Access to Chagas disease treatment in the United States after the regulatory approval of benznidazole.

Approximately 300,000 persons in the United States (US) are infected with Trypanosoma cruzi, the protozoan that causes Chagas disease, but less than 1% are estimated to have received antiparasitic treatment. Benznidazole was approved by the US Food and Drug Administration (FDA) for treatment of T. cruzi infection in 2017 and commercialized in May 2018. This paper analyzes factors that affect access to benznidazole following commercialization and suggests directions for future actions to expand access. We applied an access framework to identify barriers, facilitators, and key actors that influence the ability of people with Chagas disease to receive appropriate treatment with benznidazole. Data were collected from the published literature, key informants, and commercial databases. We found that the mean number of persons who obtained benznidazole increased from just under 5 when distributed by the CDC to 13 per month after the commercial launch (from May 2018 to February 2019). Nine key barriers to access were identified: lack of multi-sector coordination, failure of health care providers to use a specific order form, lack of an emergency delivery system, high medical costs for uninsured patients, narrow indications for use of benznidazole, lack of treatment guidelines, limited number of qualified treaters, difficulties for patients to make medical appointments, and inadequate evaluation by providers to determine eligibility for treatment. Our analysis shows that access to benznidazole is still limited after FDA approval. We suggest six areas for strategic action for the pharmaceutical company that markets benznidazole and its allied private foundation to expand access to benznidazole in the US. In addition, we recommend expanding the existing researcher-clinician network by including government agencies, companies and others. This paper's approach could be applied to access programs for benznidazole in other countries or for other health products that target neglected populations throughout the world.

Factors associated with persistence of African animal trypanosomiasis in Lango subregion, northern Uganda.

African animal trypanosomiasis (AAT) continues to inflict heavy losses on livestock production especially cattle in terms of decreased production and productivity in Uganda. AAT is a disease complex caused by tsetse fly-transmitted Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma congolense, and Trypanosoma vivax. The disease is most important in cattle but also known to cause serious losses in pigs, camels, goats, and sheep. Several control measures including live bait technology, mass treatment of cattle with trypanocidal drugs, and deployment of tsetse traps have been used in the past 10 years, but the problem still persists in some areas. This necessitated an exploration of the factors associated with continued trypanosome infections in cattle, which are also known reservoirs for the zoonotic trypanosomiasis. A structured questionnaire was administered to 286 animal owners from 20 villages purposively selected from Lira, Kole, and Alebtong districts of Lango subregion to obtain information on the factors associated with persistence of infection. Over 50% of the respondents reported trypanosomiasis as a major challenge to their livestock. Land ownership (P = 0.029), type of livestock kept (P = 0.000), disease control strategy employed (P = 0.000), source of drugs (P = 0.046), and drug preparation (P = 0.017) were associated with persistent AAT infection. We recommend continued farmer sensitization on the threat of AAT and the available prevention and control options. The use of isometamidium chloride for prophylaxis against trypanosomiasis is highly recommended. There is also a need to foster qualified private veterinary drug supply in the region.

Strategies to enhance access to diagnosis and treatment for Chagas disease patients in Latin America.

INTRODUCTION: Chagas disease, caused by infection with the parasite Trypanosoma cruzi, represents a huge public health problem in the Americas, where millions of people are affected. Despite the availability of two drugs against the infection (benznidazole and nifurtimox), multiple factors impede their effective usage: (1) gaps in patient and healthcare provider awareness; (2) lack of access to diagnosis; (3) drug toxicity and absence of treatment algorithms to address adverse effects; (4) failures in drug supply and distribution; and (5) inconsistent drug efficacy against the symptomatic chronic stage. Areas covered: We review new approaches and technologies to enhance access to diagnosis and treatment to reduce the disease burden. We also provide an updated picture of recently published and ongoing anti-T. cruzi drug clinical trials. Although there has been progress improving the research and development (R&D) landscape, it is unclear whether any new treatments will emerge soon. Literature search methodologies included multiple queries to public databases and the use of own-built libraries. Expert opinion: Besides R&D, there is a major need to continue awareness and advocacy efforts by patient associations, local and national governments, and international agencies. Overall, health systems strengthening is essential to ensure vector control commitments, as well as patient access to diagnosis and treatment.

