2008–09 saw rapid changes in the spread and nature of transmissible diseases, including transfusion-transmissible infections, and major advancements in testing and manufacturing processes.
A core focus of horizon scanning has been changes in the community infection rates of transmissible diseases, including transfusion-transmissible infections. Any upsurge in community infection—bacterial, viral or parasitic—has the capacity to increase the risk from fresh blood components unless risk-mitigation measures, such as increasing deferrals of blood donors, are introduced. Increased donor deferrals can contribute to a shortage of blood and blood components. Red cell donations from people with any of the diseases identified in the following sections cannot be used since the infectious agents in question reside only in the cellular components of blood. However, plasma from such donors remains a very valuable resource: the fractionation process is known to destroy such viruses if present in the plasma component of the donation.
During the Australian summer in 2008–09 blood supplies in Far North and North Queensland were seriously affected by a regional epidemic of dengue fever, the worst for some time, as shown in Table 3.1
TABLE 3.1 Notifications of dengue virus infection by year by jurisdiction, 1999–2008 and year to date 2009
| ACT | NSW | NT | Qld | SA | Tas | Vic | WA | Aust | |
|---|---|---|---|---|---|---|---|---|---|
| 1999 | 2 | 0 | 31 | 61 | 7 | 0 | 0 | 18 | 119 |
| 2000 | 1 | 1 | 94 | 85 | 7 | 0 | 4 | 7 | 199 |
| 2001 | 11 | 0 | 43 | 42 | 7 | 2 | 6 | 15 | 126 |
| 2002 | 3 | 16 | 32 | 81 | 8 | 1 | 11 | 18 | 170 |
| 2003 | 7 | 68 | 21 | 725 | 9 | 1 | 13 | 17 | 861 |
| 2004 | 6 | 30 | 19 | 274 | 4 | 1 | 10 | 7 | 351 |
| 2005 | 2 | 48 | 14 | 116 | 5 | 0 | 15 | 20 | 220 |
| 2006 | 6 | 51 | 21 | 77 | 11 | 0 | 5 | 16 | 187 |
| 2007 | 2 | 80 | 16 | 119 | 23 | 3 | 16 | 54 | 313 |
| 2008 | 6 | 154 | 23 | 232 | 31 | 6 | 8 | 98 | 558 |
| 2009 | 9 | 96 | 21 | 985 | 10 | 2 | 20 | 96 | 1239 |
Source: National Notifiable Diseases Surveillance System. DOHA website
Dengue fever has been a major challenge in many parts of the world in recent months, and our own region—for example, Indonesia, Singapore and Malaysia—has increased its activity in mosquito control. A number of research programs around the world have been aimed at devising affordable and easily portable equipment that will attract and destroy mosquitoes. One team has successfully halved the lifespan of the Aedes aegypti mosquito by introducing the Wolbachia bacterium into the laboratory population. The bacterium spreads through the population, being passed on by female mosquitoes.
Interestingly, many companies are now aiming to produce a commercial dengue vaccine, among them Sanofi Pasteur, Vical and Novartis. Central to much of this work is a focus on a vaccine that is effective against all four strains of the virus and on a drug to combat the associated fever.
Although the blood supply situation was manageable, with products being supplied from other areas of Australia, the affected region could become much larger in future seasons.
Countries in our region have also been coping with another mosquito-borne disease, chikungunya virus infection, which is characterised by an acute febrile phase that lasts for two to three days and is followed by prolonged arthralgic disease that affects the extremities. The pain associated with the virus persists for weeks or months, in some cases, years. The virus is not endemic to Australia at this time, but a small number of travellers do return home with it. It has, however, emerged in areas that were previously free of the virus. For example, chikungunya has infected people in northern Italy and in swampland near the France–Belgium border. International experts are concerned about the potential arrival in Europe of the Asian tiger mosquito, which could spread chikungunya more widely. This increased spread is largely attributed to unusually warm, damp weather in Europe.
Many companies are working to develop a vaccine against chikungunya, among them TopInstitute Pharma, which has formed a consortium with Wageningen University Medical Centre and Nobilon (a subsidiary of Schering–Plough) to develop a ‘proof of concept’ vaccine. In addition, trials on the genetically modified mosquito engineered by researchers at the University of Oxford—to control dengue and chikungunya—have begun at a laboratory near Chennai, India.
