In vitro and in vivo experimental models for drug screening and development for Chagas disease.

Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.

Sustaining access to antiretroviral therapy in the less-developed world: lessons from Brazil and Thailand.

ANTIRETROVIRAL ROLLOUT IN BRAZIL AND THAILAND: Brazil and Thailand are among few developing countries to achieve universal access to antiretroviral therapy. Three factors were critical to this success: legislation for free access to treatment; public sector capacity to manufacture medicines; and strong civil society action to support government initiatives to improve access. LOCAL PRODUCTION OF AFFORDABLE, NON-PATENTED DRUGS: Many older antiretroviral drugs are not patented in either country and affordable generic versions are manufactured by local pharmaceutical institutes. EFFORTS TO ENSURE ACCESS TO EXPENSIVE, PATENTED DRUGS: Developing countries were not required to grant patents on medicines until 2005, but under US government threats of trade sanctions, Thailand and Brazil began doing so at least ten years prior to this date. Brazil has used price negotiations with multi-national pharmaceutical companies to lower the price of newer patented antiretrovirals. However, the prices obtained by this approach remain unaffordable. Thailand recently employed compulsory licensing for two antiretrovirals, obtaining substantial price reductions, both for generic and brand products. Following Thailand's example, Brazil has issued its first compulsory license. LESSONS LEARNED: Middle-income countries are unable to pay the high prices of multinational pharmaceutical companies. By relying on negotiations with companies, Brazil pays up to four times more for some drugs compared with prices available internationally. Compulsory licensing has brought treatment with newer antiretrovirals within reach in Thailand, but has resulted in pressure from industry and the US government. An informed and engaged civil society is essential to support governments in putting health before trade.

[Health care to HIV/AIDS patients in Brazil]. / Assistência aos pacientes com HIV/Aids no Brasil.

This study was intended to assess care provided to those living with HIV/AIDS in Brazil and the Brazilian Unified Health System (SUS) capacity of delivering interventions to cope with the epidemic as well as to discuss the sustainability of the Brazilian initiative of providing universal free access to antiretrovirals (ARVs). Original data from a study comprising 119 respondents on the potential capacity of delivering a prospective HIV vaccine in Brazil was used. Inpatient and pharmaceutical care was based on data from the SUS Hospital Information System and Drug Logistics Management Systems of the National Program for STD/AIDS. The study results indicate good performance of the Brazilian ARV Access Program but access to treatment of opportunistic infections was, however, unsatisfactory. The rates covered by SUS for AIDS hospital admissions remained very low, on average around R$700 in 2004. Health care to HIV/AIDS patients has been considered a citizen's right strongly supported by an effective joint action of the Brazilian government and civil society. The current challenges are fine monitoring of processes and program results and ensuring sustainability of universal free ARV access.

Assistência aos pacientes com HIV/Aids no Brasil / Health care to HIV/AIDS patients in Brazil

O trabalho teve por objetivo avaliar a assistência à população com Aids no Brasil e a capacidade do Sistema Unico de Saúde (SUS) de prover intervenções para enfrentamento da epidemia e discutir a sustentabilidade da iniciativa brasileira de distribuição universal e gratuita dos anti-retrovirais. O trabalho considerou dados originais de uma pesquisa sobre a capacidade potencial de distribuição de uma futura vacina anti-HIV no Brasil, envolvendo 119 entrevistados. Nas abordagens da assistência hospitalar e da assistência farmacêutica foram utilizados dados do Sistema de Informações Hospitalares do SUS e do Sistema de Controle Logístico de Medicamentos do Programa Nacional de DST/Aids. Os resultados mostraram bom desempenho da política de distribuição de anti-retrovirais. Entretanto, o acesso ao tratamento de doenças oportunistas foi deficitário. Os valores pagos pelo Sistema Unico de Saúde pelas internações por Aids mantiveram-se muito baixos, com valor médio em torno de R$700,00, em 2004. A assistência a pacientes com HIV/Aids no Brasil tem sido tratada como um direito do cidadão, com o respaldo de uma articulação efetiva entre as esferas de governo e a sociedade civil. Os desafios que se colocam atualmente dizem respeito ao monitoramento mais fino dos processos e resultados obtidos e à sustentabilidade da distribuição universal e gratuita de anti-retrovirais.