The estimated burden of fungal disease in South Africa

Background. With a population of 56.5 million, over 7 million persons living with HIV, one of the world's highest rates of tuberculosis (TB) and a large proportion of the population living in poverty, South Africa (SA)'s fungal disease burden is probably substantial and broad in scope.Objectives. To estimate the burden of fungal disease in SA.Methods. Using total and at-risk populations and national, regional and occasionally global data, we estimated the incidence and prevalence of the majority of fungal diseases in SA.Results. Estimates for the annual incidence of HIV-related life-threatening fungal disease include cryptococcal meningitis (8 357 cases), Pneumocystis pneumonia (4 452 cases) and endemic mycoses (emergomycosis, histoplasmosis and blastomycosis, with 100, 60 and 10 cases per year, respectively). We estimate 3 885 cases of invasive aspergillosis annually. The annual burden of candidaemia and Candida peritonitis is estimated at 5 421 and 1 901 cases, respectively. The epidemic of pulmonary TB has probably driven up the prevalence of chronic pulmonary aspergillosis to 99 351 (175.8/100 000), perhaps the highest in the world. Fungal asthma probably affects >100 000 adults. Mucosal candidiasis is common, with an annual prevalence estimated at 828 666 and 135 289 oral and oesophageal cases, respectively, complicating HIV infection alone (estimates in other conditions not made), and over a million women are estimated to be affected by recurrent vulvovaginal candidiasis each year. Tinea capitis in children is common and conservatively estimated at >1 000 000 cases. The inoculation mycoses sporotrichosis, chromoblastomycosis and eumycetoma occur occasionally (with 40, 40 and 10 cases estimated, respectively). Overall, we estimate that over 3.2 million South Africans are afflicted by a fungal disease each year (7.1% of the population).Conclusions. Significant numbers of South Africans are estimated to be affected each year by fungal infections, driven primarily by the syndemics of HIV, TB and poverty. These estimates emphasise the need for better epidemiological data, and for improving the diagnosis and management of these diseases

Something wicked this way comes: What health care providers need to know about Candida auris.

Candida auris is a fungal pathogen that recently emerged and rapidly spread around the globe. It is now in Canada. C. auris can cause invasive disease with high mortality rates, is frequently resistant to one or more classes of antifungals, and can be difficult to identify in some clinical microbiology laboratories. C. auris can also involve prolonged colonization of patients' skin and contamination of surrounding environments, resulting in nosocomial outbreaks in hospitals and long-term care facilities. Clinicians, infection prevention and control practitioners and public health officials should be aware of how to mitigate the threat posed by this pathogen. Index cases of C. auris should be suspected in patients with invasive candidiasis and recent hospitalization in global regions where C. auris is prevalent, as well as in patients who fail to respond to empiric antifungal therapy and from whom unidentified or unusual Candida species have been isolated. If a case of C. auris infection or colonization is identified or suspected, the following should take place: notification of local public health authorities and infection prevention and control practitioners; placement of colonized or infected patients in single rooms with routine contact precautions; daily and terminal environmental disinfection with a sporicidal agent; contact tracing and screening for C. auris transmission; and referral of suspicious or confirmed isolates to provincial laboratories. Patients with symptomatic disease should be treated with an echinocandin pending the results of antifungal susceptibility testing, preferably in consultation with an infectious disease specialist. Through the vigilance of front-line health care workers and microbiologists, robust infection prevention and control practices, and local and national surveillance efforts, C. auris can be detected quickly, infections managed and transmissions prevented to protect patients in our health care system.

First reported case of multidrug-resistant Candida auris in Canada.

