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In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV.STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and non-academic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA12 IU/mL in Thailand and HCV RNA15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials.gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183.Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatment-emergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.National Science and Technology Development Agency, Thailand; Department of Disease Control, Ministry of Public Health, Thailand; Ministry of Health, Malaysia; UK Aid; Médecins Sans Frontières (MSF); MSF Transformational Investment Capacity; FIND; Pharmaniaga; Starr International Foundation; Foundation for Art, Research, Partnership and Education; and the Swiss Agency for Development and Cooperation.

Основные лекарства удовлетворяют приоритетные потребности населения в области здравоохранения. Политика, основанная на концепции основных лекарств, имеет решающее значение в улучшении здоровья и достижении устойчивого развития. Цель устойчивого развития 3.8 конкретно упоминает важность «доступности безопасных, эффективных, качественных и доступных по цене основных лекарств и вакцин для всех» в качестве центрального компонента всеобщего охвата медицинской помощью (ВОМП), а цель устойчивого развития 3.b подчёркивает необходимость разработки лекарств для устранения постоянно возникающих пробелов в отношении лечения. Признание важности основных лекарств - не новость. В 1985 г. на конференции в Найроби по рациональному использованию лекарств представители правительств и другие заинтересованные стороны предложили всеобъемлющий комплекс мер по разработке политики в области основных лекарств. Через 30 лет была созвана «Комиссия журнала Ланцет (Lancet) по основным лекарствам» (далее Комиссия) для изучения следующих вопросов: Какого прогресса удалось достичь? Какие проблемы ещё остаются для решения? Какие уроки были извлечены для информирования будущих подходов? И как можно использовать политику в области основных лекарств для продвижения ВОМП и внесения вклада в повестку глобального устойчивого развития? В настоящем докладе рассмотрены эти вопросы с намерением репозиционировать политику в области основных лекарств в повестке глобального развития. Комиссия определила пять областей, имеющих решающее значение для политики в области основных лекарств: оплата корзины основных лекарств, обеспечение ценовой доступности основных лекарств, гарантия их качества и безопасности, мероприятия, способствующие их качественному использованию, и разработка недостающих (отсутствующих) основных лекарств. Комиссия позиционировала политику в области основных лекарств в контексте текущих глобальных дебатов о балансировании политики в области торговли и интеллектуальной собственности с правами человека, об обеспечении безопасности здравоохранения, укреплении систем здравоохранения, ориентированных на людей, и улучшении доступности основных технологий. Во всех областях политики особое внимание было уделено совершенствованию принципов равенства и справедливости в доступе, укреплению соответствующих институтов и созданию подотчётности. В каждой из определённых областей Комиссия сформулировала рекомендации к действию, подтвердив тем самым позицию политики в области основных лекарств в качестве центрального компонента глобального здоровья и здравоохранения и повестки развития.

SUMMARY Research in visceral leishmaniasis in the last decade has been focused on how better to use the existing medicines as monotherapy or in combination. Systematic research by geographical regions has shown that a universal treatment is far from today9s reality. Substantial progress has been made in the elimination of kala-azar in South Asia, with a clear strategy on first- and second-line therapy options of single-dose liposomal amphotericin B and a combination of paromomycin and miltefosine, respectively, among other interventions. In Eastern Africa, sodium stibogluconate (SSG) and paromomycin in combination offer an advantage compared to the previous SSG monotherapy, although not exempted of limitations, as this therapy requires 17 days of painful double injections and bears the risk of SSG-related cardiotoxicity. In this region, attempts to improve the combination therapy have been unsuccessful. However, pharmacokinetic studies have led to a better understanding of underlying mechanisms, like the underexposure of children to miltefosine treatment, and an improved regimen using an allometric dosage. Given this global scenario of progress and pitfalls, we here review what steps need to be taken with existing medicines and highlight the urgent need for oral drugs. Furthermore, it should be noted that six candidates belonging to five new chemical classes are reaching phase I, ensuring an optimistic near future.