Malaria is a parasitic infection, that includes a blood phase, transmitted by bites from mosquitoes. Increased travel has led to malaria being identified more widely internationally. Researchers are using an array of strategies to combat its further spread, including:
The Murray Valley encephalitis and Ross River viruses now occur in areas well beyond their original range, and both were reported in the Northern Territory and the north of Western Australia during the summer of 2008–09.
The NBA will continue to monitor developments and is working towards the development of models to better predict the impact of these and other viruses on the long-term availability of suitable blood donations.
Each winter seasonal flu reduces the supply of blood and blood components through donor deferral, due either to sickness or to caring responsibilities, and the Australian Red Cross Blood Service is well versed in adjusting collection volumes and locations to best meet continued demand. The late and protracted flu season, from July to October in 2008, contributed to an ongoing shortage of red cells during the period, which necessitated activation of the National Blood Supply Contingency Plan.
In a pandemic a much larger proportion of the population is likely to be affected—swiftly, simultaneously and possibly more severely—and the NBA’s pandemic flu planning clearly identifies the potential for this to lead to major problems in supply. Accordingly, our research in 2008–09 not only focussed on monitoring flu patterns internationally and the impact of the pandemic (H1N1) 2009, but also on the developments that could support prevention of infection through effective vaccination and developments in the capacity to treat infection quickly and successfully.
At the onset of winter 2009 national attention was strongly focused on the impact of the pandemic (H1N1) 2009 (‘swine flu’). Jurisdictions’ efforts in attempting to prevent the virus from spreading—with testing, home quarantine and the issue of anti-viral drugs—have provided a good foundation for further modelling the impact of this and other flu pandemics on the blood supply. This will also provide useful data to inform future inventory risk management models.
Research to be undertaken through the National Health and Medical Research Council has commenced: the results, expected to be reported by December 2009, will be vitally important to future planning.
There has been intense competition between drug makers to create a commercially viable vaccine against pandemic (H1N1) 2009. The first such vaccines are, according to the World Health Organisation, likely to be approved and ready for sale after September 2009.
The increase in rapidly developed vaccines has led to some interesting innovations in the sector, including:
These technologies are important because they provide a glimpse of the changes in the time frames in the future in which intensive product management might be required for blood supplies in the event of a pandemic.
The recent emphasis on pandemic (H1N1) 2009 vaccine has not diminished the need for producing seasonal flu vaccine, although there was some discussion of whether pandemic (H1N1) 2009 vaccine could be added to the coverage of the seasonal flu vaccine. CSL Ltd expects to double shipments of its seasonal flu vaccine in 2009–10 after the vaccine sold out in US pre-season orders. CSL Ltd may generate $A102 million in sales of its Alfuria flu shot in 2009–10, exporting as many as nine million doses of the vaccine, the US military being expected to be a major buyer.
When the H1N1 2009 virus was notified as a pandemic, governments around the world relied heavily on Tamiflu, the leading relevant antiviral drug. Yet in the previous winter in the United States, the most widely circulating seasonal flu strain exhibited resistance to Tamiflu. Relenza, a powder that must be inhaled, also remained effective against the strain, but it is not recommended for children younger than seven years. The US Centers for Disease Control and Prevention recommended that doctors treat children with seasonal flu with a combination of Tamiflu and an older drug, Flumadine, to which the strain is not resistant. The emergence of a widely circulating strain that resisted Tamiflu highlighted the vulnerability of the world’s small stock of antivirals and provides yet another scenario for modelling purposes.
Both domestic and wild bird flocks around the world continue to become infected with bird flu. Most countries destroy diseased flocks. In Egypt, where there is no compensation for destroyed flocks, the reporting level is low and transmission to humans is significant, as is the number of deaths, although lower than in places such as Indonesia and Vietnam. Infectious diseases experts have expressed concern that a recent spike in human H5N1 avian influenza cases in China appears to have occurred in the absence of the hallmark of nearby poultry outbreaks, a development that could signal asymptomatic infections in birds.
Concern at a possible avian flu pandemic has led to the commercial development of a number of vaccines that it is hoped will be relevant to the prevailing strain. The US Food and Drug Administration has cleared for marketing a new, more rapid test for the detection of influenza A/H5N1, a disease-causing subtype of avian influenza A. The AVantage A/H5N1 Flu Test detects influenza A/H5N1 in throat or nose swab samples.
