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Medical Mycology Jun 2024In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority...
In response to the growing global burden of fungal infections with uncertain impact, the World Health Organization (WHO) established an Expert Group to identify priority fungal pathogens and establish the WHO Fungal Priority Pathogens List for future research. This systematic review aimed to evaluate the features and global impact of invasive candidiasis caused by Candida tropicalis. PubMed and Web of Science were searched for studies reporting on criteria of mortality, morbidity (defined as hospitalization and disability), drug resistance, preventability, yearly incidence, diagnostics, treatability, and distribution/emergence from 2011 to 2021. Thirty studies, encompassing 436 patients from 25 countries were included in the analysis. All-cause mortality due to invasive C. tropicalis infections was 55%-60%. Resistance rates to fluconazole, itraconazole, voriconazole and posaconazole up to 40%-80% were observed but C. tropicalis isolates showed low resistance rates to the echinocandins (0%-1%), amphotericin B (0%), and flucytosine (0%-4%). Leukaemia (odds ratio (OR) = 4.77) and chronic lung disease (OR = 2.62) were identified as risk factors for invasive infections. Incidence rates highlight the geographic variability and provide valuable context for understanding the global burden of C. tropicalis infections. C. tropicalis candidiasis is associated with high mortality rates and high rates of resistance to triazoles. To address this emerging threat, concerted efforts are needed to develop novel antifungal agents and therapeutic approaches tailored to C. tropicalis infections. Global surveillance studies could better inform the annual incidence rates, distribution and trends and allow informed evaluation of the global impact of C. tropicalis infections.
Topics: Candida tropicalis; Humans; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Candidiasis, Invasive; Incidence; Global Health; Risk Factors
PubMed: 38935905
DOI: 10.1093/mmy/myae040 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list. This systematic review aimed to evaluate the epidemiology and impact of eumycetoma. PubMed and Web of Science were searched to identify studies published between 1 January 2011 and 19 February 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 14 studies were eligible for inclusion. Morbidity was frequent with moderate to severe impairment of quality of life in 60.3%, amputation in up to 38.5%, and recurrent or long-term disease in 31.8%-73.5% of patients. Potential risk factors included male gender (56.6%-79.6%), younger age (11-30 years; 64%), and farming occupation (62.1%-69.7%). Mycetoma was predominantly reported in Sudan, particularly in central Sudan (37%-76.6% of cases). An annual incidence of 0.1/100 000 persons and 0.32/100 000 persons/decade was reported in the Philippines and Uganda, respectively. In Uganda, a decline in incidence from 3.37 to 0.32/100 000 persons between two consecutive 10-year periods (2000-2009 and 2010-2019) was detected. A community-based, multi-pronged prevention programme was associated with a reduction in amputation rates from 62.8% to 11.9%. With the pre-specified criteria, no studies of antifungal drug susceptibility, mortality, and hospital lengths of stay were identified. Future research should include larger cohort studies, greater drug susceptibility testing, and global surveillance to develop evidence-based treatment guidelines and to determine more accurately the incidence and trends over time.
Topics: Humans; Mycetoma; Incidence; Antifungal Agents; World Health Organization; Risk Factors; Male; Female; Quality of Life
PubMed: 38935904
DOI: 10.1093/mmy/myae044 -
Medical Mycology Jun 2024Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges,...
Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%-44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4-32 mg/l), while resistance to amphotericin B (MIC: 0.125-0.16 mg/l), itraconazole (MICs: 0.004-0.125 mg/l), and voriconazole (MICs: 0.004-0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat.
Topics: Humans; Histoplasmosis; Antifungal Agents; World Health Organization; Drug Resistance, Fungal; Histoplasma; Prevalence; Immunocompromised Host
PubMed: 38935903
DOI: 10.1093/mmy/myae039 -
Medical Mycology Jun 2024Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform...
