The new england journal of medicine n engl j med 351;2 www.nejm.or decades, syphilis infection has been treated with penicillin , and Treponema pallidum has not developed resistance to penicillin. In many countries, the recommended treatment for early syphilis is a single dose of penicillin G benzathine, which maintains bactericidal levels for weeks, killing the slowly metabolizing treponemes. Azithromycin, which has a long tissue half-life and can be administered orally, was found to be effective in the treatment of syphilis in a rabbit model 1 and in small studies in humans. 2-6 Because of its convenience and efficacy, azithromycin is increasingly being used for the treatment of syphilis by clinicians and in disease-control activities in Canada and the United States, although it is not currently recommended by the Centers for Disease Control and Prevention. 7 We discuss one patient with clinical failure of azithromycin therapy for syphilis, among several cases that have been recognized. 8 We identified a mutation in the 23S ribosomal RNA (rRNA) genes in a specimen of T. pallidum obtained from this patient, and we confirmed functional azithromycin resistance in vivo in a strain of T. pallidum that contain this mutation. Testing of T. pallidum samples obtained at four geographically diverse sites revealed a high frequency of this mutation in clinical specimens. samples Swab samples were collected from primary or moist secondary syphilis lesions in patients at

While numerous studies examine methamphetamine use and associated risky sexual behaviors in HIV-uninfected individuals, few studies have surveyed HIV-infected individuals in the health care setting. To assess the frequency and trends of methamphetamine use, sexual activity, injection drug use, patient-provider communication, and medication adherence among HIV-infected persons in care, we administered a one-page anonymous survey in 2004 and 2006. The survey was conducted at the two University of California, San Francisco outpatient HIV clinics: at Moffitt Hospital (Moffitt), serving primarily privately insured patients, and at San Francisco General Hospital (SFGH), a county hospital serving primarily patients who are uninsured or publicly insured. In 2006, 39% of men who have sex with men (MSM), 33% of heterosexual men, and 11% of women reported methamphetamine use in the prior 12 months. Methamphetamine use was significantly associated with an increased number of sex partners among MSM and heterosexual men, and poor anti-retroviral medication adherence. Among MSM, methamphetamine use was more common at the SFGH clinic. Between 2004 and 2006, reported methamphetamine use in the last 12 months decreased among MSM at Moffitt (38 to 20%, p<0.01), but increased at SFGH (40 to 50%, p<0.05). Among methamphetamine users we found a high frequency of injection of methamphetamine, which increased at SFGH from 38 to 55%, p<0.05. Patient-provider communication regarding methamphetamine use has increased from 2004 to 2006 but no significant change has been found for providers asking patients about sexual activity. Overall, we found methamphetamine use to be common among HIV-infected patients in care, and associated with an increased number of sex partners, a high frequency of injection drug use, and poor adherence to anti-retroviral medications. These findings support the need for improved screening and clinic-based interventions to reduce and treat methamphetamine abuse and associated high risk sexual behaviors.

Azithromycin-resistant T. pallidum is widespread in San Francisco. We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used.

Bartonella bacilliformis, the agent of human Oroya fever, invades erythrocytes and causes a severe hemolytic anemia. The ability of two minimally invasive strains of Escherichia coli (DH5␣ and HB101) to invade human erythrocytes was enhanced 6-to 39-fold by transformation with pIAL1, a plasmid containing a 1,469-bp BamHI fragment from the B. bacilliformis chromosome. Invasiveness was confirmed by gentamicin protection and transmission electron microscopy. DNA hybridization analysis confirmed the presence of the locus in B. bacilliformis KC583 and KC584 and its absence in E. coli chromosomal DNA. Sequencing of the DNA insert of pIAL1 revealed tandem open reading frames of 510 and 558 bp, designated ialA and ialB, respectively. Invasion assays with E. coli containing only an ialA or ialB recombinant suggest that both genes are necessary for invasiveness. The ialA gene is predicted to code for a polypeptide of 170 amino acids (20.1 kDa), and ialB is predicted to code for a polypeptide of 186 amino acids (19.9 kDa). In vitro transcription and translation of pIAL1 produced insert-specific protein bands with masses of approximately 21 and 20 kDa when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Expression of ialA and ialB in E. coli maxicells produced proteins with masses of approximately 21 kDa (IalA) and 18 kDa (IalB). Maxicell and computer analyses suggest that IalB contains an N-terminal secretory signal sequence which is posttranslationally cleaved. Searches of various DNA and protein databases revealed that IalA contains an N-terminal region of 35 amino acids with a high degree of homology to an NTPase consensus domain. There is 63.6% sequence conservation between the IalB protein and the invasion-associated protein Ail of Yersinia enterocolitica.

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A gene with homology to those encoding an unusual class of C-terminal processing proteases that flanks the invasion-associated locus ialAB of Bartonella bacilliformis has been identified. The 1302 bp gene, termed ctpA, is located immediately upstream of the ialA gene and encodes a predicted nascent product of 434 amino acids, producing a mature protein of 411 amino acid residues. The Bartonella CtpA appears to undergo autolysis in vitro, producing multiple products of 43-46 kDa, and a second group of products of 36-37 kDa. Production of CtpA in vivo gives a single product of 41.8 kDa. In addition to a computer-predicted N-terminal secretory signal sequence, the molecular mass difference in vivo versus in vitro indicates that CtpA is likely to be secreted and post-translationally modified. The full-length CtpA protein shows 30% identity to the CtpA protein of Synechocystis sp. 6803 (69% overall sequence similarity). The mature CtpA protein also has significant homology to the tail-specific protease (Tsp) of Escherichia coli, with 22 O/ O identity and 62 O/ O similarity to an internal region of the 660 amino acid Tsp. The CtpA protein does not appear to exhibit haemolysin, collagenase, or caseinase activity. The ctpA gene is conserved in all Bartonella species examined, as determined by hybridization analyses, but it was not found in Brucella abortus or E. coli. The ctpA gene does not directly affect the erythrocyte-invasion phenotype conferred by ialAB, but its homology to other stress-response processing proteases implies an important role in survival of this intracellular pathogen.The University Of

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. a b s t r a c tThe increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC 50 of 0.01 ng mL −1 and 0.16 ng mL −1 respectively.The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined.The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the combination of biological and physio-chemical techniques is optimal.