Barriers to routine G6PD testing prior to treatment with primaquine

Ley, Benedikt; Thriemer, Kamala; Jaswal, J N; Poirot, Eugenie; Alam, Mohammad Shafiul; Phru, Ching Swe; Khan, Wasif Ali; Lek, Dysoley; Gao, Qi; Kheong, Chong Chee; Shamsudin, Ummi Kalthom; Chen, Ingrid; Hwang, Jimee; Gosling, Roly; Price, Ric N.

doi:10.1186/s12936-017-1981-y

Cited by 23 publications

(23 citation statements)

References 29 publications

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“…Generating such evidence and initiating these discussions therefore becomes an important part in the decision-making process of implementing the biosensor and shorter course radical cure treatment to support P. vivax elimination. It also fuels ongoing debates about priorities at policy and practice levels ("P. vivax is benign"; "malaria is malaria"; "all forms are equally relevant"; "radical cure is a societal not an individual concern"), which were reported in this study and which persist in Bangladesh without consensus (29).…”

Section: Discussionmentioning

confidence: 68%

Implementing Radical Cure Diagnostics for Malaria: User Perspectives on G6PD Testing in Bangladesh

Engel

Ghergu

Matin

et al. 2020

Preprint

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Background: The radical cure of Plasmodium vivax requires treatment with an 8-aminoquinoline drug, such as primaquine and tafenoquine, to clear the liver of parasites which can reactivate to cause relapsing infections. Safe treatment regimens require prior screening of patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency to avoid potential life-threatening drug induced hemolysis. Testing is rarely available in malaria endemic countries, but will be needed to support routine use of radical cure. This study investigates end-user perspectives in Bangladesh on the introduction of a quantitative G6PD test (SD Biosensor STANDARD™ G6PD analyser) to support malaria elimination.Methods: The perspectives of users on the SD Biosensor test were analysed using semi-structured interviews and focus group discussions with health care providers and malaria programme officers in Bangladesh. Key emerging themes regarding the feasibility of introducing this test into routine practice, including perceived barriers, were analysed.Results: In total 63 participants were interviewed. Participants emphasized the life-saving potential of the biosensor, but raised concerns including the impact of limited staff time, high workload and some technical aspects of the device. Participants highlighted that there are both too few and too many P. vivax patients to implement G6PD testing owing to challenges of funding, workload and complex testing infrastructure. Implementing the biosensor would require flexibility and improvisation to deal with remote sites, overcoming a low index of suspicion and mutual interplay of declining patient numbers and reluctance to test. This approach would generate new forms of evidence to justify introduction in policy and carefully consider questions of deployment given declining patient numbers. Conclusions: The results of the study show that, in an elimination context, the importance of malaria needs to be maintained for both policy makers and the affected communities, in this case by ensuring P. vivax, PQ treatment, and G6PD deficiency remain visible. Availability of new technologies, such as the biosensor, will fuel ongoing debates about priorities for allocating resources that must be adapted to a constantly evolving target. Technical and logistical concerns regarding the biosensor should be addressed by future product designs, adequate training, strengthened supply chains, and careful planning of communication, advocacy and staff interactions at all health system levels.

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Section: Discussionmentioning

confidence: 68%

Implementing Radical Cure Diagnostics for Malaria: User Perspectives on G6PD Testing in Bangladesh

Engel

Ghergu

Matin

et al. 2020

Preprint

Self Cite

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“…Despite a high prevalence of G6PD deficiency and thus associated risk of drug induced hemolysis, there are few reports of PQ induced hemolytic reactions either from the local medical staff (C.S. Phru, personal communication) or in the literature [8,18]. The reasons for this are unclear, but could reflect low prescription of PQ by healthcare providers, underreporting of adverse events due to limited access to healthcare, poor treatment adherence to a prolonged course of PQ, or G6PDd individuals having partial protection against malaria [15,41,42].…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