Candida auris is a fungal pathogen that has recently emerged as a global threat to public health. It was first described in Japan in 2009 and has since been reported in 17 countries on five continents. This case report describes the first reported case of multidrug-resistant C. auris in Canada. In May 2017, a 64-year-old individual was evaluated for chronic otitis externa. Past medical history included a recent hospitalization in India for elective oral surgery that was complicated by an odontogenic brain abscess. Upon return to Canada, the individual was admitted to a hospital for neurosurgical drainage of the brain abscess and parenteral antibiotics. Early during hospitalization, the patient was identified as a carrier of carbapenem-resistant Enterobacteriaceae and was placed on contact precautions. Also early during this hospitalization, a chronic otitis media was managed with placement of a typanostomy tube with drainage of clear fluid from the ear, which continued through the admission and after discharge to a post-neurosurgical rehabilitation facility. During outpatient follow-up, swabs of the ear discharge cultured C. auris that was resistant to fluconazole and amphotericin B. There was no clinical response to ototopical antifungal therapy. Surgical evaluation for management of the otomastoiditis is pending. There is a potential for C. auris to cause infection in health care settings. It can persist in hospital environments, has the potential for transmission and can cause invasive disease. It is difficult to identify and is often resistant to antifungal medications. The application of infection prevention and control recommendations can help prevent nosocomial transmission. It is now prudent to consider the risk of C. auris, in addition to the known risk of other antimicrobial resistant organisms, in any traveller who has been hospitalized while outside the country. When identified, contacting local public health can assist in the tracking and management of this emerging disease.

Interferon-gamma release assays piloted as a latent tuberculous infection screening tool in Canadian federal inmates.

BACKGROUND: Interferon-gamma release assays (IGRAs) may be useful in diagnosing latent tuberculous infection (LTBI) in inmates; however, published experience in these settings is limited. OBJECTIVE: To identify variables associated with IGRA positivity among Canadian federal inmates with positive tuberculin skin test (TST) results. DESIGN: On intake, TST-positive (≥10 mm) inmates were offered an IGRA (QuantiFERON(®)-TB Gold), and demographic and historical data were collected. IGRA-positive and -negative inmates were compared using the χ(2) test and multivariable logistic regression; the final model's goodness of fit was assessed using Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC). RESULTS: Of 96 TST-positive inmates, 31 (32.3%) were IGRA-positive. Variables associated with positive IGRA were age >45 years (11/20 vs. 20/75, P = 0.016) and previous LTBI treatment (9/20 vs. 13/55, P = 0.032) in univariate analysis, and being from a country with a moderate or high estimated tuberculosis (TB) incidence (OR 3.5, 95%CI 1.3-9.4, P = 0.013) and absence of bacille Calmette-Guérin (BCG) vaccination (OR 3.3, 95%CI 1.2-9.0, P = 0.017) in multivariable analysis. The data fit the model well, classifying the group better than chance alone (AUC 0.67, P = 0.007). CONCLUSION: High discordance with TST, particularly among BCG-vaccinated inmates and those from low TB incidence countries, suggest that IGRA may be useful in Canadian federal penitentiary screening programmes.

Pulmonary paracoccidioidomycosis misdiagnosed as Pneumocystis pneumonia in an immunocompromised host.

Yeast cells of Paracoccidioides brasiliensis can resemble the cysts of Pneumocystis carinii in smears stained with Grocott's modification of the Gomori methanamine silver stain. Furthermore, P. brasiliensis can cross-react in material stained with a widely used P. carinii immunofluorescent stain which uses monoclonal antibodies. The need to differentiate P. brasiliensis and P. carinii will become more important as the increasing incidence of immunosuppression results in the reactivation of latent P. brasiliensis infections.

Decreased 3 alpha-hydroxysteroid dehydrogenase activity in peripheral blood lymphocytes from patients with primary open angle glaucoma.

