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The natural history of syphilis. Implications for the transmission dynamics and control of infection.

BACKGROUND: Syphilis remains a significant cause of morbidity in many developing countries and in some areas within North America and Europe. Mathematical models of the transmission dynamics of sexually transmitted infections have provided insights of relevance both to the interpretation of observed epidemiological patterns and to the design of control programs. Their use for the study of syphilis has been limited to date. GOALS AND STUDY DESIGN: The authors investigated the transmission dynamics of syphilis against a template based on the natural history of infection in individual patients with the aim of (1) identifying gaps in our understanding of the biology of infection, and (2) providing insights of relevance to the design of control policies. RESULTS: Analyses reveal that Treponema pallidum has a moderate to high probability of transmission during contact between susceptible and infectious sexual partners. This, combined with questions over the existence of any immunity to reinfection, helps to ensure the long-term persistence of syphilis within "core" activity groups. Patterns of treatment in North America are shown to have significantly altered the relative frequency of individuals in the different stages of disease. CONCLUSIONS: The analyses emphasize the benefits to be gained from treating infected people early in the primary stage of infection to reduce the effective period during which infected people can transmit to others. This form of treatment is beneficial for both the individual and the community. Treatment has greatly altered the incidence of different disease stages, but the full implications of treatment depend on whether immunity is present.

Contact Tracing↗

Human immunodeficiency virus (HIV) infection in patients attending a sexually transmitted diseases clinic in Borno State of Nigeria.

Results of a study to determine if patients attending sexually transmitted diseases (STD) clinics are at high risk to human immunodeficiency virus (HIV) infection are presented. The 206 patients who attended the STD clinic at the Maiduguri General Hospital consisted of 200 males and 6 females, most of whom were aged between 20 and 29 years and were single. Only one of the 206 serum samples (0.49%) was confirmed seropositive for HIV-1 antibodies. However, cultures from 143 of 174 swabs taken from the subjects yielded significant growth of which Staphylococcus aureus was the predominant isolate followed by Neisseria gonorrhoea. Antibodies to Treponema pallidum were also detected in 3.9% of the serum samples. This study shows that HIV-1 infection is relatively rare in Borno state of Nigeria. In spite of this, a well-planned health education campaign for STD patients is indicated if HIV infection is to be effectively controlled.

Adolescent↗

Laboratory methods of diagnosis of syphilis for the beginning of the third millennium.

Despite that the whole genome of T. pallidum, the causative agent of syphilis, has been sequenced, syphilis is, and will remain for some time, diagnosed by direct clinical observation and by laboratory methods. This review presents comprehensively most of the practical techniques used for direct detection of T. pallidum and lists all practical methods for phospholipid and treponemal antibodies detection. It describes most novel tests for syphilis, discusses problems with sero-creossreactivity in Lyme disease, immune responses in HIV-syphilis coinfected patients, and reviews serologic responses to antibiotic treatment.

Anti-Bacterial Agents↗

Periodontal infections and cardiovascular disease: the heart of the matter.

BACKGROUND: Oral infection models have emerged as useful tools to study the hypothesis that infection is a cardiovascular disease (CVD) risk factor. Periodontal infections are a leading culprit, with studies reporting associations between periodontal disease and CVD. The results, however, have varied, and it often is unclear what conclusions can be drawn from these data. SUMMARY: An association exists between periodontal disease and CVD. It is unknown, however, whether this relationship is causal or coincidental. Early studies predominantly used nonspecific clinical and radiographic definitions of periodontal disease as surrogates for infectious exposure. While most studies demonstrated positive associations between periodontal disease and CVD, not all studies were positive, and substantial variations in results were evident. More recent studies have enhanced the specificity of infectious exposure definitions by measuring systemic antibodies to selected periodontal pathogens or by directly measuring and quantifying oral microbiota from subgingival dental plaque. Results from these studies have shown positive associations between periodontal disease and CVD. CONCLUSIONS: Evidence continues to support an association among periodontal infections, atherosclerosis and vascular disease. Ongoing observational and focused pilot intervention studies may inform the design of large-scale clinical intervention studies. Recommending periodontal treatment for the prevention of atherosclerotic CVD is not warranted based on scientific evidence. Periodontal treatment must be recommended on the basis of the value of its benefits for the oral health of patients, recognizing that patients are not healthy without good oral health. However, the emergence of periodontal infections as a potential risk factor for CVD is leading to a convergence in oral and medical care that can only benefit the patients and public health.

