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STI/HIV co-infections in UCH, Ibadan, Nigeria.

Sexually transmitted infections (STIs) are poorly recognised and inadequately treated in Nigeria in spite of the fact that it constitutes a major risk for HIV transmission. This study was carried out to ascertain STI/HIV co-infection rate and to obtain relevant socio-demographic and reproductive health data associated with STIs. This information is urgently needed for designing STI/HIV control strategies. All consenting patients with history suggestive of STI, who attended STI clinic at the University College Hospital, Ibadan, between March and November 2001 were enrolled in the study. Of the 210 patients seen, 98 (46.7%) were males while 112 (53.3%) were females (p > 0.05). One hundred and fifty six (74.3%) of them were aged 20-39 years while only 10 (5.1%) were adolescents. Twenty (9.5%) had laboratory diagnosis of STIs, out of which 6 (30%) were also HIV positive. Among those with STIs, 8 (40%) had gonorrhoea, 8 (40%) had candidiasis, while 4 (25%) were positive for Trichomonas vaginalis. None of the patients' sera was positive for Treponema palladium antibody HIV prevalence rate in the study was 21.9%. Highest rate was found in patients aged 20-29 years while no adolescent and no one over 50 years old was HIV positive. Five (62.5%) of the patients with gonorrhoea were also HIV positive, a lower percentage (25%) of those with trichomoniasis were positive for HIV, while none of those infected with candidiasis was HIV positive. STI/HIV co-infection rate was 30%. This study reveals a high STI/HIV co-infection rate, indicating that there is a need for proper management of STIs as a way of reducing the spread of HIV infection in Nigeria.

Adolescent↗

A sensitive enzymatic method (SK-013) for detection and quantification of specific periodontopathogens.

Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola have been found to predominate in periodontal pockets of patients with adult periodontitis. These microorganisms hydrolyze the synthetic peptide N-benzoyl-DL-arginine-2-naphthylamide (BANA). In this study, we developed an enzymatic method, designated SK-013, to detect the existence of these microorganisms in subgingival plaque bacteria. This enzymatic method was based on the observation of the hydrolysis of N-carbobenzoxy-glycyl-glycyl-arginyl-3,5-dibromo-4-hydroxyaniline (N-CBz-Gly-Gly-Arg-DBHA) and made more sensitive by adding an enhancing system. The SK-013 was specifically positive for P. gingivalis, B. forsythus, T. denticola, and some strains of Capnocytophaga species, but was not specific for any of the other bacterial strains tested. This SK-013 system may be valuable for detection and quantification of periodontal disease-associated bacteria in subgingival plaque and thus for diagnosis of periodontal infections.

Bacteroides↗

Vaccine candidates in STD.

Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, particular scientific problems have delayed the development of an STD vaccine, such as incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of the human papillomavirus. It could be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that will include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, or (3) DNA plasmids expressing the vaccine antigen.

Bacterial Vaccines↗

Juxta-articular bone lesions in tertiary yaws.

A case of tertiary yaws in an immigrant from the Solomon Islands is presented. The report highlights the atypical features and diagnostic difficulties of late-stage treponemal infection.

Adult↗

Cell-mediated immunity in experimental syphilis in rabbits.

The development of cell-mediated immunity was studied in rabbits: a) experimentally injected with T. pallidum, and b) artificially immunized with nonviable T. pallidum. The macrophage migration inhibition test (MMI test) using ultrasonicate of T. pallidum as antigen was employed to demonstrate this type of immunologic response. Lymphocytes of syphilitic rabbits were found to exert a pronounced inhibitory effect upon macrophage migration as early as one month after infection; between the fourth and sixth month, a transient decrease of this capacity occurred, followed by a slow but steady increase during the next two years, i.e. until the end of the observation period. In rabbits in which the infection had been controlled by penicillin treatment in the fifth month, no increase but gradual diminution of this capacity was observed. In the group of rabbits artificially immunized with nonviable T. pallidum, the MMI response appeared very shortly after commencement of the immunization and persisted for about nine months after completion of the immunization procedure. Only a crude correlation could be established between levels of the MMI response of the immunized animals and their resistance to infection with T. pallidum.

Animals↗

[Sexually transmitted diseases in women, mothers, under-age females. 7th Consensus Conference on Antiinfectious therapy. Paris, 3 November 1993].

This paper is a report of a consensus conference held by the "Société de pathologie infectieuse de langue française" on diagnosis and treatment of sexually transmitted diseases in females (HIV and hepatitis B being excluded). Three subjects are concerned. 1) Diagnosis and medical treatment of salpingitis, with particular attention to salpingitis in adolescent girls, the two most common infections being Chlamydia trachomatis and Neisseria gonorrhoeae. 2) Diagnosis and treatment of sexually transmitted diseases in girls younger than 15, with the underlying question of possible sexual abuse. 3) The neonatal consequences of maternal sexually transmitted diseases and their treatment (Neisseria gonorrhoeae, Treponema Pallidum, Mycoplasma, Chlamydia trachomatis, Herpes, Cytomegalovirus, Papillomavirus).

