Immune response of lambs to vaccination with Ostertagia circumcincta surface antigens eliciting bile antibody responses.

Immune responses to surface antigens of infective larvae of Ostertagia circumcincta recognized by bile antibodies of sheep immune to challenge were studied in 5-month-old Finn-Dorset male lambs. The sheep were vaccinated subcutaneously with 2 doses of 25 micrograms/kg body weight of surface proteins immunoprecipitated by bile antibodies derived from protected lambs. These antigens were purified from immune complexes by affinity chromatography and then injected with beryllium hydroxide as an adjuvant. The immunized lambs were challenged with 5 x 10(4) L3 and the worm burdens evaluated on day 21 post challenge. These were significantly (P < 0.01) lower in the vaccinated group than in the challenged controls (72% protection). The mucosal and bile IgM, recognizing the L3 surface, showed significantly higher levels in the vaccinated lambs compared to the challenge controls. Mucosal and bile IgA antibody levels against the same antigens were low and no significant differences were observed between vaccinated and control lambs.

Pathophysiology of the periparturient egg rise in sheep: a possible role for IgA.

The relationship between anti-parasite IgA antibody levels in plasma and the periparturient egg rise in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to three groups of seven adult immune ewes from 12 weeks before until three weeks after lambing (group 1) or from six (group 2) or 14 (group 3) weeks before until three weeks before lambing. Seven additional ewes were not challenged (group 4 controls). Ewes in groups 1, 2 and 4 received anthelmintics 14 weeks before lambing. Challenge of the pregnant ewes with O circumcincta larvae resulted in substantial increases in faecal egg counts only during the periparturient period regardless of the larval dosing regimen. Furthermore, the periparturient rise in faecal egg counts was closely associated with a significant increase in anti-parasite IgA antibody levels in plasma. This rise in IgA antibody levels occurred at a time when IgA is transported from the gut to milk during early lactation. It is postulated that this may lead to a temporary reduction in abomasal antibody levels of ewes and hence permit the establishment of larvae and, or, the emergence and development of inhibited larvae and thereby lead to the periparturient rise in faecal egg count.

Survival of treponemes after treatment: comments, clinical conclusions, and recommendations.

Treponemes may persist after treatment that has been accepted as effective; the reasons for this are discussed. Nevertheless, the epidemic of syphilis after the second world war was not followed by an epidemic of late syphilis, and the results of treatment with penicillin are excellent. Neurological signs may progress in some treated patients, and the standard doses of soluble penicillin and any dose of benzathine penicillin (even with added probenecid by mouth) cannot be relied on to achieve treponemicidal concentrations in the cerebrospinal fluid (CSF). There are no large scale studies of CSF findings after treatment of early syphilis with benzathine penicillin. Standard dosage, such as procaine penicillin G 600 000 international units (IU) by intramuscular injection for 10 days, is the treatment of choice for the patient suffering from uncomplicated early syphilis; this should be preferred to benzathine penicillin, which should only be used when standard treatment as above cannot be given. Treponemicidal concentrations of penicillin should be achieved in the CSF of patients suffering from neurosyphilis by schedules of probenecid by mouth and procaine penicillin by single daily intramuscular injections; treatment should last for 17 to 21 days. Benzathine penicillin should not be used for the treatment of patients suffering from neurosyphilis or from the iritis of late syphilis including that accompanying interstitial keratitis. Treatment for interstitial keratitis should initially be as for neurosyphilis, but in recurrent cases it may have to be prolonged to eradicate Treponema pallidum that is dividing slowly. Doxycycline 200 mg by mouth daily for 21 days provides a supervisable outpatient schedule for patients allergic to penicillin. Cephaloridine (and probably cefuroxime and the new cephalosporins) may be useful for patients who are allergic to penicillin but have not developed anaphylactic allergy. If erythromycin is used for treating syphilis in pregnant women who are allergic to penicillin, then the newborn babies should be treated with penicillin.

Clinically silent anterior uveitis in secondary syphilis.

