Sita Mager, PhD
The fungal kingdom primarily functions as decomposers of organic matter and is driven by decay signals. Fungal growth can be relentless once triggered, often requiring medical interventions to delay it. Paradoxically, some modern therapeutic approaches might inadvertently promote fungal invasion by interfering with the remaining components of the immune system.
Certain pathogenic fungi, along with their mycotoxins, have been linked to cancer in humans. For instance, Aspergillus, a common environmental fungus, produces aflatoxins—known carcinogens. Mycotoxins can cause various toxicities, including hepatotoxic, mutagenic, nephrotoxic, neurotoxic, and teratogenic effects. Moreover, all mycotoxins are toxic to the immune system.
Fungi have been shown, both clinically and radiologically, to mimic or be indistinguishable from malignancies. Distinguishing between fungal infections and malignancies is critical in providing appropriate treatment and minimizing the physical, psychological, and financial burdens on patients.
Our study involved a retrospective review of published case reports involving patients initially suspected of having pulmonary malignancies but ultimately diagnosed with fungal diseases. Data were collected from PubMed, and descriptive analysis was conducted on various case report details, including patient demographics, clinical presentations, diagnostic methods, features, hypotheses, biopsies, malignant neoplasia evidence, methods for confirming final diagnoses, interventions, and outcomes.
The inclusion criteria encompassed full-text case reports, case series, letters, correspondence, and short communications presenting at least one case. Only cases with a diagnostic hypothesis of lung cancer were reviewed.
After applying inclusion and exclusion criteria, a total of 354 reports were screened, and 30 case reports met the criteria for data collection and analysis. The median patient age was 55 years, the age range was 32 to 74 years, and gender was almost evenly distributed. Patients presented with various clinical features, with cough and dyspnea being the most prominent. Some patients did not exhibit typical symptoms but were diagnosed following routine evaluations.
Chest CT scans were the most frequently used diagnostic method, followed by PET-CT and X-ray. The most common diagnostic features were lesions and masses, followed by increased uptake and nodules. Other diagnostic features included atelectasis and abnormal shadowing.
This study highlights the importance of considering fungal diseases in patients even when they do not present typical symptoms because fungal infections can produce a wide range of non-specific clinical presentations. Additionally, clinical signs can be absent in patients diagnosed with fungal diseases, underscoring the need for vigilance even in asymptomatic individuals.
This study may help raise awareness of the potential for fungal infections to mimic malignancies and highlight the importance of accurate diagnoses for appropriate and timely treatment. The fungal kingdom serves many functions in the biosphere; however, the primary function is in the area of the end of biological life – as decomposers of organic matter. Fungal growth tends to be triggered by decay signals and, once activated, the fungus will not cease invading and may perhaps be stalled only because medical procedures intervene to delay physiological death. Paradoxically, modern therapeutic approaches may encourage fungal invasion by interfering with the immune system.1
Some pathogenic fungi and their mycotoxins are known to cause cancer in humans. For example, Aspergillus, a common fungus in the environment, produces aflatoxins—naturally occurring toxins—that frequently contaminate the food supply. The International Agency for Research on Cancer (IARC) classifies aflatoxins as Group 1 carcinogens, meaning there is enough evidence to establish that they can cause cancer in humans 2–3. Mycotoxins can cause various toxicities including hepatotoxic, mutagenic, nephrotoxic, neurotoxic, and teratogenic toxicities. However, all common mycotoxins share a trait—they are toxic to the immune system.4–5
Furthermore, fungi have been shown to clinically and radiologically mimic and/or be indistinguishable from malignancy.6–7 The management and outcomes of fungal infection and malignancy are fundamentally different. Therefore, obtaining an accurate diagnosis is critical in providing appropriate and timely treatment while reducing the physical, psychological, and financial burdens on patients. Our present study conducted a retrospective review of published case reports of patients who presented with suspected pulmonary malignancy but were eventually diagnosed with fungal disease.
Data were collected from PubMed, and descriptive analysis was performed on case reports of patient demographics (age and gender), clinical presentations, diagnostic methods, diagnostic features, diagnostic hypotheses, biopsy methods, evidence of malignant neoplasia, diagnostic methods used to confirm final diagnosis, final diagnosis, interventions, and outcomes. Microsoft Excel 2019 was used for data collection, and IBM SPSS Statistics 29 was used for data reporting and analysis. The keywords “fungal infection,” “mycosis,” “misdiagnosed,” “misdiagnosis,” “differential diagnosis,” “mimic,” “mimicking,” “mistaken,” “masquerading,” “simulating,” “suspected,” “confused with,” “presenting,” “imitating,” “cancer,” and “malignant” were used in various combinations.
