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Our objective was to determine the prevalence and risk factors for HIV infection among female sex workers in Johannesburg, South Africa. A cross-sectional survey of female sex workers was conducted using interviewer-administered questionnaires. Prevalent sexually transmitted infections including HIV were evaluated through standard laboratory testing. HIV infection was identified in 137 (46.4%) of 295 subjects tested. Increasing frequency of condom use was significantly negatively associated with HIV infection (odds ratio [OR] for moderate use = 0.21; 95% confidence interval [CI]: [0.09, 0.50]; OR for high use = 0.14; 95% CI: [0.06, 0.34]). Sex workers aged ≥29 years reported significantly different patterns of behaviour than younger workers. Among women aged ≥29, a negative association with HIV infection (OR = 0.16; 95% CI: [0.07, 0.38]) was found, but only among those not infected with Neisseria gonorrhoeae. Older women in the Johannesburg sex industry may have adaptive behavioural strategies besides condom usage which reduce their risk of acquiring HIV. However, older sex workers with gonorrhoea constitute a high-risk subgroup. [ABSTRACT FROM AUTHOR]

Syphilis is a major cause of adverse outcomes in pregnancy in developing countries. Fetal death and morbidity due to congenital syphilis are preventable if infected mothers are identified and treated appropriately by the middle of the second trimester. Most pregnant women with syphilis are asymptomatic and can only be identified through serological screening. Non-treponemal tests, such as the rapid plasma reagin (RPR) test are sensitive, simple to perform, and inexpensive. However they have often not been available at primary health-care settings because they required cold storage for reagents and electricity to operate a rotator. Additionally, as many as 28% of positive RPR results in pregnant women are biological false positives. Confirmatory assays are usually available only in reference laboratories. Technological advances have resulted in improved serodiagnostic tools for syphilis. New enzyme immunoassays are available for surveillance and for large-scale screening programs. Decentralized antenatal screening with on-site confirmation is now possible since new RPR reagents that are stable at room temperature have become commercially available, as have solar-powered rotators and simple, rapid point-of-care treponemal tests that use whole blood and do not require electricity or equipment. These will be valuable tools for preventing or eliminating congenital syphilis. The development of a non-invasive rapid treponemal test that distinguishes between active and past infections remains a high priority in areas where syphilis is endemic. [ABSTRACT FROM AUTHOR]

Objectives: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998.Methods: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR assay was used to differentiate between HSV-1 and HSV-2.Results: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09).Conclusions: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa. The relative prevalence of primary syphilis has remained low. However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly. HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients. No association was found between HIV infection status and the relative prevalence of chancroid or syphilis. [ABSTRACT FROM AUTHOR]

Evaluates the impact of calendar blister drug packaging on patient compliance undergoing sexually transmitted disease therapy in South Africa. Effect of literacy on patient compliance; Use of pill count method for measuring compliance; Acceptability of the Primary Pill Pak to patients and health care workers.

The purpose of this review is to describe the immune function of the liver, guiding the reader from the homeostatic tolerogenic status to the aberrant activation demonstrated in chronic liver disease. An extensive description of the pathways behind the inflammatory modulation of the healthy liver will be provided focusing on the complex immune cell network residing within the liver. The limit of tolerance will be presented in the context of organ transplantation, seizing the limits of homeostatic mechanisms that fail in accepting the graft, progressing eventually toward rejection. The triggers and mechanisms behind chronic activation in metabolic liver conditions and viral hepatitis will be discussed. The last session will be dedicated to one of the greatest paradoxes for a tolerogenic organ, developing autoimmunity. Through the description of the three most common autoimmune liver disease, the autoimmune reaction against hepatocytes and biliary epithelial cells will be dissected.

The initial idea of a distinct group of T-cells responsible for suppressing immune responses was first postulated half a century ago. However, it is only in the last three decades that we have identified what we now term regulatory T-cells (Tregs), and subsequently elucidated and crystallized our understanding of them. Human Tregs have emerged as essential to immune tolerance and the prevention of autoimmune diseases and are typically contemporaneously characterized by their CD3 + CD4 + CD25 high CD127 low FOXP3 + phenotype. It is important to note that FOXP3 + Tregs exhibit substantial diversity in their origin, phenotypic characteristics, and function. Identifying reliable markers is crucial to the accurate identification, quantification, and assessment of Tregs in health and disease, as well as the enrichment and expansion of viable cells for adoptive cell therapy. In our comprehensive review, we address the contributions of various markers identified in the last two decades since the master transcriptional factor FOXP3 was identified in establishing and enriching purity, lineage stability, tissue homing and suppressive proficiency in CD4 + Tregs. Additionally, our review delves into recent breakthroughs in innovative Treg-based therapies, underscoring the significance of distinct markers in their therapeutic utilization. Understanding Treg subsets holds the key to effectively harnessing human Tregs for immunotherapeutic approaches., Competing Interests: The authors MG, Dl, MP-M, JS, MT and PT are employed by Poltreg S.A. The remaining 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. The author(s) PT and NM-T declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Santosh Nirmala, Kayani, Gliwiński, Hu, Iwaszkiewicz-Grześ, Piotrowska-Mieczkowska, Sakowska, Tomaszewicz, Marín Morales, Lakshmi, Marek-Trzonkowska, Trzonkowski, Oo and Fuchs.)

Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection. Furthermore, HCV treatment with interferon-α leads to specific MAIT cell activation in vivo in parallel with an enhanced therapeutic response. Moreover, TCR-independent activation of MAIT cells leads to a reduction of HCV replication in vitro mediated by IFN-γ. Together these data demonstrate MAIT cells are activated following viral infections, and suggest a potential role in both host defence and immunopathology.

Unlabelled: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix protein and cytokine, is a direct transcriptional target of the Hh pathway. Thus, we hypothesize that Hh signaling induces OPN to promote liver fibrosis in NASH. Hepatic OPN expression and liver fibrosis were analyzed in wild-type (WT) mice, Patched-deficient (Ptc(+/-) ) (overly active Hh signaling) mice, and OPN-deficient mice before and after feeding methionine and choline-deficient (MCD) diets to induce NASH-related fibrosis. Hepatic OPN was also quantified in human NASH and nondiseased livers. Hh signaling was manipulated in cultured liver cells to assess direct effects on OPN expression, and hepatic stellate cells (HSCs) were cultured in medium with different OPN activities to determine effects on HSC phenotype. When fed MCD diets, Ptc(+/-) mice expressed more OPN and developed worse liver fibrosis (P < 0.05) than WT mice, whereas OPN-deficient mice exhibited reduced fibrosis (P < 0.05). In NASH patients, OPN was significantly up-regulated and correlated with Hh pathway activity and fibrosis stage. During NASH, ductular cells strongly expressed OPN. In cultured HSCs, SAG (an Hh agonist) up-regulated, whereas cyclopamine (an Hh antagonist) repressed OPN expression (P < 0.005). Cholangiocyte-derived OPN and recombinant OPN promoted fibrogenic responses in HSCs (P < 0.05); neutralizing OPN with RNA aptamers attenuated this (P < 0.05)., Conclusion: OPN is Hh-regulated and directly promotes profibrogenic responses. OPN induction correlates with Hh pathway activity and fibrosis stage. Therefore, OPN inhibition may be beneficial in NASH., (Copyright © 2010 American Association for the Study of Liver Diseases.)

Unlabelled: Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to nonalcoholic fatty liver disease (NAFLD) progression. Livers normally contain many natural killer T (NKT) cells that produce factors that modulate inflammatory and fibrogenic responses. Such cells are relatively depleted in steatosis, but their status in more advanced NAFLD is uncertain. We hypothesized that NKT cells accumulate and promote fibrosis progression in NASH. We aimed to determine if livers become enriched with NKT cells during NASH-related fibrosis; identify responsible mechanisms; and assess if NKT cells stimulate fibrogenesis. NKT cells were analyzed in wildtype mice and Patched-deficient (Ptc(+/-)) mice with an overly active Hedgehog (Hh) pathway, before and after feeding methionine choline-deficient (MCD) diets to induce NASH-related fibrosis. Effects of NKT cell-derived factors on hepatic stellate cells (HSC) were examined and fibrogenesis was evaluated in CD1d-deficient mice that lack NKT cells. NKT cells were quantified in human cirrhotic and nondiseased livers. During NASH-related fibrogenesis in wildtype mice, Hh pathway activation occurred, leading to induction of factors that promoted NKT cell recruitment, retention, and viability, plus liver enrichment with NKT cells. Ptc(+/-) mice accumulated more NKT cells and developed worse liver fibrosis; CD1d-deficient mice that lack NKT cells were protected from fibrosis. NKT cell-conditioned medium stimulated HSC to become myofibroblastic. Liver explants were 2-fold enriched with NKT cells in patients with non-NASH cirrhosis, and 4-fold enriched in patients with NASH cirrhosis., Conclusion: Hh pathway activation leads to hepatic enrichment with NKT cells that contribute to fibrosis progression in NASH.

As long-term graft survival and mortality after liver transplantation improve, recognition that allografts may be affected by the same disease process that resulted in the failure of the liver is of both clinical and academic importance. Recipients need to be counseled about recurrence and potential impact on graft function and graft survival; clinicians need to be aware of the potential of recurrence to interpret the clinical, laboratory, radiologic, and histologic findings and alter management. Understanding which conditions recur in the allograft and factors associated with recurrence may shed light on pathogenesis. This article discusses the recurrence of nonviral diseases after liver transplantation, diagnosis, and management.

Syphilis is a major cause of adverse outcomes in pregnancy in developing countries. Fetal death and morbidity due to congenital syphilis are preventable if infected mothers are identified and treated appropriately by the middle of the second trimester. Most pregnant women with syphilis are asymptomatic and can only be identified through serological screening. Non-treponemal tests, such as the rapid plasma reagin (RPR) test, are sensitive, simple to perform, and inexpensive. However, they have often not been available at primary health-care settings because they required cold storage for reagents and electricity to operate a rotator. Additionally, as many as 28% of positive RPR results in pregnant women are biological false positives. Confirmatory assays are usually available only in reference laboratories. Technological advances have resulted in improved serodiagnostic tools for syphilis. New enzyme immunoassays are available for surveillance and for large-scale screening programmes. Decentralized antenatal screening with on-site confirmation is now possible since new RPR reagents that are stable at room temperature have become commercially available, as have solar-powered rotators and simple, rapid point-of-care treponemal tests that use whole blood and do not require electricity or equipment. These will be valuable tools for preventing or eliminating congenital syphilis. The development of a non-invasive rapid treponemal test that distinguishes between active and past infections remains a high priority in areas where syphilis is endemic.