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In South Africa, social media has become a popular public relations research topic in nongovernmental organisations (NGOs). This is because NGOs are increasingly integrating social media into their public relations strategies in an effort to engage with the variety of stakeholders by using communication platforms such as Facebook and Twitter that social life takes place, people communicate and share information. This study reviews the current uses, benefits, and limitations of social media in public relations among NGOs and analyses how South African public relations practitioners are experiencing these uses, benefits and limitations of social media in NGOs. Based on theoretical guidelines for social media public relations communication the empirical study employs a qualitative research using in-depth, semi-structured interviews with public relations practitioners in NGOs. The results provide a holistic view of their experience in social media. The key benefits of using social media were identified as the increasing public relations interactions with audience, improving the accessibility of public relations communication, increasing the speed for feedback and input, social/peer and emotional support, potential to influence the public, improving the long-term cost effective relationship of public relations communication, reaching youth and other audiences on specific issues. The limitations were identified as quality concerns, confidentiality and private information leaking to the public, and the reliability of information. [ABSTRACT FROM AUTHOR]

According to the World Health Organization, South Africa is ranked the third highest country (0.4-0.6 million), after India and China, with a tuberculosis burden, coupled with drug resistance that is threatening tuberculosis control efforts. Understanding the genetic diversity and drug resistance patterns of Mycobacterium tuberculosis is crucial. The purpose of this study was to describe the molecular characterisation and associated drug susceptibility patterns of M. tuberculosis isolates from South African children. M. tuberculosis strains from children from four South African provinces were characterised and the drug resistance patterns determined. One hundred and four isolates that were culture positive in the Bactec Mycobacterium Growth Indicator Tube 960® and positively identified by AccuProbe® assay as M. tuberculosis were used. To ensure purity, the samples were subcultured on Löwenstein-Jensen medium agar slants. Spoligotyping was performed according to the manufacturer's instructions. The international spoligotyping database 4 (SpolDB4) was used to analyse the genotypic data. First-line drugs, excluding pyrazinamide, were tested using the Middlebrook 7H11 Agar® proportion method. Twenty-one genotype families were identified in 93 isolates: Beijing (39%), T1 (14%), T2 (3%), T3 (1%), T4-CEU1 (1%), LAM3 (8%), LAM3 and S/convergent (1%), LAM4 (2%), LAM9 (1%), LAM11-ZWE (5%), H1 (2%), H2 (1%), H3 (1%), CAS (1%), CAS-KILI (1%), MANU2 (1%), EAI1-SOM (1%), EAI7-BGD2 (1%), S (3%), X3 (2%) and Bovis1-BCG (2%). Eleven (11%) isolates could not be assigned within the SpolDB4. The Beijing family was the most dominant in Gauteng (27%), followed by Mpumalanga (5%), North West (5%) and Limpopo (2%). The Beijing family was observed in 19 (18%) of isolates from children aged 0-5 years, and in 22 (21%) of isolates from children aged 6-12 years. Ninety-five (91%) isolates were susceptible to all drugs. Overall, of the 104 isolates, 3 (3%) were multidrug-resistant tuberculosis, one each from the Beijing family, T2 and LAM3. The Beijing family was the most dominant genotype, with most cases being from Gauteng, followed by T1. The Beijing genotype was distributed equally between children aged 0-5 years and those aged 6-12 years. The high prevalence of the Beijing genotype poses a serious threat to tuberculosis control owing to its high virulence and association with multi-drug resistance. Continuous surveillance programmes are needed to control tuberculosis, especially in areas with high tuberculosis and human immunodeficiency virus rates, such as those where the study was conducted. [ABSTRACT FROM AUTHOR]

