Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described. METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury. RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively. CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

Mediastinoscopy as a diagnostic tool in a South African tertiary hospital.

BACKGROUND: Mediastinoscopy is an effective and safe diagnostic tool for anterior mediastinal lesions. The study was done to assess the usefulness of mediastinoscopy as a diagnostic modality for mediastinal lesions. METHODS: A retrospective study of patients who had mediastinoscopy over 12 years at the Groote Schuur Hospital, Cape Town. Preoperative data, intraoperative and postoperative data were collected. RESULTS: The records of 115 patients were reviewed. Male to female ratio was 1.4:1 with a mean age of 48.5 (± 16.8) years. Preoperative computerised tomography (CT) scan was done in 98.3%. The most common indications for mediastinoscopy were mediastinal lymphadenopathy (87.8%) and anterior mediastinal mass (12.2%). Prior endobronchial ultrasound (EBUS) biopsy was done in 11.3%. All the patients had conventional cervical mediastinoscopy. Lung cancer staging accounted for 16.5% of the procedures. A biopsy was successfully done in 103 patients (89.6%). The most common lymph node station biopsied was 2R (55.7% of 76 patients), though the information on stations biopsied could not be ascertained in 25.2% of patients. The complication rate was 1.7 % (suprasternal haematoma and brachiocephalic artery injury). Histopathologic diagnoses were obtained in 89.5% (103/115 patients). Benign diagnoses accounted for 72.8% (75), while malignant diagnoses were 27.2% (28). Intensive care unit (ICU) stay and mechanical ventilation were required in 5% and 2.5% of patients, respectively. The median postoperative hospital stay was 2 days. There were no postoperative deaths. The median follow-up period was 14 days. CONCLUSION: Mediastinoscopy's diagnostic role is assured, still required and is safe with minimal morbidity and no mortality.

Prevalence of methicillin resistance in Staphylococcus pseudintermedius isolates from dogs with skin and ear infections in South Africa.

ABSTRACT: Staphylococcus pseudintermedius (SP) is an important opportunistic pathogen, frequently associated with pyoderma and otitis in dogs. The emergence and rapid expansion of methicillin-resistant Staphylococcus pseudintermedius (MRSP) is problematic due to multidrug resistance and reduced treatment options. The aim of this study was to determine i) the prevalence of MRSP in dogs with pyoderma or otitis externa, ii) the antimicrobial resistance patterns of MRSP from South African isolates, and iii) the risk factors for MRSP-associated pyoderma or otitis externa in dogs in South Africa (RSA). Sixty-eight presumptive clinical SP isolates (collected from 65 dogs) from five geographically dispersed laboratories in RSA were collected over 2 years. Possible MRSP isolates were flagged when resistance to oxacillin was observed. Thereafter, all isolates were confirmed as SP by polymerase chain reaction (PCR) and further genotyped for the mecA gene. Fifty-seven of 68 isolates were confirmed to be SP (83.8%), while 49/57 (85.9%) carried mecA. Our findings showed that preliminary phenotypic methods supplemented by genotypic methods increased the accuracy of correctly identifying SP. All isolates were resistant to at least one antimicrobial drug. There was a high incidence of amoxicillin (70.1%) and enrofloxacin (65%) resistance. Important risk factors for mecA positive carriage were previous hospital admission, pruritus, and previous antibacterial failure. This study demonstrates a high prevalence of mecA positive carriage (85.9% of samples) in MRSP pyoderma and otitis in dogs in RSA. There is an urgent need for better laboratory diagnosis of MRSP and surveillance of dogs presenting with pyoderma and otitis in South Africa.

Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV.

BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.

Antimicrobial resistance at the livestock-human interface: implications for Veterinary Services.

