Rapid Diagnostics

Fighting emerging diseases

Lok Ting Lau

COO & General Manager, Hai Kang Life Corporation, Hong Kong

Albert Cheung-Hoi Yu

Chairman & CEO, Hai Kang Life Corporation, Hong Kong

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Hospitals must learn to incorporate new technologies for diagnosis for the simple reason that vaccination, drug treatment and other containment efforts cannot be maximised unless emerging diseases are quickly identified.

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Despite impressive advances in the field of antimicrobials and vaccination, the world is still facing the threat of emerging diseases. A new disease makes headlines almost every year. Are we witnessing more diseases now than any time in the past?

From the plague to the 1918 influenza pandemic, infectious diseases have always played havoc. Several factors have played a role in the rise of emerging diseases, including genetic variation in hosts and pathogens, environmental changes and population pressures. Furthermore, air travel has compounded the problem. People are traveling more often and so are germs. Travellers may be exposed to germs they do not have immunity to and hence have a higher chance of contracting an infectious disease, bringing it home and spreading to others. During the Severe Acute Respiratory Syndrome (SARS) outbreak, infected travellers carried SARS around China to Hong Kong, Singapore, Vietnam and Canada. Therefore, every serious infectious disease today is of global importance, not restricted to the country of origin.

Emerging diseases can also result from re-emerging old infections, new infections like SARS or infectious diseases which become difficult to treat due to drug resistance. More and more germs that were once easily controlled now defy treatment.

This is due to the indiscriminate and extensive use of treatments. Doctors cite diagnostic uncertainty, time pressure on physicians and patient demand as the main reasons for over-prescription of antibiotic.

Southeast Asia has experienced several emerging diseases in the past decade, e.g. the avian flu (H5N1) in Hong Kong in 1997, Nipah virus encephalitis in Malaysia in 1998, the SARS outbreak in Southern China in 2002, dengue fever in India in 2005 followed by chickungunya outbreak in India in 2006. Currently, H5N1 poses the greatest danger to humans because of its increased host range, rapid mutation, resistance to antiviral drugs and absence of vaccination.

Dengue fever, first recognised in 1950s, is the leading cause of childhood mortality in South Asia. Before 1970, only nine countries had experienced dengue fever but by 1995, the number had increased four fold. It is re-emerging in the tropics and had reached epidemic levels in India last year. Rapid growth of cities in tropical countries has led to overcrowding and decrease in sanitation, allowing more mosquitoes to live closer to more people. Many of the affected countries are some of the poorest.

The Nipah virus caused a severe outbreak of viral encephalitis in Malaysia in 1998-1999. It affects pigs and people. Large scale production of live stock e.g high concentration of pigs in limited space, have lead to the spread of Nipah virus. Recent outbreaks have occurred in India in 2001.

Tackling the challenges

Hospital workers are at the frontline battling emerging diseases. They are at a high risk of acquiring the infection because patients do not display obvious symptoms or in most cases, the symptoms are unknown. During the first few weeks of the SARS outbreak, Hong Kong, Singapore, Vietnam and Canada witnessed a large number of healthcare associated infections. Cases were either not identified quickly due to vague respiratory symptoms or inexperience in dealing with known SARS cases. In Hong Kong, 25% of patients with SARS were healthcare workers. Consequently, rapid diagnostic tests are of great importance for the management of emerging diseases in the future.

Molecular diagnostic tools have been around for years and are advancing with time. They have allowed us to discover diseases that may appear new but have been loitering around for some time. One example is Helicobacter pylori, the bacteria responsible for stomach ulcers. A few decades ago, the very idea of bacteria causing ulcers seemed far-fetched. But now, it is a proven fact, thanks to diagnostic tools available to test for Helicobacter pylori infection. The infection has not changed, but the only thing that has is our knowledge and perception of it.

Hospitals must learn to incorporate new technologies for diagnosis for the simple reason that vaccination, drug treatment and other containment efforts cannot be maximised unless emerging diseases are quickly identified. Vaccination cannot protect against the rapidly changing viruses of tomorrow and drug treatment cannot limit the spread. In the case of bird flu, drug treatment is effective only if administered within 48 hours after the onset of the symptoms.

Conventional methods vs rapid molecular

Most traditional or conventional microbiological and immunological approaches for identifying diseases work best when high concentrations of the pathogens are present, i.e. when the patient is already critically ill. They are also limited by the time required to obtain a satisfactory answer. Even with these concerns, they still remain as the most widely used method for identifying a broad range of biological agents. There are two reasons for this. Firstly, people have become accustomed to this method and are hesitant to adopt any changes. Secondly, these are well established methods and do not require significant investment in new technology or equipment and can be put into operation in a broad range of private and public laboratories. However, traditional methods tend to be labour and resource intensive and require sufficient expertise.