Tuberculosis is a global health problem. Continuous efforts are needed to understand the genetic diversity and geographical distribution of Mycobacterium tuberculosis. The objective of this study was to determine the genetic diversity of M. tuberculosis strains in Soshanguve, Pretoria. Eighty-nine isolates that were sputum culture-positive in Mycobacterium Growth Indicator Tube 960®, and positively identified by Accuprobe Probe assay as M. tuberculosis complex, were used in the study. The samples were sub-cultured on Lowenstein-Jensen (L-J) slants to ensure purity. Spoligotyping was performed, with slight modifications according to the manufacturer's specifications. Genotypic data were compared to the international spoligotyping database 4 (SpolDB4) and that suggested by Streicher et al. Spoligotyping identified 12 genotypes. Of the 89 isolates studied, 75 could be grouped into 11 clusters. The Beijing genotype family formed the largest group, with 21 isolates (28%). The remaining isolates were distributed among the Latino-American-Mediterranean (LAM) family: LAM3 (13%), LAM4 (4%), LAM9 (3%); the T family: T1 (23%), T2 (9%), and T3 (3%); the S family (8%); the X3 family (4%); CAS1-KILI (3%); and LAM11-ZWE (3%). Fourteen (16%) of the isolates had spoligotypes that did not match any of the spoligotype patterns deposited in the SpolDB4 database. Beijing was the most common genotype family, identified in 28% of the cases, followed by T1 (23%). The high prevalence of Beijing and T1 in this study reflects transmission of these genotype families within this community. The results of this study showed the dire need for more robust prevention strategies in tuberculosis control programmes. Other genotyping methods with a higher discriminatory power, such as restriction fragment length polymorphism, will be useful in defining the transmission patterns in this community. [ABSTRACT FROM AUTHOR]

BACKGROUND A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox-protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cel-lular responses in a phase 1-2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS In this phase 2b-3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections ofALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gpl20-MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS In January 2020, prespecified criteria for nonefficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P=0.84). CONCLUSIONS The ALVAC-gpl20 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence ofimmunogenicity. (HVTN 702 ClinicalTrials .gov number, NCT02968849.). [ABSTRACT FROM AUTHOR]

This study aimed to investigate phenotypic and genotypic characteristics of carbapenem-resistant Enterobacterales isolates (CRE) at a tertiary laboratory in South Africa. A total of 99 CRE isolates were collected between 2019 and 2021. Carbapenemase production was tested using modified carbapenem inhibitory method. Colistin susceptibility testing was performed using the ComASP™ Colistin broth microdilution method. Conventional PCR assays were conducted for detection of mcr-1 gene and common carbapenemase genes (blaVIM, blaNDM, blaIMP, blaKPC, blaOXA-23, blaOXA-51 and blaOXA-48). Rep-PCR assay was conducted to determine the genetic relatedness of the study isolates. Majority of the isolates were Klebsiella pneumoniae (83%). Carbapenem resistant K. pneumoniae cluster was observed from ICU and surgical ward samples. Colistin resistance was observed in 13% (12/93) of the isolates namely, in 11 K. pneumoniae and one Enterobacter cloacae. The blaOXA-48 (65%) was the most prevalent gene detected followed by blaNDM (25%) and blaVIM (22%). Several K. pneumoniae isolates concomitantly carried multiple carbapenemase genes with one isolate carry up to 5 five genes blaVIM, blaNDM, blaOXA-48, blaOXA-23 and blaOXA-51. The mcr-1 gene was not detected in the isolates. Rep-PCR assay showed that most isolates matched cluster A (50%). The high prevalence of blaOXA-48, blaNDM and emerging colistin resistant isolates is of concern for patient management at this institution and needs close monitoring. Rep-PCR is a valuable tool in establishing infection clusters in resource-limited settings.

