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A positive rapid plasma reagin (RPR) result in children under the age of 2 years indicates either passive transplacental transfer of maternal antibodies or active infection with syphilis (possible congenital syphilis). We describe trends in RPR seropositivity in this population using centralized laboratory data. A secondary analysis of laboratory data collected through the National Health Laboratory Service, Corporate Data Warehouse from 2010 to 2019 was conducted. Of the 127 150 children <2 years included in the analysis, 10 969 [8.6%; 95% confidence interval (95% CI) 85-88]) were RPR seropositive. RPR seropositivity increased from 6.5% to 13.0% between 2010 and 2019. Overall, the annual rate of RPR seropositivity was relatively stable between 2010 and 2018 with a range of 89-127/100 000 live births, increasing sharply to 165/100 000 livebirths in 2019. KwaZulu-Natal and North West provinces recorded the largest increases in annual seropositivity rate, while Eastern Cape and Western Cape had the most significant declines. Although this analysis is limited to laboratory results, in the absence of major changes in testing practices, there may be a rise in the burden of antenatal syphilis exposure in utero indicating an increase in maternal syphilis and syphilis transmission in the general population. South Africa needs to intensify Mother-to-Child Transmission of syphilis elimination efforts to reach the WHO target of ≤50 cases per 100 live births by 2030. [ABSTRACT FROM AUTHOR]

RNA remains the most informative and accurate biomarker for human immunodeficiency virus type 1 load diagnostics and for surveillance of drug resistance markers. Viral load testing by nucleic acid amplification currently is a complex and expensive test that is restricted to centralized laboratory testing. Successful extension of centralized viral load testing to rural or remote settings is a major challenge. Emerging nucleic acid-based technologies are progressing rapidly toward platforms appropriate for field use in low-resource settings, leaving a growing gap for sample processing technologies that complement them. One area in which new technologies could be applied to improve access is clinical specimen preservation and processing. Novel technologies that extract nucleic acid from clinical specimens and stabilize it at the point of specimen collection could fill this gap. In addition, these technologies may provide alternative viral load detection and surveillance solutions to the current centralized laboratory testing paradigm. [ABSTRACT FROM AUTHOR]

Background. Our study evaluated correlates of human immunodeficiency virus (HIV)-1 lesional shedding among men with genital ulcer disease (GUD). Methods. Participants were recruited at primary health care clinics as part of a randomized trial of episodic acyclovir among men with GUD. This analysis was done among HIV-positive men identified at baseline. Participants were serologically screened for HIV infection, syphilis, and herpes simplex virus type 2 infection and for urethritis and ulcer etiology by polymerase chain reaction. Plasma and genital ulcer HIV-1 loads and CD4 cell counts were quantified. We evaluated variables associated with the presence and quantity of HIV-1 in ulcers. Results. Among 387 HIV-positive men, the median plasma HIV-1 load and CD4 cell count were 87,200 copies/ mL and 282 cells/mm3. Overall, 173 (45.6%) had detectable HIV-1 RNA in ulcers. Men with Trichomonas vaginalis infection had higher ulcer viral loads on average than did those who were not infected (mean difference, 0.62; 95% confidence interval [CI], 0.07-1.2; P=.027). After multivariable analysis, higher plasma HIV-1 load (odds ratio [OR], 2.5; 95% CI, 1.7-3.5; P < .001), larger lesions (OR, 2.5; 95% CI, 1.5-4.1; P < .001), purulent ulcers (OR, 2.2; 95% CI, 1.1-4.2; P=.02), multiple ulcers (>5; OR, 3.6; 95% CI, 1.6-8.4; P=.002), and herpes seropositivity (OR, 3.4; 95% CI, 1.7-7.0; P < .001) remained associated with increased odds of HIV-1 lesional shedding. Ulcers associated with herpes simplex virus type 2 infection were less likely to shed (OR, 0.6; 95% CI, 0.3-1.0; P=.05), compared with ulcers with unknown etiology. Conclusions. HIV-positive men should be screened and treated for GUD to minimize HIV shedding and transmission to uninfected sexual partners. [ABSTRACT FROM AUTHOR]

