Evaluating the Efficacy of Chloroquine for the Treatment of Plasmodium Vivax Infections in Central Vietnam

• Status: Unknown status
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Understanding the extent and regional distribution of CQR vivax malaria and detecting early signs of resistance is critical to prevent the spread of resistant strains, optimize treatment guidelines, and reduce the risk of recurrent and severe malaria. In Vietnam, CQR in P.vivax has been reported sporadically. One study carried out in Binh Thuan province (central-south Vietnam) at the end of the 1990s demonstrated early P.vivax recurrences (7%) by Day 16 after a 3-day CQ treatment. However, in a summary report to World Health Organization (WHO) including data from 11 sentinel sites, from studies conducted between 2006 and 2011 in central and southern Vietnam (total 350 patients), P.vivax is still considered sensitive to CQ. More recently in a cohort study conducted in Quang Nam province (Central Vietnam) in which P.vivax patients were treated radically with CQ and primaquine (10-day at 0.5mg/kg/day) following national guidelines, the 28-day failure rate was measured at 3.45% and CQ blood concentrations measured at day of recurrence (>100ng/ml) confirmed resistance in three patients. The current national guidelines for the radical cure regimen of P.vivax infections recommends 3 days of CQ (total 25 mg/kg body weight (bw)) together with 14 days of primaquine at 0.25 mg/kg bw/ day.

The current WHO protocol recommends a 28-day follow-up to assess the efficacy of CQ for the treatment of P.vivax infections. However, recurrence of early stage resistant parasites may occur after Day 28 in the presence of CQ blood levels above the minimum efficacy concentration (MEC, ≥100ng/ml) and relapses could occur as early as 36 days after standard CQ treatment. Therefore, in order to confirm CQR it is recommended to extend the follow-up period, to Day 42 or 63 and measure whole blood CQ level at Day 28 and at the time of recurrence. Moreover, it has been shown that emerging drug resistance in P.vivax is associated with delayed parasite clearance after treatment, i.e. some parasites are still detectable at Day 3. The aim of the present study is to assess the in vivo and ex vivo susceptibility of P.vivax to CQ in Central Vietnam following the currently recommended radical cure regimen and using GMP certified CQ.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Malariology, Parasitology and Entomology, Vietnam
• Collaborator: Institute of Tropical Medicine, Belgium
• Treatments: Chloroquine; Chloroquine diphosphate

Criteria

Inclusion Criteria:

• Mono-infection of P. vivax by light microscopy (LM) with asexual parasite density >250/µl

• Age ≥1year

• Axillary temperature ≥ 37.5º C and/or history of fever during the previous 48 hours;

• Patient or caregiver consent to enrolment and agree to sampling and return visits;

Exclusion Criteria:

• General danger signs or symptoms of severe malaria (as per WHO definitions; Annex I);

• Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values, Annex II);

• Slide confirmed infection with any other Plasmodium species (including mixed infections);

• Severe anaemia, defined as haemoglobin (Hb) <7g/dl in adults and <5g/dl in children;

• Known hypersensitivity to any of the drugs being evaluated;

• Presence of fever due to illness other than malaria;

• History of serious and/or chronic medical condition (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS);

• Pregnancy (confirmed by rapid test) or breastfeeding;

• Regular use of medication that may interfere with antimalarial pharmacokinetics;