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Multidrug-resistant tuberculosis (MDR-TB) is associated with lengthy treatment, expensive and potentially toxic regimens, and high rates of treatment failure and death. This study describes the outcomes of 351 MDR-TB patients who started treatment between 2004 and 2007 at the provincial MDR-TB referral hospital in Johannesburg, South Africa, and investigates risk factors associated with death. The study involved the assessment of factors associated with treatment outcomes using a retrospective review of patient records, drug-susceptibility data and spoligotyping of isolates. Treatment success (completion/cure) was recorded in 158 (48.8 %) patients, while 65 (20 %) died, 93 (28.7 %) defaulted, 8 (2.5 %) failed treatment, 11(3.1 %) were transferred out to other health facilities and 16 (4.6 %) had no recorded final outcome. The proportion of successful treatment increased significantly over time. Univariable and multivariable analysis (P = 0.05) identified the year of MDR-TB diagnosis and spoligotype-defined families as factors associated with treatment outcome. No associations were found between treatment outcome and human immunodeficiency virus (HIV) status, previous TB and additional MDR resistance to streptomycin or ethambutol. Molecular typing of the strains revealed a diverse group of spoligotypes, with Beijing, LAM4 and H3 making up the largest groups. This is the first published study to investigate treatment outcomes at this facility and to find a link between genotype and treatment outcome, suggesting that genotype determination could potentially serve as a prognostic factor

Rift Valley fever (RVF) is an emerging arthropod-borne zoonoses of global agricultural and public health importance. In December 2006, an RVF outbreak was recognized in Kenya which led to the deployment of international response laboratory teams to the area.A field laboratory was operated in Malindi, Kenya to provide safe sample handling and molecular testing for RVF virus (RVFV) as well as selected other pathogens for differential diagnosis.Safe sample handling was carried out using a negative pressure flexible film isolator (glovebox) and commercial reagents to inactivate clinical specimens and purify nucleic acid. Whole blood was routinely used for diagnostic testing although paired plasma samples were also tested in select cases. Subsequently, human macrophages were tested in vitro for their susceptibility to RVFV.The field laboratory received samples from 33 individuals and a definite laboratory diagnosis was provided in 16 of these cases. Using molecular diagnostic techniques, RVFV was more consistently detected in whole blood than in plasma samples most likely due to association of RVFV with blood cells. Subsequent in vitro studies identified macrophages as a target cell for RVFV replication.RVFV appears to replicate in blood cells such as macrophages. Thus, the sensitivity of molecular diagnostic testing is improved if whole blood is used as the clinical specimen rather than plasma or serum.

Background A pivotal phase III study of the RTS,S/AS01 malaria candidate vaccine is ongoing in several research centres across Africa. The development and establishment of quality systems was a requirement for trial conduct to meet international regulatory standards, as well as providing an important capacity strengthening opportunity for study centres. Methods Standardized laboratory methods and quality assurance processes were implemented at each of the study centres, facilitated by funding partners. Results A robust protocol for determination of parasite density based on actual blood cell counts was set up in accordance with World Health Organization recommendations. Automated equipment including haematology and biochemistry analyzers were put in place with standard methods for bedside testing of glycaemia, base excess and lactacidaemia. Facilities for X-rays and basic microbiology testing were also provided or upgraded alongside health care infrastructure in some centres. External quality assurance assessment of all major laboratory methods was established and method qualification by each laboratory demonstrated. The resulting capacity strengthening has ensured laboratory evaluations are conducted locally to the high standards required in clinical trials. Conclusion Major efforts by study centres, together with support from collaborating parties, have allowed standardized methods and robust quality assurance processes to be put in place for the phase III evaluation of the RTS, S/AS01 malaria candidate vaccine. Extensive training programmes, coupled with continuous commitment from research centre staff, have been the key elements behind the successful implementation of quality processes. It is expected these activities will culminate in healthcare benefits for the subjects and communities participating in these trials. Trial registration Clinicaltrials.gov NCT00866619

Eighty-two percent of 320 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates from various infection sites collected throughout South Africa were separated into five major globally prevalent clusters by SmaI pulsed-field gel electrophoresis, spa , and SCC mec typing. Only one Panton-Valentine leukocidin-positive isolate was detected. This is the first detailed MRSA epidemiology study for the whole country.

Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata . We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50–100% S), AME (48–86.9%), EU (44.8–88%), LA (43–92%), and NA (74.5–91.6%). Voriconazole was more active than fluconazole (range, 82.3–84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata ), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata . Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.

An outbreak of Enterobacter cloacae in the neonatal intensive care unit of a provincial hospital in Gauteng, South Africa, resulting in nine deaths was investigated. Macrorestriction analysis using pulsed-field gel electrophoresis revealed that three isolates of E. cloacae from blood cultures of patients, six from environmental sources, and one from the hands of a staff member belonged to the same genotypic cluster.

To write a guideline for the management and prevention of nosocomial infections in South Africa in view of the following: Nosocomial infections are a common and increasing problem globally, including South Africa. Widely varying standards of prevention and management of these important infections. Increasing and emerging antimicrobial resistance among commonly isolated pathogens. The significant economic burden of these infections on the health care system as well as their impact on patient morbidity and mortality. The main aims of the guideline are to provide recommendations for the initial choice of antimicrobial agents and the appropriate management of these infections encompassing the following conditions: (i) nosocomial pneumonia, health care-associated pneumonia and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections; (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract infections; (v) nosocomial intra-abdominal infections; and (vi) nosocomial surgical skin and soft-tissue infections.Working group of clinicians from relevant disciplines, following detailed literature review.These include details of the likely pathogens, an appropriate diagnostic approach, antibiotic treatment options and appropriate preventive strategies.The guideline document was endorsed by the South African Thoracic Society, the Critical Care Society of Southern Africa and the Federation of Infectious Diseases Societies of Southern Africa.

