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The Lancet. Infectious Diseases Jul 2024Current estimates of fungal disease incidence and mortality are imprecise. Population at risk denominators were used to estimate annual incidence for 2019-21. Extensive... (Review)
Review
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.
Topics: Humans; Incidence; Global Health; Mycoses
PubMed: 38224705
DOI: 10.1016/S1473-3099(23)00692-8 -
Nature Reviews. Disease Primers Jul 2023Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People... (Review)
Review
Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People living with HIV are at increased risk of both acute and chronic lung diseases. Although the use of effective antiretroviral therapy has diminished the burden of infectious lung disease, people living with HIV experience growing morbidity and mortality from chronic lung diseases. A key risk factor for HIV-associated lung disease is cigarette smoking, which is more prevalent in people living with HIV than in uninfected people. Other risk factors include older age, history of bacterial pneumonia, Pneumocystis pneumonia, pulmonary tuberculosis and immunosuppression. Mechanistic investigations support roles for aberrant innate and adaptive immunity, local and systemic inflammation, oxidative stress, altered lung and gut microbiota, and environmental exposures such as biomass fuel burning in the development of HIV-associated lung disease. Assessment, prevention and treatment strategies are largely extrapolated from data from HIV-uninfected people. Smoking cessation is essential. Data on the long-term consequences of HIV-associated lung disease are limited. Efforts to continue quantifying the effects of HIV infection on the lung, especially in low-income and middle-income countries, are essential to advance our knowledge and optimize respiratory care in people living with HIV.
Topics: Humans; HIV Infections; Lung Diseases; Lung; Pulmonary Disease, Chronic Obstructive; Risk Factors
PubMed: 37500684
DOI: 10.1038/s41572-023-00450-5 -
JAMA Jul 2023
Topics: Adult; Humans; Immunocompromised Host; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; Chemoprevention
PubMed: 37358837
DOI: 10.1001/jama.2023.9844 -
Clinical Microbiology Reviews Mar 2024is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest... (Review)
Review
is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.
Topics: Female; Humans; Male; Pneumonia, Pneumocystis; Pneumocystis carinii; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 38235979
DOI: 10.1128/cmr.00101-22 -
Blood Cancer Journal Aug 2023Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more... (Review)
Review
Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required. This review provides consensus recommendations from a panel of 13 global experts, following a meeting in August 2022. The meeting objective was to review existing literature and identify relevant information on infections with all BsAbs in patients with MM, as well as to discuss clinical experience of experts in managing these infections. The recommendations outlined here can be used to guide management of infection risk factors, such as hypogammaglobulinemia and neutropenia. In addition, they can be used to guide the monitoring, prophylaxis, and treatment of bacterial, viral and fungal infections, including emerging infections of interest, such as coronavirus 2019 (COVID-19), and the use of vaccinations prior to and during BsAb treatment. The recommendations have been graded by the panel based on level of data available. Key recommendations include universal herpes simplex and varicella zoster virus prophylaxis, screening for hepatitis B virus reactivation risk in all patients, monthly intravenous immunoglobulin treatment for immunoparesis and in the absence of life-threatening infectious manifestations, use of colony-stimulating factors in patients with Grade 3 neutropenia, universal pneumocystis jirovecii pneumonia prophylaxis and no routine anti-fungal prophylaxis.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; Consensus; Agammaglobulinemia; COVID-19; Neutropenia
PubMed: 37528088
DOI: 10.1038/s41408-023-00879-7 -
Molecular Aspects of Medicine Aug 2023The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp.,... (Review)
Review
The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as Aspergillus spp., Candida spp. and Pneumocystis jirovecii. In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system. In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies. Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology. The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches.
Topics: Humans; Antifungal Agents; Mycoses; Risk Factors; Immunocompromised Host
PubMed: 37207579
DOI: 10.1016/j.mam.2023.101190