Cell-mediated immune response in gonococcal infections.

Peripheral blood lymphocyte (PBL) transformation stimulated by gonococcal and meningococcal antigens was studied in 29 men and 21 women with uncomplicated gonorrhoea. The blastogenic responses of PBLs from these men and women were substantially higher than from normal controls. Cross-reactivity between Neisseria gonorrhoeae and Neisseria meningitidis was manifested by the PBL transformation responses in patients with gonorrhoea to non-purified meningococcal antigen (MGC-I). In both male and female patients the PBLs were stimulated by non-purified gonococcal antigen (GC-I) and by non-purified meningococcal antigen. The extent of the blastogenic response in women was much greater than in men. Partial purification of these antigens by gel chromatography resulted in reduced cross-reactive responses to the semi-purified meningococcal antigen (MGC-II). Female patients demonstrated marked stimulation with the semi-purified gonococcal antigen (GC-II), while male patients showed slight stimulation with GC-II. It is possible that cell-mediated immunity may act to limit the spread of gonococcal infection beyond the genital mucous membranes.     

Lymphocyte reactivity in patients with gonococcal urethritis.

Lymphocyte reactivity to virulent gonococcal antigen T2 and the non-pathogenic Neisseria pharyngis (NPN) has been studied by using the 14C-thymidine uptake in cell cultures from 42 patients with gonococcal urethritis and from 18 controls. The DNA synthesis in cell cultures with T2 antigen was higher in 21 female patients than in the 18 controls. No differences in DNA synthesis were observed in antigen-stimulated cell cultures from patients with single or multiple infections, from patients with urogenital complication, or from controls. Gonococcal antibodies in the serum were detected by the gonococcal complement-fixation test (GCFT). A study of the possible correlation between the outcome of the serological test and the cellular response to gonococcal antigen showed that 14C-thymidine uptake in lymphocyte cultures from male patients with negative GCFT, stimulated with T2 antigen, was much lower than the thymidine uptake in stimulated cell cultures from all the other male and female patients (P less than 0.001). The DNA synthesis was higher in cell cultures from seronegative women than from seronegative men (P less than 0.01). A significant difference (P less than 0.01) was also noted in the lymphocyte reactivity to gonococcal antigen between controls and all patients, except in those men who gave negative results to the serological tests. There were no differences between these two groups with respect to the thymidine uptake in NPN-stimulated cell cultures.     

Asymptomatic male and female gonorrhoea.

Three hundred and ninety-nine patients attending the out-patient clinic of the Department of Dermatology and Venereology, Rigshospital, Copenhagen, for various venereal complaints were examined during a three-month trial. Neisseria gonorrhoeae was found in 75 female and 89 male patients. 43 women (57%) and 13 men (15%) were asymptomatic at the first visit. The duration of the asymptomatic period exceeded 3 weeks in 25 female (33%) and 7 male (8%) patients. The asymptomatic period in the male group varied from 15 to 90 days and from 4 to 180 days in the females. The majority of the patients with asymptomatic gonorrhoea had been exposed to a sexual contact with proven gonococcal infection, thus emphasizing the importance of contact investigation.     

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.     

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.     

Ciprofloxacin for treating urethral gonorrhoea in men.

The effectiveness of a single oral dose of ciprofloxacin in eradicating urethral gonorrhoea was assessed in 18 men who received 250 mg and 26 men who were given 100 mg. All patients, including two infected with beta lactamase (penicillinase) producing strains of Neisseria gonorrhoeae (PPNG), were cured. The drug had no effect on infection with Chlamydia trachomatis or on the incidence of post gonococcal urethritis. Ciprofloxacin may be useful in patients hypersensitive to penicillins and cephalosporins, and the drug may also be useful in urethral gonorrhoea caused by PPNG strains.     

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).     

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).     

Enzyme-linked immunosorbent assay for detecting gonococcal antibodies using two antigenically different gonococcal pili as antigen.

Antibodies to pilar antigens of two gonococcal strains isolated in Rotterdam (6650 and 1443) were detected using enzyme-linked immunosorbent assays (ELISA). Paired sera (the first sample taken at the first examination (D1) and the second 11-22 days later (D2)) from women with and without gonorrhoea attending a sexually transmitted disease (STD) clinic were studied. The sensitivity of the ELISA using gonococcal pili 6650 as antigen (ELISA 6650) was significantly higher than that using gonococcal pili 1443 as antigen (ELISA 1443). The specificity of the two tests differed little. On D1 the sensitivity in women with uncomplicated gonorrhoea was 69% in the ELISA 6650 and 45% in the ELISA 1443; the corresponding values in asymptomatic infected women were 75% and 57% respectively. The agreement (both in positive and in negative results) between the two tests was less than might have been expected (kappa = 0.41).     

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.     

Gonorrhoea in 1972. A 1-year study of patients attending the VD Unit in Uppsala.

