Prevalence of rectal and pharyngeal infection in women with gonorrhoea in Sheffield.

The prevalence of gonococcal infection of the rectum and pharynx in 239 consecutive women with gonorrhoea presenting as named contacts was 47% and 10% respectively. In 2% of all patients the rectum and pharynx were each the sole sites of infection. Treatment failure occurred in three patients given a single dose of aqueous procaine penicillin 2.4 megaunits intramuscularly, two of whom had rectal infections; no treatment failures occurred in patients with pharyngeal infections. The incidence of rectal gonorrhoea significantly increased with the duration of infection (P less than 0.001). This suggests that autoinoculation from infected vaginal material is of major importance in the transmission of gonococcal infection to the rectum.     

Epidemiological treatment and tests of cure in gonococcal infection: evidence for value.

OBJECTIVES: To evaluate the evidence for value of using epidemiological treatment and of using tests of cure in the management of gonococcal infections. METHODS: Medline was used to search the literature for well-conducted studies that had a bearing on the evaluation of these issues. CONCLUSIONS: Epidemiological treatment is treatment given to named contacts of patients after a history of exposure to disease but without or in advance of confirmatory pathological findings. It may be given when the clinician considers that the risk to the patient of unnecessary treatment is outweighed by the risk of complications of the infection or the probability of transmission of the infection to other contacts. It may be appropriate where detection by microscopy is relatively unreliable such as when infection of the cervix, rectum, or pharynx is suspected. If epidemiological treatment is given, then it does not obviate the need for confirmatory tests to be sent, tests of cure to be done, or for contact tracing. At least one test of cure is mandatory following treatment of gonorrhoea. The test of cure in women should include a blind rectal swab. For infection of the pharynx and rectum the chances of a false negative test of cure are higher and, therefore, more than one test of cure is required. An additional test of cure is also necessary in patients with salpingitis or disseminated gonococcal infection. This paper is a discussion of two interrelated issues in the management of gonorrhoea. It is based on two presentations by the author at a workshop organised by Dr Mark Fitzgerald entitled Development of audit measures and guidelines for good practice in the management of gonorrhoea and held at the Royal College of Physicians, London, in May 1995. The conclusions reached are based on the consensus view of the participants. For simplicity the two issues are dealt with consecutively.     

Non-cultural detection of rectal and pharyngeal gonorrhoea by the Gen-Probe PACE 2 assay.

OBJECTIVE: To assess the sensitivity and specificity of the Gen-Probe PACE 2 assay, which uses a chemiluminescent labelled single-stranded DNA probe to detect gonococcal ribosomal RNA (rRNA), for the non-cultural detection of rectal and pharyngeal gonorrhoea in homosexual men. SUBJECTS: 161 homosexual men attending the Department of Genitourinary Medicine, Edinburgh Royal Infirmary during the latter half of 1995 and the first quarter of 1996. METHODS: Duplicate rectal and pharyngeal swabs were collected for culture on modified New York City (MNYC) medium and detection of gonococcal nucleic acid by the Gen-Probe assay. Repeatedly reactive Gen-Probe specimens from culture negative patients were also tested by the Gen-Probe competition assay (PCA). RESULTS: Of the 161 patients, 23 (14.3%) gave a positive culture at one or both sites (rectum 10, throat 8, rectum and throat 5) compared with 28 (16.7%) who gave a positive Gen-Probe result at one or both sites (rectum 9, throat 11, rectum and throat 8). After resolution of discrepant results by PCA the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gen-Probe was 94.1%, 100%, 100% and 99.3% for rectal specimens while the corresponding values for pharyngeal specimens were 86.4%, 100%, 100%, and 97.9%. The sensitivity and NPV of rectal culture were 88.2% and 98.6% while the corresponding values for pharyngeal culture were 59% and 93.9%. Gen-Probe was significantly more sensitive than throat culture (p < 0.05) but not rectal culture (p > 0.2). The average Relative Light Units (RLU) value for the cut-off was 386 (range 351-450) while the average for a positive result was 20306 (range 403-110104): this was, however, significantly higher (p = 0.019) in rectal specimens 31325 (range 1705-110104) than in throat specimens 10447 (range 403-15633). CONCLUSIONS: Gen-Probe PACE 2 assay is a sensitive and specific method for the detection of rectal and pharyngeal gonorrhoea. As the Gen-Probe assay may detect nucleic acid from non viable gonococci the clinical significance of a probe positive culture negative specimen from a patient without culture evidence of gonorrhoea at another site is uncertain and requires further consideration. Nevertheless a positive result does indicate exposure to infection and could be important in ensuring appropriate partner notification action. If non-cultural methods are used to screen for gonococcal infection cultures should be obtained from patients with positive results in order that the antibiotic susceptibility and molecular epidemiology of the gonococcal population can be monitored.     