et al. 2020

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The proportion of Plasmodium vivax malaria among all malarias is increasing worldwide. Treatment with 8-aminoquinolines remain the only radical cure. However, 8-aminoquinolines can cause severe hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. The population of the multi-ethnic Chittagong Hill Tracts (CHT) carry the highest malaria burden within Bangladesh. As in many countries the national treatment guidelines recommend 8-aminoquinoline based radical cure without routine G6PD deficiency (G6PDd) testing to guide treatment. Aim of this study was to determine the need for routine testing within a multi-ethnic population by assessing the prevalence of G6PDd among the local population. Participants from 11 ethnicities were randomly selected and malaria status was assessed by microscopy, rapid diagnostic test (RDT) and polymerase chain reaction (PCR). G6PD status was determined by spectrophotometry and G6PD genotyping. The adjusted male median (AMM) was defined as 100% G6PD activity, participants were categorized as G6PD deficient (<30% activity), G6PD intermediate (30% to 70% activity) or G6PD normal (>70% activity). Median G6PD activities between ethnicities were compared and the association between G6PD activity and malaria status was assessed. 1002 participants were enrolled and tested for malaria. G6PD activity was measured by spectrophotometry in 999 participants and host G6PD genotyping undertaken in 323 participants. Seven participants (0.7%) had peripheral parasitaemia detected by microscopy or RDT and 42 by PCR (4.2%). Among 106 participants (32.8%) with confirmed genotype, 99 (93.4%) had the Mahidol variant. The AMM was 7.03U/gHb with 90 (9.0%) G6PD deficient participants and 133 (13.3%) with intermediate G6PD activity. Median G6PD activity differed significantly between ethnicities (p<0.001), proportions of G6PD deficient individuals ranged from 2% to 26% but did not differ between participants with and without malaria. The high G6PDd prevalence and PLOS NEGLECTED TROPICAL DISEASES

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“…This assay requires a properly equipped, cold chain-supplied laboratory having staff certified to be competent in conducting this relatively sophisticated measurement. Many referral hospitals in areas where malaria is endemic, much less the health care facilities at the periphery of reach of these services, lack this capacity (287). The vast majority of malaria patients do not have access to standard quantitative G6PD testing.…”

Section: Safety Of 8-aminoquinolines In Patients Screened For G6pd Stmentioning

confidence: 99%

8-Aminoquinoline Therapy for Latent Malaria

2019

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SUMMARYThe technical genesis and practice of 8-aminoquinoline therapy of latent malaria offer singular scientific, clinical, and public health insights. The 8-aminoquinolines brought revolutionary scientific discoveries, dogmatic practices, benign neglect, and, finally, enduring promise against endemic malaria. The clinical use of plasmochin—the first rationally synthesized blood schizontocide and the first gametocytocide, tissue schizontocide, and hypnozoitocide of any kind—commenced in 1926. Plasmochin became known to sometimes provoke fatal hemolytic crises. World War II delivered a newer 8-aminoquinoline, primaquine, and the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency as the basis of its hemolytic toxicity came in 1956. Primaquine nonetheless became the sole therapeutic option against latent malaria. After 40 years of fitful development, in 2018 the U.S. Food and Drug Administration registered the 8-aminoquinoline called tafenoquine for the prevention of all malarias and the treatment of those that relapse. Tafenoquine also cannot be used in G6PD-unknown or -deficient patients. The hemolytic toxicity of the 8-aminoquinolines impedes their great potential, but this problem has not been a research priority. This review explores the complex technical dimensions of the history of 8-aminoquinolines. The therapeutic principles thus examined may be leveraged in improved practice and in understanding the bright prospect of discovery of newer drugs that cannot harm G6PD-deficient patients.

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Barriers to routine G6PD testing prior to treatment with primaquine

Cited by 23 publications

References 29 publications

Implementing Radical Cure Diagnostics for Malaria: User Perspectives on G6PD Testing in Bangladesh

Implementing Radical Cure Diagnostics for Malaria: User Perspectives on G6PD Testing in Bangladesh

Wide range of G6PD activities found among ethnic groups of the Chittagong Hill Tracts, Bangladesh

8-Aminoquinoline Therapy for Latent Malaria

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