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Problem

Invasive Candidiasis

On an annual basis, invasive candidiasis (IC) afflicts approximately 750,000 individuals globally and is the 4th most prevalent bloodborne infection in the United States[1][2]. Although statistics vary by location, 30-day mortality rates for the afflicted are close to 50% [3].

Invasive candidiasis occurs when a yeast from the Candida genus passes through the epithelial layer lining the gastrointestinal or respiratory tract and infects the blood and/or internal organs2. C. albicans is the most common culprit for these infections and is the pathogen responsible in approximately 50% of IC infections [4]. Patients with compromised immune systems, damaged mucosal membranes, and under treatment with broad spectrum antibiotics are at an increased risk for contracting IC; for this reason, IC primarily impacts patients in the ICU, patients receiving chemotherapy, and recent transplant recipients [5][6]

Should physicians not detect or misdiagnose the IC, patients are put at a severe disadvantage; a delay of more than 12 hours in administering proper antifungal therapy was linked with a 22% increase in patient mortality [7].

			Test Requirements
	Sensitivity	Specificity	Time (hr)	Cost	Equipment	Skill
BG[8]-[11]	78%	81%	12-16	Low	Medium	High
Mn/Anti-Mn Antibodies[12]-[13]	83%	86%	3	High	High	Medium
PCR[14]-[16]	95%	92%	4-12	Low	Medium	High
Blood Culture[16]	50%	100%	48-72	Low	Low	Low
T2Candida[17]-[18]	91%	99%	3	Medium	Very High	Low

*click test methods for more information

BDG: These diagnostics tests work by testing patient blood for the presence of 1-3-Beta-D Glucan, a component of fungal cell walls secreted in the event of a systemic fungal infection. BDG Assays cannot differentiate between yeast species, however, and additional testing is often required before the appropriate antifungal can be prescribed. BDG tests used by hospitals must be shipped to the diagnostic manufacturer for analysis, requiring an additional 8-12 hours, as the effort needed to standardize the protocols in hospital labs is extensive. Each test would cost $120 to perform.

Mn/Anti-Mn Antibodies: These diagnostic tests functional by testing patient blood for the presence of the Mannan antigen, a component of fungal cell walls, or anti-Mannan antibodies secreted in response by the human hosts. While these tests can be performed independently, they are often performed simultaneously to increase diagnostic accuracy (statistics shown in table). Together, these tests costs ~$850 to perform.

PCR: Although boasting high sensitivities and specificities, PCR as a diagnostic tool has not yet become the gold standard due to a general lack of standardization in protocol. The statistics describing test accuracy pool the results of over 50 individual studies utilizing different protocols. As of 2016 no commercial PCR kits developed for this purpose have been created; no research conducted by Purdue iGEM has since shown otherwise.

Blood Culture: In many clinics blood culture is still the most prevalent diagnostic for IC. While this may be the simplest test to run, it has a very low accuracy and in the best-case scenario takes 2 days to complete; in rare instances, however, the assay can take up to 8 days. Blood culture is also incapable of detecting deep-seated candidiasis, the infection of sub-mucosal tissues by C. albicans which can later spread to the blood and cause IC.

T2Candida: The T2Candida Assay is the current gold standard for the detection of IC. By using magnetic resonance, the machine is able to detect the yeast from blood samples in 3 hours. T2Candida’s only downfall? Its price-tag. The machine used to perform the test costs approximately $150,000, limiting its typical use to larger hospitals in urban environments.

What is a vulvovaginal candidiasis?

When you hear the phrase “yeast infection”, you probably associate it with vulvovaginal candidiasis. Three in every four women fall victim to vaginal yeast infections in their lifetime [19]. Approximately 36% of women have one annually and about 3% claim to have them regularly [20]. However, yeast infections do not only affect women; infections have been reported amongst men after sexual contact with an infected woman[19]. Among other symptoms, untreated infections can cause severe irritation and can prevent or delay pregnancy [19],[21].

