Background review for the '2020 European guideline for the diagnosis and treatment of gonorrhoea in adults'.

Gonorrhoea is a major public health concern globally. Increasing incidence and sporadic ceftriaxone-resistant cases, including treatment failures, are growing concerns. The 2020 European gonorrhoea guideline provides up-to-date evidence-based guidance regarding the diagnosis and treatment of gonorrhoea. The updates and recommendations emphasize significantly increasing gonorrhoea incidence; broad indications for increased testing with validated and quality-assured nucleic acid amplification tests (NAATs) and culture; dual antimicrobial therapy including high-dose ceftriaxone and azithromycin (ceftriaxone 1 g plus azithromycin 2 g) OR ceftriaxone 1 g monotherapy (ONLY in well-controlled settings, see guideline for details) for uncomplicated gonorrhoea when the antimicrobial susceptibility is unknown; recommendation of test of cure (TOC) in all gonorrhoea cases to ensure eradication of infection and identify resistance; and enhanced surveillance of treatment failures when recommended treatment regimens have been used. Improvements in access to appropriate testing, test performance, diagnostics, antimicrobial susceptibility surveillance and treatment, and follow-up of gonorrhoea patients are essential in controlling gonorrhoea and to mitigate the emergence and/or spread of ceftriaxone resistance and multidrug-resistant and extensively drug-resistant gonorrhoea. This review provides the detailed background, evidence base and discussions, for the 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults (Unemo M, et al. Int J STD AIDS. 2020).

Active anti-interferon-alpha immunization: a European-Israeli, randomized, double-blind, placebo-controlled clinical trial in 242 HIV-1--infected patients (the EURIS study).

This randomized, double-blind, placebo-controlled, phase II/III study was designed to evaluate safety, immunogenicity, and efficacy of an active anti-interferon-alpha (anti-IFN-alpha) vaccine in asymptomatic HIV-1-infected patients. The active immunization was aimed at inducing anti-IFN-alpha antibodies to counteract IFN-alpha overproduction. In all, 242 patients, recruited between December 1995 and July 1996 in eight centers in Europe and Israel, with CD4+ counts from 100 to 634 cells/mm3 who were receiving or not receiving antiretroviral therapy (including protease inhibitors) were randomized to receive either anti-IFN-alpha vaccine or placebo. The anti-IFN-alpha immunization regimen consisted of three priming injections delivered intramuscularly at 1-month intervals in a water-in-oil emulsion of inactivated recombinant IFN-alpha-2b (i-IFN-alpha) followed by intramuscular booster injections of i-IFN-alpha adsorbed onto calcium phosphate every 3 months. Immunogenicity to vaccine was defined as an increase of anti-IFN-alpha antibody level of more than twofold the preimmunization value. Clinical progression, changes in antiretroviral treatment, and decrease of CD4+ counts to <200 cells/mm3 were considered endpoints for efficacy evaluation. Contrary to our previous experience, in which six to seven oil priming injections induced a >90% response rate, the three oil-adjuvanted injections in this trial were suboptimal because only 40 of 122 vaccinees (33%) had raised anti-IFN-alpha antibody following immunization. In vaccinees, both antibody responders (AbRV) and nonresponders (AbNRV), the tolerance to the vaccine was good and was without evidence of significant safety concerns. During the course of the trial, 62% of vaccine responders, 64% of nonresponders, and 63% of placebo patients elected to add protease inhibitor-containing regimens as new treatment guidelines were established, resulting in a marked decrease in clinical and laboratory progression such that the expected endpoints of the study could not be achieved and further follow-up was halted. Despite the unexpectedly low immunogenicity and fewer than expected endpoints, anti-IFN-alpha vaccine recipients, in comparison with placebo recipients, showed a lower rate of disease progression, nonelective treatment changes, and/or CD4+ count decrease to <200 cells/mm3, but the difference was not statistically significant. Nevertheless, the subgroup of patients immunized to IFN-alpha who experienced a rise in anti-IFN-alpha antibodies had a significantly lower rate of occurrence of HIV-1-related events and of any combination of the endpoints compared with those of either placebo patients or vaccinees who failed to develop anti-IFN-alpha antibodies, the latter two groups behaving similarly. Further studies of this approach are warranted because these data suggest a beneficial effect of this adjuvant approach.

Acyclovir resistance/susceptibility in herpes simplex virus type 2 sequential isolates from an AIDS patient.

The biological characterization of a number of sequential herpes simplex virus type 2 (HSV-2) isolates obtained from an AIDS patient undergoing sequential courses of antiviral treatment due to an extended mucocutaneous genital lesion is reported. Resistance to acyclovir (ACV) and related compounds was linked to a thymidine kinase-deficient (TK-) phenotype. After ACV discontinuation and a course of treatment with foscarnet, a new isolate was recovered, characterized by loss of the ACV-resistant trait and production of a functional TK enzyme. Data presented stress the need for monitoring chemosensitivity of HSV isolates in AIDS patients while suggesting that for better control of the infection, these patients should benefit from alternative treatments with drugs aimed at different viral targets.