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Passive transfer of humoral immunity to experimental syphilis in rabbits was accomplished with large doses of hyperimmune serum. When the serum was administered before inoculation of Treponema pallidum, the onset of chancres was delayed; when it was given early in the course of infection, a transient period of arrest and healing of the chancres was imposed.
A spirochete with two periplasmic flagella was isolated from the blood or tissues of spleens and kidneys from short-tailed shrews (Blarina brevicauda) and white-footed mice (Peromyscus leucopus) in Connecticut and Minnesota. After inoculation, the shrew-mouse spirochete infected Swiss mice and Syrian hamsters. This spirochete is morphologically and serologically distinct from the species of Treponema, Borrelia, Leptospira, and Spirochaeta examined.
A model for congenital syphilis in rabbits was developed based on multiple intravenous injections of pregnant does with high concentrations of Treponema pallidum. A total of 48 pregnant does and 394 newborns were evaluated. Indications of in utero infection included a 7- to 10-fold increase in fetal mortality and a 49% reduction in birth weight. The size of the stillborns varied. Some developed to normal size, whereas others were poorly developed, hemorrhagic, and 1/10th normal size. Fetuses were surgically removed after 25 to 28 days of gestation and extracts of the fetal tissues were injected into adult rabbits. Syphilitic lesions resulted demonstrating the presence of T. pallidum within the fetal tissues. Treponemes were also demonstrated within splenic tissue from a 1-week-old newborn. Isolated amniotic membranes were placed in Franz Biologic chambers. Viable organisms readily penetrated through the amnion but heat-inactivated organisms did not. Further evidence for in utero transmission of organisms was provided by intradermal injection of 6- to 7-week-old newborns. In control newborns in which the does were not infected during pregnancy, lesions occurred at 90% of the sites injected and developed in typical fashion. In newborns from does infected during pregnancy, lesions occurred in 18% of the sites injected and developed in atypical fashion (flat, nonulcerating, rapid healing). Finally, overt congenital syphilis did not occur if the does were immune prior to pregnancy, then infected with T. pallidum during pregnancy. The percent mortalities and birth weights of newborns were equivalent to control newborns from noninfected does.
In investigations of syphilis various Treponema pallidum antigens are used to study the immune responses of naturally or experimentally infected hosts. In the past these antigen preparations have rarely been examined for their antigenic contents and activity. In the present study, supernatant, sediment, and solubilised preparations of T pallidum Nichols strain (20 X 10(9) organisms/ml) and T phagedenis biotype Reiter were examined by modified counterimmunoelectrophoresis and immunoblotting for their antigenic contents. No T pallidum antigen was seen in the supernatant fraction, which contained cross reacting (Reiter) antigens and rabbit serum proteins. The remaining T pallidum preparations contained T pallidum antigens, cross reacting treponemal (Reiter) antigens, and rabbit serum proteins. These findings suggest that T pallidum preparations should be examined qualitatively and quantitatively before they are used for monitoring immune responses and interpreting data. Technology for these examinations is available.
A comparative study of 224 serum samples certified in different serological tests for syphilis has established the high diagnostic effectiveness of the new linear enzyme immunoassay test system (immune blotting assay "Improved INNO-Lia Syphilis ("IMMO-Lia Syphilis Score")) (Immunogenetics, Gent, Belgium). The assay showed a 100% sensitivity and 98% specificity; the reproducibility of positive and negative results was 100%. It is proposed to use the test system in the laboratories engaged in the expert diagnosis of syphilis as an additional or alternative Treponema pallidum immobilization test and immunofluorescence test supporting the assay of serum or plasma samples for this infection, which has yielded positive results on screening.
