Chlamydial biology and its associated virulence blockers.

Chlamydiales are obligate intracellular parasites of eukaryotic cells. They can be distinguished from other Gram-negative bacteria through their characteristic developmental cycle, in addition to special biochemical and physical adaptations to subvert the eukaryotic host cell. The host spectrum includes humans and other mammals, fish, birds, reptiles, insects and even amoeba, causing a plethora of diseases. The first part of this review focuses on the specific chlamydial infection biology and metabolism. As resistance to classical antibiotics is emerging among Chlamydiae as well, the second part elaborates on specific compounds and tools to block chlamydial virulence traits, such as adhesion and internalization, Type III secretion and modulation of gene expression.

[Infertility in women: latest developments]. / Infertilität bei Frauen : Neueste Entwicklungen.

BACKGROUND: The incidence of female infertility has not changed since the early 1990s. Based on new data from basic research on infertility, novel options in the diagnostics and treatment of infertility have emerged, besides in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). AIM: This review summarizes the current knowledge on female infertility and on modern concepts in diagnostics and treatment. METHODS: A literature research on the causes of infertility and on treatment options was performed, including demographic factors, infectiology, anatomy, endocrinology and metabolism, endometriosis, lifestyle and environmental factors, and psychological factors. RESULTS: Chlamydial infection is still the major cause of tubal infertility. Improvement of the patient's fertility by correction of endocrine and metabolic disorders, in particular thyroid dysfunction and glucose metabolism, as well as fertility surgery are of main interest. CONCLUSIONS: Besides assisted reproductive techniques, concepts to optimize individual fertility have gained increasing importance.

[Chlamydial infections]. / Infecciones por clamidias.

Chlamydiae are a singular group of bacteria, with a vital cycle that is intracellular in part. These microorganisms adhere to epithelia, where they may provoke infection. There are three pathogenic species for humans: Chlamydia trachomatis, which produce infections mainly in the genital and urinary tracts, and C. psittaci and C. pneumoniae, which mostly produce respiratory infections. The last two microorganisms are now classified in a different genus, known as Chlamydophila.

Versatility of Simkania negevensis infection in vitro and induction of host cell inflammatory cytokine response.

OBJECTIVE: Simkania negevensis (Sn) is an intracellular microorganism belonging to the family Simkaniaceae in the order Chlamydiales and has been associated with respiratory tract infections in infants and adults. The aim of this study was to analyze the outcome of Sn infection in different cell types. METHODS: The results of Sn infection were examined by infectivity assays, PCR and EM. The cellular response to infection was evaluated by following the synthesis of mRNA for inflammatory cytokines and cytokine secretion. RESULTS: Infections could be active, with production of progeny and cytopathic effects (CPE); persistent, induced by iron depletion or in minimally permissive cell types, with small numbers of infectious progeny; or cryptic, with no CPE or infectious progeny, but with Sn DNA detected. EM showed an abundance of EB and multiplying RB in active infection, small inclusions with mainly single RB particles in persistent infection, and aberrant inclusions in cryptic infection. We report reversion to active infection of iron-induced or spontaneous persistence; attempts to "cure" persistence with antibiotic treatment resulted in the absence of infectivity but not in the eradication of Sn DNA. CONCLUSION: Sn infections are versatile and induce a host cell inflammatory response, which may be relevant to potential Sn pathologies in vivo.

Epitheliocystis in fish.

Epitheliocystis is a condition affecting the gills and skin of fish, which has been reported from more than 50 freshwater and marine species. It is caused by intracellular Gram-negative bacteria. Mortalities have been associated with epitheliocystis infections in cultured fish. This review provides an update of our current understanding of this condition, including characterization of the pathogen using immunohistochemical and molecular studies. In most fish species the epitheliocystis agent was negative to an antibody specific for chlamydial genus-specific lipopolysaccharide antigen. Recently, four epitheliocystis agents from four different fish species have been characterized using molecular analysis. While they all belong to the order Chlamydiales, in a lineage separate from the Chlamydiaceae, they are distinct organisms and similarity analysis showed that they had highest similarity values with other chlamydia-like bacteria isolated from various sources, including humans or pig. This confirms the high diversity and host specificity of the pathogen. Further molecular analysis should result in an increased understanding of this condition. To date the pathogen has not been cultured, making experimental studies difficult. High stocking densities, presence of nutrients, season, temperature and fish age have been identified as potential risk factors for the manifestation of this condition.

Ocular chlamydiales infections of western barred bandicoots (Perameles bougainville) in Western Australia.

