Hybrid positron emission tomography–magnetic resonance of the heart:current state of the art and future applications

Hybrid Positron Emission Tomography-Magnetic Resonance (PET-MR) imaging is a novel imaging modality with emerging applications for cardiovascular disease. PET-MR aims to combine the high spatial resolution morphological and functional assessment afforded by MRI with the ability of PET for quantification of metabolism, perfusion and inflammation. The fusion of these two modalities into a single imaging platform not only represents an opportunity to acquire complementary information from a single scan, but also allows motion correction for PET with reduction in ionising radiation. This article presents a brief overview of PET-MR technology followed by a review of the published literature on the clinical cardio-vascular applications of PET and MRI performed separately and with hybrid PET-MR

Comparison of the VersaTREK blood culture system against the Bactec9240 system in patients with suspected bloodstream infections

BACKGROUND: To evaluate the VersaTREK (TREK Diagnostic Systems, Cleveland, Ohio) blood culture system against the Bactec9240 (BD Microbiology, Cockeysville, MD), for the recovery of bloodstream pathogens. METHODS: Venous blood from patients with suspected bacterial sepsis was evenly distributed into bottles of each system. Positive signals were recorded and bottles processed onto standard media for organism recovery. False positive signals were regarded if no organisms were seen on Gram stain and no growth was observed. RESULTS: 177 bottles were available for analysis; the Bactec9240 system yielded 43 positive, 134 negative results and no false positive signals. The VersaTREK system had 58 positive signals with 14 being false positives. CONCLUSIONS: In our setting with high background burden of immuno-compromised patients, the VersaTREK system compared favourably with the Bactec9240 in recovering blood stream aerobic and facultative anaerobic pathogens from patients with suspected bacterial sepsis. A concern is the high false positivity rate. Due to its versatility to accommodate small and large workloads as well as using smaller volumes of blood, this system may establish itself as a useful alternative for the recovery of bloodstream pathogens

The Centre for Tuberculosis : from reference laboratory to public health institution

Tuberculosis (TB) continues to be one of the biggest public health challenges of our time, and as epidemiology of the disease evolves in an era of high HIV prevalence in South Africa, so must the response. With exciting developments in diagnostics, treatment options and vaccine candidates at various stages of development, South Africa needs a centre that can synthesise all these options and advise government on preventing TB transmission and caring for those infected. The new Centre for Tuberculosis (CTB) of the National Institute for Communicable Diseases (NICD) is well placed to provide this service for the South African government and people.http://www.sajei.co.za/index.php/SAJE

Whole genome sequencing for drug resistance determination in Mycobacterium tuberculosis

South Africa remains challenged with a high tuberculosis burden accompanied by an increase in drug resistant cases. We assessed the use of the Illumina MiSeq, a next-generation sequencing platform for whole genome sequencing, followed by bioinformatic analysis using a commercial software package to determine resistance to selected drugs used for Mycobacterium tuberculosis treatment in our setting. Whole genome sequencing shows potential as a diagnostic platform for the detection of drug resistance in Mycobacterium tuberculosis with the provision of information for several drugs simultaneously

Nationwide and regional incidence of microbiologically confirmed pulmonary tuberculosis in South Africa, 2004-12 : a time series analysis

BACKGROUND : South Africa has the highest incidence of tuberculosis in the world, largely resulting from a high population prevalence of HIV infection. We investigated the incidence of microbiologically confirmed pulmonary tuberculosis, and new cases of pulmonary tuberculosis registered for treatment, nationally and provincially in South Africa from 2004 to 2012, during which time there were changes in antiretroviral therapy (ART) coverage among individuals with HIV infection. METHODS : We identifi ed cases of microbiologically confi rmed pulmonary tuberculosis from 2004 to 2012 from the National Health Laboratory Service Corporate Data Warehouse. New cases registered for treatment were identifi ed from National Department of Health electronic registries. A time series analysis, using autoregressive models, was undertaken on incidence of microbiologically confi rmed pulmonary disease nationally and provincially; this trend was also examined relative to ART coverage of adults with HIV infection. FINDINGS : During the 9-year period, 3 523 371 cases of microbiologically confirmed pulmonary tuberculosis were recorded nationally. Annual incidence (per 100 000 population) increased from 650 (95% CI 648–652) in 2004 to 848 (845–850) in 2008, declining to 774 (771–776) by 2012 (9% decrease from 2008 to 2012). Incidence varied by age group, sex, and province. There was an inverse association between incidence of microbiologically confirmed disease and ART coverage among HIV-infected individuals nationally and provincially. Trends in incidence of tuberculosis cases registered for treatment mirrored those of microbiologically confirmed cases nationally and provincially; however, incidence of microbiologically confirmed cases was consistently higher than cases registered for treatment nationally and in seven of nine provinces. INTERPRETATION : Since its peak in 2008, the incidence of microbiologically confirmed pulmonary tuberculosis in South Africa had declined by 2012; this decline is associated with an increase in ART coverage. Future integration of registries for microbiologically confirmed cases and new cases registered for treatment would improve the assessment of the burden of pulmonary tuberculosis in South Africa. FUNDING : National Institute for Communicable Diseases: Division of the National Health Laboratory Service, South Africa.SAM has received grants and personal fees from GlaxoSmithKline, Pfizer, and Sanofi Pasteur, and grants from Novartis.http://www.thelancet.com/infectionhb2017Medical Microbiolog