Background. It is uncertain whether episodic acyclovir will enhance ulcer healing if delivered at primary health care settings, because there is often a delay in treatment initiation. Methods. A double-blind, randomized, placebo-controlled trial of 5-day acyclovir (400 mg 3 times daily) was conducted among men with genital ulcers in South Africa. Participants received syndromic management; were tested for ulcer etiology, human immunodeficiency virus (HIV), syphilis, and herpes simplex virus type 2 (HSV-2); and were seen over the course of a month to evaluate ulcer healing and HIV-1 RNA shedding. Outcomes were ulcer duration and HIV-1 RNA shedding, assessed on day 7 among HIV-1-seropositive participants with a herpetic ulcer. Results. A total of 309 men received acyclovir, and 306 received placebo; 63% were HIV-1 positive. There were 295 HIV-1-positive participants with a herpetic ulcer. Acyclovir improved ulcer healing-61% of those receiving acyclovir healed by day 7, compared with 42% of those receiving placebo (adjusted relative risk, 1.4 [95% confidence interval, 1.1-1.8]; P = .003). Acyclovir also improved healing by a median of 3 days (P = .002) and reduced HIV-1 ulcer shedding on day 7 (24% for acyclovir vs 37% for placebo; P = .05). Conclusions. Addition of acyclovir to syndromic management will improve healing of genital ulcers and may potentially reduce HIV transmission in combination with other interventions. Trial registration. ClinicalTrials.gov identifier: NCT00164424. [ABSTRACT FROM AUTHOR]

Background. The objectives of this study were to assess the impact among young men of herpes simplex virus type 2 (HSV-2) status on the acquisition of human immunodeficiency virus (HIV) and on the protective effect of male circumcision against HIV acquisition. Methods. We used data collected during a male circumcision trial conducted in Orange Farm, South Africa. We estimated adjusted incidence rate ratios (IRRs) for HIV acquisition, using survival analysis and background characteristics, HSV-2 status, male circumcision status, and sexual behavior as covariates. Results. Compared with subjects who remained HSV-2 negative throughout the study, subjects who were HSV-2 positive at enrollment had an adjusted IRR of 3.3 (95% confidence interval [CI], 1.5-7.4; P = .004), and those who became HSV-2 positive during follow-up had an adjusted IRR of 7.0 (95% CI, 3.9 -12.4; P < .001). The population fraction of incident HIV infection attributable to HSV-2 was 27.8% (95% CI, 17.7%-37.2%). Intention-to-treat analysis of the protective effect of male circumcision on HIV acquisition was the same among men with and men without HSV-2 (0.38 vs. 0.37; P = .93). Conclusions. This study shows that HSV-2 has a substantial impact on HIV acquisition among young South African men. It suggests that HSV-2 infection enhances HIV acquisition and is responsible for~25% of incident cases of HIV infection. However, the protective effect of male circumcision against HIV acquisition appears independent of HSV-2 serostatus. Trial registration. ClinicalTrials.gov identifier: NCT00122525. [ABSTRACT FROM AUTHOR]

Background. A causal association links high-risk human papillomavirus (HR-HPV) and cervical cancer, which is a major public health problem. The objective of the present study was to investigate the association between male circumcision (MC) and the prevalence of HR-HPV among young men. Methods. We used data from aMC trial conducted in Orange Farm, South Africa, among men aged 18-24 years. Urethral swab samples were collected during a period of 262 consecutive days from participants in the intervention (circumcised) and control (uncircumcised) groups who were reporting for a scheduled follow-up visit. Swab samples were analyzed using polymerase chain reaction. HR-HPV prevalence rate ratios (PRRs) were assessed using univariate and multivariate log Poisson regression. Results. In an intention-to-treat analysis, the prevalences of HR-HPV among the intervention and control groups were 14.8% (94/637) and 22.3% (140/627), respectively, with a PRR of 0.66 (0.51- 0.86) (P = .002). Controlling for propensity score and confounders (ethnic group, age, education, sexual behavior [including condom use], marital status, and human immunodeficiency virus status) had no effect on the results. Conclusions. This is the first randomized controlled trial to show a reduction in the prevalence of urethral HR-HPV infection after MC. This finding explains why women with circumcised partners are at a lower risk of cervical cancer than other women. [ABSTRACT FROM AUTHOR]

