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This paper proposes a model to provide better access to fairly priced antiretroviral (ARV) drugs for HIV-infected people in poor countries, while also safeguarding the interests of ARV manufacturers.

The authors explain what governments and brand and generic companies are doing to increase the availability of ARVs in developing countries, taking examples from Brazil, Canada, China, India, the United States and Thailand. They also discuss the implications of creating more South–South partnerships to produce and market ARVs; and the impact that the UNTAID–Clinton Foundation coalition has had on lowering ARV prices in developing countries.

The authors recommend an incentive-based strategy that includes international donors bulk-purchasing generic ARVs, individual governments providing financial relief packages for generic companies, and the WHO brokering negotiations between brand and generic companies.

This series of commentaries and research articles — published by The Lancet, the Peking University Health Sciences Centre and the China Medical Board — addresses China's major health challenges, strategies and future. It has been produced by a group of 63 scientists from 10 countries with Chinese scientists making up two-thirds of the authors.

The research papers give scientific evidence on key health issues including the emergence and control of both infectious and chronic non-infectious diseases in China as well as the performance of China's healthcare system.

Authors of the series' commentaries further discuss a range of topical issues affecting China's health system, including the state of biomedical science and technology (see 'Progress in Chinese biomedicine a massive challenge'), medical research ethics, the lessons learnt from China's schistosomiasis control programme and the challenges the country faces in controlling HIV/AIDS.

This series of five articles outlines new challenges and unsolved problems since the journal's last series in 2005. The first article ([189kB]) predicts the disease burden and economic losses that developing countries would face from chronic diseases such as cardiovascular disease, cancer, chronic respiratory disease, and diabetes. In the 23 countries that the authors incorporated into a model, chronic disease was responsible for 50% of the disease burden in 2005. If no action is taken, they say, about US$84 billion of economic production will be lost from heart disease, stroke, and diabetes alone in these 23 countries between 2006 and 2015. The second article ([105kB]) looks at how to scale-up strategies to fight chronic diseases in developing countries. The authors review evidence to identify which methods are cost-effective and financially feasible, and therefore ready to be scaled-up.

Tobacco control, salt reduction (both of which are detailed in the series' third paper ([177kB])), and a multidrug strategy to treat individuals with high-risk cardiovascular disease (see an in-depth look in paper four ([220kB])) are prime candidates for scaling-up. What effect improving health systems has on the level of chronic diseases should be properly evaluated, say the authors. For some health interventions, such as preventing or controlling diabetes, there is little cost-effectiveness data for low or middle-income countries, but their scientific effectiveness is so compelling that countries should consider how best to incorporate them. The final paper ([92kB]) is a call to action to incorporate existing interventions into healthcare programmes, which in 2005 was costed at US$5.8 billion.

1990 saw the first major effort to estimate the main causes of illness and the biggest killer diseases in different countries. The data are important for public-health officials to allocate their resources wisely but also for feeding into estimates to plan for the future. Importantly, these need to be regularly updated to ensure that health programmes are still going in the right direction. This paper updates the 1990 study and offer predictions up to 2030.

The most forceful change in disease trends is in developing countries, with the proportion of people affected by non-communicable diseases set to increase. Proportionally, the number of people with infectious diseases is set to fall, though not when it comes to HIV/AIDS.

Because the authors also rely on predicting socio-economic development trends, they created best-case and worst-case scenarios for economic growth. In the pessimistic scenario, by 2030, the three leading causes of illness will be HIV/AIDS, depression, and ischaemic heart disease; in the optimistic scenario, road-traffic accidents will replace heart disease as the third leading cause.

The WHO has provided its own estimates of how non-communicable diseases are set to rise in developing countries. These authors pool data from national registries and international databases to compare data on the differing burden from individual diseases. They outline the risk factors associated with the diseases.

The main three killers are cardiovascular disease, diabetes, and cancer. The paper ranks different types of cancer by how many people in developing countries they kill (lung and breast cancer are the deadliest) and also ranks diabetes prevalence by country (India, followed by China, has the highest prevalence).