Aggregatibacter actinomycetemcomitans↗

[Issues of congenital syphilis in the past twenty years. II. Clinical picture].

The paper describes the clinical picture and management of congenital syphilis. In the introduction the origin of syphilis is mentioned. The etiologic agent -- Treponema pallidum subsp. pallidum (Tp) -- is transmitted to fetus almost exclusively via placenta. Perinatal infections are less frequent, and postnatal infections are only exceptionally. The symptoms of congenital syphilis may be divided into prenatal (syphilis materno-fetalis), neonatal, and rarely seen postnatal. Prenatal symptoms causing the immaturity of fetus are recognizable from the 7th month of pregnancy and associated with miscarriages, premature deliveries of still-born babies or live neonates with congenital syphilis. Neonatal and postnatal symptoms are manifested only after birth. They may present immediately at birth, develop within first two years of life as early congenital syphilis, or (similarly to acquired syphilis) later in life as a late localized form, often seen many years after birth, even at puberty -- late congenital syphilis. The clinical picture depends on many factors -- primarily on the duration of the infection in mother and the stage of pregnancy.

Female↗

[Methods of silver impregnation in morphological diagnosis of gastric syphilis].

Comparative assessment of methods of silver impregnation for pathohistological identification of Treponema pallidum in gastric syphilis was performed. Levaditi impregnation is preferable in cases of gastrectomy. Silver impregnation in histological slides is performed for studying endoscopic biopsies in view of their small size as well as for retrospective analysis when paraffin blocks only are available. Steiner's method in modification with the use of microwave stove allows better identification of Treponema pallidum than impregnation by Vartin-Starri. Helicobacter pylori may also be identified by silver impregnation. Association of syphilitic and Helicobacter infections deteriorates inflammatory and destructive lesions in the stomach.

Bacteriological Techniques↗

Molecular detection of Treponema pallidum in secondary and tertiary syphilis.

Treponema pallidum can be detected by conventional techniques such as dark-field microscopy, immunofluorescence or the rabbit infectivity test, in large numbers in the skin lesions of primary and early secondary syphilis. In the skin lesions of late secondary and tertiary syphilis, conventional techniques fail to detect spirochaetes in general, perhaps due to increasing degeneration and the disappearance of treponemal spirochaetes in late syphilitic skin lesions. We used the highly sensitive technique of polymerase chain reaction (PCR) to prove the presence of Treponema pallidum-specific DNA in six lesions of late secondary syphilis and seven lesions of tertiary syphilis, including one syphilitic gumma. A Whartin-Starry stain was carried out in all 13 specimens and did not reveal any treponemal structures. Treponema pallidum-specific DNA was amplified by PCR in four of six cases of secondary syphilis and in the syphilitic gumma. These results are in favour of a direct cell-mediated immune reaction directed against treponemal antigen rather than the concept of an Id-reaction. Beside the usefulness of a PCR-based assay for understanding the aetiology of lesions of late syphilis, the assay described can be of clinical importance in various situations where traditional methods fail to detect Treponema pallidum because of lack of sensitivity.

DNA, Bacterial↗

Adherence of periodontopathic bacteria to bioabsorbable and non-absorbable barrier membranes in vitro.

Guided tissue regeneration (GTR) techniques are increasingly used for the treatment of periodontal defects, or in conjunction with dental implant procedures. As adhesion of bacteria to barrier membranes used in these techniques may lead to failure, a prerequisite for treatment success is an infection-free healing process. The present study examined the adhesion of 3 periodontal pathogenic bacteria: Actinobacillus actinomycetemcomitans, Treponema denticola and Porphyromonas gingivalis, to 3 barrier membranes: Collagen, (Biomend) PTFE, (TefGen-FD) and e-PTFE, (Gore-Tex). The membranes were incubated with 3[H]-thymidine labeled bacteria, and the number of adherent bacteria was calculated using a scintillation counter. The effect of albumin coating on bacterial adherence to the membranes was also studied. Bacterial adherence to the membranes was further examined by scanning electron microscopy (SEM). The results show that the adherence of all bacterial strains to collagen membranes was significantly higher than to the other membranes tested. Precoating of the membranes with albumin did not change the bacterial adherence significantly. These findings are of importance in evaluating the ability of periodontal bacteria to colonize and infect different types of barrier membranes.