The inclusion criteria were full-text case reports, case series, letters, correspondence, and short communications presenting at least one case. Cases with suspicion of malignancy that were ultimately diagnosed with fungal disease were included and only cases with diagnostic hypotheses of lung cancers were reviewed. The exclusion criteria were articles that consisted solely of an abstract or did not involve human subjects. Articles with findings that regarded fungal diseases to be a result of cancer and articles following its treatment protocol (i.e., effects) were excluded. Furthermore, articles that are not in English language were excluded. Finally, cases with no diagnostic hypothesis of lung cancers were excluded.
A total of 354 records were screened based on the inclusion and exclusion criteria, leading to the exclusion of 256 records. An additional 2 case reports were eliminated due to duplication. Out of the remaining 96 records, 6 were discarded because their text was not in English. Consequently, 90 eligible case reports were left; however, a further 63 cases that are not related to lung cancers were excluded. Finally, the total number of case reports included for analysis was 27, with 2 of them presenting multiple case series. One paper consisted of 2 cases and another had 3 cases. Therefore, the total number of cases used for data collection and analysis was 30. The papers that were included in the present study are listed in the Appendix (below).
Reports that were excluded involved fungal diseases mimicking basal cell carcinoma,8–10 bile duct conditions,11–14 bone disorders,15–17 brain conditions,18–21 breast abnormalities,22 colon diseases,23–26 colorectal disorders,27 duodenal problems,28 esophageal conditions,29-30 laryngeal disorders,31–33 leukemia,34 liver conditions,35 lymphoma,36–45 melanoma,46–48 pancreatic diseases,49-50 prostate conditions,51-52 rectal problems,53 renal diseases,54 stomach conditions,55 soft tissue sarcoma,56–58 squamous cell carcinoma,59–62 and tracheal cancer. 63
The cases reviewed showed the median age of the patients to be 55 years. The youngest patient was 32, and the oldest was 74 years. The distribution of gender was nearly equal, with 53.3% being male (n = 16) and 46.7% female (n = 14).
The patients presented with various clinical features, including cough (19.4%; n = 14), dyspnea (13.9%; n = 10), chest pain (9.7%; n = 7), fever (6.9%; n = 5), weight loss (6.9%; n = 5), hemoptysis (4.2%; n = 3), fatigue (4.2%; n = 3), headache (2.8%; n = 2), loss of appetite (2.8%; n = 2), malaise (2.8%; n = 2), dysphagia (1.4%; n = 1), disorientation (1.4%; n = 1), hoarseness (1.4%; n = 1), memory loss (1.4%; n = 1), nausea (1.4%; n = 1), night sweats (1.4%; n = 1), sore throat (1.4%; n = 1), vomiting (1.4%; n = 1), wheezing (1.4%; n = 1), and abdominal distention (1.4%; n = 1). However, some patients (12.5%; n = 9) did not present symptoms but were subjected to routine evaluation following cancer treatments.
Our review indicated that cough and dyspnea are the most important clinical presentations. Clinicians are required to maintain high suspicion of fungal diseases even when patients may not present typical symptoms because fungus produces secondary by-products, leading to a wide range of non-specific clinical presentations.64 As reflected in the results, the symptoms that do not suggest pulmonary problems include abdominal distention and memory loss.
Furthermore, many of the patients did not report any symptoms. However, diagnostic investigations were initiated during routine evaluations. Histoplasmosis, for example, can present with an array of symptoms—from being asymptomatic in over 99% of cases to causing advanced disseminated histoplasmosis, where no organ is spared—depending on the patient’s immune system and the extent of exposure.65 The present study showed that clinical signs can be absent in patients diagnosed with histoplasmosis, aspergillosis, blastomycosis, and pneumocystis pneumonia.
The most frequently used diagnostic method is a CT scan (49.1%; n = 28), followed by PET-CT and X-ray, and both are equally prevalent (19.3%; n = 11). Another method used is the PET scan (10.5%; n = 6), and the least commonly used diagnostic method is MRI (1.8%; n = 1).
