Dual time-point FDG PET/CT for differentiating benign from malignant solitary pulmonary nodules in a TB endemic area

Objective. Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is an accurate non-invasive imaging test for differentiating benign from malignant solitary pulmonary nodules (SPNs). We aimed to assess its diagnostic accuracy for differentiating benign from malignant SPNs in a tuberculosis (TB)-endemic area. Methods. Thirty patients, 22 men and 8 women, mean age 60 years, underwent dual time point FDG-PET/computed tomography (CT) imaging, followed by histological examination of the SPN. Maximum standard uptake values (SUVmax) with the greatest uptake in the lesion were calculated for two time points (SUV1 and SUV2), and the percentage change over time per lesion was calculated (%DSUV). Routine histological findings served as the gold standard. Results. Histological examination showed that 14 lesions were malignant and 16 benign, 12 of which were TB. SUVmax for benign and malignant lesions were 11.02 (standard deviation (SD) 6.6) v. 10.86 (SD 8.9); however, when tuberculomas were excluded from the analysis, a significant difference in mean SUV1max values between benign and malignant lesions was observed (p=0.0059). Using an SUVmax cut-off value of 2.5, a sensitivity of 85.7% and a specificity of 25% was obtained. Omitting the TB patients from analysis resulted in a sensitivity of 85.7% and a specificity of 100%. Mean %DSUV of benign lesions did not differ significantly from mean %DSUV of malignant lesions (17.1% (SD 16.3%) v. 19.4% (SD 23.7%)). Using a cut-off of %DSUV >10% as indicative of malignancy, a sensitivity of 85.7% and a specificity of 50% was obtained. Omitting the TB patients from the analysis yielded a sensitivity of 85.7% and a specificity of 75%. Conclusion. Our findings suggest that FDG-PET cannot distinguish malignancy from tuberculoma and therefore cannot reliably be used to reduce futile biopsy/thoracotomy

Multi-drug resistant tuberculosis in women

The World Health Organisation (WHO) estimates a staggering 8.6 million new tuberculosis cases every year (Global TB report, 2013).1 Seventy five percent of the 8.6 million cases are from the Africa region. More than 500 000 of these cases are new multi-drug resistant tuberculosis (MDR TB) that has doubled from 2009 as well as 2011 and this number is currently doubling annually. Many of these cases are primary MDR TB infection or re-infection rather than previously treated tuberculosis progressing to MRD TB.2 Evidence is growing for increased transmission in congregate settings and hospitals. Currently drug susceptible tuberculosis treatment rapidly induces negative transmission compared to multi- and extreme drug resistant tuberculosis treatment that is not effective and the patient can be positive for months and still transmitting disease.http://reference.sabinet.co.za/sa_epublication/medogam201

Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst

Heteroaromatic compounds containing carbon–silicon (C–Si) bonds are of great interest in the fields of organic electronics and photonics1, drug discovery, nuclear medicine and complex molecule synthesis, because these compounds have very useful physicochemical properties. Many of the methods now used to construct heteroaromatic C–Si bonds involve stoichiometric reactions between heteroaryl organometallic species and silicon electrophiles or direct, transition-metal-catalysed intermolecular carbon–hydrogen (C–H) silylation using rhodium or iridium complexes in the presence of excess hydrogen acceptors. Both approaches are useful, but their limitations include functional group incompatibility, narrow scope of application, high cost and low availability of the catalysts, and unproven scalability. For this reason, a new and general catalytic approach to heteroaromatic C–Si bond construction that avoids such limitations is highly desirable. Here we report an example of cross-dehydrogenative heteroaromatic C–H functionalization catalysed by an Earth-abundant alkali metal species. We found that readily available and inexpensive potassium tert-butoxide catalyses the direct silylation of aromatic heterocycles with hydrosilanes, furnishing heteroarylsilanes in a single step. The silylation proceeds under mild conditions, in the absence of hydrogen acceptors, ligands or additives, and is scalable to greater than 100 grams under optionally solvent-free conditions. Substrate classes that are difficult to activate with precious metal catalysts are silylated in good yield and with excellent regioselectivity. The derived heteroarylsilane products readily engage in versatile transformations enabling new synthetic strategies for heteroaromatic elaboration, and are useful in their own right in pharmaceutical and materials science applications

Auditory, video head impulse test and vestibular evoked myogenic potentials findings in adults with human immunodeficiency virus