Cryptococcosis causes a high burden of disease worldwide. This systematic review summarizes the literature on Cryptococcus neoformans and C. gattii infections to inform the World Health Organization's first Fungal Priority Pathogen List. PubMed and Web of Science were used to identify studies reporting on annual incidence, mortality, morbidity, antifungal resistance, preventability, and distribution/emergence in the past 10 years. Mortality rates due to C. neoformans were 41%-61%. Complications included acute renal impairment, raised intracranial pressure needing shunts, and blindness. There was moderate evidence of reduced susceptibility (MIC range 16-32 mg/l) of C. neoformans to fluconazole, itraconazole, ketoconazole, voriconazole, and amphotericin B. Cryptococcus gattii infections comprised 11%-33% of all cases of invasive cryptococcosis globally. The mortality rates were 10%-23% for central nervous system (CNS) and pulmonary infections, and ∼43% for bloodstream infections. Complications described included neurological sequelae (17%-27% in C. gattii infections) and immune reconstitution inflammatory syndrome. MICs were generally low for amphotericin B (MICs: 0.25-0.5 mg/l), 5-flucytosine (MIC range: 0.5-2 mg/l), itraconazole, posaconazole, and voriconazole (MIC range: 0.06-0.5 mg/l). There is a need for increased surveillance of disease phenotype and outcome, long-term disability, and drug susceptibility to inform robust estimates of disease burden.
Topics: Humans; Cryptococcosis; Antifungal Agents; Cryptococcus gattii; Cryptococcus neoformans; Drug Resistance, Fungal; World Health Organization; Microbial Sensitivity Tests
PubMed: 38935902
DOI: 10.1093/mmy/myae043 -
Medical Mycology Jun 2024The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This...
The World Health Organization, in response to the growing burden of fungal disease, established a process to develop a fungal priority pathogens list (FPPL). This systematic review aimed to evaluate the epidemiology and impact of invasive fungal disease due to Mucorales. PubMed and Web of Science were searched to identify studies published between January 1, 2011 and February 23, 2021. Studies reporting on mortality, inpatient care, complications and sequelae, antifungal susceptibility, risk factors, preventability, annual incidence, global distribution, and emergence during the study time frames were selected. Overall, 24 studies were included. Mortality rates of up to 80% were reported. Antifungal susceptibility varied across agents and species, with the minimum inhibitory concentrations lowest for amphotericin B and posaconazole. Diabetes mellitus was a common risk factor, detected in 65%-85% of patients with mucormycosis, particularly in those with rhino-orbital disease (86.9%). Break-through infection was detected in 13.6%-100% on azole or echinocandin antifungal prophylaxis. The reported prevalence rates were variable, with some studies reporting stable rates in the USA of 0.094-0.117/10 000 discharges between 2011 and 2014, whereas others reported an increase in Iran from 16.8% to 24% between 2011 and 2015. Carefully designed global surveillance studies, linking laboratory and clinical data, are required to develop clinical breakpoints to guide antifungal therapy and determine accurate estimates of complications and sequelae, annual incidence, trends, and global distribution. These data will provide robust estimates of disease burden to refine interventions and better inform future FPPL.
Topics: Humans; Mucorales; Antifungal Agents; Mucormycosis; World Health Organization; Risk Factors; Invasive Fungal Infections; Microbial Sensitivity Tests; Prevalence; Drug Resistance, Fungal; Incidence; Global Health
PubMed: 38935901
DOI: 10.1093/mmy/myad130 -
Medical Mycology Jun 2024The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and...
The World Health Organization (WHO) in 2022 developed a fungal priority pathogen list. Candida auris was ultimately ranked as a critical priority pathogen. PubMed and Web of Science were used to find studies published from 1 January 2011 to 18 February 2021, reporting on predefined criteria including: mortality, morbidity (i.e., hospitalization and disability), drug resistance, preventability, yearly incidence, and distribution/emergence. Thirty-seven studies were included in the final analysis. The overall and 30-day mortality rates associated with C. auris candidaemia ranged from 29% to 62% and 23% to 67%, respectively. The median length of hospital stay was 46-68 days, ranging up to 140 days. Late-onset complications of C. auris candidaemia included metastatic septic complications. Resistance rates to fluconazole were as high as 87%-100%. Susceptibility to isavuconazole, itraconazole, and posaconazole varied with MIC90 values of 0.06-1.0 mg/l. Resistance rates to voriconazole ranged widely from 28% to 98%. Resistance rates ranged between 8% and 35% for amphotericin B and 0%-8% for echinocandins. Over the last ten years, outbreaks due to C. auris have been reported in in all WHO regions. Given the outbreak potential of C. auris, the emergence and spread of MDR strains, and the challenges associated with its identification, and eradication of its environmental sources in healthcare settings, prevention and control measures based on the identified risk factors should be evaluated for their effectiveness and feasibility. Global surveillance studies could better inform the incidence rates and distribution patterns to evaluate the global burden of C. auris infections.
