Biomedical subjects

A R Ronald

Publications and source records attributed to A R Ronald.

At least 37 records · Page 2Linked to original sources

PubMed1992

Evaluation of new anti-infective drugs for the treatment of chancroid. Infectious Diseases Society of America and the Food and Drug Administration.

Chancroid is a mucocutaneous infection caused by Haemophilus ducreyi that produces ulcerative lesions and enhances the efficiency of transmission of human immunodeficiency virus (HIV). Confirmation of infection by culture of H. ducreyi is essential in therapeutic trials. Minimal inhibitory concentrations of antibiotics for the isolate should be determined by agar dilution. Patients should be evaluated by appropriate laboratory tests for syphilis, infection with herpes simplex virus, gonorrhea, and (in North America) infection with Chlamydia trachomatis. The clinical history of the disease should be recorded and ulcers, buboes, and lymphadenitis mass described. Whenever possible, study participants also should be tested for HIV infection. Randomized, prospective, double-blind, active-control comparative clinical trials are preferred for evaluation of the safety and efficacy of new anti-infective drugs. Otherwise-healthy men and women should be enrolled in these studies. Patients with active syphilis or genital herpes should be excluded. Microbiological and clinical outcomes are paramount.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of vaginal infections. Infectious Diseases Society of America and the Food and Drug Administration.

The three major vaginal infections are yeast vulvovaginitis, Trichomonas vaginalis vaginitis, and bacterial vaginosis. In terms of signs and symptoms, these disorders overlap substantially with one another and with other infections. Therefore, the diagnosis of candidiasis and trichomoniasis requires isolation of the responsible pathogen. For the diagnosis of bacterial vaginosis, all other potential causes of vaginal infection must be excluded and specified laboratory criteria must be met. Clinical trials must be carefully designed to control for coexisting pathogens, for potential efficacy of treatment against more than one microbe, and for variable end points used to define clinical response. Prospective, randomized, double-blind, active-control comparative studies are preferred. Follow-up evaluations 5-7 days and 4-6 weeks after the completion of therapy are required for the assessment of outcome. Laboratory studies of vaginal fluid (culture and/or microscopic examination) are paramount in the final appraisal of outcome.

Anti-Infective Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of uncomplicated gonorrhea in adults and adolescents. Infectious Diseases Society of America and the Food and Drug Administration.

Gonorrhea is among the most common sexually transmitted diseases. Treatment for uncomplicated gonorrhea should be efficacious in > or = 95% of cases. Because patients with gonococcal infections often have other sexually transmitted diseases concurrently, individuals enrolled in clinical trials of therapy for gonorrhea should also be evaluated for infection with Chlamydia trachomatis and for syphilis. Testing for other pathogens should be considered in light of the clinical presentation. The presence of gonococcal infection is defined by a positive culture of a specimen obtained from an appropriate mucosal site. Patients enrolled in clinical trials should be otherwise-healthy adults who agree to return for follow-up assessment. These patients should be stratified by gender and anatomic site of infection. The preferred study design is a prospective, randomized, double-blind, active-control comparison. In some circumstances, however, historical controls may suffice. The study drug must have an efficacy rate of > or = 95% in genital and rectal infections. Microbiological eradication, demonstrated by negative cultures of samples from all potentially infected mucosal sites at follow-up, is the sole determinant of efficacy.

Adolescent↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of sexually transmitted chlamydial infections and related clinical syndromes. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline addresses clinical trials of new antimicrobial agents in the treatment of uncomplicated genital infections caused by Chlamydia trachomatis and of syndromes resembling chlamydial infections. The most common clinical manifestations of chlamydial infection are urethritis in men and mucopurulent cervicitis in women. However, many chlamydial infections are not associated with inflammatory symptoms or signs. Culture is the diagnostic standard for defining the presence of C. trachomatis, although nonculture tests may be used in screening patients for enrollment in clinical trials. Susceptibility testing for C. trachomatis is laborious and difficult to standardize; only a few clinical isolates need to be tested in vitro. Prospective, randomized, double-blind, active-control comparative studies are recommended. Eradication of C. trachomatis defines both microbiological success and overall cure for chlamydial infection, but clinical and nonmicrobiological laboratory criteria are paramount in assessing the therapeutic response in nonchlamydial urethritis or cervicitis.

Anti-Bacterial Agents↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of syphilis. Infectious Diseases Society of America and the Food and Drug Administration.