Syphilitic genital ulcers are cofactors for the bidirectional transmission of human immunodeficiency virus (HIV). U937 human promonocytic cells chronically infected with HIV-1 (U1 cells) or transiently transfected with wild type or mutant HIV long terminal repeat (LTR) reporter constructs were used to examine mechanisms that likely underlie Treponema pallidum-induced immune cell activation and consequent induction of HIV. Virulent T. pallidum, a representative native treponemal lipoprotein (NTp47), or synthetic lipoprotein analogues (lipopeptides) all induced HIV replication in U1 cells. These stimuli also induced HIV gene expression from a wild type HIV LTR. HIV gene expression correlated with the translocation of NF-kappaB, and mutations within the NF-kappaB binding sites of the HIV LTR abrogated HIV gene expression. This study implicates treponemal lipoproteins as key mediators of immune cell activation and provides insights into the cellular and molecular bases for enhanced HIV transmission in syphilitic persons.
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STUDY OBJECTIVES: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.
The prevalence of sexually transmitted diseases (STD) among women visiting antenatal (ANC) and gynaecological clinics in Gondar, north-west Ethiopia, was investigated. Between April and August 1995, 728 women consented to enter the study. Prevalence rates were 5.9% (41/693) for chlamydial antigen in cervix, 18.8% (113/600) for syphilis (Treponema pallidum haemagglutination assay [TPHA]) and 25.3% (150/593) for HIV. Active syphilis (RPR)+, TPHA+ was detected in 74% (44/597). HIV infection rate was higher among women with higher age of first marriage and low gravidity. It was significantly associated with young age, urban residence, and presence of genital ulcer (odds ratio [OR] = 6.3), and lymphadenopathy (OR = 2.8) on examination. Women seropositive for syphilis had married at an earlier age, were significantly older and had changed husbands. Low gravidity and age < 30 were independently significant risk factors for cervical chlamydial antigen positivity which was predominantly asymptomatic. Significant association was observed between HIV infection and syphilis (OR = 2.6). Active syphilis was associated with chlamydial (OR = 3.4) and HIV infection (OR = 4.1). The rate of 23.4% and 15.1% of HIV seropositivity among ANC attenders and rural women respectively is an indicator of the rapid progression of the HIV epidemic in the area.
From ticks of the type Ixodes ricinus, 19 strains of a spirochete were isolated at three places of infection of erythema chronicum migrans disease. The spirochete was immunologically related to Borrelia duttoni, Treponema pallidum and Ixodes dammini spirochete, the causative organism of North American erythema chronicum migrans disease (Lyme disease). The isolated spirochete differed from the North American one in its reaction with monoclonal antibodies and possibly in its electronmicroscopic structure. A corresponding spirochete was isolated from the blood of a woman with erythema chronicum migrans. Of 39 patients with erythema chronicum migrans mostly treated with antibiotics 50% had increased IgG antibody titre (1:64 to 1:1024) against the isolated spirochete, while among 51 untreated patients with tick-transmitted meningopolyneuritis 90% had increased IgG antibody titres. Fourfold antibody titres increases or falls were found on 50 occasions. IgG antibody titres up to 1:64 were demonstrated also in CSF, in 22 instances with significant changes. Increased serum IgM antibody titres of 1:32 to 1:256 were observed in 20% and 68%, respectively, of patients. These findings suggest that the isolated spirochete is the causative agent of erythema chronicum migrans disease in Europe. Its antigen structure and arrangement is similar to that of the causative agent of Lyme disease.
From 1995 to 2001, five rounds of sentinel surveillance were carried out for young women attending antenatal care clinics at four health centers in Addis Ababa, the capital city of Ethiopia, to monitor trends in the prevalence of HIV infection and syphilis. Serum samples were tested for antibodies to HIV (enzyme-linked immunosorbent assay and Western blotting) and antibodies to Treponema pallidum (T. pallidum hemagglutination assay and rapid plasma reagin test). Prevalence ratios for an increase in one calendar year were estimated using log-binomial models. Between 1995 and 2001, the prevalence of HIV infection among young women (age range, 15-24 years) attending antenatal care clinics in inner city health centers declined from 24.2% to 15.1% (prevalence ratio for an increase in one calendar year, 0.91; 95% confidence interval, 0.87-0.95). No change was observed for older age groups or in outer city health centers. The decline in the prevalence of active syphilis (T. pallidum hemagglutination assay and rapid plasma reagin testing positive for antibodies to T. pallidum) was more pronounced among and also restricted to the young age groups (age range, 15-24 years) in the inner city (from 7.6% in 1995 to 1.3% in 2001; prevalence ratio, 0.69; 95% confidence interval, 0.59-0.80). The declining trends in the prevalence of HIV infection and syphilis among young women attending antenatal care clinics in the inner city are encouraging, but these findings require confirmation in future years and for other population groups.