Candida is a genus of yeasts which live in moist areas of the body including mouth, rectum, and vagina. Of the 5 Candida species responsible for vulvovaginal yeast infections, approximately 20% of healthy women harbor at least 1 species in their vaginal microbiome [22]. Pathogenicity varies from species to species, however; overgrowth of Candida albicans (C. albicans) is responsible for 90% of all vulvovaginal yeast infections [19].

What causes yeast infections?

The vagina is a self-regulating organ which is home to a diverse array of microbial species. The relative populations of each species, both bacterial and eukaryotic, are dependent on temperature, humidity, pH, and the concentrations of too many chemicals to count. If any of these variables fluctuate too greatly, however, the delicate balance of power can shift to favor different organisms, often resulting in some form of vaginal infection [23].

What increases the chances of getting a yeast infection?

Although the vagina of a healthy adult is usually quite adept at maintaining this balance, the following factors have been found to increase an individual’s risk of developing a yeast infection:

Controllable Risk Factors

• Douching
• Obesity
• Oral Contraceptive Use
• Stress
• Tight Underwear
• Underwear made from synthetic fabrics
• Wearing sweaty clothing

Uncontrollable Risk Factors

• Chemotherapy
• Diabetes
• HIV/AIDS
• Pregnancy
• Weakened Immune System

What are the symptoms of a yeast infection?

Vaginal yeast infections cause irritation, redness, swelling, burning, and itching in and around the vagina. Additionally, vaginal discharge becomes thick, discolored, and chunky. Pain can increase during sex or urination [19]. These symptoms are unfortunately consistent with bacterial infections of the vagina, making it difficult to self-diagnose using symptoms alone. If left untreated, yeast infections can spread to other parts of the body and cause “digestive issues, new food allergies, mood swings, brain fog, mental confusion, [among] unexplained weight gain” among other maladies [21].

What are treatment options for a yeast infection?

Those experiencing the aforementioned symptoms have 4 options: diagnose the infection with an OTC test and then seek out treatment options, visit an OBGYN or other healthcare provider for diagnosis and treatment options, self-medicate without diagnosis, or wait out the infection. Each option has its pitfalls.

Virtually all over-the-counter (OTC) tests used to diagnose vaginal infections rely on pH to determine whether or not the culprit is a bacteria or a yeast. If the vagina has a basic or neutral pH the test will conclude the infection is caused by yeast; if the vagina has an acidic pH the test will conclude the infection is caused by a bacteria. Although sufficiently accurate in ideal test conditions, test conditions are ideal far too infrequently for pH-based diagnostics to be considered incredibly useful. The best-selling pH-based test in America, Monistat, states that an individual’s results may be skewed if they are pregnant, nursing, menstruating, have had sex in the last 48 hours, or are menstruating. For a female aged 12-51, conditions are ideal, on average, ~35% of the time. An incorrect diagnosis will prompt patients to seek out the wrong antimicrobial drug; taking these drugs will not only propagate antimicrobial resistance but will further disrupt the health of the vaginal microbiome, leading to a worsening of symptoms.

Alternatively, many women immediately seek a medical professional to diagnose and treat vaginal infections. Although doctors and specialists are a more reliable way to address such infections, scheduling and attending an appointment requires the patient to invest significantly more time and money. Once in the clinic, a doctor will likely use a test to identify the pH of the vaginal environment, thoroughly examine the vagina and cervix for redness and swelling, take a mucosal sample, and screen it for yeast. Sample screening requires a trained doctor to search for individual yeast cells under a microscope for approximately 10 minutes, a significant amount of time for a doctor to personally devote to an assay, but successfully identifies yeast only 75-80% of the time [25].

Only 11% of women who self-diagnose and medicate from symptoms alone are correct, as the common symptoms of vaginal yeast infections can also occur with bacterial vaginosis, dermatitis, trichomoniasis and other sexually transmitted diseases, and urinary tract infections [24][26]. Those who choose to do nothing are almost guaranteed to have a worsening of symptoms.

References

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