Primaquine alternative dosing schedules for preventing malaria relapse in people with<i>Plasmodium vivax</i>

Milligan, Rachael; Daher, André; Villanueva, Gemma; Graves, Patricia M.

doi:10.1002/14651858.cd012656.pub3

Cited by 15 publications

(13 citation statements)

References 85 publications

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“…The current primaquine dosages used for radical cure are considered safe in males and females not classified as G6PD deficient with widely used qualitative tests such as the FST, and more recently the CareStart G6PD test [19,37]. Higher dose regimens of primaquine-such as 1 mg/Kg/day for seven days-may be less safe for females with intermediate G6PD activity [36,38].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

Zobrist

Brito

Garbin³

et al. 2021

PLoS Negl Trop Dis

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Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency, prevalent in many malaria-endemic countries. G6PD-deficient individuals are susceptible to hemolysis during oxidative stress, which can occur from exposure to certain medications, including 8-aminoquinolines used to treat Plasmodium vivax malaria. Accordingly, access to point-of-care (POC) G6PD testing in Brazil is critical for safe treatment of P. vivax malaria. Methodology/Principal findings This study evaluated the performance of the semi-quantitative, POC STANDARD G6PD Test (SD Biosensor, Republic of Korea). Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. G6PD and hemoglobin measurements were obtained from capillary samples at the POC using the STANDARD and HemoCue 201+ (HemoCue AB, Sweden) tests. A thick blood slide was prepared for malaria microscopy. At the laboratories, the STANDARD and HemoCue tests were repeated on venous samples and a quantitative spectrophotometric G6PD reference assay was performed (Pointe Scientific, Canton, MI). G6PD was also assessed by fluorescent spot test. In Manaus, a complete blood count was performed. Samples were analyzed from 1,736 participants. In comparison to spectrophotometry, the STANDARD G6PD Test performed equivalently in determining G6PD status in venous and capillary specimens under varied operating temperatures. Using the manufacturer-recommended reference value thresholds, the test’s sensitivity at the <30% threshold on both specimen types was 100% (95% confidence interval [CI] venous 93.6%–100.0%; capillary 93.8%–100.0%). Specificity was 98.6% on venous specimens (95% CI 97.9%–99.1%) and 97.8% on capillary (95% CI 97.0%–98.5%). At the 70% threshold, the test’s sensitivity was 96.9% on venous specimens (95% CI 83.8%–99.9%) and 94.3% on capillary (95% CI 80.8%–99.3%). Specificity was 96.5% (95% CI 95.0%–97.6%) and 92.3% (95% CI 90.3%–94.0%) on venous and capillary specimens, respectively. Conclusion/Significance The STANDARD G6PD Test is a promising tool to aid in POC detection of G6PD deficiency in Brazil. Trial registration This study was registered with ClinicalTrials.gov (identifier: NCT04033640).

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Section: Discussionmentioning

confidence: 99%

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

Zobrist

Brito

Garbin³

et al. 2021

PLoS Negl Trop Dis

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“…Only two randomized controlled trials, with follow up to 6 months, have compared 14 days of high-versus low-dose primaquineboth were conducted in India where the risk of relapse is generally low [59,60]. The combined relative risk at 6 months was 0.82, although the 95% confidence intervals crossed parity [61]. These meta-analyses are confounded by comparison of trials with different durations of follow up, marked heterogeneity in the risk and timing of relapse in different locations, differing endpoints, and small sample sizes.…”

Section: Ineffective Treatment Of P Vivaxmentioning

confidence: 99%

Plasmodium vivax in the Era of the Shrinking P. falciparum Map

Price

Commons

Battle

et al. 2020

Trends in Parasitology

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163

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Plasmodium vivax is an important cause of malaria, associated with a significant public health burden. Whilst enhanced malaria-control activities have successfully reduced the incidence of Plasmodium falciparum malaria in many areas, there has been a consistent increase in the proportion of malaria due to P. vivax in regions where both parasites coexist. This article reviews the epidemiology and biology of P. vivax, how the parasite differs from P. falciparum, and the key features that render it more difficult to control and eliminate. Since transmission of the parasite is driven largely by relapses from dormant liver stages, its timely elimination will require widespread access to safe and effective radical cure. Extent and Burden of Plasmodium vivaxOf the five Plasmodium species that cause human malaria, Plasmodium vivax is the most geographically widespread. The parasite is capable of surviving quiescent for prolonged periods when conditions are not conducive to its ongoing transmission. A century ago P. vivax was prevalent in almost all countries; even though the vivax endemic world has shrunk considerably, over four billion people remain at risk of infection [1]. In 2017, transmission was reported from 49 countries across Central and South America, the Horn of Africa, Asia, and the Pacific islands (Figure 1). In almost two-thirds of coendemic countries P. vivax is the predominant species of malaria (Figure 2), the proportion of malaria attributable to the parasite being greatest in areas where the prevalence of malaria is low (Figure 3) [2,3].Until recently the global burden of P. vivax malaria was derived from estimates of P. falciparum, the most prevalent species causing human malaria. However, a growing awareness of the public health importance of P. vivax has led to the strengthening of surveillance systems and better reporting practices of all of the Plasmodium species. The World Health Organization (WHO) first included P. vivax case estimates in its World Malaria Report (WMR) in 2013, documenting between 11.9 and 22 million P. vivax clinical cases per year [4]. Recent estimates, incorporating national surveillance data, prevalence surveys, and geospatial mapping, have revised the global burden to between 13.7 and 15 million cases in 2017 [1]. An estimated 82% (11.7 million cases) of the global vivax burden comes from four high-burden countries: India, Pakistan, Ethiopia, and Sudan.In sub-Saharan Africa, where the burden of malaria is overwhelmingly attributable to P. falciparum (Figure 1), the low prevalence of P. vivax is attributed to a high proportion of the population having a Duffy-negative blood group. The Duffy antigen is an important molecule for the erythrocytic invasion of P. vivax, and the lack of the receptor on red blood cells reduces the risk of infection [5]. However, a recent review of clinical and vector data has shown that P. vivax is present across almost all malaria-endemic regions of Africa [6].Biological Differences between P. falciparum and P. vivaxThe control and elimination of ...