Despite some success in reducing the substantial mortality many challenges remain, say Suman Rijal and colleagues

Today, the World Health Organization recognizes 17 major parasitic and related infections as the neglected tropical diseases (NTDs). Despite recent gains in the understanding of the nature and prevalence of NTDs, as well as successes in recent scaled-up preventive chemotherapy strategies and other health interventions, the NTDs continue to rank among the world's greatest global health problems. For virtually all of the NTDs (including those slated for elimination under the auspices of a 2012 London Declaration for NTDs and a 2013 World Health Assembly resolution [WHA 66.12]), additional control mechanisms and tools are needed, including new NTD drugs, vaccines, diagnostics, and vector control agents and strategies. Elimination will not be possible without these new tools. Here we summarize some of the key challenges in translational science to develop and introduce these new technologies in order to ensure success in global NTD elimination efforts.

A significant number of product-development partnerships have arisen in the past 10 years to tackle diseases that mainly affect developing countries. With their coherent research and development leadership, they have become key players in identifying gaps and overcoming bottlenecks in order to deliver medicines to those who need them most in the developing world. Dr Bernard Pécoul is the Executive Director of one such partnership, the Drugs for Neglected Diseases Initiative (DNDi). Under his leadership, the DNDi has built the largest and most robust R&D portfolio for three of the most neglected diseases. He speaks to Future Medicinal Chemistry about challenges facing neglected disease R&D and the DNDi’s ongoing work.

Anti-microbial resistance, emerging infectious diseases, and neglected diseases are all important public health concerns and priorities with serious market failures, deficits, and identified needs in biomedical innovation. It is important to reconcile, rather than fragment, the needs of these three priority areas by considering an umbrella framework for specifically financing and coordinating research and development (R&D) that delivers innovation while securing patient access. A sizeable, sustainably financed global R&D fund and mechanism that promotes coordination, collaboration, and utilization of new and innovative incentives should be set up to cover all three priority areas.

Summary Background In 1975–99, only 1·1% of new therapeutic products had been developed for neglected diseases. Since then, several public and private initiatives have attempted to mitigate this imbalance. We analysed the research and development pipeline of drugs and vaccines for neglected diseases from 2000 to 2011. Methods We searched databases of drug regulatory authorities, WHO, and clinical trial registries for entries made between Jan 1, 2000, and Dec 31, 2011. We defined neglected diseases as malaria, tuberculosis, diarrhoeal diseases, neglected tropical diseases (NTDs; WHO definition), and other diseases of poverty according to common definitions. Findings Of the 850 new therapeutic products registered in 2000–11, 37 (4%) were indicated for neglected diseases, comprising 25 products with a new indication or formulation and eight vaccines or biological products. Only four new chemical entities were approved for neglected diseases (three for malaria, one for diarrhoeal disease), accounting for 1% of the 336 new chemical entities approved during the study period. Of 148 445 clinical trials registered in Dec 31, 2011, only 2016 (1%) were for neglected diseases. Interpretation Our findings show a persistent insufficiency in drug and vaccine development for neglected diseases. Nevertheless, these and other data show a slight improvement during the past 12 years in new therapeutics development and registration. However, for many neglected diseases, new therapeutic products urgently need to be developed and delivered to improve control and potentially achieve elimination. Funding None.

Summaryobjectives To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. methods This paper presents two analyses: a 1983–97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. results Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. conclusion The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of ‘diseases of exception’.

It is shocking that at the start of the 21st century, when science and technology are advancing exponentially, 35,000 people worldwide still die every day from neglected diseases such as AIDS, mala...