Syphilis is caused by Treponema pallidum, a spirochetal bacterium pathogenic only for humans. The clinical course of disease is divided into three stages interspersed by periods of latency. Penicillin remains the treatment of choice for all stages of infection; tetracycline or erythromycin may be used as therapeutic alternatives in defined circumstances. Patients enrolled in clinical trials should be evaluated clinically, microscopically, and serologically for the presence of the spirochete. All participants, after undergoing counseling and giving informed consent, should be tested for infection with human immunodeficiency virus. Specific criteria exist for diagnosis of syphilis and response to therapy. It may be desirable to perform a small, uncontrolled, open trial of a new anti-infective drug for the collection of preliminary evidence of efficacy. A larger-scale, randomized, active-control comparative clinical trial is necessary to prove efficacy.

Animals↗

PubMed1992

Special issues in clinical trials of new anti-infective drugs for the treatment of sexually transmitted diseases. Infectious Diseases Society of America and the Food and Drug Administration.

Several special issues arise in relation to clinical trials of therapy for sexually transmitted diseases. These issues include the desirability of including adolescents and both pregnant and nonpregnant women in the trial, the use of unapproved control regimens, problems with antimicrobial susceptibility testing due to inadequate methodology and the need for prompt treatment, the need to assess agents for treatment of syndromes of unknown microbial etiology, toxicity considerations related to the use of single-dose regimens, management of the sexual partners of the participants in the trial, analysis of data despite the high frequency of minor protocol violations, sexual reexposure to infection during the trial, and the potential for loss, alteration, or falsification of data because of the relative simplicity of the usual protocol design and the diagnostic reliance on specimens that are routinely discarded.

Adolescent↗

PubMed1992

Evaluation of new anti-infective drugs for the treatment of genital infections due to herpes simplex virus. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline addresses clinical trials of new therapies for genital infections due to herpes simplex virus (HSV). Of the two types of virus, HSV-2 is the more common pathogen. Both HSV-1 and HSV-2 become latent in sacral nerve root ganglia and intermittently reactivate. Patients who have frequent recurrences (more than four per year) may be candidates for long-term suppressive therapy. In both first-episode and recurrent genital HSV infections, lesions should be cultured for HSV. Testing for human immunodeficiency virus is encouraged but not required. Serum antibodies to HSV-1 and HSV-2 should be quantitated at enrollment and 3-5 weeks thereafter. Randomized, double-blind, active-control comparative studies are generally recommended. Placebo-controlled trials may be appropriate for recurrent genital herpes or for suppression of recurrences. Final evaluation should generally take place 10-15 days after the completion of therapy.

Anti-Infective Agents↗

PubMed1992

A randomized, double-blind study of the efficacy of fleroxacin versus trimethoprim-sulfamethoxazole in men with culture-proven chancroid.

Chancroid is linked to the spread of human immunodeficiency virus type 1 (HIV-1) in East Africa. Effective, easily administered therapy is a priority for the control of Haemophilus ducreyi. The efficacy of a single oral dose of fleroxacin, 400 mg, was compared to a 3-day oral course of trimethoprim-sulfamethoxazole (TMP-SMZ), 160/800 mg, twice daily for the treatment of chancroid in 98 HIV-1-seronegative men in Nairobi, Kenya. No differences were noted between the two groups with respect to demographic characteristics, sexual behavior, and clinical characteristics. Culture-proven failure occurred in 1 (3%) of 36 fleroxacin-treated patients and in 11 (30%) of 37 TMP-SMZ-treated patients (P = .005). Fleroxacin, as a single oral dose, is an effective treatment for culture-proven chancroid in patients who are HIV-1 seronegative. TMP-SMZ is no longer predictably effective due to the recent emergence of resistance to both sulfonamides and to trimethoprim.

Administration, Oral↗

PubMed1992

Human immunodeficiency virus type 1 infection in women attending a sexually transmitted diseases clinic in Kenya.

A cross-sectional study was conducted among women attending a sexually transmitted diseases clinic in Nairobi, kenya, to determine the prevalence of and associated risk factors for human immunodeficiency virus (HIV) type 1 infection. HIV-1 antibody was detected in 13.8% of 600 women. This virus was found most frequently in prostitutes (odds ratio [OR], 7.2), in women reporting a history of genital ulcers (OR, 2.3), and in those with a current diagnosis of genital ulcers (OR, 5.1). Lifetime duration of oral contraceptive use was significantly greater in HIV-1-positive women. Multivariate analysis revealed an association between genital ulcers and HIV-1 infection (OR, 3.8). The strongest association for HIV-1 infection, however, occurred with genital ulcers in combination with the use of oral contraceptives (OR, 25.7).