During 1972 a total of 2,090 men and 1,489 women were seen in the VD clinic in Uppsala, Sweden. The most frequent diagnosis among the men was non-gonococcal urethritis (38 per cent.) and among the women non-gonococcal vaginitis (34 per cent.), N. gonorrhoeae was found in 22 per cent. of the men and in 33 per cent. of the women, 68 per cent. of the men with gonorrhoea attended because of symptoms, but 67 per cent. of the men without gonococcal infections came for the same reason. 39 per cent. of the women with gonorrhoea attended after being told by their sexual partner; it was found that women coming because of symptoms were most likely to have non-gonococcal infection. Gonorrhoea without subjective symptoms was found in 23 per cent. of the men and 50 per cent. of the women. Gonorrhoea was found in association with scabies in 9 out of 18 men and in 3 out of 5 women. A rising incidence of pharyngeal gonococcal infections has been noticed at the clinic and the figures for 1972 were 6 per cent. of the men and 9 per cnet. of the women with gonorrhoea. The route of infection was usually oro-genital contact, but in some cases other routes had to be considered. It was not possible to define a promiscuous group of patients suitable for a planned study of prophylactic treatment, as only 2 per cent. of the men and 1 per cent. of the women had had nore than one gonococcal infection during the preceding year. The standard treatment for genital gonorrhoea (ampicillin 2 times 1 g. orally with a 5-hour interval) was very satisfactory and gave a 98 per cent. cure rate. This was possible because there were few gonococcal strains with decreased panicillin sensitivity. There were considerable problems in treating the pharyngeal infections, the standard treatment failing in 61 per cent.     

Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease

OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p < 0.003). The median SI to the recall antigen PPD was similar in the urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could be because low sensitivity of CT culture failed to diagnose some cases of C trachomatis. However, it may also signify earlier exposure of the patients to chlamydial antigens (for example, C pneumoniae), cross reacting antigens such as heat shock proteins from other microbial species, or a "bystander" activation of chlamydia specific memory T cells trafficking through mucosal lymphoid tissue during urethritis. These results suggest evidence of T cell mediated response to C trachomatis cannot be used as a diagnostic tool.     

Serum and secretory antibody responses to Neisseria gonorrhoeae in patients with gonococcal infections.

The present study was conducted to characterize the nature and pattern of serum and secretory antibody responses to N. gonorrhoeae by haemagglutination inhibition, opsonization, and immunofluorescence techniques in male and female patients with different clinical manifestations of gonorrhoea. Most male patients with acute gonococcal infection developed serum IgG and, less frequently, IgM antibodies against pilated gonococci within 2 weeks of infection and these antibodies declined to normal levels 1 to 2 months after treatment. This response was not noticeably different from the responses developed in male patients with subacute infection and female patients with chronic infection. Immunological analyses of the seminal plasmas and cervical fluids from these patients showed that antibodies reactive with both pilated and non-pilated N. gonorrhoeae are present in some of the cases. A small percentage of male patients who recovered from subacute gonococcal infection but not from acute infection possessed low levels of IgG and, less frequently, IgA antibodies to gonococcal antigens in their seminal plasmas. In contrast, more than half of the females with gonorrhoea had IgG antigonococcal antibodies in the cervical fluid. However, a small number of samples also showed the presence of IgA and IgM antibodies. IgA antibody in most of these IgA-positive samples was of the secretory type. The presence of secretory IgA (SIgA) in secretions and the lack of correlation between the antibody titres in serum and in secretions of these patients suggest that infection with N. gonorrhoeae may independently stimulate both a systemic and a local humoral immune response.     

Direct immunofluorescent test for the detection of gonorrhoea.

In the course of 4 years we have examined a total of 1,100 women with chronic gynaecological complaints. The direct fluorescent antibody test was used successfully for the detection of gonorrhoea. In Group 1 (200 patients) we found 39-1 per cent. with gonorrhoea. In group 2 (220 patients) the percentage fell to 27-7 per cent, in Group 3 (220 patients) to 23-2 per cent., in Group 4 (220 patients) to 12-3 per cent., and in Group 5 (220 patients) to 11-8 per cent. By employing a consistent programme of diagnosis and therapy we succeeded in reducing the incidence of gonorrhoea in the Prague 3 District from 39-1 per cent. in 1970 to 11-8 per cent. in 1973-74. In all we discovered 251 female patients suffering from gonorrhoea, who would otherwise have escaped observation and registration. When patients are not registered as sources of gonococcal infection, special cultures are not performed as a routine, and these women would therefore infect the same number of men at least. The immunofluorescent method proved to be of great value. The direct FAT is a superior test; even in cases in which, because of damage by such factors as antibiotics, Neisseria gonorrhoeae does not grow on artificial media, gonorrhoea can be detected by this method.     

Gonorrhoea of the throat at a venereological clinic. Incidence and Results of Treatment.

Among 3,271 consecutive cases of gonorrhoea seen during the years 1971 to 1974, the incidence of tonsillar gonorrhoea was 3-6% in men and 5-8% in women. Oro-genital intercourse was admitted by 34% of men and 33% of women. Among these patients the incidence of tonsillar gonorrhoea was 7% in men and 16% in women. Only two cases of gonococcal septicaemia were seen, and there were no other complications. Few patients experienced symptoms from the throat. Tonsillar cultures was positive on the first examination in only 74%, it was negative until after single-dose treatment had been given in 18%.     