Diagnosis of rectal gonorrhoea by blind anorectal swabs compared with direct vision swabs taken via a proctoscope.

Eight hundred and twenty-three examinations were carried out on 662 homosexual patients. At each examination a blind anorectal swab and a rectal swab taken via a proctoscope were inoculated on to a culture plate. From a total of 100 gonococcal infections of the rectum 96 gave positive results from blind anorectal swabs and 99 from swabs taken via a proctoscope. Blind anorectal swabs proved to be a reliable method in the diagnosis of rectal gonorrhoea.     

Diagnosis of rectal gonorrhoea by blind anorectal swabs compared with direct vision swabs taken via a proctoscope.

Eight hundred and twenty-three examinations were carried out on 662 homosexual patients. At each examination a blind anorectal swab and a rectal swab taken via a proctoscope were inoculated on to a culture plate. From a total of 100 gonococcal infections of the rectum 96 gave positive results from blind anorectal swabs and 99 from swabs taken via a proctoscope. Blind anorectal swabs proved to be a reliable method in the diagnosis of rectal gonorrhoea.     

Pharyngeal colonisation by Neisseria gonorrhoeae and Neisseria meningitidis in black and white patients attending a venereal disease clinic.

Pharyngeal colonisation by Neisseria gonorrhoeae and Neisseria meningitidis was studies in 2000 patients attending a venereal disease clinic. Of these patients, 64% were white and 36% were black. The incidence of gonococcal infections was highest in the period from June to August. The incidence of genital or rectal infections or both was higher in the black patients. Pharyngeal colonisation by gonococci was present in 1.3% of the patients. There was no significant associations between pharyngeal colonisation and the pharyngeal symptoms, race, sex, or marital state of the patients. Pharyngeal colonisation was more frequent in patients with gonococcal infections at other sites. However, in 40.7% of the patients with pharyngeal colonisation, the pharynx was the only culture-positive site. There was no significant difference in the auxotypes or in the antibiotic susceptibility of the pharyngeal and the rectal-genital isolates except in the susceptibility to spectinomycin. Our findings do not indicate that gonococci isolated from the pharynx differ significantly from gonococci isolated from rectal or genital sites. It was notable that meningococcal colonisation of the pharynx was significantly more frequent in the white patients. This may be a genetically determined phenomenon.     

Pharyngeal colonisation by Neisseria gonorrhoeae and Neisseria meningitidis in black and white patients attending a venereal disease clinic.

