Recent Advances of Fungal Diagnostics in Asian Laboratories

Professor Arunaloke Chakrabarti
Head
Department of Medical Microbiology
Postgraduate Institute of Medical Education and Research
Chandigarh, India

Mortality due to invasive fungal infection is up to 100% if not treated and about 50% even with proper treatment. The poor outcome is attributed to absence of diagnosis due to nonspecific clinical signs and symptoms. Common clinical situations include inappropriate use of broad-spectrum antibacterial drugs in inaccurately diagnosed fungal sepsis and failure to diagnose chronic pulmonary aspergillosis in smear-negative pulmonary tuberculosis, among others.¹ These scenarios point to the importance of access to advanced fungal diagnostics to improve clinical outcomes, promote antimicrobial stewardship and control antimicrobial resistance.

Current methods detect clinical infection

Currently available methods include T2 magnetic resonance for detection of candidemia,² molecular identification of the fungus in the tissue – immunohistochemistry, DNA sequencing and fluorescence in situ hybridization (FISH)³ and the proteomic-based matrix-assisted laser desorption ionization (MALDI) for the identification of various fungi.⁴ These methods, however, are only able to detect pathogens upon clinical infection. Improvement of outcomes, however, will rely on detection at biological infection and prompt administration of targeted prophylaxis or pre-emptive therapy.

New diagnostic tests

Several new prospective diagnostic tests have been developed in recent years, each with their own pros and cons. These include the combination of polymerase chain reaction (PCR) and galactomannan tests,⁵ proximity ligation assay,⁶ detection of siderophore production⁶ and electronic nose technology for Aspergillus detection,⁷ and cryptococcal antigen lateral flow assay.⁸ These methods have various rates of success and need further validation. Current consensus for diagnostic tests serves as a guide for choosing appropriate methods (Table). 

Table. Current consensus on diagnostic tests for fungal infections

Infection	Culture/ histopathology	Biomarker (antibody)	Biomarker (antigen)	Response to treatment
Aspergillosis	Yes – invasive	No	GM/BDG/PCR	Increasing evidence
Cryptococcosis	Routine	No	Antigen/PCR	Yes (CSF antigen)
Histoplasmosis	Culture – delay	Limited	Antigen	Yes (antigen)
Mucormycosis	Yes – invasive	No	Investigational	No
Other molds	Yes – invasive	No	Investigational	No
Candidiasis	Routine	Investigational (anti-mannan)	PCR/mannan/BDG	No

BDG, β-D-glucan; CSF, cerebrospinal fluid; GM, galactomannan; PCR, polymerase chain reaction    

Present scenario in Asian countries

A recent study involving 241 laboratories in 7 Asian countries revealed poor access to biomarker tests like galactomannan, β-D-glucan and PCR in Indonesia, the Philippines and Thailand.⁹ The authors called for the need for the development of quality laboratories, accreditation and training of manpower in existing laboratories, as well as access to advanced non–culture-based diagnostic tests for improved diagnosis of fungal infections in Asia.  

Highlights of the Medical Mycology Training Network Conference, August 5–6, 2017, Kuala Lumpur, Malaysia.

References

1. Denning DW, et al. Emerg Infect Dis 2017;177-183.
2. Beyda ND, et al. Diagn Microbiol Infect Dis 2013;77:324-326.
3. Zaman K, et al. J Med Microbiol 2017;66:1124-1129.
4. Ghosh AK, et al. Clin Microbiol Infect 2015;21:372-378.
5. Arvanitis M, et al. Clin Infect Dis 2015;61:1263-1272.
6. Johnson G, et al. Biomark Med 2014;8:429-451.
7. de Heer K, et al. J Clin Microbiol 2013;1490-1495.
8. Nalintya E, et al. Cur Fungal Infect Rep 2016;10:62-67.
9. Chindamporn A, et al. Med Mycol 2017 [Epub ahead of print].