Resistance of infection by Plasmodium vivax to chloroquine in Bolivia

Añez, Arletta; Moscoso, Manuel; Laguna, A. López; Garnica, Cecilia; Melgar, Viviana; Cuba, Mauren; Gutiérrez, Sonia; Ascaso, Carlos

doi:10.1186/s12936-015-0774-4

Cited by 22 publications

(19 citation statements)

References 18 publications

(14 reference statements)

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“…This contrasts with results of a similar trial in Bolivia that documented ACPR of 89.6% at Day 28. 27 The study in Bolivia and ours are comparable in design; however, the Bolivia trial did not include primaquine, and the combination of chloroquine and primaquine is more effective in treating chloroquine-sensitive and chloroquineresistant P. vivax strains. 28 On the other hand, our study shows a moderate rate of recurrent episodes occurring between Day 28 and the end of follow-up (Day 168).…”

Section: Discussionmentioning

confidence: 85%

Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

Negreiros¹,

Farias²,

Viana

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. We evaluated the efficacy of chloroquine and primaquine on uncomplicated Plasmodium vivax malaria in Cruzeiro do Sul, Brazil, in 2014. Patients ≥ 5 years of age with either fever or history of fever, and laboratoryconfirmed P. vivax monoinfection received chloroquine (total dose = 25 mg/kg) and primaquine (total dose = 3.5 mg/kg), and were followed up for 168 days (24 weeks). We used microsatellite genotyping to differentiate recurrent infections caused by heterologous parasites from those caused by homologous ones. No new P. vivax episode occurred by Day 28 among 119 enrolled patients, leading to Day 28, with adequate clinical and parasitological response (ACPR) of 100% (95% confidence interval [CI] = 96.7-100%). Twenty-eight P. vivax episodes occurred by Day 168, with uncorrected ACPR of 69.9% (95% CI = 59.5-79.0%). Fifteen of these episodes were caused by either homologous haplotypes or haplotypes that could not be determined. Excluding the 13 recurrent episodes caused by heterologous parasites, Day 168 microsatellite-corrected ACPR was estimated at 81.2% (95% CI = 71.0-89.1%). Chloroquine and primaquine remain efficacious to treat acute uncomplicated P. vivax infection, but moderate recurrence rates were observed within 24 weeks of follow-up.

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Section: Discussionmentioning

confidence: 85%

Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

Negreiros¹,

Farias²,

Viana

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…P. vivax resistance to CQ has been documented in the major Amazonian port city of Manaus, in northwestern Brazil, with parasitological failure rates of 6.4% to 10.1% over 28 days of follow-up in patients treated with CQ alone (8,9), compared with 5.2% failures in patients treated according to the current malaria therapy guidelines in Brazil with concomitant CQ and primaquine (PQ) (10). Moreover, P. vivax resistance to CQ has been occasionally described in countries sharing borders with Brazil, such as Bolivia (11), Peru, and Guyana (12). However, recrudescences at day 28 were not observed following CQ-PQ treatment of vivax malaria in other settings of endemicity in Brazil (13), including Juruá Valley, the region with the highest malaria rates in this country (14).…”

mentioning

confidence: 99%

Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

Ladeia‐Andrade

et al. 2019

Antimicrob Agents Chemother

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Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo. In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax-infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.)

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“…Two patients presented TF diagnosed by PCR, both within CQ therapeutic range (CQ + DECQ ³ 100 ng/mL), 50 similar to results in other locations. 18,51,52 Therapeutic failures in the presence of CQ levels above its MICs, are very suggestive of a case of CQ-resistant P. vivax.…”

Section: Discussionmentioning

confidence: 99%

“…In the early 2000s, publications reported Adequate Clinical and Parasitological Response (ACPR) to CQ in malaria vivax, with no recurrent parasitemia within the next 28 days after receiving treatment [13][14][15] alongside others with clinical treatment failures suggesting CQ resistance. [16][17][18][19] More recent studies show the presence of P. vivax isolates harboring CQ-resistant mutations in French Guiana and Brazil. 20,21 Reported cases of TF with CQ alone in South America suggest that it is necessary to monitor the clinical and parasitological response to the drug because of a possible unrecognized emergence of resistant P. vivax strains in Colombia, although the extent of the threat to national malaria control efforts remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Chloroquine–Primaquine Therapeutic Efficacy, Safety, and Plasma Levels in Patients with Uncomplicated Plasmodium vivax Malaria in a Colombian Pacific Region

Mesa-Echeverry

Niebles-Bolivar

Tobón-Castaño

2019

The American Journal of Tropical Medicine and Hygiene

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In Colombia, published studies for the treatment of uncomplicated Plasmodium vivax malaria with chloroquine-primaquine (CQ-PQ) are scarce. The aim of the study was to evaluate the therapeutic efficacy and safety profile of this combination. A clinical trial was performed in adults with uncomplicated P. vivax malaria using the 28-day World Health Organization validated protocol. Patients received supervised antimalarial treatment and the primary efficacy end point was the clinical and parasitological response. Safety was assessed through adverse events surveillance, and plasma levels of antimalarial drugs were measured. A total of 77 patients were included. Adequate clinical and parasitological response rate diagnosed by thick blood smear examination was achieved in 72 of 73 patients (98.6%) with a complete 28-day follow-up. There were two parasitological therapeutic failures (TFs) (2.9%) on day 28, established by polymerase chain reaction among 68 patients, one of them with a positive film. No adverse events were detected. After completing the antimalarial treatment, all patients reached adequate plasma concentrations of CQ and desethylchloroquine (DECQ), with medians of 302.9 and 104.0 ng/mL, respectively. Uncomplicated P. vivax malaria treatment with CQ-PQ standard treatment was effective and safe in the study population; TFs were not associated with low plasma levels of CQ and DECQ.

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Resistance of infection by Plasmodium vivax to chloroquine in Bolivia

Cited by 22 publications

References 18 publications

Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

Efficacy of Chloroquine and Primaquine for the Treatment of Uncomplicated Plasmodium vivax Malaria in Cruzeiro do Sul, Brazil

Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil

Chloroquine–Primaquine Therapeutic Efficacy, Safety, and Plasma Levels in Patients with Uncomplicated Plasmodium vivax Malaria in a Colombian Pacific Region

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