Molecular diagnostics, on the other hand, are sensitive, can be performed more rapidly with high throughput and at a lower cost. However, molecular diagnostic tests are not commonly used and virus culture still remains the method of choice. Also, most technicians in developing countries are not well trained to use molecular diagnostic tests. At the moment, microarray technology is developing rapidly but it still lacks the sensitivity for direct application to clinical specimens. Nevertheless, these new technologies are an option and through the availability of portable machines for conducting tests, they may change the face of diagnosis of emerging diseases in the future.

Routine methods in use today for diagnosis of emerging diseases can be divided into three categories:

  • Culture method, conventional method
  • Laboratory antigen detection tests, rapid test
  • Tests using Nucleic acid Amplification Techniques (NATs), rapid test Virus/bacterial culture is considered as the ‘gold standard’ for identification of viral/bacterial infections. However, in an outbreak, time is the limiting factor and the sooner the disease is diagnosed, sooner the control measures can be put into place.

The second type of tests are the antigen detection tests and they have to be carried out in a laboratory. These include the Immunofluorescence Assay and Enzyme-Linked Immunosorbent Assay (ELISA). Although these tests cost less, they are easy to operate and provide results within hours, they are prone to co-reactivity between proteins, affecting results. These methods are also less sensitive than Polymerase Chain Reaction (PCR), described below, and their sensitivity is inferior to virus/cultural isolation.

The third type of tests, NATs, give results within a few hours. This type of testing helps provide convenient and fast automated result analysis, achieve higher sensitivity as compared to virus isolation, and higher specificity than the traditional immunological testing. NAT tests include PCR and Nucleic Acid Sequence-Based Amplification (NASBA). NASBA offers advantage over other testing methods in that it requires no expensive machines for the whole process.

Cost effectiveness of rapid diagnosis of emerging diseases

Developed countries have the facilities to conduct diagnosis but the on-going challenge is to bring cost-effective and efficient diagnosis to highly affected developing regions with minimal resources. Asia has been the epicenter of many emerging diseases. Considering that 60% of the world’s population resides in Asia, emerging diseases are an important cause of death in developing countries, it is vital to make these rapid diagnostic tests available at rural healthcare centres because the vast movement of people between cities and rural areas will continue to introduce emerging microbes.

Advantages of employing rapid diagnostic methods

There are several clinical and financial benefits of rapid diagnostic methods. They reduce the number of tests required and their associated charges, reduce casual antibiotic use, side effects, the length of stay in the hospital, and increase appropriate antiviral usage. They also allow community surveillance by informing physicians quickly about what agents are in the community. Rapid diagnosis also prevents physicians from using drugs on wrong indications, possibly delaying proper treatment of other infections and thus enabling doctors to prescribe more effective drugs to patients.

Diagnostic laboratories in developing countries are confronted with several challenges including financial constraints to purchase equipment, supplies and reagents. They face problems in executing sample collection schemes for disease surveillance. Overall, the smaller hospitals have been slow to adapt to new technologies due to the lack of capital and clinicians' enthusiasm for them. It is important to support the development of tests that are quick, sensitive and inexpensive.

Peking University has initiated a low cost project to help eliminate the need for expensive machines for diagnosis in remote areas. A mobile unit based on the NASBA technology has been set up to conduct diagnosis on site. This saves time as it cancels the need to send results to one of the few designated laboratories for confirmation, in case of an outbreak. The mobile unit will be able to make the rounds of villages during any season, facilitating early diagnosis and treatment.

Prompt recognition and identification is the first and vital step in confronting any disease, regardless of whether it is a prevalent, a newly emerging one or deliberately released. It is important to develop and implement non-traditional methods for public health surveillance and a system that allows a wide and immediate dissemination of information.

References:

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Ho KY, Singh KS, Habib AG, Ong BK, Lim TK, Ooi EE, Sil BK, Ling AE, Bai XL, Tambyah PA.J Mild illness associated with severe acute respiratory syndrome coronavirus infection: lessons from a prospective seroepidemiologic study of health-care workers in a teaching hospital in Singapore. Infect Dis. 189(4):642-7, 2004.

Lau LT, Banks J, Aherne R, Brown IH, Dillon N, Collins RA, Chan KY, Fung YW, Xing J, Yu AC. Nucleic acid sequence-based amplification methods to detect avian influenza virus. Biochem Biophys Res Commun. 313(2):336-42, 2004.

Peruski LF Jr, Peruski AH. Rapid diagnostic assays in the genomic biology era: detection and identification of infectious disease and biological weapon agents. Biotechniques. 35(4):840-6, 2003.

Yu AC, Lau LT, Fung YW. Boosting the sensitivity of real-time polymerase-chain-reaction testing for SARS. N Engl J Med. 350(15):1577-9, 2004.

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