The emergence of antimicrobial resistance (AMR) is a major global public health issue, but it also jeopardises the effectiveness of antimicrobials as a means of curing infections in animals that threaten their health, welfare and productivity. Several reports show that infections in humans caused by antimicrobial-resistant pathogens may be linked to antimicrobial use (AMU) and AMR in food-producing animals; however, to what extent this happens is unknown. Use of antimicrobials drives the emergence of AMR, therefore, their extensive over-use and misuse in livestock is of concern. Robust AMU and AMR data are important to monitor the progress of interventions aiming to reduce AMR in the livestock sector. However, not all countries have complete data on antibiotic sales or use, so our current knowledge of global AMU is primarily based on modelling estimates. Antimicrobial resistance prevalence data are limited, particularly in low- and middle-income countries, but in some high-income regions fairly robust data are available. It should also be noted that monitoring guidelines and protocols are available to provide globally harmonised AMR data. Using antimicrobials rationally and not using them for disease prevention purposes is key to reducing AMU. To ensure that these drugs are used appropriately we must ensure that: a) veterinary services are accessible and affordable for farmers; b) antibiotics are only sold on prescription; c) veterinarians earn no revenue linked to the sale or prescription of antibiotics; d) veterinarians have substantial skills in preventive medicine (good animal husbandry, efficient biosecurity and vaccinology); and e) the benefits of preventive measures must appeal to farmers so that they are willing to pay for them.

L'émergence de la résistance aux agents antimicrobiens (RAM) constitue un problème majeur de santé publique à l'échelle mondiale, qui compromet également l'efficacité des agents antimicrobiens utilisés chez les animaux pour traiter les infections menaçant leur santé, leur bien-être et leur productivité. Plusieurs rapports montrent que les infections humaines par des agents pathogènes résistants aux agents antimicrobiens sont probablement liées à l'utilisation d'agents antimicrobiens (UAM) et à la RAM chez les animaux servant à la production de denrées alimentaires ; toutefois, on ignore la portée exacte de ce phénomène. L'utilisation d'agents antimicrobiens étant à l'origine de l'émergence de la RAM, l'utilisation excessive ou le mauvais usage de ces produits chez les animaux d'élevage sont des sujets de préoccupation. Il est important de disposer de données solides sur l'UAM et la RAM afin de suivre les progrès des interventions visant à réduire la RAM dans le secteur de l'élevage. Plusieurs pays ont des données incomplètes sur les ventes ou l'utilisation d'antibiotiques au niveau national et nos connaissances actuelles sur l'UAM à l'échelle mondiale proviennent principalement d'estimations basées sur des modélisations. Les données sur la prévalence de la résistance aux agents antimicrobiens sont souvent éparses, en particulier dans les pays à revenu faible ou intermédiaire tandis que dans d'autres régions à revenu élevé, les données disponibles sont assez solides. Il convient à cet égard de signaler l'existence de lignes directrices et de protocoles de surveillance permettant de fournir des données harmonisées sur la RAM à l'échelle mondiale. Pour réduire l'UAM, il est essentiel d'appliquer des méthodes de prévention des maladies qui ne fassent pas appel aux agents antimicrobiens, et de n'utiliser ces derniers qu'en suivant des principes rationnels. Cela suppose de faire en sorte que : a) les services vétérinaires soient accessibles et abordables pour les éleveurs ; b) les antibiotiques ne soient vendus que sur ordonnance ; c) les vétérinaires ne tirent pas de revenus de la vente ou de la prescription d'antibiotiques ; d) les vétérinaires praticiens soient dotés de compétences solides en médecine préventive, y compris concernant les bonnes pratiques d'élevage, les mesures efficaces de biosécurité et la vaccinologie ; e) la valeur ajoutée de ces mesures soit bien perçue par les éleveurs afin qu'ils soient disposés à payer pour ces services.