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“…In addition to the baseline global costs, 2 scenario analyses were explored to quantify the potential impact of the global implementation of a policy in which high-dose primaquine radical cure (total dose of 7 mg/kg) was administered to eligible patients after screening for G6PD deficiency. In both scenarios, the cost of a high total dose of primaquine (7 mg/kg) was used, given its high efficacy across multiple and diverse locations [13,14]; however, this potentially overestimates the cost of primaquine in areas where a lower total dose may have sufficed [37]. In the first scenario, Supervised radical cure, it was assumed that daily supervision of primaquine therapy administered to eligible patients would result in perfect adherence.…”

Section: Cost-benefit Of Global Implementation Of G6pd Testing With Radical Curementioning

confidence: 99%

Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study

et al. 2021

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Background In 2017, an estimated 14 million cases of Plasmodium vivax malaria were reported from Asia, Central and South America, and the Horn of Africa. The clinical burden of vivax malaria is largely driven by its ability to form dormant liver stages (hypnozoites) that can reactivate to cause recurrent episodes of malaria. Elimination of both the blood and liver stages of the parasites (“radical cure”) is required to achieve a sustained clinical response and prevent ongoing transmission of the parasite. Novel treatment options and point-of-care diagnostics are now available to ensure that radical cure can be administered safely and effectively. We quantified the global economic cost of vivax malaria and estimated the potential cost benefit of a policy of radical cure after testing patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Methods and findings Estimates of the healthcare provider and household costs due to vivax malaria were collated and combined with national case estimates for 44 endemic countries in 2017. These provider and household costs were compared with those that would be incurred under 2 scenarios for radical cure following G6PD screening: (1) complete adherence following daily supervised primaquine therapy and (2) unsupervised treatment with an assumed 40% effectiveness. A probabilistic sensitivity analysis generated credible intervals (CrIs) for the estimates. Globally, the annual cost of vivax malaria was US$359 million (95% CrI: US$222 to 563 million), attributable to 14.2 million cases of vivax malaria in 2017. From a societal perspective, adopting a policy of G6PD deficiency screening and supervision of primaquine to all eligible patients would prevent 6.1 million cases and reduce the global cost of vivax malaria to US$266 million (95% CrI: US$161 to 415 million), although healthcare provider costs would increase by US$39 million. If perfect adherence could be achieved with a single visit, then the global cost would fall further to US$225 million, equivalent to $135 million in cost savings from the baseline global costs. A policy of unsupervised primaquine reduced the cost to US$342 million (95% CrI: US$209 to 532 million) while preventing 2.1 million cases. Limitations of the study include partial availability of country-level cost data and parameter uncertainty for the proportion of patients prescribed primaquine, patient adherence to a full course of primaquine, and effectiveness of primaquine when unsupervised. Conclusions Our modelling study highlights a substantial global economic burden of vivax malaria that could be reduced through investment in safe and effective radical cure achieved by routine screening for G6PD deficiency and supervision of treatment. Novel, low-cost interventions for improving adherence to primaquine to ensure effective radical cure and widespread access to screening for G6PD deficiency will be critical to achieving the timely global elimination of P. vivax.

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Primaquine alternative dosing schedules for preventing malaria relapse in people withPlasmodium vivax

Abstract: Trusted evidence. Informed decisions. Better health. Cochrane Database of Systematic Reviews Analysis 4.2. Comparison 4: 1.0 mg/kg/day primaquine 7 days versus high-standard 0.5 mg/kg/day 14 days, Outcome 2: Recurrence by 12 months' follow-up subgrouped by geographical region.

Cited by 15 publications

References 85 publications

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil

Plasmodium vivax in the Era of the Shrinking P. falciparum Map

Global economic costs due to vivax malaria and the potential impact of its radical cure: A modelling study

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