Alcohol and drug use during sex and its association with sexually transmitted infections: a retrospective cohort study among young people aged under 25 years visiting Dutch STI clinics.

INTRODUCTION: Alcohol use and drug use are common behaviours among young people. STI positivity is higher in young people than in people aged above 25 years. While there is an increasing amount of knowledge about drug use during sex among men who have sex with men (MSM), data on this behaviour among young women and heterosexual men are scarce. Therefore, this study aims to assess the proportion and characteristics of women and heterosexual men aged under 25 years reporting alcohol and/or drug use during sex and its association with STI positivity. METHODS: Surveillance data of heterosexual individuals younger than 25 years visiting two Dutch STI clinics between 2016 and 2019 were assessed (n=11 714). We used multivariable logistic regression analyses to assess associations between alcohol and drug use during sex and STI positivity (Chlamydia trachomatis and/or Neisseria gonorrhoeae diagnosis), adjusting for sociodemographic characteristics (sex, age, ethnicity, educational level, socioeconomic status and urbanisation) and sexual behaviour (condom use, number of sex partners). RESULTS: Alcohol use during sex was reported by 45.3% (5311/11 714; 49.5% in men vs 43.2% in women, p<0.001) and drug use during sex by 22.0% (2580/11 714; 30.7% in men vs 17.6% in women, p<0.001). The most reported drugs were cannabis (17.9%), ecstasy (XTC)/methylenedioxymethamphetamine (MDMA) (6.9%) and cocaine (4.7%). The use of at least one of the following drugs (XTC/MDMA, cocaine, speed, ketamine, gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL), heroin, crystal meth and/or designer drugs) was significantly associated with STI positivity after adjustment for sociodemographic characteristics (adjusted OR (aOR): 1.3, 95% CI 1.1 to 1.4), but this association did not remain significant after adjustment for sexual behaviour (aOR: 1.12, 95% CI 0.94 to 1.34). Significant associations between drug use during sex and inconsistent condom (aOR: 2.5, 95% CI 1.9 to 3.2) use and having four or more sex partners (aOR: 3.2, 95% CI 2.8 to 3.6) in the past 6 months were assessed. DISCUSSION: Alcohol and drug use during sex was highly prevalent among young women and heterosexual men visiting the STI clinic and drug use during sex was associated with an increased risk for STI, probably mediated by sexual behaviour. This indicates that a holistic health promotion strategy, addressing STI prevention and alcohol and drug use-related harm reduction, is important in this group. STI clinics should address this behaviour not only among MSM, but also among young women and heterosexual men.

Randomized controlled trial of the relative efficacy of high-dose intravenous ceftriaxone and oral cefixime combined with doxycycline for the treatment of Chlamydia trachomatis and Neisseria gonorrhoeae co-infection.

OBJECTIVES: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the commonest bacterial causes of sexually transmitted infections in humans with high incidence of co-infection. Treatment with high doses of ceftriaxone (CRO) and cefixime (CFM) is strongly recommended due to the reduced drug susceptibility of NG. However, their safety and efficacy have not been confirmed. We compared the safety and efficacy of a single 1 g intravenous (IV) dose of ceftriaxone (CRO) plus doxycycline (DOX) versus a single 800 mg oral dose of cefixime (CFM) plus DOX for the treatment of NG-CT co-infection. METHODS: An open-label randomized controlled trial was conducted on 125 individuals aged > 18 years with untreated gonorrhea and chlamydia to compare a single 1 g intravenous dose of CRO + DOX and a single 800 mg oral dose of CFM + DOX. The primary outcome was the clearance of NG from all the initially infected sites. Secondary outcomes included symptom resolution, changes in the serum clearance levels, glomerular filtration rate, and antibiotic minimum inhibitory concentrations. RESULTS: Both regimens were highly effective in treating gonorrhea with success rates of 96.7% (95% confidence interval [CI] 88.8-99.1%) for CRO and 95.3% (95% CI 87.1-98.4%) for CFM. However, CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection (odds ratio 4.41, 95% CI 1.11-25.7). The safety profiles of the two regimens were similar. CONCLUSIONS: CRO + DOX was superior to CFM + DOX for the treatment of NG-CT co-infection. CFM + DOX may be indicated in patients with CRO allergy and in settings where CRO is unavailable. Trial registration ClinicalTrials.gov (NCT05216744) on 31/01/22.

Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.

Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine pathway enzymes have promise as narrow-spectrum antibiotic targets, but the activity and essentiality of chlamydial menaquinone biosynthesis have yet to be established. In this work, menaquinone-7 (MK-7) was identified as a C. trachomatis-produced quinone through liquid chromatography-tandem mass spectrometry. An immunofluorescence-based assay revealed that treatment of C. trachomatis-infected HeLa cells with the futalosine pathway inhibitor docosahexaenoic acid (DHA) reduced inclusion number, inclusion size, and infectious progeny. Supplementation with MK-7 nanoparticles rescued the effect of DHA on inclusion number, indicating that the futalosine pathway is a target of DHA in this system. These results open the door for menaquinone biosynthesis inhibitors to be pursued in antichlamydial development.

In vitro inhibitory effect of Hydrocotyle bonariensis Lam. extracts over Chlamydia trachomatis and Chlamydia pneumoniae on different stages of the chlamydial life cycle.

Chlamydial infections in humans are widely distributed and are responsible for a variety of acute and chronic diseases. Both Chlamydia trachomatis and Chlamydia pneumoniae can lead to chronic conditions that have been linked to complications and sequelae. This study aimed to develop a culture method in order to detect in vitro antichlamydial activity of different extracts obtained from native Argentinian plants used as antimicrobials in local ethnomedicine and to evaluate their inhibitory activity over Chlamydia trachomatis and Chlamydia pneumoniae growth. The inhibitory activity over different stages of the chlamydial life cycle on cell culture was assessed: the entry, the inclusion developing after entry, and the exponential growth stage. Also, the capability of rendering the cell refractory to chlamydial infection by pre-incubation with the extracts was assayed. Inhibitory activity of water-based and organic-based extracts obtained from Hydrocotyle bonariensis Lam. (Araliaceae), Lithraea molleoides (Vell.) Engl. (Anacardiaceae) and Hybanthus parviflorus (Mutis ex L.f.) Baill. (Violaceae) were tested against five strains of Chlamydia trachomatis (L2/434/BU and four clinical isolates form both neonatal conjunctivitis and adult genital infections, genotypes D, E, and K) and against Chlamydia pneumoniae AR39. The Hydrocotyle bonariensis dichloromethane extract showed a broad inhibitory activity over the exponential growth stage of Chlamydia trachomatis and Chlamydia pneumoniae independently from the chlamydial strain and the cell line. These results suggest a high inhibitory potential on both Chlamydiae species. In order to characterize the Hydrocotyle bonariensis dichloromethane active extract, an 1H-NMR was performed. The 1H-NMR characterization showed a spectrum with characteristic signals of the fatty acid moiety of lipids or cerebrosides, volatile phenolics, phytosterols, methyl triterpenes signals, and glucose moiety of the cerebrosides.

Maraviroc, celastrol and azelastine alter Chlamydia trachomatis development in HeLa cells.

