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Effects of cefetamet (Ro 15-8074) on Treponema pallidum and experimental syphilis.

Cefetamet pivoxil (Ro 15-8075) is a newly developed, expanded-spectrum cephalosporin that is orally active. In vitro, the active form, cefetamet (Ro 15-8074), at a concentration of 0.05 micrograms/ml killed and lysed Treponema pallidum. Rabbit serum did not diminish its effectiveness. The antibiotic rapidly entered the circulation following intramuscular injection into rabbits, attaining its highest levels of 24 to 37 micrograms/ml within 10 to 30 min. Animals were infected intradermally with T. pallidum and then treated with different doses of cefetamet. Accelerated healing was detected following treatment with 15 and 30 mg/kg of body weight. The antibiotic was also effective in killing organisms that had disseminated to distant tissues. In three separate sets of experiments, rabbits were infected with treponemes and then treated with cefetamet intramuscularly at 1, 15, or 30 mg/kg as follows: (i) after lesions had just become clinically apparent, (ii) after lesions were enlarged and well developed, or (iii) prior to the appearance of clinical lesions. Antibiotic effectiveness was determined by sacrificing the animals 1 week after antibiotic treatment and examining splenic tissue for residual, disseminated treponemes. Cefetamet was treponemicidal in all three situations. Maximum effects occurred when the antibiotic was injected before lesions had become clinically apparent (incubation period). These results suggest that cefetamet pivoxil might be useful for treating syphilitic infections.

Animals↗

Management issues in syphilis.

Syphilis is a sexually transmitted infection which is systemic from the outset and has increased in incidence worldwide over the last decade. There has been concern as to whether or not co-infection with HIV can modify the clinical presentation of syphilis and, as a genital ulcer disease, it can facilitate the transmission of HIV infection. Diagnosis is based on the microscopic identification of the causative treponeme and serological testing. Recommendations for the treatment of syphilis have been based on expert opinion, case series, some clinical trials and 50 years of clinical experience. Penicillin, given intramuscularly, is the mainstay of treatment and the favoured preparations for early infectious syphilis are benzathine penicillin as a single injection or a course of daily procaine penicillin injections for 10 to 14 days. The duration of treatment is longer for late syphilis. There has been concern that benzathine penicillin may not prevent the development of neurosyphilis but that is a rare outcome with this therapy. The main alternative to penicillin is doxycycline, but the place of azithromycin and ceftriaxone is yet to be established. It is not necessary to carry out examination of the cerebrospinal fluid in patients with early infectious syphilis but it should be performed in those with neurological or ocular signs, psychiatric signs or symptoms, when there is evidence of treatment failure and in those who are co-infected with HIV. Follow-up is an essential part of management and should be particularly assiduous, for at least 24 months, in those co-infected with HIV. Partner notification should be mandatory to try to contain the spread of infection.

Contact Tracing↗

Immunization with Treponema pallidum endoflagella alters the course of experimental rabbit syphilis.

Rabbits were immunized over a 32-week period with a total of 450 micrograms of purified Treponema pallidum endoflagella. As measured by enzyme-linked immunosorbent assay, sera from immunized rabbits had antiendoflagellar antibody titers that were fivefold greater than titers of sera from infected immune rabbits and patients with secondary disease. Sera from all immunized animals possessed complement-dependent treponemicidal activity as measured by in vitro immobilization. Immunized animals challenged with virulent T. pallidum were not protected from symptomatic infection but showed an altered course of lesion development.

Animals↗

Ultrasound markers of fetal infection, Part 2: Bacterial, parasitic, and fungal infections.

Up to 1% of all pregnancies have clinically overt intra-amniotic bacterial infections, and an even larger percentage of pregnant women may be affected by silent infections. Although most pregnant women with overt intra-amniotic bacterial infection have experienced prolonged rupture of membranes (PROM), symptomatic and most silent nonviral intra-amniotic infections may occur with intact membranes. The etiology of intra-amniotic infection after PROM is almost always polymicrobial and consists of genital tract pathogens, such as group B streptococci, Chlamydia trachomatis, Neisseria gonorrhoeae, mycoplasmas, aerobic Gram-negative bacilli, such as the coliforms, and facultative and anaerobic endogenous organisms, such as peptococci, peptostreptococci, and Bacteroides species. These organisms gain access to the uterine cavity by the ascending route. Organisms such as Treponema pallidum, Listeria monocytogenes, Toxoplasma gondii, trypanosomes, and plasmodia are capable of gaining access to the amniotic cavity by transplacental hematogenous spread, and cause devastating fetal infections. Symptomatic intra-amniotic infection is usually a diagnosis of exclusion. Diagnostic criteria based on both clinical and laboratory findings lack sensitivity and are nonspecific. It is difficult to obtain uncontaminated intra-amniotic samples, especially when there is PROM. The problem is even greater with silent infections. In most cases, fetal infection is suspected after an unexplained and unexpected adverse outcome. Maternal morbidity is increased with intra-amniotic infection; although maternal mortality is extremely rare in developed countries, this is not the case in societies where pregnant women have limited or no access to medical care. Although infected women who are treated early and aggressively with wide-spectrum antibiotics do well, more than 10% of these women develop bacteremia and up to half of them will require cesarean delivery because of poor uterine contractions and arrest of labor. The overwhelming majority of term neonates exposed to intrauterine infection after PROM do well, but up to 30% of these neonates require treatment of neonatal pneumonia or bacteremia. Outcomes for preterm neonates or for neonates who experienced silent fetal infections are more severe. Morbidity and mortality rates in these cases are high, and survivors may have long-term devastating sequelae. The ability to identify ultrasound markers of fetal infection will help clinicians identify etiologic agents with greater accuracy and correlate these infections with specific antepartum and postpartum syndromes. The recognition of markers of intrauterine infection will also reduce unexpected adverse outcomes that result from undiagnosed fetal infections.