The most common diagnostic features observed are lesions (30.9%; n = 17) and masses (27.3%; n = 15). The number of results demonstrating increased uptake or hypermetabolic areas and nodules are equal (18.2%; n = 10). Other diagnostic features observed are atelectasis (3.6%; n = 2) and abnormal shadowing (1.8%; n = 1).
There were 30 unique case reports of patients who were initially diagnosed with lung cancers, with primary lung cancer being the most frequently diagnosed lung cancer (46.7%; n = 14), followed by equal numbers of lung cancer with metastasis and cancer patients who presumably have metastasis to the lungs (26.7%; n = 8).
In this review, virtually all patients underwent CT scans for the initial lung cancer diagnosis but were eventually diagnosed with fungal diseases after further investigation. According to a GLOBOCAN (Global Cancer Observatory by IARC) report, CT scans can help with early cancer diagnosis and are part of global initiatives.66 Low-dose CT scans for early diagnosis are recommended for individuals who are at high risk for lung cancer, such as smokers and former heavy smokers. Several independent, international, randomized controlled clinical trials reported that annual low-dose CT scans reduced lung cancer mortality.67–70
However, relying on the results of CT scans alone has proven to be problematic. Radiologic features such as lesions, masses, increased uptake or hypermetabolic areas, and nodules could lead to a potential misdiagnosis. It has been noted that clinical and radiological features of mycosis may be indistinguishable from lung cancer or metastatic lung cancer, causing patients to be misdiagnosed and leading to a delay in the delivery of appropriate treatment.6–7,71–72
The majority of the biopsies were taken from postsurgical specimens (40.0%; n = 12), followed by needle biopsies (core needle = 20%; n = 6 and fine needle aspiration = 10%; n = 3) and bronchoscopies (10%; n = 3). There were cases where the biopsy method was unspecified (10%; n = 3) as well as a case in which no biopsy was done (3.3%; n = 1). Also, there were cases where the tissue sample was taken during autopsy (6.7%; n = 2).
None of the cases reported malignant neoplasia (n = 0); however, a histopathologic examination revealed negative and unspecified results in 53.3% (n = 16) and 46.7% (n = 14) of the cases, respectively. In a clinical setting, as soon as evidence of malignant neoplasia is found, patients are immediately subjected to cancer treatments, sometimes without further examination. False-positive radiologic findings may also lead to unnecessary medical procedures. Recognizing the diligent and careful observations of others, which are highlighted in the following paragraphs, leads to an obligation to subject the patient to mycology investigation.
It has been reported that mice exposed to Aspergillus spores can develop lung tumors and lymphomas.73 Also, a patient was reported to have possibly developed lung cancer from aflatoxin inhalation when exposed to A. flavus in the work environment for 3 months.74 In Puglia, Italy, a team of researchers performed exhaled breath condensate and bronchial brushing collection and discovered fungal colonization of A. niger, A. ochraceus, and Penicillium spp. These fungi were detected only in lung cancer patients—not in any of the healthy patients.75
The observations of an Italian oncologist, Dr. Simoncini, demonstrated that, frequently, biopsy samples are taken only from the surface of an affected tissue, which is part of the tissue trying to contain the fungus. Therefore, it is possible that a diagnosis of fungal invasion is not made because the biopsy was taken only from the surface.76
Another interesting observation was made by Dr. Arnán, a medical doctor and pathologist. Based on an examination of living cancer cells, both in mice and human cancers and under light and electron microscopy studies, she concluded that fungi may cause cancer. Dr. Arnán found that in 100% of samples, including lung cancer samples, when exposed to UV light, there were green, glowing granules within human cancer tissues, while non-cancer controls were 100% negative.77 Likewise, this fluorescence appearance under UV light (blue or green) characterizes four major aflatoxins—B1, B2, G1, and G2.78
Several published cases have reported mycosis exists within or co-exists with lung cancer79–85 and, in a few clinical observations of cutaneous and subcutaneous mycotic lesions, are believed to lead to the development of cancer.86–87
Further, researchers have reportedly discovered fungal DNA in various cancer types they examined, including lung cancer. They believe that fungi may have a substantial effect on cancer biology and fungal DNA associated with cancers could serve as diagnostic or prognostic biomarkers.88–89 Considering these findings and observations, it should be an obligation to advocate further mycology investigations even after a positive malignant neoplasia diagnosis or, ideally, as a proactive initiative.