Adult↗

PubMed1992

Identification of highly conserved and species-specific polypeptides of Haemophilus ducreyi.

Chancroid is a sexually transmitted diseased caused by Haemophilus ducreyi. The pathological manifestations of chancroid are unique among Haemophilus species and the virulence factors of H. ducreyi that account for these features have not been identified. Some of these virulence factors may be unique components of H. ducreyi, but attempts to identify H. ducreyi-specific components have been unsuccessful. Four polypeptides--A, B, C and D of 83, 77, 56 and 28 kDa, respectively--were identified with a panel of nine H. ducreyi-specific monoclonal antibodies (MAbs). Polypeptide C was one of the five major proteins in H. ducreyi and demonstrated micro-heterogeneity in SDS-PAGE. Polypeptides A, B and D were present in only small amounts in whole-cell lysates of H. ducreyi. The relative amounts of A and B varied, suggesting that they may be precursor molecules. The unique polypeptides C and D were not exposed on the surface. Polypeptide C was highly soluble and did not appear to be membrane-bound, whereas polypeptide D appeared to partition with the cytoplasmic membrane and was soluble in Sarkosyl. All four polypeptides appeared to be unique to H. ducreyi since MAbs directed against them did not cross-react with H. influenzae, H. parainfluenzae or Neisseria gonorrhoeae. The mol. wts of all of these polypeptides were conserved throughout 35 clinical isolates collected from 15 cities in eight countries and one reference strain of H. ducreyi that were tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗

PubMed1992

Identification of a ROB-1 beta-lactamase in Haemophilus ducreyi.

A collection of 100 clinical isolates of Haemophilus ducreyi from Thailand were all found to harbor a 5.4-kb plasmid, designated pTH126, which was shown to contain the bla ROB-1 gene. Restriction enzyme analysis and DNA-DNA hybridization studies confirmed that pTH126 was similar to the ROB-1 beta-lactamase plasmid pVM105 from Actinobacillus pleuropneumoniae. In approximately one-half of the isolates, pTH126 was found together with pHD131, which mediates TEM-1 beta-lactamase production.

Centrifugation, Density Gradient↗

PubMed1992

Standardization of an enzyme immunoassay for human antibody to Haemophilus ducreyi.

We standardized a serologic enzyme immunoassay (EIA) for human immunoglobulin G and M antibodies against Haemophilus ducreyi. We evaluated the performance of this test with respect to the time from acute chancroid and coinfection with human immunodeficiency virus (HIV). Antibody to a crude, soluble bacterial antigen of one H. ducreyi strain was detected in a panel of serum samples from clinically and microbiologically confirmed cases of chancroid and from controls. Test interpretation was standardized for optimal sensitivity and specificity. Performance of the EIA was enhanced in the period of early convalescence from acute primary chancroid and was not diminished in the presence of HIV coinfection. The EIA performed adequately as a serologic screening test for field evaluation and epidemiologic application in conjunction with sexually transmitted disease and HIV detection and control efforts.

Antibodies, Bacterial↗

PubMed1992

The role of the laboratory in a Chlamydia control programme in a developing country.

The laboratory components of a Chlamydia trachomatis disease control programme for a developing country are reviewed. Early diagnosis of chlamydial infections is the most cost effective means of preventing the long term sequelae of trachoma, pelvic inflammatory disease, ectopic pregnancy and infertility, which are now a major public health burden to the health care system in developing countries. Public health strategies are required to establish both a co-ordinated limited system of laboratory services, and to promote the diagnosis and treatment of disease syndromes in the absence of laboratory support. Laboratory tests for the specific diagnoses of chlamydial infections requiring different levels of expertise and equipment can be instituted within settings appropriate to the resources and technical expertise available. Emphasis is given to appropriate cost effective utilization of laboratory testing.

Chlamydia Infections↗

PubMed1991

How long should catheter-acquired urinary tract infection in women be treated? A randomized controlled study.