Treatment outcomes among children, adolescents, and adults on treatment for tuberculosis in two metropolitan municipalities in Gauteng Province, South Africa

BACKGROUND : Gauteng Province has the second lowest tuberculosis (TB) incidence rate in South Africa but the greatest proportion of TB/HIV co-infection, with 68% of TB patients estimated to have HIV. TB treatment outcomes are well documented at the national and provincial level; however, knowledge gaps remain on how outcomes differ across detailed age groups. METHODS : Using data from South Africa’s National Electronic TB Register (ETR), we assessed all-cause mortality and loss to follow-up (LTFU) among patients initiating treatment for TB between 01/2010 and 12/2015 in the metropolitan municipalities of Ekurhuleni Metropolitan Municipality and the City of Johannesburg in Gauteng Province. We excluded patients who were missing age, had known drug-resistance, or transferred into TB care from sites outside the two metropolitan municipalities. Among patients assigned a treatment outcome, we investigated the association between age group at treatment initiation and mortality or LTFU (treatment interruption of ≥2 months) within 10 months after treatment initiation using Cox proportional hazard models and present hazard ratios and Kaplan-Meier survival curves. RESULTS : We identified 182,890 children (<10 years), young adolescent (10–14), older adolescent (15–19), young adult (20–24), adult (25–49), and older adult (≥50) TB cases without known drug-resistance. ART coverage among HIV co-infected patients was highest for young adolescents (64.3%) and lowest for young adults (54.0%) compared to other age groups (all over 60%). Treatment success exceeded 80% in all age groups (n = 170,017). All-cause mortality increased with age. Compared to adults, young adults had an increased hazard of LTFU (20–24 vs 25–49 years; aHR 1.43 95% CI: 1.33, 1.54) while children, young adolescents, and older adults had lower hazard of LTFU. Patients with HIV on ART had a lower risk of LTFU, but greater risk of death when compared to patients without HIV. CONCLUSIONS : Young adults in urban areas of Gauteng Province experience a disproportionate burden of LTFU and low coverage of ART among co-infected patients. This group should be targeted for interventions aimed at improving clinical outcomes and retention in both TB and HIV care.The American People and the President’s Emergency Plan for AIDS Relief (PEPFAR) through USAID under the terms of Cooperative Agreements AID- 674-A-12-00029 and 72067419CA00004 to HE2RO.https://bmcpublichealth.biomedcentral.comam2020Medical Microbiolog

Drug-resistance mechanisms and tuberculosis drugs.

This publication presents independent research supported by the Health Innovation Challenge Fund (HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust.This is the final version of the article. It first appeared at http://dx.doi.org/10.1016/S0140-6736(14)62450-8

Simultaneous 13N-Ammonia and gadolinium first-pass myocardial perfusion with quantitative hybrid PET-MR imaging: a phantom and clinical feasibility study

