Barriers to and strategies for diagnosis of cryptococcal meningitis in people living with HIV in low-income countries.

Introduction: Cryptococcal meningitis (CM) is the second leading cause of AIDS-related mortality where the burden of advanced HIV disease is concentrated. Advances in diagnostics and treatment, including cryptococcal antigen (CrAg) screening and short-course antifungal regimens, have improved clinical outcomes in trials, but replicating these same benefits in routine care has proven more difficult.

Areas Covered: This review outlines the biological rationale for CrAg screening and examines the major operational barriers to effective CM diagnosis in low-income countries.

Genomic epidemiology of in Africa.

Histoplasmosis, the disease caused by thermally dimorphic fungi in the genus , is usually associated with pulmonary involvement in healthy individuals and a disseminated syndrome in immunocompromised patients. Among African patients, lung disease is less commonly reported than skin, lymph node, or bone disease. Because different species or strains may be associated with different disease presentations and outcomes, understanding genetic and phenotypic variation in the genus is important for accurate diagnosis and treatment.

Effectiveness of a national reflex laboratory cryptococcal antigen screening programme for people with advanced HIV disease in South Africa: a nationwide-sampled cohort study (CAST-NET).

Background: Cryptococcal antigen (CrAg) screening and pre-emptive treatment of antigenaemia can reduce mortality among people living with HIV.

Setting: We evaluated the effectiveness of a national CrAg screening program in South Africa.

Methods: We enrolled a retrospective cohort of adults aged ≥18 years with a CD4 count <100 cells/µL and antigenaemia at 442 facilities in a stratified-random sample of 27 sub-districts, 2017-2019.

The Burden of Neonatal Invasive Candidiasis in Low- and Middle-income Countries: A Systematic Review and Meta-analysis.

Background: Invasive infection remains a significant threat to neonates worldwide. Most evidence on neonatal invasive candidiasis (NIC) comes from high-income countries, leaving the burden and characteristics of NIC in low- and middle-income countries (LMICs) poorly described. This study aimed to investigate the incidence, case-fatality rates (CFR), epidemiology, and etiology of NIC in LMICs.

Comparative analysis of glucuronoxylomannogalactan (GXMGal) and glucuronoxylomannan (GXM) antibody responses and their associations with cryptococcal disease status in people living with HIV.

Background: Cryptococcosis remains a major cause of mortality in people with HIV (PWH). While glucuronoxylomannan-binding immunoglobulin G (GXM-IgG) levels have been associated with disease status and survival, the clinical significance of glucuronoxylomannogalactan-binding IgG (GXMGal-IgG) has not been investigated.

Methods: We analyzed serological data from two previously reported cohorts of PWH: a prospective asymptomatic South African cohort (67 cryptococcal antigen [CrAg]-positive, 130 CrAg-negative), and a Vietnamese case-control cohort (30 with symptomatic cryptococcal meningitis [CM], 30 without), both followed for mortality for six months.

Use of minimally invasive tissue sampling to determine the contribution of diarrheal diseases to under-five mortality and associated co-morbidities and co-infections in children with fatal diarrheal diseases in Africa and Bangladesh.

Achieving the Sustainable Development Goal of reducing child mortality to <25 deaths per 1000 live births by 2030 requires strategies to prevent diarrheal disease-related morbidity and mortality. Accurate etiological diagnosis is essential. This study used postmortem diagnostics to investigate the contribution of diarrhea to under-5 mortality and examine co-morbidities and co-infections in Africa and South Asia.

mGem: Sepsis and antimicrobial resistance in the context of advanced HIV disease.

Sepsis triggered by bloodstream infections (BSI) is a significant driver of HIV-related mortality, particularly among in-patients with advanced HIV disease (AHD). Currently, the incidence, etiology, and outcomes of BSI in this population are poorly defined. We review the existing evidence, which shows an increased risk of BSI, particularly with antimicrobial-resistant (AMR) organisms, and higher BSI-associated mortality in patients with AHD.

Favourable outcome of prosthetic valve endocarditis in a patient with an Ebstein anomaly.

Unlabelled: Fungal endocarditis is rare, challenging to diagnose and treat and associated with high mortality. We describe a case of endocarditis in a patient with Ebstein's anomaly with a favourable outcome.

Contribution: We emphasise that surgical intervention with source control of the infective vegetation is still the mainstay of treatment and highlight the importance of submitting infected source material for histology, culture and molecular testing to identify the causative organism.

Pathogen aetiology and risk factors for death among neonates with bloodstream infections at lower-tier South African hospitals: a cross-sectional study.

Background: Infections are among the top causes of neonatal mortality, particularly in low-income and middle-income countries. We aimed to describe the clinical characteristics of neonates diagnosed with culture-confirmed bloodstream infections at six lower-tier hospitals in South Africa.

Methods: We did a cross-sectional study of culture-confirmed bloodstream infections among neonates (aged 0-27 days) at six lower-tier hospitals in South Africa.

Defining and responding to the contextual drivers for implementation of antimicrobial stewardship in 14 neonatal units in South Africa.