Access to benznidazole for Chagas disease in the United States-Cautious optimism?

Drugs for neglected tropical diseases (NTD) are being excessively priced in the United States. Benznidazole, the first-line drug for Chagas disease, may become approved by the Food and Drug Administration (FDA) and manufactured by a private company in the US, thus placing it at risk of similar pricing. Chagas disease is an NTD caused by Trypanosoma cruzi; it is endemic to Latin America, infecting 8 million individuals. Human migration has changed the epidemiology causing nonendemic countries to face increased challenges in diagnosing and managing patients with Chagas disease. Only 2 drugs exist with proven efficacy: benznidazole and nifurtimox. Benznidazole has historically faced supply problems and drug shortages, limiting accessibility. In the US, it is currently only available under an investigational new drug (IND) protocol from the CDC and is provided free of charge to patients. However, 2 companies have stated that they intend to submit a New Drug Application (NDA) for FDA approval. Based on recent history of companies acquiring licensing rights for NTD drugs in the US with limited availability, it is likely that benznidazole will become excessively priced by the manufacturer-paradoxically making it less accessible. However, if the companies can be taken at their word, there may be reason for optimism.

[Estimating demand for anti-Chagas drugs: a contribution for access in Latin America]. / Estimación de la demanda de medicamentos antichagásicos: una contribución para el acceso en América Latina.

OBJECTIVE: Describe a tool to estimate demand for benznidazole and nifurtimox to treat Chagas disease, and report on its implementation in a group of Latin American countries. METHODS: The project was carried out in the following stages: 1) development of a tool to estimate demand, and definition of the evaluation and decision variables to estimate demand 2) data collection via a questionnaire completed by representatives of control programs, complemented with data from the literature; 3) presentation of the tool, followed by validation, and adaptation by representatives of the control programs in order to plan drug procurement for 2012 and 2013; and 4) further analysis of the obtained data, especially regarding benznidazole, and comparison of country estimates. RESULTS: Fourteen endemic countries of Latin America took part in the third stage, and a consolidated estimate was made. The number of estimated treatments, based on the number of tablets per treatment established in the regimen of reference was: 867 in the group under 1 year of age; 2 042 835 in the group from 1 to 15 years old; 2 028 in the group from 15 to 20 years old; and 10 248 in adults over 20. This means that it is possible to provide benznidazole to less than 1% of people for whom treatment is indicated. CONCLUSIONS: The development and systematic use of demand management tools can play a key role in helping to provide access to the anti-Chagas drugs. There is a significant gap between the projected demand for drugs and current estimates of prevalence rates.

Benznidazole shortage makes chagas disease a neglected tropical disease in developed countries: data from Spain.

Chagas disease is a neglected tropical disease endemic in Latin America. The first-line treatment option is benznidazole, but stocks are expected to run out in the coming months. Spain would need around 5 million benznidazole tablets. This drug shortage could make Chagas disease a neglected tropical disease also in developed countries.

Waking up to sleeping sickness.

Devastating epidemics of human African trypanosomiasis are currently re-emerging in many sub-Saharan countries. In the past three decades, clinical research into this important disease has been neglected, as have urgently needed initiatives on drug development, disease surveillance and vector control. Recent impetus has aimed to provide a free supply of antitrypanosomal drugs, to develop a new orally active trypanocidal agent and to attack the tsetse vector with modern technology. In addition, pan-African initiatives to co-ordinate control efforts have begun. These all provide some hope for the future, but they might not be enough to reverse the resurgence of this deadly disease in the heart of Africa.

[The return of sleeping sickness in an epidemic form: international action for drugs]. / Terugkeer van slaapziekte in epidemische vorm; internationale actie voor geneesmiddelen.

In Central Africa, the number of people suffering and dying from sleeping sickness is the same as it was in 1920, whereas the disease was under control in the 1950s. In Zaire (Congo), Gambiense sleeping sickness was virtually under control by 1960. Due to war, chaos, population movements, lack of resources, and collapse of public health, the situation is now as it was 80 years ago and some years ago it was even more bleak as the supply of drugs seemed to halt. Due especially to the action of Médecins sans Frontières, the availability of the four essential drugs pentamidine, suramine, melarsoprol and eflornithine is now secure until 2006. Control of the epidemic in Central Africa can be achieved once peace and order and a basic infrastructure have been restored, and under the condition that adequate resources will be available.