The present study presented several diagnostic methods that were useful in arriving at the correct diagnosis. Histopathologic examinations, with special staining, were highly useful in these cases, particularly Grocott–Gömöri’s methenamine silver (GMS) staining (34.0%; n = 16) and periodic acid–Schiff (PAS) staining (6.4%; n = 3) as well as both GMS and PAS (6.4%; n = 3). Histopathologic examination using just hematoxylin and eosin (4.3%; n = 2) was also done, and was, in certain cases, sufficient. Another useful method to confirm the final diagnosis was IgG testing (14.9%; n = 7) and tissue cultures (12.8%; n = 6). Finally, every tissue should be cultured, and it should be noted that no further growth of the fungus was possible if tissues had already been fixed in formalin.48 Nonetheless, sporadic diagnosis based on positive tissue culture may be linked to the low index of clinical suspicion for fungal infection as well as the delayed histopathological results.24 In some cases, an infection may be localized, and a culture of the submitted specimen may not detect a fungal organism.90
Aspergillosis was the most frequently diagnosed fungal disease among the patients in this study (30%; n = 9), followed by histoplasmosis (26.7%; n = 8), cryptococcosis (20.0%; n = 6), blastomycosis (6.7%; n = 2) and coccidioidomycosis (6.7%; n = 2), and mucormycosis (3.3%; n = 1) and pneumocystic pneumonia (3.3%; n = 1) and paracoccidioidomycosis (3.3%; n = 1).
Azoles (50%; n = 15) were the most prescribed class of antifungal agents, followed by polyenes, particularly amphotericin B (10.8%; n = 4). Studies that did not present the details of interventions as well as those where the patients received no interventions account for the same number of cases (16.2%; n = 6). Patients who did not receive antifungal treatment underwent surgical resection prior to diagnosis, and the procedure was deemed an adequate treatment. Reducing and/or completely ceasing the use of immunosuppressive agents (5.4%; n = 2), prescription of anti-diabetic medication, lifestyle modifications, such as diet and exercise (2.7%; n = 1), and ventilator support (2.7%; n = 1) were also noted to be part of the intervention.
Among the patients, 36.7% (n = 11) had a complete resolution, while the condition improved for 30.0% (n = 9) of them. Finally, 23.3% (n = 7) of them had no documented follow-up. However, 10% (n = 3) of the patients succumbed to the spread of the fungal invasion despite intervention. A patient diagnosed with mucormycosis was prescribed posaconazole, a patient diagnosed with cryptococcosis received amphotericin B, while one patient diagnosed with paracoccidioidomycosis received ventilator support.
The use of a ventilator in certain cases may have adverse effects. A study was conducted to investigate the risk factors of pulmonary mycosis related to mechanical ventilation and the prognosis. Old age, multi-organ dysfunction, uncontrolled diabetes, and the extended use of steroids are often multiple risk factors associated with pulmonary mycosis related to mechanical ventilation. The results showed that patients with pulmonary mycosis had significantly higher mortality compared to patients with no fungal infection (chi2 = 3.910; p < 0.05).91
Surgery and antifungal treatments are standard treatment protocols for the management of fungal diseases. The removal of risk factors such as iatrogenic immunosuppression and correction of underlying disorders, namely diabetes and metabolic health, should be encouraged. Most patients with invasive fungal infection suffer from severe underlying conditions,92 which is consistent with the observations, and suggests that the effective management of mycosis is contingent upon the correction of underlying conditions.93
Misclassification of the cause of death is possible because fungal infections are difficult to diagnose. Accordingly, in autopsy studies, many patients were considered to have died from a fungal infection that was previously unsuspected or confirmed before death.94 Also, due to low autopsy rates, the prevalence of fungal infections is likely underestimated because the disease indicators are rarely distinctive. Consequently, many invasive fungal diseases go unnoticed while the patient is still alive.1 Further, fungal infections are dubbed as “The Great Masquerader”64 and “Hidden Killers,” 95 and, accordingly, the true burden of fungal diseases remains unknown. The current focus on the Covid-19 pandemic has only further sidelined fungal diseases, which continue to be an ignored global health problem.96–98
Ultimately, the present study has key clinical importance: in evaluating clinical and radiological findings, when clinicians are suspicious of malignancy, they should, nevertheless, be skeptical regarding the absence of fungal infections. This skepticism should persist even in the event of a positive malignant histological examination because, based on previous observations, fungal organisms can exist with or co-exist with lung cancer 79–85 and it is advisable to be mindful of the depth of masses during biopsies. Other methods for confirming mycological criteria, such as mycotoxin testing and exhaled breath condensate analysis, may also be helpful.
