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Patulin (PAT) is a food-borne mycotoxin produced by Penicillium and Byssochlamys species. It is widely known for its mutagenic, carcinogenic, and genotoxic effects and has been associated with kidney injury; however, the mechanism of toxicity remains unclear. To address this gap, we conducted a study to explore the changes in α-adrenergic receptor signalling pathways and epigenetic modifications induced by PAT in the kidneys of C57BL/6 mice during acute (1 day) and prolonged (10 days) exposure. The mice (20-22 g) were orally administered PAT (2.5 mg/kg; at 1 and 10 days), and post-treatment, the kidneys were harvested, homogenised and extracted for RNA, DNA, and protein. The relative gene expression of the α-adrenergic receptors (ADRA1, ADRA2A, ADRA2B) and associated signalling pathways (MAPK, MAPK14, ERK, PI3K, and AKT) was assessed by qPCR. The protein expression of ERK1/2 and MAPK was determined by western blot. The impact of PAT on DNA methylation was evaluated by quantifying global DNA methylation; qPCR was used to determine gene expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and demethylase (MBD2). PAT downregulated the expression of ADRA1, ADRA2A, ADRA2B, PI3K, and AKT and upregulated ERK1/2 and MAPK protein expression. Furthermore, PAT induced alterations in DNA methylation patterns by upregulating DNMT1 and MBD2 expressions and downregulating DNMT3A and DNMT3B expressions, resulting in global DNA hypomethylation. In conclusion, PAT disrupts α-1 and α-2 adrenergic receptor signalling pathways and induces epigenetic modifications, that can lead to kidney injury., (© 2024. The Author(s).)

Introduction: Neutrophils play a complex and important role in the immunopathology of TB. Data suggest they are protective during early infection but become a main driver of immunopathology if infection progresses to active disease. Neutrophils are now recognized to exist in functionally diverse states, but little work has been done on how neutrophil states or subsets are skewed in TB disease., Methods: To address this, we carried out comprehensive phenotyping by flow cytometry of neutrophils in the blood and airways of individuals with active pulmonary TB with and without HIV co-infection recruited in Durban, South Africa., Results: Active TB was associated with a profound skewing of neutrophils in the blood toward phenotypes associated with activation and apoptosis, reduced phagocytosis, reverse transmigration, and immune regulation. This skewing was also apparently in airway neutrophils, particularly the regulatory subsets expressing PDL-1 and LOX-1. HIV co-infection did not impact neutrophil subsets in the blood but was associated with a phenotypic change in the airways and a reduction in key neutrophil functional proteins cathelicidin and arginase 1., Discussion: Active TB is associated with profound skewing of blood and airway neutrophils and suggests multiple mechanisms by which neutrophils may exacerbate the immunopathology of TB. These data indicate potential avenues for reducing neutrophil-mediated lung pathology at the point of diagnosis., 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 © 2024 Nhamoyebonde, Chambers, Ndlovu, Karim, Mazibuko, Mhlane, Madziwa, Moosa, Moodley, Hoque and Leslie.)

SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants., (© 2024. The Author(s).)

Introduction: Multipurpose prevention technologies (MPTs) simultaneously prevent HIV, other sexually transmitted infections, and/or unintended pregnancy. Key gatekeepers, [healthcare providers (HCPs) and key stakeholders] require proactive engagement before product implementation. This manuscript identifies HCP demand creation strategies, key stakeholder considerations for the adoption of MPTs in South Africa., Methods: Formative research was conducted in three districts in three South African provinces (July to November 2022). Nurses initiating oral PrEP at facility and mobile study sites participated in 4-hour participatory workshops, exploring HIV prevention, including MPTs, demand creation strategies, and preferred MPTs training packages. Activities were observed, transcribed, and thematically analysed. Five online in-depth interviews (IDIs) with Key informants (KIs) (National/district programme implementers and technical leads) and one in person, exploring key programmatic and policy considerations for MPT adoption. IDIs were approximately 40 min long, audio recorded, transcribed, and thematically analysed., Results: Twenty-one Professional Nurses completed workshops: 19 female. Six IDIs were conducted with 4 Facility Managers, 1 NDoH representative and 1 DoH Provincial Deputy Director. All participants were females, aged 30-60+ years with >10 years' in SRH/HIV policy/advocacy/research. Community conversations and information at the clinic were the best MPT demand creation methods among HCPs. KIs identified five considerations for future MPT implementation: HCP training; demand creation and messaging; existing PrEP policy amendments; preparing users for additional choice; and sustaining MPT provision., Conclusion: Contraceptive implant and oral PrEP implementation lessons learned should be proactively considered when preparing for MPT introduction. HCP training and demand creation are of particular importance before MPT introduction., 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., (© 2024 Kutywayo, Mataboge, Mthimkhulu, Martin, Muhwava, Mazibuko, Makalela, Kwatsha, Butler and Mullick.)

