Sumner E. Thompson

Pelvic Inflammatory Disease and Fertility: A Cohort Study of 1,844 Women with Laparoscopically Verified Disease and 657 Control Women with Normal Laparoscopic Results

From 1960 10 1984, 2,501 women underwent diagnostic laparoscopy (index laparoscopy) because of a clinical suspicion of acute pelvic inflammatory disease (PID). Of these women, 1,844 had abnormal laparoscopic findings (patients) and 657 had normal findings (control subjects). The reproductive events after index laparoscopy of 1,732 patients and 601 control subjects were followed. The patients and control subjects were followed for a total of 13,400 and 3,958 woman-years, respectively. During the follow-up period, 1,309 (75.6%) of the patients and 451 (75.0%) of the control subjects attempted to conceive. Of these women, 209 (16.0%) of the patients and 12 (2.7%) of the control subjects failed to conceive. A total of 141 (10.8%) of the patients and 0 (0%) of the control subjects had confirmed tubal factor infertility, 21 (1.6%) of the patients and 3 (0.7%) control subjects had other causes of infertility, and 47 (3.6%) patients and 9 (2.0%) control subjects did not have a complete infertility evaluation. Additional information on tubal morphology (hysterosalpingography, laparoscopy, or laparotomy) in women from couples for whom evaluation was incomplete indicated that 165 (12.2%) patients and 4 (0.9%) of the control subjects had abnormal tubal function or morphology after index laparoscopy. Tubal factor infertility after PID was associated with number and severity of PID episodes. The ectopic pregnancy rate for first pregnancy after index laparoscopy was 9.1% among the patients and 1.4% among control subjects.

Long-Term Immunogenicity and Efficacy of Hepatitis B Vaccine in Homosexual Men

To study the duration of antibody persistence and protection provided by the hepatitis B vaccine, we followed 773 homosexual men for five years after completion of vaccination. Among the 635 participants in whom antibody levels above 9.9 sample ratio units (SRU) developed after vaccination, 15 percent lost antibody altogether, and in another 27 percent, antibody levels declined below 10 SRU within five years. The extent of the maximal antibody response strongly predicted the persistence of protective antibody. Hepatitis B infection occurred in 55 men; 8 of these infections were clinically important (characterized by the presence of the hepatitis B surface antigen and elevation of liver-enzyme levels), and two of the patients became hepatitis B virus carriers. The long-term risk of hepatitis B infection was inversely related to the maximal antibody response to vaccine. Most severe infections occurred among those who responded poorly or had no response to the vaccination. The risk of late infection with hepatitis B in those with an initially adequate vaccine response increased markedly when antibody levels decreased below 10 SRU, but only 1 of 34 late infections resulted in viremia and liver inflammation. A second series of vaccinations induced a moderate antibody response in 50 percent of the subjects who initially had no response or a poor response; however, the persistence of antibody was poor. Both antibody loss and the risk of severe disease should be considered when booster-dose strategies for the hepatitis B vaccine are being designed.

Comparison of Amphotericin B with Fluconazole in the Treatment of Acute AIDS-Associated Cryptococcal Meningitis

BACKGROUND Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.

The Prevention of Hepatitis B with Vaccine: Report of the Centers for Disease Control Multi-Center Efficacy Trial Among Homosexual Men

A randomized, double-blind, vaccine/placebo trial of the Merck 20-micrograms hepatitis B virus (HBV) vaccine was done among 1402 homosexual men attending venereal disease clinics in five American cities. Vaccination was followed by only minimal side effects. Two doses of vaccine induced antibody in 80% of vaccine recipients. A booster dose 6 months after the first dose induced antibody in 85% of recipients and markedly increased the proportion of recipients who produced high antibody titers. The incidence of HBV events was markedly less in the vaccine recipients compared to that in the placebo recipients (p = 0.0004). Between month 3 and 15 after the first dose, 56 more significant HBV events (hepatitis, or hepatitis B surface antigen positive, or both) occurred in the placebo group while only 11 occurred in the vaccine group. Ten of the 11 HBV events in the vaccine recipients occurred in hypo- or nonresponders to the vaccine. This vaccine appears to be safe, immunogenic, and efficacious in preventing infection with hepatitis B virus.

The Response of Symptomatic Neurosyphilis to High-Dose Intravenous Penicillin G in Patients with Human Immunodeficiency Virus Infection

BACKGROUND Infection with the human immunodeficiency virus (HIV) may affect both the natural course of syphilis and the response to treatment. We examined the response to treatment with high-dose penicillin G in HIV-infected patients with symptomatic neurosyphilis. METHODS Neurosyphilis was defined by reactivity in serum treponemal tests for syphilis, neurologic manifestations consistent with neurosyphilis, and a positive Venereal Disease Research Laboratory (VDRL) test on cerebrospinal fluid. We identified 11 HIV-infected patients with symptomatic neurosyphilis; 5 had been treated previously for early syphilis with penicillin G benzathine. Patients were treated with 18 million to 24 million units of penicillin G per day administered intravenously for 10 days. Cerebrospinal fluid was examined approximately 6 and 24 weeks after treatment, when the polymerase chain reaction and rabbit inoculation were used to detect Treponema pallidum. RESULTS In four of the seven patients studied 24 weeks after treatment, the serum titers on rapid plasma reagin (RPR) testing decreased by at least two doubling dilutions, and four patients had reductions in the cerebrospinal fluid titers on VDRL testing or reverted to nonreactive results. In two patients there was no normalization or improvement in serum titers on RPR testing or cerebrospinal fluid titers on VDRL testing, cell counts, or protein concentrations. One patient relapsed with meningovascular syphilis six months after therapy. T. pallidum was detected by the polymerase chain reaction in cerebrospinal fluid from 3 of 10 patients before treatment, but in none of the 10 post-treatment specimens. CONCLUSIONS In patients with early syphilis who are also infected with HIV, therapy with penicillin G benzathine may fail, and neurosyphilis may develop. The regimen of high-dose penicillin recommended for neurosyphilis is not consistently effective in patients infected with HIV.