There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospective analysis used data from the HVTN 702 HIV vaccine clinical trial (October 2016 to July 2021). We evaluated multiple variables. Polymerase chain reaction testing was conducted on urine and rectal samples to detect Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) every 6 months. Syphilis serology was conducted at month 0 and thereafter every 12 months. We calculated STI prevalence and the associated 95% confidence intervals until 24 months of follow-up. The trial enrolled 183 participants who identified as male or transgender female, and of homosexual or bisexual orientation. Of these, 173 had STI testing done at month 0, median age was 23 (IQR 20-25) years, with median 20.5 (IQR 17.5-24.8) months follow-up (FU). The clinical trial also enrolled and performed month 0 STI testing on 3389 female participants, median age 23 (IQR 21-27) years, median 24.8 (IQR 18.8-24.8) months FU and 1080 non-MSM males with a median age of 27 (IQR 24-31) years, median 24.8 (IQR 23-24.8) months FU. At month 0, CT prevalence was similar in MSM and females (26.0% vs 23.0%, p = 0.492) but was more prevalent in MSM compared to non-MSM males (26.0% vs 14.3%, p = 0.001). CT was the most prevalent STI among MSM at months 0 and 6 but declined from month 0 to month 6 (26.0% vs 17.1%, p = 0.023). In contrast, NG did not decline in MSM between months 0 and 6 (8.1% vs 7.1%, p = 0.680) nor did syphilis prevalence between months 0 and 12 (5.2% vs 3.8%, p = 0.588). Bacterial STI burden is higher in MSM compared to non-MSM males, and CT is the most prevalent bacterial STI amongst MSM. Preventive STI vaccines, especially against CT, may be helpful to develop., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mashingaidze et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Men having sex with men (MSM) are at increased risk of acquiring sexually transmitted infections (STIs), including extra-urethral infections. This study aimed to provide information on the presence of genital and extra-genital non-viral STIs and associated risk factors among MSM in the Tshwane district of South Africa., Method: Samples were collected from 200 MSM in the North-western area of Tshwane. After the completion of a questionnaire including demographics and sexual history and an HIV test, three swabs (pharyngeal, rectal, and urethral) were collected and tested for the presence of Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV)., Results: Data were collected from 199 participants and 77/199 (38.7%) participants had at least one infection regardless of specimen site. Of these 34 (17.1%) were infected with NG; 36 (18.1%) with CT, 16 (8.1%) with MG and 14 (7.0%) with TV. NG and CT were most frequently detected in rectal specimens. The HIV prevalence in this study was 66.8% (133/199), with 56 (28.1%) of participants both STI and HIV positive . Being between 18 and 20 years, and difficulty having safe sex (more sex partners and more often condomless anal sex) when high/drunk were significantly associated with having an STI. Factors with increased odds of having an STI were being HIV positive, having two or more sexual partners, depending on partner financially, performing and receiving rimming, or receiving anal sex., Conclusions: This study has highlighted the high burden of STIs in MSM in the local community, especially the prevalence of these pathogens in extra-genital sites.

Objectives: Providing country-specific estimates of case fatality and sequelae from bacterial meningitis (BM) is important to evaluate and monitor progress toward the World Health Organization's roadmap to "defeating meningitis by 2030"., Methods: From 2016-2020, GERMS-SA conducted enhanced surveillance at 26 hospitals across South Africa. Episodes of laboratory-confirmed BM due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis were included. Risk factors for in-hospital death and sequelae at hospital discharge among survivors were analyzed., Results: Of 12,717 invasive bacterial infections reported nationally, 39% (4980) were from enhanced surveillance sites, including 4159 pneumococcal, 640 H. influenzae, and 181 meningococcal infections. BM accounted for 32% (1319/4159) of pneumococcal, 21% (136/640) of H. influenzae, and 83% (151/181) of meningococcal invasive diseases. Clinical data were available for 91% (1455/1606) of BM: 26% (376/1455) were aged <5 years, 50% (726/1455) were female, and 62% (723/1171) with known HIV results, were HIV-infected. In-hospital case fatality was 37% (534/1455), and 24% (222/921) of survivors had adverse sequelae. Risk factors for death included altered mental status, HIV infection, and comorbidities. Risk factors for adverse sequelae included altered mental status and antimicrobial nonsusceptibility., Conclusion: BM in South Africa has a high case fatality, and adverse sequelae frequently occur among survivors. Those