To tackle these diseases, say the authors, people need to look closely at the risk factors in their life – eating healthily and exercising can do much to reduce the chances of getting one of these diseases.

Cardiovascular diseases are set to rise dramatically in developing countries, partly because of an increase in risk factors for the diseases, which include diet, physical activity, smoking. The authors looked at cardiovascular disease risks such as being overweight or obese, systolic blood pressure, and total cholesterol, and related them to national income, food purchase constraints, and urbanisation. Body mass index (BMI) and cholesterol increased as national income increased, then flattened, and eventually declined. BMI also rose with increasing urbanisation.

The authors suggest that cardiovascular disease risks will increasingly be concentrated in low-income and middle-income countries. Thus, preventing obesity should be considered a priority in these countries, along with measures to control blood pressure, cholesterol, and tobacco use.

Researchers looked at global patterns of antibiotic resistance to assess how best to tackle the problem. They looked at three geographically separated, and culturally and economically distinct countries — China, Kuwait and the US: the theory was that if these very different countries had different patterns of resistance, a country-specific approach could still work: if the patterns were similar, a coordinated international response would be needed.

China had the fastest growing rate of increasing resistance, followed by Kuwait and then the US. The authors note that surveillance data are urgently needed to clarify the scope of the problem. Despite the paucity of data, preliminary data show China is doing worst — resistance of SPN (Streptococcus pneumoniae) to erythromycin is 73 per cent, compared with 23 per cent in Kuwait, and its MRSA levels are at 90 per cent

The authors say that although these countries have different trends at the moment, increasing globalisation means this might not last long. Also needed are better methods of data aggregation and analysis of how resistance is transmitted across national boundaries.

The first of this two-part series looks in detail at how antibiotic resistance affects the treatment of different types of illnesses — those that attack the gut (such as salmonella or cholera) and respiratory system (such as the tuberculosis bacterium), and the bacterium that causes gonorrhoea.  Treating these diseases in developing countries is increasingly difficult because the cheap antibiotics that were once effective are growing to be useful against bacteria that have developed resistance. These changes are pushing up treatment costs in developing countries. Drug-resistant tuberculosis, for example, is more expensive to treat than the non-drug-resistant type.

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The second half of this series focuses on action needed to contain antimicrobial resistance. It outlines the risk factors that can lead to resistance emerging and spreading, particularly in developing countries: using poor-quality drugs or inadequate infection control in hospitals, for example. The article outlines strategies to stop the problem getting worse but points out that developing countries differ widely in the state of their healthcare systems and their resources, so a one-size-fits-all model is not useful.

The authors emphasise the importance of education of the public and of medical practitioners because otherwise the only information available to most healthcare professionals is from pharmaceutical companies that may not fit government or local priorities. In developing countries, unsanctioned providers are a particular problem because they might give people counterfeit or substandard antibiotics that can fuel resistance.

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Good prescribing practices are important in tackling antibiotic resistance, and diagnostics are key to ensuring good practice. Knowing who not to treat is as important as knowing who to treat. The article reports on analyses by the Global Health Diagnostic Forum of the Bill & Melinda Gates Foundation to assess how many lives could be saved by better diagnostics for six major illnesses, including malaria and tuberculosis. The researchers assessed the technical issues associated with implementing the diagnostic tests in developing countries for three classes of laboratory infrastructure — none, minimal, or moderate to advanced.

They found that for acute lower respiratory infections, syphilis, gonorrhoea, chlamydia and TB, outcomes could be much improved if tests were sent to sites with minimal or no laboratory infrastructure. In these types of settings, the practicality of obtaining a specimen is important. For example, obtaining a blood sample correctly to test HIV viral load is almost impossible where there are no laboratory facilities. Using sputum to test for TB has similar issues because of the impracticability of the sample medium. Thus, new biomarkers might be needed to test for diseases with specimens different from those currently used. Combination tests that look for a range of infectious organisms in one sample would be useful in resource-poor settings.

