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Invasive fungal diseases are on the increase globally. The World Health Organization fungal priority pathogens list highlights fungi of critical or high importance to human health and provides pathways for action. The report calls for improved surveillance (diagnostics and antifungal resistance monitoring), research and innovation (implementation research) and public-health interventions.

Background Mycetoma, a chronic infection of the skin and underlying structures, affects those with a close relationship to the land, often in resource-poor areas of the world. Whether caused by any one of a variety of fungus or bacteria, mycetoma causes significant disability and mortality. Acknowledged as a neglected tropical disease (NTD) by the World Health Organization (WHO) in 2016, mycetoma is susceptible to being misunderstood, misdiagnosed, and mismanaged. In an effort to shift the balance in favor of recognition and effective treatment, sound epidemiological understanding is required. Methods and findings In this paper, a literature review of case reports and series (332 papers in total) is presented as three maps. We identified 19,494 cases dating from 1876 to 2019, with cases contracted in 102 countries. The first map shows where mycetoma has ever been reported, the second shows how many cases have been reported, and the third shows the ratio of eumycetoma (fungal) to actinomycetoma (bacterial). Most cases are found in Mexico, India, and Sudan, where mycetoma is studied rigorously. We identified emergence of new geographical loci, including the United States, Venezuela, Italy, China, and Australia. Notably, mycetoma is reported far outside the tropics. In the Americas, bacterial forms dominate, whereas, in Africa and Asia, the picture is more varied. Conclusions With better understanding of the epidemiology of mycetoma, more can be done to direct education, preventive measures, and treatment to at-risk areas, enabling a reduction in disease burden.

Few drugs are coming to market, but opportunities for drug development exist About 1.2 billion people worldwide are estimated to suffer from a fungal disease ( 1 , 2 ). Most are infections of the skin or mucosa, which respond readily to therapy, but a substantial minority is invasive or chronic and difficult to diagnose and treat. An estimated 1.5 to 2 million people die of a fungal infection each year, surpassing those killed by either malaria or tuberculosis ( 3 ). Most of this mortality is caused by species belonging to four genera of fungi: Aspergillus, Candida, Cryptococcus , and Pneumocystis. Although great strides were made in the 1990s, drug development has largely stalled since then. Opportunities exist for accelerating development, particularly in fungal asthma, and to treat chronic and invasive aspergillosis.

Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. None.

Current estimates of fungal disease incidence and mortality are imprecise. Population at risk denominators were used to estimate annual incidence for 2019–21. Extensive literature searches from 2010 to 2023 were combined with over 85 papers on individual country and global disease burden. Crude and attributable mortality were estimated using a combination of untreated mortality, the proportion of patients who are treated, and percentage survival in treated patients. Awareness, guidelines, and accessibility of diagnostics and therapies informed the ratio of treated to untreated cases. Estimates do not include influenza or COVID-19 outbreaks. Data from more than 120 countries were included. Annually, over 2 113 000 people develop invasive aspergillosis in the context of chronic obstructive pulmonary disease, intensive care, lung cancer, or haematological malignancy, with a crude annual mortality of 1 801 000 (85·2%). The annual incidence of chronic pulmonary aspergillosis is 1 837 272, with 340 000 (18·5%) deaths. About 1 565 000 people have a Candida bloodstream infection or invasive candidiasis each year, with 995 000 deaths (63·6%). Pneumocystis pneumonia affects 505 000 people, with 214 000 deaths (42·4%). Cryptococcal meningitis affects 194 000 people, with 147 000 deaths (75·8%). Other major life-threatening fungal infections affect about 300 000 people, causing 161 000 deaths (53·7%). Fungal asthma affects approximately 11·5 million people and might contribute to 46 000 asthma deaths annually. These updated estimates suggest an annual incidence of 6·5 million invasive fungal infections and 3·8 million deaths, of which about 2·5 million (68%; range 35–90) were directly attributable.

Fungal diseases kill more than 1.5 million and affect over a billion people. However, they are still a neglected topic by public health authorities even though most deaths from fungal diseases are avoidable. Serious fungal infections occur as a consequence of other health problems including asthma, AIDS, cancer, organ transplantation and corticosteroid therapies. Early accurate diagnosis allows prompt antifungal therapy; however this is often delayed or unavailable leading to death, serious chronic illness or blindness. Recent global estimates have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over 10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur annually. Since 2013, the Leading International Fungal Education (LIFE) portal has facilitated the estimation of the burden of serious fungal infections country by country for over 5.7 billion people (>80% of the world’s population). These studies have shown differences in the global burden between countries, within regions of the same country and between at risk populations. Here we interrogate the accuracy of these fungal infection burden estimates in the 43 published papers within the LIFE initiative.

It would be of considerable interest to clinicians if the burden of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA) in India were known. Herein, we estimate the burden of CPA following pulmonary tuberculosis (PTB), and ABPA (and severe asthma with fungal sensitization [SAFS]) complicating asthma. We used the population estimates for India from the 2011 census data. The burden of asthma was estimated using three different methods (Global Initiative against Asthma [GINA] report statement, World Health Survey [WHS] estimates, Indian study on the epidemiology of asthma and chronic bronchitis [INSEARCH]). Global and India-specific figures were used for calculating the prevalence of ABPA and SAFS. The World Health Organization estimates were used for calculating PTB rates while the frequency of CPA was assessed from a previously published scoping review. Sensitivity analysis was performed to determine the burden in various scenarios. The total Indian population in 2011 was 1.2 billion. The asthma prevalence in adults was estimated at about 27.6 (range, 17-30) million. The burden of ABPA ranged from 0.12-6.09 million with different assumptions (best estimate, 1.38 [range, 0.86-1.52] million). The prevalence of SAFS was approximated at about 0.52-1.21 million (best estimate, 0.96 [range, 0.6-1.06] million). The incident TB cases were about 2.1 million while the annual incidence of CPA varied 27,000-0.17 million cases, with different estimates. If the mortality of CPA is estimated as 15% annually, the 5-year prevalence of CPA was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000. There is a significant burden of ABPA, SAFS and CPA in India. Prospective community-based studies are required to accurately determine the prevalence of these disorders.

We evaluated the expression of biomarkers of innate and adaptive immune response in correlation with underlying conditions in 144 patients with chronic pulmonary aspergillosis (CPA). Patients with complete medical and radiological records, white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56 lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six (4%) patients had lymphopenia in all five CD variables. There were 62 (43%) patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%) had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15 (10%) of whom had absolute CD4 counts <200/μL. Multivariable logistic regression showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR), 5.53; 95% Confidence Interval (CI), 1.43–21.33; p = 0.013), and emphysema (OR, 4.58; 95% CI; 1.36–15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27; 95% CI, 0.10–0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR, 2.95; 95% CI, 1.30–6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI, 1.39–17.57; p = 0.014). Several subtle immune defects are found in CPA.