La aparición de resistencias a los antimicrobianos no solo supone un importante problema de salud pública mundial, sino que también puede restar eficacia a los antimicrobianos para curar infecciones que amenazan la salud, el bienestar y la productividad de los animales. Varios informes han dejado patente que las infecciones humanas causadas por patógenos resistentes a los antimicrobianos pueden guardar relación con el uso de estos fármacos y la resistencia a ellos en animales de producción alimentaria, aunque se ignora la amplitud del fenómeno. Dado que el uso de antimicrobianos provoca la aparición de resistencias, su utilización excesiva o incorrecta en el ganado, tan extendida, resulta preocupante. Para seguir de cerca el progreso de las intervenciones destinadas a reducir la resistencia a los antimicrobianos en el sector ganadero es importante disponer de datos robustos sobre la utilización de estos fármacos y las resistencias a ellos. Varios países tienen datos incompletos sobre las ventas o el uso de antibióticos, de tal modo que lo que hoy sabemos sobre el uso de antimicrobianos a escala mundial reposa principalmente en estimaciones obtenidas por modelización. Los datos sobre la prevalencia de resistencias a los antimicrobianos son fragmentarios, especialmente en los países de renta baja o mediana, pero en algunas regiones de renta alta existen datos bastante robustos. Conviene señalar también la existencia de directrices y protocolos de seguimiento que permiten disponer de datos mundialmente armonizados en la materia. Para reducir las resistencias a los antimicrobianos, dos factores clave son la prevención de enfermedades sin recurrir a estos fármacos y el uso racional de los mismos, factores que pasan por lo siguiente: a) servicios veterinarios accesibles y asequibles para los productores; b) venta de antibióticos únicamente con receta; c) los veterinarios no deben percibir ingresos ligados a la venta o prescripción de antibióticos; d) los veterinarios deben contar con sólidos conocimientos de medicina preventiva, lo que incluye cuestiones de buena producción animal, seguridad biológica eficaz y vacunología; y e) tales medidas deben aportar un valor añadido que resulte atractivo para los ganaderos, de forma que estén dispuestos a pagar por ese servicio.

The effect of different antimicrobial treatment regimens on the faecal shedding of ESBL-producing Escherichia coli in horses.

Fourth-generation cephalosporins can select for extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae in horses, but it is unknown to what extent this occurs compared to penicillin/gentamicin combination treatment. The objective was to evaluate the effect of different antimicrobial treatments on faecal shedding and diversity of ESBL-producing Escherichia coli (ESBL-EC) in horses. Upon hospital admission, 86 horses in need of antimicrobial treatment or prophylaxis were randomly allocated to receive penicillin and gentamicin (PG) or cefquinome (CEF). Untreated horses were included as controls (NOAMD, n = 33). Faecal samples from admission (T1), 3 days after admission (T2), and faecal swabs 28 days after discharge (T3) were cultured selectively. Differences in prevalence (T1, T2, T3) and counts (T1, T2) of ESBL-EC between groups and over time were analysed. On a subset of ESBL-EC isolates, antimicrobial susceptibility testing (n = 45) and whole-genome sequencing followed by SNP-analysis (n = 46) were performed. The prevalence of ESBL-EC at T1 was 12 % with no significant difference between groups. In all groups, significantly higher carriage rates were observed at T2 and T3 compared to T1. Carriage and counts of ESBL-EC at T2 were significantly higher in treated compared to untreated horses. There was no significant difference between PG and CEF at any time points. Despite a large genetic diversity, indistinguishable ESBL clones were observed in different horses over time. In conclusion, antimicrobial treatment and hospitalization increased prevalence and counts of ESBL-EC, and transmission of ESBL-EC in the hospital was suspected. These findings highlight the importance of antimicrobial stewardship and infection control practices in equine medicine.

Carbapenem-resistant Enterobacteriaceae in patients with bacteraemia at tertiary hospitals in South Africa, 2015 to 2018.