Background: Research on the contextual drivers of antimicrobial stewardship (AMS) programme interventions in neonatal units is limited.

Methods: As part of a prospective mixed-methods multidisciplinary neonatal AMS (NeoAMS) interventional study in 14 South African hospitals, we applied a three-phased process to assess implementation barriers and contextual drivers experienced by participating health professionals. The study included: (Phase one; P1) a survey of pre-intervention barriers and enablers; (P2) written feedback during the study intervention phase; and (P3) semi-structured exit interviews.

AIDS-related mycoses: advances, challenges, and future directions.

Fungal infections are a major contributor to mortality for people with HIV/AIDS. Recently, researchers, clinicians, industry experts, and policymakers convened for the triennial AIDS-Related Mycoses Meeting to address critical gaps in the management of AIDS-related mycoses. Delegates highlighted several scientifically driven milestones that have significantly reduced fungal-related deaths, and the need to address outstanding challenges in diagnosis, treatment, and research.

Exploring polyamine metabolism of the yeast-like fungus, Emergomyces africanus.

Emergomyces africanus is a thermally dimorphic pathogen causing severe morbidity and mortality in immunocompromized patients. Its transition to a pathogenic yeast-like phase in the human host is a notable virulence mechanism. Recent studies suggest polyamines as key players in dimorphic switching, yet their precise functions remain enigmatic.

Prospective antimicrobial stewardship interventions by multidisciplinary teams to reduce neonatal antibiotic use in South Africa: The Neonatal Antimicrobial Stewardship (NeoAMS) study.

Background: Hospitalized neonates are vulnerable to infection and have high rates of antibiotic utilization.

Methods: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions.

Candida parapsilosis: A systematic review to inform the World Health Organization fungal priority pathogens list.

Candida parapsilosis is globally distributed and recognised for causing an increasing proportion of invasive Candida infections. It is associated with high crude mortality in all age groups. It has been particularly associated with nosocomial outbreaks, particularly in association with the use of invasive medical devices such as central venous catheters.

Features and global impact of invasive fungal infections caused by Pneumocystis jirovecii: A systematic review to inform the World Health Organization fungal priority pathogens list.

This systematic review evaluates the current global impact of invasive infections caused by Pneumocystis jirovecii (principally pneumonia: PJP), and was carried out to inform the World Health Organization Fungal Priority Pathogens List. PubMed and Web of Science were used to find studies reporting mortality, inpatient care, complications/sequelae, antifungal susceptibility/resistance, preventability, annual incidence, global distribution, and emergence in the past 10 years, published from January 2011 to February 2021. Reported mortality is highly variable, depending on the patient population: In studies of persons with HIV, mortality was reported at 5%-30%, while in studies of persons without HIV, mortality ranged from 4% to 76%.

Optimizing the Treatment of Invasive Candidiasis-A Case for Combination Therapy.

Invasive candidiasis is a rising global health threat with increasing incidence, persistently high mortality, and diminishing treatment options. Antifungal resistance has rapidly emerged and spread, with multidrug-resistant species deemed an urgent and serious threat. While acknowledging the key role of antifungal stewardship and infection control in curbing spread, we examine the role of antifungal monotherapy in driving resistance and the potential for combination therapy to prevent stress adaptation and emergence of drug resistance.

Lived experience of people with cryptococcal meningitis: A qualitative study.

Background: The high burden of cryptococcal meningitis (CM) among people living with HIV persists despite widespread access to antiretroviral therapy. Efforts to prevent CM among people living with HIV could be hindered by a limited understanding of their lived experiences of CM and its diagnosis.

Objectives: To explore and describe the experiences of people diagnosed with HIV-associated CM in routine care.

Invasive candidiasis.

Invasive candidiasis is an important fungal disease caused by Candida albicans and, increasingly, non-albicans Candida pathogens. Invasive Candida infections originate most frequently from endogenous human reservoirs and are triggered by impaired host defences. Signs and symptoms of invasive candidiasis are non-specific; candidaemia is the most diagnosed manifestation, with disseminated candidiasis affecting single or multiple organs.

Bacterial and Candida Colonization of Neonates in a Regional Hospital in South Africa.

Background: Neonatal colonization with multidrug-resistant (MDR) Enterobacter spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterococcus faecium (ESKAPE) and Candida spp. often precedes invasive hospital-acquired infections.

Fungal diseases in Africa: Closing the gaps in diagnosis and treatment through implementation research and advocacy.

Fungal diseases impose an escalating burden on public health in Africa, exacerbated by issues such as delayed diagnosis, inadequate therapy, and limited access to healthcare resources, resulting in significant morbidity and mortality. Effectively tackling these challenges demands a comprehensive approach encompassing research, training, and advocacy initiatives. Recent clinical mycology surveys conducted by Global Action for Fungal Infection (GAFFI) and the European Confederation of Medical Mycology/International Society for Human and Animal Mycology (ECMM/ISHAM) have underscored gaps in fungal diagnostics and the availability and accessibility of antifungal therapy in Africa.