Introduction: Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method; however, males over 15 years face challenges with its effective use. Long-acting prevention products could address barriers to effective PrEP use. This study aimed to estimate the potential uptake of a mono-PrEP implant and the factors influencing uptake among males in South Africa. The study also examined messaging and demand creation tactics that males perceive will improve HIV prevention uptake., Methods: We conducted a mixed methods study comprising participatory workshops and a self-administered survey among 142 PrEP-eligible males (18-40 years) in three provinces (Gauteng, Eastern Cape, and Kwa-Zulu Natal) in South Africa from July to November 2022. Logistic regression was used to assess the relationship between the potential uptake of a hypothetical, non-biodegradable mono-PrEP implant and socioeconomic and behavioural factors. Workshop data were analysed using content analysis., Results: The top three HIV prevention products that males would consider using were the monthly pill (74.6%), the mono-PrEP implant (62.7%), and event-driven oral PrEP (59.2%). If one prevention option was available, 31.7% of participants stated that they would use the monthly oral pill, 28.2% would use the six-monthly injection, and 19.7% the mono-PrEP implant. Four key themes were noted as influential to potential mono-PrEP uptake: "Health Over Everything", "Mono-PrEP Implant Concerns", "Potential Disclosure of Mono-PrEP Use", and "Information Distribution Channels". Participants preferred social and mainstream media as information distribution channels to receive information on HIV prevention services, including the mono-PrEP implant., Conclusion: In this study among predominantly heterosexual men in South Africa, there was interest in long-acting HIV prevention methods but concerns about the mono-PrEP implant. A comprehensive and participatory introduction will be needed for the implant, to improve acceptability and address potential concerns. Demand-creation strategies utilising social media and health campaigns should be considered to engage and reach males., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2024 Mthimkhulu 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: South African women, including female sex workers (FSWs), are disproportionately affected by HIV, experience a high unmet need for contraception and high rates of sexually transmitted infections (STIs). Products that address the interlinked risk between HIV, unplanned pregnancy, and other STIs are needed. There are several multipurpose-prevention technologies (MPTs) in development, aimed at preventing both HIV and pregnancy. This study aimed to explore educational messaging and demand creation channels to improve the potential uptake of a hypothetical MPT implant, using participatory action research. It also aimed to look at product and service provision attributes preferred by potential end users., Methods: Between July and August 2022, 303 PrEP-eligible adolescent girls and young women (AGYW) (18-24 years), women > 24 years, and FSW's (≥ 18 years) participated in 4-hour workshops, where they were asked about their ideal messaging and demand creation channels and their preferences for different attributes of an MPT implant. Quantitative descriptive analysis was conducted to determine the frequency and ranking for each demand creation message, channel, and each product and service provision attribute, by population group. A chi-square test was used to assess MPT implant characteristics associated with age. Qualitative data were analysed using deductive and thematic analysis., Results: A total of 104 AGYW, 157 women > 24 years, and 42 FSWs participated in the PAR workshops. Participants preferred demand creation messages that were empowering, motivational and encouraged body autonomy. The use of slang was popular. Community radio stations and newspapers, social media, and information at hospitals and clinics were participants' preferred MPT demand creation channels because they were easily accessible. Providing long-term and dual HIV and pregnancy protection, receiving implant services at the local clinic, manageable side effects, discreet and private implant, and numbing the area before insertion and removal, were the most preferred product and service provision attributes., Conclusion: Early considerations for women's product preferences are key to product development. Educational messaging around the MPT implant should be empowering and in local languages, this may motivate women to learn more about it and use it. Multiple demand creation channels should be used to engage both young and older populations, which may ensure better reach., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The functionalization of sp 3 carbons is deemed challenging in synthetic organic chemistry yet has tremendous potential in producing potent organic compounds. A facile synthesis of 2,4,5-trisubstituted oxazoles through an oxidative, copper-catalyzed, and solvent-free annulation is described. Various arylated oxazoles were efficaciously synthesized at a mild temperature from readily available substrates under a molecular oxygen atmosphere. Preliminary mechanistic studies suggested that the reaction proceeds via an anionic-type mechanism and indicated the formation of a keto-imine intermediate. The reaction is notable for the abstraction of six hydrogen atoms, the functionalization of one sp 2 carbon and two sp 3 carbons, and the formation of C-O and C-N bonds.