Two distinct teams of scientists announced they had found an antibody with affinity for both seasonal flu virus and the H5N1 pandemic flu strains. This discovery was suggested as leading to new treatments and possibly a universal flu vaccine.
During the reporting year the Spanish Government confirmed Spain’s fifth fatality from vCJD.
In the United Kingdom, the Health Protection Agency reported that vCJD prions had been identified at post-mortem in the spleen of a haemophilia patient. The patient was aged over 70, and had died of an unrelated condition. He had been treated with UK-sourced clotting factors prior to 1999.
Australia remains free of vCJD due to a high level of vigilance in our animal and food product trade. In response to the UK case, the Transmissible Spongiform Encephalopathy Advisory Committee assessed the risks to the blood sector of the reported situation and confirmed there was no need for any change in current policies. The policies in place, including donor deferral if the donor had lived in the United Kingdom for more than six months between 1 January 1980 and 31 December 1996, and adoption of the use of recombinant products for frequent users of clotting factors, plus prion clearance standards for Therapeutic Goods Administration registered products, provide a strong framework for protection against this disease.
During 2008–09 the NBA provided detailed comments on Australia’s draft response to the vCJD Plan. The plan now allows for the transfer of information to, and the involvement of, the blood sector in tracking and assessing the potential impact of any confirmed case of vCJD on the blood supply.
Tuberculosis is a major cause of illness and death worldwide but, despite 14.4 million prevalent cases, 9.2 million new cases and 1.7 million deaths in 2006, the small and rapidly declining burden of disease in the seven major markets has limited drug and vaccine development activities until recently. Drug developers and research foundations are trialling several novel vaccines and therapeutic strategies for prevention and treatment of tuberculosis.
Developments in testing and manufacturing processes are of major interest because they are often designed to lead to increased safety for the recipients of blood products. One of the challenges for blood sectors worldwide, however, is to ensure that increases in the safety profiles of products outweigh the often very large costs of moving to new technology and in determining an appropriate time frame for the implementation. Development of the multi-criteria analysis framework for assessing proposals submitted under Schedule 4 of the National Blood Agreement will present an opportunity for governments to make an informed examination of the benefits and costs of such innovations.
There were many potentially relevant developments in testing and manufacturing in 2008–09; the areas of pathogen inactivation and viral detection provide examples.
Foremost among innovations globally during 2008–09 are the changes in, and the increasing uptake of, pathogen inactivation technologies for fresh blood components. These include:
At present Australia uses testing and donor deferral rather than pathogen inactivation. These strategies have been very effective in reducing the risk of transfusion-transmitted diseases, but are principally effective against known pathogens, as opposed to currently unknown infectious agents. The developments in pathogen inactivation technology raise the possibility of increasing pressure to consider the move to this new approach to reducing the risk of transfusion-transmitted diseases. This could have significant impact on the overall cost of manufacturing and processing of blood products.
Technology to test for viral infection in blood using improved assays also changed during the reporting year:
During the reporting year work on oxygen carriers has been against the backdrop of a 2008 United States analysis of studies of five different blood-substitute products. The analysis suggested that, as a class, the products were linked to relatively high rates of death and myocardial infarction.
The prospective use of stem cells as the basis for extending the supply of blood and blood products is controversial, and there are a number of projects under way overseas. While research is progressing, the core question is scalability, so it is unlikely that these activities could contribute to the blood supply in the short term. The following are examples of this research in 2008–09:
Internationally there is increasing interest in the scope for reducing the need for red cell transfusions through the more targeted use of a range of blood and blood products and through the use of other products and techniques. The National Health and Medical Research Council guidelines that are being redeveloped will provide a detailed assessment of the current evidence and make recommendations for immediate adoption in Australia.
The NBA produced the initial national haemovigilance report for Australia in February 2008. The first haemovigilance tracking capacity in the United States was announced during 2008–09. At the same time the European Haemovigilance Network decided to change its focus to reflect a broader scope of engagement; it is now known as the International Haemovigilance Network (IHN) to ensure increased engagement by blood services and government agencies in its agenda. The NBA’s Principal Medical Officer attends network meetings on behalf of the Australian program. International developments should provide valuable benchmarking data and further stimulate the collection, analysis and understanding of adverse events arising from, or associated with, blood transfusions.