Human African trypanosomiasis (HAT), also known as “sleeping sickness”, is a parasitic disease that is fatal if left untreated. The disease is transmitted by the tsetse fly and is endemic to sub-Saharan Africa, where it mainly affects impoverished rural communities. There are two forms of HAT; the West African variant caused by Trypanosoma brucei gambiense is the most common and accounts for over 90% of the current case load. The disease occurs in two stages, the haemato-lymphatic stage (stage 1) with no or few specific symptoms, followed by the meningo-encephalitic stage (stage 2), which occurs when the parasite has crossed the blood-brain barrier. This second stage is characterized by neurological signs and personality changes; damage to the hypothalamus can lead to disturbances of the normal sleep/wake cycle, hence the name “sleeping sickness” [1]. The ominous reputation of HAT is linked to a history of devastating epidemics, controlled with sometimes draconian measures, only to re-emerge again once control measures were abandoned. At the turn of the 20th century, an estimated 300,000 to 500,000 people died from HAT; another major epidemic occurred in the 1920s–'30s [2]. By the mid-1960s, the disease was almost eliminated, but 30 years later incidence levels were back to where they had been in the 1920s [3]. This is illustrated by data from the Democratic Republic of the Congo (DRC), the worst affected country (Figure 1). After independence in 1960, the strict and costly HAT control measures put in place by the colonial authorities were relaxed and the number of HAT cases gradually increased. Operations of the national sleeping sickness control programme (Programme National de Lutte contre la Trypanosomiase Humaine Africaine, PNLTHA) continued to be funded mainly by the Belgian government. When in 1991 all Belgian bilateral aid, including the support to the PNLTHA, was suspended because of international sanctions against the Mobutu regime, the epidemiological situation soon became dramatic. Figure 1 Annual case notification of HAT in DRC, 1926–2011. In 1998, a total of 40,000 cases were reported worldwide, 66% of which (26,318 cases) in the DRC. The WHO estimates that 300,000 cases remained undetected and therefore untreated [4]. An emergency HAT control program was launched and followed up by the current program, which is largely funded through bilateral cooperation with Belgium. Active screening was resumed, reaching up to 3 million persons per year, at an annual cost of 2.8 million US$. However, in the perspective of this external funding being phased out, and with no alternative funding sources identified as of yet, the PNLTHA has been forced to gradually scale down active case finding campaigns. In 2009, T.b. gambiense HAT was still focally endemic in 24 Sub-Saharan African countries, but out of the 9,688 cases reported globally, 7,326 (76%) occurred in the DRC [5]. The provinces of Bandundu and Kasai Oriental remain heavily affected; the situation in Province Orientale is unclear, because on-going armed conflict interferes with screening campaigns, but more than 3,000 cases have been diagnosed over the last 5 years [6].

Background This case study describes how a public-private partnership initiated to develop a new anti-malarial combination, ASAQ Winthrop, has evolved over time to address issues posed by its effective deployment in the field. Case description In 2002, DNDi created the FACT project to develop two fixed-dose combinations, artesunate-amodiaquine and artesunate-mefloquine, to meet the WHO anti-malarial treatment recommendations and international regulatory agencies approval standards. In 2002, Sanofi-aventis had started a development programme for a fixed-dose combination of artesunate and amodiaquine, to replace its co-blister combination. DNDi and sanofi-aventis joined forces in 2004, with the objective of developing within the shortest possible time frame a non-patented, affordable and easy to use fixed-dose combination of artesunate and amodiaquine adapted to the needs of patients, in particular, those of children. The partners developed Coarsucam®/Artesunate Amodiaquine Winthrop® ("ASAQ Winthrop") which was prequalified by the WHO in 2008. Additional partnerships have since been established by DNDi and sanofi-aventis to ensure: 1) the adoption of this new medicine by malaria-endemic countries, 2) its appropriate usage through a broad range of information tools, and 3) the monitoring of its safety and efficacy in the field through an innovative Risk Management Plan. Discussion and evaluation The partnership between DNDi and sanofi-aventis has enabled the development and pre-qualification of ASAQ Winthrop in a short timeframe. As a result of the multiple collaborations established by the two partners, as of late 2010, ASAQ Winthrop was registered in 30 sub-Saharan African countries and in India, with over 80 million treatments distributed in 21 countries. To date, 10 clinical studies, involving 3432 patients with ASAQ Winthrop were completed to document efficacy and safety issues identified in the Risk Management Plan. Conclusions The speed at which ASAQ Winthrop was adopted in the field shows that this drug fits the needs of patients and health authorities. It also demonstrates the power of partnerships that combine different sets of strengths and skills, and that evolve to include additional actors to meet new global health challenges for poverty-related diseases.

