Barbara J. Molini

An HIV-infected patient in San Francisco with primary syphilis was treated with azithromycin, but the lesion did not resolve. The authors of this case report confirmed resistance to azithromycin and identified a mutation in the 23S rRNA genes of T. pallidum. The mutation was also found in samples collected in Baltimore, Seattle, and Dublin.

BACKGROUND: Bacterial contamination of platelet (PLT) concentrates can result in transfusion-transmitted sepsis. A photochemical treatment (PCT) process with amotosalen HCl and long-wavelength ultraviolet light (UVA), which cross-links nucleic acids, was developed to inactivate bacteria and other pathogens in PLT concentrates. STUDY DESIGN AND METHODS: High titers of pathogenic aerobic and anaerobic Gram-positive bacteria (10 species), aerobic Gram-negative bacteria (7 species), and spirochetes (2 species) were added to single-donor PLT concentrates containing 3.0 x 10(11) to 6.0 x 10(11) PLTs in approximately 300 mL of 35 percent plasma and 65 percent PLT additive solution (InterSol, Baxter Healthcare) or saline. After PCT with 150 micro mol per L amotosalen and 3 J per cm(2) UVA, residual bacterial levels were detected by sensitive microbiologic methods. RESULTS: The level of inactivation of viable bacteria was expressed as log reduction. Log reduction of Gram-positive bacteria for Staphylococcus epidermidis was > 6.6; for Staphylococcus aureus, 6.6; for Streptococcus pyogenes, > 6.8; for Listeria monocytogenes, > 6.3; for Corynebacterium minutissimum, > 6.3; for Bacillus cereus (vegetative), > 5.5; for Lactobacillus sp., > 6.4; for Bifidobacterium adolescentis, > 6.0; for Propionibacterium acnes, > 6.2; and for Clostridium perfringens, > 6.5. Log reduction of Gram-negative bacteria for Escherichia coli was > 6.4; for Serratia marcescens, > 6.7; for Klebsiella pneumoniae, > 5.6; for Pseudomonas aeruginosa, 4.5; for Salmonella choleraesuis, > 6.2; for Yersinia enterocolitica, > 5.9; and for Enterobacter cloacae, 5.9. Log reduction of spirochetes for Treponema pallidum was 6.8 to 7.0, and for Borrelia burgdorferi, > 6.9. CONCLUSION: PCT inactivates high levels of a broad spectrum of pathogenic bacteria. The inactivation of bacteria in PLT concentrates offers the potential to prospectively prevent PLT-transfusion-associated bacteremia.

The tprK gene sequence of Treponema pallidum subspecies pallidum (T. pallidum) is heterogeneous within and among isolates. Heterogeneity in the tprK open reading frame is localized in seven discrete variable (V) regions, and variability results from apparent base changes, insertions or deletions. The TprK V regions are the focus of anti-TprK antibodies arising during infection. To test our hypothesis that V region sequences change during infection and passage, we developed a clonal isolate from the Chicago strain of T. pallidum and confirmed V region diversification during passage of this isolate. We describe the sequence anatomy of the seven V regions of tprK and the identification of putative donor sites for new V region sequences, and we propose a model for generation of new V regions by segmental gene conversion. These findings suggest that antigenic variation of TprK occurs in T. pallidum and may be important in immune evasion and persistence.

Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.