Enhanced surveillance for CREs was established at national sentinel sites in South Africa. We aimed to apply an epidemiological and microbiological approach to characterise CREs and to assess trends in antimicrobial resistance from patients admitted to tertiary academic hospitals. A retrospective analysis was conducted on patients of all ages with CRE bacteraemia admitted at any one of 12 tertiary academic hospitals in four provinces (Gauteng, KwaZulu-Natal, Western Cape and Free State) in South Africa. The study period was from July 2015 to December 2018. A case of CRE bacteraemia was defined as a patient admitted to one of the selected tertiary hospitals where any of the Enterobacteriaceae was isolated from a blood culture, and was resistant to the carbapenems (ertapenem, meropenem, imipenem and/or doripenem) or had a positive result for the Modified Hodge Test (MHT) according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. A positive blood culture result obtained after 21 days of the last blood culture result was regarded as a new case. To distinguish hospital-acquired (HA) from the community-acquired (CA) bacteraemia, the following definitions were applied: the HA CRE bacteraemia was defined as a patient with CRE isolated from blood culture ≥ 72 h of hospital admission or with any prior healthcare contact, within 1 year prior to the current episode or referral from a healthcare facility where the patient was admitted before the current hospital. A case of the CA CRE bacteraemia was defined as a patient with CRE isolated from blood culture < 72 h of hospital admission and with no prior healthcare contact. The majority of carbapenem-resistant Enterobacteriaceae (CRE) (70%) were hospital-acquired (HA) with Klebsiella pneumoniae being the predominant species (78%). In-hospital mortality rate was 38%. The commonest carbapenemase genes were bla-OXA-48 (52%) and bla-NDM (34%). The high mortality rate related to bacteraemia with CRE and the fact that most were hospital-acquired infections highlights the need to control the spread of these drug-resistant bacteria. Replacement with OXA-48 is the striking finding from this surveillance analysis. Infection control and antibiotic stewardship play important roles in decreasing the spread of resistance.

Haemoptysis secondary to a complicated hydatid cyst of the lung: A case report.

Pulmonary hydatid disease is almost exclusively caused by the infestation of the larval stage of Echinococcus granulosus. Humans are infected, accidentally, through the faeco-oral route by the ingestion of food and milk, contaminated by dog faeces containing the ova of parasites or direct contact with dogs. We describe an unusual cause of massive haemoptysis in a young male who had bilateral lung hydatid cysts as well as a large splenic hydatic cyst. He underwent bilateral thoracotomies for cyst excision for relief of haemoptysis.

Could there be any merit in lumping primary open-angle glaucoma, idiopathic intracranial hypertension and Meniere's disease into a novel and discrete category of fluid tension disorders?

Open-angle glaucoma, idiopathic intracranial hypertension, and Meniere's disease are disorders managed by different specialties in medicine viz. ophthalmology, neurology, and otorhinolaryngology respectively. By working in silos, the similarity of these disorders is overlooked. Close inspection of these disorders reveals the presence of signs and symptoms triggered by fluid under high pressure within relatively closed chambers. There is a similarity in the capillary production of fluid, which then circulates and drains into the venous system. Management practices that reduce fluid production, decrease fluid pressure or enhance fluid drainage are employed for the treatment of all three disorders. A search for a unifying mechanism explaining the pathophysiology of all three disorders may unlock effective and perhaps curative measures for these disorders.

Is the intravenous giving set a reliable alternative to the spinal manometer in measuring cerebrospinal fluid opening pressure?