Topics: Humans; Antifungal Agents; Drug Resistance, Fungal; World Health Organization; Candidiasis; Candida auris; Microbial Sensitivity Tests; Candidemia; Disease Outbreaks; Candida; Incidence
PubMed: 38935900
DOI: 10.1093/mmy/myae042 -
PloS One 2024Health technology assessment uses a multidisciplinary approach to support health benefits package design towards universal health coverage. The evidence-informed... (Review)
Review
Health technology assessment for sexual reproductive health and rights benefits package design in sub-Saharan Africa: A scoping review of evidence-informed deliberative processes.
BACKGROUND
Health technology assessment uses a multidisciplinary approach to support health benefits package design towards universal health coverage. The evidence-informed deliberative process framework has been used alongside Health technology assessment to enhance stakeholder participation and deliberations in health benefits package design. Applying the evidence-informed deliberative framework for Health assessment could support the morally diverse sexual reproductive health and rights (SRHR) benefits package design process. However, evidence on participation and deliberations for stakeholders in health technology assessment for SRHR benefits package design has not been curated in sub-Saharan Africa. This study synthesises literature to fill this gap.
METHODS
This scoping review applies the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews, and deductive analysis following the evidence-informed deliberative processes framework. The search strategy uses the Guttmacher-Lancet Commission-proposed comprehensive definition of SRHR and the World Health Organisation's universal health coverage compendium of SRHR interventions to generate search terms. Six databases and biographical hand searches were used to identify studies in Sub-Saharan Africa from 1994.
RESULTS
A total of 14 studies met the inclusion criteria. Evidence for yearly public budgets and explicit SRHR health technology assessment processes was not found. In 12 of the studies reviewed, new advisory committees were set up specifically for health technology assessment for SRHR priority-setting and benefits package design. In all decision-making processes reviewed, the committee member roles, participation and deliberations processes, and stakeholder veto powers were not clearly defined. Patients, the public, and producers of health technology were often excluded in the health technology assessment for the SRHR benefits package design. Most health technology assessment processes identified at least one decision-making criterion but failed to use this in their selection and appraisal stages for SRHR benefits design. The identification, selection, and scoping stages in health technology assessment for SRHR were non-existent in most studies. In 11 of the 14 processes of the included studies, stakeholders were dissatisfied with the health policy recommendation from the appraisal process in health technology assessment. Perceived benefits for evidence-informed deliberative processes included increased stakeholder engagement and fairness in decision-making.
CONCLUSION
To support the integration of diverse social values in health technology assessment for fairer SRHR benefits package design, evidence from this review suggests the need to institutionalise health technology assessment, establish prioritisation decision criteria, involve all relevant stakeholders, and standardise the process and assessment methodological approaches.
Topics: Africa South of the Sahara; Humans; Technology Assessment, Biomedical; Reproductive Health; Sexual Health
PubMed: 38935794
DOI: 10.1371/journal.pone.0306042 -
PloS One 2024The HIV program in Newfoundland and Labrador (NL) provides care for all persons living with HIV (PLWH) in NL, yet progress toward UNAIDS 95-95-95 goals for diagnosis,...
The HIV program in Newfoundland and Labrador (NL) provides care for all persons living with HIV (PLWH) in NL, yet progress toward UNAIDS 95-95-95 goals for diagnosis, linkage to care and viral suppression has not previously been documented. This analysis describes engagement in HIV care and virologic outcomes for the NL cohort in 2016 and 2019 and compares this data to the Canadian HIV Observational Cohort (CANOC). A retrospective review of the NL clinic included adults aged >18 years and descriptive statistics for demographics, risk factors, and clinical variables were assessed and compared using χ2 test or Fisher's Exact test (categorical) or Wilcoxon Sum Rank test (continuous). Engagement in care and virologic outcomes for the NL cohort were consistently high over the 2016 to 2019 period with > 98% on antiretroviral therapy (ART), and > 96% having a suppressed virus load. Engagement in care and virologic outcomes among PLWH in NL is high and compares favorably to a national cohort.
