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Introduction: Antimicrobial resistant bacterial infections are widespread globally and increases in antimicrobial resistance presents a major threat to public health. Pseudomonas aeruginosa is an opportunistic healthcare-associated pathogen with high rates of morbidity and mortality and an extensive range of resistance mechanisms. This study describes the antibiotic susceptibility profiles of P. aeruginosa isolates from patients with bacteraemia submitted by sentinel laboratories in South Africa from 2014 to 2015. Methodology: Organism identification and antimicrobial susceptibility testing were done using automated systems. Molecular methods were used to detect common resistance genes and mechanisms. Methodology: Organism identification and antimicrobial susceptibility testing were done using automated systems. Molecular methods were used to detect common resistance genes and mechanisms. Results: Overall the susceptibility was high for all antibiotics tested with a decrease over the two-year period. There was no change in the MIC50 and MIC90 breakpoints for all antibiotics from 2014 to 2015. The MIC50 was within the susceptible breakpoint range for most antibiotics and the MIC90 was within the susceptible breakpoint range for colistin only. Phenotypically carbapenem non-susceptible isolates harboured the following plasmid-mediated genes: blaVIM (n = 81, 12%) and blaGES (n = 6, 0.9%); blaNDM (n = 4, 0.6%) and blaOXA-48 and variants (n = 3, 0.45%). Porin deletions were observed in one meropenem non-susceptible isolate only, and multi-drug resistance efflux pumps were expressed in the majority of the non-susceptible isolates investigated. BlaVEB-1, blaIMP and blaKPC were not detected. Conclusion: The prevalence of resistance to commonly used antibacterial agents was low for P. aeruginosa isolates and similarly, tested resistance mechanisms were detected in a relatively small proportion of isolates. Findings in this study represent baseline information for understanding antimicrobial susceptibility patterns in P. aeruginosa isolates from blood. Our surveillance report may assist in contributing to hospital treatment guidelines. [ABSTRACT FROM AUTHOR]

The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. [ABSTRACT FROM AUTHOR]

Summary: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed. [Copyright &y& Elsevier]

This study evaluated the performance of the Xpert Carba-R assay for detecting the five common carbapenemases in carbapenemase-producing organisms in Johannesburg, South Africa between April 2021 and September 2021. The assay demonstrated 98% sensitivity and 97% specificity. It was also able to detect all the carbapenemases in double carbapenemase producers, as well as carbapenemases in non-fermenter organisms. The Xpert Carba-R assay, therefore, allows the rapid (< 1 h) and accurate identification of the common carbapenemases in pure bacterial cultures and rectal swabs. This assay can aid in the timeous institution of appropriate treatment and infection prevention and control measures. [ABSTRACT FROM AUTHOR]

Background: Correctional centres provide ideal conditions for tuberculosis (TB) transmission and disease progression. Despite the high TB incidence and incarceration rate in South Africa, data from South African correctional centres are scarce. Thus, the study evaluated TB diagnosis, treatment initiation and completion, and identified prevalent Mycobacterium tuberculosis strains among detainees entering a South African correctional centre. Methods: This study was a prospective observational study that enrolled participants between February and September 2017 from a correctional centre located in the Western Cape, South Africa. All adult male detainees who tested positive for TB during admission screening were eligible to participate in the study. Sputum samples from enrolled participants underwent smear microscopy and culture. Strain typing was performed on culture-positive samples. The time between specimen collection and diagnosis, the time between diagnosis and treatment initiation, and the proportion of detainees completing TB treatment at the correctional centre were calculated. Results: During the study period, 130 TB cases were detected through routine admission screening (126 male, 2 female, 2 juvenile). Out of the 126 eligible male detainees, 102 were enrolled in the study (81%, 102/126). All TB cases were detected within 30 hrs of admission screening. The majority (78%, 80/102) of participants started treatment within 48 hrs of TB diagnosis. However, only 8% (9/102) of participants completed treatment at the correction centre. Sputa from 90 of the 102 participants were available for smear and culture. There was a high smear positivity, with 49% (44/90) of isolates being smear positive. The Beijing family was the most frequent lineage (55.2%) in the study. Conclusion: The strengths of the current TB control efforts at the correctional centre include rapid detection of cases through admission screening and prompt treatment initiation. However, a high number of detainees exiting before treatment completion highlights the need to strengthen links between correctional TB services and community TB services to ensure detainees complete TB treatment after release and prevent TB transmission. [ABSTRACT FROM AUTHOR]

