Last data update: May 20, 2024. (Total: 46824 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Henning TC [original query] |
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In vitro activity of EDTA and TOL-463 against Neisseria gonorrhoeae
Nash EE , Henning TC , Pham CD , Pettus K , Sharpe S , Kersh EN . Diagn Microbiol Infect Dis 2018 93 (4) 369-371 Neisseria gonorrhoeae quickly develops drug resistance. Time-kill curves revealed that EDTA and TOL-463 inhibit growth similar to penicillin, ciprofloxacin, and azithromycin. Furthermore, synergistic and additive antimicrobial interactions occurred when EDTA and TOL-463 were combined with penicillin or azithromycin, respectively, suggesting that further investigations into these unconventional antimicrobials may be advantageous. |
Population attributable fraction of tubal factor infertility associated with chlamydia
Gorwitz RJ , Wiesenfeld HC , Chen PL , Hammond KR , Sereday KA , Haggerty CL , Johnson RE , Papp JR , Kissin DM , Henning TC , Hook EW 3rd , Steinkampf MP , Markowitz LE , Geisler WM . Am J Obstet Gynecol 2017 217 (3) 336 e1-336 e16 BACKGROUND: Chlamydia trachomatis infection is highly prevalent among young women in the United States. Prevention of long-term sequelae of infection, including tubal factor infertility, is a primary goal of chlamydia screening and treatment activities. However, the population attributable fraction of tubal factor infertility associated with chlamydia is unclear, and optimal measures for assessing tubal factor infertility and prior chlamydia in epidemiologic studies have not been established. Black women have increased rates of chlamydia and tubal factor infertility compared to white women, but have been underrepresented in prior studies of the association of chlamydia and tubal factor infertility. OBJECTIVES: To estimate the population attributable fraction of tubal factor infertility associated with Chlamydia trachomatis infection by race (black, non-black), and assess how different definitions of C. trachomatis seropositivity and tubal factor infertility affect population attributable fraction estimates. STUDY DESIGN: We conducted a case-control study, enrolling infertile women attending infertility practices in Birmingham, AL and Pittsburgh, PA during October 2012 - June 2015. Tubal factor infertility case status was primarily defined by unilateral or bilateral fallopian tube occlusion (cases) or bilateral fallopian tube patency (controls) on hysterosalpingogram. Alternate tubal factor infertility definitions incorporated history suggestive of tubal damage or were based on laparoscopic evidence of tubal damage. We aimed to enroll all eligible women, with an expected ratio of one and three controls per case for black and non-black women, respectively. We assessed C. trachomatis seropositivity with a commercial assay and a more sensitive research assay; our primary measure of seropositivity was defined as positivity on either assay. We estimated C. trachomatis seropositivity and calculated C. trachomatis-TFI odds ratios and population attributable fraction, stratified by race. RESULTS: We enrolled 107 black women (47 cases, 60 controls) and 620 non-black women (140 cases, 480 controls). C. trachomatis seropositivity by either assay was 81% (95% confidence interval 73%, 89%) among black and 31% (95% confidence interval 28%, 35%) among non-black participants (P<0.001). Using the primary C. trachomatis seropositivity and tubal factor infertility definitions, no significant association was detected between chlamydia and tubal factor infertility among blacks (odds ratio 1.22, 95% confidence interval 0.45, 3.28) or non-blacks (odds ratio 1.41, 95% confidence interval 0.95, 2.09), and the estimated population attributable fraction was 15% (95% confidence interval -97%, 68%) among blacks and 11% (95% confidence interval -3%, 23%) among non-blacks. Use of alternate serologic measures and tubal factor infertility definitions impacted the magnitude of the chlamydia-tubal factor infertility association, and resulted in a significant association among non-blacks. CONCLUSIONS: Low population attributable fraction estimates suggest factors in addition to chlamydia contribute to tubal factor infertility in the study population. However, high background C. trachomatis seropositivity among controls, most striking among black participants, could have obscured an association with tubal factor infertility and resulted in a population attributable fraction that underestimates the true etiologic role of chlamydia. Choice of chlamydia and tubal factor infertility definitions also impacts odds ratio and population attributable fraction estimates. |
Practical Experience with Analysis and Design of Repeat Low-Dose SHIVSF162P3 Exposure Studies in Female Pigtail Macaques with Varying Susceptibility During Menstrual Cycling