What is the best strategy to approve novel drugs for disease such as sleeping sickness that predominantly affect patients in Africa? How can African regulators best be supported to evaluate these drugs for their own populations? For many years, African medicines regulatory authorities (MRAs) have relied on stringent regulators in developed countries to assess novel pharmaceutical products such as drugs and vaccines for use in African populations. However, a recent shift in the drug product environment for Africa has put this approach under strain. A score of new products are now being, or have been, developed specifically for diseases of the developing world (Table 1), creating new challenges for regulators in Africa and elsewhere. Table 1 Sample of novel neglected disease products presented to regulators since 2005 [8],[11],[12],[20]–[23]. However, it is not at all certain that African regulatory authorities currently have the capacity to meet these new demands. A study conducted by the World Health Organization (WHO) in 2010 concluded that 90% of MRAs in sub-Saharan Africa “were in a situation which did not allow them to adequately carry out regulatory functions,” and thus could not guarantee the safety and efficacy of medicines to be used in their country [1]–[3]. While undoubtedly improving, growth in African regulatory capacity is not keeping up with these new challenges. The growing demand to assess novel neglected disease (ND) products for African use has generated a range of responses from policymakers and product developers, as outlined below. While each approach offers unique benefits, none is ideally suited as a primary vehicle for drug registration for Africa. There is also no guidance to product developers in choosing between approaches, and little or no integration between approval mechanisms (see Figure 1). It is now critical to review how novel ND drugs are assessed and approved for African use. This article is based on research conducted for a report titled “Registering New Drugs: The African Context” [4], commissioned by the Drugs for Neglected Diseases initiative (DNDi), and builds upon this work with additional research and analysis. Figure 1 Neglected disease drug registration timeline [7],[9],[11]–[19]. Western Regulatory Approval Routes Historically, the majority of new ND drugs have been first submitted to well-established Western regulatory authorities (e.g., United States Food and Drug Administration [FDA], European Medicines Agency [EMA], SwissMedic), either for routine regulatory review or under specific pathways such as Orphan Drug legislation (ODL) or expedited approval mechanisms. Multinational pharmaceutical companies and some Product Development Partnerships (PDPs) have typically used this approach because it offers clear protocols and rules, liability management and, in the case of ODL, tax breaks, free scientific advice, and market exclusivities. Firms also welcome the access Western regulatory approval provides to early commercial returns on products with overlapping rich and poor markets. While bringing decades of regulatory experience to the table, use of Western authorities to review ND drugs also has drawbacks. It delays access for African patients since African MRAs often wait for the Western MRA decision before commencing action, and it puts ND product decisions in the hands of regulators who have less experience in tropical disease products, presentations, and epidemiology, and who are not accountable for the needs and safety of target African patients. For instance, Western regulations may omit data requirements vital for safe large-scale use in Africa (e.g., trials assessing the safe interaction of HIV and malaria drugs). Rifapentine, a novel tuberculosis (TB) drug registered under US Orphan Drug provisions, ultimately could not be used in African TB patients despite being approved by the FDA because the trial design excluded HIV-positive patients. While HIV is less commonly associated with TB in the US, it represents up to 70% of TB patients in some sub-Saharan Africa countries, making the efficacy data submitted to the FDA inadequate for use in African populations [5]. Furthermore, the relative risk-benefit of ND drugs can be dramatically different in Africa and the West, where analysis against the same criteria can lead to completely different conclusions. For example, the first rotavirus vaccine, RotaShield, developed by Wyeth-Ayerst and licensed by the FDA in August 1998, was withdrawn from the US market in October 1999 due to a one in 10,000 risk of intussusception in children. This precluded its subsequent introduction in the developing world. While this risk-benefit analysis may have been valid for the US, where rotavirus causes less than 60 deaths per year, the vaccine was likely to have a much more favorable risk-benefit ratio in Africa, where rotavirus is responsible for approximately 5% of deaths in children under the age of five (a mortality rate of 183/100,000). Many of these problems are heightened in the case of regulatory pathways such as Orphan Drug approval and FDA Accelerated Review, which allow clinical trials to be abridged or downsized in order to expedite registration of treatments for diseases that are rare and life-threatening in the Western context (such as malaria), but affect millions of patients in the developing world.

New data show earlier treatment of HIV vastly reduces transmission risk, but “test and treat” and “treatment as prevention” are well recognized notions in pediatric HIV care. Yet children with HIV in low- or middle-income countries remain a largely neglected population.

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.