1 In a series of twenty patients with secondary syphilis, ten showed signs of overt or subclinical iritis alone. Nine showed signs of purely subclinical iritis. 2 Nineteen were Caucasian men and the one woman was an unmarried Caribbean nurse. 3 Of the nineteen men, fourteen were homosexuals. 4 All received adequate anti-syphilitic treatment as soon as the diagnosis was made, and all ocular signs of inflammation disappeared within 14 days.

Benign transient lymphangiectasis (sclerosing lymphangitis) of the penis.

The literature on benign transient lymphangiectasis of the penis (BTLP) was reviewed; reports of 45 cases were collected and a further series, comprising 21 cases, is presented. Both the published and present series support the view that BTLP is associated with recent sexual activity; little support is given for an infective cause and it is confirmed that BTLP is a benign, self-limiting condition presenting in the sexually active man between 20 and 40 years old. There can be recurrences, and susceptibility to them may be encouraged by circumcision in which disturbances of lymphatic drainage may play a part. As so few cases have been reported and few were diagnosed in the present series these comments can only be pointers to further studies. The descriptions in six histological examinations, the reports as `phlebitis' of apparently similar lesions, the report of `sclerosing lymphangitis' in other sites, and the known histological similarity between veins and lymphatics suggest that `sclerosing lymphangitis' is too specific a term. Until further knowledge is available, we suggest that this condition is best regarded as simple dilatation of a lymphatic vessel-namely, lymphangiectasis. As the condition is both benign and transient we propose the term benign transient lymphangiectasis of the penis for the condition formerly known as sclerosing lymphangitis.

Gonorrhoea in the asymptomatic patient: presentation and the role of contact tracing for heterosexual men and women and for homosexual men.

Clinically silent gonorrhoea is the major problem in the control of the disease. Only 12 per cent of infected women reported in 1974 because of symptoms, compared with 97 per cent of infected heterosexual men and only 35 per cent of homosexual men with gonococcal proctitis alone. Homosexual men, compared with heterosexual men, had twice as many subsequent sexual contacts after infection and had a higher incidence of early syphilis. Eighty-four per cent had experienced passive anorectal intercourse. Ninety-seven per cent of men with gonococcal urethritis reported because of symptoms, but occasionally (particularly after unsuccessful treatment) urethral gonorrhoea in men may be clinically silent and even require tests of the overnight urethral secretion for diagnosis. For women, and for homosexual men who have had passive anorectal (or oral) intercourse, the indication for attendance for tests for gonorrhoea should be having run the risk, and not the presence of symptoms. Routine tests of the anorectum for gonorrhoea are essential in cases of 80 women at risk, and for most homosexual men since over 80 per cent of these men will have had passive anorectal intercourse. Because gonococcal infections following treatment-failure are often clinically silent in both women and men, symptoms cannot be relied upon to indicate such failure. Follow-up smears and cultures are always essential.

Epidemiology of infection by serotypes D to K of chlamydia trachomatis.

Non-specific urethritis (NSU) is a sexually transmitted disease; 50% of cases are due to Chlamydia trachomatis, so that this is the commonest sexually transmitted infection in the developed world. Chlamydial infection is now readily diagnosable and the evidence increasingly suggests that it is underdiagnosed. Chlamydial conjunctivitis (in the newborn baby or the adult) in the developed world is a complication of sexually transmitted genital infection by C trachomatis and it indicates a large reservoir of such infections. Because of the association of sexually transmitted diseases, systemic treatment for such chlamydial conjunctivitis should not be given until full genital and serological investigators have been carried out. Chlamydial infection causes serious complications (that were formerly often thought to be gonococcal), such as epididymitis in young men and salpingitis on young women. It may cause local complications in the eye of the newborn baby and even pneumonia in babies and fatal endocarditis in adults. The diagnosis of NSU should lead to the correct treatment of the male patient and of his sexual partners. It is the promiscuous woman, who does not have a regular sexual partner to report back to her that he has NSU, who is at particular risk of undiagnosed chlamydial infection. Routine genital investigations for chlamydia are particularly indicated in her case. Following the parallel of gonorrhoea, it seems that the use of contact tracers may be an effective method for controlling chlamydial infection.

