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

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.

Glucose-6-phosphate dehydrogenase deficiency and the use of primaquine: top-down and bottom-up estimation of professional costs.

The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60.71, and the bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and nursing technician (R$5.93), estimated a total cost of R$52.68. The difference was only R$8.03, which shows that the amounts paid by the Hospital Inpatient Authorization (AIH) are estimates close to those obtained by the bottom-up technique for the professionals directly involved in the care.

Glucose-6-phosphate dehydrogenase deficiency and the use of primaquine: top-down and bottom-up estimation of professional costs / Deficiência de glicose-6-fosfato desidrogenase e uso de primaquina: estimativa de custos de profissionais por macrocusteio e microcusteio

ABSTRACT The aim of this study has been to study whether the top-down method, based on the average value identified in the Brazilian Hospitalization System (SIH/SUS), is a good estimator of the cost of health professionals per patient, using the bottom-up method for comparison. The study has been developed from the context of hospital care offered to the patient carrier of glucose-6-phosphate dehydrogenase (G6PD) deficiency with severe adverse effect because of the use of primaquine, in the Brazilian Amazon. The top-down method based on the spending with SIH/SUS professional services, as a proxy for this cost, corresponded to R$60.71, and the bottom-up, based on the salaries of the physician (R$30.43), nurse (R$16.33), and nursing technician (R$5.93), estimated a total cost of R$52.68. The difference was only R$8.03, which shows that the amounts paid by the Hospital Inpatient Authorization (AIH) are estimates close to those obtained by the bottom-up technique for the professionals directly involved in the care.

RESUMO A pesquisa teve por objetivo estudar se o macrocusteio, baseado no valor médio identificado no Sistema de Internação Hospitalar (SIH/SUS), constitui um bom estimador do custo de profissionais de saúde por paciente, tendo como comparação o método de microcusteio. O estudo foi desenvolvido no contexto da assistência hospitalar oferecida ao portador da deficiência de glicose-6-fosfato desidrogenase (dG6PD) do sexo masculino com evento adverso grave devido ao uso da primaquina, na Amazônia Brasileira. O macrocusteio baseado no gasto em serviços profissionais do SIH/SUS, como proxy desse custo, correspondeu a R$60,71, e o microcusteio, baseado nos salários do médico (R$30,43), do enfermeiro (R$16,33) e do técnico de enfermagem (R$5,93), estimou um custo total de R$52,68. A diferença foi de apenas R$8,03, mostrando que os valores pagos pela Autorização de Internação Hospitalar (AIH) são estimadores próximos daqueles obtidos por técnica de microcusteio para os profissionais envolvidos diretamente no cuidado.

G6PD deficiency in male individuals infected by Plasmodium vivax malaria in the Brazilian Amazon: a cost study.

BACKGROUND: Deficiency of the enzyme G6PD (G6PDd) is caused by mutations in the gene G6PD, which plays an important role in protecting the red blood cell against oxidizing agents; it is linked to chromosome X, and it may affects both sexes. The clinically relevant manifestations, such as acute haemolytic anaemia, mainly occur in men, however. The 8-aminoquinoline primaquine, which is the medication used in the radical treatment of malaria caused by Plasmodium vivax, represents the main factor that triggers complications associated with G6PDd. The current study aims to estimate the costs of G6PDd among male individuals infected by P. vivax in the Brazilian Amazon. METHODS: This is an economic analysis developed within the Brazilian National Health System perspective for the years of 2009, 2010 and 2011. Direct medical and non-medical costs were estimated for G6PDd in the Brazilian Amazon, considering among those suffering from the deficiency the costs of diagnosing infection by P. vivax, its treatment and severe adverse events that require hospitalization and were connected to the use of primaquine. RESULTS: The estimates of the average costs of diagnosing vivax malaria, of its treatment and of severe adverse events after using primaquine among the carriers of G6PDd, over the three evaluated years, corresponded to US$ 739,410.42; US$ 2,120.04 and US$ 4,858,108.87, respectively. The results indicate that the average total cost in the study period corresponded to US$ 5,599,639.33, varying in accordance with the sensitivity analysis between US$ 4,439,512.14 and US$ 6,702,619.24. CONCLUSION: The results indicate that the use of primaquine among men with G6PDd who are infected by P. vivax represents a heavy burden on the public health service of Brazil.

Cost-benefit analysis of G6PD screening in Lebanese newborn males.

INTRODUCTION: G6PD deficiency is one of the most prevalent genetic diseases in Lebanon (1% in Lebanese males). Easy and effective screening methods exist to detect this deficiency early in newborns. OBJECTIVE: To assess the cost-effectiveness of G6PD deficiency screening in the routine work-up of every male newborn in Lebanon. METHODS: Of 299 babies with G6PD deficiency detected between 1999 and 2004, 139 (46.5%) were located, contacted, and surveyed for their experience of acute anemia crises. RESULTS: A previous community survey had indicated a 77.8% risk for an acute anemia crisis necessitating hospitalization in unscreened patients, most often associated with consuming fava beans raw or in combination products. In contrast, only 5 (3.8%) of the 139 screened G6PD-deficient babies had ever developed a severe acute anemia crisis. The risk for hospitalization following a crisis had thus been reduced by 95% among patients screened for G6PD deficiency, compared to those unscreened. The estimated mean cost of each hospitalization, which lasts on average 7 days, is 1450 USD. The cost of screening is about 3 USD. The analysis indicates that, given the current prevalence of the deficiency and the reduction in hospitalization rates associated with knowing one's status, the cost of systematic screening is about 2.58 times lower than that of anemia-related hospitalizations in an unscreened population. CONCLUSION: The efficiency of routinely testing evidenced here supports changes in screening policies for boys.

Identifying risk of neonatal hyperbilirubinaemia and early discharge for glucose-6-phosphate dehydrogenase deficient newborns in Singapore.

INTRODUCTION: This study aims to compare and assess usefulness of day 3 and 4 (49 to 96 hours) pre-phototherapy total serum bilirubin (TSB) in predicting subsequent significant hyperbilirubinaemia (SHB) in glucose-6-phosphate dehydrogenase (G6PD) deficient neonates. MATERIALS AND METHODS: This prospective study was on all the G6PD deficient newborns weighing >2500 g. Day 3 and 4 pre-phototherapy TSB and phototherapy requirements in their first 2 weeks of life were analysed for its value in predicting subsequent SHB. RESULTS: The frequency of G6PD deficiency was 2.4%, 1 per 42 live births (1.3% in males and 1.1% in females). Phototherapy was required in 51% of G6PD deficient infants, all within the first week of life. In the absence of SHB in the first week, the probability of its development in the second week was zero (95% confidence interval, 0 to 0.051). The day 4 pre-phototherapy TSB of <160 micromol/L predicted no measurable risk of subsequent SHB (sensitivity, 94%; 95% confidence interval, 83.5% to 97.9%; specificity 82.8%; 95% confidence interval, 71.1% to 90.4%). CONCLUSIONS: G6PD deficient newborns without SHB in their first week of life were at no measurable risk of its development in the second week. Day 4 pre-phototherapy has better sensitivity and specificity compared to day 3 pre-phototherapy TSB in predicting the risk of subsequent SHB. Low-risk infants, thus identified, may be eligible for discharge on or before day 7 of life. Infants with Day 4 TSB <160 can be even discharge on day 4 with follow-up appointment. Evidence-based early discharge can decrease the social, emotional and financial burden of G6PD deficiency in Singapore.