Simulation-based economic evaluation of the Wolbachia method in Brazil: a cost-effective strategy for dengue control.

Background: Dengue virus (DENV) is an arbovirus transmitted by Aedes aegypti mosquitoes, which can cause severe conditions such as hemorrhagic fever and dengue shock syndrome. These conditions are associated with adverse social, clinical, and economic consequences in Brazil. Herein, the Wolbachia mosquito replacement method is a promising dengue control strategy. Methods: We estimated the economic impact of implementing the Wolbachia mosquito replacement method in seven Brazilian cities. A mathematical microsimulation model tracked nearly 23 million inhabitants over a 20-year period, considering the transitions between five different health states (susceptible, inapparent, outpatient, hospitalised and death). Direct costs included local dengue control programs, Wolbachia implementation and dengue care. Indirect costs related to death and productivity loss, as well as disability-adjusted life-years (DALY) averted were also considered. Findings: Without Wolbachia, the model projected 1,762,688 reported dengue cases over 20 years. Implementing the Wolbachia method would avert at least 1,295,566 dengue cases, resulting in lower costs and greater effectiveness in all simulated cities. On average, for every 1000 inhabitants followed for 20 years, the Wolbachia method yielded a cost difference of USD 538,233.68 (BRL 2,691,168.40) and averted 5.56 DALYs. Net monetary benefits (NMB) were positive in all seven cities, ranging from USD 110.72 (BRL 553.59) to USD 1399.19 (BRL 6995.95) per inhabitant. Alternative scenarios have also shown a favourable return on investment with a positive benefit-cost ratio (BCR). Interpretation: Wolbachia is likely a cost-effective strategy in the Brazilian context, consistent with international studies. Sensitivity analysis and alternative scenarios confirmed the robustness of the results. Funding: This study was funded by the Wellcome Trust under a grant (224459/Z/21/Z).

Epidemiological burden of Chikungunya fever in Brazil, 2016 and 2017.

OBJECTIVES: To describe Chikungunya fever (CHIKF) cases and estimate the burden of the disease in Brazil between 2016 and 2017. METHODS: The first stage of this study consisted of a descriptive epidemiological study with estimations of incidence, mortality and case-fatality rates for each Brazilian state. The second stage provided estimates of the disease burden using DALY, an indicator that aggregates measures of morbidity (years lived with disability - YLD) and mortality (years of life lost - YLL) into a single value. RESULTS: In Brazil, the incidence rate in 2016 was 114.70 per 100,000 inhabitants, while the mortality rate was 0.15 per 100,000, for a case-fatality rate of 0.13%. In 2017, these figures were 87.59 and 0.12 per 100,000 inhabitants and 0.14%, respectively. The estimated CHIKF burden for Brazil in 2016 was 77,422.61 DALY or 0.3757 per 1000 inhabitants. In 2016, the YLL share of DALY was 10.04%, with YLD accounting for the remaining 89.96%. In 2017, the estimated burden was 59,307.59 DALY or 0.2856 per 1000 inhabitants, with YLL accounting for 9.65% of the total and YLD for 90.35%. CONCLUSION: CHIKF causes a significant disease burden in Brazil. The chronic phase of CHIKF is responsible for the largest portion of DALY. Deaths from CHIKF are a significant component of the disease burden, with YLL accounting for approximately 10% of the total DALY value.

Costs of Guillain-Barré Syndrome in the Brazilian Federal District: the patients' perspective.

BACKGROUND: Although rare, Guillain-Barré Syndrome (GBS) has a high economic burden, with consequences for families and society. This study aimed to estimate the total cost of GBS, per individual and per variant of the disease, as well as its effect on household income, from the perspective of patients. METHODS: This was a cost-of-illness study from the perspective of patients and their families, with a time horizon from disease onset to 6 mo after discharge. The total cost of GBS was estimated by bottom-up microcosting, considering direct and indirect costs. RESULTS: The median cost of GBS per individual was US$1635.5, with direct costs accounting for 64.3% of this amount. Among the variants analyzed, acute motor sensory axonal neuropathy (US$4660.1) and acute inflammatory demyelinating polyneuropathy (US$2017.0) exhibited the highest costs compared with acute motor axonal neuropathy (US$1635.5) and Miller Fisher Syndrome (US$1464.8). The costs involved compromise more than 20% of the household income of 22 (47.8%) patients. CONCLUSIONS: This study demonstrated how costly GBS can be. It is hoped that decision-makers will analyze these results with a view to improving the structure of healthcare services.