with comorbidities (including HIV) are at the highest risk., Competing Interests: Declaration of Competing interest Susan Meiring reports a grant from Sanofi Pasteur for research outside the submitted work. Anne von Gottberg and Cheryl Cohen report grants from US CDC, PATH, Wellcome Trust, Sanofi, and from South African MRC, outside the submitted work. All other authors declare that they have no commercial or other associations that may pose a conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition., Methods: Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition., Results: The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; Pmag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint)., Conclusions: HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T cells with HIV-1 acquisition. Clinical Trials Registration . NCT02968849., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients who complete a standard course of anti-tuberculous treatment (ATT) for pulmonary tuberculosis and are declared cured according to the current standard of care commonly have residual metabolic activity (RMA) in their lungs on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PER/CT) imaging. RMA seen in this setting has been shown to be associated with relapse of tuberculosis. The routine clinical use of FDG PET/CT imaging for treatment response assessment in tuberculosis is hindered by cost and availability. CT is a more readily available imaging modality. We sought to determine the association between CT features suggestive of active tuberculosis and RMA on FDG PET/CT obtained in patients who completed a standard course of ATT for pulmonary tuberculosis. We prospectively recruited patients who completed a standard course of ATT and declared cured based on negative sputum culture. All patients had FDG PET/CT within 2 weeks of completing ATT. We determined the presence of RMA on FDG PET images. Among the various lung changes seen on CT, we considered the presence of lung nodule, consolidation, micronodules in tree-in-bud pattern, FDG-avid chest nodes, and pleural effusion as suggestive of active tuberculosis. We determine the association between the presence of RMA on FDG PET and the CT features of active tuberculosis. We include 75 patients with a mean age of 36.09 ± 10.49 years. Forty-one patients (54.67%) had RMA on their FDG PET/CT while 34 patients (45.33%) achieved complete metabolic response to ATT. There was a significant association between four of the five CT features of active disease, p < 0.05 in all cases. Pleural effusion (seen in two patients) was the only CT feature of active disease without a significant association with the presence of RMA. This suggests that CT may be used in lieu of FDG PET/CT for treatment response assessment of pulmonary tuberculosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lawal, Mokoala, Mathebula, Moagi, Popoola, Moeketsi, Nchabeleng, Hikuam, Ellner, Hatherill, Fourie and Sathekge.)

Data lag is evident when observing studies focussing on human papillomavirus (HPV) prevalence in the head and neck of men who have sex with men (MSM) in Southern Africa. Sexual behaviours other than anal intercourse, and associated factors are similarly underreported. HPV vaccination has not yet commenced for this population group. One hundred and ninety-nine MSM were enrolled in this study. Participants completed a questionnaire followed by a clinical oral examination, and a rinse-and-gargle specimen in Thinprep ® vials containing Preservcyt ® solution was collected. Detection and genotyping for high-risk HPV were done by an automated system (Abbott ® m2000sp). Six percent of MSM in this cohort had high-risk HPV present in the mouth/oropharynx. This cohort averages 29 years of age, more than half were unemployed (53.3%), and 66.8% were human immunodeficiency virus (HIV) seropositive. The most common sexual practice was anal sex (69.4%) followed by oral sex (28.6%), and by rimming (9.6%). A significant association between oral insertive sex and oral/oropharyngeal HPV status was demonstrated (p = 0.0038; phi coefficient = 0.20). An incidental but significant association between rimming and HIV status was found (p = 0.0046; phi coefficient = 0.19), and HIV seropositive participants had higher oral/oropharyngeal HPV presence. The HPV prevalence of 6% reported in this study is in alignment with global reports. The prevalence of oral/oropharyngeal HPV in this MSM cohort was influenced by sexual practices. MSM participants who practiced rimming appear to be at higher risk of HIV acquisition. Given the transmission routes of HPV in this vulnerable population, vaccination must be urgently studied as an intervention for prevention., Competing Interests: Conflict of interest: The authors declare that they have no conflicts of interest emanating from the publication of this paper., (© 2022 the Author(s), licensee AIMS Press.)

