Executive summary

In the last decade, the incidence of opportunistic fungal infections has increased dramatically. The enhanced recognition of fungi as important medical pathogens has resulted from both increased awareness and increased incidence. The reasons for the increase has been the expanding populations that are at risk of fungal infections. Concomitant with the AIDS epidemic there has been a dramatic increase in the occurrence of fungal infections. Three of the top AIDS-specific diseases were fungal diseases such as Pneumocystis carinii pneumonia, candidiasis and cryptococcosis. New developments in medicine such as the increased use of prophylactic antibiotics, indwelling catheters, prosthetic devices, intensive cancer chemotherapeutic regimens and immunosuppressive drugs in organ and bone marrow transplants have become standard healthcare for critically ill patients. Yet these same lifesaving medical advances predispose these patients to a variety of fungal infections. For example, the incidence of Candida infection in neonates and outbreaks in neonatal intensive care units are increasing and threatening the lives of low birth weight infants. The invasive, disseminated, life-threatening form of candidiasis is seen in patients in intensive care, post-surgical and neutropenic patients. The case fatality rate of systemic fungal infections of 70-90% is nearly three times higher than that for bacterial infections. The Candida species of clinical importance reported in this country include C. parapsilosis (51%), C. albicans (11.8 %), C. tropicalis (25.5%), C. glabrata (3.8%), , C. rugosa(7%) and C. gullliermondii (1%) (Ng et al., 1999; Ng et al., 2000). This differs from Western data where C.albicans represent 40 % of systemic candidiasis.

Early detection of systemic infection has a great impact on the clinical outcome of candidiasis. The Candida species needs to be identified as some of the Candida species are inherently resistant to the standard antifungal drugs. For example, C. krusei is resistant to fluconazole and C. glabrata is resistant to fluconazole and itraconazole. The wide spectrum antifungal drug, amphotericin has side effects. Thus, it is important to identify the Candida species in order to prescribe the suitable antifungal drug for the management of the patient. The current laboratory diagnosis relies on blood culture, biochemical tests and morphological identification.

 

Project Title:

Alternative Control of Haemorrhagic Septicaemia in Cattle

 

These procedures take at least 3-7 days as the Candida is slow to grow, the tests are time-consuming and laborious. Consequently, when these results are obtained, it is too late to save the life of the patient. Thus, there is a dire need for the development of improved rapid diagnostic tests. The importance of Candida as a pathogen of medical importance is underestimated. A study in Australian suggest that 30% of patients admitted to hospital die of infections acquired at hospital such as systemic candidiasis and not of the disease that they were initially suffering from.

The objectives of this project are to:

1. develop PCR diagnostic assays for rapid detection of systemic candidiasis
2. develop molecular typing methods for DNA fingerprinting of Candida species
3. produce antibodies for the development of ELISAs for detection of systemic candidiasis
4. identify the genetic variations of virulence factors such as phospholipase and aspartyl proteinase by nucleotide sequencing
5. discover novel genes which contribute to the pathogenecity of systemic candidiasis

The team members have diverse skills such as molecular biology, immunology and microbiology. Initial work has started to identify new primers and diagnostic targets which have potential intellectual property value. The development of our diagnostic tests will provide tools for rapid, sensitive and accurate identification of Candida species which are of relevance to our country. The commercialization of these diagnostic kits will create wealth for our biotechnology industry. The applications of advanced technology such as microarray and realtime PCR will also be applied. The budget requested is RM1.8 million over 3 years.

Period of the project : 3 Years (2003 - 2005)

Project Status

- On-going