Pharyngeal colonisation by Neisseria gonorrhoeae and Neisseria meningitidis was studies in 2000 patients attending a venereal disease clinic. Of these patients, 64% were white and 36% were black. The incidence of gonococcal infections was highest in the period from June to August. The incidence of genital or rectal infections or both was higher in the black patients. Pharyngeal colonisation by gonococci was present in 1.3% of the patients. There was no significant associations between pharyngeal colonisation and the pharyngeal symptoms, race, sex, or marital state of the patients. Pharyngeal colonisation was more frequent in patients with gonococcal infections at other sites. However, in 40.7% of the patients with pharyngeal colonisation, the pharynx was the only culture-positive site. There was no significant difference in the auxotypes or in the antibiotic susceptibility of the pharyngeal and the rectal-genital isolates except in the susceptibility to spectinomycin. Our findings do not indicate that gonococci isolated from the pharynx differ significantly from gonococci isolated from rectal or genital sites. It was notable that meningococcal colonisation of the pharynx was significantly more frequent in the white patients. This may be a genetically determined phenomenon.     

Relationship of the interval between infections and the similarity of gonococcal strains in recurrent gonorrhoea.

Paired gonococcal isolates from 38 patients with recurrent episodes of gonorrhoea at varying intervals were examined for similarity by means of gonococcal auxotyping and susceptibility to antibiotics. A different gonococcal strain was the cause of the second infection in 53% of the patients. Longer intervals between infections were significantly associated with greater numbers of dissimilar strains as a cause of the second infection. The same strain was usually found in infections occurring within 60 days of each other whereas different strains were more likely to cause infections occurring more than 60 days apart. The isolates causing the second infection were significantly more susceptible to penicillin.     

Relationship of the interval between infections and the similarity of gonococcal strains in recurrent gonorrhoea

Paired gonococcal isolates from 38 patients with recurrent episodes of gonorrhoea at varying intervals were examined for similarity by means of gonococcal auxotyping and susceptibility to antibiotics. A different gonococcal strain was the cause of the second infection in 53% of the patients. Longer intervals between infections were significantly associated with greater numbers of dissimilar strains as a cause of the second infection. The same strain was usually found in infections occurring within 60 days of each other whereas different strains were more likely to cause infections occurring more than 60 days apart. The isolates causing the second infection were significantly more susceptible to penicillin.     

Studies on the influence of antigens on the results with the gonococcal complement fixation test in patients with uncomplicated and complicated gonorrhoea.

The gonococcal complement fixation test (GCFT) was investigated with regard to its sensitivity and specificity by testing serum specimens from (a) female patients attending a VD out-patient clinic because of suspected gonorrhoea, (b) patients with a proven, uncomplicated, urogenital gonococcal, infection, (c) patients with disseminated gonococcal infection (DGI). Three different pools of gonococcal (GC) antigens were used which were comprised of GC strains from two different geographical areas. It was found that 39% of the females with culture-proven uncomplicated gonorrhoea had a positive GCFT whereas 10% of the females with negative GC cultures had a positive GCFT. The latter were found to have either a history of gonorrhoea or strong clinical suspicion of recent GC infection. One of the GC antigen pools gave a much lower diagnostic yield than the other two pools in the GCFTs with serum specimens from patients with uncomplicated gonorrhoea. However, no differences were found between the antigen pools in the tests with serum specimens from patients with DGI. These findings indicate the presence of various strain antigens participating in the immune response to complicated as well as uncomplicated GC infections. The results are presented in detail and discussed.     

Single dose ciprofloxacin for treating gonococcal infections in men.

A single oral dose of ciprofloxacin 500 mg was used to treat five men with gonococcal urethritis and five men with gonococcal proctitis, and all were cured. In a subsequent study the dose of ciprofloxacin was reduced to 250 mg, and 54 men with 57 gonococcal infections (47 urethral, seven rectal, and three pharyngeal) were treated; of the isolates of Neisseria gonorrhoeae, four were penicillinase producing strains. All the patients were cured of gonococcal infection. Urethral specimens from nine of the men with gonococcal urethritis yielded Chlamydia trachomatis before treatment. These organisms were isolated again from all these patients seven days after treatment, and from a further seven men who had been chlamydia negative before treatment. It is concluded that a single oral dose of ciprofloxacin is an effective treatment for uncomplicated gonorrhoea, but is ineffective against C trachomatis. Of the 54 men given 250 mg ciprofloxacin, six (11%) showed minor abnormalities of liver function tests after treatment.     