Background: During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission., Setting: Nine sites in 4 South African provinces., Methods: Women aged 18-30 years were randomized to receive pericoital tenofovir 1% gel or placebo gel and required to use reliable modern contraception. We compared HIV incidence in women before, during, and after pregnancy and used multivariate Cox Proportional hazards models to compare HIV incidence by pregnancy status., Results: Rates of pregnancy were 7.1 per 100 woman-years (95% confidence interval [CI]: 6.3 to 8.1) and highest in those who reported oral contraceptive use (25.1 per 100 woman-years; adjusted hazard ratio 22.97 higher than other women; 95% CI: 5.0 to 105.4) or had 2 children. Birth outcomes were similar between trial arms, with 59.8% having full-term live births. No difference was detected in incident HIV during pregnancy compared with nonpregnant women (2.1 versus 4.3%; hazard ratio = 0.56, 95% CI: 0.14 to 2.26). Sexual activity was low in pregnancy and the early postpartum period, as was consistent condom use., Conclusions: Pregnancy incidence was high despite trial participation being contingent on contraceptive use. We found no evidence that rates of HIV acquisition were elevated in pregnancy when compared with those in nonpregnant women. Risks from reductions in condom use may be offset by reduced sexual activity. Nevertheless, high HIV incidence in both pregnant and nonpregnant women supports consideration of introducing antiretroviral-containing pre-exposure prophylaxis for pregnant and nonpregnant women in high HIV prevalence settings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Acinetobacter baumannii ( A . baumannii ) has developed several resistance mechanisms. The bacteria have been reported as origin of multiple outbreaks. This study aims to investigate the use of efflux pumps and quinolone resistance-associated genotypic mutations as mechanisms of resistance in A . baumannii isolates at a tertiary hospital. A total number of 103 A . baumannii isolates were investigated after identification and antimicrobial susceptibility testing by VITEK2 followed by PCR amplification of bla OXA-51 . Conventional PCR amplification of the AdeABC efflux pump ( adeB , adeS , and adeR ) and quinolone ( parC and gyrA ) resistance genes were performed, followed by quantitative real-time PCR of AdeABC efflux pump genes. Phenotypic evaluation of efflux pump expression was performed by determining the difference between the MIC of tigecycline before and after exposure to an efflux pump inhibitor. The Sanger sequencing method was used to sequence the parC and gyrA amplicons. A phylogenetic tree was drawn using MEGA 4.0 to evaluate evolutionary relatedness of the strains. All the collected isolates were bla OXA-51 -positive. High resistance to almost all the tested antibiotics was observed. Efflux pump was found in 75% of isolates as a mechanism of resistance. The study detected parC gene mutation in 60% and gyrA gene mutation in 85%, while 37% of isolates had mutations on both genes. A minimal evolutionary distance between the isolates was reported. The use of the AdeABC efflux pump system as an active mechanism of resistance combined with point mutation mainly in gyrA was shown to contribute to broaden the resistance spectrum of A . baumannii isolates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Noel-David Nogbou et al.)