Neglected tropical diseases (NTDs) are the most common infections of the world's poorest people and the leading causes of chronic disability and poverty in low- and middle-income countries [1]–[3]. NTDs (Table 1) especially affect children and young women of reproductive age [4], and consequently deprive them of their health and economic potential [3]. NTDs also impair agricultural productivity and are an important reason why the world's poorest 1.4 billion people who live below the poverty line cannot escape destitution and despair [3]. Despite the devastating effect of these diseases on health and development, with evidence that their global burden is as great as that of any other serious disease [1]–[3], financial support for control and elimination efforts, as well as research and development (R&D), have been inadequate [2], [5]. Indeed, in Millennium Development Goal 6 (to “combat HIV/AIDS, malaria and other diseases”), NTDs were not even specifically mentioned but merely considered as part of the “other diseases” [6]. However, policy makers are slowly beginning to appreciate the importance of NTDs. Table 1 Neglected tropical diseases. The World Health Organization (WHO) has a new Department of Neglected Tropical Diseases, and WHO-TDR (Special Programme for Research and Training in Tropical Diseases) has a new 10-year strategic plan with support from UN agencies, member states, and private philanthropies. At the same time, funding for integrated NTD preventive chemotherapy control from the governments of the US and UK has increased dramatically and is approaching US$100 million annually, while support remains strong for product development partnerships from the Bill & Melinda Gates Foundation, Medecins Sans Frontieres (MSF), and a few European governments. Recently, the new Director of the US National Institutes of Health, Francis Collins, has targeted NTDs as a research priority, and the UK charity Wellcome Trust has agreed with the multinational pharmaceutical company Merck & Co. to allocate substantial funds for a joint, not-for-profit research center in India to develop inexpensive “antipoverty” vaccines against neglected diseases [7], [8]. Additional efforts to combat NTDs are also being shared among major multinational pharmaceutical companies (i.e., Novartis, GlaxoSmithKline, Pfizer, Sanofi-Aventis, Merck & Co.) and others who have also committed resources and made investments in research and development for these conditions. Thus, although at present only about 10% of the global funds required for preventive chemotherapy and NTD mass drug administration have been committed, and although R&D for NTDs has not even reached the so-called 10/90 gap [9], (meaning only 10% of available global R&D spending is committed for diseases that disproportionately affect 90% of the world living in low-income and middle-income countries), there is cautious optimism that such disparities could diminish in the coming decade. With a combination of funds from the group of eight (G8) nations, emerging economies (e.g., Brazil, India), multinational companies, and private philanthropic sources, together with a community of scientists, physicians, and other healthcare workers, global public health experts and policy makers committed to NTDs have begun to deliberate about how future resources and investments should be best allocated, particularly in terms of an appropriate balance between implementation and R&D. The leadership of key international agencies such as WHO, ministries of health in disease-endemic countries, and the communities themselves is key to achieve any ambitious strategy. With a global dialogue now underway, this is an appropriate time to present an eight-point manifesto (“a public declaration of motives and intentions by a government or by a person or group regarded as having some public importance” [2], [11]) for NTDs.

At a recent meeting (Sept 18, 2009) in which reasons for the limited access to artemisinin-based combination therapy (ACT) in sub-Saharan Africa were discussed, policy and market surveys on anti-malarial drug availability and accessibility in Burundi and Sierra Leone were presented in a highly interactive brainstorming session among key stakeholders across private, public, and not-for-profit sectors. The surveys, the conduct of which directly involved the national malaria control programme managers of the two countries, provides the groundwork for evidence-based policy implementation. The results of the surveys could be extrapolated to other countries with similar socio-demographic and malaria profiles. The meeting resulted in recommendations on key actions to be taken at the global, national, and community level for better ACT accessibility. At the global level, both public and private sectors have actions to take to strengthen policies that lead to the replacement of loose blister packs with fixed-dose ACT products, develop strategies to ban inappropriate anti-malarials and regulate those bans, and facilitate technology and knowledge transfer to scale up production of fixed-dose ACT products, which should be readily available and affordable to those patients who are in the greatest need of these medicines. At the national level, policies that regulate the anti-malarial medicines market should be enacted and enforced. The public sector, including funding donors, should participate in ensuring that the private sector is engaged in the ACT implementation process. Research similar to the surveys discussed is important for other countries to develop and evaluate the right incentives at a local level. At the community level, community outreach and education about appropriate preventive and treatment measures must continue and be strengthened, with service delivery systems developed within both public and private sectors, among other measures, to decrease access to ineffective and inappropriate anti-malarial medicines. What was clear during the meeting is that continuing commitment, strengthened interaction and transparency among various stakeholders, with focus on communities, national governments, and evidence-based policy and action are the only way to sustainably address the control of malaria, a disease which continues to have a significant health and socio-economic impact worldwide, particularly in sub-Saharan Africa. Details on the methodology employed in carrying out the studies discussed at this meeting, as well as more detailed results, data analysis and discussion of the studies are soon to be published.