Burden of Disease of Guillain-Barré Syndrome in Brazil before and during the Zika virus epidemic 2014-2016.

OBJECTIVE: To estimate the burden of disease of Guillain-Barré syndrome (GBS) in Brazil in 2014, 1 year before the Zika virus epidemic, and in 2015 and 2016 during the epidemic. METHODS: The burden of disease of GBS was estimated using the summary measure of population health: Disability Adjusted Life Years (DALY), that combines both mortality (Years of Life Lost YLLs) and morbidity (Years Lived with Disability) components. The study population was composed of GBS hospitalised cases and deaths from the information systems of the Brazilian Unified Health System. RESULTS: The GBS incidence rate in 2014, 2015 and 2016 was 0.74, 0.96, 1.02/100 000 respectively, and the mortality rate in the same period was 0.08, 0.009 and 0.11/100 000 habitants. The DALYs calculated using the point estimate of GBS disability weight and its values of the confidence interval (0.198 and 0.414) were 5725.90 (5711.79-5742.89) in 2014, 6054.61 (6035.57-6077.54) in 2015 and 7588.49 (7570.20-7610.51) in 2016. The DALYs were high among the male population and in age groups between 20 and 50 years. CONCLUSIONS: The increase in DALYs in the years 2015 and 2016 compared to 2014 probably resulted from the introduction of ZIKV in Brazil, reinforcing the importance of investments in the prevention of ZIKV infection and in the care of GBS patients.

OBJECTIF: Estimer la charge de morbidité du syndrome de Guillain-Barré (SGB) au Brésil en 2014, un an avant l'épidémie du virus Zika (ZIKV) et en 2015 et 2016 pendant l'épidémie. MÉTHODES: La charge de la maladie du SGB a été estimée à l'aide de la mesure récapitulative de la santé de la population: années de vie ajustées en fonction de l'incapacité (AVCI), qui combine à la fois les composantes de la mortalité (années de vie perdues AVP) et de la morbidité (années vécues avec une incapacité). La population de l'étude était composée de cas hospitalisés du SGB et de décès provenant des systèmes d'information du système de santé unifié brésilien. RÉSULTATS: Le taux d'incidence du SGB en 2014, 2015 et 2016 était de 0,74 ; 0,96 et 1,02/100.000 respectivement et le taux de mortalité au cours de la même période était de 0,08 ; 0,009 et 0,11/100.000 habitants. Les AVCI calculées à l'aide des points d'estimation du poids de l'incapacité du SGB et de ses valeurs de l'intervalle de confiance (0,198 et 0,414) étaient de 5.725,90 (5.711,79-5.742,89) en 2014 ; 6.054,61 (6.035,57-6.077,54) en 2015 et 7.588,49 (7.570,20 - 7.610,51) en 2016. Les AVCI étaient élevés parmi la population masculine et dans les groupes d'âge entre 20 et 50 ans. CONCLUSIONS: L'augmentation des AVCI en 2015 et 2016 par rapport à 2014 résulte probablement de l'introduction du ZIKV au Brésil, renforçant l'importance des investissements dans la prévention de l'infection par le ZIKV et dans la prise en charge des patients atteints de SGB.

Treatment With Liposomal Amphotericin B for All Confirmed Cases of Human Visceral Leishmaniasis in Brazil: A Budget Impact Analysis.

