Judith N. Wasserheit

Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases.

&NA; Understanding the role of other sexually transmitted diseases (STDs) in the transmission of human immunodeficiency virus (HIV), the role of STDs in progression of HIV disease, and the role of HIV infection in alterations of natural history, diagnosis, or response to therapy of STDs is critical to the development of optimal strategies for HIV control. One hundred sixty‐three studies on the interrelationships between HIV infection and other STDs were examined. Of 75 studies on the role of STDs in HIV transmission, the 15 analyses of examination or laboratory evidence of STDs adjusted for sexual behavior showed that both ulcerative and nonulcerative STDs increase the risk of HIV transmission approximately 3‐ to 5‐fold. Due to limited data, the role of STDs in progression of disease remains unclear. Preliminary data from 83 reports on the impact of HIV infection on STDs suggest that, at a community level, HIV infection may increase the prevalence of some STDs (e.g., genital ulcers). If coinfection with HIV prolongs or augments the infectiousness of individuals with STDs, and if the same STDs facilitate transmission of HIV, these infections may greatly amplify one another. This “epidemiological synergy” may be responsible for the explosive growth of the HIV pandemic in some populations. Effective STD control programs will be essential to HIV prevention in these communities.

Towards a common definition of global health

This commentary makes the argument for the necessity of a common definition of global health.

Genital chlamydial infections: epidemiology and reproductive sequelae.

Genital chlamydial infection is increasing and is now more common than gonorrhea. A sizable percentage of chlamydial infections of the lower genital tract in women progress to endometritis and salpingitis. Tubal infertility and ectopic pregnancy are important sequelae. Failure to control chlamydial infections reflects the following four factors: (1) Many cases are mild or asymptomatic; (2) diagnostic tests are expensive and technically demanding; (3) at least 7 days of multiple-dose therapy are currently required; and (4) partner notification is not routinely performed. Thus early identification of infected persons and compliance with curative therapy are less likely than with other sexually transmitted bacterial diseases.

Combination HIV Prevention: Significance, Challenges, and Opportunities

No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop “prevention packages” that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

Endometrial histopathology in patients with culture-proved upper genital tract infection and laparoscopically diagnosed acute salpingitis.

To define and quantitate histologic changes in the endometrium that best correlate with documented upper genital tract infection (UGTI) and laparoscopically diagnosed acute salpingitis, we studied endometrial biopsy specimens from 69 consecutive patients with clinically suspected acute pelvic inflammatory disease (PID) who underwent microbiological evaluation for UGTI and laparoscopic examination for acute salpingitis. Both UGTI and acute laparoscopically confirmed salpingitis were present in 37 patients (54%), UGTI without salpingitis in 1 (1%), salpingitis without UGTI in 11 (16%), and neither UGTI nor salpingitis in 20 (29%). Chlamydia trachomatis or Neisseria gonorrhoeae UGTI was found in 34 women, Escherichia coli in two patients, Peptococcus magnus in one woman, and with Streptococcus agalactiae in one woman. The following features were correlated both with UGTI and with salpingitis: presence of any neutrophils in the endometrial surface epithelium; neutrophils within gland lumens; dense subepithelial stromal lymphocytic infiltration; any stromal plasma cells; and germinal centers containing transformed lymphocytes. The simultaneous presence of five or more neutrophils per x400 field in endometrial surface epithelium, together with one or more plasma cell per x 120 field in endometrial stroma, was the best predictor of UGTI plus salpingitis. This combination had a sensitivity of 92% and a specificity of 87% for predicting the diagnosis of both UGTI and laparoscopically confirmable acute salpingitis. Prospective studies are needed to assess the usefulness of these criteria.

Weighing the gold in the gold standard: challenges in HIV prevention research.

Objective(s):Few HIV prevention interventions have been evaluated in randomized controlled trials (RCTs). We examined design, implementation, and contextual considerations that may limit detection of a positive or adverse effect in HIV prevention trials. Design:A systematic review of late phase RCTs for prevention of sexual transmission of HIV that randomly allocated intervention and comparison groups; evaluated interventions to prevent sexual transmission in nonpregnant populations; and reported HIV incidence as the primary or secondary outcome. Methods:PubMed/MEDLINE, other electronic databases, and electronic conference proceedings of recent HIV/AIDS-related conferences were searched to identify published or unpublished trials meeting the inclusion criteria. Descriptive, methodological, and contextual factors were abstracted from each trial. Results:The review included 37 HIV prevention RCTs reporting on 39 unique interventions. Only six RCTs, all evaluating biomedical interventions, demonstrated definitive effects on HIV incidence. Five of the six RCTs significantly reduced HIV infection: all three male circumcision trials, one trial of sexually transmitted infection treatment and care, and one vaccine trial. One microbicide trial of nonoxynol-9 gel produced adverse results. Lack of statistical power, poor adherence, and diluted versions of the intervention in comparison groups may have been important issues for the other trials that demonstrated ‘flat’ results. Conclusion:Almost 90% of HIV prevention trials had ‘flat’ results, which may be attributable to trial design and/or implementation. The HIV prevention community must not only examine evidence from significant RCTs, but must also examine flat trials and address design and implementation issues that limit detection of an effect.

The emerging threat of untreatable gonococcal infection

It is time to sound the alarm. During the past 3 years, the wily gonococcus has become less susceptible to our last line of antimi crobial defense, threatening our ability to cure gonorrhea and prevent severe sequelae.

Microbial Causes of Proven Pelvic Inflammatory Disease and Efficacy of Clindamycin and Tobramycin

Thirty-six women with suspected pelvic inflammatory disease were examined by laparoscopy and endometrial biopsy. Acute salpingitis was diagnosed by laparoscopy in 22. Among women with evaluable biopsy samples, plasma cell endometritis was present in 14 of 20 with acute salpingitis and in 1 of 13 without acute salpingitis (p less than 0.001). Chlamydia trachomatis, Neisseria gonorrhoeae, or both were identified in the endometrium or fallopian tubes in 11 of 14 women with both salpingitis and endometritis, in 2 of 9 with salpingitis or endometritis alone, and in 0 of 13 without salpingitis or endometritis (p less than 0.0001). Anaerobic or facultative bacteria or mycoplasmas were isolated from tubes or peritoneum from 9 of 14 women with both salpingitis and endometritis, 2 of 9 with salpingitis or endometritis alone, and 3 of 13 without salpingitis or endometritis. Therapy with clindamycin plus tobramycin produced an adequate short-term clinical response in 16 of 19 patients, although patients with severe salpingitis at laparoscopy responded slowly.

The significance and scope of reproductive tract infections among Third World women

Due to biomedical, behavioral and societal factors, reproductive tract infections are widespread in the Third World. Without early diagnosis and accurate therapy, their complications severely compromise womens health, fertility and productivity; infant health and survival; and the effectiveness of family planning programs. Clinicians and public health planners can address these treatable syndromes through research and services in socially acceptable settings including family planning, prenatal and MCH clinics. Specific approaches are discussed.

HIV Vaccines: New Frontiers in Vaccine Development

A human immunodeficiency virus (HIV) vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual. Because safety concerns limit the use of live, attenuated HIV and inactivated HIV, a variety of alternate approaches is being investigated. Traditional antibody-mediated approaches using recombinant HIV envelope proteins have shown no efficacy in 2 phase III trials. Current HIV vaccine trials are focusing primarily on cytotoxic T lymphocyte-mediated products that use viral vectors, either alone or as boosts to DNA plasmids that contain viral genes. The most immunogenic of these products appear to be the recombinant adenovirus vector vaccines, 2 of which are now in advanced clinical development.