Bacterial Infections↗

The microbiological flora of penile ulcerations.

The penile ulcerations of 100 consecutive men were tested for microorganisms. A polymicrobial flora was identified in the ulcers of 97 men. The microorganisms recovered from these ulcers included combinations of anaerobic and aerobic bacteria (including Mycoplasma), herpes simplex virus, yeasts, and filamentous fungi. Fifty-three study entrants had microorganisms, identified by culture or serologic tests, that were considered primary in ulcer pathogenesis. Herpes simplex virus was the most prevalent and Treponema pallidum was the next most prevalent pathogen identified. Of our patients, 5% had two recognized pathogens confirmed by laboratory tests, and only one of these was suspected at clinical examination. In addition, the study suggests that microorganisms other than Haemophilus ducreyi can produce ulcers with a morphology mimicking chancroid.

Adolescent↗

Development of an experimental model allowing discrimination between virulent and avirulent isolates of Serpulina (Treponema) hyodysenteriae.

Variation in virulence among different strains of Serpulina hyodysenteriae was studied by oral inoculation of specific pathogen free piglets and CD-1 mice. Piglets infected with serotype 2 reference strain B204 and an untypable field strain LHV-90-9-I had severe diarrhea tainted intermittently with mucus and fresh blood. The piglets inoculated with B169, B8044, B6933, and ACK300-8 reference strains representing serotypes 3, 5, 6, and 7 respectively developed moderate diarrhea. However, reference strains B234 and A-1 of serotypes 1 and 4, respectively, failed to cause any diarrhea. None of the S. hyodysenteriae strains caused diarrhea in mice. The results indicate a great variation in virulence among strains of different serotypes of S. hyodysenteriae. Mice were less susceptible to infection with S. hyodysenteriae.

Animals↗

With this eruption, there is not a second to lues.

A 28-year-old white man presented to the Emergency Department with a 24-hour history of an eruption on his extremities, trunk, and face. The patient was known to be HIV positive with a CD4 count of 527 and a viral load of 20,300. He denied fever, chills, malaise, and headache. His social history was significant for the fact that he was in a monogamous homosexual relationship. He had no recent travel, pet exposures, or sick contacts. Physical examination revealed stable vital signs and no documented fever. A maculopapular eruption was present on his face, trunk, and extremities (Figures 1 and 2). There was no palmar or plantar involvement. He was treated with diphenhydramine and topical 2.5% hydrocortisone and advised to return if his condition did not improve. Twelve days after the initial evaluation, the patient consulted us again due to progression of his dermatitis. He had no additional complaints other than an eruption on both palms but neither sole. (Figure 3). The eruption now demonstrated erythematous pink-red oval macules and papules 1-2 cm in size distributed on his scalp, face, trunk, and arms. A few papules contained fine collarettes of scale. Further questioning revealed that the patient had experienced a tender rectal ulcer 2 months previously. A punch biopsy and rapid plasma reagin were performed. The histopathologic examination revealed interface dermatitis with lymphocytes, plasma cells, occasional neutrophils, and a prominent lymphoplasmacytic perivascular dermatitis with infiltration of the vessel walls. Warthrin-Starry and Steiner methods demonstrated spirochetes at the dermal-epidermal junction and in vessel walls, consistent with Treponema pallidum (Figure 4). Rapid plasma reagin and fluorescent Treponema antibody were both reactive with a Venereal Disease Research Laboratory (VDRL) of 1:16. The patient was diagnosed as having secondary syphilis and treated with 2.4 million units of IM benzathine penicillin for 3 weeks. His eruption resolved after the initial treatment and he did not experience a Jarisch-Herxheimer reaction.