Background: In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings: We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions: Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation. Author Summary: Viral hemorrhagic fever is a syndrome often associated with high fatality and risk of secondary transmission. In 2008, an outbreak of a novel hemorrhagic fever virus called Lujo occurred in Johannesburg, South Africa, with secondary transmission from the index patient to four healthcare workers. Four of the five patients died. Lujo belongs to the arenavirus family and is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because most viral hemorrhagic fevers occur in remote, resource-poor settings, few in-depth controlled studies of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options are possible. We describe the clinical features of the five cases in this outbreak and summarize the clinical management, as well as providing additional epidemiologic detail. Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. The treatment options used in these five cases are discussed as well as the recommended precautions to prevent secondary transmission. [ABSTRACT FROM AUTHOR]

Background: In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. Methods and Findings: We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Conclusions: Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation. [ABSTRACT FROM AUTHOR]

Background: The 2017–2018 listeriosis outbreak in South Africa warranted testing for Listeria monocytogenes in food products and processing environments. Diagnostic tests are needed to accurately differentiate L. monocytogenes from other Listeria species. Objective: The study assessed the performance of the commonly used tests in our setting to accurately identify L. monocytogenes. Methods: The study was conducted in a public health laboratory in South Africa. Cultured isolates from food and environmental samples were tested both prospectively and retrospectively between August 2018 and December 2018. Isolates were phenotypically identified using tests for detecting β-haemolysis, Christie-Atkins-Munch-Peterson, alanine arylamidase (AlaA), mannosidase, and xylose fermentation. Listeria monocytogenes isolates were identified using automated systems, Microscan Walkaway Plus 96, Vitek® MS, Vitek® 2 and Surefast Listeria monocytogenes PLUS PCR. All results were compared to whole-genome sequencing results. Results: β-haemolysis and Christie-Atkins-Munch-Peterson tests gave delayed positivity or were negative for L. monocytogenes and falsely positive for one strain of Listeria innocua. The AlaA enzyme and Colorex Listeria agar lacked specificity for L. monocytogenes identification. Based on a few phenotypic test results, an aberrant L. monocytogenes strain and Listeria seeligeri strain were reported. All automated platforms overcalled L. monocytogenes in place of other Listeria species. Conclusion: No test was ideal in differentiating Listeria species. This is an issue in resource-limited settings where these tests are currently used. Newer technologies based on enzyme-linked immunosorbent assay and other molecular techniques specific to L. monocytogenes detection need to be investigated. [ABSTRACT FROM AUTHOR]

The Global Action Plan on antimicrobial resistance calls for the use of antimicrobial medicines in human and animal health to be optimized, in tandem with a strengthening of the knowledge and evidence base through surveillance and research. However, there is a paucity of consumption data for African countries such as South Africa. Determining antimicrobial consumption data in low-resource settings remains a challenge. This article describes alternative mechanisms of assessing antimicrobial consumption data, such as the use of Intercontinental Marketing Services (IMS) data and contract data arising from tenders (an open Request for Proposal, RFP), as opposed to the international norms of daily defined doses per 100 patient-days or per 1000 population. Despite their limitations, these serve as indicators of antimicrobial exposure at the population level and represent an alternative method for ascertaining antimicrobial consumption in human health. Furthermore, South Africa has the largest antiretroviral treatment programme globally and carries a high burden of tuberculosis. This prompted the inclusion of antiretroviral and anti-tuberculosis antibiotic consumption data. Knowledge of antimicrobial utilization is imperative for meaningful future interventions. Baseline antimicrobial utilization data could guide future research initiatives that could provide a better understanding of the different measures of antibiotic use and the level of antibiotic resistance. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the availability of drugs for communicable diseases.

Introduction: We aimed to obtain an in-depth understanding on recent antimicrobial resistance trends and molecular epidemiology trends of S. aureus bacteraemia (SAB). Methods: Thirteen academic centres in South Africa were included from June 2010 until July 2012. S. aureus susceptibility testing was performed on the MicroScan Walkaway. Real-time PCR using the LightCycler 480 II was done for mecA and nuc. SCCmec and spa-typing were finalized with conventional PCR. We selected one isolate per common spa type per province for multilocus sequence typing (MLST). Results: S. aureus from 2709 patients were included, and 1231 (46%) were resistant to methicillin, with a significant decline over the three-year period (p-value = 0.003). Geographical distribution of MRSA was significantly higher in Gauteng compared to the other provinces (P<0.001). Children <5 years were significantly associated with MRSA with higher rates compared to all other age groups (P = 0.01). The most prevalent SCCmec type was SCCmec type III (531 [41%]) followed by type IV (402 [31%]). Spa-typing discovered 47 different spa-types. The five (87%) most common spa-types were t037, t1257, t045, t064 and t012. Based on MLST, the commonest was ST612 clonal complex (CC8) (n = 7) followed by ST5 (CC5) (n = 4), ST36 (CC30) (n = 4) and ST239 (CC8) (n = 3). Conclusions: MRSA rate is high in South Africa. Majority of the isolates were classified as SCCmec type III (41%) and type IV (31%), which are typically associated with hospital and community- acquired infections, respectively. Overall, this study reveals the presence of a variety of hospital-acquired MRSA clones in South Africa dominance of few clones, spa 037 and 1257. Monitoring trends in resistance and molecular typing is recommended to detect changing epidemiological trends in AMR patterns of SAB. [ABSTRACT FROM AUTHOR]