OBJECTIVES: To estimate the budget impact of the expansion of liposomal amphotericin B use for all confirmed cases of visceral leishmaniasis (VL) in Brazil. Currently, the first-line medicine for VL treatment is meglumine antimoniate. Liposomal amphotericin B is indicated only for patients with a greater risk of severity by the disease. METHODS: The analysis was performed from the perspective of the Brazilian public healthcare system over 3 years, considering the following 2 scenarios: the reference scenario with the current recommendations for VL treatment and the alternative scenario based on the use of liposomal amphotericin B for all patients. A diffusion rate of 60% was used in the first year, 80% in the second year, and 100% in the third year. The epidemiological parameters used in the analysis came from the Notifiable Diseases Information System and from a clinical trial that evaluated the efficacy and safety of medicines for the treatment of VL in the country. The costs were related to the treatment of VL and to hospital and outpatient care. RESULTS: In the reference scenario, the total cost for treatment of the 3453 VL confirmed cases in 2014 was $1 447 611.75. The incremental budget impact with the use of liposomal amphotericin B for all the VL confirmed cases was $299 646.43 in the third year. CONCLUSIONS: The analysis presented will support the decision process for the use and expansion of liposomal amphotericin B for all VL confirmed cases in Brazil.

Snakebite envenomation in the Brazilian Amazon: a cost-of-illness study.

BACKGROUND: Snakebites account for significant morbidity and mortality. Their occurrence in the Brazilian Amazon warrants an analysis that will enable better understanding of their economic impact and thus contribute to their management and prevention. This study aimed to estimate the cost of snakebite envenomation in the Brazilian Amazon in 2015. METHODS: We conducted a cost-of-illness study of snakebite in the Brazilian Amazon in 2015 based on official surveillance data to estimate burden from a societal, patient and public health system perspective. Direct medical costs were estimated via a top-down approach. Loss of productivity was estimated by a human capital approach. RESULTS: The study included 11 503 cases and 56 deaths. The estimated cost to the health system was US$3.115.861,28. The estimated cost due to premature death caused by snakebite was US$3031 300.38. The cost attributed to the loss of productivity due to absence from work was US$1539 518.62. The estimated cost from the patient's perspective was US$268 914.18. Therefore the total cost of snakebite in the Brazilian Amazon was estimated to be almost than US$8 million in 2015. CONCLUSIONS: The economic burden of snakebite in Brazilian Amazon is notably high. Snakebites cause loss of productivity through inpatient treatment or deaths.

Treatment for human visceral leishmaniasis: a cost-effectiveness analysis for Brazil.

OBJECTIVE: To estimate the cost-effectiveness of strategies for the treatment of VL in Brazil. METHODS: Cost-effectiveness study comparing three therapeutic options: meglumine antimoniate (MA), liposomal amphotericin B (LAMB) and a combination of LAMB plus MA (LAMB plus MA), from public health system and societal perspectives. An analytical decision-making model was used to compare strategies for the following outcomes: early therapeutic failure avoided at 30 days, days of hospitalisation avoided and VL cure at 180 days. The efficacy and safety parameters of the drugs came from a randomised, open-label trial and the cost data came from a cost-of-illness study, both carried out in Brazil. RESULTS: For all outcomes analysed, the LAMB strategy was more effective. The MA strategy was inferior to the LAMB plus MA strategy for the outcomes early therapeutic failure avoided and cure. When only LAMB and MA were compared from a societal perspective, a cost of US$ 278.56 was estimated for each additional early therapeutic failure avoided, a cost of US$ 26.88 for each additional day of hospitalisation avoided and a cost of US$ 89.88 for each additional case of cured VL, for the LAMB strategy vs. MA. CONCLUSION: In Brazil, the LAMB strategy proved to be cost-effective for treating VL, considering a GDP per capita as the willingness-to-pay threshold, for all of the outcomes analysed in comparison to MA.