Adolescent↗

Retroviral infections (HIV-1, HIV-2, and HTLV-I) in rural northwestern Tanzania. Clinical findings, epidemiology, and association with infections common in Africa.

During a three-week period in March/April 1987, the authors examined 253 consecutive patients referred to a rural hospital in northwestern Tanzania. Sera were tested for antibodies to human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and human T-lymphotropic virus type I (HTLV-I), as well as for various parasites, hepatitis B virus, and Treponema pallidum. Neopterin (urinary and serum) was chosen as the immunologic parameter. In eight of the 253 patients (3.2%), a clinical diagnosis of acquired immunodeficiency syndrome (AIDS) was established. Three of the AIDS patients had HIV-1 antibodies, two had HIV-1 antigen, one had both HIV-1 and HIV-2 antibodies, and in one patient, only HIV-2 antibodies were found. The total HIV-1 and HIV-2 seroprevalence (antibodies plus antigen) was 4.3%; HTLV-I seroprevalence was 9.9%. No correlation could be found between HIV (or HTLV-I) seropositivity and raised levels of antibody to the above pathogens. There was, however, a significantly positive correlation between HIV seropositivity and history of gonorrhea, whereas a history of operations, injections, vaccinations, blood transfusions, or scarification did not influence the level of HIV seropositivity. The most frequently noted epidemiologic association with HIV seropositivity was traveling to or coming from Uganda or Rwanda. Two thirds of the studied Tanzanians had elevated neopterin levels, and all seven HIV-seropositive patients with clinical signs of AIDS had extremely high serum and urinary neopterin levels compared with HIV-seropositive patients without signs of AIDS. Increased neopterin levels reflect a stimulation of the T-cell/macrophage system.

Acquired Immunodeficiency Syndrome↗

Production of rheumatoid factor in adoptively immune guinea-pigs after challenge with Treponema pallidum.

Guinea-pigs of inbred strains 2 and C4D were infused with various concentrations (1 x 10(8) to 4 x 10(8) of syngeneic nylon wool-purified Treponema pallidum-immune T lymphocytes (TPI-T) and challenged 24 hr later with virulent T. pallidum (10(8) organisms). The degree of protection depended on the number of infused T cells and was associated with an accelerated production of IgM rheumatoid factor (RF). Fully protected animals (4 x 10(8) TPI-T) did not produce treponemal antibodies or circulating immune complexes (CIC) but produced IgM RF detectable 10 days after infection. Partially protected animals (< or = 2 x 10(8) TPI-T) produced, 30 days post-infection, relatively low levels of treponemal antibodies but high levels of CIC and RF. Control animals infused with 2 x 10(8) TPI-T lymphocytes but not infected with T. pallidum, when monitored for a period of 6 weeks, did not produce treponemal antibodies, CIC, or RF, excluding the possibility that IgM RF could be generated by the donor's B cells contaminating (circa 3%) the TPI-T lymphocytes. Moreover, unprotected syngeneic control animals infused, prior to infection, with T. phagedenis biotype Reiter-immune T cells or with T. pallidum-free testicular inflammatory fluid-immune T cells responded with increasing levels of treponemal antibodies; only a few animals produced RF and CIC 5 months after infection similarly to control guinea-pigs infected only. The production of RF in partially protected animals responding to infection with treponemal antibodies and CIC was apparently associated with the presence of the CIC; but the mechanism of RF production in fully protected animals in which no antibodies or CIC were detected is currently unknown.

Animals↗

Detection of Treponema pallidum in skin lesions of secondary syphilis and characterization of the inflammatory infiltrate.

BACKGROUND: Syphilis is an ancient sexually transmitted disease. However, the pathogenesis of mucocutaneous lesions of secondary syphilis is not completely understood. METHODS: We analyzed the presence of Treponema pallidum in formalin-fixed, paraffin-embedded biopsy specimens from mucocutaneous lesions of secondary syphilis using highly sensitive nested polymerase chain reaction (PCR). The inflammatory infiltrates from the same specimens are also characterized using immunohistochemical methods. RESULTS AND CONCLUSIONS: Ten out of 24 (41.7%) specimens are T. pallidum positive using nested PCR, whereas none of them is T. pallidum positive using traditional silver staining. The presence of T. pallidum in the mucocutaneous lesions indicates that mucocutaneous lesions of secondary syphilis might be caused by direct T. pallidum invasion rather than by an allergic reaction. Furthermore, the majority of inflammatory infiltrating cells are CD45RO-positive T cells and CD68-positive macrophages, suggesting that cellular immunity plays an important role in the host reaction against T. pallidum infection in secondary syphilis.