From 1995 to 2001, five rounds of sentinel surveillance were carried out for young women attending antenatal care clinics at four health centers in Addis Ababa, the capital city of Ethiopia, to monitor trends in the prevalence of HIV infection and syphilis. Serum samples were tested for antibodies to HIV (enzyme-linked immunosorbent assay and Western blotting) and antibodies to Treponema pallidum (T. pallidum hemagglutination assay and rapid plasma reagin test). Prevalence ratios for an increase in one calendar year were estimated using log-binomial models. Between 1995 and 2001, the prevalence of HIV infection among young women (age range, 15-24 years) attending antenatal care clinics in inner city health centers declined from 24.2% to 15.1% (prevalence ratio for an increase in one calendar year, 0.91; 95% confidence interval, 0.87-0.95). No change was observed for older age groups or in outer city health centers. The decline in the prevalence of active syphilis (T. pallidum hemagglutination assay and rapid plasma reagin testing positive for antibodies to T. pallidum) was more pronounced among and also restricted to the young age groups (age range, 15-24 years) in the inner city (from 7.6% in 1995 to 1.3% in 2001; prevalence ratio, 0.69; 95% confidence interval, 0.59-0.80). The declining trends in the prevalence of HIV infection and syphilis among young women attending antenatal care clinics in the inner city are encouraging, but these findings require confirmation in future years and for other population groups.
Despite vaccines, new antimicrobials, and improved hygienic practices, congenital infections remain an important cause of death and long-term neurologic morbidity among infants world-wide. Important agents include Toxoplasma gondii, cytomegalovirus, Treponema pallidum, herpes simplex virus types 1 and 2, and rubella virus. In addition, several other agents, such as the varicella zoster virus, human parvovirus B19, and Borrelia burgdorferi, can potentially infect the fetus and cause adverse fetal outcomes. This article provides an overview of these infectious disorders and outlines current strategies for acute treatment and long-term management.
In the companion paper (L. A. Borenstein, M. E. Selsted, R. I. Lehrer, and J. N. Miller, Infect. Immun. 59:1359-1367, 1991), we report that rabbit alveolar macrophage and neutrophil derived defensins possess antimicrobial activity against Treponema pallidum subsp. pallidum, the etiologic agent of syphilis. In this study, antisera specific for NP-1 and NP-2 (defensins present in certain macrophages and polymorphonuclear leukocytes) and NP-5 (a defensin produced only in neutrophils) were used to detect these peptides by immunoperoxidase staining in testicular lesions from infected rabbits. Profound amounts of cell-free and cell-associated defensins were detected in the tunica albuginea and interstitial spaces during the first 24 h of infection. The presence of defensins was transient and almost undetectable by day 4. Interstitial defensins were detected again at day 10 and increased through day 16, at which time lesion healing was evident by hematoxylin and eosin staining. The appearance and increase in detectable defensins between days 10 and 16 of infection correlated with a reduction in numbers and disappearance of T. pallidum, as demonstrated by using silver staining. The extent and pattern of immunostaining for NP-1 and NP-2 corresponded with immunostaining for NP-5 and identified neutrophils as the cellular source of the defensins. These findings indicate that defensins may contribute to the control of local T. pallidum infection and suggest a role for acute inflammatory processes in the resolution of early experimental syphilis.
The ability of the macrolide antibiotic azithromycin and its epimer CP-63,956 to inhibit protein synthesis in two pathogenic strains of Treponema pallidum was investigated. Using an in-vitro radiolabelling procedure employing treponemes freshly extracted from infected rabbit testes, our results indicate that both antibiotics were comparable with erythromycin in their ability to inhibit protein synthesis in T. pallidum Nichols strain. An erythromycin-resistant clinical isolate of T. pallidum, designated Street strain 14, exhibited only partial inhibition of protein synthesis at the highest antibiotic concentration tested.