The western barred bandicoot (Perameles bougainville) is an endangered species, free ranging on only two islands off the coast of Western Australia (Dorre and Bernier Islands). Conservation efforts are currently directed at reintroducing these marsupials into predator-proof enclosures and habitats in historical distribution ranges on the mainland in the southwest of Western Australia and in South Australia. In September 2000, 19 western barred bandicoots were captured on Bernier Island for translocation, and 11 of these had evidence of at least one of the following eye conditions: corneal opacity, conjunctivitis, ocular discharge, and blepharitis. Five bandicoots were examined, and conjunctival and cloacal swabs were collected. Polymerase chain reaction for Chlamydiales was positive in four bandicoots. Four Chlamydiales types were identified by gene sequencing, including a strain of Chlamydia pecorum different from strains previously found in koalas and several new Chlamydiales genotypes. The bandicoots responded excellently to treatment with oxytetracyline weekly for 6 wk, and topical oxytetracycline and neomycin were administered topically to both eyes s.i.d. for 4 mo.

A comparison of cost-effectiveness of three protocols for diagnosis and treatment of gonococcal and chlamydial infections in women in Africa.

BACKGROUND: The cost-effectiveness of different STD diagnosis and treatment approaches has not been evaluated previously. GOALS: The goals of the study were to compare the cost-effectiveness of "gold standard" care (GS), syndromic management (SM), and mass treatment (MT) protocols for the treatment of cervical gonococcal and chlamydial infections in a hypothetical model of 1 million women in Africa. STUDY DESIGN: A decision tree model was constructed for each of the protocols. Sensitivity analyses were conducted and 10,000 Monte Carlo simulations were run to test the robustness of the cost-effectiveness estimates to changes in underlying assumptions. RESULTS: MT with doxycycline for chlamydia was the most cost-effective protocol in terms of cost per cure. SM protocol had the lowest total programmatic costs. For the GS protocol, using azithromycin for chlamydial infections was found to be more cost-effective than using doxycycline. For both the GS and SM protocols, the total cost of the program was most sensitive to the percentage of women seeking STD treatment and the prevalence of non-STD vaginal discharge, whereas the cost of MT was almost exclusively determined by coverage rates. CONCLUSIONS: No single protocol carries with it all the desired conditions of an optimal cost-effective program. The treatment-seeking behavior, STD prevalence, and coverage of each locale must be evaluated to determine the most cost-effective and highest impact program. MT was found to be the most cost-effective protocol in terms of cost per woman treated when compared with the SM and GS protocols for STDs in women.

Vaccines for Chlamydia trachomatis infections.

Members of the genus, Chlamydia, are obligate intracellular bacteria that have a unique developmental cycle. These organisms are widespread in nature and are common human pathogens. In this review, we describe new data related to the characterization of acquired immunity to Chlamydia trachomatis that is relevant to vaccine development. We also discuss recent work on vaccine candidates against this ubiquitous pathogen.

Treatment practices for chlamydial infection in New Zealand.

AIMS: To identify prescribing and treatment practices for chlamydial infection in New Zealand. METHODS: Postal survey to doctors and nurses at all sexual health, family planning, student and youth health centres, and randomly selected general practitioners. RESULTS: There was considerable variation in treatment regimes used for chlamydial infection with few respondents treating in accordance with international guidelines regarding dose, frequency, and duration of treatment. Doxycycline (88.4%) was most commonly used to treat uncomplicated chlamydial infection in non-pregnant patients. Most respondents (70.2%) stipulated doxycycline for longer durations than the seven day regimen international guidelines recommend, with doxycycline 100 mg twice a day for ten days most frequently specified. Among the 259 respondents who would treat pregnant women with erythromycin, 51 different treatment regimens were specified, and 51.7% recorded regimens less than that recommended by international guidelines. When treating a patient presumptively, the majority of respondents tested for chlamydial infection. In contrast to other respondents, sexual health clinic staff rarely provide patients with a prescription for a patient's partner without seeing the partner. CONCLUSIONS: Standardised treatment guidelines are required for patients diagnosed with chlamydial infection. Guidelines should include recommendations for the treatment of partners, and encourage the laboratory confirmation of diagnosis.

Aerosolized prostacyclin in acute respiratory distress syndrome caused by Chlamydiaceae spp. pneumonia.

