Confirmed Plasmodium vivax Resistance to Chloroquine in Central Vietnam

Abstract

Plasmodium vivax resistance to chloroquine (CQ) is currently reported in almost all countries where P. vivax is endemic. In Vietnam, despite a first report on P. vivax resistance to chloroquine published in the early 2000s, P. vivax was still considered sensitive to CQ. Between May 2009 and December 2011, a 2-year cohort study was conducted in central Vietnam to assess the recommended radical cure regimen based on a 10-day course of primaquine (0.5 mg/kg/day) together with 3 days of CQ (25 mg/kg). Here we report the results of the first 28-day follow-up estimating the cumulative risk of P. vivax recurrences together with the corresponding CQ blood concentrations, among other endpoints. Out of 260 recruited P. vivax patients, 240 completed treatment and were followed up to day 28 according to the WHO guidelines. Eight patients (3.45%) had a recurrent P. vivax infection, at day 14 (n = 2), day 21 (n = 1), and day 28 (n = 5). Chloroquine blood concentrations, available for 3/8 recurrent infections (days 14, 21, and 28), were above the MIC (>100 ng/ml whole blood) in all of these cases. Fever and parasitemia (both sexual and asexual stages) were cleared by day 3. Anemia was common at day 0 (35.8%), especially in children under 10 years (50%), and hemoglobin (Hb) recovery at day 28 was substantial among anemic patients (median change from day 0 to 28, +1.7 g/dl; interquartile range [IQR], +0.7 to +3.2). This report, based on CQ blood levels measured at the time of recurrences, confirms for the first time P. vivax CQ resistance in central Vietnam and calls for further studies using standardized protocols for accurately monitoring the extent and evolution of P. vivax resistance to chloroquine in Vietnam. These results, together with the mounting evidence of artemisinin resistance in central Vietnam, further highlight the increasing threat of antimalarial drug resistance to malaria elimination in Vietnam.

Population Genetics of Plasmodium vivax in Four Rural Communities in Central Vietnam

“…Samples were collected from April 2009 to December 2010 in four communities ( Fig 1 ) in the South Tra My district of Quang Nam, Central Vietnam during a prospective cohort study aiming to assess the short- and long-term efficacy of CQ and high-dose piperaquine (PQ) for the treatment of P . vivax mono-infections [ 12 ]. Detailed sociodemographic characteristics of the local population have been already reported elsewhere [ 3 ].…”

“…falciparum to artemisinin derivatives and partner drugs and for P . vivax to chloroquine (CQ) [ 2 , 11 , 12 ].…”

Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination

“…Chloroquine (CQ) has been withdrawn from treating P. falciparum malaria in most endemic countries due to widespread resistance to this drug [8,9], but CQ-primaquine (PQ) combination is still the first-line treatment for P. vivax infections in most endemic countries [10,11]. Unfortunately, there is an increased number of reports of reduced susceptibility of P. vivax parasites to CQ from malaria-endemic areas, including the GMS countries [2,8,[12][13][14][15][16][17][18][19][20][21]. Despite this, there is still a lack of a confirmed marker(s) for CQ resistance in P. vivax.…”

Ending Malaria Transmission in the Asia Pacific Malaria Elimination Network (APMEN) Countries: Challenges and the Way Forward

“…A number of APMEN countries have reported P. vivax resistance to chloroquine. There are reports of resistance in some States of India [59][60][61][62], central Vietnam [63], and Thai-Myanmar border [64]. However, P. vivax is still sensitive to chloroquine in Cambodia [65], border area of Yunnan Province of China and Myanmar [66], central China [67], and Nepal [68,69].…”