Introduction . Chlamydia trachomatis (Ct) is an obligate intracellular bacterium, causing a range of diseases in humans. Interactions between chlamydiae and antibiotics have been extensively studied in the past.Hypothesis/Gap statement: Chlamydial interactions with non-antibiotic drugs have received less attention and warrant further investigations. We hypothesized that selected cytokine inhibitors would alter Ct growth characteristics in HeLa cells.Aim. To investigate potential interactions between selected cytokine inhibitors and Ct development in vitro.Methodology. The CCR5 receptor antagonist maraviroc (Mara; clinically used as HIV treatment), the triterpenoid celastrol (Cel; used in traditional Chinese medicine) and the histamine H1 receptor antagonist azelastine (Az; clinically used to treat allergic rhinitis and conjunctivitis) were used in a genital in vitro model of Ct serovar E infecting human adenocarcinoma cells (HeLa).Results. Initial analyses revealed no cytotoxicity of Mara up to 20 µM, Cel up to 1 µM and Az up to 20 µM. Mara exposure (1, 5, 10 and 20 µM) elicited a reduction of chlamydial inclusion numbers, while 10 µM reduced chlamydial infectivity. Cel 1 µM, as well as 10 and 20 µM Az, reduced chlamydial inclusion size, number and infectivity. Morphological immunofluorescence and ultrastructural analysis indicated that exposure to 20 µM Az disrupted chlamydial inclusion structure. Immunofluorescence evaluation of Cel-incubated inclusions showed reduced inclusion sizes whilst Mara incubation had no effect on inclusion morphology. Recovery assays demonstrated incomplete recovery of chlamydial infectivity and formation of structures resembling typical chlamydial inclusions upon Az removal.Conclusion. These observations indicate that distinct mechanisms might be involved in potential interactions of the drugs evaluated herein and highlight the need for continued investigation of the interaction of commonly used drugs with Chlamydia and its host.

Protection of outbred mice against a vaginal challenge by a Chlamydia trachomatis serovar E recombinant major outer membrane protein vaccine is dependent on phosphate substitution in the adjuvant.

Chlamydia trachomatis is the most common bacterial sexually-transmitted pathogen for which there is no vaccine. We previously demonstrated that the degree of phosphate substitution in an aluminum hydroxide adjuvant in a TLR-4-based C. trachomatis serovar E (Ser E) recombinant major outer membrane protein (rMOMP) formulation had an impact on the induced antibody titers and IFN-γ levels. Here, we have extended these observations using outbreed CD-1 mice immunized with C. trachomatis Ser E rMOMP formulations to evaluate the impact on bacterial challenge. The results confirmed that the rMOMP vaccine containing the adjuvant with the highest phosphate substitution induced the highest neutralizing antibody titers while the formulation with the lowest phosphate substitution induced the highest IFN-γ production. The most robust protection was observed in mice vaccinated with the formulation containing the adjuvant with the lowest phosphate substitution, as shown by the number of mice with positive vaginal cultures, number of positive cultures and number of C. trachomatis inclusion forming units recovered. This is the first report showing that vaccination of an outbred strain of mice with rMOMP induces protection against a vaginal challenge with C. trachomatis.

Structures of glyceraldehyde 3-phosphate dehydrogenase in Neisseria gonorrhoeae and Chlamydia trachomatis.

Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) are the most commonly reported sexually transmitted bacteria worldwide and usually present as co-infections. Increasing resistance of Ng to currently recommended dual therapy of azithromycin and ceftriaxone presents therapeutic challenges for syndromic management of Ng-Ct co-infections. Development of a safe, effective, and inexpensive dual therapy for Ng-Ct co-infections is an effective strategy for the global control and prevention of these two most prevalent bacterial sexually transmitted infections. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a validated drug target with two approved drugs for indications other than antibacterials. Nonetheless, any new drugs targeting GAPDH in Ng and Ct must be specific inhibitors of bacterial GAPDH that do not inhibit human GAPDH, and structural information of Ng and Ct GAPDH will aid in finding such selective inhibitors. Here, we report the X-ray crystal structures of Ng and Ct GAPDH. Analysis of the structures demonstrates significant differences in amino acid residues in the active sites of human GAPDH from those of the two bacterial enzymes suggesting design of compounds to selectively inhibit Ng and Ct is possible. We also describe an efficient in vitro assay of recombinant GAPDH enzyme activity amenable to high-throughput drug screening to aid in identifying inhibitory compounds and begin to address selectivity.

Water Filtered Infrared A and Visible Light (wIRA/VIS) Irradiation Reduces Chlamydia trachomatis Infectivity Independent of Targeted Cytokine Inhibition.