Mycobacterium kansasii (M. kansasii) is a major cause of non-tuberculous mycobacterial pulmonary disease in the South African gold-mining workforce, but the source of infection and molecular epidemiology are unknown. This study investigated the presence of M. kansasii in gold and coal mine and associated hostel water supplies and compared the genetic diversity of clinical and environmental isolates of M. kansasii. Five M. kansasii and ten other potentially pathogenic mycobacteria were cultured mainly from showerhead biofilms. Polymerase chain reaction-restriction analysis of the hsp65 gene on 196 clinical and environmental M. kansasii isolates revealed 160 subtype I, eight subtype II and six subtype IV strains. Twenty-two isolates did not show the typical M. kansasii restriction patterns, suggesting that these isolates may represent new subtypes of M. kansasii. In contrast to the clonal population structure found amongst the subtype I isolates from studies in other countries, DNA fingerprinting of 114 clinical and three environmental subtype I isolates demonstrated genetic diversity amongst the isolates. This study demonstrated that showerheads are possible sources of M. kansasii and other pathogenic non-tuberculous mycobacterial infection in a gold-mining region, that subtype I is the major clinical isolate of M. kansasii strain and that this subtype exhibits genetic diversity. [ABSTRACT FROM AUTHOR]

Abstract: Background: 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. Objectives: 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. Study design: 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. Results: 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. Conclusions: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

A nosocomial outbreak of disease involving 5 patients, 4 of whom died, occurred in South Africa during September-October 2008. The first patient had been transferred from Zambia to South Africa for medical management. Three cases involved secondary spread of infection from the first patient, and 1 was a tertiary infection. A novel arenavirus was identified. The source of the first patient's infection remains undetermined. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Summary: The global problem of antimicrobial resistance is particularly pressing in developing countries, where the infectious disease burden is high and cost constraints prevent the widespread application of newer, more expensive agents. Gastrointestinal, respiratory, sexually transmitted, and nosocomial infections are leading causes of disease and death in the developing world, and management of all these conditions has been critically compromised by the appearance and rapid spread of resistance. In this first part of the review, we have summarised the present state of resistance in these infections from the available data. Even though surveillance of resistance in many developing countries is suboptimal, the general picture is one of accelerating rates of resistance spurred by antimicrobial misuse and shortfalls in infection control and public health. Reservoirs for resistance may be present in healthy human and animal populations. Considerable economic and health burdens emanate from bacterial resistance, and research is needed to accurately quantify the problem and propose and evaluate practicable solutions. In part II, to be published next month, we will review potential containment strategies that could address this burgeoning problem. [Copyright &y& Elsevier]

• Despite advanced diagnostic approaches for Mtb, sub-Saharan Africa with high HIV and TB co-infections continues to suffer. • Epigenetic mechanisms can be used in such co-infections to bypass host's immune responses. • Epigenetic modifications in the expression profile of different genes in MDR TB-HIV co-infection patients was studied. • Modulation in gene expression can be used for diagnostic, drug and vaccine development in MDR TB-HIV co-infection patients. Background: Mycobacterium tuberculosis (Mtb) is an airborne pathogenic microorganism that causes tuberculosis (TB). This pathogen invades lung tissues causing pulmonary infections and disseminates into other host organs. The Bacillus Calmette-Guérin (BCG) vaccine is employed to provide immune protection against TB; however, its efficacy is dependent on the age, immune status and geographic location of vaccinated individuals. Advanced diagnostic approaches such as GeneXpert MTB/RIF® and line probe assays (LPAs) have allowed rapid detection of drug-resistant, multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains. However, in sub-Saharan Africa, public and private health institutions are further burdened by the high prevalence of Human Immunodeficiency Virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) and TB co-infections across different age groups. Epigenetic mechanisms have been widely exploited by Mtb and HIV to bypass the host's innate and adaptive immune responses, leading to microbial proliferation and disease manifestation. In the current study, we investigated the impact of epigenetic mechanisms in regulating target gene expression in healthy and patients co-infected with MDR TB-HIV. [ABSTRACT FROM AUTHOR]

The article discusses declaration of African government regarding availability of insulin to every resident of Africa so as to reduce the risk of diabetes causing. Topics discussed include need of availability of insulin to people who cannot afford it; availability of medical supplies; and monitoring of patients.

The article discusses diagnosis of diabetic foot complications caused due to diabetes that may lead to preventable loss of limbs and lives. Topics discussed include implementation of evidence informed interprofessional diabetic foot care; prevention of diabetic foot complications by availability of pressure offloading devices; and need for early treatment of surface critical colonization.