Gonorrhoea of the throat at a venereological clinic. Incidence and Results of Treatment.

Among 3,271 consecutive cases of gonorrhoea seen during the years 1971 to 1974, the incidence of tonsillar gonorrhoea was 3-6% in men and 5-8% in women. Oro-genital intercourse was admitted by 34% of men and 33% of women. Among these patients the incidence of tonsillar gonorrhoea was 7% in men and 16% in women. Only two cases of gonococcal septicaemia were seen, and there were no other complications. Few patients experienced symptoms from the throat. Tonsillar cultures was positive on the first examination in only 74%, it was negative until after single-dose treatment had been given in 18%.     

Problems posed by potential gonococcal vaccines viewed from the vantage point of a control agency.

Progress in the characterisation of Neisseria gonorrhoeae and other bacterial pathogens has suggested that immunoprophylaxis for gonorrhoea may be possible despite the well-known propensity for reinfection. Pili, outer membrane proteins, a capsular polysaccharide, and the lipopolysaccharide may be important gonococcal virulence factors, and immune components (probably antibodies) to more than one of these antigens may be required to confer immunity. A study of antigenic polymorphism of these structures should identify disease isolates more precisely and provide information about the relationship between variants of these gonococcal structures and gonococcal virulence.     

Detection of the gonococcal antigen with an enzyme immunoassay (Gonozyme). Results of the original and modified test procedure

Urogenital specimens of 2,485 patients were examined by an enzymeimmunoassay for the detection of Neisseria gonorrhoeae antigen (Gonozyme, Abbott). The results of the original test (Gonozyme A) and a modified version (Gonozyme B) were compared to bacterial culture. Three different groups were examined by Gonozyme A: 526 men and 464 women from the clinic for sexually transmitted diseases (STD) and 548 registered prostitutes. Sensitivity in men was 98%, in women from the STD clinic 89%, and in prostitutes 81%. Specificity in men was 99.5%, in women from the STD clinic 94%, and in prostitutes 88%. One of the reasons for the decreased specificity in women could be cross reacting bacteria from the genital secretions of the women. The assay was modified by optimizing the antigonococcal antibody and increased incubation times. These modifications improved the specificity of Gonozyme B by reducing the number of cross reactions with other bacterial antigens. Four different groups were examined by Gonozyme B: 261 men and 220 women from the STD clinic, 121 women from an infertility clinic, and 345 registered prostitutes. Sensitivity in men was 100%, in women from the infertility clinic 100%, in women from the STD clinic 94%, and in prostitutes 77%. Specificity in men was 99%, in women from the infertility clinic 100%, in women from the STD clinic 99%, and in prostitutes 96.5%. Analysis of the Gonozyme-positive/culture-negative test results suggested that most patients (85%) did not have gonorrhoea. In 15% of these specimens it is possible that patients had pretreated gonorrhoea which was only detected by Gonozyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spectinomycin resistant gonococcal infections in West Germany. Detection in 7 patients and occurrence of post-gonorrheal epididymitis caused by the spectinomycin-resistant PPNG strain

Seven patients (four men, three women) with gonococcal urethritis resistant to spectinomycin treatment were seen in May and June 1989 in the Department of Dermatology in Berlin (West), and strains of Neisseria gonorrhoeae (NG) resistant to spectinomycin were detected, cultured in vitro from these individuals. In five of the seven patients penicillin-resistant strains were found, including a penicillinase-producing strain in one case; the other two patients had penicillin-sensitive strains. In all cases the NG-populations detected were sensitive to cephalosporin and cipro(oxo)floxacin. In a 17-year-old young man with the PPNG strain severe gonococcal epididymitis developed after repeated infection that had been inadequately treated with spectinomycin. All seven patients mentioned sexual contact with individuals who lived in Southeast Asia or had their origins there; in at least four cases the contact persons came from Thailand. This is the first report on spectinomycin-resistant Neisseria gonorrhoeae infections (PPNG and non-PPNG) in the Federal Republic of Germany. The necessity for monitoring the results of penicillin and/or spectinomycin treatment of gonorrhoea are underlined for the dermatovenereologist, and some guidelines for therapy are given.     

Problems posed by potential gonococcal vaccines viewed from the vantage point of a control agency.

Progress in the characterisation of Neisseria gonorrhoeae and other bacterial pathogens has suggested that immunoprophylaxis for gonorrhoea may be possible despite the well-known propensity for reinfection. Pili, outer membrane proteins, a capsular polysaccharide, and the lipopolysaccharide may be important gonococcal virulence factors, and immune components (probably antibodies) to more than one of these antigens may be required to confer immunity. A study of antigenic polymorphism of these structures should identify disease isolates more precisely and provide information about the relationship between variants of these gonococcal structures and gonococcal virulence.