BACKGROUND: Measurement of the cerebrospinal fluid (CSF) opening pressure (OP) during lumbar puncture (LP) should be routine practice. In resource-limited centres, spinal manometers are seldom available and alternative procedures to measure CSF OP are undertaken. OBJECTIVES: To investigate whether the intravenous giving set (IVGS) with a measuring tape is a reliable alternative to the spinal manometer. METHODS: One hundred patients requiring CSF examination by LP were consecutively recruited in the Department of Medicine at Edendale Hospital, Pietermaritzburg, South Africa. A three-way stopcock was attached to the end of a 22G spinal needle and the IVGS and spinal manometer were attached to the other two openings of the stopcock. CSF OP was consecutively recorded between the two techniques with 50 patients in each group. RESULTS: The mean (standard deviation (SD)) CSF OP of the 100 patients was 22.7 (10.0) cm CSF measured with the manometer v. 16.2 (9.3) cm CSF measured with the IVGS (p<0.001). Subgroup analysis showed similarly significant findings of consistently lower CSF OP with the IVGS, regardless of whether the IVGS reading was done first or second. The manometer detected 34 cases of elevated CSF OP of >25 cm CSF, but the IVGS detected 11 cases only (p<0.001, McNemar's χ2 test). Similar differences were noted for the subgroups of manometer first and IVGS first. Despite this, linear correlation showed very good correlation (r=0.78) and a 75% agreement between the two techniques. The relationship between the manometer reading and the IVGS reading was M = 0.85V + 8.9 in cm CSF, where M was the manometer reading and V the IVGS reading. CONCLUSIONS: The IVGS consistently underestimated the CSF OP against the tried-and-tested spinal manometer, which should be the preferred method of measuring CSF OP. Based on the equation that describes the relationship between the spinal manometer and IVGS reading, the upper limit of normal CSF OP of 25 cm CSF on the manometer is equivalent to 19 cm CSF on the IVGS.

Phenotypic and genotypic correlation of carbapenememase-producing Enterobacteriaceae and problems experienced in routine screening.

BACKGROUND: The emergence and transmission of carbapenem-resistant Enterobacteriaceae (CRE) is a concern in both the clinical and public health arenas. Reliable and accurate detection of these organisms is required for patient management and infection prevention and control purposes. In the routine laboratory, phenotypic methods are utilised for identification of CRE. OBJECTIVES: To investigate the phenotypic profiles of suspected carbapenemase-producing Enterobacteriaceae (CPE) isolates generated by the automated MicroScan Walkaway system making use of the Clinical and Laboratory Standards Institute (CLSI) guidelines, and correlate these with carbapenemase production by molecular methods. METHODS: Antimicrobial susceptibility testing was performed using the MicroScan Walkaway system, and the presence of six carbapenemase genes (blaNDM, blaVIM, blaIMP, blaOXA-48and variants, blaGESand blaKPC) was screened for using a multiplex real-time polymerase chain reaction. RESULTS: A total of 2 678 isolates were evaluated. Klebsiella pneumoniae accounted for 62.9% of the isolates (n=1 685), followed by Enterobacter cloacae (n=361, 13.5%). Carbapenemases accounted for 75.2% of isolates; blaOXA-48 and its variants predominated (n=978, 36.5%), followed by blaNDM (n=904, 33.8%), blaVIM (n=108, 4.0%), blaIMP (n=35, 1.3%), blaGES (n=24, 0.9%) and blaKPC (n=18, 0.7 %). CONCLUSIONS: A considerable number of isolates expressing a carbapenemase or carbapenemases (the majority of which were blaOXA-48 producing) were susceptible to third-and fourth-generation cephalosporins and carbapenems, demonstrating that confirmed carbapenemase-producing isolates are not presenting as possible carriers of carbapenemases using routine diagnostic methods. Similar results were obtained when CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints were applied and are suitable for the purpose of patient management. However, since genotyping assays are costly, it is suggested that routine laboratories first perform comprehensive phenotypic screening for CPE.

Frequency, antimicrobial susceptibility and clonal distribution of methicillin-resistant Staphylococcus pseudintermedius in canine clinical samples submitted to a veterinary diagnostic laboratory in Italy: A 3-year retrospective investigation.

