We aimed to establish the prevalence of amphotericin B deoxycholate (AmBd)-related toxicities among South African patients with cryptococcosis and determine adherence to international recommendations ...to prevent, monitor and manage AmBd-related toxicities.
Clinical data were collected from cases of laboratory-confirmed cryptococcosis at 25 hospitals, October 2012 -February 2013. Anemia was defined as hemoglobin (Hb) concentration <10 g/dl, hypokalemia as serum potassium (K) <3.4 mEq/L and nephrotoxicity as an increase in serum creatinine (Cr) to >1.1 times the upper limit of normal. To determine adherence to toxicity prevention recommendations, we documented whether baseline Hb, K and Cr tests were performed, whether pre-emptive hydration and IV potassium chloride (KCl) was administered prior to 80% and 60% of AmBd doses and whether daily oral KCl supplementation was given ≥60% of the time. To determine adherence to monitoring recommendations, we ascertained whether a daily fluid chart was completed, Hb was monitored weekly and K or Cr were monitored bi-weekly.
Of 846 patients, clinical data were available for 76% (642/846), 82% (524/642) of whom received AmBd. Sixty-four per cent (n = 333) had documented baseline laboratory tests, 40% (n = 211) were given pre-emptive hydration and 14% (n = 72) and 19% (n = 101) received intravenous and oral KCl. While on AmBd, 88% (n = 452) had fluid monitoring; 27% (n = 142), 45% (n = 235) and 44% (n = 232) had Hb, K and Cr levels monitored. Toxicities developed frequently during treatment: anemia, 16% (86/524); hypokalemia, 43% (226/524) and nephrotoxicity, 32% (169/524).
AmBd-related toxicities occurred frequently but were potentially preventable with adequate monitoring, supplemental fluid and electrolyte therapies.
Blastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in North America and caused by ...Blastomyces dermatitidis and Blastomyces gilchristii.
We reviewed published cases of human and veterinary blastomycosis from Africa and the Middle East. We abstracted epidemiological and clinical features of cases, including sites of disease, diagnosis, management, outcomes, and, where available, genetic and antigenic typing of case isolates. In addition, we sequenced nucleic acids from 9 clinical isolates from Africa deposited in global collections as B. dermatitidis; for 5, we sequenced the internal transcribed spacer regions, and for the other 4 we sequenced the whole genomes.
We identified 172 unique human patients with blastomycosis, including 159 patients from 25 African countries and 12 patients from 5 Middle Eastern countries, and also identified 7 reports of veterinary blastomycosis. In humans, cutaneous disease predominated (n = 100/137, 73%), followed by pulmonary (n = 73/129, 57%) and osteoarticular involvement (n = 61/128, 48%). Unusual direct microscopy/histopathological presentations included short hyphal fragments in tissues (n = 23/129, 18%). There were 34 genotyped case isolates that comprised 4 species: Blastomyces percursus (n = 22, 65%), from 8 countries throughout all regions; Blastomyces emzantsi (n = 9, 26%), from South Africa; B. dermatitidis (n = 1, 3%), from the Democratic Republic of Congo; and B. gilchristii (n = 2, 6%), from South Africa and Zimbabwe.
Blastomycosis occurs throughout Africa and the Middle East and is caused predominantly by B. percursus and, at least in South Africa, B. emzantsi, resulting in distinct clinical and pathological patterns of disease.