Purpose: Antimicrobial resistance is now globally recognised amongst the greatest threat to human health. Acinetobacter baumannii's' (A. baumannii) clinical significance has been driven by its ability to obtain and transmit antimicrobial resistance factors. In South Africa, A. baumannii is a leading cause of healthcare associated infections (HAI). In this study, we investigated the genetic determinants of multi-drug resistant A. baumannii (MDRAB) at a teaching hospital in Pretoria, South Africa., Methods: One hundred non repetitive isolates of A. baumannii were collected for the study. Antimicrobial susceptibility testing was performed using the VITEK2 system. The prevalence of antibiotic resistance associated genes and AdeABC efflux pump system were investigated using conventional PCR. Genetic relatedness of isolates was determined using rep-PCR., Results: Seventy (70) of 100 isolates collected were confirmed multi-drug resistant and were bla OXA51 positive. Phenotypically, the isolates where resistant to almost all tested antibiotics. One isolate showed intermediate susceptibility to tigecycline while all were susceptible to colistin. Oxacillinase gene bla OXA-23 was the most detected at 99% and only 1% was positive for bla OXA-40 . For Metallo-betalactamases (MBL), bla VIM was the most frequently detected at 86% and bla SIM-1 at 3% was the least detected. Fifty-six isolates had the required gene combination for an active efflux pump. The most prevalent clone was clone A at 69% of the isolates. Colistin and tigecycline are the most effective against investigated isolates., Conclusion: The major genotypic determinant for drug resistances is oxacillinases bla OXA-23 . The study reports for the first time, bla OXA-40 and bla SIM-1 detection in A. baumannii in South Africa., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Benign ethnic neutropenia (BEN) is defined as a neutrophil count of <1.5×109 cells/L in healthy individuals and is more common in populations of certain ethnicities, e.g. African or Middle Eastern ethnicity. Neutrophil values are commonly included in eligibility criteria for research participation, but little is known about the relationship between BEN, HIV acquisition, and the occurrence of adverse events during clinical trials. We investigated these relationships using data from an HIV vaccine efficacy trial of healthy adults from 5 South African sites. We analysed data from the double-blind, placebo-controlled, randomized trial HVTN 503, and its follow-on study HVTN 503-S to assess the prevalence of BEN, its association with HIV infection, and adverse event reporting. These data were then compared with a time- and age-matched, non-pregnant cohort from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007-2008 in the United States (US). The 739 South African participants had a median age of 22.0 years (interquartile range = 20-26) and 56% (n = 412) were male. Amongst the US cohort of 845 participants, the median age was 26 (IQR: 21-30) and the majority (54%, 457/745) were also male. BEN was present at enrolment in 7.0% (n = 52) of South African participants (6% in the placebo group versus 8% in the vaccine group); 81% (n = 42) of those with BEN were male. Pretoria North had the highest prevalence of BEN (11.6%, 5/43), while Cape Town had the lowest (0.7%, 1/152). Participants with BEN had a lower median neutrophil count (1.3 vs. 3.2x109 cells/L; p<0.001) and BMI (20.8 vs. 22.3 kg/m2; p<0.001) when compared to those without BEN. A greater proportion of Black South Africans had neutrophil counts <1.5×109 cells/L compared to US non-Hispanic Whites from the NHANES cohort (7% [52/739] vs. 0.6% [3/540]; p<0.001). BEN did not increase the odds for HIV infection (adjusted odds ratio [aOR]: 1.364, 95% confidence interval [95% CI]: 0.625-2.976; p = 0.4351). However, female gender (aOR: 1.947, 95% CI: 1.265-2.996; p = 0.0025) and cannabis use (aOR: 2.192, 95% CI: 1.126-4.266; p = 0.0209) increased the odds of HIV acquisition. The incidence rates of adverse events were similar between participants in the placebo group with BEN, and those without: 12.1 (95% CI: 7.3-20.1) vs. 16.5 (95% CI: 14.6-18.7; p = 0.06) events per 100 person-years (py) were noted in the infections and infestations system organ class, respectively. The vaccine group had an event incidence rate of 19.7 (95% CI: 13.3-29.2) vs. 14.8 (95% CI: 13.0-16.8; p = 0.07) events per 100py in the group with, and without BEN, respectively. BEN is more prevalent in Black South Africans compared to US Non-Hispanic Whites. Our data do not support excluding populations from HIV vaccine trials because of BEN. BEN was not associated with increased risk for HIV infection or Adverse events on a vaccine trial. Predictors of HIV infection risk were females and cannabis use, underlying the continued importance of prevention programmes in focusing on these populations., Competing Interests: The authors have declared that no competing interests exist.