Absorbable Implants↗

High rates of sexually transmitted diseases among male transvestites in Jakarta, Indonesia.

Many male transvestites (waria) in Jakarta, Indonesia engage in unprotected receptive anal and oral intercourse with homosexual and bisexual men for pay. Although this behaviour clearly puts them at risk of sexually transmitted diseases (STDs), including HIV infection, little is known about the prevalence of STD among them. To learn the STD prevalence and its risk factors, we conducted an STD prevalence survey among waria in North Jakarta, Indonesia. From August to December 1999 we offered screening for rectal and pharyngeal infections with Neisseria gonorrhoeae (Ng), Chlamydia trachomatis (Ct) by DNA probe (GenProbe PACE 2) and for Treponema pallidum (Tp) by non-treponemal and treponemal serological tests. Of 296 participants (median age 28 years), 93% reported having been paid for sex. A total of 96% reported having had oral sex (median five times/week) and/or anal sex (median three times/week) in the last week. Ng was found in the rectum of 12.8% and the pharynx of 4.2%; Ct was found in 3.8% and 2.4%, respectively. A total of 43.6% had reactive non-treponemal and treponemal tests. Of the 129 with positive treponemal tests, 42.6% had non-treponemal test titres greater than 1:8. In the logistic regression model, waria who were younger (< or =25 years old) had a significantly 3.5 times risk of Ng and/or Ct infections than older waria (>25 years old). Because only 12% of waria stated that they consistently used condoms during any sex act, it is important to warn them that STD/HIV transmission can occur with either anal or oral sex and that the risk of either anal or oral transmission can be reduced by condom use. In addition, high rates of asymptomatic syphilis and rectal gonorrhoea warrant a periodic screening and treatment for these infections in this population. Because waria have the highest rates of HIV and their clients consist of homosexual and bisexual men, successful prevention efforts in waria could help curb the spread of the epidemic.

Adult↗

Humoral immunity in experimental syphilis. II. The relationship of neutralizing factors in immune serum to acquired resistance.

Evidence for a humoral mechanism in immunity to experimental syphilis was provided by the demonstration of immune rabbit serum factor(s) capable of inactivating virulent Treponema pallidum, Nichols strain, in an in vitro-in vivo neutralization test. After intratesticular infection, rabbits were bled periodically and their resistance to reinfection was determined by challenge with T. pallidum. The results of challenge showed that resistance to reinfection begins to develop by 11 days after infection, becomes complete by 3 months, and persists for at least 2 years. In the neutralization test, a mixture of treponemal suspension and serum from the infected animals was incubated anaerobically at 34 degrees C and the virulence of the treponemes was determined by intradermal inoculation into normal rabbits. Complete inactivation of treponemes by immune serum required heat-stable and heat-labile (56 degrees C, 30 min) serum components and 16 hr of incubation, and was accelerated by pre-incubation of the treponemes for 4 hr with nonimmune serum but not by 100 mug/ml of added lysozyme. Serum-neutralizing activity, first demonstrable 1 month postinfection, was quantitated by a neutralizing endpoint (NEP). A relatively close quantitative correlation was shown between the development of resistance to symptomatic reinfection and the appearance and persistence of both TPI antibody and neutralizing serum factor(s). The nature of the serum factor(s), the mechanism of treponemal inactivation, and the application of the test in assessing the immune status are discussed.

Animals↗

Seroprevalence of HIV among female sex workers in Bangkok: evidence of ongoing infection risk after the "100% condom program" was implemented.

BACKGROUND: After implementation in 1991 of a nationwide campaign to promote condom use during commercial sex, HIV-1 seroprevalence among young men began to decrease in 1994. However, it is unknown to what degree female sex workers (FSWs) have been protected from infection. METHODS: FSWs attending a government clinic in Bangkok in 1997 and 1998 were interviewed, counseled, and tested for evidence of prior syphilis by Treponema pallidum hemagglutination assay (TPHA) and for HIV-1 antibodies. RESULTS: Among the 500 participants, women who began sex work more recently reported less risky sex behavior when they were first potentially exposed to HIV infection, and TPHA reactivity rates were lower among these women. However, their HIV infection rates were higher. HIV seroprevalence was 5.5% among 91 women who began sex work before 1989, 8.0% among 87 women who began during 1990 to 1993, and 12.5% among 322 women who had begun since 1994. CONCLUSIONS: Although condom use is critical to HIV prevention, women in this study who began sex work after the condom promotion campaign was implemented were still at high risk for HIV infection. Additional measures are needed to prevent HIV infection among the many young women who initiate or continue to engage in commercial sex.