Adult↗

Infections in IVF: review and guidelines.

Since the inception of in-vitro fertilization (IVF), questions about contamination and the transmission of infection have been raised. In this review, screening for Chlamydia trachomatis, as well as medical and ethical considerations on IVF in couples infected with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), are discussed. IVF is not contraindicated in case of HBV or HCV infection, but the decision is far more delicate in case of HIV infection. If donor gametes or embryos are used, prevention of infectious disease transmission resides in accurate donor selection, including screening for C. trachomatis, HIV, HBV, cytomegalovirus and Treponema pallidum. In the embryology laboratory, microbial contamination of the IVF system deserves attention, and can be prevented by using sterile technique and supplementing culture media with screened sera or serum substitutes and antibiotics. Persons whose biological material is to be cryopreserved should be screened for HBV, HCV and HIV, and separate containers should be used for infected and non-infected material. Finally, transmission of infectious diseases to laboratory personnel can be prevented by adherence to strict safety guidelines, wearing of protective clothing, HBV vaccination, prohibition of mouth pipetting, and developing a plan for the disposal of bio-hazardous material.

Chlamydia Infections↗

Activation of macrophages by products of lymphocytes from normal and syphilitic rabbits.

The production of soluble macrophage-activating factors by lymphocytes from syphilitic and normal rabbits was examined. Culture supernatants of splenic lymphocytes cultured with Treponema pallidum antigens or concanavalin A were incubated with rabbit peritoneal macrophages in vitro. The macrophage monolayers were then washed and infected with log-phase Listeria monocytogenes. Activation of the macrophages by lymphocyte products was measured by the ability of the macrophages to resist intracellular multiplication of Listeria and thus survive infection. Macrophages incubated with supernatants of unstimulated lymphocytes or T. pallidum-stimulated lymphocytes from normal rabbits were unable to resist intracellular multiplication of Listeria. Specifically stimulated lymphocytes from syphilitic rabbits and mitogen-stimulated lymphocytes from both normal and syphilitic rabbits demonstrated a clear ability to produce soluble factors which conferred upon macrophages the ability to limit the intracellular growth of the bacteria. Antigen or mitogen alone was unable to activate the macrophages; the presence of lymphocyte products was required.

Animals↗

[Syphilis. An up-to-date physio-biological view of the main topics. IV.--The problem of the treatment by penicillin (author's transl)].

Can penicillin be considered as an infallible treatment for syphilis? Some practitioners have hoped and even believed that this antibiotic would be able to eradicate this infection. To support their thesis, they have put forward an uniform standard therapeutic plan capable of being applied to any stage of the disease and which is based upon the following syllogism: a) all T.p. would divide every 30-33 hours. b) a level of penicillinemia of 0.03 IU/ml would destroy all Treponema when they divide. c) thus, a penicillin therapy administered 3 times giving such levels in serum during a period of 33 hours would produce a bacteriological sterilization of the infected organism. But statistics have shown that these conceptions were wrong. As a matter of fact: 1) every biological research has clearly proved that it is wrong to assert such a rhythm of division for all T.p. Since this multiplication is submitted to a succession of factors that we know more or less well, thus, during the latency phase, T.p. vegetate inside the tissues without apparently multiplying so quickly. 2) For lack of being able to cultivate T.p., it is not possible to state which is the activity level of penicillin on this germ. 3) Finally, the kinetic elimination of penicillin varies extremely, particularly depending on the drug which is used with patients, and on the localization of these germs. All experimental and clinical studies agree and insist on the fact that penicillin therapy must be given early in the infection, at a prolonged and high dose; results having to be estimated on the serological answers, especially with repeated TPI and FTA tests. As far as the late phases of the disease are concerned, for lack of being able to cultivate T. pallidum and because we do not have any absolute criterion of any bacteriological sterilization, the serological answers being often positive, circumspection has always to be a rule: it is better to admit what we do not know rather than to assert without any proof.

Animals↗

Rapid seroconversion to Treponema pallidum and HIV positivity in a patient with retinal vasculitis.

A patient with idiopathic retinal vasculitis was found to have rapid conversion of serological tests for Treponema pallidum and HIV. The diagnosis was confirmed by Venereal Disease Research Laboratory (VDRL) testing and dark ground illumination for T. pallidum, and enzyme-linked immunosorbent assay (ELISA) and Western blot assay tests for HIV. Following treatment with intravenous penicillin, the fundus lesions resolved and visual acuity recovered from inaccurate light projection to 6/24 in the right eye and from counting fingers close to face to 2/60 in the left eye. Serological tests for T. pallidum in patients with concurrent HIV infection may be unpredictable. Hence, it is important to repeat these tests even in the early treatment phase of patients with retinal vasculitis who have shown initial seronegativity. This enables earlier diagnosis and initiation of specific treatment.