Chlamydia trachomatis is the major cause of infectious blindness and represents the most common bacterial sexually transmitted infection worldwide. Considering the potential side effects of antibiotic therapy and increasing threat of antibiotic resistance, alternative therapeutic strategies are needed. Previous studies showed that water filtered infrared A alone (wIRA) or in combination with visible light (wIRA/VIS) reduced C. trachomatis infectivity. Furthermore, wIRA/VIS irradiation led to secretion of pro-inflammatory cytokines similar to that observed upon C. trachomatis infection. We confirmed the results of previous studies, namely that cytokine secretion (IL-6, IL-8, and RANTES/CCL5) upon wIRA/VIS treatment, and the subsequent reduction of chlamydial infectivity, are independent of the addition of cycloheximide, a host protein synthesis inhibitor. Reproducible cytokine release upon irradiation indicated that cytokines might be involved in the anti-chlamydial mechanism of wIRA/VIS. This hypothesis was tested by inhibiting IL-6, IL-8, and RANTES secretion in C. trachomatis or mock-infected cells by gene silencing or pharmaceutical inhibition. Celastrol, a substance derived from Trypterygium wilfordii, used in traditional Chinese medicine and known for anti-cancer and anti-inflammatory effects, was used for IL-6 and IL-8 inhibition, while Maraviroc, a competitive CCR5 antagonist and anti-HIV drug, served as a RANTES/CCL5 inhibitor. HeLa cell cytotoxicity and impact on chlamydial morphology, size and inclusion number was evaluated upon increasing inhibitor concentration, and concentrations of 0.1 and 1 µM Celastrol and 10 and 20 µM Maraviroc were subsequently selected for irradiation experiments. Celastrol at any concentration reduced chlamydial infectivity, an effect only observed for 20 µM Maraviroc. Triple dose irradiation (24, 36, 40 hpi) significantly reduced chlamydial infectivity regardless of IL-6, IL-8, or RANTES/CCL5 gene silencing, Celastrol or Maraviroc treatment. Neither gene silencing nor pharmaceutical cytokine inhibition provoked the chlamydial stress response. The anti-chlamydial effect of wIRA/VIS is independent of cytokine inhibition under all conditions evaluated. Thus, factors other than host cell cytokines must be involved in the working mechanism of wIRA/VIS. This study gives a first insight into the working mechanism of wIRA/VIS in relation to an integral component of the host immune system and supports the potential of wIRA/VIS as a promising new tool for treatment in trachoma.

Tratamientos alternativos de medicina tradicional para Chlamydia trachomatis, agente causal de una infección asintomática / Alternative Treatments of Traditional Medicine for Chlamydia trachomatis, Causal Agent of an Asympomatic Infection

Resumen En la actualidad, Chlamydia trachomatis (CT) es una de las causas más frecuentes de infecciones de transmisión sexual (ITS) y morbilidad reproductiva en el mundo, Incluye tanto países desarrollados como en vía de desarrollo, con un reporte alrededor de 92 millones de casos anuales. CT es una bacteria intracelular obligada cuyo inicio de la infección es asintomático, causa infección crónica, puede generar infección persistente y complicaciones como cáncer de ovario. Las infecciones por CT son asintomáticas en el 70% de las mujeres y el 40% de los hombres, lo que dificulta el diagnóstico en las fases tempranas de la infección y el tratamiento oportuno, lo que conlleva a un aumento en los contagios en la población. De acuerdo con la Organización Mundial de la Salud (OMS), el tratamiento para CT incluye la utilización de antibióticos tipo tetraciclinas, macrólidos y fluoroquinolonas. Sin embargo, a pesar de su alta tasa de eficacia, cada vez son más recurrentes las infecciones. Reportes recientes han demostrado resistencia por parte de los cuerpos elementales y se ha podido determinar que los antibióticos disminuyen la población de lactobacillus vaginales beneficiosos, causando mayores complicaciones en los pacientes. Basados en estos hallazgos, las investigaciones actuales se han centrado en terapias alternativas que reduzcan la actividad antichlamydial y que sean de libre acceso, generando el menor daño posible en los pacientes.

