Search

1 Administration of the potent 5-hydroxytryptamine (5-HT) re-uptake inhibitor fluvoxamine (25 mg/kg i.p. for 14 days) to adult cycling female rats did not alter either the number of oestrous episodes or the plasma concentrations of luteinizing hormone determined on days 2, 9 and 14 of treatment. 2 Fluvoxamine (25 mg/kg i.p.) induced in male rats a clear-cut lowering of beta-endorphin-like immunoreactivity from the anterior pituitary, but not the neurointermediate lobe, and increased concomitantly plasma levels of beta-endorphin and beta-lipotropin. 3 Fluvoxamine (12.5 and 25 mg/kg i.p.) stimulated, although not strikingly, prolactin (PRL) secretion in adult male rats, and at 25 mg/kg i.p. potentiated the PRL-releasing effect of 5-hydroxytryptophan (30 mg/kg i.p.). 4 In male rats treated daily with fluvoxamine (25 mg/kg i.p.) the PRL-releasing effect of an additional acute fluvoxamine administration (same dose) was abolished after 4 days maintenance treatment. One week after withdrawal of maintenance, which had been given for 14 days, the challenge dose of fluvoxamine was still unable to raise plasma PRL levels. 5 The endocrine effects of acute fluvoxamine administration are compatible with activation of 5-HT neurotransmission in the central nervous system. The mechanism(s) underlying tolerance to the PRL-releasing action of the drug is presently obscure. Its elucidation should provide insight into the mechanism of action of antidepressant drugs affecting 5-HT function. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is a dysbiosis of vaginal microbiota characterized by a shift from Lactobacillus species predomination to a heterogeneous mixture of anaerobes. We compared the performance characteristics of the Allplex ™ BV molecular assay with the reference test, Nugent score microscopy, for vaginal swab specimens from symptomatic South African women. A total of 213 patients were enrolled, of whom 99 (46.5%) and 132 (62.0%) were diagnosed with BV by Nugent and Allplex™, respectively. The Allplex™ BV assay displayed a sensitivity of 94.9% (95% CI, 88.7%-97.8%) and a specificity of 66.7% (95% CI, 57.6%-74.6%), with an agreement of 79.8% (95% CI, 73.9%-84.7%) (κ = 0.60). Assay design may be enhanced for improved specificity by accounting for differences in healthy and BV-associated vaginal microbiomes among women of different ethnicities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Acyclovir (ACV) is currently included in the syndromic management algorithm for genital ulcer disease in South Africa, and is the recommended first-line treatment for herpes simplex virus 2 (HSV-2). In the majority of cases, HSV-2 resistance to ACV is due to amino acid changes within the viral thymidine kinase (TK). Phenotypic and genotypic ACV resistance surveillance of HSV-2 derived from genital ulcer disease swab specimens was conducted at a primary healthcare facility in Johannesburg between 2018 and 2020. The objectives of this surveillance were to identify ACV resistance-associated mutations and polymorphisms in HSV-2 TK, and to determine the phenotypic ACV resistance profiles of the corresponding clinical HSV-2 isolates. Genotypic analysis of TK from 67 HSV-2 positive genital ulcer swabs revealed 48 specimens with TK mutations, conferring 113 nucleotide changes. No resistance-associated mutations were found, however, we identified nine known natural polymorphisms (R26H, A27T, S29A, G39E, N78D, L140F, T159I, R220K and R284S) and five amino acid changes of unknown significance (R18C, G39K, M70R, P75S and L263P). Phenotypic susceptibility testing of 52 cultivable HSV-2 isolates revealed all to be susceptible to ACV with IC 50 values of <2 μg/ml. The five amino acid changes of unknown significance identified by genotypic testing were not correlated to phenotypic ACV resistance, and therefore grouped as natural polymorphisms. We did not detect any unknown or resistance-associated mutations in specimens that could not be phenotypically tested for ACV resistance. Our findings will supplement existing databases of HSV antiviral resistance-associated mutations and polymorphisms that could be used for genotypic ACV resistance screening., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: We used an in-house molecular assay for the detection of Klebsiella granulomatis in ulcer specimens collected over a 12-year surveillance period in order to determine whether a diagnosis of donovanosis could be ascribed to genital ulcer disease (GUD) of unknown aetiology in our setting., Methods: Between 2007 and 2018, a total of 974 genital ulcer specimens with no previously identified sexually transmitted (STI) pathogens were selected from STI aetiological surveys conducted in all nine provinces of South Africa. Giemsa-stained ulcer smears from the same participants had previously been routinely analysed for the presence of typical Donovan bodies within large mononuclear cells. A Klebsiella screening assay targeting the phoE (phosphate porin) gene was used in combination with restriction digest analysis and sequencing to confirm the presence of K. granulomatis ., Results: The Klebsiella screening assay tested positive in 19/974 (2.0%) genital ulcer specimens. Restriction digest analysis and nucleotide sequencing of the phoE gene confirmed that none of these specimens was positive for K. granulomatis DNA. Similarly, Donovan bodies were not identified in the Giemsa stained ulcer smears of these specimens., Conclusions: This is the first study to assess K. granulomatis as a cause of genital ulceration in South Africa over a 12-year surveillance period using molecular methods. The results demonstrate that K. granulomatis is no longer a prevalent cause of GUD in our population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To estimate the prevalence, incidence and persistence of anal HPV infection and squamous intra-epithelial lesions (SILs) among men living with HIV (MLHIV), and determine their risk factors., Methods: We enrolled MLHIV ≥18 years, who attended 6-monthly visits for 18 months. Socio-behavioural data were collected by questionnaire. Clinicians collected blood sample (CD4+ count and HIV plasma viral load), anal swabs (HPV DNA testing) and anal smears (Bethesda classification) at each visit. HPV DNA testing and classification of smears were done at enrolment and last follow-up visit (two time points). Factors associated with persistent anal HPV infection and SILs were evaluated with generalized estimating equations logistic regression and standard logistic regression respectively., Results: Mean age of 304 participants was 38 (Standard Deviation, 8) years; 25% reported >1 sexual partner in the past 3 months. Only 5% reported ever having sex with other men. Most (65%) participants were taking antiretroviral treatment (ART), with a median CD4+ count of 445 cells/μL (IQR, 328-567). Prevalence of any-HPV infection at enrolment was 39% (88/227). In total, 226 men had anal HPV DNA results at both enrolment and final visits. Persistence of any-anal HPV infection among 80 men who had infection at enrolment was 26% (21/80). Any persistent anal HPV infection was more frequent among MLHIV with low CD4+ count (<200 vs. >500 cells/μL; aOR = 6.58; 95%CI: 2.41-17.94). Prevalence of anal SILs at enrolment was 49% (118/242) while incidence of SILs among MLHIV who had no anal dysplasia at enrolment was 27% (34/124). Of the 118 men who had anal dysplasia at enrolment, 15% had regressed and 38% persisted by month 18. Persistent anal HPV infection was associated with persistent SILs (aOR = 2.95; 95%CI: 1.08-10.89). ART status or duration at enrolment were not associated with persistent anal HPV infection or persistent SILs during follow-up., Conclusion: In spite of a high prevalence of anal HPV, HIV-positive heterosexual men have a low burden of anal HPV related disease. HPV vaccine and effective ART with immunological reconstitution could reduce this burden of infection., Competing Interests: The authors have declared that no competing interests exist.