Pulmonary infection with Pneumocystis carinii was detected in two aged owl monkeys (Aotus trivirgatus) and two young chimpanzees (Pan troglodytes). The clinical histories of the owl monkeys were similar and included progressive weight loss, anorexia, failure to thrive, and death. One of the owl monkeys had no concurrent disease, whereas the other had been experimentally inoculated with Treponema pallidum 44 months before death. In both chimpanzees, an underlying myeloproliferative malignant neoplasm was associated with Pneumocystis infection. Pneumocystis organisms were found in alveolar spaces and alveolar lining cells by light and electron microscopy. Pathologic features of these untreated cases and a case in a chimpanzee treated with pentamidine isethionate were similar to those described in humans. To our knowledge, this is the first report of pulmonary pneumocystosis associated with death in nonhuman primates.
OBJECTIVE: To study the prevalence and risk factors for HIV infection among sex workers of Addis Ababa, Ethiopia. DESIGN AND METHODS: Cross-sectional survey on socio-demographic characteristics, behaviours, and HIV serological status of sex workers attending two health centres of Addis Ababa. RESULTS: HIV prevalence among sex workers was 274 of 372 (73.7%). Several factors were significantly associated with an increased risk of being HIV-infected [among others, working in 'shared rooms', high number of clients, use of injectable hormones, and positive Treponema pallidum particle agglutination (TPPA) serology], and others with a decreased risk (being born in Addis Ababa, high level of education, peer education on sex work, condom use, use of oral pill, and use of condoms for contraception). Of interest, sex workers who were using condoms for contraception were, compared with others, more likely to use condoms consistently (65 versus 24%, respectively; P < 0.001), and less likely to be HIV-infected (55 versus 86%, respectively; P < 0.001). In multivariate analysis [log-binomial model, giving estimates of the prevalence ratio (PR)], being born in Addis Ababa (PR = 0.74; 95% confidence interval (CI), 0.61-0.91), using condoms for contraception (PR = 0.73; 95% CI, 0.64-0.85), and a positive TPPA serology (PR = 1.21; 95% CI, 1.09-1.36), remained significantly associated with HIV infection. CONCLUSIONS: HIV prevalence was remarkably high among sex workers of Addis Ababa. Condom use was higher, and HIV prevalence lower, in sex workers using condoms not only for prevention of HIV and sexually transmitted diseases, but also for contraceptive purpose. This finding is of particular interest for its implications for prevention strategies among sex workers in the developing world.
In early 1996, 481 women visiting the antenatal services of the 3 major governmental health centres in the capital city of the Central African Republic (CAR) were included in the study. All study participants underwent the health centre's routine gynaecological examination, including laboratory diagnosis of trichomoniasis, candidiasis, gonorrhoea, syphilis and bacterial vaginosis. Cervical secretions and blood samples from study participants were sent to the National STD Reference Centre for diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans, Treponema pallidum, and HIV. Overall, 34% of the study women were diagnosed with at least one sexually transmitted infection (STI) (3.1% N. gonorrhoeae, 6.2% C. trachomatis, 9.9% T. vaginalis, 6.7% T. pallidum, 12.2% HIV-1). In addition, 29.1% of women were diagnosed with bacterial vaginosis and 46.6% with candidiasis. Only a small proportion of these women had sought treatment during the weeks before, despite the recognition of genital symptoms. Self-reported and health worker-recognized symptoms, signs and laboratory results exhibited only low sensitivities, specificities, and positive predictive values in the diagnosis of STIs. These findings confirm the high vulnerability of young African women to STIs and emphasize the need for specific control interventions which should include affordable and user-friendly services. Moreover, these results call for more effective quality control in case of laboratory-based STI control strategies and question the validity of syndromic STI management strategies in women attending antenatal care services in Africa.