Microbial culture is the gold standard for determining the effectiveness of tuberculosis treatment. End-of-treatment (EOT) 18 F-FDG PET/CT findings are variable among patients with negative microbial culture results after completing a standard regimen of antituberculous treatment (ATT), with some patients having a complete metabolic response to treatment whereas others have residual metabolic activity (RMA). We herein determine the impact of findings on EOT 18 F-FDG PET/CT on tuberculosis relapse in patients treated with a standard regimen of ATT for drug-sensitive pulmonary tuberculosis (DS-PTB). Methods: Patients who completed a standard regimen of ATT for DS-PTB and were declared cured based on a negative clinical and bacteriologic examination were prospectively recruited to undergo EOT 18 F-FDG PET/CT. Images were assessed for the presence of RMA. Patients were subsequently followed up for 6 mo looking for symptoms of tuberculosis relapse. When new symptoms developed, relapse was confirmed with bacteriologic testing. Repeat 18 F-FDG PET/CT was done in patients who relapsed. Results: Fifty-three patients were included (mean age, 37.81 ± 11.29 y), with 62% being male and 75% HIV-infected. RMA was demonstrated in 33 patients (RMA group), whereas 20 patients had a complete metabolic response to ATT (non-RMA group). There was a higher prevalence of lung cavitation in the RMA group ( P = 0.035). The groups did not significantly differ in age, sex, presence of HIV infection, body mass index, or hemoglobin level ( P > 0.05). On follow-up, no patients in the non-RMA group developed tuberculosis relapse. Three patients in the RMA group developed relapse. All patients who developed tuberculosis relapse had bilateral disease with lung cavitation. Conclusion: A negative EOT 18 F-FDG PET/CT result is protective against tuberculosis relapse. Nine percent of patients with RMA after ATT may experience tuberculosis relapse within 6 mo of completing ATT. Bilateral disease with lung cavitation is prevalent among patients with tuberculosis relapse., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Global roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms., Methods: We screened records of 37 644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service-Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution., Findings: Ile491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa., Interpretation: A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community., Funding: VLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Young women in southern Africa have substantial risk of HIV acquisition. Female-controlled biomedical interventions are needed to mitigate this risk. We aimed to assess the safety and efficacy of a pericoitally applied tenofovir 1% gel., Methods: We did a phase 3, double-blind, randomised, placebo-controlled trial at nine community-based clinical trial sites in South Africa to evaluate the safety and efficacy of tenofovir 1% gel. Sexually active women who were HIV negative and aged 18-30 years were enrolled. Participants were randomly assigned (1:1) using sequential participant numbers to either tenofovir 1% gel or a placebo gel (one dose within 12 h before sex and one dose within 12 h after sex [BAT-24 regimen]), using dynamic permuted block sizes of 8 and 16 within each site. Women received monthly HIV-1 testing, risk reduction support, physical examinations, and product dispensing for up to 27 months. The primary efficacy outcome was incident HIV infection and the primary safety outcome was occurrence of grade 2-4 adverse events, both analysed in the modified intention-to-treat population. To assess the efficacy of tenofovir gel, the cumulative probability of HIV infection was calculated for each treatment using the Kaplan-Meier method. This trial is registered with ClinicalTrials.gov, number NCT01386294., Findings: From Oct 11, 2011, to Aug 29, 2014, 3844 women were screened, 2059 enrolled, and 2029 included in the primary analysis (1032 in the tenofovir group and 1027 in the placebo group); 39 (4%) in the tenofovir group and 36 (4%) in the placebo group were lost to follow-up. 123 HIV-1 infections occurred over 3036 woman-years of observation; 61 in the tenofovir group (HIV incidence 4·0 per 100 woman-years, 95% CI 3·1-5·2) and 62 in the placebo group (4·0 per 100 woman-years, 3·1-5·2; incidence rate ratio [IRR] 0·98, 95% CI 0·7-1·4). A higher incidence of grade 2 adverse events was observed in the tenofovir group than in the placebo group (IRR 1·09, 95% CI 1·0-1·2; p=0·02). The most common grade 2 or higher product-related adverse events were hypophosphataemia (n=22 for tenofovir vs n=22 for placebo), genital symptoms (n=6 for tenofovir vs n=2 for placebo), or elevated transaminases (n=2 for tenofovir