Antimicrobial Resistance in Neisseria gonorrhoeae in the United States, 1988–1994: The Emergence of Decreased Susceptibility to the Fluoroquinolones

Antimicrobial susceptibilities of Neisseria gonorrhoeae have been prospectively determined in the Gonococcal Isolate Surveillance Project of the Centers for Disease Control and Prevention. From 1988 through 1994, susceptibilities were determined for 35,263 isolates from 27 clinics. Patients were demographically similar to those in nationally reported gonorrhea cases. In 1994, 30.5% of isolates had chromosomally or plasmid-mediated resistance to penicillin or tetracycline. Penicillin resistance increased from 1988 (8.4%) to 1991 (19.5%) and then decreased in 1994 (15.6%). Tetracycline resistance decreased from 1988 (23.4%) to 1989 (17.3%) and then increased in 1994 (21.7%). Most isolates (99.9%) were highly susceptible to broad-spectrum cephalosporins. Isolates with decreased susceptibility to ciprofloxacin increased from 1991 (0.4%) to 1994 (1.3%); 4 isolates were ciprofloxacin-resistant. Ciprofloxacin-resistant strains may not respond to therapy with recommended doses of fluoroquinolones, and the clinical importance of strains with decreased susceptibility is unknown. The emergence of fluoroquinolone resistance in N. gonorrhoeae in the United States threatens the future utility of this class of antimicrobials for gonorrhea therapy.

The microbiology and therapy of acute pelvic inflammatory disease in hospitalized patients

We examined microbial isolates from the endocervical and peritoneal cavity of 30 women hospitalized with acute PID. Patients were randomly assigned to one of two antibiotic regimens: amoxicillin, 6 gm by mouth every 24 hours, or aqueous penicillin G, 30 million units and gentamicin, 180 to 240 mg intravenously every 24 hours. We measured response by quantifying physical examination findings. Neisseria gonorrhoeae was isolated from the cervix of 24 patients (80%) and from the peritoneal cavity of 10 (33%). Other peritoneal isolates included Enterobacteriaceae in five patients, Ureaplasma urealyticum in five, Mycoplasma hominis in six, and Chlamydia trachomatis in three. Bacteroides melaninogenicus, the most frequent anaerobe, was isolated in 11 cases. Bacteroides fragillis was not isolated from any specimen. The cure rates were the same for both regimens: three patients failed on each. Four women required total abdominal hysterectomy and unilateral or bilateral salpingo-oophorectomy.

The Changing Epidemiology of Human Immunodeficiency Virus Infection in Older Persons

OBJECTIVE: To describe the epidemiology of human immunodeficiency virus (HIV) infection diagnosed in persons aged 60 years and older at a large urban county hospital.

Declining CD4+ T-lymphocyte counts are associated with increased risk of enteric parasitosis and chronic diarrhea: results of a 3-year longitudinal study.

From January 1991 through September 1994, we observed people who were infected with HIV to assess the impact of enteric parasite-associated diarrhea. Respondents answered comprehensive questionnaires covering clinical and epidemiologic information and provided stool specimens monthly, which were examined unstained as well as stained with trichrome, chromotrope 2R, and with Kinyoun carbol-fuchsin, and with indirect immunofluorescence for Cryptosporidium. In all, 602 participants, who were interviewed, provided stool specimens at 3254 monthly visits. Parasites were associated with 50 of 354 (14.1%) acute diarrheal episodes (lasting < or = 28 days) and with 97 of 279 (34.8%) chronic episodes (lasting > 28 days). A parasite was associated with 31 of 222 (14.0%) episodes that occurred when CD4+ counts were > or = 200 cells/microl and with 150 of 566 (26.5%) episodes that occurred when CD4+ counts were < 200 cells/microl. The most commonly identified parasite was C. parvum, which was associated with 18 of 354 (5.1%) acute episodes and 36 (12.9%) of the 279 chronic episodes of diarrhea. In this patient population, enteric protozoan parasites were commonly associated with illness, particularly as immunosuppression worsened, and were more likely to be associated with chronic rather than acute diarrhea.

Presence of antibodies to the major anaerobically induced gonococcal outer membrane protein in sera from patients with gonococcal infections.

Anaerobically grown Neisseria gonorrhoeae induces and represses the synthesis of outer membrane proteins. One of the anaerobically induced proteins, Pan 1, reacted strongly on Western blots with sera from patients with uncomplicated gonococcal infection, pelvic inflammatory disease, and disseminated gonococcal infection, but not with normal human serum. The pattern of reactivity of the sera against Pan 1 from several gonococcal strains suggested that the protein was antigenically heterogeneous, containing both common and unique epitopes. Staphylococcus aureus V8 protease digestion of Pan 1 from four gonococcal strains revealed the presence of common peptides, with one strain also containing some unique peptides and lacking others. The class of the antibody reactive with gonococcal outer membrane antigens was examined; anti-Pan 1 antibody was found to be IgG or IgM, but not IgA. The IgM antibody present reacted predominantly with Pan 1. These data indicate that the Pan 1 protein is expressed in vivo and strongly suggest that N. gonorrhoeae can grow anaerobically in vivo.