Background Positron emission tomography (PET) is the non-invasive reference standard for myocardial blood flow (MBF) quantification. Hybrid PET-MR allows simultaneous PET and cardiac magnetic resonance (CMR) acquisition under identical experimental and physiological conditions. This study aimed to determine feasibility of simultaneous 13N-Ammonia PET and dynamic contrast-enhanced CMR MBF quantification in phantoms and healthy volunteers. Methods Images were acquired using a 3T hybrid PET-MR scanner. Phantom study: MBF was simulated at different physiological perfusion rates and a protocol for simultaneous PET-MR perfusion imaging was developed. Volunteer study: five healthy volunteers underwent adenosine stress. 13N-Ammonia and gadolinium were administered simultaneously. PET list mode data was reconstructed using ordered subset expectation maximisation. CMR MBF was quantified using Fermi function-constrained deconvolution of arterial input function and myocardial signal. PET MBF was obtained using a one-tissue compartment model and image-derived input function. Results Phantom study: PET and CMR MBF measurements demonstrated high repeatability with intraclass coefficients 0.98 and 0.99, respectively. There was high correlation between PET and CMR MBF (r = 0.98, p < 0.001) and good agreement (bias − 0.85 mL/g/min; 95% limits of agreement 0.29 to − 1.98). Volunteer study: Mean global stress MBF for CMR and PET were 2.58 ± 0.11 and 2.60 ± 0.47 mL/g/min respectively. On a per territory basis, there was moderate correlation (r = 0.63, p = 0.03) and agreement (bias − 0.34 mL/g/min; 95% limits of agreement 0.49 to − 1.18). Conclusion Simultaneous MBF quantification using hybrid PET-MR imaging is feasible with high test repeatability and good to moderate agreement between PET and CMR. Future studies in coronary artery disease patients may allow cross-validation of techniques

Comparison between the BACTEC MGIT 960 system and the agar proportion method for susceptibility testing of multidrug resistant tuberculosis strains in a high burden setting of South Africa

BACKGROUND: The increasing problem of multi-drug-resistant (MDR) tuberculosis (TB) [ie resistant to at least isoniazid (INH) and rifampicin (RIF)] is becoming a global problem. Successful treatment outcome for MDR-TB depends on reliable and accurate drug susceptibility testing of first-line and second-line anti-TB drugs. METHOD: Consecutive M. tuberculosis isolates identified as MDR-TB during August 2007 to January 2008 using the BACTEC MGIT 960 systems and the agar proportion method were included in this study. Susceptibility testing of MDR-TB isolates against ethambutol (EMB) and streptomycin (STR) as well as two second-line anti-TB drugs, kanamycin (KAN) and ofloxacin (OFX) was performed using the BACTEC MGIT 960 systems at a routine diagnostic laboratory. The results were compared to those obtained by the agar proportion method. RESULT: The agreement between the BACTEC MGIT 960 system and the agar proportion method was 44% for EMB, 61% for STR and 89% for both KAN and OFX. The sensitivity and specificity of the BACTEC MGIT 960 system using the agar proportion method as a gold standard was 92% and 37% for EMB, 95% and 37% for STR, 27% and 97% for KAN and 84% and 90% for OFX, respectively. CONCLUSIONS: The BACTEC MGIT 960 system showed acceptable sensitivity for EMB, STR, and OFX; however, the BACTEC MGIT 960 system was less specific for EMB and STR and demonstrated a low sensitivity for KAN. The lower agreement found between the two methods suggests the unreliability of the BACTEC MGIT 960 system for the drugs tested. The reasons for the lower agreement between the two methods need to be investigated and further studies are needed in this setting to confirm the study finding.The project was supported by a grant from the NHLS.http://www.biomedcentral.com/1471-2334/12/369am2013ay201

Molecular detection of Mycobacterium tuberculosis from sputum transported in PrimeStore(®) from rural settings

SETTING : Mopani District, South Africa. OBJECTIVE : To explore remote, molecular detection of Mycobacterium tuberculosis from sputum transported using PrimeStorew Molecular Transport Medium (PSMTM) compared to settings where microscopy or Xpertw MTB/RIF is used as the baseline test. DESIGN : Two sputum specimens were collected from patients with cough of72 weeks at clinics in rural South Africa. Shortly after expectoration and before processing using Xpert, microscopy and liquid culture, a flocked swab was swirled in each of these specimens and placed in PS-MTM. Swabs were stored and transported to the United States at ambient temperature for real-time PrimeMixw polymerase chain reaction (PM-PCR). RESULTS : Of 132 patients, 23 (17%) were positive on microscopy, 39 (30%) on Xpert and 44 (33%) by PSMTM/PSMTM/ PM-PCR. Concordance of PS-MTM/PM-PCR with positive microscopy and Xpert was respectively 96% and 85%. Of 107 microscopy-negative samples, 22 (21%) were positive using PS-MTM/PM-PCR, while 11/91 (12%) Xpert-negative samples were PS-MTM/ PM-PCR-positive. PS-MTM/PM-PCR positivity was significantly higher than smear microscopy positivity (P , 0.001), but similar to Xpert (P ¼ 0.33). CONCLUSION: PCR testing of specimens transported in PS-MTM would enhance TB diagnosis in settings where smear microscopy is the baseline diagnostic test, and could provide an alternative in settings where Xpert testing is not available.http://www.ingentaconnect.comcontent/iuatld/ijtld2015-11-30hb201