, 44: 3414-3424. 10.1128/AAC.44.12.3414-3424.2000.PubMedCentralCrossRefPubMed Simpson JA, Watkins ER, Price RN, Aarons L, Kyle DE, White NJ: Mefloquine pharmacokinetic-pharmacodynamic models: implications for dosing and resistance. Antimicrob Agents Chemother. 2000, 44: 3414-3424. 10.1128/AAC.44.12.3414-3424.2000.PubMedCentralCrossRefPubMed
Metadata
Title
Effect of artesunate-mefloquine fixed-dose combination in malaria transmission in amazon basin communities
Authors
Ana C Santelli
Isabela Ribeiro
André Daher
Marcos Boulos
Paola B Marchesini
Roseli La Corte dos Santos
Marize BF Lucena
Izanelda Magalhães
Antonio P Leon
Washington Junger
José LB Ladislau
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2012
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-11-286

Other articles of this Issue 1/2012

Malaria Journal 1/2012 Go to the issue