HIV immunology

"Objectives: To ascertain if syphilis screening reliably detects latent disease, including in the HIV context, by comparing standard syphilis testing with newly-developed techniques, using either recombinant antigen based treponemal serology or direct detection by DNA amplification.

Methods: (1) 500 patients at a downtown Toronto HIV clinic were screened from 1988-1992 with both RPR and quantified treponemal tests, including MHA-Tp (TPHA). (2) Serum aliquots from a further 250 patients from the University of Toronto's AIDS Epi-Study were similarly tested in 1992. (3) 557 patients from another downtown HIV/STD clinic were screened in 2000 as above, and also monitored with the Trep-Chek, a more sensitive, FDA-approved, recombinant ag-based EIA test. (4) Recently, 183 patients from two dermatology clinics in Budapest were tested for T. pallidum DNA with a nested PCR.

Results: (1) None of 500 patients were RPR(+), while 60/500 were TPHA (+), 11 of whom had no syphilis history. Six with a syphilis history were TPHA (-) with CD4 < 80/ul. (2) Of 125/250 Epi-Study patients with HIV, 24 had dropping treponemal titres during B-cell polyclonal activation, while only one HIV(-) case lost treponemal antibody selectively in this way. (3) Of 557 clinic patients, none were RPR(+), while 27 had evidence of syphilis by Trep-Chek, 24 of whom were WB (+) or equivocal. Nine were TPHA(+). Only 4/27 had ever been followed up. (4) 13/183 of the Budapest group were syphilis PCR(+), while only four had ever been treated. These four were the only TPHA (+) persons in the group.

Conclusions: Diagnostically, early acute syphilis is one thing and latent syphilis is quite another. RPR(+) findings were extremely rare among these nearly 1500 high-risk patients. Screening for syphilis with anti-lipoidal tests, based on a 1906 concept, is inappropriate. The persistence of treponemal antibody may indicate ongoing syphilis infection despite therapy, and such patients may need re-treatment and follow-up using gene amplification. Some patients with latent syphilis seem to have little or no treponemal antibody. It is therefore unclear to what extent undetected latent syphilis overlaps with HIV, and HIV/AIDS."

Publication of the first efficacious large-scale HIV vaccine trial in 2009 prompted fresh hope that design of a protective vaccine against HIV may be achievable. In this review we explore the difficult task of eliciting protective immune responses to HIV and highlight the hurdles that vaccine design must still overcome.

This review argues that syphilis has been underdiagnosed and undertreated, a problem that goes back to the beginning of the Wassermann era, and indeed long before. Non-treponemal tests do not detect the larger pool of persons with latent syphilis, the immunological consequences of which have not been systematically investigated in the context of HIV infection and progression to AIDS. Recent efforts to confirm the prevalence of syphilis in high-risk patients by reverse sequence screening, i.e. using a treponemal test first, as the screening test, have revealed untreated syphilis at higher rates than expected. Further testing using PCR discovered even more previously undetected cases. We suggest that latent syphilis is a chronic active immunological condition that drives the AIDS process and cannot be managed with the older Wassermann-based algorithm, and that non-treponemal tests have failed to associate syphilis with immune suppression since this screening concept was developed in 1906. In light of the overwhelming association between a past history of syphilis and HIV seroconversion, more sensitive tools, including recombinant antigen-based immunological tests and direct detection (PCR) technology, are needed to adequately assess the role of latent syphilis in persons with HIV/AIDS. Repeating older syphilis reinoculation studies may help establish a successful animal model for AIDS, and resolve many paradoxes in HIV science.

As the only state with close-to universal health care, Massachusetts has a unique role in ending a viral epidemic. Because treatment reduces infectiousness very dramatically, at least 92%, and because of easy access to testing, pre- and post-exposure prophylaxes, and HAART rapid treatment, the number of "new cases" is down 58% in 6 years, and probably much more due to long-standing, "undercounted" infected by non-symptomatic cases.

These conclusions have much more significance in other locales, since they signal the end of a worldwide epidemic.

Objective: To assess whether the culture technique recently developed to isolate Borrelia burgdorferi from patients with chronic lyme disease would improve the sensitivity of the diagnosis of syphilis, especially in HIV infected individuals at high risk for re-exposure to Treponema pallidum. Methods: A review of the historical literature on cell-wall deficient forms of various spirochetes, especially T. pallidum, was undertaken in an attempt to trace parallels between the apparent insensitivity of serologic and gene amplification techniques used in lyme and what may be a similar insensitivity in syphilis diagnosis. Results: The sensitivity of non-treponemal tests in the diagnosis of syphilis has historically been questioned. Many pre-1970 authors repeatedly stated that latent syphilis was most likely maintained in part by a spirochetal life cycle distinct from the easily demonstrated binary fission of T. pallidum. This research was abandoned in light of the efficacy of penicillin. T...