Talampicillin and probenecid compared with ampicillin and probenecid for the treatment of gonococcal urethritis in men.

Two hundred and ten men suffering from uncomplicated gonococcal urethritis were treated with one of two treatment schedules. Of 109 patients treated with 3 g ampicillin and 2 g probenecid (group A) there were two recurrences in the first week after treatment and none in the second week. Of 101 patients treated with 1.5 g talampicillin and 2 g probenecid (group B), there were three recurrences in the first week and none in the second week. Both antibiotics were well tolerated, but one patient vomited two hours after taking talampicillin. The sensitivity pattern of Neisseria gonorrhoeae to penicillin at The London Hospital has shown an increase in the proportion of more sensitive strains during the last three years. Talampicillin given in a single dose with probenecid is satisfactory in the treatment of acute gonococcal urethritis but, apart from the smaller dosage, it does not offer any advantage over ampicillin with probenecid.

Triple-culture tests for diagnosis of chlamydial infection of the female genital tract.

By use of triple-culture tests of each site, Chlamydia trachomatis was isolated from 112 women: from cervical material from 110, urethral material from 32, and rectal material from 19. Triple swabs provided 89 (81%) of 110 diagnoses of cervical infection; the first swab yielded 65 (59%), the second an additional 15 (14%), and the third an additional nine (8%). Three sets of cervical scrapings provided 102 (93%) of 110 diagnoses of cervical infections; the first scrapings yielded 76 (69%), the second an additional 22 (20%), and the third another four (4%). Of 32 women with positive urethral cultures, the first swab was positive in 28 (88%), and the second in the remaining four. Of 19 women with positive rectal cultures, the first swab yielded 11 (58%), the second an additional five (26%), and the third an additional three (16%). The results show that positive culture results obtained by use of a single swab underestimate the prevalence of chlamydial infection.

A rapid and sensitive culture test for the laboratory diagnosis of genital herpes in women.

A rapid and sensitive cell culture test has been developed to detect herpes simplex virus (HSV) in women with genital herpes. The virus is cultured by inoculation and centrifugation of cell monolayers, and the virus inclusions are detected using an indirect immunofluorescence test. The test takes only 48 hours to complete compared with the conventional cell culture test, which may take up to eight days. Of a total of 2100 cervical specimens collected from unselected women attending a sexually transmitted diseases (STD) clinic and inoculated in parallel, HSV was isolated from 55 specimens by either or both tests. Of these 55 positive specimens, 54(98%) were positive by the rapid test but only 24(44%) by the conventional test (McNemars test; p less than 0.001).

Colposcopy, biopsy, and cytology results in women with chlamydial cervicitis.

Colposcopy and biopsy were carried out at diagnosis and at follow up of 222 women. Of 322 cervical biopsy specimens taken, 174 were from women with chlamydial cervicitis (patients) and 48 from control women (both at diagnosis) and 100 from 76 patients and seven controls at follow up. Of the 174 patients with chlamydial cervicitis, 158 (91%) had erythema compared with 9/48 (19%) controls, and 140 (81%) had "follicles" and lumps compared with three (6%) controls. The cervical polymorphonuclear leucocyte (PMNL) count in a high power (x 1000) field (HPF) was 85 in patients compared with 47/HPF in controls. Cervical ectopia was found in 154 (89%) patients compared with 32 (67%) controls. After treating the 174 patients, we found erythema in nine (5%) and "follicles" in 16 (9%); both conditions were disappearing. Lymphocytic germinal follicles were found on histology in only 5/165 patients compared with none in controls or in patients at follow up examination (after treatment for chlamydial cervicitis). Inclusions were found in 6/165 patients compared with none in controls or patients at follow up. Chlamydiae were found on electron microscopy in slides from seven out of 159 patients compared with none from controls or 81 subjects at follow up. Estimating numbers of inflammatory cells and measuring vascularity showed diffuse increases in lymphocytes and plasma cells and increases in vascularity in both endocervical and exocervical tissue of patients with chlamydial cervicitis. These increases were lessened by treatment.

