Human cystic echinococcosis in South Africa

Cystic echinococcosis (CE) is caused by the tapeworm, Echinococcus granulosus. The tapeworms resides in the small intestines of canids and the lifecycle involves both intermediate and definitive hosts. Humans are accidental intermediate hosts. Cystic echinococcosis is an economically important infection constituting a threat to public health, and is considered an emerging disease around the world. There are at least 10 Echinococcus strain types (G1 – G10), each exhibiting diversity of morphology, development and host range. The epidemiology of CE is poorly understood in South Africa. A retrospective data analysis of the National Health Laboratory Service (NHLS) laboratory information system on echinococcosis serology, microscopy and histopathology results in eight provinces (excluding KwaZula-Natal) showed an overall positivity rate in submitted diagnostic samples of 17.0% (1056/6211), with the Eastern Cape (30.4%), North West (19.0%) and Northern Cape (18.0%) provinces showing highest rates. The data showed considerable variability between provinces. The review also showed that most proven cases were negative on serology, implying that the actual number of patients could be underestimated. To our knowledge, no data exist about the prevalent strains of E. granulosus and this prospective study will attempt to fill that gap. The aim is to genotype strains causing the disease in South Africa. Two different polymerase chain reaction (PCR) methods will be used to respectively target the 12S rRNA and nad 1 genes. To date, three samples have been genotyped as G1, G5 and G6; suggesting diversity of strains prevalent in the country, but more data is needed for a clearer picture

Factors influencing specialist care referral of multidrug- and extensively drug-resistant tuberculosis patients in Gauteng/South Africa : a descriptive questionnaire-based study

BACKGROUND: Sizwe Tropical Diseases Hospital is the only specialized hospital for the management of multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB cases in Gauteng Province. In South Africa, there is a mismatch between numbers of individuals with a laboratory diagnosis of drug-resistant tuberculosis (TB) and those being referred for the initiation of specialist treatment. We determined reasons for non-referral of MDR-TB and XDR-TB cases. METHODS: We conducted a descriptive questionnaire-based study amongst provincial primary health care facilities (PHC) and hospitals providing routine care for (drug-susceptible) TB, regarding specialist care referral of patients whose TB culture and susceptibility testing confirmed MDR-TB or XDR-TB diagnoses in the first half of 2008. RESULTS: In total 148 cases were analyzed; 144/148 (97%) had MDR-TB and 4/148 (3%) had XDR-TB. The main reason for non-referral to specialist care was loss to follow up, for patients diagnosed in-hospital (74/97; 76%) as well as in PHCs (11/21; 52%). Nineteen per cent (18/97) of patients diagnosed in hospital versus 33% (7/21) of patients diagnosed in PHCs deceased before referral. CONCLUSIONS: A significant problem in the fight to control DR-TB is follow-up after diagnosis with a delay in patient tracing. TB Focal Points in hospital need to be strengthened in order to improve on patient follow-up and care, and tracer teams should assist with community follow up.http://www.biomedcentral.com/1472-6963/13/268am2014ai201

Bioprospection of Natural Sources of Polyphenols with Therapeutic Potential for Redox-Related Diseases

Funding: iNOVA4Health-UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. This work was supported by Fundação para a Ciência e Tecnologia (IF/01097/2013 to C.N.S.), by The Scottish Government Rural and Environment Science and Analytical Services Division (A.F. and D.S.), and BacHBerry FP7-KBBE-2013-613793 (R.M., A.F., C.J., I.C., G.G., R.R.-R., J.P., A.M., C.D., D.S. and C.N.S.). T.F.O. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), and is currently supported by the DFG under Germany’s Excellence Strategy—EXC 2067/1-390729940.Plants are a reservoir of high-value molecules with underexplored biomedical applications. With the aim of identifying novel health-promoting attributes in underexplored natural sources, we scrutinized the diversity of (poly)phenols present within the berries of selected germplasm from cultivated, wild, and underutilized Rubus species. Our strategy combined the application of metabolomics, statistical analysis, and evaluation of (poly)phenols' bioactivity using a yeast-based discovery platform. We identified species as sources of (poly)phenols interfering with pathological processes associated with redox-related diseases, particularly, amyotrophic lateral sclerosis, cancer, and inflammation. In silico prediction of putative bioactives suggested cyanidin-hexoside as an anti-inflammatory molecule which was validated in yeast and mammalian cells. Moreover, cellular assays revealed that the cyanidin moiety was responsible for the anti-inflammatory properties of cyanidin-hexoside. Our findings unveiled novel (poly)phenolic bioactivities and illustrated the power of our integrative approach for the identification of dietary (poly)phenols with potential biomedical applications.publishersversionpublishe

