Gold standard genetic diagnosis of fetal chromosomal abnormalities using fetal cells collected through invasive procedures such as chorionic villus sampling and amniocentesis is precise, but is associated with a small risk of 0.5-1% of procedural miscarriage¹.

The first detection of cell-free fetal DNA in pregnant mother’s blood in 1997 by Lo et al.² has now led to the risk-free non-invasive prenatal testing (NIPT) clinically available since 2011, to understand the fetal genetic condition such as Down Syndrome and other chromosomal abnormalities of the fetus³.

Thanks to the concerted effort of several researchers and clinicians all over the world, NIPT is offered in many countries including Singapore.

Although NIPT is not a diagnostic test, if used appropriately, it increases the detection rate of fetal chromosomal abnormalities and thus decreases the number of invasive tests required. For example, the test is sensitive enough (99%) to detect Down syndrome with a false positive rate less than 0.1%⁴. It is also employed for the detection of other chromosomal abnormalities such as Edward syndrome and Patau syndrome.

DNA sequencing (arrangement of genetic information) of fetal and maternal DNA fragments in mother’s plasma are analysed and the data subjected to rigorous statistical analysis to ensure accuracy of the test.

Accuracy of NIPT is affected by various biological factors including fetal DNA fraction in maternal plasma, which is influenced by maternal body mass index, gestational age, fetal aneuploidy etc. Low fetal fraction in samples and assay failures necessitates the invasive testing⁵.

NIPT is considered a superior screening test when compared to traditional combined first trimester screening (cFTS), with a detection rate of 99% for Down syndrome, 96% for Edward syndrome and 91% for Patau syndrome with a cumulative false positive rate less than 0.4% ^1,4.

Apart from cell-free DNA, fetal cells circulating in mother’s blood are also considered novel candidates for prenatal diagnosis. Placental trophoblasts and fetal nucleated red blood cells⁶ are the two major fetal cell types that are being explored for prenatal diagnosis.

This approach involves the enrichment of these cells from maternal blood, extraction of their DNA and sequencing using the available gene sequencing methods⁷. This technology is under development and is expected to be available for clinical application soon.

Reference:

1 Harraway J. Non-invasive prenatal testing. Aust. Fam. Physician. 2017 46(10):735-739.

2. Lo Y.M.D., Corbetta N., Chamberlain P.F., Rai V., Sargent I.L., Redman C.W.G. and Wainscoat, J.S. Presence of fetal DNA in maternal plasma and serum. Lancet. 1997; 350:485–487.
3. Bianchi and Wilkins-Haug. Integration of Noninvasive DNA Testing for Aneuploidy into prenatal Care: What Has Happened Since the Rubber Met the Road? Clin. Chem. 014;60(1):78–87.
4. Gil, M. M., Quezada, M. S., Revello, R., Akolekar, R., and Nicolaides, K.H. Analysis of cell-free DNA in maternal blood in screening for fetal aneuploidies: updated meta-analysis. Ultrasound in Obstetrics and Gynaecology, 2015;45, 249–266.
5. Gregg A.R., Skotko B.G., Benkendorf J.L., Monaghan K.G., Bajaj K., Best R.G., Klugman S. and Watson M.S. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18(10):1056–65.
6. S. Ponnusamy, N. Mohammed, S.S.Y Ho, H.M. Zhang, Y.H Chan, Y.W.Ng, L.L.Su, A.P. Mahyuddin, A. Venkat, J. Chan, M. Rauff, A. Biswas and M. Choolani (2008). In vivo model to determine fetal-cell enrichment efficiency of novel noninvasive prenatal diagnosis methods. Prenat Diagn. 28:494-502.
7. Beaudet, A.L. Using fetal cells for prenatal diagnosis: History and recent progress. Am. J. Med. Genet. C. Semin. Med. Genet. 2016;172(2):123-7.

This article is written by Dr Sukumar Ponnusamy, a lecturer of 51±¬ÁÏ School of Life Sciences.

To begin with, C. auris is a species of fungus that grows as yeast under the Candida genus. It is a relatively new species, its first reported appearance inside a 70-year old Japanese woman’s ear canal in 2009, hence the name ‘auris’ (ear in Latin). Since its initial discovery, C. auris infections have been reported in 20 countries all over the world, though the true number is suspected to be a lot higher. C. auris is one of the few species able to cause candidiasis in humans, in which the fungus invades and infects our circulatory and central nervous systems, as well as certain organs like the kidneys, liver and even our eyes. C. auris infections are typically heralded by a fever accompanied by chills that are both resistant to treatment with antibiotics. What sets C. auris apart from most other Candida species is a series of problematic and worrying traits, such as the difficulty of identification, its prevalent outbreaks in healthcare environments and its multiple drug resistance.

For starters, why is C. auris so difficult to correctly identify? One of the main reasons is its cultures share many similarities to other more common species of Candida, especially C. haemulonii. The standard laboratory testing methods of blood and bodily fluid cultures are unable to differentiate C. auris from other Candida species without specialised technology and equipment such as matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). This can lead to misidentification and eventually, infection mismanagement, placing patients at a great health risk.

Majority of C. auris infections happen in healthcare facilities such as hospitals and nursing homes, where its risk factors are most prevalent. These factors are similar to that of other Candida infections and include diabetes, compromised immune systems whether due to disease or recent surgical procedures, usage of broad-spectrum antibiotics or antifungals and invasive tubes/lines in the body. In these facilities, the fungus grows on practically any surface, from the handles of doors to our own skin, due to its virulence factors promoting environmental persistence and the ability to colonise on human skin, and is further extrapolated by the alarming infrequency of hand-washing practices in these facilities.

Finally, the most concerning aspect of C. auris is its multiple drug resistance. Recent isolates have been shown to be resistant to the three main classes of antifungals, namely: azoles, polyenes and echinocandins. The only way to treat such infections is to use multiple classes of antifungals all at high doses, though some such as Amphotericin B are expensive, not easily available and tend to also have severe side effects. The limited methods of treatment, combined with its difficulty of identification have made C. auris a dangerous threat in healthcare settings and a hot topic of research amongst the global biological community.

The article is contributed by Wong Ming Li, who is pursuing the , awarded by Northumbria University, UK