The researchers also highlight the importance of taking into account cultural and social sensitivities when designing interventions – blood sampling is not always accepted in some regions of the world, for example.

In this research article, Victor Konde of the University of Zambia argues that industrial biotechnologies can improve food security in Africa through improved livestock feeds and vaccines, as well as biotechnological pesticides, fertilisers and herbicides. He adds that biotechnology can also help farmers process crop and livestock products for new markets.

But Africa must first overcome a number of key challenges, says Konde — including restrictions on agricultural exports, weaknesses in scientific capacity and investment, and a lack of diplomatic strength to effectively promote its interests in international negotiations.

The author proposes ways for African policymakers to encourage biotech enterprise and investment, collaborative and interdisciplinary research, strategic alliances and public–private partnerships.

This research article assesses the potential for biotechnological approaches to overcome major pests, diseases and weeds undermining food security in Africa. The eight authors review three major constraints — parasitic weeds and herbicide-resistant grasses, insect pests, including those carrying plant diseases, and mycotoxins that damage stored grains.

They note that biotechnological solutions to some of these are already being explored, such as insect resistance in maize, but they say that others, like the control of parasitic weeds, will require longer-term study. The authors argue that these should be prioritised in public research programmes and supported by the private sector through donations of useful genes and technologies.

Their methodical discussion helps identify key priority areas for crop biotech research in Africa. This article will be useful to policy analysts, decision makers and research managers working in the field.

This collection of articles forms an operational guide on how to conduct evaluations of diagnostic tests for malaria. It was published as a special supplement in Nature Reviews Microbiology. The collection includes an introduction, two review articles and a relevant set of guidelines.

The first review, A guide for diagnostic evaluations, provides background information, discussing why good quality diagnostic tests for malaria are needed, how they are evaluated and how regulatory standards can control the introduction and use of diagnostic tests. The second, Ensuring quality and access for malaria diagnosis: how can it be achieved?, focuses on the availability and use of diagnostic tests that perform reliably and accurately under field conditions and emphasises the need for community-based health management.

The guidelines, Evaluation of rapid diagnostic tests: malaria, outline the principles for evaluating malaria rapid diagnostic tests (RDTs). It stresses the need for field tests and describes the issues that can affect study design, RDT performance, standards and quality assurance and the effects of storage and cultured parasites in lab-based trials.

In this editorial* (J Infect Dis 189:2149-53, 15 June 2004), Marc Butlerys and his co-authors review the success and progress of strategies aimed at the prevention of MTCT during breastfeeding, and outlines the challenges for future research. These include the refinement of antiretroviral drug regimens, and the use of (still experimental) alternatives such as antibodies to clear any HIV that crosses to the baby during breastfeeding.  

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This 'sounding board' article in the New England Journal of Medicine is the most substantive of the three articles that stimulated international debate about the ethics of placebo-controlled trials in developing countries (the other two were editorials in the New England Journal of Medicine (see above) and The Lancet).

Lurie and Wolfe take the view that placebo-controlled trials of a less expensive course of antiretrovirals to prevent mother-to-child transmission of HIV were unethical and would lead to hundreds of preventable HIV infections in infants. They identify 18 placebo-controlled trials involving more than 17,000 women, of which two trials were conducted in the United States and the remainder in developing countries. All the participants in the US studies received some form of antiretroviral treatment. In contrast, some or all of the participants in 15 of the trials in developing countries (nine of which were funded by the US) were not provided with such treatment.
 
The authors list areas of agreement between the critics and supporters of such trials, and conclude that the sole point of disagreement is over what is the most appropriate standard of care to provide to the control group. They argue that given the current scientific evidence it would be possible to design shorter, more affordable antiretroviral treatment programmes without the need to conduct placebo-controlled trials.