Summary The growing threat from resistant organisms calls for concerted action to prevent the emergence of new resistant strains and the spread of existing ones. Developing countries have experienced unfavourable trends in resistance—as detailed in part I, published last month—and implementation of many of the containment strategies recommended by WHO is complicated by universal, as well as developing country-specific, factors. The control of selective pressure for resistance could potentially be addressed through educational and other interventions for orthodox and unorthodox prescribers, distributors, and consumers of antimicrobials. At national levels, the implementation of drug use strategies—eg, combination therapy or cycling—may prove useful to lengthen the lifespan of existing and future agents. Programmes such as the Integrated Management of Childhood Illnesses (IMCI) and directly observed short-course therapy (DOTS) for tuberculosis are prescriber-focused and patient-focused, respectively, and have both been shown to positively influence factors that contribute to the selective pressure that affects resistance. The institution of interventions to prevent the transmission of infectious diseases could also lead to beneficial effects on the prevalence of resistance, as has vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae . There has been an upsurge in the number of organisations and programmes that directly address issues of resistance, and collaboration could be one way to stem the dire trend. Additional factors such as unregulated drug availability, inadequate antimicrobial drug quality assurance, inadequate surveillance, and cultures of antimicrobial abuse must be addressed to permit a holistic strategy for resistance control.

Background Acinetobacter species infections are increasingly found to cause nosocomial infections, particularly in intensive care units. These pathogens are difficult to eliminate from the hospital environment, and the emergence of multiple-drug-resistant strains complicates patient treatment. In this retrospective study, several strains were analyzed to study the possible spread of pan-resistant strains. Methods Macrorestriction analysis was performed on isolates collected in July 2001 from Johannesburg Hospital and strains collected from a number of hospitals in Johannesburg a year later. Results A strain endemic to Johannesburg Hospital that was cefepime and ceftazidime sensitive in 2001 developed resistance to these antibiotics within 1 year. This and other resistant strains were found to have spread among academic and private hospitals in the area by July 2002. Conclusions The development of resistance is believed to be a response to antibiotic pressure and the spread of resistant strains a result of health care worker and/or patient transfer among hospitals. This snapshot epidemiologic study highlights the need to institute stricter infection control measures to limit the spread of organisms such as Acinetobacter among hospitals.

An outbreak of vancomycin-resistant enterococci (VRE) occurred in an adult oncology ward of a large teaching hospital in Johannesburg, South Africa. The outbreak strain was identified as an Enterococcus faecium carrying the vanA resistance genotype. Macro-restriction analysis showed that the majority of strains were clonally related. Modified infection control interventions were implemented and control of the outbreak was achieved. Although the epidemiology of VRE is well documented in Europe, North America and Australia, this problem has only recently emerged in South Africa. The epidemiology of the outbreak appears similar to that described for outbreaks elsewhere.

To describe the clinical manifestations of viral hemorrhagic fever, and to increase clinicians' awareness and knowledge of these illnesses.Retrospective study of the clinical and laboratory data and management of two cases of Ebola virus infection with key epidemiologic data provided.Two tertiary care hospitals.Two adult patients, the index case and the source patient, both identified as having Ebola, one of whom originated in Gabon.One patient was admitted to the intensive care unit. The other was managed in a general ward.Clinical and laboratory data are reported. One patient, a healthcare worker who contracted this illness in the course of her work, died of refractory thrombocytopenia and an intracerebral bleed. The source patient survived. Despite a long period during which the diagnosis was obscure, none of the other 300 contacts contracted the illness.Identification of high-risk patients and use of universal blood and body fluid precautions will considerably decrease the risk of nosocomial spread of viral hemorrhagic fevers.

The use of generic pharmaceutical agents is entrenched in South Africa, with resource limitation being the primary motivation. The clinical efficacy, in vivo performance and subsequently the role of generic antimicrobial formulations in treating serious bacterial infections, is much debated. 1 We evaluated the in vitro microbiological efficacy of a generic ceftriaxone product against several clinically significant organisms collected from sterile sites. The minimum inhibitory concentration (MIC) of each was determined simultaneously with the reference and the generic ceftriaxone product. Comparative analysis of MICs between the two products for each isolate was performed using both categorical (interpretive) agreement and essential (actual MIC value) agreement. A total of 260 isolates were tested. Overall, there was categorical agreement of 98.9% and essential agreement of 95.8%. The categorical agreement for all isolates (96.7 - 100%) accorded with international standards, as no very major errors were seen and the major error rate was less than 3%. Of the 90 isolates of E. coli (40), Klebsiella spp. (40) and Salmonella spp. (10), 87.6% had an MIC less than or equal to 0.12 mg/l. The generic ceftriaxone product showed equivalent efficacy by MIC determination to the reference formulation. Ceftriaxone remains a viable and useful antimicrobial agent against a variety of clinically relevant organisms in our setting.

This congress edition of the journal is a bumper issue and is particularly exciting for a number of reasons. This edition appears in association with the first combined congress of the various infectious disease societies of South Africa and with the impending launch of FIDSSA, the Federation of the Infectious Diseases Societies of South Africa.