Management of respiratory failure in acute respiratory distress syndrome (ARDS) typically requires ventilatory assistance. If traditional approaches to mechanical ventilation and adjunctive measures fail to succeed in achieving adequate oxygenation, alternative measures should be considered. We describe an ARDS patient with respiratory failure caused by a severe Chlamydiaceae species community-acquired pneumonia (CAP). Aerosolized prostacyclin (PGI(2)) treatment was successfully instituted for refractory hypoxemia.

Is there an infective aetiology to atherosclerosis?

Conventional cardiovascular risk factors fail to completely explain the observed variations in the prevalence and severity of coronary heart disease (CHD). Common chronic infections may have an aetiological role in the development of atherosclerosis and CHD, either independently or by interacting with traditional atherogenic risk factors. The evidence for Chlamydia pneumoniae as a potential causative agent is strongest, and is based on findings of numerous sero-epidemiological studies, examination of atheromatous plaque specimens, in vitro animal models and, recently, pilot antichlamydial antibiotic intervention trials. However, the complete natural history of C. pneumoniae, its mechanisms of damage in atherosclerotic disease, and the temporal sequence of infection and CHD remain unclear. Confirmation of true causality for the link between C. pneumoniae and CHD could come after the results of large-scale prospective antibiotic trials, which are to be conducted over the next few years. A proven association could have important implications for public health worldwide, potentially leading to novel and relatively inexpensive therapeutic measures in the secondary prevention of CHD--broad-spectrum antibiotics.

Comparison of chlamydial culture with Chlamydiazyme assay during erythromycin PCE treatment of Chlamydia genital infections.

We compared chlamydial culture with the chlamydial antigen detection enzyme immunoassay system (Chlamydiazyme, Abbott Diagnostic Products; Abbott Park, IL) during treatment of Chlamydia genital infections. Participants received 333 mg of erythromycin PCE (Abbott Laboratories; Abbott Park, IL) 3 times per day for 7 days. On days 0, 3, 7, and 14, chlamydial cultures were positive in 30/30 (100%), 5/29 (17.2%), 0/27, and 0/25 participants, respectively. Concurrent Chlamydiazyme assays were positive in 30/30 (100%), 11/30 (37%), 1/28 (4%), and 0/25 participants. Twenty-eight of 28 persons who received erythromycin PCE for at least 3 days had negative test results for both chlamydial culture and Chlamydiazyme at their last clinic visit. Chlamydiazyme assay tended to remain positive longer than chlamydial culture during treatment, but 7 days after therapy was completed, no Chlamydia trachomatis antigens were detectable by this assay. Erythromycin PCE was well tolerated and rapidly eliminated Chlamydia genital infections in 83% of persons showing negative cultures by the third day of therapy.

Infecçöes por Clamídia / Chlamydia infections

Faz-se uma revisäo atualizada sobre a infecçöes do trato genital-feminino, causados por Chlamydia tracomatis, sendo considerada uma infecçäo sexualmente transmíssivel e de incidência cada vez maior nos países desenvolvidos. Relatam-se dados de transmissäo, quadro clínico e tratamento. A infecçäo clamídica da cérvix uterina (cervical) é a origem da contaminaçäo no homem e no neonato, assim como das complicaçöes na própria mulher portadora. Devido à cervicite clamídica ser freqüentemente assintomática, o diagnóstico e tratamento desta condiçäo säo importantes para o controle destas infecçöes na comunidade

Treatment of chlamydial pneumonia of infancy.

Infants with untreated chlamydial pneumonia shed Chlamydia trachomatis and are symptomatic for may weeks. We used sulfisoxazole, 150 mg/kg/day, or erythromycin ethyl succinate, 40 mg/kg/day, for approximately 14 days to treat 32 patients with chlamydial pneumonia of infancy, and observed them for nasopharyngeal shedding of C trachomatis and changing clinical status. All infants stopped shedding chlamydiae soon after treatment was started. After treatment, three of the 25 infants tested again became culture positive (but did not have clinical relapse). All infants improved clinically. In 24 (83%) of 29 infants, where the onset of improvement could be times, improvement began within seven days of starting treatment. Progression to complete recovery was observed in 27 of 28 infants examined between two weeks and two months of treatment completion. Neither the existence of concomitant viral infection nor the duration of illness or hospitalization before starting treatment influenced the interval between initiation of treatment and onset of clinical improvement. While these observations do not prove, they are at least compatible with the hypotheses that C trachomatis plays a central etiologic role in this illness and that termination of chlamydial infection is beneficial clinically. Pending the availibility of data from controlled studies, we believe that either of the treatment programs outlined warrant consideration in the clinical management of patients with chlamydial pneumonia of infancy.