In the last decade there has been a rapid global spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) clones displaying multidrug resistance in dogs. We investigated prevalence, antimicrobial susceptibility and clonal distribution of MRSP isolated from clinical canine samples between during 2011-2014. Following species identification by nuc PCR, MRSP were confirmed by the presence of mecA and characterized by antimicrobial susceptibility testing, Pulsed Field Gel Electrophoresis (PFGE), SCCmec typing, and Multi-Locus Sequence Typing (MLST) of a few isolates having distinct PFGE profiles. Both the MRSP isolation frequency in the 175 samples tested (12%) and the prevalence of methicillin resistance amongst the 63S. pseudintermedius isolates (33%) were high compared to a previous study in Italy. Sequence type (ST)71 carrying SCCmec type II-III, described as the epidemic European MRSP clone, accounted for approximately half of the isolates. The remaining isolates belonged to ST410-SCCmec type II-III, ST258-SCCmec type IV and other three clones associated with SCCmec type IV (ST261, ST290 and ST477). MRSP were consistently resistant to potentiated sulfonamides, and more frequently to clindamycin, ciprofloxacin and doxycycline than methicillin-susceptible isolates. Gentamicin was the only antibiotic showing good in vitro activity on all MRSP with 20 of the 21 isolates being susceptible. Results confirm a high prevalence of MRSP amongst clinical samples in Italy, revealing the emergence of new clones other than ST71, such as ST258, ST410, ST261, ST290 and ST477, here describe for the first time. Implementation of antimicrobial stewardship and surveillance programmes are required to prevent the emergence of new MRSP clones and reducing transmission in small animal practice.

A small proportion of community-associated methicillin-resistant Staphylococcus aureus bacteraemia, compared to healthcare-associated cases, in two South African provinces.

We compared the proportion of cases of community-associated and healthcare-associated methicillin-resistant Staphylococcus aureus (CA-MRSA and HA-MRSA, respectively) bacteraemia among patients at five hospitals in the Gauteng and Western Cape provinces in South Africa and described the molecular characteristics and antimicrobial susceptibility trends. This was a cross-sectional study using data collected by enhanced surveillance for S. aureus bacteraemia. A total of 2511 cases of S. aureus bacteraemia were identified from January 2013 to January 2016. Among 1914 cases of S. aureus, 557 (29.1%) cases were identified as MRSA infection. Forty-four cases (44/1914 [2.3%] of all S. aureus cases) were considered CA-MRSA infection and 513/1914 (26.8% of all cases) had HA-MRSA infection; the majority were neonates. CA-MRSA constituted 7.9% (44/557) of all cases of MRSA infection. Staphylococcus aureus isolates demonstrated significantly reduced susceptibility to the following classes of antimicrobial agents: macrolides, tetracyclines, aminoglycosides and cotrimoxazole, in 2015 compared to 2013 (p < 0.05). Of the 557 MRSA isolates, 484 (87%) were typed for SCCmec elements and spa types: the most common SCCmec type was type III (n = 236, 48.76%), followed by type IV (n = 144, 29.76%). The most common spa types were t037 (n = 229, 47.31%) and t1257 (n = 90, 18.60%). Of 28 isolates selected for multilocus sequence typing (MLST), the most common sequence types (STs) were ST239 and ST612 of clonal complex 8 (CC8) (n = 8 each) and a novel ST (ST4121) was obtained for one isolate. This study demonstrates that S. aureus bacteraemia is common in South African academic centres and characterised by HA-MRSA SCCmec types III and IV. A small proportion of CA-MRSA cases were caused by a few different sequence types.

Molecular detection of carbapenemase-producing genes in referral Enterobacteriaceae in South Africa: A short report.

Molecular confirmation of carbapenemase-producing Enterobacteriaceae (CPE) was introduced in South Africa (SA) at the end of 2011. We report on the detection of these resistance genes based on referral isolates. Enterobacteriaceae with non-susceptibility to any of the carbapenems according to defined criteria for antimicrobial susceptibility testing results were sent to a reference laboratory. A proportion of isolates had limited demographic, epidemiological and clinical data available. Organism identification was reconfirmed using reference laboratory methods, and the presence of carbapenemases was confirmed with a real-time polymerase chain reaction. We analysed 1 503 significant isolates received for confirmation from the National Health Laboratory Service and some private laboratories during 2012 - 2015 and confirmed one or more carbapenemase-producing genes in 68% of isolates, the most common organism being Klebsiella pneumoniae (60%). The most common carbapenemase genes were blaNDM, followed by blaOXA-48 and its variants. BlaOXA-48 and its variants demonstrated non-susceptibility to ertapenem in 89% of the isolates when analysed by the phenotypic method, and to ceftazidime in 34%. Overall, the detection rate for carbapenemases in K. pneumoniae blood isolates in the public sector was 1.9% during the 4-year period. This report indicates the presence of CPE in SA, and it is important for all healthcare workers to be aware of this major public health threat so that infection prevention and control measures can be implemented to prevent the spread of CPE in healthcare facilities.