Diagnosis and management of anorectal gonorrhoea in women.

A retrospective assessment of 159 female patients who had undergone proctoscopy was carried out between January and September 1977. One hundred and twenty-seven (80%) were known contacts of gonorrhoea; of these, 63 (49.6%) were found to be infected with Neisseria gonorrhoeae. Of these, 29 (46%) harboured gonococci in the rectum as well as in the urethra and cervix while four (6.3%) harboured gonococci only in the rectum. Gram-stained smears gave positive results in only 12 of the 29 cases of rectal gonorrhoea, which indicates the importance of culturing rectal material. It is recommended that the management of anorectal gonorrhoea should be similar to that already established for urogenital infection.     

Gonorrhoea in men: clinical and diagnostic aspects.

AIM: To review the features of gonococcal infection in men in the 1990s. METHODS: A retrospective study of all men with gonorrhoea presenting to an inner city department of genitourinary medicine in the years 1990 to 1992. RESULTS: 1749 cases of gonorrhoea were seen in 1382 men. A high incidence of gonorrhoea was found in attenders of African or Caribbean extraction. In 228 men with a known date of infection, the incubation period, a mean of 8.3 days, was longer than previously described. The mean infectious period was 12.0 days. By 14 days 86.2% of men had developed symptoms. Of 1615 men with urethral infection 81.9% complained of discharge, while dysuria occurred in 52.8%. Discharge with dysuria were present in only 48.1% of patients. In 10.2% episodes of urethral infection the patients had no symptoms referable to their gonorrhoea. Urethral gonorrhoea was diagnosed by microscopy in 94.4% of symptomatic men and in only 81.1% of asymptomatic men. Microscopy of rectal samples were positive in 46.4% of cases. In this population, a dose of 2 g of ampicillin with 1 g of probenecid gave a high cure rate of gonorrhoea as long as infection was not due to penicillinase-producing organisms. CONCLUSIONS: These data suggest that the incubation and infectious period of urethral gonorrhoea has increased compared with previous studies and that symptoms have altered. Only 48.1% of men described the classical symptoms of discharge with dysuria. Microscopy of urethral smears remains useful in symptomatic men but is less sensitive in those without symptoms.     

Response of pharyngeal gonorrhoea to single dose penicillin treatment.

The prevalence of gonococcal infection of the pharynx in 205 women, 331 heterosexual men, and 11 homosexual men with gonorrhoea was 6.8%, 4.2%, and 27.3% respectively. In only one patient, a heterosexual man, was the pharynx the sole site of infection. Throat symptoms were found in 7% of women, 21% of heterosexual men, and none of the homosexual men. Orogenital contact was reported by 29% of women, 36% of heterosexual men, and all the homosexual men. A single intramuscular dose of 1.8 g Bicillin (procaine penicillin 1.5 g plus benzyl penicillin 300 mg) cured 90% of patients.     

Evaluation of ligase chain reaction for the non-cultural detection of rectal and pharyngeal gonorrhoea in men who have sex with men