Adult↗

Protection against syphilis correlates with specificity of antibodies to the variable regions of Treponema pallidum repeat protein K.

Syphilis has been recognized as a disease since the late 1400s, yet there is no practical vaccine available. One impediment to the development of a vaccine is the lack of understanding of multiple reinfections in humans despite the development of robust immune responses during the first episode. It has been shown that the Treponema pallidum repeat protein K (TprK) differs in seven discrete variable (V) regions in isolates and that the antibody response during infection is directed to these V regions. Immunization with TprK confers significant protection against infection with the homologous strain. We hypothesize that the antigenic diversity of TprK is involved in immune evasion, which contributes to the lack of heterologous protection. Here, using the rabbit model, we show a correlation between limited heterologous protection and tprK diversity in the challenge inoculum. We demonstrate that antibody responses to the V regions of one TprK molecule show limited cross-reactivity with heterologous TprK V regions.

Amino Acid Sequence↗

Men who have sex with men and transgenders in Mumbai, India: an emerging risk group for STIs and HIV.

BACKGROUND: Men who have sex with men and transgenders are an important risk group for sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). They have risky sexual behaviors but low risk perception. OBJECTIVES: To assess the sexual behavior, STIs, HIV and identify factors associated with HIV in men who have sex with men (MSM) and transgenders (TGs) in Mumbai. METHODS: Participants were enrolled from two clinics in Mumbai. They completed an interviewer-administered questionnaire and were evaluated for STIs and HIV infection. RESULTS: A total of 150 participants, 122 MSM and 28 TGs were evaluated; 17% of MSM and 68% of the TGs were HIV infected. HIV infection in MSM was associated with serological positivity for HSV2 IgG [adjusted odds ratio (aOR), 95% confidence interval (CI): 9.0 (2.2-36.9)], a positive Treponema pallidum hemagglutination assay (TPHA) [aOR (95% CI): 6.0 (1.5-24.0)], greater than five acts of receptive anal sex in the past six months [aOR (95% CI): 4.3 (1.2-15.0)] and per category increase in age (18-24 yrs, 25-29 yrs, > 30 yrs) [aOR (95% CI): 3.1 (1.3-7.1)] in multivariate analysis. Consistent condom use during receptive anal sex in the past six months was low (27%). Many MSM were married (22%) or had sex with females and may act as a 'bridge population'. HIV infection in TGs was associated with a positive TPHA [OR (95% CI): 9.8 (1.5-63.9)] and HSV 2 IgG [OR (95% CI): 6.7 (1.1-40.4)] in univariate analysis. CONCLUSION: Prior STIs were strongly associated with HIV infection in MSM and TGs. These groups should be the focus of intensive intervention programs aimed at STI screening and treatment, reduction of risky sexual behavior and promotion of HIV counseling and testing.

Adult↗

Lymphocyte transformation in syphilis: an in vitro correlate of immune suppression in vivo?

Suppression of cellular immunity during primary and secondary infection may explain, in part, the unusual clinical evolution of syphilis. We have previously shown that lymphocytes from normal subjects undergo blastic transformation when exposed in vitro to Treponema refringens. This response was suppressed in patients with syphilis. the suppression being unrelated to serum factors. In the present paper we studied lymphocyte response in vitro to T. refringens, T. reiter, and T. pallidum as well as to monilia and trychophytins. The response to these antigens was suppressed in patients with syphilis although the response to phytohemagglutinin. pokeweed mitogen, and streptolysin was normal. These data support the hypothesis that human infection with T. pallidum is followed by a complex interaction between cellular and humoral immunity, the former being suppressed in primary and secondary stages.

Antigens, Bacterial↗

International adoption: issues in infectious diseases.

International adoptions have become increasingly common in the United States. Children awaiting international adoption and families traveling to adopt these children can be exposed to a variety of infectious diseases. Compared with the United States, foreign countries often have different immunization practices and methods of diagnosing, treating, and monitoring disease. Reporting of medical conditions can also differ from that of the United States. The prevalence of infectious diseases varies from country to country and may or may not be common among adopted children. The transmission of tuberculosis, hepatitis B, and measles from adopted children to family members has been documented. Furthermore, infectious organisms (e.g., intestinal parasites), bacterial pathogens (e.g., Bordetella pertussis and Treponema pallidum), and viruses (e.g., human immunodeficiency virus and hepatitis viruses) may cause clinically significant morbidity and mortality among infected children. Diseases such as severe acute respiratory syndrome or avian influenza have not been reported among international adoptees, but transmission is possible if infection is present. Family members may be infected by others during travel or by their adopted child after returning home. Families preparing to adopt a child from abroad should pay special attention to the infectious diseases they may encounter and to the precautions they should take on returning home.

Adoption↗