We report the clinical symptoms and examination findings of Mycoplasma genitalium (MG) in women living with human immunodeficiency virus in South Africa. If we relied on syndromic management alone to treat MG, only 15 of 46 MG-infected women would have received. appropriate treatment: sensitivity of 32.6% (95% confidence interval, 19.5-48.0) and specificity of 67.4% (95% confidence interval, 63.4-71.2).

This prospective cohort study of 622 women living with human immunodeficiency virus (HIV) from Johannesburg (2012) detected Mycoplasma genitalium in 7.4% (95% confidence interval [CI]: 5.5-9.7, 46/622), with detection more likely with lower CD4 counts(adjusted odds ratio [AOR] 1.02 per 10 cells/μL decrease, 95% CI: 1.00-1.03) and higher plasma HIV-1 RNA (AOR 1.15 per log copies/mL increase, 95% CI: 1.03-1.27). No mutations for macrolide/quinolone resistance was detected., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To estimate the incidence; persistence and correlates of human papillomavirus (HPV) infection and anogenital warts (AGW) among men living with human immunodeficiency virus (MLHIV)., Methods: Overall, 304 MLHIV 18 years or older were enrolled and attended follow-up visits at 6, 12, and 18 months. Clinicians examined for AGW, collected blood, and penile swabs for HPV testing (Roche Linear Array) at each visit. Time to AGW incidence or clearance was estimated by Kaplan-Meier method. Factors associated with persistent HPV infection and AGW clearance were evaluated with generalized estimating equations and Cox regression, respectively., Results: Mean age of participants was 38 years (standard deviation, 8 years); 25% reported more than 1 sexual partner in the past 3 months. Most (65%) participants were on antiretroviral treatment (ART) with a median CD4 count of 445 cells/μL (interquartile range, 328-567). Prevalence of HPV infection and AGW at enrolment were 79% (224 of 283) and 12% (36 of 304), respectively. Two hundred fifty-nine men were followed up for a median (interquartile range) 1.4 years (0.5-1.7 years). Incidence of any-genital HPV infection was 2.9 (95% confidence interval, 1.5-5.5) per 100 person-years. Persistence of any-genital HPV infection was 35% (68 of 192) and was higher among MLHIV with low CD4 count (adjusted odds ratio, 3.54; 95% confidence interval, 2.07-6.05). Incidence of AGW was 1.4 per 100 person-years. Men living with human immunodeficiency virus with high CD4 count were more likely to clear AGW than those with low CD4 count (adjusted hazard ratio, 3.69; 95% confidence interval, 1.44-9.47). No associations were observed between persistent genital HPV infection, AGW clearance with enrolment ART status or duration., Conclusions: Human immunodeficiency virus-positive men have a high burden of genital HPV infection and AGW. The ART and HPV vaccine could reduce this burden.