The possibility of misdiagnosis should not be underestimated. Many significant fungi have spores that are less than 5 μm in aerodynamic diameter and can, therefore, easily penetrate the lungs. These fungi may also contain substantial amounts of mycotoxins.99 It is almost impossible to avoid fungi as they are ubiquitous organisms found in our natural environments, including soils, plants, animals, and the human body. Considering the ubiquitous nature of fungi and the fact that humans inhale between 1,000 and 10 billion spores on a daily basis,100 fungi may be the reason why lung cancer is prevalent in global cancer statistics. According to GLOBOCAN 2020, among the estimated 2.2 million new cancer diagnosis cases and 1.8 million deaths, lung cancer was the second most commonly diagnosed cancer, representing approximately 1 in 10 (11.4%) cases and lung cancer is the leading cause of cancer-related death, representing approximately 1 in 5 (18.0%) incidents.66
Dr. Enby’s observation is noteworthy: breast cancer had surpassed lung cancer and was leading in global cancer incidence in 2020. With an estimated 2.3 million new cases, breast cancer represents 11.7% of all cancer incidence.66 Dr. Enby described the morphological structures in the breast cancer samples used in research as entirely consistent with the distinctive features of spore–sac fungus division, presenting evidence that cancer could well be fungal growth. He added that it is nearly impossible to comprehend how anyone could argue that cancer tissue can consist of a spore–sac fungus if they are unfamiliar with or have no knowledge of mycology.101
The role of fungi in cancer pathology is underrated, which leads to the possibility of misdiagnosis. For example, according to Toda, an epidemiologist at the Mycotic Diseases Branch of the Center for Disease Control and Prevention, histoplasmosis can be misdiagnosed as lung cancer; therefore, some patients are subjected to extensive oncology workups as opposed to antifungal treatment often because fungal infections are not considered in the differential diagnosis.102 Conversely, fungal lesions, just as with cancer, can occur anywhere in the body and are not limited to the pulmonary site,103 which compounds the challenge of diagnosing cancer.
In wildlife, mycosis can be highly lethal, with a mortality rate that is virtually 100%.100 Furthermore, fungi have been conclusively shown to be the only organisms that can cause the extinction of a species.104 Fungal ability to destroy could be partly explained by the fact that they continue to attack a host because they have no need for the host to be alive in order to exist or thrive, thereby destroying every member of a host species. Conversely, other pathogens such as bacteria and viruses, when introduced into an ecosystem, eventually become less virulent, preventing an infection from killing the host. Such adaptations are beneficial to both the host and pathogen in that the host survives and the pathogen avoids an “evolutionary dead end.” 104
Invasive fungal diseases are a major public health problem and, depending on the pathogen and patient population, have high mortality rates of 30% to 90%. Aspergillus, Cryptococcus, Candida, and Pneumocystis species caused approximately 90% of deaths due to fungal infections, with additional threats posed by Coccidioides and Histoplasma, which have the ability to cause infections even in immunocompetent individuals in endemic regions.105 In comparison, Covid-19 had an overall death rate estimated at 0.66%,106 whereas Covid-19-associated pulmonary aspergillosis mortality was reported to reach 60%.107 There have also been cases where fungal diseases mimicked and/or were initially diagnosed as Covid-19.108–109
The fact that medicine is confronted by an adversary that is much more formidable than what global public health has focused on during these last few years can no longer be ignored.
It is time to face the threat from fungal menace.