Background: In South Africa, youth experience challenges with oral Pre-Exposure Prophylaxis (PrEP) access and uptake. Taking services out of healthcare settings has the potential to increase reach and overcome these challenges. This paper presents young and older people's preferences for decentralized, simplified PrEP service delivery and new long-acting HIV prevention methods, in Ga-Rankuwa, South Africa., Methods: Between May and August 2021, both PrEP user and non-user adolescent girls and young women (AGYW), pregnant AGYW, female sex workers, adolescent boys and young men (ABYM), and men who have sex with men (MSM) were recruited to participate in focus group discussions (FDGs) in Ga-Rankuwa, Gauteng. Twenty-two FGDs were conducted. Participants were asked about PrEP uptake, potential acceptability of long-acting HIV prevention products, provision of integrated, simplified, and decentralized services, and digital tools to facilitate access to PrEP and other SRH services. A qualitative approach using inductive thematic analysis was carried out to explore emerging themes on decentralized, simplified delivery and the acceptability of long-acting methods., Results: Of the 109 participants included in the study approximately 45% ( n  = 50) were female, the median age was 23 years ± 5.3. A third ( n  = 37) were current or previous PrEP users, of which, 59.5% ( n  = 22) collected PrEP refills from the clinic. Decentralized, simplified service delivery was appealing; health facilities, pharmacies and institutions of learning were preferred as service points for PrEP and SRH services, and recreational spaces preferred for dissemination of health information and engagement. ABYM were more open to having recreational spaces as service points. Long-acting Cabotegravir was preferred over the Dapivirine Vaginal Ring due to concerns around perceived side-effects, efficacy, and comfort., Conclusion: Providing long-acting PrEP methods through decentralized, simplified service delivery was appealing to this population. They provided practical locations for decentralized service provision to potentially increase their engagement with and uptake of HIV prevention and SRH services., 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., (© 2023 Mataboge, Nzenze, Mthimkhulu, Mazibuko, Kutywayo, Butler, Naidoo and Mullick.)

Background: HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections., Methods: We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features., Results: This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal centre (GC) activity, homing capacity, and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naïve B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2-specific EF response in PLWH was confirmed using viral spike and RBD bait proteins., Conclusions: Despite similar disease severity, these trends were highest in participants with uncontrolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge., Funding: This work was supported by a grant from the Wellcome Trust to the Africa Health Research Institute (Wellcome Trust Strategic Core Award [grant number 201433/Z/16/Z]). Additional funding was received from the South African Department of Science and Innovation through the National Research Foundation (South African Research Chairs Initiative [grant number 64809]), and the Victor Daitz Foundation., Competing Interests: RK, JS, HS, DM, FK, YG, AN, YZ, IG, MB, KK, MM, NM, DR, OL, JJ, DS, IW, AS, HK, TN, AL No competing interests declared, WH Reviewing editor, eLife, (© 2022, Krause et al.)

Background: Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses., Methods: We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE 1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF 1 α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE 4 ). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy., Results: PGE-M and LTE 4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE 4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE 4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status., Conclusion: The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia., 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 Arriaga, Karim, Queiroz, Araújo-Pereira, Barreto-Duarte, Sales, Moosa, Mazibuko, Milne, Maruri, Serezani, Koethe, Figueiredo, Kritski, Cordeiro-Santos, Rolla, Sterling, Leslie, Andrade and the RePORT Brazil and South Africa consortia.)

The extent to which Omicron infection 1-9 , with or without previous vaccination, elicits protection against the previously dominant Delta (B.1.617.2) variant is unclear. Here we measured the neutralization capacity against variants of severe acute respiratory syndrome coronavirus 2 in 39 individuals in South Africa infected with the Omicron sublineage BA.1 starting at a median of 6 (interquartile range 3-9) days post symptom onset and continuing until last follow-up sample available, a median of 23 (interquartile range 19-27) days post symptoms to allow BA.1-elicited neutralizing immunity time to develop. Fifteen participants were vaccinated with Pfizer's BNT162b2 or Johnson & Johnson's Ad26.CoV2.S and had BA.1 breakthrough infections, and 24 were unvaccinated. BA.1 neutralization increased from a geometric mean 50% focus reduction neutralization test titre of 42 at enrolment to 575 at the last follow-up time point (13.6-fold) in vaccinated participants and from 46 to 272 (6.0-fold) in unvaccinated participants. Delta virus neutralization also increased, from 192 to 1,091 (5.7-fold) in vaccinated participants and from 28 to 91 (3.0-fold) in unvaccinated participants. At the last time point, unvaccinated individuals infected with BA.1 had low absolute levels of neutralization for the non-BA.1 viruses and 2.2-fold lower BA.1 neutralization, 12.0-fold lower Delta neutralization, 9.6-fold lower Beta variant neutralization, 17.9-fold lower ancestral virus neutralization and 4.8-fold lower Omicron sublineage BA.2 neutralization relative to vaccinated individuals infected with BA.1. These results indicate that hybrid immunity formed by vaccination and Omicron BA.1 infection should be protective against Delta and other variants. By contrast, infection with Omicron BA.1 alone offers limited cross-protection despite moderate enhancement., (© 2022. The Author(s).)