Topics: Humans; HIV Infections; Newfoundland and Labrador; Female; Male; Adult; Retrospective Studies; Middle Aged; World Health Organization; Viral Load; Anti-HIV Agents
PubMed: 38935671
DOI: 10.1371/journal.pone.0305898 -
PloS One 2024The role of non-kin caregivers, such as friends, neighbours, and acquaintances, in providing end-of-life care is significant but often overlooked in research and policy...
BACKGROUND
The role of non-kin caregivers, such as friends, neighbours, and acquaintances, in providing end-of-life care is significant but often overlooked in research and policy discussions. These caregivers provide extensive support for individuals in end-of-life care, in addition to or instead of family members. However, there is limited evidence in the literature regarding the experiences, burdens, and benefits of non-kin caregivers.
AIMS
The aim of this research is to examine the role and contributions of non-kin caregivers in end-of-life care. The study intends to uncover their experiences, associated challenges, benefits, and requirements for support.
METHODS
In order to achieve this objective, a mixed-methods approach will be employed, gathering data through structured questionnaires from approximately 150 non-kin caregivers and in-depth interviews with up to 25 participants. The questionnaires will measure the impact, burden, and benefits of caregiving. The Burden Scale for Family Caregivers, the Benefits of Being a Caregiver Scale, the Family Inventory of Needs, the Positive Mental Health Scale, a Graphic Closeness Scale, and selected items of the Eurofamcare Common Assessment Tool for socio-demographic and caregiving-related data will be used. Quantitative data will be analysed using IBM SPSS Statistics 28 for descriptive analysis and group comparison. The objective of the qualitative in-depth interviews is to obtain a comprehensive picture of the personal experiences, motivations and support needs of members of the non-kin caregivers cohort, who are as heterogeneous as possible in terms of gender, socio-economic status, and facility with the German language. The qualitative data from the interviews will be examined using MAXQDA software, adopting a grounded theory approach for analysis.
DISCUSSION
This research will develop a comprehensive framework that captures the nuanced experiences of non-kin caregivers at the end of life. The framework will identify areas where support for non-kin caregivers is lacking and where further research is needed.
TRIAL REGISTRATION
The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00033889; date of registration: 05 April 2024). The study is searchable under the International Clinical Trials Registry Platform Search Portal of the World Health Organization, under the German Clinical Trials Register number.
Topics: Humans; Caregivers; Terminally Ill; Surveys and Questionnaires; Terminal Care; Family; Male; Female
PubMed: 38935665
DOI: 10.1371/journal.pone.0306282 -
PLoS Neglected Tropical Diseases Jun 2024Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds...
BACKGROUND
Lymphatic filariasis (LF) remains a significant global issue. To eliminate LF as a public health problem, the World Health Organization (WHO) recommends multiple rounds of mass drug administration (MDA). In certain scenarios, including when elimination targets have not been met with two-drug MDA, triple-drug MDA (using ivermectin, diethylcarbamazine and albendazole) is recommended. In this study, we report on antigen (Ag) and microfilaria (Mf) prevalence in eight primary sampling units (PSUs) in Samoa 4.5 years after one round of triple-drug MDA.
METHODOLOGY
In 2023, community surveys were conducted in eight PSUs that had been surveyed previously in 2018 (between 1.5 and 3.5 months post triple-drug MDA) and 2019 (six to eight-months post triple-drug MDA). Fifteen houses were randomly selected in each PSU with household members aged ≥ 5 years invited to participate. Blood samples were tested for Ag and Mf.
PRINCIPAL FINDINGS
Ag-positive participants were observed in six of the eight PSUs, and Ag prevalence was significantly above the 1% threshold in four PSUs. The presence of Mf-positive participants in five PSUs confirms the presence of residual active infections.
CONCLUSIONS/SIGNIFICANCE
This study provides evidence of persistent LF transmission in Samoa 4.5 years after one round of triple-drug MDA, confirming that one round was insufficient for interruption of transmission in this setting. Our findings highlight the negative impact of delaying MDA rounds, for example, due to public health emergencies.
Topics: Elephantiasis, Filarial; Humans; Mass Drug Administration; Albendazole; Samoa; Diethylcarbamazine; Ivermectin; Male; Female; Adult; Filaricides; Middle Aged; Adolescent; Animals; Young Adult; Child; Prevalence; Antigens, Helminth; Drug Therapy, Combination; Child, Preschool; Wuchereria bancrofti; Aged
PubMed: 38935622
DOI: 10.1371/journal.pntd.0012236