Effectiveness of Malaria Treatment in Mexico

Summary

In the context of malaria elimination in the Americas, solid evidence is necessary of the effectiveness of anti-malarial control measures delivered to the affected individuals. In the Americas, most P. vivax infections are sensitive to Chloroquine (CQ) and Primaquine (PQ), and the most effective treatment worldwide comprises administration of a total dose of 25 milligrams (mg)/Kilogram (kg) weight of CQ distributed in three days and 3.5 mg/kg body weight of PQ administered during 14 days (T14). In Mexico, CQ and PQ have been administered since the late 50´s to treat malarious patients. In 1999 the National Malaria Control Program implemented an intermittent single doses treatment (ISD) as part of the overall strategy. After the blood sample was obtained for diagnosis of symptomatic patients, a single combined dose of CQ and PQ was administered, and after malaria infection confirmation, additional doses were administered monthly alternating each three months, during 3 years. Although, the number of malaria cases were reduced in most affected regions, in Southern México, many patients under ISD present recurrent blood infections, presumably relapse episodes were observed. Working hypothesis: the administration of ISD is low effective to eliminate relapse episodes and its effectiveness depends on the coincidence of the relapse episodes and the administration of the medication), while the T14 is highly effective to eliminate P. vivax primary and relapse infections. Objective: To determine the antimalarial drug effectiveness of the ISD and T14, based on CQ and PQ for the treatment of uncomplicated P. vivax infection (primary and recurrent blood infections) in Southern Mexico. Methods: The study was carried out in malaria affected communities of Southern Mexico, following the WHO recommendations for clinical studies. Symptomatic patients diagnosed with P. vivax infection that meet the inclusion criteria, were invited to participate. After they accepted by informed consent, patients were semi-randomized and treated with either T14 (14-day treatment) or ISD (18 intermittent single doses of CQ-PQ). Clinical, parasitological, molecular and serological parameters were monitor over a 12-month follow up period to evaluate the treatment outcomes to cure blood infection and relapsing episodes. The study was conducted from February-2007 to October-2010. The results of this study will be used to assist the Ministry of Health of México in assessing the current national treatment guidelines for uncomplicated P. vivax malaria

Timeline

Start

2008-02

Primary completion

2010-09

Completion

2010-09

Publications

• Background Rodriguez MH, Betanzos-Reyes AF; Grupo de Trabajo de Malaria del Sistema Mesoamericano de Salud Publica. [Plan to improve malaria control towards its elimination in Mesoamerica]. Salud Publica Mex. 2011;53 Suppl 3:S333-48. Spanish.
• Background White NJ. Preventing antimalarial drug resistance through combinations. Drug Resist Updat. 1998 Mar;1(1):3-9. doi: 10.1016/s1368-7646(98)80208-2.
• Background COATNEY GR. Pitfalls in a discovery: the chronicle of chloroquine. Am J Trop Med Hyg. 1963 Mar;12:121-8. doi: 10.4269/ajtmh.1963.12.121. No abstract available.
• Background Baird JK, Basri H, Subianto B, Fryauff DJ, McElroy PD, Leksana B, Richie TL, Masbar S, Wignall FS, Hoffman SL. Treatment of chloroquine-resistant Plasmodium vivax with chloroquine and primaquine or halofantrine. J Infect Dis. 1995 Jun;171(6):1678-82. doi: 10.1093/infdis/171.6.1678.
• Background Galappaththy GN, Omari AA, Tharyan P. Primaquine for preventing relapses in people with Plasmodium vivax malaria. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004389. doi: 10.1002/14651858.CD004389.pub2.
• Background Murphy GS, Basri H, Purnomo, Andersen EM, Bangs MJ, Mount DL, Gorden J, Lal AA, Purwokusumo AR, Harjosuwarno S, et al. Vivax malaria resistant to treatment and prophylaxis with chloroquine. Lancet. 1993 Jan 9;341(8837):96-100. doi: 10.1016/0140-6736(93)92568-e.
• Background malERA Consultative Group on Drugs. A research agenda for malaria eradication: drugs. PLoS Med. 2011 Jan 25;8(1):e1000402. doi: 10.1371/journal.pmed.1000402.
• Background Ruebush TK 2nd, 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 Apr;68(4):391-7.
• Background Rubio JM, Benito A, Roche J, Berzosa PJ, Garcia ML, Mico M, Edu M, Alvar J. Semi-nested, multiplex polymerase chain reaction for detection of human malaria parasites and evidence of Plasmodium vivax infection in Equatorial Guinea. Am J Trop Med Hyg. 1999 Feb;60(2):183-7. doi: 10.4269/ajtmh.1999.60.183.
• Background Gonzalez-Ceron L, Rodriguez MH. An enzyme-linked immunosorbent assay using detergent-soluble Plasmodium vivax antigen for seroepidemiological surveys. Trans R Soc Trop Med Hyg. 1991 May-Jun;85(3):358-61. doi: 10.1016/0035-9203(91)90289-b.
• Background Gonzalez-Ceron L, Rodriguez MH, Betanzos AF, Abadia A. [Efficacy of a rapid test to diagnose Plasmodium vivax in symptomatic patients of Chiapas, Mexico]. Salud Publica Mex. 2005 Jul-Aug;47(4):282-7. doi: 10.1590/s0036-36342005000400005. Spanish.
• Background Gonzalez-Ceron L, Mu J, Santillan F, Joy D, Sandoval MA, Camas G, Su X, Choy EV, Torreblanca R. Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico. Parasit Vectors. 2013 Apr 18;6:109. doi: 10.1186/1756-3305-6-109.
• Gonzalez-Ceron L, Rodriguez MH, Sandoval MA, Santillan F, Galindo-Virgen S, Betanzos AF, Rosales AF, Palomeque OL. Effectiveness of combined chloroquine and primaquine treatment in 14 days versus intermittent single dose regimen, in an open, non-randomized, clinical trial, to eliminate Plasmodium vivax in southern Mexico. Malar J. 2015 Oct 30;14:426. doi: 10.1186/s12936-015-0938-2.

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