OBJECTIVE: To determine the optimal management of catheter-acquired bacteriuria after short-term catheter use in women. PATIENTS: Asymptomatic patients (119) with catheter-acquired bacteriuria were randomly assigned to receive no therapy, a single dose (320-1600 mg) of therapy with trimethoprim-sulfamethoxazole, or 10 days (160-800 mg twice daily) of therapy. Thirty-two patients with lower tract symptoms alone received a single dose or 10 days of therapy, and 10 patients with upper tract symptoms or signs received 10 days of therapy. MAIN RESULTS: The mean and median durations of catheter use were 6 and 4 days, respectively. Bacteriuria resolved within 14 days without therapy in 15 of 42 (36%; 95% CI, 21% to 51%) asymptomatic patients. Seven of the remaining patients developed symptoms. Single-dose therapy resolved infection in 30 of 37 patients (81%; CI, 68% to 94%); 10 days of therapy resolved infection in 26 of 33 (79%; CI, 65% to 93%). For patients with lower tract symptoms alone, resolution rates with single-dose therapy or 10 days of therapy were similar (11 of 14 [79%] and 13 of 16 [81%], respectively). Ten days of therapy resolved infection in 6 of 9 (67%) patients with upper tract symptoms. Infection was resolved more often in women who were less than or equal to 65 years than in older women (62 of 70 [89%] versus 24 of 39 [62%]; P less than 0.001). Bacteriuria resolved spontaneously more frequently in younger (14 of 19 [74%] compared with 1 of 23 older women [4%]; P less than 0.001). Single-dose therapy resolved infection in 31 of 33 (94%) patients who were less than or equal to 65 years. CONCLUSIONS: Asymptomatic bacteriuria after short-term catheter use frequently becomes symptomatic and should be treated. For asymptomatic patients and patients with lower tract symptoms alone, single-dose therapy was as effective as 10 days of therapy; it was very effective in women who were less than or equal to 65 years. Bacteriuria resolved spontaneously within 14 days after catheter removal more commonly in women who were less than or equal to 65 years and both types of therapy were less effective in older women.

Adult↗

PubMed1991

Chlamydial infections and the quinolones.

Some of the newer fluoroquinolones may be suitable agents for the treatment of Chlamydia trachomatis infections and non-gonococcal urethritis. To date, small studies with both ofloxacin and fleroxacin appear to achieve cure rates of 85-100% for urethritis and cervicitis due to Chlamydia trachomatis. However, large well-designed clinical trials are required to determine the efficacy and acceptance of these and other fluoroquinolones in the treatment of patients with genital or respiratory syndromes due to chlamydiae or other bacterial pathogens causing infections with similar manifestations.

4-Quinolones↗

PubMed1991

The natural history of urinary infection in adults.

The vast majority of otherwise healthy adults with anatomically and functionally normal urinary tracts experience few untoward long-term consequences from symptomatic or asymptomatic UTIs. Effective early treatment of symptomatic infection rapidly curtails bacterial invasion and the resulting inflammatory response. Rarely, uncomplicated acute pyelonephritis causes suppuration and renal scarring. Urinary infections in patients with renal calculi, obstructed urinary tract, neurogenic bladder, or diabetes are frequently much more destructive and have ongoing sequelae. Strategies to treat both the infection and the complications are often necessary to alter this outcome.

Adult↗

PubMed1991

Cofactors in male-female sexual transmission of human immunodeficiency virus type 1.

In a study of human immunodeficiency virus type 1 (HIV-1)-uninfected African prostitutes, 83 (67%) of 124 seroconverted to HIV-1. Oral contraceptive use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.6; P less than .03), genital ulcers (mean annual episodes, 1.32 +/- 0.55 in seroconverting women vs. 0.48 +/- 0.21 in seronegative women; P less than .02) and Chlamydia trachomatis infections (OR, 3.6; CI, 1.3-11.0; P less than .02) were associated with increased risk of HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR, 0.11; CI, 0.05-0.27; P less than .0001). Stepwise logistic regression analysis confirmed independent associations between HIV-1 infection and oral contraceptive use, condom use, genital ulcers, and C. trachomatis. The presence of other sexually transmitted diseases may in part explain the heterosexual HIV-1 epidemic in Africa and may represent important targets for intervention to control HIV-1 infection.

Adult↗

PubMed1990

Chancroid and the role of genital ulcer disease in the spread of human retroviruses.

Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease.

Acquired Immunodeficiency Syndrome↗