Adult↗

Surface characterization of virulent Treponema pallidum.

Characterization of the surface of Treponema pallidum was accomplished by [(125)I]lactoperoxidase-catalyzed iodination of intact organisms and sensitive radioimmunoprecipitation and gel electrophoresis technology. At least 11 outer membrane proteins with molecular weights ranging from 89,000 (89K) to 20K were identified, and all elicited high titers of antibody in experimentally infected rabbits. Proteins of 89.5K, 29.5K, and 25.5K previously implicated as ligands involved in attachment (J. B. Baseman and E. C. Hayes, J. Exp. Med. 151:573-586, 1980) were found to reside on the treponemal surface. Low levels of the 89.5K treponemal protein were released by high salt concentrations, whereas the remaining comigrating material was neither radioiodinated nor released with selective detergents. Other lower-molecular-weight (60K, 45K, and 30K) surface proteins were extracted with octyl glucoside detergent, suggesting their hydrophobic interaction with the external membrane. The molecular organization of surface proteins was studied by employing the cross-linker dithiobis(succinimidyl)-propionate, and data suggested the presence of a highly fluid envelope resulting in random collisions by the surface proteins. The biological function of the treponemal outer envelope proteins was evaluated using, as the indicator system, adherence of T. pallidum to monolayer cultures of eucaryotic cells. Trypsin treatment of motile, freshly harvested organisms decreased the extent of surface parasitism to normal rabbit testicular cells, reinforcing the idea of the proteinaceous nature and role of treponemal ligands for attachment. Other data supported functional and antigenic relatedness among the implicated ligands. Finally, brief periodate treatment of human epithelial (HEp-2) and normal rat testicular cells as well as casein-elicited rabbit peritoneal macrophages significantly reduced the extent of treponemal parasitism, suggesting a role of specific host membrane molecules as mediators of attachment.

Antibody Formation↗

[Classification of spirochetes infecting man].

The systematics od spirochetes must from now own fulfil the genomic criteria recently laid down. Formerly, these parasites were classified on the basis of various phenotypic features, among which the pathogenicity and epidemiological criteria played the predominant role. At present, the order of Spirochaetales is divided into two families: Spirochaetaceae and Leptospiraceae. Two of the four genera of Spirochaetaceae, Treponema and Borrelia, include species that are pathogenic to man. Among Leptospiraceae, only one genus, Leptospira, has pathogenic species. The phenotypic characteristics of the various taxons are detailed, the role of each actor (causative agent, vector, reservoir) in the main pathological complexes and the progress of genotypic studies are briefly described.

Humans↗

Attachment of Treponema pallidum to fibronectin, laminin, collagen IV, and collagen I, and blockage of attachment by immune rabbit IgG.

As shown by scanning electron and phase contrast microscopy, Treponema pallidum attached in vitro to basement membranes purified from kidney cortex tissues or from retinal vessels. This organism also attached to the extracellular matrix remaining after cultured cells had been solubilised with Triton X. Fibronectin, laminin, collagen, IV, collagen I, and hyaluronic acid are structural components of basement membranes and extracellular matrices. Experiments were performed to investigate the in vitro attachment of T pallidum to each of these components. Viable or heat inactivated treponemes were added to glass coverslips precoated with different concentrations of each component. After various times of incubation, coverslips were washed and the attached organisms were counted. Large numbers of viable organisms attached to each of these five components. In contrast, heat inactivation sharply reduced numbers of attached organisms. The IgG fractions of immune and non-immune rabbit serum samples were affinity purified using protein A. T pallidum was preincubated with both fractions, then incubated with either intact cultured cells or with coverslips coated with the five tissue components. The IgG from immune serum blocked treponemal attachment to the cultured cells and to fibronectin, laminin, collagen IV, and collagen I, but not to hyaluronic acid. These results are discussed in terms of attachment mechanisms of T pallidum and potential applications to in vivo infection.

Adhesiveness↗

Lyme disease-a tick-borne spirochetosis?

A treponema-like spirochete was detected in and isolated from adult Ixodes dammini, the incriminated tick vector of Lyme disease. Causally related to the spirochetes may be long-lasting cutaneous lesions that appeared on New Zealand White rabbits 10 to 12 weeks after infected ticks fed on them. Samples of serum from patients with Lyme disease were shown by indirect immunofluorescence to contain antibodies to this agent. It is suggested that the newly discovered spirochete is involved in the etiology of Lyme disease.

Animals↗

The bacteriology of acute necrotizing ulcerative gingivitis.