In this commentary article, timed to precede the international microbicides conference held in London in March 2004, researchers Robin Shattock (United Kingdom) and Suniti Solomon (India) provide a brief overview of the scientific strategies being used in microbicides research and development.

Written for general readers with a scientific or medical background, the article contains some technical terms but also has a useful graphical illustration showing the targets of microbicide action. These include directly killing or immobilising HIV, and preventing cells that line the female genital tract from transporting the virus to deeper tissues in the body.

In this commentary article, HIV vaccine researcher Ron Desrosiers presents his view that the main reason we do not yet have a vaccine for HIV is due to unsolved scientific questions rather than a bottleneck in conducting clinical trials. Accordingly, he advocates a "renewed, coordinated and focused effort" on basic research rather than clinical trials for "feeble" candidates that "stand little chance of being effective".

Desrosiers is well known and respected in the HIV research field for his contribution to the scientific debate, and presents five lines of evidence for his contentions. These include the failure of immune responses elicited by current vaccines in HIV-infected individuals to control the virus; the failure of the animal models much favoured by researchers to fully represent HIV infection in humans; and the ability of new strains of HIV to 'super-infect' individuals already infected with another strain, even if their immune system appears to be controlling the first infection. He also disagrees with the aim of the recently formed "Global Vaccine Research Enterprise" of placing more candidates in clinical trials more quickly. 

The article is written for general readers with a scientific background, and assumes knowledge of how the immune system works and relevant technical terms. Nonetheless, it is a well-argued piece that provides much food for thought for the vaccine community and policymakers alike.

In this article, David R Bentley explores the potential role of genomics in diagnosis and treatment of human diseases. He summarises current knowledge of the human genome and describes research into disease-related human genes — more than 1,400 of which have been identified. He then discusses ways that this knowledge might be used to develop predictive tests or target research towards effective cures that correct or replace defective proteins.

The article describes various 'roadblocks' to the application of genomics to medicine such as a limited understanding of when and where genes are expressed, and what causes their expression. A limited understanding of how molecules function and interact and a lack of knowledge about the functional sections of DNA outside genes are further constraints.

Major advances in diagnosis and treatment of disease are likely to emerge from a fuller understanding and annotation of all of the functionally important elements in the human genome. Bentley calls for all new human genome data to continue to be made freely available to promote continued innovation and further progress towards this goal.

Reference: Nature 429, 440 (2004)

This article briefly considers the ways in which developing countries could benefit from the new drugs and vaccines that will result from mapping the human genome.

The impact of potential scientific advances will, the authors note, vary according to each country’s burden of disease, financial resources, educational attainment and health systems. But they suggest that even if only 10 per cent of the genome represents targets for new drugs, the possibility exists for creating at least 3,000 new molecular entities to combat disease.

Knowledge of the genome, the article goes on, should encourage medical researchers to seek out new interventions that are population-based and emphasis should be put on developing inexpensive drugs and vaccines that prevent disease and disability in populations. If not, the Human Genome Project has the potential to widen the gap in health care between the rich and poor on an unprecedented scale.

This optimistic review, by Marc Bulterys and colleagues at the US Centers for Disease Control and Prevention, summarises recent advances in preventing mother to child transmission (MTCT) of HIV-1. Without any intervention, the risk of MTCT is 15 to 40 per cent, amounting to 1,700 new paediatric infections a day.

In the West, interventions combining elective caesarean section and antiretroviral drugs have reduced this risk to around one per cent. However, such measures require a well-established infrastructure and healthcare system that is expensive and lacking in most of the developing world. The authors state that it is therefore necessary to explore the potential of simpler, less expensive treatment options.

The article includes a detailed account of individual clinical trials on the use of antiretroviral drugs to prevent MTCT, as well as pilot programmes to expand prevention of MTCT in developing countries. It also contains useful tables summarising the current knowledge of factors affecting MTCT, a list of completed phase II/III clinical trials of antiretrovirals (up to February 2002), and outlines a model for implementing a programme preventing MTCT in developing countries.