Adult↗

Molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern Thailand: predominance of herpes simplex virus infection.

A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens for 38 sequential patients with GUD at a Thai sexually transmitted disease clinic. Subjects received clinical diagnoses and syndromic treatment. Swab specimens for H. ducreyi cultures and M-PCR were obtained. No H. ducreyi cultures were positive. Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%) for both HSV and T. pallidum, and none for H. ducreyi or T. pallidum alone; 6 (15.8%) were negative for all 3 pathogens. Clinical diagnoses corresponded poorly to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed by M-PCR. Human immunodeficiency virus infection status was known for 24 of 38 subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR. HSV appeared to be the most common pathogen overall.

Chancroid↗

Similarity between the 38-kilodalton lipoprotein of Treponema pallidum and the glucose/galactose-binding (MglB) protein of Escherichia coli.

The recent discovery that abundant and immunogenic lipoproteins constitute the integral membrane proteins of Treponema pallidum has prompted efforts to investigate their importance in the physiology and ultrastructure of the organism and in immune responses during infection. Earlier studies identified a 38-kDa lipoprotein of T. pallidum believed to be specific to the pathogen. In the present study, monoclonal antibodies generated against the 38-kDa lipoprotein of T. pallidum reacted with cognate 37-kDa molecules in the nonpathogens Treponema phagedenis, Treponema denticola, and Treponema refringens. Cloning and expression of the 38-kDa-lipoprotein gene of T. pallidum in Escherichia coli revealed that the recombinant product displayed a slightly larger (39-kDa) apparent molecular mass but remained reactive with anti-38-kDa-protein monoclonal antibodies. The recombinant product was processed and acylated in E. coli. DNA and amino acid sequence analyses indicated an open reading frame encoding 403 amino acids, with the first 25 amino acids corresponding to a leader peptide terminated by a signal peptidase II processing site of Val-Val-Gly-Cys. The predicted mature protein is 378 amino acids in length with a deduced molecular weight of 40,422 (excluding acylation). Southern blotting failed to demonstrate in nonpathogenic treponemes genomic sequences homologous with the 38-kDa-lipoprotein gene of T. pallidum. Computer analysis revealed that the 38-kDa lipoprotein of T. pallidum had 34.2% identity and 58.9% similarity with the glucose/galactose-binding protein (MglB) of E. coli and Salmonella typhimurium. Furthermore, of the 19 amino acids of MglB involved in carbohydrate binding, the 38-kDa lipoprotein had identity with 11. These studies have allowed the first putative functional assignment (carbohydrate binding) to a T. pallidum integral membrane protein. Recognition of this potential physiological role for the 38-kDa lipoprotein underscores the possibility that the membrane biology of T. pallidum may more closely resemble that of gram-positive organisms, which also utilize lipoproteins as anchored transporters, than that of gram-negative bacteria to which T. pallidum often is analogized.

Amino Acid Sequence↗

Genital ulcers associated with human immunodeficiency virus-related immunosuppression in female sex workers in Abidjan, Ivory Coast.

A cross-sectional study among female sex workers in Abidjan was conducted to study the association between sexually transmitted diseases and human immunodeficiency virus (HIV) infection and HIV-related immunosuppression. Among 1209 women tested for HIV, 962 (80%) were seropositive. HIV infection was independently associated with a longer duration of sex work, a lower price for intercourse, being an immigrant, and having a positive Treponema pallidum hemagglutination test (P < .05). Genital ulcers (25% vs. 5%), genital warts (14% vs. 4%), Neisseria gonorrhoeae (32% vs. 16%), Trichomonas vaginalis (27% vs. 17%), and syphilis (27% vs. 17%) were more frequent (P < .05) in HIV-infected than -uninfected women. Among HIV-infected women, the proportions with a genital ulcer were 17%, 25%, and 36% for those with > 28%, 14%-28%, and < 14% CD4 cells, respectively (P < .001). This study suggests that genital ulcers are an opportunistic disease in female sex workers in Abidjan.

AIDS-Related Opportunistic Infections↗