Plaque samples from 22 ulcerated sites in eight patients with ANUG were cultured using quantitative anaerobic procedures and were examined microscopically. The partial characterization of the predominant cultivable flora revealed a constant flora comprised of a limited number of bacterial types and a variable flora composed of a heterogeneous array of bacterial types. This constant flora would appear to be pathognomonic of acute necrotizing ulcerative gingivitis (ANUG) and included the various Treponema and Selenomonas sp., which comprised about 32 and 6%, respectively, of the microscopic count; B. melaninogenicus ssp. intermedius and Fusobacterium sp., which averaged 24 and 3%, respectively, of the viable count. One week of metronidazole treatment caused a prompt resolution of clinical symptoms, which coincided with a significant reduction in the plaque proportions of the Treponema sp., B. melaninogenicus ssp., intermedius and Fusobacterium sp. for at least 2 to 3 months following treatment. Thus, the same anaerobic species which were numerically associated with the ANUG lesion were also selectively reduced in the plaque flora following resolution of the infection. This supports a role for the above species in the ulcerative stage of the lesion but does not demonstrate that these specific anaerobes initiated the infection. although not confirmed by the data, it was proposed that these particular anaerobic species gained ascendency in the plaque as a result of being selected through the availability of host-derived nutrients in individuals who had undergone certain physiological and psychological stresses.

Bacteria↗

Magic bullets need accurate guns--syphilis eradication, elimination, and control.

When cases of early syphilis are treated promptly, the spread of the bacteria within a population is interrupted. However, if complacency is induced by successful control, then upsurges in syphilis incidence can occur. The methods and aims of syphilis control in industrialised countries are reviewed in the light of the potential for regional elimination and global eradication programmes. While the medical means to eliminate syphilis are at hand, acceptable means for finding and treating cases that transmit infection need to be developed, particularly in the marginalized communities with limited access to care.

Communicable Disease Control↗

Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis.

AIM: To evaluate and compare the effects of adjunctive metronidazole plus amoxicillin, doxycycline and metronidazole on clinical and microbiological parameters in patients with generalized aggressive periodontitis. MATERIAL AND METHODS: Forty-three patients participated in this randomized clinical trial divided into four groups. Six weeks after scaling and root planning (SRP), groups 1-3 received adjunctive metronidazole, plus amoxicillin, doxycycline and metronidazole respectively, and group 4 acted as controls. Clinical recordings concerning probing depth, probing attachment level and bleeding on probing were performed at baseline, 6 weeks after SRP and 6 months from baseline. Subgingival samples were analysed using the 'checkerboard' DNA-DNA hybridization for Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythia and Treponema denticola. RESULTS: All treatments resulted in improvement of clinical parameters (ANOVA p > 0.05). Systemic administration of metronidazole plus amoxicillin or metronidazole resulted in statistically significant greater reduction of the proportion of sites > 6 mm than SRP (z-test, p < 0.05). These antimicrobials yielded a significant effect on levels of important periodontal pathogens for 6 months. CONCLUSION: Adjunctive metronidazole plus amoxicillin or metronidazole alone (when A.actinomycetemcomitans is not involved) is effective in deep pockets of aggressive periodontitis patients.

Adult↗

Analysis of Borrelia burgdorferi membrane architecture by freeze-fracture electron microscopy.

Freeze-fracture electron microscopy was used to investigate the membrane architectures of high-passage Borrelia burgdorferi B31 and low- and high-passage isolates of B. burgdorferi N40. In all three organisms, fractures occurred almost exclusively through the outer membrane (OM), and the large majority of intramembranous particles were distributed randomly throughout the concave OM leaflet. The density of intramembranous particles in the concave OM leaflet of the high-passage N40 isolate was significantly greater than that in the corresponding leaflet of the low-passage N40 isolate. Also noted in the OMs of all three organisms were unusual structures, designated linear bodies, which typically were more or less perpendicular to the axis of the bacterium. A comparison of freeze-fractured B. burgdorferi and Treponema pallidum, the syphilis spirochete, revealed that the OM architectures of these two pathogens differed markedly. All large membrane blebs appeared to be bounded by a membrane identical to the OM of B. burgdorferi whole cells; in some blebs, the fracture plane also revealed a second bilayer closely resembling the B. burgdorferi cytoplasmic membrane. Aggregation of the lipoprotein immunogens outer surface protein A (OspA) and OspB on the bacterial surface by incubation of B. burgdorferi B31 with specific polyclonal antisera did not affect the distribution of OM particles, supporting the contention that lipoproteins do not form particles in freeze-fractured OMs. The expression of poorly immunogenic, surface-exposed proteins as virulence determinants may be part of the parasitic strategy used by B. burgdorferi to establish and maintain chronic infection in Lyme disease.

Antigens, Bacterial↗