A longitudinal study of stavudine-associated toxicities in a large cohort of South African HIV infected subjects

<p>Abstract</p> <p>Background</p> <p>There has been major improvement in the survival of HIV-1 infected individuals since the South African Government introduced highly active anti-retroviral therapy (HAART) in the public sector in 2004. This has brought new challenges which include the effects of stavudine-related toxicities.</p> <p>Methods</p> <p>Prospective analysis of a cohort of 9040 HIV-infected adults who were initiated on HAART at the Themba Lethu Clinic (TLC) in Johannesburg between April 1, 2004 to December 31, 2007, and followed up until June 30, 2008.</p> <p>Results</p> <p>Amongst the 9040 study subjects, 8497(94%) were on stavudine based therapy and 5962 (66%) were women. The median baseline CD4 count was 81 cells/mm³(IQR 29-149). Median follow up on HAART was 19 months (IQR: 9.1-31.6). The proportion of HAART-related side effects for stavudine compared to non-stavudine containing regimens were, respectively: peripheral neuropathy,17.1% vs. 11.2% (p < 0.001); symptomatic hyperlactataemia, 5.7% vs. 2.2% (p < 0.0005); lactic acidosis, 2.5 vs. 1.3% (p = 0.072); lipoatrophy, 7.3% vs. 4.6% (p < 0.05). Among those on stavudine-based regimens, incidence rates for peripheral neuropathy were 12.1 cases/100 person-years (95%CI 7.0-19.5), symptomatic hyperlactataemia 3.6 cases/100 person-years (95%CI 1.2-7.5), lactic acidosis 1.6 cases/100 person-years (95%CI 0.4-5.2) and lipoatrophy 4.6 cases/100 person-years (95%CI 2.1-9.6). Females experienced more toxicity when compared to males in terms of symptomatic hyperlactataemia (p < 0.0001), lactic acidosis (p < 0.0001), lipoatrophy (p < 0.0001) and hypertension (p < 0.05).</p> <p>Conclusions</p> <p>We demonstrate significant morbidity associated with stavudine. These data support the latest WHO guidelines, and provide additional evidence for other resource limited HAART rollout programs considering the implementation of non-stavudine based regimens as first line therapy.</p

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study

SummaryBackgroundData from Kwazulu Natal, South Africa, suggest that almost all patients with extensively drug-resistant (XDR) tuberculosis are HIV-positive, with a fatal outcome. Since, there are few data for the treatment-related outcomes of XDR tuberculosis in settings with a high HIV prevalence, we investigated the associations of these diseases in such settings to formulate recommendations for control programmes.MethodsIn a retrospective cohort study, we analysed the case records of patients (>16 years old) with XDR tuberculosis (culture-proven at diagnosis) between August, 2002, and February, 2008, at four designated provincial treatment facilities in South Africa. We used Cox proportional hazards regression models to assess risk factors associated with the outcomes—mortality and culture conversion.Findings195 of 227 patients were analysed. 21 died before initiation of any treatment, and 174 patients (82 with HIV infection) were treated. 62 (36%) of these patients died during follow-up. The number of deaths was not significantly different in patients with or without HIV infection: 34 (41%) of 82 versus 28 (30%) of 92 (p=0·13). Treatment with moxifloxacin (hazard ratio 0·11, 95% CI 0·01–0·82; p=0·03), previous culture-proven multidrug-resistant tuberculosis (5·21, 1·93–14·1; p=0·001), and number of drugs used in a regimen (0·59, 0·45–0·78, p<0·0001) were independent predictors of death. Fewer deaths occurred in patients with HIV infection given highly active antiretroviral therapy than in those who were not (0·38, 0·18–0·80; p=0·01). 33 (19%) of 174 patients showed culture conversion, of which 23 (70%) converted within 6 months of initiation of treatment.InterpretationIn South Africa, patients with XDR tuberculosis, a substantial proportion of whom are not infected with HIV, have poor management outcomes. Nevertheless, survival in patients with HIV infection is better than previously reported. The priorities for the country are still prevention of XDR tuberculosis, and early detection and management of multidrug-resistant and XDR tuberculosis through strengthened programmes and laboratory capacity.FundingSouth African Medical Research Council, European Union Framework 7 program, and European Developing Countries Clinical Trials Partnership