Appendix I
Case Reports
| No. | AGE | GENDER | DIAGNOSTIC HYPOTHESIS | FINAL DIAGNOSIS | AUTHORS | PubMed ID |
| 1 | 35 | Female | Lung cancer | Histoplasmosis | D’Ambrosio, et al. (2022) | 35475862 |
| 2 | 68 | Male | Metastasis (history of rectal cancer) | Pneumocystis pneumonia | Dai, et al. (2021) | 33058528 |
| 3 | 56 | Female | Lung cancer + metastasis | Histoplasmosis | Ruegg, et al. (2021) | 33671319 |
| 4 | 45 | Male | Lung cancer | Aspergillosis | Luo, et al. (2021) | 34034813 |
| 5 | 67 | Female | Metastasis (primary cancer – liposarcoma) | Coccidioidomycosis | Nassif, et al. (2021) | 34589500 |
| 6 | 46 | Female | Lung cancer + metastasis | Mucormycosis | Yang, et al. (2019) | 30553628 |
| 7 | 65 | Male | Lung cancer + metastasis | Histoplasmosis | Tanaka, et al. (2018) | 30570681 |
| 8 | 32 | Male | Lung cancer | Cryptococcosis | Anadpara, et al. (2018) | 29599641 |
| 9 | 54 | Male | Lung cancer | Blastomycosis | Hussaini, et al. (2018) | 30021526 |
| 10 | 65 | Female | Lung cancer + metastasis | Aspergillosis | Vanfleteren, et al. (2018) | 29922593 |
| 11 | 61 | Male | Metastasis (primary cancer – laryngeal) | Aspergillosis | Demirtaş, et. al. (2016) | 26980939 |
| 12 | 45 | Male | Lung cancer | Cryptococcosis | Pawar, et. al. (2016) | 27735154 |
| 13 | 70 | Female | Lung cancer | Histoplasmosis | George, et. al. (2015) | 26664188 |
| 14 | 44 | Female | Metastasis (primary cancer – thyroid) | Aspergillosis | Karuppusamy, et. al. (2015) | 26458651 |
| 15 | 50 | Male | Metastasis (history of rectal cancer) | Histoplasmosis | Ye, et. al. (2015) | 25666013 |
| 16 | 53 | Female | Metastasis (history of esophageal cancer) | Histoplasmosis | Ye, et. al. (2015) | 25666013 |
| 17 | 70 | Male | Lung cancer + metastasis | Histoplasmosis | Kooblall, et. al. (2014) | 24728897 |
| 18 | 34 | Female | Lung cancer + metastasis | Cryptococcosis | Wang, et. al. (2014) | 24129292 |
| 19 | 71 | Female | Lung cancer | Aspergillosis | Yasuda, et. al. (2013) | 23792483 |
| 20 | 64 | Female | Metastasis (history of melanoma) | Histoplasmosis | dall Bello, et. al. (2013) | 23740014 |
| 21 | 74 | Female | Lung cancer + metastasis | Cryptococcosis | Kim, et. al. (2012) | 23166553 |
| 22 | 45 | Female | Lung cancer | Aspergillosis | Nowicka, et. al. (2012) | 22187181 |
| 23 | 54 | Male | Lung cancer | Aspergillosis | Baxter, et. al. (2011) | 21460371 |
| 24 | 52 | Male | Lung cancer | Aspergillosis | Baxter, et. al. (2011) | 21460371 |
| 25 | 55 | Male | Lung cancer | Aspergillosis | Baxter, et. al. (2011) | 21460371 |
| 26 | 60 | Male | Lung cancer + metastasis | Paracoccidioidomycosis | dall Bello, et. al. (2011) | 21430109 |
| 27 | 47 | Female | Lung cancer | Coccidioidomycosis | Chung, et. al. (2011) | 21193791 |
| 28 | 48 | Male | Lung cancer | Cryptococcosis | Chang, et. al. (2008) | 18443173 |
| 29 | 64 | Male | Lung cancer | Cryptococcosis | Oliveira, et. al. (2007) | 17823759 |
| 30 | 67 | Male | Metastasis (primary cancer – laryngeal) | Blastomycosis | Vahid, et. al. (2006) | 16915161 |
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Published May 18, 2024
About the Author
Dr. Sita Mager received her PhD in integrative medicine with summa cum laude from the University of Natural Medicine. Her main research interests are mycosis and mycotoxicosis and her purpose is to bring focus on fungal threats; its ability to mimic various diseases, including cancer; the extent of human exposure; and notably, the clinical impact that it can have on patients. Such awareness in the broader research community, healthcare providers, funders, media organizations and the public will help to catalyze support and progress for this important but neglected group of pathogens.
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