OBJECTIVES : Even though there is an association between hearing loss and human immunodeficiency virus (HIV), particularly in low- and middle-income countries, further research is needed to investigate the nature of such hearing loss. Likewise, despite documented vestibular alterations in people with HIV, the true occurrence, presentation, and nature of these manifestations are yet to be established. Advances in technology for vestibular testing has allowed for objective site-of-lesion tests such as the video head impulse test (vHIT), cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potential (oVEMPs). The current study aimed to compare and describe auditory, vHIT, cVEMPs and oVEMPs findings in adults with and without HIV. METHODS : The current study included an HIV positive group (n = 30) and an HIV negative group (n = 30) who underwent an auditory assessment (tympanometry and pure tone audiometry) and objective vestibular assessments. RESULTS : The occurrence of hearing loss was 53.3% in the HIV positive group compared to 33.3% in the HIV negative group. A higher occurrence of vestibular involvement was documented in the HIV positive group (73.3%) compared to 13.3% in the HIV negative group. CONCLUSION : Auditory assessment and objective measures of vestibular end-organ function (vHIT and VEMPs) can be useful to detect sub-clinical alterations. The equipment is mobile and can be performed in any health care setting such as infectious disease clinics for surveillance and monitoring purposes.http://www.elsevier.com/locate/anl2020-12-18hj2020Speech-Language Pathology and Audiolog

Impact of optimized PET imaging conditions on F-18-FDG uptake quantification in patients with apparently normal aortas

Background The cardiovascular committee of the European Association of Nuclear Medicine (EANM) recently published recommendations on imaging conditions to be observed during F-18-FDG PET imaging of vascular inflammation. This study aimed to evaluate the impact of applying these optimized imaging conditions on PET quantification of arterial F-18-FDG uptake. Methods and Results Fifty-seven patients were prospectively recruited to undergo an early F-18-FDG PET/CT imaging at 60 minutes and repeat delayed imaging at >= 120 minutes post tracer injection. Routine oncologic F-18-FDG PET protocol was observed for early imaging, while delayed imaging parameters were optimized for vascular inflammation imaging as recommended by the EANM. Aortic SUVmax of the ascending aorta and SUVmean from the lumen of the superior vena cava (SVC SUVmean) were obtained on early and delayed imaging. Target-to-background ratio (TBR) was obtained for the early and delayed imaging. Aortic SUVmax increased by a mean of 70%, while SVC SUVmean decreased by a mean of 52% between early and delayed imaging (P 180 minutes. Aortic SUVmax significantly increased at imaging time-points between 120 and 180 minutes. No significant improvement in aortic SUVmax was seen at imaging time-points beyond 180 minutes. Conclusions F-18-FDG PET imaging conditions optimized for vascular inflammation imaging lead to an improved quantification through an increase in the quantified vascular tracer uptake and decrease in blood-pool background activity

Vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in four South African antenatal clinics

INTRODUCTION : There is a risk of mother-to-child transmission of HIV (MTCT) during pregnancy and breastfeeding. The aim of this study was to assess vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in South African antenatal care (ANC) clinics. METHODS : Pregnant participants were enrolled in a diagnostic study that used nucleic acid amplification testing (NAAT) to screen for early HIV infection among individuals who tested negative on rapid HIV tests used at the point-of-care (POC) facilities. Participants were enrolled from four ANC clinics in the Tshwane district of South Africa. All NAAT-positive participants were recalled to the clinics for further management. Vertical transmission was assessed among exposed infants whose HIV polymerase chain reaction (PCR) results were available. RESULTS : This study enrolled 8208 pregnant participants who tested negative on rapid HIV tests between 2013 and 2016. Their median age was 26 years (interquartile range [IQR]: 23–30). NAAT detected HIV infections in 0.6% (n = 49; 95% confidence interval {CI}: 0.5–0.8) of all study participants. The distribution of these infections among the four clinics ranged from 0.3%– 1.1%, but this was not statistically significant (p = 0.07). Forty-seven participants (95.9%) were successfully recalled and referred for antiretroviral treatment initiation as part of prevention of MTCT (PMTCT). Most women with newly diagnosed HIV infection presented for the first ANC visit in the second (61.9%, n = 26) and third (31.0%, n = 13) trimesters. HIV PCR results were available for thirty-two infants, three of whom tested positive (9.4%; 95% CI: 1.98–25.02). CONCLUSIONS : This study showed that supplemental HIV testing for pregnant women led to earlier linkage to the PMTCT programme. Inaccurate diagnosis of HIV infection at ANC clinics is likely to undermine the efforts of eliminating MTCT particularly in HIV-endemic settings.S1 Table. Characteristics of participants diagnosed with early or chronic HIV infection. Initial tests were performed from samples obtained at enrolment (i.e. after a negative rapid HIV test result). HIV viral load (VL) tests were performed first to screen for HIV infection, and all the serology tests were performed later. Follow-up (F/U) VL was only performed for participants who had an initial VL <5000 copies/ml [16]. Pt ID = participant’s study identity, F = female, gen = generation, ELISA = enzyme-linked immunosorbent assay, W. Blot = Western Blot, LAg = limiting antigen, Insuf = insufficient, LT = long term (chronic) infection, --- = not available (participant did not return for follow-up), + = positive,— = negative. Units: HIV VL = copies/ml; p24 antigen = cut-off index (COI); Genscreen ELISA = sample cut-off (S/CO); LAg avidity = normalized optical density (OD-n); LAg avidity <1.5 OD-n = early infection; LAg avidity >1.5 OD-n = LT (chronic) infection. ¥ = participant 6738 was previously misclassified as having chronic infection [16], but testing on her follow-up sample revealed low avidity antibodies consistent with early infection; this was confirmed on repeat testing of 6738 sample. P24 antigen, W. Blot and F/U LAg were not performed for the last participants identified with newly diagnosed HIV infection owing to cost limitations. This also applies to the F/U VL for participant 1692, as this was supposed to have been performed according to the diagnostic study protocol [14].This work was supported by SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.http://www.plosone.orgam2020Internal Medicin

Vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in four South African antenatal clinics

INTRODUCTION : There is a risk of mother-to-child transmission of HIV (MTCT) during pregnancy and breastfeeding. The aim of this study was to assess vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in South African antenatal care (ANC) clinics. METHODS : Pregnant participants were enrolled in a diagnostic study that used nucleic acid amplification testing (NAAT) to screen for early HIV infection among individuals who tested negative on rapid HIV tests used at the point-of-care (POC) facilities. Participants were enrolled from four ANC clinics in the Tshwane district of South Africa. All NAAT-positive participants were recalled to the clinics for further management. Vertical transmission was assessed among exposed infants whose HIV polymerase chain reaction (PCR) results were available. RESULTS : This study enrolled 8208 pregnant participants who tested negative on rapid HIV tests between 2013 and 2016. Their median age was 26 years (interquartile range [IQR]: 23–30). NAAT detected HIV infections in 0.6% (n = 49; 95% confidence interval {CI}: 0.5–0.8) of all study participants. The distribution of these infections among the four clinics ranged from 0.3%– 1.1%, but this was not statistically significant (p = 0.07). Forty-seven participants (95.9%) were successfully recalled and referred for antiretroviral treatment initiation as part of prevention of MTCT (PMTCT). Most women with newly diagnosed HIV infection presented for the first ANC visit in the second (61.9%, n = 26) and third (31.0%, n = 13) trimesters. HIV PCR results were available for thirty-two infants, three of whom tested positive (9.4%; 95% CI: 1.98–25.02). CONCLUSIONS : This study showed that supplemental HIV testing for pregnant women led to earlier linkage to the PMTCT programme. Inaccurate diagnosis of HIV infection at ANC clinics is likely to undermine the efforts of eliminating MTCT particularly in HIV-endemic settings.S1 Table. Characteristics of participants diagnosed with early or chronic HIV infection. Initial tests were performed from samples obtained at enrolment (i.e. after a negative rapid HIV test result). HIV viral load (VL) tests were performed first to screen for HIV infection, and all the serology tests were performed later. Follow-up (F/U) VL was only performed for participants who had an initial VL <5000 copies/ml [16]. Pt ID = participant’s study identity, F = female, gen = generation, ELISA = enzyme-linked immunosorbent assay, W. Blot = Western Blot, LAg = limiting antigen, Insuf = insufficient, LT = long term (chronic) infection, --- = not available (participant did not return for follow-up), + = positive,— = negative. Units: HIV VL = copies/ml; p24 antigen = cut-off index (COI); Genscreen ELISA = sample cut-off (S/CO); LAg avidity = normalized optical density (OD-n); LAg avidity <1.5 OD-n = early infection; LAg avidity >1.5 OD-n = LT (chronic) infection. ¥ = participant 6738 was previously misclassified as having chronic infection [16], but testing on her follow-up sample revealed low avidity antibodies consistent with early infection; this was confirmed on repeat testing of 6738 sample. P24 antigen, W. Blot and F/U LAg were not performed for the last participants identified with newly diagnosed HIV infection owing to cost limitations. This also applies to the F/U VL for participant 1692, as this was supposed to have been performed according to the diagnostic study protocol [14].This work was supported by SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.http://www.plosone.orgam2020Internal Medicin

Detection and genome characterization of Middelburg virus strains isolated from CSF and whole blood samples of humans with neurological manifestations in South Africa

BACKGROUND : The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients from Gauteng, South Africa. METHODS : This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR. Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using Epi Info. RESULTS : MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria. Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample). Two of the four Middelburg virus positive cases, for which clinical information was available, had other comorbidities or infections at the time of infection. CONCLUSION : Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.The G7 Global Health Fund program, the National Research Foundation, Poliomyelitis Research Foundation and the German Federal Ministry of Education and Research.https://journals.plos.org/plosntdsdm2022Paraclinical Science