Background. In the absence of interventions and breastfeeding, the in utero transmission rate of human immunodeficiency virus (HIV) is estimated to be 10%–15%, and the role that amniotic fluid (AF) plays in this is unclear. Objectives. Levels of cytomegalovirus (CMV) in AF and levels of HIV-1 in AF, maternal blood, and fetal cord blood were assessed. Study design. We enrolled 23 HIV-1-positive women with healthy, singleton pregnancies who underwent elective cesarean section (CS) at full term. The Roche Amplicor HIV-1 Monitor test (version 1.5) was used for determination of maternal plasma VLs. The NASBA Nuclisens assay was used for determination of VLs in other samples. To determine the feasibility of detecting viral infections in AF, CMV polymerase chain reaction DNA extraction was performed on the AF samples by use of the QIAamp DNA kit. Results. HIV-1 RNA was not detected in either AF or fetal cord blood. CMV was detected in 4 AF samples. Maternal CD4+ T cell counts were 158–654 cells/mL (mean, 405 cells/mL). The maternal plasma VLs ranged from below detectable limits to 169,990 copies/mL (mean, 33,700 copies/mL). Conclusions. In the absence of medical complications and before labor, AF collected during elective CS from women who had received either zidovudine or nevirapine during late-stage pregnancy was free of HIV. [ABSTRACT FROM AUTHOR]

Interleukin-18 (IL-18) is a newly described cytokine, formerly called interferon-γ (IFN-γ)— inducing factor. In a simple 24-h human whole blood culture, IFN-γ was produced by the combination of lipopolysaccharide (LPS) plus IL-18. To liberate cytokines in the leukocyte and red cell compartments, the detergent Triton X-100 was added to the entire blood culture. The combination of low concentrations of LPS plus IL-18 induced a 3- to 5-fold greater production of IFN-γ than did either stimulant alone. Tumor necrosis factor-α (TNF-α), IL-6, and IL-8 were also produced. The presence of IL-10 completely suppressed the production of IFN-γ and reduced that of TNF-α, IL-6, and IL-8. Thus, IFN-γ, TNF-α, IL-8, and IL-6 are produced in a single whole blood culture, making correlations in the synthesis of a T helper type 1 cytokine and proinflammatory cytokines with disease activity possible in a single culture. [ABSTRACT FROM PUBLISHER]

Background. Data about respiratory coinfections with 2009 pandemic influenza A virus subtype H1N1 during the 2009–2010 influenza pandemic in Africa are limited. We used an existing surveillance program for severe acute respiratory illness to evaluate a new multiplex real-time polymerase chain reaction assay and investigate the role of influenza virus and other respiratory viruses in pneumonia hospitalizations during and after the influenza pandemic in South Africa.Methods. The multiplex assay was developed to detect 10 respiratory viruses, including influenza A and B viruses, parainfluenza virus types 1–3, respiratory syncytial virus (RSV), enterovirus, human metapneumovirus (hMPV), adenovirus (AdV), and rhinovirus (RV), followed by influenza virus subtyping. Nasopharyngeal and oropharyngeal specimens were collected from patients hospitalized with pneumonia at 6 hospitals during 2009–2010.Results. Validation against external quality controls confirmed the high sensitivity (91%) and specificity (100%) and user-friendliness, compared with other PCR technologies. Of 8173 patients, 40% had single-virus infections, 17% had coinfections, and 43% remained negative. The most common viruses were RV (25%), RSV (14%), AdV (13%), and influenza A virus (5%). Influenza virus, RSV, PIV type 3, and hMPV showed seasonal patterns.Conclusion. The data provide a better understanding of the viral etiology of hospitalized cases of pneumonia and demonstrate the usefulness of this multiplex assay in respiratory disease surveillance in South Africa. [ABSTRACT FROM AUTHOR]