Higher cryptococcal antigen (CrAg) titers are strongly associated with mortality risk in individuals with HIV-associated cryptococcal disease. Rapid tests to quantify CrAg levels may provide ...important prognostic information and enable treatment stratification. We performed a laboratory-based validation of the IMMY semiquantitative cryptococcal antigen (CrAgSQ) lateral flow assay (LFA) against the current gold standard CrAg tests. We assessed the diagnostic accuracy of the CrAgSQ in HIV-positive individuals undergoing CrAg screening, determined the relationship between CrAgSQ scores and dilutional CrAg titers, assessed interrater reliability, and determined the clinical correlates of CrAgSQ scores. A total of 872 plasma samples were tested using both the CrAgSQ LFA and the conventional IMMY CrAg LFA, of which 692 were sequential samples from HIV-positive individuals undergoing CrAg screening and an additional 180 were known CrAg-positive plasma samples archived from prior studies. Interrater agreement in CrAgSQ reading was excellent (98.17% agreement, Cohen's kappa 0.962,
< 0.001). Using the IMMY CrAg LFA as a reference standard, CrAgSQ was 93.0% sensitive (95% confidence interval CI 80.9% to 98.5%) and 93.8% specific (95% CI, 91.7% to 95.6%). After reclassification of discordant results using CrAg enzyme immunoassay testing, the sensitivity was 98.1% (95% CI, 90.1% to 100%) and specificity 95.8% (95% CI, 93.9% to 97.2%). The median CrAg titers for semiquantitative score categories (1+ to 4+) were 1:10 (interquartile range IQR, 1:5 to 1:20) in the CrAgSQ 1+ category, 1:40 (IQR, 1:20 to 1:80) in the CrAgSQ 2+ category, 1:640 (IQR, 1:160 to 1:2,560) in the CrAgSQ 3+ category, and 1:5,120 (IQR, 1:2,560 to 1:30,720) in the CrAgSQ 4+ category. Increasing CrAgSQ scores were strongly associated with 10-week mortality. The IMMY CrAgSQ test had high sensitivity and specificity compared to the results for the IMMY CrAg LFA and provided CrAg scores that were associated with both conventional CrAg titers and clinical outcomes.
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. We investigated the prevalence and dynamics of neonatal ESKAPE and Candida spp. colonization from hospital admission until discharge (or death) and followed up for invasive disease.
Prospective longitudinal surveillance for neonatal ESKAPE and Candida spp. colonization was conducted over 6 months at a South African regional hospital. Neonates enrolled at birth had swabs (nasal, 2× skin and rectal) collected within 24 hours and every 48-96 hours thereafter, until discharge or death. ESKAPE and Candida spp. were cultured for and antimicrobial susceptibility was performed on bacterial isolates. Whole-genome sequencing was undertaken on paired samples with the same bacterial species from colonizing and invasive disease episodes in the same child.
Of 102 enrolled neonates, 79% (n = 81) were colonized by ≥1 ESKAPE organism by time of discharge or death. Forty-four percent (36/81) were colonized within 24 hours of birth. Common colonizers were K. pneumoniae (70%; n = 57) and Enterobacter spp. (43%; n = 35). Almost all MDR organisms (93%) were Gram-negative. Forty-two (45%, 42/93) newborns acquired Candida spp. (skin only) colonization, commonly Candida parapsilosis (69%; n = 29). For 2 children with K. pneumoniae colonization and sepsis, the bloodstream and colonizing isolates were genetically different, whereas the single A. baumannii colonizing and blood isolate pair were genetically identical.
We report a high prevalence of MDR ESKAPE and Candida spp. colonization in a regional neonatal unit. Interventions to reduce the high incidence of hospital-acquired neonatal infections should include reducing high colonization rates.
On May 30th and 31st, 2023, delegates representing various African subregions, together with global representatives from the International Society of Human and Animal Mycology (ISHAM), the European ...Confederation of Medical Mycology (ECMM), the United States Centre for Disease Control and Prevention (CDC), and Global Action for Fungal Infections (GAFFI), convened in Nairobi, Kenya under the aegis of the Pan African Mycology Working Group, a working group of ISHAM. The meeting objectives were, amongst others, to deliberate on a continental response to the World Health Organisation Fungal Priority Pathogen List and facilitate interaction between global and regional leaders. Country delegates and international speakers addressed Africa's fungal disease burden; capacity for diagnosis and management; ongoing surveillance; knowledge gaps and trends in invasive fungal diseases such as Candida auris, mucormycosis, aspergillosis, and Acquired Immune Deficiency Syndrome (AIDS)-related mycoses; and current laboratory practice. During the technical sessions, expert panels deliberated on establishing and financing of national/regional surveillance networks for mycoses; establishing and sustaining African-led collaborations; expanding on existing laboratory and point-of-care diagnostic capacity as well as planning a mycology reference laboratory service and network in Africa. The meeting also highlighted successful African-led collaborations, capacity building, and clinical trial initiatives. The meeting conclusions informed the resolutions of the Nairobi Declaration calling for improved awareness; strong collaborations between clinical and laboratory teams across Africa; improved fungal disease surveillance within the continent; access to antifungals and diagnostics; and leveraging qualified human resources for mycology present within and outside Africa to facilitate trainings, collaborations, and exchanges.
sequencing of 28 Candida auris clade III isolates revealed the presence of concomitant V125A and F126L substitutions. Heterologous expression of Erg11-V125A/F126L in Saccharomyces cerevisiae led to ...reduced fluconazole and voriconazole susceptibilities. Generation of single substitution gene variants through site-directed mutagenesis uncovered that F126L primarily contributes to the elevated triazole MICs. A similar yet diminished pattern of reduced susceptibility was observed with the long-tailed triazoles posaconazole and itraconazole for the V125A/F126L, F126L, Y132F, and K143R alleles.