Periodontal Biological Events Associated with Orthodontic Tooth Movement: The Biomechanics of the Cytoskeleton and the Extracellular Matrix.

The mechanical stimuli generated by orthodontic forces cause deformation of extracellular matrices and cells, vascular changes, inflammation, and the release of active biological agents generating a complex multifactorial sequence of biological events culminating in bone remodelling enabling orthodontic tooth movement. Orthodontic forces on the teeth generate stresses in periodontal tissues according to a number of variables including the type (continuous, interrupted, or intermittent), magnitude, direction, and frequency of the applied load. Whether the strain is compressive or tensile determines whether bone deposition or bone resorption will occur. The mechanically induced strains mediate structural changes in extracellular matrices and in cells, consequently affecting cellular gene expression and function. In the extracellular matrix, mechanosensing molecules integrated into the structure of various proteins can be activated upon load-induced protein unfolding. These specialized molecules have the capacity to sense and then to convert microenvironmental biomechanical stimuli into intracellular biochemical signals that interact to generate a coordinated tissue response. It is also possible that the applied force may directly cause nuclear deformation with configurational changes in chromatin, thus influencing gene expression. In this review article we summarize the current general concepts of mechanotransduction influencing the remodelling of periodontal tissues thus enabling tooth movement in response to applied orthodontic loads.

MRSA carrying mecC in captive mara.

OBJECTIVES: To characterize the staphylococcal cassette chromosome mec (SCCmec), virulence and antimicrobial susceptibility of Staphylococcus aureus ST130 isolated from mara (Dolichotis patagonum), a large rodent species native to South America and kept in captivity at Copenhagen Zoo. METHODS: The presence of mecC was confirmed by PCR in 15 S. aureus ST130 isolated from mara during a previous study. WGS was performed on two randomly selected isolates to characterize their genomes with respect to SCCmec, virulence and resistance gene content. Antimicrobial susceptibility was tested using commercial broth microdilution tests. RESULTS: All the isolates belonged to spa type t528 ST130 and carried mecC. Based on WGS, mecC was 100% identical to the prototype sequence of S. aureus strain LGA251. The sequence of SCCmec type XI in the mara isolates had 23 SNPs compared with the one described in LGA251. The two sequenced strains harboured a set of virulence factors and other genomic features previously observed in ST130. Both strains carried norA as the only putative antimicrobial resistance gene in addition to mecC. CONCLUSIONS: Our findings support the notion that a genetically conserved mecC-carrying MRSA ST130 clone is widespread in a variety of unrelated hosts in Denmark. Since the mara at Copenhagen Zoo have limited contact with humans and other animal species, it remains unclear whether mara are natural hosts of ST130 or acquired this lineage from unknown sources. The broad host range of MRSA ST130 supports its designation as a generalist lineage.

Neurological, visual, and MRI brain scan findings in 87 South African patients with HIV-associated cryptococcal meningoencephalitis.