Abstract Currently, Chlamydia trachomatis (CT) is one of the most frequent causes of sexually transmitted infections (STIs) and reproductive morbidity in the world, including both developed and developing countries, with a report of around 92 million annual cases. CT is an obligate intracellular bacterium whose onset's infection is asymptomatic, causes chronic infection, can generate persistent infection and complications such as ovarian cancer. CT infections are asymptomatic in 70% of women and 40% of men, which makes diagnosis difficult in the early stages of infection and timely treatment, which leads to an increase in infections in the population. According to the World Health Organization (WHO), treatment for TC includes the use of antibiotics such as tetracyclines, macrolides and fluoroquinolones. However, despite their high efficacy rate, infections are becoming more frequent. Recent reports have shown resistance on the part of elementary bodies and it has been determined that antibiotics decrease the beneficial vaginal lactobacillus population, causing greater complications in patients. Based on these findings, current research has focused on alternative therapies that reduce antichlamydial activity and that are freely accessible, generating the least possible harm to patients.

Subtle changes in host cell density cause a serious error in monitoring of the intracellular growth of Chlamydia trachomatis in a low-oxygen environment: Proposal for a standardized culture method.

We monitored Chlamydia trachomatis growth in HeLa cells cultured with either DMEM or RPMI medium containing 10% FCS under 2% or 21% O2 conditions for 2 days. Bacterial numbers, host cell numbers, and fibrosis-related gene expression in the host cells were estimated by an inclusion forming unit assay, a cell counting assay, and a PCR array, respectively. In contrast to RPMI, bacterial growth under low oxygen conditions in DMEM rapidly decreased with increasing host cell density. The addition of supplements (glucose, glutamine, vitamin B12, D-biotin, non-essential amino acids, glutathione) to the media had no effect. The growth of host cells in DMEM under low oxygen conditions rapidly decreased, although the cells remained healthy morphologically. Furthermore, the downregulation of 17 genes was observed under low oxygen in DMEM. Whereas no effect on bacterial growth was observed when culturing in RPMI medium at low oxygen, and the downregulation of three genes (CTGF, SERPINE1, JUN) was observed following bacterial infection compared with the uninfected control cells. Thus, our findings indicate the need for carefully selected culture conditions when performing experiments with C. trachomatis under low-oxygen environments, and RPMI (rather than DMEM) is recommended when a low host cell density is to be used, proposing the major modification of cell culturing method of C. trachomatis in a low-oxygen environment.

Identification of chlamydial T3SS inhibitors through virtual screening against T3SS ATPase.

Chlamydia trachomatis is a widespread sexually transmitted pathogen that resides within a special vacuole inside host cells. Although acute infection can be treated with antibiotics, chlamydia can enter persistent state, leading to chronic infection that is difficult to cure. Thus, novel anti-chlamydial compounds active against persistent chlamydia are required. Chlamydiae rely upon type III secretion system (T3SS) to inject effector proteins into host cell cytoplasm, and T3SS inhibitors are viewed as promising compounds for treatment of chlamydial infections. C. trachomatis ATPase SctN is an important T3SS component and has not been targeted before. We thus used virtual screening against homology modeled SctN structure to search for SctN inhibitors. Selected compounds were tested for their ability to inhibit chlamydial survival and development within eukaryotic cells, and for the ability to suppress normal T3SS functioning. We identified two compounds that were able to block normal protein translocation through T3SS and inhibit chlamydial survival within eukaryotic cells in 50-100 µm concentrations. These two novel T3SS inhibitors also possessed relatively low toxicity toward eukaryotic cells. A small series of derivatives was further synthesized for the most active of two inhibitors to probe SAR properties.

Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation.

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated.