There are conflicting reports on the effects of HIV on COVID-19. Here, we analyzed disease severity and immune cell changes during and after SARS-CoV-2 infection in 236 participants from South Africa, of which 39% were people living with HIV (PLWH), during the first and second (Beta dominated) infection waves. The second wave had more PLWH requiring supplemental oxygen relative to HIV-negative participants. Higher disease severity was associated with low CD4 T cell counts and higher neutrophil to lymphocyte ratios (NLR). Yet, CD4 counts recovered and NLR stabilized after SARS-CoV-2 clearance in wave 2 infected PLWH, arguing for an interaction between SARS-CoV-2 and HIV infection leading to low CD4 and high NLR. The first infection wave, where severity in HIV negative and PLWH was similar, still showed some HIV modulation of SARS-CoV-2 immune responses. Therefore, HIV infection can synergize with the SARS-CoV-2 variant to change COVID-19 outcomes., Competing Interests: FK, IG, SC, YZ, RK, MB, KK, YG, HR, NM, MM, DM, DR, TN, WH, BG, RL, EW, Td, MM, GL, AL, HK, AS No competing interests declared, (© 2021, Karim et al.)

Tuberculosis remains a leading cause of death globally despite curative treatment, partly due to the difficulty of identifying patients who will not respond to therapy. Simple host biomarkers that correlate with response to drug treatment would facilitate improvement in outcomes and the evaluation of novel therapies. In a prospective longitudinal cohort study, we evaluated neutrophil count and phenotype at baseline, as well as during TB treatment in 79 patients [50 (63%) HIV-positive] with microbiologically confirmed drug susceptible TB undergoing standard treatment. At time of diagnosis, blood neutrophils were highly expanded and surface expression of the neutrophil marker CD15 greatly reduced compared to controls. Both measures changed rapidly with the commencement of drug treatment and returned to levels seen in healthy control by treatment completion. Additionally, at the time of diagnosis, high neutrophil count, and low CD15 expression was associated with higher sputum bacterial load and more severe lung damage on chest x-ray, two clinically relevant markers of disease severity. Furthermore, CD15 expression level at diagnosis was associated with TB culture conversion after 2 months of therapy (OR: 0.14, 95% CI: 0.02, 0.89), a standard measure of early TB treatment success. Importantly, our data was not significantly impacted by HIV co-infection. These data suggest that blood neutrophil metrics could potentially be exploited to develop a simple and rapid test to help determine TB disease severity, monitor drug treatment response, and identify subjects at diagnosis who may respond poorly to treatment., (Copyright © 2020 Ndlovu, Peetluk, Moodley, Nhamoyebonde, Ngoepe, Mazibuko, Khan, Karim, Pym, Maruri, Moosa, van der Heijden, Sterling and Leslie.)

Objective: This study assesses whether circulating sTie2 and sHER2 are altered in HIV-negative and HIV-positive pregnant normotensive and preeclamptic women., Methods: Serum samples were obtained from 80 pregnant women, stratified into four groups, namely, HIV-negative normotensives (20); HIV-positive normotensives (20); HIV-negative preeclamptics (20); and HIV-positive preeclamptics (20). The concentration of sTie2 and sHER2 was analyzed by Bio-Plex multiplex immunoassay and generated from a standard curve., Results: sTie2 differed significantly by pregnancy type (p = 0.0403) but not by HIV status (p = 0.5214). sHER2 did not show a significant difference between normotensive and preeclampsia (p = 0.3677) and by HIV status (p = 0.5249)., Conclusion: Irrespective of HIV status, reduced concentrations of sTie2 were evident in preeclampsia (PE) reflecting a dysregulation of the angiogenic process. sHER2 was similar between pregnancy types, attributable to the oxidative stressed microenvironment which promotes dysregulation of the MAPK and P13K/Akt signaling. HIV status did not influence sTie2 and sHER2 expression, reflecting the immune reconstitution of highly active antiretroviral therapy. sTie2 and sHER2 were not influenced by PE comorbid with HIV infection.