Between 1 February 1987 and 31 May 1988 an evaluation of a nutritional rehabilitation centre in Tahoua, Niger was conducted. Among the 381 children admitted to the centre, 61 (16%) had kwashiorkor and 347 (91.3%) were aged between 6 and 29 months. Recovery and death rates were 46.2% and 14.4%, respectively. The median duration of stay until recovery was 21 days. Sixty-two per cent of deaths occurred during the 1st week of hospitalization. Three risk factors for death were identified by the study: patients with kwashiorkor with a weight/height (W/H) less than -3 SD, those with marasmus with a W/H less than -5 SD, and those dehydrated with marasmus. Among children included in the follow-up study after leaving the centre, the risk of dying during the follow-up period among children who absconded was 7.1 times higher than the risk observed among children who recovered. Among the children who recovered, no relapse was observed 3-18 months after they left the centre. This investigation indicates the importance of intensive therapeutic feeding centres in areas with a high prevalence of malnutrition.

Neglected diseases are diseases restricted to poor areas; diseases for which there exist no commercial incentives to invest in the development of new treatments. Patients suffering from these diseases often have no access to essential drugs; this can be a matter of life and death. Lack of research and patent protection play a crucial role. Both are cost driven; greed in the West curtails the availability of life-saving drugs for all. Treatment options for trypanosomiasis and visceral leishmaniasis are lacking. It is recommended that drugs for the treatment of 'neglected diseases' be developed via a centralised, public approach that is not based on profit, rather than leaving it to free enterprise.

Vincent Brown and colleagues review Epicentre's 20 years of experience conducting research during complex humanitarian emergencies.

Mortality data collected from 1984 to 1987 through a routine standardized health information system in the five main refugee populations of Honduras were reviewed. The direct standardized mean annual death rate for all refugees was 5.5 per 1000 population (Honduras population as reference; Honduras mortality rate: 10.1 per 1000). Mortality decreased or remained stable among Salvadoran refugees from 1984 to 1987, but increased among Nicaraguan refugees after 1985. The highest neonatal (56.1 per 1000 livebirths), infant (126.1 per 1000 livebirths) and under-five-year-olds (35.7 per 1000 child less than five years of age) mortality rates were observed in the two Nicaraguan camps. These two camps had the highest rate of newly arriving refugees. Deaths in infants and under-five-year-olds accounted for 42 and 54.1% of all deaths respectively. Of all deaths under five years of age, respiratory infections, diarrhoeal diseases and measles accounted for 21.4%, 22.1% and 4.7%, respectively. Mortality rates, particularly among under-five-year-olds and infants increased when the rate of newly arriving refugees was higher. The importance of adapted health surveillance in refugee settlements is discussed.

Infectious diseases cause the suffering of hundreds of millions of people, especially in tropical and subtropical areas. Effective, affordable and easy-to-use medicines to fight these diseases are nearly absent. Although science and technology are sufficiently advanced to provide the necessary medicines, very few new drugs are being developed. However, drug discovery is not the major bottleneck. Today's R&D-based pharmaceutical industry is reluctant to invest in the development of drugs to treat the major diseases of the poor, because return on investment cannot be guaranteed. With national and international politics supporting a free market-based world order, financial opportunities rather than global health needs guide the direction of new drug development. Can we accept that the dearth of effective drugs for diseases that mainly affect the poor is simply the sad but inevitable consequence of a global market economy? Or is it a massive public health failure, and a failure to direct economic development for the benefit of society? An urgent reorientation of priorities in drug development and health policy is needed. The pharmaceutical industry must contribute to this effort, but national and international policies need to direct the global economy to address the true health needs of society. This requires political will, a strong commitment to prioritize health considerations over economic interests, and the enforcement of regulations and other mechanisms to stimulate essential drug development. New and creative strategies involving both the public and the private sector are needed to ensure that affordable medicines for today's neglected diseases are developed. Priority action areas include advocating an essential medicines R&D agenda, capacity-building in and technology transfer to developing countries, elaborating an adapted legal and regulatory framework, prioritizing funding for essential drug development and securing availability, accessibility, distribution and rational use of these drugs.

In North America, Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) was first reported in Mexico in 1940 [1] and in the United States in Texas in 1955 [2]. However, based on ancient mummified remains discovered in the Rio Grande Valley, human T. cruzi infection has been present in North America since prehistoric times [3].