2016 European guideline on the management of non-gonococcal urethritis.

We present the updated International Union against Sexually Transmitted Infections (IUSTI) guideline for the management of non-gonococcal urethritis in men. This guideline recommends confirmation of urethritis in symptomatic men before starting treatment. It does not recommend testing asymptomatic men for the presence of urethritis. All men with urethritis should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae and ideally Mycoplasma genitalium using a nucleic acid amplification test (NAAT) as this is highly likely to improve clinical outcomes. If a NAAT is positive for gonorrhoea, a culture should be performed before treatment. In view of the increasing evidence that azithromycin 1 g may result in the development of antimicrobial resistance in M. genitalium, azithromycin 1 g is no longer recommended as first line therapy, which should be doxycycline 100 mg bd for seven days. If azithromycin is to be prescribed an extended course of 500 mg stat, then 250 mg daily for four days is to be preferred over 1 g stat. In men with persistent NGU, M. genitalium NAAT testing is recommended if not previously undertaken, as is Trichomonas vaginalis NAAT testing in populations where T. vaginalis is detectable in >2% of symptomatic women.

Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis.

Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020. An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020. Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes. Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.

2015 UK National Guideline on the management of non-gonococcal urethritis.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

An optimized, fast-to-perform mouse lung infection model with the human pathogen Chlamydia trachomatis for in vivo screening of antibiotics, vaccine candidates and modified host-pathogen interactions.

Chlamydia trachomatis causes sexually transmitted diseases with infertility, pelvic inflammatory disease and neonatal pneumonia as complications. The duration of urogenital mouse models with the strict mouse pathogen C. muridarum addressing vaginal shedding, pathological changes of the upper genital tract or infertility is rather long. Moreover, vaginal C. trachomatis application usually does not lead to the complications feared in women. A fast-to-perform mouse model is urgently needed to analyze new antibiotics, vaccine candidates, immune responses (in gene knockout animals) or mutants of C. trachomatis. To complement the valuable urogenital model with a much faster and quantifiable screening method, we established an optimized lung infection model for the human intracellular bacterium C. trachomatis serovar D (and L2) in immunocompetent C57BL/6J mice. We demonstrated its usefulness by sensitive determination of antibiotic effects characterizing advantages and limitations achievable by early or delayed short tetracycline treatment and single-dose azithromycin application. Moreover, we achieved partial acquired protection in reinfection with serovar D indicating usability for vaccine studies, and showed a different course of disease in absence of complement factor C3. Sensitive monitoring parameters were survival rate, body weight, clinical score, bacterial load, histological score, the granulocyte marker myeloperoxidase, IFN-γ, TNF-α, MCP-1 and IL-6.

Bubonic lymphogranuloma venereum with multidrug treatment failure.

A patient with proctitis and inguinal buboes diagnosed with lymphogranuloma venereum (LGV) was treated with doxycycline 21 days, azithromycin 20 days and moxifloxacin for a further 12 days because of progressive worsening of inguinal symptoms. Despite extensive antibiotic treatment, the inguinal LGV lesions persisted; however, the patient recovered spontaneously after three months.

Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding protein 201-216 prevents autoimmune uveoretinitis by acting as altered peptide ligand.

We report here identification of novel mimicry epitopes for interphotoreceptor retinoid-binding protein (IRBP) 201-216, a candidate ocular antigen that causes experimental autoimmune uveoretinitis (EAU) in A/J mice. One mimicry epitope from Ehrlichia canis (EHC), designated EHC 44-59, induced cross-reactive T cells for IRBP 201-216 capable of producing T helper (Th)1 and Th17 cytokines, but failed to induce EAU in A/J mice. In addition, animals first primed with suboptimal doses of IRBP 201-216 and subsequently immunized with EHC 44-59 did not develop EAU; rather, the mimicry epitope prevented the disease induced by IRBP 201-216. However, alteration in the composition of EHC 44-59 by substituting alanine with valine at position 49, similar to the composition of IRBP 201-216, enabled the mimicry epitope to acquire uveitogenicity. The data provide new insights as to how microbes containing mimicry sequences for retinal antigens can prevent ocular inflammation by acting as naturally occurring altered peptide ligands.