OBJECTIVES: To compare a nucleic acid amplification test (ligase chain reaction) with culture for detecting rectal and pharyngeal gonorrhoea in men who have sex with men (MSM). METHODS: Duplicate rectal and throat swabs from MSM attending a genitourinary medicine clinic were collected for culture on modified New York City medium and detection of gonococcal nucleic acid by the Abbott ligase chain reaction (LCR) utilising probes based on opa 1 gene sequences. LCR positive culture negative specimens were tested by a second LCR utilising probes based on pilin gene sequences. Patients with rectal and/or pharyngeal cultures yielding Gram negative diplococci confirmed as Neisseria gonorrhoeae by biochemical and immunological methods were diagnosed with rectal and/or pharyngeal gonorrhoea. The criteria for diagnosing rectal and pharyngeal infection by LCR included a positive opa LCR with a positive culture from the same site or, in the case of a negative culture, a positive opa LCR and a positive pilin LCR. RESULTS: Duplicate rectal samples were obtained from 227 MSM. The results of LCR and culture were concordant in 219 samples (96.5%). The prevalence of rectal gonorrhoea by LCR and culture was 7.0% (16/227) and 4.0% (9/227), respectively. Duplicate throat samples were obtained from 251 MSM. The results of LCR and culture were concordant in 230 (91.6%) cases. The prevalence of pharyngeal gonorrhoea by LCR and culture was 12.7% (32/251) and 6.0% (15/251), respectively. The specificity of LCR was 99.5% (210/211) for rectal and 98.2% (215/219) for pharyngeal specimens. CONCLUSIONS: The high prevalence and asymptomatic nature of pharyngeal and rectal gonococcal infection suggests that routine screening for infection at these sites by a nucleic acid amplification test method such as LCR should be considered as part of the overall strategy to control gonorrhoea in MSM.     

Indirect haemagglutination test using gonococcal pilus antigen: how useful to diagnose gonorrhoea?

In 1979 an indirect haemagglutination test (gonococcal antibody test) using gonococcal pilus antigen replaced the gonococcal complement fixation test as our routine procedure to show gonococcal antibodies. In the diagnosis of current gonorrhoea the sensitivity of the gonococcal antibody test was far superior to that of the gonococcal complement fixation test (about 55% versus 9% for first episode gonorrhoea). To evaluate the usefulness of the test result the following population groups were studied: 1376 patients undergoing medical examination for gonorrhoea (386 had gonorrhoea), 1384 healthy people aged 15-65, 54 patients with meningococcal disease, 30 children with respiratory tract infection, and 254 patients with evidence of various diseases other than neisserial infections that might be associated with symptoms of arthritis. These investigations showed that (1) non-specific positive gonococcal antibody test results occur rarely, (2) at least half the people who have had gonorrhoea remain seropositive (with titres of 1/40 to 1/160), and (3) a positive test result is more significant the younger the patient and the higher the titre. For younger people a positive test result should always be followed up by bacteriological examination; in all age groups titres of 1/320 or more should indicate medical examination for current gonorrhoea.     

Induction of phenotypically determined resistance of neisseria gonorrhoeae to human serum by sera from patients with gonorrhoea

Some human sera contain factors which induce in gonococci a resistance to killing by fresh human sera. Individuals with serum containing these factors might possibly be more prone to gonorrhoea. A survey of the sera of 50 female and 50 male patients with gonorrhoea for resistance-inducing capacity showed, however, that the proportions of positive sera (24% for women, 28% for men) were not significantly different from those (16% for women, 24% for men) from an equal number of controls. Examination of the results, however, in relation to the type of gonococcal infection showed that: (a) the sera of 15 female patients with complicated (salpingitis) or successive infection or both did not induce resistance (statistically significant); (b) a greater proportion (34%) of sera from female patients with single gonococcal infections induced higher gonococcal resistance than for control sera (16%) (at the borderline of statistical significance); and (c) a greater proportion (38%) of sera from the few male patients with successive infections induced higher resistance than for control sera (24%) (not statistically significant).     

Gonorrhoea in men with homosexual contacts. Serogroups of isolated gonococcal strains related to antibiotic susceptibility, site of infection, and symptoms.

