ArticleJournal of the International AIDS Society2014
Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.
Article in Journal of the International AIDS Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Management of Adult Syphilis: Key Questions to Inform the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infections Treatment Guidelines.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Pooled it
- Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2025Trial
- Jarisch-Herxheimer reaction as a complication of penicillin G and ceftriaxone treatment in neurosyphilis.BMC infectious diseases · 2026Article
- Increased serum APOC3 in patients with syphilis can predict the absence of Jarisch-Herxheimer reaction after benzathine penicillin treatment.Journal of the Chinese Medical Association : JCMA · 2025Article
- An Updated Review of Recent Advances in Neurosyphilis.Frontiers in medicine · 2022Review
- A 2021 Update on Syphilis: Taking Stock from Pathogenesis to Vaccines.Pathogens (Basel, Switzerland) · 2021Review
- High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch-Herxheimer Reaction in Patients with Active Syphilis.Infection and drug resistance · 2021Article
- [Evolution of treatment of syphilis through history].Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2018Review
- The Jarisch-Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis.The American journal of tropical medicine and hygiene · 2017Review
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated.
methodsIn HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance.
resultsThe overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted.
conclusionsTreatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.
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