Monitoring of clinical efficacy and in vitro sensitivity of Plasmodium vivax to chloroquine in area along Thai Myanmar border during 2009-2010

Abstract

Background: In Thailand, the proportion of Plasmodium vivax infection has become equal to Plasmodium falciparum. Reports of a trend of gradual decline of in vitro sensitivity of P. vivax to chloroquine in some areas of the country, together with accumulating evidences of chloroquine resistance P. vivax in other parts of the world, emphasize the need for closely and continuously monitoring clinical efficacy in conjunction with in vitro sensitivity of P. vivax isolates. Methods: The study was conducted at Mae Tao clinic for migrant workers, Tak Province during March 2008 -August 2009. A total of 130 patients (17 Thais and 113 Burmeses; 64 males and 66 females) with mono-infection of P. vivax malaria, aged between 15-60 years and weighing more than 40 kg, were included in the study. Patients received treatment with chloroquine (2,000 mg chloroquine phosphate over three days) and the anti-relapse drug primaquine (15 mg for 14 days). In vitro sensitivity of P. vivax isolates was evaluated by schizont maturation inhibition assay. Results: All patients showed satisfactory response to treatment. The cure rate was virtually 100% within the followup period of 42 days. Neither recurrence of P. vivax parasitaemia nor appearance of P. falciparum occurred during the investigation period. In vitro data showed a stable sensitivity of chloroquine in this area since 2006. Geometric mean and median (95% CI) values of IC 50 for chloroquine were 100.1 and 134.7 (1.1-264.9) nM, respectively. Conclusion: In vivo results suggest that the standard regimen of chloroquine was still very effective for the treatment of blood infections with P. vivax in the Thai-Myanmar border area. In vitro sensitivity data however, raise the possibility of potential advent of resistance in the future. Regular monitoring of the chloroquine sensitivity of P. vivax is essential to facilitate the early recognition of treatment failures and to expedite the formulation of appropriate changes to the drug policy.

Therapeutic Responses of Plasmodium vivax Malaria to Chloroquine and Primaquine Treatment in Northeastern Myanmar

“…Clinical observations in Thailand in the past showed either complete sensitivity (29)(30)(31)(32) or only small proportions of patients developing recurrent parasitemia within 28 days (33,34). Similarly, in the neighboring region of China's Yunnan Province, longitudinal monitoring suggested that CQ efficacy remained relatively unchanged, with 1.5% (9/603) patients experiencing late clinical failure (35).…”

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

“…This improvement in systemic exposure of CQ/DECQ should benefit treatment of patients, particularly in the light of accumulating reports on increasing level of CQ resistant P. vivax. Results of high clinical efficacy of CQ (100%) from various studies in Thailand in larger numbers of patients support this supposition (Muhamad et al, 2011). Since all patients responded well to treatment with no reappearance of parasitemia during the follow up period, relationship between MIC of CQ/DECQ and clinical efficacy could not be assessed in this study.…”

“…The study was conducted 15 years after the first study in a larger number of patients admitted to Mae Tao clinic for migrant workers in Tak province of Thailand, the area with multidrug resistant P. falciparum along the ThaiMyanmar border. This population-based pharmacokinetic study was also part of the clinical study carried out during 2010-2011 to monitor the clinical efficacy and in vitro sensitivity of P. vivax isolates to CQ in 75 patients with P. vivax malaria (Muhamad et al, 2011). A two-compartment model was best fit with the concentration-time profiles of both CQ and DECQ, with a one transit compartment model for the absorption of CQ.…”

“…Clinical efficacy of CQ for treatment of P. vivax malaria in Thailand during the past decades up to now remains satisfactory, with cure rate of approximately 100% (NaBangchang et al, 1994a;Congpuong et al, 2002;Muhamad et al, 2011). This high efficacy is observed despite an observation of a trend in gradual decline of in vitro sensitivity of P. vivax isolates to CQ in some areas of the country, particularly along the Thai-Myanmar border (Congpuong et al, 2002;Tasanor et al, 2006; Bureau of Vector Borne Diseases of Thailand, 2015).…”

“…The drug has now been rendered completely ineffective for treatment and prophylaxis of P. falciparum due to drug resistance. The clinical efficacy of a threeday CQ for P. vivax infection in Thailand is conserved with cure rate of virtually 100% (Tasanor et al, 2006;Vijaykadga et al, 2006;Muhamad et al, 2011), although a trend in gradual decline of in vitro sensitivity to the drug has been documented in some areas of the country, particularly along the Thai-Myanmar border (Bureau of Vector Borne Diseases of Thailand, 2015). Nevertheless, the accumulating reports of CQ resistant P. vivax in other parts of the world during the past three decades, particularly in Southeast Asian region including Indonesia, Papua New Guinea, Irian Jaya and Vietnam (WHO, 2016), emphasize the need for closely and continuously monitoring clinical efficacy of CQ in conjunction with in vitro sensitivity with confirmed adequacy of systemic drug exposure.…”