The purpose of the present study was to determine whether peripheral blood lymphocytes (PBL) from primary open angle glaucoma (POAG) patients have reduced 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity as was previously found in POAG-derived cultured trabecular meshwork cells. The availability of PBL from both POAG and control patients makes this a useful system for studying the association of decreased 3 alpha-HSD activity with POAG. PBL were isolated from the venous blood of 17 POAG patients and 22 non-glaucoma controls and assayed for 3 alpha-HSD activity with tritiated 5 beta-dihydrocortisol as a substrate. The mean 3 alpha-HSD activity +/- S.E.M., expressed in comparable units of specific activity, of the POAG derived PBL was 13.8 +/- 1.3 U as compared to 32.8 +/- 2.0 U for control cells. This reduction (> 50%) was statistically significant (P < 0.001). Quantitative immunoblot analysis of PBL indicated that the POAG and control cells, despite their difference in 3 alpha-HSD activity, had nearly identical amounts of 3 alpha-HSD protein. The molecular weight of PBL 3 alpha-HSD from both groups of patients was 38,000, the same as previously reported for human liver. The results of this study show an association of decreased PBL 3 alpha-HSD activity and POAG which was not related to antiglaucoma therapy. The reduced levels of 3 alpha-HSD activity in the readily obtainable PBL may serve as a marker for POAG or those at risk for developing the disease.

Overdentures. Principles and procedures.

Although advances in methods and improved materials have contributed to better treatment results, caries and periodontal problems still remain significant threats to overdenture service life. The prevention of caries and recurrent periodontal disease thus becomes a most important aspect of postinsertion care. Undoubtedly, there are a number of successful overdenture methods. This article outlines two treatment sequences previously described by Brewer and Morrow that continue to be effective (Fig. 23). Common to most overdenture techniques is that an overdenture may be the only treatment that permits retention using the patient's last few retainable teeth. A conservative approach to root preservation still is a valid and practical measure in preventative dentistry.

Color stability of selected dual-cure composite resin cements.

PURPOSE: This in vitro study was conducted to determine the color stability of five dual-cure composite resin cements: Kerr Porcelite (Kerr Manufacturing Co, Romulus, NY), Jelenko PVS System (J.F. Jelenko and Co, Armonk, NY), Vivadent Heliolink (Vivadent USA, Amherst, NY), Mirage FLC (Chameleon Dental Products, Inc, Kansas City, KS), and Den-Mat Ultra Bond (Den-Mat Corp, Santa Maria, CA). MATERIALS AND METHODS: Each cement was used to lute two 10 mm circular Vita VMK porcelain disks 0.75 mm in thickness. The surfaces to be luted were sand blasted and a silane coupling agent applied. The natural glaze was unaltered. Manufacturer's directions were followed for manipulation of the cements. A jig was used during the application of the resins to control cement thickness. The samples were stored in distilled water at 37 degrees C. Using a Hunter Tristimulus Colorimeter (Hunter Associates Laboratory, Inc, Reston, VA), values were obtained for each specimen immediately, at 24 hours, and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks. RESULTS: An analysis of variance (ANOVA) showed significant differences for all specimens. Using the Scofield Hunter formula for identifying color differences (delta E), at 24 hours, and 24 weeks, Vivadent Heliolink showed the least color changes (24 hours delta E = 0.82, 24 weeks delta E = 0.98) and Kerr Porcelite the greatest (24 hours delta E = 3.94, 24 weeks delta E = 4.73). CONCLUSIONS: All dual-cure composite resin cements in this study showed short-term and long-term color change. Vivadent Heliolink showed the least color change, while Kerr Porcelite showed the most change.

Purification and properties of human hepatic 3 alpha-hydroxysteroid dehydrogenase.

3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500-fold from human liver cytosol. The purification was monitored using 5 beta-[3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous enzyme was obtained using a procedure that involved ammonium sulfate precipitation and three successive column chromatography steps: DEAE-cellulose, hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column, and the denatured subunit molecular weight was determined to be 38,500, by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated 4,5 double bond was required for substrate activity. The conformation at the 5 position, however, did not influence substrate activity since 5 alpha- and 5 beta-DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18 microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing 10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in a large loss of activity during early stages of the purification. This is the first report of the purification to homogeneity of 3 alpha-HSD from human tissue.