Penicillin levels in blood and CSF achieved by treatment of syphilis.

Treponemicidal levels of penicillin in the CSF were not obtained following intramuscular (IM) injections of 600,000 IU of penicillin G procaine along with 2% aluminum monostearate (PAM). Treponemicidal levels of penicillin in the CSF were achieved in 31 patients by probenecid, 500 mg/6 hr by mouth, with penicillin G, 500,000 IU by IM injection, and by probenecid every six hours by mouth and IM injections of penicillin G procaine once a day in two of three patients following injections of 600,000 IU, in four of five following 1.2 million IU, and in three (now all nine) following 2.4 million IU.

Diagnosis of ophthalmia neonatorum.

Ninety consecutively seen babies with eye discharge in the first three weeks of life were examined. Four babies had "sticky eyes" with no evidence of ophthalmia and had uniformly negative cultures and test results for antichlamydial antibody; these babies were excluded. Of the 86 babies with ophthalmia neonatorum, Neisseria gonorrhoeae was isolated from eight, Chlamydia trachomatis from 44, other bacteria alone from 20, and 14 had negative cultures. Three babies with negative cultures had longstanding conjunctivitis and had been treated with chloramphenicol eye ointment; all had antichlamydial IgM antibodies, indicating that the conjunctivitis was chlamydial. Hence the total number of babies whose conjunctivitis was chlamydial was 47. The result of the Gram stained conjunctival smear correlated well with that of culture and final assessment by the microimmunofluorescence test, enabling an immediate presumptive diagnosis to be made of gonococcal, chlamydial, or bacterial conjunctivitis. Prompt and effective treatment of babies was started. Explanation to the mother and contact tracing were carried out when the confirmatory cultures and antibody tests were completed. The Gram stained conjunctival smear is a highly sensitive, specific, and predictive test for the aetiological agent of ophthalmia neonatorum. By virtue of its simplicity and rapidity the test may be useful in developing countries.

Urethritis due to Chlamydia trachomatis.

Ninety-five men suffering from gonococcal urethritis were treated and observed. Forty-nine developed postgonococcal non-specific urethritis (PGU). Seventeen men were demonstrated to be free from PGU after careful observation; these formed a control group. Chlamydia trachomatis was isolated from urethral material from 26 (53%) of the PGU group but from none of the controls. This difference was highly significant (P less than 0-001). It confirms that C. tachomatis is a pathogen in the urethra. The presence of specific IgM antibody to C. trachomatis in serum from some men developing PGU, from whom that organism was isolated, suggests that the infection was recent in those cases. Ureaplasma urealyticum (T strain mycoplasma) was isolated from urethral material taken from 22 (45%) of the 49 men in the PGU group, and from 12 (71%) of the 17 in the control group. Mycoplasma hominis was isolated from 10 (20%) of the 49 men in the PGU group, and from four (24%) of the 17 men in the control group. Thus, no evidence was obtained that mycoplasmas (U. urealyticum, M. hominis) are patogenic in the urethra.

Subclinical pneumonia due to serotypes D-K of Chlamydia trachomatis. Case reports of two infants.

Pneumonia due to serotypes D-K of Chlamydia trachomatis occurred in a 10-week-old baby, who had been successfully treated with chlortetracycline eye ointment for chlamydial ophthalmia neonatorum, and in a 7-week-old baby being treated for the same condition. Clinical signs of pneumonia were minimal. Such chlamydial pneumonia in infants must be under-diagnosed. Infants with chlamydial ophthalmia neonatorum are now routinely treated with erythromycin suspension by mouth in addition to chlortetracycline eye ointment.