Case Report of Nasal Rhinosporidiosis in South Africa.

We describe a classic case of nasal rhinosporidiosis in a woman who resided in Johannesburg, South Africa, but originated from a rural area in Eastern Cape Province. We confirmed histologic diagnosis using PCR testing and compared details with those from records on 17 other cases from South Africa.

A novel adenovirus isolated from the Egyptian fruit bat in South Africa is closely related to recent isolates from China.

Recently a number of novel adenoviruses have been isolated from diverse bat species and from diverse geographical locations. We describe the isolation of a novel adenovirus (Family Adenoviridae, genus Mastadenovirus) from a pool of liver and spleen tissue of an apparently healthy wild-caught Egyptian fruit bat (Rousettus aegyptiacus) in South Africa. Genetically the virus is most closely related to four mastadenoviruses recently isolated in China, from Miniopterus schreibersi and Rousettus leschenaultii bats, which are highly divergent from previously identified bat adenoviruses. The length of the Rousettus aegyptiacus adenovirus-3085 (RaegAdV-3085) genome, at 29,342 bp is similar to its closest relatives, and contains 27 open reading frames. The RaegAdV-3085 genome has a low G + C content (36.4%) relative to other viruses in the genus (between 43.6 and 63.9%) but similar to its closest relatives. The inverted terminal repeat (ITR) of RaegAdV-3085 is only 40 bp compared to between 61 and 178 bp of its closest relatives. The discovery of RaegAdV-3085 expands the diversity of known adenoviruses in bats and might represent a member of a new mastadenovirus species in bats.

Molecular characterization of invasive capsule null Neisseria meningitidis in South Africa.

BACKGROUND: The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear. We identified four invasive cnl meningococci through laboratory-based surveillance in South Africa from 2003 through 2013, which we aimed to characterize using whole genome data. RESULTS: One isolate [NG: P1.7-2,30: F1-2: ST-53 (cc53)] contained cnl allele 12, and caused empyema in an adult male with bronchiectasis from tuberculosis, diabetes mellitus and a smoking history. Three isolates were NG: P1.18-11,42-2: FΔ: ST-192 (cc192) and contained cnl allele 2. One patient was an adolescent male with meningitis. The remaining two isolates were from recurrent disease episodes (8 months apart) in a male child with deficiency of the sixth complement component, and with the exception of two single nucleotide polymorphisms, contained identical core genomes. The ST-53 (cc53) isolate possessed alleles for NHBA peptide 191 and fHbp variant 2; whilst the ST-192 (cc192) isolates contained NHBA peptide 704 and fHbp variant 3. All four isolates lacked nadA. Comparison of the South African genomes to 61 additional cnl genomes on the PubMLST Neisseria database ( http://pubmlst.org/neisseria/ ), determined that most putative virulence genes could be found in both invasive and carriage phenotypes. CONCLUSIONS: Although rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.

Disulfiram/copper-disulfiram Damages Multiple Protein Degradation and Turnover Pathways and Cytotoxicity is Enhanced by Metformin in Oesophageal Squamous Cell Carcinoma Cell Lines.

Disulfiram (DSF), used since the 1950s in the treatment of alcoholism, is reductively activated to diethyldithiocarbamate and both compounds are thiol-reactive and readily complex copper. More recently DSF and copper-DSF (Cu-DSF) have been found to exhibit potent anticancer activity. We have previously shown that the anti-diabetic drug metformin is anti-proliferative and induces an intracellular reducing environment in oesophageal squamous cell carcinoma (OSCC) cell lines. Based on these observations, we investigated the effects of Cu-DSF and DSF, with and without metformin, in this present study. We found that Cu-DSF and DSF caused considerable cytotoxicity across a panel of OSCC cells, and metformin significantly enhanced the effects of DSF. Elevated copper transport contributes to DSF and metformin-DSF-induced cytotoxicity since the cell-impermeable copper chelator, bathocuproinedisulfonic acid, partially reversed the cytotoxic effects of these drugs, and interestingly, metformin-treated OSCC cells contained higher intracellular copper levels. Furthermore, DSF may target cancer cells preferentially due to their high dependence on protein degradation/turnover pathways, and we found that metformin further enhances the role of DSF as a proteasome inhibitor. We hypothesized that the lysosome could be an additional, novel, target of DSF. Indeed, this acid-labile compound decreased lysosomal acidification, and DSF-metformin co-treatment interfered with the progression of autophagy in these cells. In summary, this is the first such report identifying the lysosome as a target of DSF and based on the considerable cytotoxic effects of DSF either alone or in the presence of metformin, in vitro, and we propose these as novel potential chemotherapeutic approaches for OSCC.

Microsporidiosis in pediatric renal transplant patients in Cape Town, South Africa: two case reports.

Microsporidia are an emerging group of pathogens associated with life-threatening opportunistic infections in immunocompromised hosts, particularly human immunodeficiency virus (HIV)-infected individuals. There have, however, been recent reports of infection in adult solid organ transplant recipients. We report two cases in children, to our knowledge the first in the paediatric literature. Two 13-yr-old, HIV-seronegative females received deceased donor renal transplants from the same donor. Both patients suffered acute cell-mediated rejection and CMV infection reactivation, managed with intensified immunosuppression and ganciclovir. Pyrexia of unknown origin and intermittent diarrhea in both prompted extensive investigations. In both patients, numerous spores of a microsporidial species were demonstrated in renal tissue on biopsy and in the urine, using modified trichrome and quick-hot Gram-chromotrope staining. Electron microscopy and PCR confirmed Encephalitozoon cuniculi infections. Both patients were successfully treated with 400 mg twice daily of albendazole, with sustained clinical improvement. We recommend that microsporidiosis be considered in the differential diagnosis of pyrexia of unknown origin in severely immunocompromised pediatric solid organ transplant recipients, particularly when associated with diarrhea.