BACKGROUND: HIV-associated cryptococcal meningoencephalitis (CM) is a leading cause of adult meningitis in sub-Saharan Africa. Neuroradiological data is however limited to case reports and small case series from developed countries and/or immunocompetent patients. METHODS: Eighty seven patients aged ≥18 hospitalized with a first episode of CM had magnetic resonance (MRI) imaging during the first two weeks of admission. A subset of eleven patients had follow-up scans approximately one month from their initial MRI scan. All had prospectively-recorded detailed neurological and visual examinations. RESULTS: An abnormal finding on neurological examination was detected in 33 (39%) patients. 38 (48%) patients experienced some visual loss. Neuroradiological lesions presumed to be cryptococcosis-related, as defined by the presence of dilated Virchow Robin spaces, pseudocysts or cryptococcomas, enhancing nodules, hydrocephalus, meningitis, focal perilesional oedema and infarcts, were detected in 55 (63%) patients. MRI findings suggestive of a second diagnosis were found in 18 (21%) patients. Visual loss was associated with the presence of cryptococcal-related lesions (p = 0.02). Blindness was associated with raised intracranial pressure (ICP) (p = 0.02). Of eleven patients with paired scans, brain swelling was identified on the initial scan in only one patient. CONCLUSION: The majority of patients had MRI brain scan abnormalities presumed secondary to CM. Dilated Virchow Robin spaces were the commonest neuroradiological lesion. Visual loss was associated with the degree of cerebral involvement as reflected by the presence of MRI abnormalities. Blindness was associated with the presence of raised ICP. Initial generalised brain swelling does not appear to be common, but further studies with paired scans are needed.

Antimicrobial susceptibility of methicillin-resistant Staphylococcus pseudintermedius isolated from veterinary clinical cases in the UK.

Staphylococcus pseudintermedius is a leading aetiologic agent of pyoderma and other body tissue infections in dogs and cats. In recent years, an increased prevalence of methicillin-resistant S. pseudintermedius (MRSP) has been reported. Isolation of MRSP in serious infections poses a major therapeutic challenge as strains are often resistant to all forms of systemic antibiotic used to treat S. pseudintermedius -related infections. This study investigates the occurrence of MRSP from a total of 7183 clinical samples submitted to the authors' laboratories over a 15-month period. Identification was based on standard microbiological identification methods, and by S. pseudintermedius-specific nuc polymerase chain reaction (PCR). Methicillin resistance was confirmed by PBP2a latex agglutination and mecA PCR. Susceptibility against non-beta-lactam antibiotics was carried out using a disc-diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, susceptibility to pradofloxacin--a new veterinary fluoroquinolone--was also investigated. SCCmec types were determined by multiplex PCR. Staphylococcus pseudintermedius was isolated from 391 (5%) samples and 20 were confirmed as MRSP from cases of pyoderma, otitis, wound infections, urinary tract infection and mastitis in dogs only. All 20 isolates were resistant to clindamycin and sulphamethoxazole/trimethoprim. Nineteen were resistant to chloramphenicol, enrofloxacin, gentamicin, marbofloxacin and pradofloxacin; additionally, seven isolates were resistant to tetracycline. Fifteen isolates carried SCCmec type II-III, four isolates had type V and one harboured type IV. To date, only a few scientific papers on clinical MRSP strains isolated from the UK have been published, thus the results from this study would provide additional baseline data for further investigations.

The relationship between periodontitis and diabetes: a brief review.

It has been reported that a close association exists between inflammatory periodontal diseases and diabetes through which one exerts a reciprocal influence on the other. This two-way relationship is based on the extensively reported assumption that the one condition so modifies the systemic and local environments that the progress of the other is favoured. On the other hand, treating and eliminating inflammatory periodontal diseases results in improved glycaemic control which minimises the microvascular complications of diabetes. This paper provides a brief review in an endeavour to create a better understanding of the interaction between these two relatively common conditions.

Oral medicine case book 51: actinic cheilitis in a patient with oculocutaneous albinism.

Patients with oculocutaneous albinism are more prone to sun-induced damage due to the lack of melanin. Actinic cheilitis is a potentially malignant disorder that occurs due to chronic UV-B radiation to the vermillion region of the lip, a region that is already at risk due to its morphology. A case of actinic cheilitis in a patient with oculocutaneous albinism is presented with a literature review.