Background

The global burden of fungal infections

Fungal pathogens are a major public health threat with significant global effects which, surprisingly, is not being addressed as it should. Globally, around 1.5 million people die each year of invasive fungal infections and the number of people who die each year from the top 10 invasive fungal diseases is at least equal to those dying from tuberculosis or malaria. Moreover, the mortality rate of invasive fungal infections is usually greater than 50%.

In contrast, funding for medical mycology is highly underrepresented, accounting for 1.4-2.5% of the total of what the Welcome Trust, the U.K. Medical Research Council and the U.S. National Institutes of Health spent in 5 years during the late 2010s. This under representation could be just an effect of the number of applications for funding in the area, but even so, the need for an increased awareness and engagement by funding institutions and researchers is no less urgent: the development of new diagnostic and therapeutic tools is critical to improve the situation of high-risk patients.

The most common fungal infections are superficial skin, nails and mucosal infections, which are caused in most cases by fungi of the genus Candida. These infections are usually not life threatening and have such common manifestations as athlete's foot and vulvovaginal candidiasis.

Invasive fungal infections, on the other hand, have unacceptably high mortality rates. Patients with a compromised immune system -such as AIDS patients and post-transplantation patients taking immunosupresants- are at special risk as they don't have the usual barriers that prevent invasive infections in healthy individuals.

According to Brown, et al., (2012), more than 90% of the reported deaths caused by fungi are associated with species from four genera: Cryptococcus, Candida, Aspergillus and Pneumocystis, but epidemiological data for fungal infections is poor, as these infections are often misdiagnosed and there is a lack of accurate data from the developing world.

Endemic dimorphic mycoses

Endemic mycoses occur in geographically localized hotspots where even immunocompetent individuals are at risk. The following map is an adaptation of the information presented in Brown, et al., (2012), where the authors make some comments regarding the quality of that information: 1) The data is extrapolated from a few and geographically localized studies and 2) accurate data is lacking from the developing world and the calculations may underestimate the true values of the presented statistics.

Hover your pointer over the colored circles to see the data

Opportunistic invasive mycoses

Opportunistic mycoses affect those patients with a compromised immune system, such as AIDS patients and patients taking immmuno-suppressants, particularly those that were intervened with a solid transplantation. The following interactive graphic is also an adaption of the information presented in Brown et al., (2012).

From top to bottom, the data on the upper-right corner is the following: 1) Disease name, 2) The causative organism 3) Mortality rates (% in infected populations) and 4) Estimated number of life threatening infections per year worldwide.

Hover your pointer over the colored circles to see the data

The diagnostic tools currently employed to detect fungal pathogens:

The diagnostic methods employed to diagnose fungal infections at present vary in performance as each type of pathogen has a greater proclivity for being detected by some tests than others. However, microscopy has always been the mainstay as far as diagnosis of fungal infections is concerned. We look forward to improve the diagnostic capabilities of conventional microscopy by enhancing specificity and visibility through the application molecular biology.The following table was compiled from Fungal Infection Thrust.

Fungal infection	Diagnostic technique
	Microscopy	Agar culture	Xrays/scans	Antigen	Blood antibody	DNA detection
Thrush	+++	+++	-	-	-	-
Candida bloodstream	-	+++	+	+	+	+++
Candida abdominal	+	+++	+	-	-	-
Cryptococcal meningitis	++	+++	+	+++	-	-
Invasive aspergillosis	+	+	+++	++	-	++
Chronic aspergillosis	+	+	+++	-	+++	++
Allergic aspergillosis	+	+	++	-	+++	+
Coccidioidomycosis	+	++	++	-	+++	-
Histoplasmosis	+	++	+	++	-	-
Zygomycosis	+++	+	++	-	-	-

Detection by Polymerase Chain Reaction

The table above denotes a summary of the techniques used at present to detect the leading fungal pathogens in world. Note that the column titled "DNA detection" is a term that mainly involves the use of the Polymerase Chain Reaction (PCR)to detect pathogens. Although it is touted as a reliable technique, it has several disadvantages such as high cost, requirement of laboratory settings of high standards and false positives due to detection of pathogenic DNA EVEN AFTER the resolution(clearance) of the disease. Finally, PCR amplifies the DNA in a sample and only gives qualitative results. While Real-Time PCR can give information on the initial amount of the sample, it requires RNA samples which are degraded by RNases in the body and even if it isn't, it requires a well equipped laboratory to prevent further degradation.Therefore, this method cannot be used reliably in many parts of the world (especially in the underdeveloped countries).

Another technique that can be used to detect pathogens through their DNA is DNA-hybridization, but the downside with this method is that it is labor intensive and involves the use of radio-labelled probes.

Detection by Microscopy

As mentioned before, microscopy has been the mainstay for detection of pathogenic fungi. This is primarily due to the fact that it's one of the oldest and most widely available means of detection. It only requires a microscope, a stain for contrast, the sample from a patient and a user with some experience. Furthermore, this technique requires neither the consideration of multiple parameters (such as in a PCR) nor much time (agar plate cultures need at least a day) to yield results.

Thus, we believe that improving detectability through microscopy by giving it the advantage of molecular biology (specificity and a better scope for visualization) while maintaining the advantages of conventional microscopy.

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References

1. 1. Brown et al., (2012), Hidden Killers: Human Fungal Infections, Sci Transl Med, Vol. 4, Issue 165.