OBJECTIF: Estimer la rentabilité des stratégies de traitement de la leishmaniose viscérale (LV) au Brésil. MÉTHODES: Etude coût-efficacité comparant trois options thérapeutiques: l'antimoniate de méglumine (AM), amphotéricine B liposomale (LAMB) et une combinaison de LAMB et MA (LAMB plus AM), du point de vue du système de santé publique et sociétal. Un modèle décisionnel analytique a été utilisé pour comparer les stratégies pour les résultats suivants: échec thérapeutique précoce évité à 30 jours, jours d'hospitalisation évités et guérison de la LV à 180 jours. Les paramètres d'efficacité et de sécurité des médicaments provenaient d'un essai randomisé ouvert et les données relatives aux coûts, d'une étude sur le coût de la maladie, toutes deux menées au Brésil. RÉSULTATS: Pour tous les résultats analysés, la stratégie LAMB était plus efficace. La stratégie AM était inférieure à la stratégie LAMB plus AM pour les résultats: échec thérapeutique précoce évité et guérison. Lorsque seules les stratégies LAMB et AM ont été comparées d'un point de vue sociétal, un coût de 278,56 USD a été estimé pour chaque échec thérapeutique précoce additionnel évité, un coût de 26,88 USD pour chaque jour d'hospitalisation additionnel évité et un coût de 89,88 USD pour chaque cas additionnel de LV guéri, pour la stratégie LAMB par rapport à AM. CONCLUSION: Au Brésil, la stratégie LAMB s'est avérée rentable pour traiter la LV, considérant un PIB par habitant comme seuil de volonté de payer, pour tous les résultats analysés par rapport à l'AM.

Guillain-Barré syndrome associated with Zika virus infection in Brazil: a cost-of-illness study.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious, acute paralytic neuropathy of autoimmune aetiology, usually associated with a previous infection. The current study aims to estimate the costs of GBS associated with Zika virus (ZIKV) infection in Brazil. METHODS: A cost-of-illness study was conducted from the perspective of the Brazilian public health system (Sistema Único de Saúde [SUS]) and Brazilian society for the year 2016. Direct and indirect costs were estimated by a mixed macrocosting and microcosting approach. RESULTS: The total cost of ZIKV-associated GBS in Brazil was US$11 997 225.85, consisting of the costs of symptomatic ZIKV infection before onset of GBS (direct costs US$2011.51, indirect costs US$19 780.53) and the costs that followed development of GBS (direct costs US$4 722 980.89, indirect costs US$7 252 452.92). The cost of treatment with human immunoglobulin (US$3 263 210.50) and the cost of productivity losses associated with potential years of working life lost due to early mortality (US$4 398 551.72) were particularly noteworthy. CONCLUSIONS: These findings suggest that ZIKV-associated GBS is costly to Brazil, especially due to productivity losses and hospitalization. This highlights the importance of investing in the prevention of ZIKV infection and in the care of patients with GBS.

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.

Cost of visceral leishmaniasis care in Brazil.

OBJECTIVE: To estimate the Brazilian direct and indirect costs of human visceral leishmaniasis (VL) in 2014. METHODS: Cost-of-illness study on the Brazilian public health system and societal perspective. VL cases registered in the Notifiable Diseases Information System in the year of 2014 were considered. Direct medical costs regarding diagnostic, treatment and care provided to patients with VL were estimated through the top-down approach. The indirect costs related to productivity loss due to premature mortality and morbidity were estimated by means of the human-capital method. RESULTS: In 2014, 9895 suspected cases of VL were reported in the Notifiable Diseases Information System, and 3453 were later confirmed. There were 234 patients with Leishmania-HIV coinfection underwent a secondary prophylaxis. The total cost of VL in Brazil was US$ 14 190 701.50 (US$ 14 189 150.10 to 14 199 940.53) that varied according to the sensitivity analysis. The total of direct medical costs corresponded to US$ 1 873 681.96 (US$1 872 130.55 to 1 882 920.99), and the majority of costs was associated with hospitalisation (40%), followed by treatment (22%), and secondary prophylaxis (18%). Productivity loss corresponded to US$ 11 421 683.37 for premature mortality and US$ 895 336.18 for work absence due to hospitalisation by the illness. CONCLUSIONS: VL represents an expensive health problem for the Brazilian public health system and society, mainly because of its productivity loss due to premature mortality. Interventions to reduce VL lethality could have a great impact on decreasing the cost of illness.

Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

OBJECTIVE: The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. METHODS: The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. RESULTS: The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. CONCLUSION: A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon.

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.