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.

Cost-utility of tafenoquine vs. primaquine for the radical cure (prevention of relapse) of Plasmodium vivax malaria.

The aim of this study was to compare cost-utility of tafenoquine (TQ) and primaquine (PQ) for a radical cure (prevention of relapse) of Plasmodium vivax (PV) malaria in Serbia using A five-state, 1-month cycle Markov model. The perspective of Republic Health Insurance Fund was chosen, and the time horizon was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. After base case analysis PQ was dominated by TQ, as the net monetary benefit was positive (20,713.84 ± 7,167.46 RSD (99% CI) (174.95 ± 60.54 €)) and incremental cost-effectiveness ratio was below the willingness-to-pay line of 1 Serbian gross national product per capita per quality-adjusted life year gained. Multiple one-way sensitivity analysis and probabilistic sensitivity analysis confirmed the results of the base case simulation. In conclusion, TQ was cost-effective in comparison to PQ for radical cure of PV malaria in socio-economic settings of a South-Eastern European country.

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.

Ethics, economics, and the use of primaquine to reduce falciparum malaria transmission in asymptomatic populations.

Yoel Lubell and colleagues consider ethical and economic perspectives on mass drug administration of primaquine to limit transmission of P. falciparum malaria. Please see later in the article for the Editors' Summary.

Primaquine administration after falciparum malaria treatment in malaria hypoendemic areas with high incidence of falciparum and vivax mixed infection: pros and cons.

Mixed infections of Plasmodium falciparum and Plasmodium vivax is high (approximately 30%) in some malaria hypoendemic areas where the patients present with P. falciparum malaria diagnosed by microscopy. Conventional treatment of P. falciparum with concurrent chloroquine and 14 days of primaquine for all falciparum malaria patients may be useful in areas where mixed falciparum and vivax infections are high and common and also with mild or moderate G6PD deficiency in the population even with or without subpatent vivax mixed infection. It will be possibly cost-effective to reduce subsequent vivax illness if the patients have mixed vivax infection. Further study to prove this hypothesis may be warranted.

Cost considerations of malaria chemoprophylaxis including use of primaquine for primary or terminal chemoprophylaxis.

The costs of mefloquine, chloroquine, doxycycline, primaquine, and atovaquone/proguanil are calculated for various durations of exposure to malaria. The cost is included for detecting glucose 6-phosphate dehydrogenase (G6PD) deficiency before administering primaquine for primary or terminal prophylaxis. For durations of exposure ranging from 3 to 730 days, if no terminal prophylaxis is given, doxycycline (generic) is the least expensive regimen. Compared with doxycycline hyclate, chloroquine costs three to four times more, and primaquine, after screening for G6PD, costs about eight times more. Atovaquone/proguanil is less expensive than mefloquine for a 3-day exposure, but more expensive for 7 or more days. When terminal chemoprophylaxis with primaquine for 14 days is used in addition to doxycycline, mefloquine, chloroquine, or atovaquone/proguanil, primaquine alone is the least expensive regimen for exposures of < 10 days. Thereafter, doxycycline plus 14 days of primaquine is most economical. For subsequent exposures when G6PD status is already known, primaquine alone is the least expensive regimen for up to 9 days of exposure, but doxycycline is less expensive thereafter. In general, generic doxycycline hyclate is the least expensive regimen. Primaquine alone is economically attractive. Mefloquine, doxycyline monohydrate, and atovaquone/proguanil, the most expensive regimens, are similar in cost for a 7-day exposure, but thereafter, atovaquone/proguanil is much more expensive.