Availability and affordability of treatment for Human African Trypanosomiasis.

Human African Trypanosomiasis (HAT) is a re-emerging disease whose usual treatments are becoming less efficient because of the increasing parasite resistance. Availability of HAT drugs is poor and their production in danger because of technical, ecological and economic constraints. In view of this dramatic situation, a network involving experts from NGOs, WHO and pharmaceutical producers was commissioned with updating estimates of need for each HAT drug for the coming years; negotiations with potential producers of new drugs such as eflornithine; securing sustainable manufacturing of existing drugs; clinical research into new combinations of these drugs for first and second-line treatments; centralizing drug purchases and their distribution through a unique non-profit entity; and addressing regulatory and legal issues concerning new drugs.

The use of trypanocides and antibiotics by Maasai pastoralists.

Information was collected on the use of veterinary drugs by Maasai pastoralists in an area of Kenya where tsetse flies and trypanosomosis occur. Three herds of cattle were followed for between 4 and 5 years and records were kept of every veterinary drug treatment given by the livestock owners. Almost all treatments were either with the trypanocides homidium or diminazene, or with oxytetracycline by intramuscular injection. The rate of trypanocide use varied between 0.66 and 1.56 treatments per animal per year, while oxytetracycline use was between 0.20 and 1.00 treatments per animal per year. Farmers were injecting these drugs in the absence of veterinary supervision, obtaining their supplies mainly from local village shops or informal traders. Underdosing with trypanocides appeared to be uncommon and the indications were that farmers generally gave the drugs at dosage rates above the recommended standard dose. Accurate information on the dose rates of oxytetracycline could not be obtained, but it was noted that in most cases farmers gave a single injection rather than a course of treatment. In a proportion of cases, trypanocides and antibiotics were mixed together before injection. The farmers administered the drugs when disease was recognized and were rarely using trypanocides as prophylactics. Although necessity forces the livestock owners to obtain and use these drugs without veterinary supervision, there are concerns with regard to the possibility of drug misuse and the development of drug resistance.

In the heart of darkness: sleeping sickness in Zaire.

PIP: Human African trypanosomiasis (HAT) control programs existed during the colonial era in the Belgian Congo. HAT cases peaked in 1930 at 33,562. They declined gradually to about 1000 cases in 1959. The civil war that erupted after Zaire's independence in 1960 crippled the public health system. During 1960-1967, no active case finding was conducted and notification of HAT cases fell greatly. Mismanagement and corruption maintained a severe social and economic crisis after the civil war. At the end of the 1980s, the number of new HAT cases began to increase from the relatively stable numbers of 4000-6000 during 1969-1981 to almost 10,000. Socioeconomic conditions deteriorated quickly in the 1990s. The withdrawal of foreign aid in 1991 devastated many governmental health facilities that had been dependent on these funds. In much of Zaire, Catholic and Protestant missions were the only health care providers. The breakdown of the health system contributed to epidemics of Ebola fever, dysentery, the plague, and cholera. The specialized mobile teams providing trypanocidal drugs to HAT patients could no longer operate, resulting in drug shortages and thousands of deaths. The teams were somewhat remobilized during 1993-1994, when some foreign aid was again available. A return to neglected areas in 1994 found the HAT prevalence to be 15.4/1000 in the Equator region. In Kimbanzi, Bandundu region, it was 718/1000 among 241 persons examined. Had the teams not arrived when they did, the entire village of Kimbanzi could have disappeared within 1-2 years. The high prevalence rates in neglected areas were the highest rates recorded this century. The neglect brought about an increase in the number of infectious people, an increase in transmission, and a higher cost and toxicity of treatment due to an increase in late-stage HAT cases. The estimated true total incidence of HAT in Zaire in 1994 was about 34,400 new cases. The number of HAT deaths in 1994 was probably at least 80 times higher than that of Ebola deaths in 1995. Proper HAT control methods need to be fully funded and implemented to control this curable disease.^ieng