vs n=2 for placebo). No product-related serious adverse events were reported, and no differences in product-related adverse events (p=0·78), grade 3 events (p=0·64), or grade 4 events (p=0·74) were observed between treatment groups., Interpretation: Overall, pericoital tenofovir gel did not prevent HIV-1 acquisition in this population of young women at risk of HIV infection in South Africa. Alternate safe and effective products that are less user dependent than this product or do not require high adherence are needed., Funding: The US Agency for International Development (USAID), the Bill & Melinda Gates Foundation, and the South African Department of Science and Technology and Department of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Neonatal candidaemia is a common, deadly and costly hospital-associated disease. To determine the genetic diversity of Candida parapsilosis causing fungaemia in South African neonatal intensive care units (NICUs). From February 2009 through to August 2010, cases of candidaemia were reported through laboratory-based surveillance. C. parapsilosis isolates from neonatal cases were submitted for identification by internal transcribed spacer (ITS) region sequencing, antifungal susceptibility testing and microsatellite genotyping. Cluster analysis was performed using Unweighted Pair Group Method with Arithmetic Mean (UPGMA). Of 1671 cases with a viable Candida isolate, 393 (24%) occurred among neonates. Isolates from 143 neonatal cases were confirmed as C. parapsilosis sensu stricto. Many isolates were resistant to fluconazole (77/143; 54%) and voriconazole (20/143; 14%). Of 79 closely-related genotypes, 18 were represented by ≥2 isolates; 61 genotypes had a single isolate each. Seven clusters, comprised of 82 isolates, were identified at five hospitals in three provinces. Isolates belonging to certain clusters were significantly more likely to be fluconazole resistant: all cluster 7 isolates and the majority of cluster 4 (78%), 5 (89%) and 6 (67%) isolates (P<.001). Candida parapsilosis-associated candidaemia in public-sector NICUs was caused by closely related genotypes and there was molecular evidence of undetected outbreaks as well as intra-hospital transmission., (© 2017 Blackwell Verlag GmbH.)

Background: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa., Methods: The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 μg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4(+) T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4(+) T-cell counts and therapy compliance., Results: Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4(+) T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4(+) T-cell numbers over study entry levels as compared to placebo., Conclusions: The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012.

Introduction: Streptococcus agalactiae (group B streptococcus; GBS) is globally recognised as one of the leading causes of neonatal sepsis and meningitis. It also causes adverse pregnancy outcomes such as stillbirth and miscarriages. Incidence of invasive disease is increasing in non-pregnant adults with underlying medical conditions (e.g., diabetes mellitus). Epidemiological studies of GBS infections are based on capsular serotyping. Genotyping of the surface anchored protein genes is also becoming an important tool for GBS studies. Currently ten different GBS serotypes have been identified. This study was performed to determine the prevalence of GBS capsular types (CTs) and surface anchored protein genes in isolates from colonized pregnant women attending antenatal clinic, at Dr George Mukhari Academic Hospital, Garankuwa, Pretoria, South Africa., Methods: The samples were collected over 11 months and cultured on selective media. GBS was identified using different morphological and biochemical tests. Capsular typing was done using latex agglutination test and conventional PCR. Multiplex PCR with specific primers was used to detect the surface anchored protein genes., Results: Of the 413 pregnant women recruited, 128 (30.9%) were colonized with GBS. The capsular polysaccharide (CPS) typing test showed that CPS type III (29.7%) was the most prevalent capsular type followed by CPS type Ia (25.8%), II (15.6%), IV (8.6%), V (10.9%) and Ib (8.6%); 0.7% of the isolates were nontypeable. Multiplex PCR revealed that the surface proteins genes were possessed by all the capsular types: rib (44.5%), bca (24.7%), alp2/3 (17.9%), epsilon (8.6%) and alp4 (4.7%)., Conclusion: The common capsular types found in this study are Ia, III, and II. The most common protein genes identified were rib and bca, and the distribution of the surface protein genes among the isolates of different capsular types showed similar trends to the distribution reported from previous studies.