Objective: To quantify the impact of tuberculosis (TB) co-infection on death and loss to follow-up (LTFU) 12 months after entry into an ART program., Design: Prospective intervention study., Methods: From May 2007 to 2008, patients undergoing pre-ART training in Durban, South Africa, were screened for pulmonary TB using mycobacterial culture. Subjects missing appointments for >3 months were phoned. Patients who could not be reached were considered LTFU. Deaths were ascertained by report from family members. We used the Kaplan-Meier method to estimate time to LTFU or death for 3 groups at enrollment as follows: (1) newly diagnosed with TB by sputum culture; (2) on TB treatment (ie, previously diagnosed); and (3) TB free. We evaluated the role of TB on mortality and LTFU using Cox proportional hazards models., Results: Nine hundred fifty-one HIV-infected subjects were enrolled; 59% were female, and median baseline CD4 count was 90 cells per microliter (IQR: 41-148 cells/μL). One hundred forty-four (15%) were newly diagnosed with TB by sputum culture; an additional 199 (21%) were already on TB treatment. By 12 months, 26% newly diagnosed with TB at enrollment died or were LTFU, compared with 19% already on TB treatment, and 14% who were TB free (P = 0.001). Controlling for age, sex, smoking, CD4, and opportunistic infection history, subjects newly diagnosed with pulmonary TB were 76% more likely to die or be LTFU (hazard ratio: 1.76, 95% confidence interval: 1.20 to 2.60) than those without TB., Conclusions: HIV/TB co-infected individuals are more likely to die or be LTFU within 12 months of ART clinic entry in South Africa. These patients require intensive follow-up during ART initiation.

Objective: To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa., Design: Cross-sectional cohort study., Methods: Consecutive HIV-infected adults (≥ 18y/o) initiating HIV care were enrolled from May 2007-May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed., Results: 1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42-150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0-12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9-30.5) compared to 5.2% (95% CI 2.1-8.9) among those with no prior TB. 5.1% (95% CI 2.4-9.5) had rifampin or rifampin plus INH resistance., Conclusions: The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence.

Background: The World Health Organization (WHO) recommends cough as the trigger for tuberculosis screening in human immunodeficiency virus (HIV)-infected patients, with acid-fast bacillus (AFB) smear as the initial diagnostic test. Our objective was to assess the yield and cost of a more intensive tuberculosis screening in HIV-infected patients starting antiretroviral therapy (ART) in Durban, South Africa., Methods: We prospectively enrolled adults, regardless of tuberculosis signs/symptoms, who were undergoing ART training from May 2007 to May 2008. After the symptom screen, patients expectorated sputum for AFB smear, tuberculosis polymerase chain reaction (PCR), and mycobacterial culture. Sensitivity and specificity of different symptoms and tests, alone and in combination, were compared with the reference standard of 6-week tuberculosis culture results. Program costs included personnel, materials, and cultures., Results: Of 1035 subjects, 487 (59%) were female; median CD4 cell count was 100 cells/microL. A total of 210 subjects (20%) were receiving tuberculosis treatment and were excluded. Of the remaining 825 subjects, 158 (19%) had positive sputum cultures, of whom 14 (9%) had a positive AFB smear and 82 (52%) reported cough. The combination of cough, other symptoms, AFB smear, and chest radiograph had 93% sensitivity (95% confidence interval, 88%-97%) and 15% specificity (95% confidence interval, 13%-18%). The incremental cost of intensive screening including culture was $360 per additional tuberculosis case identified., Conclusions: Nearly 20% of patients starting ART in Durban, South Africa, had undiagnosed, culture-positive pulmonary tuberculosis. Despite WHO recommendations, neither cough nor AFB smear were adequately sensitive for screening. Tuberculosis sputum cultures should be performed before ART initiation, regardless of symptoms, in areas with a high prevalence of HIV and tuberculosis.

Objective: To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa., Design: Retrospective cohort study., Methods: We reviewed data from ART eligible adults (> or = 18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count < or = 200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression., Results: During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3-3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (< or = 100 cells/microL) and unemployment were independently associated with being lost., Conclusions: Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts.

A two and a half year review of 39 peripartum hysterectomies done at Ga-Rankuwa Hospital from 1 January 1993 to 30 June 1995 was conducted. There were a total of 21,108 deliveries, 4,894 (23.19 pc) of which were caesarean deliveries. The ages of the patients ranged from 17 to 46 years and parity from 0 to 9. A large number, 31 (79.5 pc) of the patients were unbooked. The commonest indications were ruptured uterus 14 (35.9 pc) puerperal sepsis 13 (33.3 pc) and post partum haemorrhage four (10.3 pc). The complications included wound dihescence, sepsis, bladder injury, ureteral injury and two deaths occurred.