Human hepatic 3 alpha-hydroxysteroid dehydrogenase: possible identity with human hepatic chlordecone reductase.

3 alpha-Hydroxysteroid dehydrogenase is a cytosolic, monomeric, NADPH-dependent oxidoreductase which reduces 3-keto-5-dihydrosteroids to their tetrahydro products. We present here the first partial amino acid sequence data for the human liver enzyme and show these sequences to be identical to the deduced amino acid sequence for human hepatic chlordecone reductase. In addition, these two enzymes exhibit similar substrate and cofactor specificities and immunological reactivity. The results suggest that the natural substrates for chlordecone reductase are 3-keto-5-dihydrosteroids and that these two proteins may be identical.

An unusual organoid tumor. Alveolar soft part sarcoma or paraganglioma?

The histogenesis of alveolar soft part sarcoma (ASPS) is a subject of continued debate. Although many recent reports suggest a muscle origin, others advocate a neuroendocrine derivation. A tumor in the chest wall of a 16-year-old woman was diagnosed and treated as ASPS. The light microscopic, electron microscopic, and immunohistochemical findings showed features of both ASPS and paraganglioma. In addition, this lesion was positive for antibody to glucagon, a characteristic of neither ASPS nor paraganglioma, although seen in a few gangliocytic paragangliomas. This case demonstrates the need for continued inquiry into the histogenesis of ASPS.

Sudden asphyxial death due to a prolapsed esophageal fibrolipoma.

Fibrolipomas of the esophagus are extremely uncommon benign tumors. Accurate diagnosis and resection are essential, due to their tendency to become impacted and obstruct the airway. The case is presented of a 56-year-old man who died suddenly of asphyxia because of upper airway obstruction by a prolapsed fibrolipoma of the esophagus.

Social validity assessments: is current practice state of the art?

The use of evaluative feedback from consumers to guide program planning and evaluation is often referred to as the assessment of social validity. Differing views of its role and value in applied behavior analysis have emerged, and increasingly stereotyped assessments of social validity are becoming commonplace. This paper argues that current applications of social validity assessments are straying from the point originally proposed for them. Thus, several suggestions for improving current social validity assessment are proposed, including (a) expanding the definition of consumers to acknowledge the variety of community members able and likely to affect a program's survival, (b) increasing the psychometric rigor of social validity assessments, (c) extending assessment to heretofore underrepresented populations, (d) implementing widespread application of well-designed social validity assessments, (e) increasing meaningful consumer involvement in the planning and evaluation of behavioral programs, and (f) educating consumers to make better informed programming decisions.

Human hepatic cortisol reductase activities: enzymatic properties and substrate specificities of cytosolic cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase(s).

The metabolism of cortisol by human liver homogenates has been studied. Cortisol delta 4-reductase and dihydrocortisol-3-oxidoreductase activities were distributed in all subcellular fractions. The products of the soluble enzymes were identified. Cortisol and 5 beta-dihydrocortisol were reduced to 3 alpha,5 beta-tetrahydrocortisol, and 5 alpha-dihydrocortisol was reduced to 3 alpha,5 alpha-tetrahydrocortisol. The soluble enzymes showed a wide range of substrate specificity. The 21 substituted cortisol derivatives were not metabolized. The apparent Km values of cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase for their substrates (cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol) all ranged from 18 to 27 microM. Dexamethasone inhibited the reduction of all of these substrates and the inhibition was abolished by 21 substitution of the dexamethasone. Testosterone was a competitive inhibitor of the reduction of cortisol, 5 alpha-dihydrocortisol, and 5 beta-dihydrocortisol with a Ki ranging from 11 to 32 microM. NADPH was the preferred cofactor for the cortisol delta 4-5 beta-reductase and dihydrocortisol-3 alpha-oxidoreductase. No end product inhibition was observed.