Conjuntivite neonatal com ênfase na sua prevenção / Neonatal conjunctivitis with emphasis on its prevention

Nos últimos tempos, a necessidade da utilização de medicamentos para prevenção da conjuntivite neonatal (CN) passou a ser questionada em alguns países desenvolvidos, devido ao elevado nível de assistência pré-natal. Ao contrário, no Brasil, embora não haja dados oficiais sobre sua ocorrência, vários trabalhos recentes comprovam elevada prevalência da infecção genital em mulheres em idade fértil e em gestantes. Isso, aliado ao fato de que o índice de transmissão da infecção genital por clamídia e gonococo, da mãe infectada para o recém-nascido é de 30 a 50 por cento, leva à conclusão de que a profilaxia medicamentosa está mais que justificada. A CN implica em importante potencial de complicações locais e sistêmicas, além da necessidade de exames laboratoriais para seu diagnóstico etiológico. Por isso, constitui importante problema de saúde pública, negligenciado no Brasil, onde não há padronização do método de prevenção. Embora o uso do nitrato de prata pareça ainda ser o método oficial, seu uso tem sido questionado devido à incompleta proteção contra clamídia, principal agente da conjuntivite neonatal nos dias atuais, e pela frequente ocorrência de conjuntivite química. Por isso, tem sido substituído por outros agentes, como a eritromicina, a tetraciclina, além de outros antibióticos. A superioridade da Iodopovidona em relação a esses antibióticos, nos vários quesitos analisados, tem sugerido que esse é o mais adequado entre os produtos, testados até o momento, para prevenção da CN.

Nowadays the use of drugs for prevention of neonatal conjunctivitis (NC) has been questioned in some developed countries, due to the high level of prenatal care. In Brazil, although no official data on the occurrence of NC is available, several recent studies has shown high prevalence of genital infection in childbearing age and pregnant women. This, coupled with the 30 percent to 50 percent transmission rate of genital chlamydia and gonococcus from mother to newborn, leads to the conclusion that chemoprophylaxis is justified. The potential for local and systemic complications and the need for laboratory tests for its diagnosis have made NC an important public health problem, overlooked in Brazil, where there is no standardization of the method of prevention. Although the use of silver nitrate still appears to be the official method, it has been questioned due to incomplete protection against chlamydia, nowadays the leading agent of NC, and by the frequent occurrence of chemical conjunctivitis. So, it has been replaced by other agents such as erythromycin, tetracycline and other antibiotics. The advantages of povidone-iodine compared to these agents in the various items analyzed, has suggested that it is the best, among the products tested so far, for the prevention of NC.

Doxycycline in the Treatment of Non-Gonococcal Urethritis / 대한비뇨기과학회지

A retrospective study of 152 heterosexual male patients with non-gonococcal urethritis (NGU) was carried out to find out the efficacious treatment of NGU. We obtained urethral swabs for analysis by Chlamydiazyme (Abbott, North Chicago, IL) and Gram's stain from all patients. We classified the patients into two groups: 72 patients with no history of treatment (group I), and 80 patients with recurrent or persistent NGU (group II). Doxycycline was initially administered to 130 patients about two weeks. Ciprofloxacin, erythromycin, or doxycycline as second-line antibiotics were used in the patients with recurrent or persistent NGU after treatment with doxycycline. C. trachomatis was detected in 50 (32.9%) of the 152 patients: a larger proportion (40.3%) of the group I than the group II (26.3%) was chlamydia-positive, but the difference between two groups was not significant (p>0.05). After treatment with doxycycline, a higher cure rate was observed in the chlamydia-positive men (72.5% ; 29 of 40 patients) than in the chlamydia- negative men (50.0% ; 45 of 90 patients): in 90 chlamydia-negative men, 27 (75.0%) of 36 patients of the group I and 18 (33.3%) of 64 patients of the group II was cured (p<0.05). Doxycycline was efficacious for the chlamydia-positive men. But the patients with recurrent or persistent chlamydia-negative NGU were tend to be resistant to doxycycline therapy.