Am. J. Trop. Med. Hyg., 80(6), 2009, pp. 889–895 Copyright © 2009 by The American Society of Tropical Medicine and Hygiene 889 * Address correspondence to Mario H. Rodriguez, Centro de Inves- tigaciones en Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Av. Universidad 655, Cuernavaca, Morelos 62508, Mexico. E-mail: mhenry@insp.mx The Participation of Secondary Clinical Episodes in the Epidemiology of Vivax Malaria during Pre- and Post-Implementation of Focal Control in the State of Oaxaca, Mexico Mario H. Rodriguez,* Ángel F. Betanzos-Reyes, Juan E. Hernández-Ávila, Jorge F. Méndez-Galván, Rogelio Danis-Lozano, and Armando Altamirano-Jiménez Center for Research in Infectious Diseases, National Institute of Public Health, Cuernavaca, Morelos, Mexico; Regional Center for Research in Public Health, National Institute of Public Health, Tapachula, Chiapas, Mexico; Pan-American Health Organization/World Health Organization Representation, Mexico City, Mexico; Department of Informatics and Medical Geography, National Institute of Public Health, Cuernavaca, Morelos, Mexico; Children’s Hospital of Mexico, Mexico City, Mexico; Secretariat of Health of the State of Oaxaca, Oaxaca City, Oaxaca, Mexico Abstract. The participation of vivax malaria secondary clinical was researched in a retrospective cohort of 33,414 confirmed cases occurring between 1994 and 2005 in the state of Oaxaca, Mexico. Secondary episodes occurred in 23.4% of all primary cases. An increase in secondary episodes was associated with primary cases occurring during the dry sea- sons (risk ratio [RR] = 1.68, 95% CI: 1.45–1.96). The incidence of secondary episodes peaked at an older age, occurred similarly in men and women mostly during low mosquito abundance, and had a uniform distribution among localities. A reduction in secondary episodes was associated with the administration of an increased dose and early administration of primaquine (RR = 0.32, 95% CI: 0.26–0.38). However, limitations to distinguish relapses from re-infections impede assessment of the new treatment effect on relapses and its contribution to malaria control in the area. These findings highlight the need for new therapeutic schemes to radical cure of P. vivax infections and operational research aimed at parasite pool elimination. INTRODUCTION Plasmodium vivax strategy for survival as dormant forms in the liver of patients and the production of gametocytes during pre-symptomatic blood infection add difficulty to the control of its transmission. The resulting chronicity of the infection, manifested in symptomatic and asymptomatic relapses, enable P. vivax parasites to persist under unstable environmental con- ditions that determine seasonal mosquito abundance. 1–3 Plasmodium vivax is responsible for more than 99% of malaria cases in Mexico, and the frequency of secondary epi- sodes is estimated at 20% to 30%, similar to that observed in other parts of the world. 4–7 After the last epidemic outbreak that occurred in the 1980s, malaria is under control in most parts of the country, but persists in residual foci located on the coast of the Pacific Ocean. The main residual focus is located in the state of Oaxaca, which concentrated more than 42% of the 118,602 malaria cases occurring in the country between 1994 and 2005 (records of the National Program for Vector Borne Diseases of the National Center for Disease Surveillance and Control, NCDSC). Until 1998, malaria vector control consisted of DDT indoor spraying, and one dose of chloroquine was administered to pre- sumptive malaria (febrile) patients at the time of blood sam- pling for diagnosis. A complete treatment with chloroquine and primaquine was administered once the diagnosis was confirmed. Starting in 1999, a new control strategy (named focal control) was progressively introduced. This includes environmental management of mosquito breeding sites and home improve- ments, 8 and a single increased dose of primaquine plus the same dose of chloroquine administered to febrile patients at the time of blood sampling, followed by two monthly doses (chlo- roquine and primaquine) upon confirmation of the diagnosis. After the introduction of the focal control, the incidence of malaria cases in Oaxaca decreased from 5.11 cases/1,000 inhab- itants in 1998 to 0.2 cases/1,000 inhabitants during the period 2000–2005 (Table 1). In this work, we describe the main characteristics of the epidemiology of malaria before and after the introduction of focal control in the State of Oaxaca, including a decrease in the proportion of malaria secondary clinical episodes in patients treated with the new therapeutic scheme. The limita- tions in separating relapses from re-infections make it difficult to assess the effect of the new treatment scheme on relapses and its contribution to malaria control in the area. MATERIAL AND METHODS Design. The protocol of the study was approved by the Ethics Committee of the National Institute of Public Health, Mexico. This was a population-based retrospective longitudi- nal observational study of a cohort that included all P. vivax malaria cases detected and confirmed by the Malaria Control Program (MCP) of the state of Oaxaca between 1994 and 2005. Malaria incidence was calculated using the 1995, 2000, and 2005 population census (Table 1) and National Population Counts (National Institute of Geography and Information) to calculate the annual population at risk. The secondary clinical episode incidence was calculated using the primary cases in the year as population at risk. This made it possible to estimate relative risks instead of odds ratios. Study site. The study population included residents of six sanitary jurisdictions, of which the Pochutla-Coast region (Sanitary Jurisdiction IV) and the Loxichas and Central Valley regions (Sanitary Jurisdiction I) concentrated the greatest malaria incidence (Figure 1). Malaria transmission is seasonal and peaks are reached during the dry seasons when there is an abundance of the main vector Anopheles pseudopunctipennis. 9 Detection of malaria cases. Malaria cases were detected and diagnosed by the State’s Malaria Control Program surveil- lance system. In this system, passive detection of malaria cases is carried out in established community posts. In addition,