Drugs offer a simple, cost-effective solution to many health problems, provided they are available, affordable, and properly used. However, effective treatment is lacking in poor countries for many diseases, including African trypanosomiasis, Shigella dysentery, leishmaniasis, tuberculosis, and bacterial meningitis. Treatment may be precluded because no effective drug exists, it is too expensive, or it has been withdrawn from the market. Moreover, research and development in tropical diseases have come to a near standstill. This article focuses on the problems of access to quality drugs for the treatment of diseases that predominantly affect the developing world: (1) poor-quality and counterfeit drugs; (2) lack of availability of essential drugs due to fluctuating production or prohibitive cost; (3) need to develop field-based drug research to determine optimum utilization and remotivate research and development for new drugs for the developing world; and (4) potential consequences of recent World Trade Organization agreements on the availability of old and new drugs. These problems are not independent and unrelated but are a result of the fundamental nature of the pharmaceutical market and the way it is regulated.

In the next five years, we can now project that 200,000 people living with Chagas disease will die from heart disease and related complications. We urgently need to redouble our efforts to identify and treat young people who are still in the early stages of their illness, but ultimately we need to find better treatments and new cures. According to recent estimates, there are 5.7–9.4 million people living with Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi), a neglected tropical disease and leading cause of heart disease and cardiomyopathy, especially in Latin America and the United States [1,2]. Today, less than 1% of people infected with T. cruzi have access to diagnosis and treatment [3], a consequence of the fact that Chagas disease mostly affects those living in extreme poverty and in marginal surroundings. This finding is especially sad given new information by the World Health Organization (WHO) stating that more than one-half of Chagas disease sufferers live in Latin America’s three wealthiest countries—Argentina, Brazil, and Mexico [1]. Moreover, there are hundreds of thousands of infected people living in the US, with emerging evidence for significant T. cruzi transmission in Texas [4,5]. In this sense, Chagas disease represents one of the Western Hemisphere’s greatest health disparities. Moreover, in recent years we also have seen the globalization of Chagas disease to Spain and elsewhere in Europe and worldwide [6]. For years, the community of scientists, physicians, and other health care providers and Chagas disease patients has been awaiting the results of the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial, which was designed to evaluate the safety and efficacy of benznidazole in patients with Chagasic cardiomyopathy [7]. Approximately 20%–30% of T. cruzi-infected individuals progress to Chagasic cardiomyopathy, a debilitating heart condition associated with conduction disturbances, heart failure, and sudden death. While it is established that benznidazole is effective in curing Chagas disease patients during their early acute phase [8–11], very few individuals are diagnosed at this stage of the disease. The BENEFIT trial aimed to determine if the 1.17 million people now living with Chagasic cardiomyopathy (WHO estimate [1]) might also experience improved clinical outcomes or even cures with benzimidazole treatment. Unfortunately, the answer appears to be “no.” Compared to a placebo control, benznidazole did not result in a statistically significant improvement in cardiac clinical outcomes. Although the study was not sufficiently powered to show incremental benefits in cardiac outcome (on the order of 5%–15%), it is clear that our current strategies for antiparasitic chemotherapy need to be revisited for patients with evidence of Chagasic heart disease. But there is additional bad news—the BENEFIT trial found that in both treated and placebo arms (comprising almost three thousand patients), 17%–18% died over a five-year time frame, most from cardiac complications [7]. If we extrapolate from the WHO estimate, this means that roughly 200,000 people will die from Chagasic cardiomyopathy over the next five years. To put this number in perspective, it is almost identical to the number of women living in the US who will die from breast cancer over the same period [12]. Whereas breast cancer is now linked with a highly successfully and accomplished advocacy and awareness campaign that promotes early detection and treatment, as well as research and development (R&D) into an exciting portfolio of new and innovative therapies, we are now facing almost the opposite situation with Chagas disease and cardiomyopathy. Today, there are few advocates for the millions of Chagas disease sufferers mostly living in poor and marginalized conditions. As a result, the vast majority have no access to diagnosis and treatment, and far too little is invested into R&D for new drugs, vaccines, and other tools (including tests for cure). From our perspective, the BENEFIT trial is a wake-up call to aggressively pursue a global initiative of diagnosis, treatment, and research, emphasizing the following specific points