We aimed to describe the epidemiology of candidemia among children in South Africa.
We conducted laboratory-based surveillance among neonates (≤28 days), infants (29 days to <1 year), children (1-11 ...years) and adolescents (12-17 years) with Candida species cultured from blood during 2012-2017. Identification and antifungal susceptibility of viable isolates were performed at a reference laboratory. We used multivariable logistic regression to determine the association between Candida parapsilosis candidemia and 30-day mortality among neonates.
Of 2996 cases, neonates accounted for 49% (n = 1478), infants for 27% (n = 806), children for 20% (n = 589) and adolescents for 4% (n = 123). The incidence risk at tertiary public sector hospitals was 5.3 cases per 1000 pediatric admissions (range 0.39-119.1). Among 2943 cases with single-species infections, C. parapsilosis (42%) and Candida albicans (36%) were most common. Candida auris was among the 5 common species with an overall prevalence of 3% (n = 47). Fluconazole resistance was more common among C. parapsilosis (55% 724/1324) versus other species (19% 334/1737) (P < 0.001). Of those with known treatment (n = 1666), 35% received amphotericin B deoxycholate alone, 32% fluconazole alone and 30% amphotericin B deoxycholate with fluconazole. The overall 30-day in-hospital mortality was 38% (n = 586) and was highest among neonates (43% 323/752) and adolescents (43% 28/65). Compared with infection with other species, C. parapsilosis infection was associated with a reduced mortality among neonates (adjusted odds ratio 0.41, 95% confidence interval: 0.22-0.75, P = 0.004).
Candidemia in this setting mainly affected neonates and infants and was characterized by fluconazole-resistant C. parapsilosis with no increased risk of death.
Abstract
Blood cryptococcal antigen (CrAg) titers >160 are associated with concurrent subclinical cryptococcal meningitis (CM). When lumbar puncture (LP) is not immediately available in a CrAg ...screening program, semi-quantitative CrAg assays may provide risk stratification for CM. Two semi-quantitative assays (SQ Immuno-Mycologics, Norman, OK, USA and CryptoPS Biosynex, Strasbourg, France) were evaluated against a qualitative lateral flow assay (LFA) using 194 plasma samples from a cohort of HIV-seropositive individuals with CD4 counts <100 cells/μl. We compared SQ and CryptoPS results to titers for LFA-positive samples. Among patients with LP, we examined the association between semi-quantitative CrAg results and CM. We used a Cox proportional hazards model to determine the association between SQ score and mortality. Of 194 participants, 60 (31%) had positive LFA results, of whom 41 (68%) had a titer of ≤160 and 19 (32%) a titer >160. Fifty individuals with antigenemia had an LP; a clinically useful SQ score that identified all ten cases of subclinical CM was ≥3 (100% sensitivity, 55% specificity). Patients with an SQ score of 3 or 4 also had a 2.2-fold increased adjusted hazards of 6-month mortality (95% CI: 0.79–6.34; p = 0.13) versus those with score of <3. Nine of ten patients with subclinical CM had a strong-positive CryptoPS result versus 10/40 without subclinical CM (p < 0.001). Semi-quantitative assays offered a sensitive though not specific means of gauging the risk of concurrent CM in this patient population.
Lay summary
We evaluated two single-step laboratory tests that can quantify the amount of cryptococcal antigen in plasma of patients with advanced HIV disease and could thus gauge the risk of concurrent cryptococcal meningitis and subsequent mortality. These tests are not a substitute for a lumbar puncture.
...there should be improvements in clinical care in settings with scarce resources, including for people living with HIV who are admitted to hospital. NPG reports grants from the National Institutes ...of Health, UK Medical Research Council, Bill & Melinda Gates Foundation, Centers for Disease Control and Prevention, and National Health Laboratory Service Research Trust, outside the submitted work. JNJ reports grants from European and Developing Countries Clinical Trials Partnership, National Institute for Health Research, National Institutes of Health, and UK Medical Research Council, outside the submitted work.
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