Human papillomavirus (HPV) infection is a necessary but not sufficient cause of cervical cancer. While chlamydia infection has been associated with cervical cancer, the meaning of this association remains unclear. The authors' objective was to investigate this association by evaluating whether concurrent genital tract infections are associated with HPV persistence, a precursor to cervical cancer. Interview data and biologic samples for HPV, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis testing were collected from female adolescents in an Atlanta, Georgia, longitudinal cohort study at 6-month visits (1999-2003). Associations with persistence (detection of the same HPV type at two sequential visits (visit pair)) were assessed among subjects with 2-5 visits and > or =6 months of follow-up. Associations were evaluated by logistic regression using methods for correlated data. Type-specific persistence of high-risk HPV types was detected in 77 of 181 (43%) analyzed visit pairs. Concurrent infection with C. trachomatis was independently associated with persistence of high-risk HPV types (adjusted odds ratio = 2.1, 95% confidence interval: 1.0, 4.1). Infection with more than one HPV type at the initial visit was also associated with high-risk persistence (adjusted odds ratio = 2.8, 95% confidence interval: 1.6, 4.9). The association between chlamydia infection and cervical cancer may be due to an effect of chlamydia infection on persistence of high-risk HPV.

Abstract. Invasion of mammalian cells by the protozoan parasite Trypanosoma cruzi occurs by an actinindependent mechanism distinct from phagocytosis. Clusters of host lysosomes are observed at the site of parasite attachment, and lysosomal markers are detected in the vacuolar membrane at early stages of the entry process. These observations led to the hypothesis that the trypanosomes recruit host lysosomes to their attachment site, and that lysosomal fusion serves as a source of membrane to form the parasitophorous vacuole.Here we directly demonstrate directional migration of lysosomes to the parasite entry site, using time-lapse video-enhanced microscopy of L6E 9 myoblasts exposed to T. cruzi trypomastigotes. BSA-gold-loaded lysosomes moved towards the cell periphery, in the direction of the parasite attachment site, but only when their original position was less than 11-12 Ixm from the invasion site. Lysosomes more distant from the invasion area exhibited only the short multi-directional saltatory movements previously described for lysosomes, regardless of their proximity to the cell margins.Specific depletion of peripheral lysosomes was obtained by microinjection of NRK cells with antibodies against the cytoplasmic domain of lgp 120, a treatment that aggregated lysosomes in the perinuclear area and inhibited T. cruzi entry. The microtubule-binding drugs nocodazole, colchicine, vinblastine, and taxol also inhibited invasion, in both NRK and LrE 9 cells. Furthermore, microinjection of antibodies to the heavy chain of kinesin blocked the acidification-induced, microtubule-dependent redistribution of lysosomes to the host cell periphery, and reduced trypomastigote entry.Our results therefore demonstrate that during T. cruzi invasion of host cells lysosomes are mobilized from the immediately surrounding area, and that availability of lysosomes at the cell periphery and microtubule/kinesin-mediated transport are requirements for parasite entry.

Previous studies have demonstrated that protection against New World leishmaniasis caused by Leishmania amazonensis can be elicited by immunization with the developmentally regulated Leishmania amastigote antigen, P-8. In this study, several independent experimental approaches were employed to investigate the protective immunological mechanisms involved. T-cell subset depletion experiments clearly indicate that elicitation of CD8 ؉ (as well as CD4 ؉ ) effector responses is required for protection. Further, mice lacking ␤ 2 -microglobulin (and hence deficient in major histocompatibility complex class I antigen presentation) were not able to control a challenge infection after vaccination, indicating an essential protective role for CD8 ؉ T effector responses. Analysis of the events ongoing at the cutaneous site of infection indicated a changing cellular dynamic involved in protection. Early postinfection in protectively vaccinated mice, a predominance of CD8 ؉ T cells, secreting gamma interferon (IFN-␥) and expressing perforin, was observed at the site of infection; subsequently, activated CD4؉ T cells producing IFN-␥ were primarily found. As protection correlated with the ratio of total IFN-␥-producing cells (CD4 ؉ and CD8 ؉ T cells) to macrophages found at the site of infection, a role for IFN-␥ was evident; in addition, vaccination of IFN-␥-deficient mice failed to provide protection. To further assess the effector mechanisms that mediate protection, mice deficient in perforin synthesis were examined. Perforin-deficient mice vaccinated with the P-8 antigen were unable to control infection. Thus, the elicitation of CD8 ؉ T cell effector mechanisms (perforin, IFN-␥) are clearly required in the protective immune response against L. amazonensis infection in vaccinated mice.

We found high HIV incidence among a high-risk population of US men diagnosed with P&S syphilis in STD clinics in Atlanta, San Francisco, and Los Angeles. Intensive integrated HIV/STD prevention programs are needed for this population.

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