Kersh EN , Henning TC , Dobard C , Heneine W , McNicholl JM . AIDS Res Hum Retroviruses 2015 31 (11) 1166-9 BACKGROUND: Vaginal SHIVSF162P3 acquisition in pigtail macaques (Macaca nemestrina) is dependent on time point during the menstrual cycle. Susceptibility is higher around menstruation and lower at ovulation in mid cycle. This complicates design of repeat low-dose (RLD) SHIV exposure studies because virus challenges given during low susceptibility periods have lower chances to infect. To account for fluctuating susceptibility, we analyzed menstrual cycles rather than exposures until infection following virus challenges. FINDINGS: We first re-analyzed infection data of 41 macaques receiving placebo or no treatment during once (n=18) or twice (n=23) weekly virus exposures. The same number of cycles was required for infection with either challenge frequency, while it took a median 4 or 6 challenges for once or twice weekly exposures, respectively. More virus challenges to infection likely reflect frequent unsuccessful exposures in frequently exposed animals. When re-analyzing two previously reported biomedical HIV intervention studies, we found 1% Tenofovir gel was 74 or 86 % efficacious based on cycles or exposures (p = 0.019 or = 0.003, respectively, Fisher's exact test), while 1% Raltegravir gel was 84 or 89 % efficacious, respectively (p = 0.047 or = 0.031). CONCLUSIONS: Evaluating number of menstrual cycles rather than exposures until infection can account for varying susceptibility during the menstrual cycle. Our observations have implications for future study designs such as planning frequency of virus exposures. Menstrual cycle analysis may also avoid potential over-estimation of efficacy against vaginal challenges during low susceptibility periods in the cycle that are unlikely to cause infection. |
Relationship of menstrual cycle and vaginal infection in female rhesus macaques challenged with repeated, low doses of SIVmac251
Morris MR , Byrareddy SN , Villinger F , Henning TC , Butler K , Ansari AA , McNicholl JM , Kersh EN . J Med Primatol 2015 44 (5) 301-5 Varying susceptibility during menstrual cycling could be a factor for S(H)IV infection risk in female rhesus macaques. We retrospectively determined vaginal SIV infection time points relative to the menstrual cycle in a group of rhesus macaques (n=11) enrolled in an HIV transmission trial. Eight of nine rhesus macaques became infected around menstruation time. |
Rectal application of a highly osmolar personal lubricant in a macaque model induces acute cytotoxicity but does not increase risk of SHIV infection
Vishwanathan SA , Morris MR , Wolitski RJ , Luo W , Rose CE , Blau DM , Tsegaye T , Zaki SR , Garber DA , Jenkins LT , Henning TC , Patton DL , Hendry RM , McNicholl JM , Kersh EN . PLoS One 2015 10 (4) e0120021 BACKGROUND: Personal lubricant use is common during anal intercourse. Some water-based products with high osmolality and low pH can damage genital and rectal tissues, and the polymer polyquaternium 15 (PQ15) can enhance HIV replication in vitro. This has raised concerns that lubricants with such properties may increase STD/HIV infection risk, although in vivo evidence is scarce. We use a macaque model to evaluate rectal cytotoxicity and SHIV infection risk after use of a highly osmolar (>8,000 mOsm/kg) water-based lubricant with pH of 4.4, and containing PQ15. METHODS: Cytotoxicity was documented by measuring inflammatory cytokines and epithelial tissue sloughing during six weeks of repeated, non-traumatic lubricant or control buffer applications to rectum and anus. We measured susceptibility to SHIVSF162P3 infection by comparing virus doses needed for rectal infection in twenty-one macaques treated with lubricant or control buffer 30 minutes prior to virus exposure. RESULTS: Lubricant increased pro-inflammatory cytokines and tissue sloughing while control buffer (phosphate buffered saline; PBS) did not. However, the estimated AID50 (50% animal infectious dose) was not different in lubricant- and control buffer-treated macaques (p = 0.4467; logistic regression models). CONCLUSIONS: Although the test lubricant caused acute cytotoxicity in rectal tissues, it did not increase susceptibility to infection in this macaque model. Thus neither the lubricant-induced type/extent of inflammation nor the presence of PQ15 affected infection risk. This study constitutes a first step in the in vivo evaluation of lubricants with regards to HIV transmission. |
Non-human primate models of hormonal contraception and HIV
McNicholl JM , Henning TC , Vishwanathan SA , Kersh EN . Am J Reprod Immunol 2014 71 (6) 513-22 PROBLEM: Recent concerns that hormonal contraception (HC) may increase risk of HIV acquisition has led to keen interest in using non-human primates (NHP) to understand the underlying mechanism and the magnitude of the risk. This is, in part, because some experiments which would be difficult or logistically impossible in women are more easily conducted in NHP. METHOD OF STUDY: NHP models of HIV can inform HIV acquisition and pathogenesis research and identify and evaluate biomedical preventions and treatments for HIV/AIDS. Widely used species include rhesus, pigtail, and cynomolgous macaques. RESULTS: This paper reviews past, current and proposed NHP research around the intersection of HIV and HC. CONCLUSION: NHP research may lead to the identification of hormonally regulated biomarkers that correlate with HIV-acquisition risk, to a ranking of existing or next-generation HC along an HIV-acquisition risk profile, and inform research around new biomedical preventions for HIV. |
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