In 37 homosexual men the incidences of urethral, rectal, and pharyngeal gonorrhoea were 45.9%, 56.8%, and 27% respectively. Local symptoms were present in all men with urethral gonorrhoea but in only 25% of those with pharyngeal or rectal gonorrhoea or both. Infection at two sites was found in 29.7% of the patients. Forty-nine gonococcal isolates from the 37 patients were serogrouped by coagglutination into one of the serogroups WI, WII, and WIII, and their susceptibility to benzylpenicillin, ampicillin, cefuroxime, doxycycline, and spectinomycin tested. Only one gonococcal isolate from each patient was counted when two isolates belonged to the same serogroup and had the same antibiotic susceptibility. Thus, 15.4%, 76.9%, and 7.7% of the gonococcal strains belonged to serogroups WI, WII, and WIII respectively. There was a significantly lower incidence of WI strains and a significantly higher incidence of WII strains among men with homosexual contacts than among other patients with gonorrhoea from the same geographical region. Gonococcal strains of serogroup WI were significantly more resistant to all antibiotics tested, except to spectinomycin, than randomly chosen WI strains. Among WII and WIII strains the incidence of diminished susceptibility to all antibiotics tested was about the same.     

Induction of phenotypically determined resistance of neisseria gonorrhoeae to human serum by sera from patients with gonorrhoea.

Some human sera contain factors which induce in gonococci a resistance to killing by fresh human sera. Individuals with serum containing these factors might possibly be more prone to gonorrhoea. A survey of the sera of 50 female and 50 male patients with gonorrhoea for resistance-inducing capacity showed, however, that the proportions of positive sera (24% for women, 28% for men) were not significantly different from those (16% for women, 24% for men) from an equal number of controls. Examination of the results, however, in relation to the type of gonococcal infection showed that: (a) the sera of 15 female patients with complicated (salpingitis) or successive infection or both did not induce resistance (statistically significant); (b) a greater proportion (34%) of sera from female patients with single gonococcal infections induced higher gonococcal resistance than for control sera (16%) (at the borderline of statistical significance); and (c) a greater proportion (38%) of sera from the few male patients with successive infections induced higher resistance than for control sera (24%) (not statistically significant).     

Rectal gonorrhoea as an independent risk factor for HIV infection in a cohort of homosexual men.

OBJECTIVE--To determine whether certain sexually transmitted diseases are independent risk factors for HIV transmission in a cohort of homosexual men. METHODS--Eligible cases were identified as those who had seroconverted between November 1982 and November 1990. Two persistently HIV-seronegative control participants were randomly selected for each case from all participants who remained seronegative in November 1990. For cases, risk factor data were taken from an index visit which was defined as the first seropositive visit, while for controls these data were obtained from a matched visit which occurred within two months of the index visit for the corresponding case. Mantel-Haenszel methods and logistic regression were used to compare differences in risk factors for seroconversion between cases and controls. RESULTS--A total of 125 cases and 250 controls were eligible for this study. Cases were significantly more likely to have had reported any gonorrhoea (17% versus 6%; OR = 2.94; 95% CI: 1.51-5.73) or syphilis (7% versus 2%; OR = 3.78; 95% CI: 1.33-10.79) than controls during the seroconversion period. Multivariate logistic regression revealed rectal gonorrhoea to be independently associated with risk of seroconversion (odds ratio = 3.18; p = 0.044), whereas urethral gonorrhoea (p = 0.479) and pharyngeal gonorrhoea (p = 0.434) were not after inclusion of rectal gonorrhoea. In addition, the following variables were also shown to exert an independent effect on seroconversion: frequency of anal intercourse, use of illicit drugs, number of male sexual partners, and lack of a post-secondary education. CONCLUSIONS--In this observational study, rectal gonorrhoea was found to be associated with HIV seroconversion after adjustment for a number of HIV risk factors. We cannot rule out that rectal gonorrhoea was not directly associated with HIV infection but rather with other residual lifestyle factors not fully adjusted for in the analysis. However, the relationship with gonococcal involvement of a specific anatomic site lends support to a biological association between gonorrhoea and HIV infection, rather than to alternative non-biologic explanations. Our findings are consistent with previous studies reporting an association between HIV infection and non-ulcerative sexually transmitted diseases. Such a direct association might be explained by postulating that gonorrhoea results in inflamed rectal mucosa and compromised epithelial integrity, thereby predisposing an individual to subsequent HIV infection.