Adrian Eley

Can Chlamydia trachomatis directly damage your sperm

Although Chlamydia trachomatis causes symptomatic infection in the lower genital tract of approximately 50% of men, its role in the upper genital tract is less well known. Moreover, for a number of reasons, mostly based on methodological aspects, the impact of chlamydia on semen quality is controversial. Overall, in-vivo studies of C trachomatis in men have provided conflicting evidence as to whether it is associated with reduced fertility. By contrast, in-vitro studies show that co-incubation of spermatozoa with chlamydia causes a significant decline in numbers of motile sperm and results in premature sperm death. Since evidence suggests that chlamydial lipopolysaccharide is the principal factor leading to sperm apoptosis, a new line of inquiry would be to measure the levels of lipopolysaccharide in semen and relate these to parameters of semen quality, including that of sperm function. If these new lines of inquiry are proven, this could lead to potentially novel approaches in the treatment of infertile men.

Infectivity of chlamydia trachomatis serovar LGV but not E is dependent on host cell heparan sulfate

ABSTRACT The ability of heparan sulfate, heparin, and other glycosaminoglycans to inhibit the infectivity of Chlamydia trachomatis serovars E and LGV was examined using a simple competitive inhibition assay with three cell types from the human female reproductive tract, including primary human endosalpingeal cells. With the majority of the glycosaminoglycans tested, LGV was more significantly inhibited than serovar E. We have compared chlamydial infectivity between a wild-type Chinese hamster ovary cell line and two glycosaminoglycan-deficient cell lines. LGV was shown to be unable to infect heparan sulfate-deficient and GAG-deficient Chinese hamster ovary cell lines, whereas the E serovar infected these cells as efficiently as the control (nondeficient) cells. These two sets of experiments confirmed that serovar LGV is more dependent on a heparan sulfate-related mechanism of infectivity than is serovar E. This is further supported by the fact that attempts to purify a heparan sulfate-like molecule from either serovar cultured in glycosaminoglycan-deficient cell lines were nonproductive. Previous reports have suggested that chlamydia are able to produce a heparan sulfate-like molecule that is important for attachment and infectivity. We have attempted to detect possible binding of a specific heparan sulfate antibody to C. trachomatis by flow cytometry. Results showed no binding of the heparan sulfate antibody to C. trachomatis serovar LGV or E. Our results strongly indicate that chlamydiae do not produce a heparan sulfate-like molecule but rather use host cell heparan sulfate in order to infect cells.

Virulence properties of clinically significant Aeromonas species: evidence for pathogenicity

Members of the genus Aeromonas are responsible for a significant number of intestinal and extra-intestinal infections in humans as well as other animals. However, their true role in enteric disease has been hindered by an inadequate human volunteer study, lack of an appropriate animal model and deficiencies in diagnostic procedures. The latter are probably responsible in part for the small number of outbreaks that have been reported. Despite these difficulties, several recent outbreaks and epidemiological studies have indicated a strong association between isolation of Aeromonas and enteric disease. This has further stimulated research into potential pathogenic properties of Aeromonas, and much progress has been made over the last few years with regard to colonization, protection from the host and extracellular factors. It is hoped that these advances in elucidating the role of potential pathogenicity factors will be matched by interest and diagnostic studies, so that together the true nature of Aeromonas in disease will be more closely understood.

The prevalence of Chlamydia trachomatis in fresh tissue specimens from patients with ectopic pregnancy or tubal factor infertility as determined by PCR and in-situ hybridisation

The prevalence of chlamydial DNA determined by PCR and in-situ hybridisation (ISH) in fresh tissue specimens (endometrium, fallopian tube and ovary) was investigated in 33 women presenting with ectopic pregnancy (EP), 14 women with tubal factor infertility (TFI) and 50 control patients from the UK and the West Indies. In the UK EP group, chlamydial DNA was detected by PCR in 56% of patients; similar results were found in the Trinidad EP group (67%). In the TFI group, chlamydial DNA was detected in (71%) of patients by PCR. The detection of Chlamydia trachomatis DNA by ISH was highest in the TFI group (43%). Women presenting with EP and TFI showed evidence of previous or current genital C. trachomatis infection, underlining the importance of this microorganism in the development of these conditions. Importantly, chlamydial DNA could be detected in DNA preparations from the endometrium, fallopian tube and ovary of EP and TFI patients at the time of surgery.

The relation between immunoglobulin G antibodies to Chlamydia trachomatis and poor ovarian response to gonadotropin stimulation before in vitro fertilization

OBJECTIVE To determine whether a relation exists between previous exposure to Chlamydia trachomatis and impaired ovarian response to gonadotropin stimulation. DESIGN Controlled clinical study. SETTING Two university IVF centers. PATIENT(S) Two hundred forty-two patients receiving IVF treatment and 81 control patients. Ninety-four patients with a poor response to IVF, defined by cycle cancellation in response to a daily stimulation dose of 300 IU of FSH, and 148 patients with a good response were matched for age. Twenty-eight pregnant controls and 53 controls of proven fertility also were included. INTERVENTION(S) Serum samples were obtained from patients and controls. Serum levels of immunoglobulin (Ig) G antibodies to C. trachomatis were determined by ELISA. MAIN OUTCOME MEASURE(S) The prevalence of serum IgG antibodies to C. trachomatis in critically defined poor responders was compared with that of age-matched good responders. RESULT(S) A significantly higher proportion of poor responders had serum IgG antibodies to C. trachomatis compared with good responders (44.7% and 30.4%, respectively). Patients undergoing IVF had a significantly higher prevalence of IgG antibodies to C. trachomatis (36%) than did either pregnant or nonpregnant controls (12%). CONCLUSION(S) A significantly higher prevalence of serum IgG antibodies to C. trachomatis was observed in critically defined poor responders, suggesting a possible detrimental effect of C. trachomatis on subsequent ovarian function.

Raised Inflammatory Markers in Semen From Men With Asymptomatic Chlamydial Infection

The aim of this study was to determine whether interleukin (IL)-6 and IL-8 concentrations, as well as numbers of seminal leukocytes in a population of infertile men, some of whom were Chlamydia trachomatis positive, were related to chlamydial infection. Our patient group included 255 men attending for diagnostic semen analysis as part of infertility investigations. Significantly raised levels of IL-8, but not IL-6, were found in C trachomatis-infected patients but not in uninfected patients. Raised IL-8 levels in semen were also associated with an increase in semen volume. There was a relationship between C trachomatis infection and lower progressive motile sperm, as well as an increase in seminal leukocytes. The overall prevalence rate for C trachomatis was 6.2%, and more infections were detected in semen than in first void urine. This study supports the suggestion that IL-8 might be used as a marker for male genital tract infection, especially when due to C trachomatis. In this study, there was a relationship between the presence of C trachomatis in semen and alterations of some semen parameters. Further investigations should be performed to understand the disparities of first void urine and semen testing for detection of C trachomatis in males.

Adherence of Aeromonas caviae to human cell lines Hep-2 and Caco-2

Adherence of Aeromonas caviae to HEp-2 and Caco-2 cell monolayers was investigated with 24 clinical isolates. Growth phase, temperature, multiplicity of infection and length of incubation affected adherence. Treatment of the bacteria with trypsin, sodium metaperiodate, mechanical shearing and the addition of cytochalasin B and cycloheximide to the monolayer significantly reduced the adherence capabilities of the strains investigated. The use of chloramphenicol to inhibit protein synthesis reduced the adhesive capabilities of bacteria grown in liquid medium and those subjected to mechanical shearing. Light microscopy, scanning and transmission electron microscopy were employed in the investigation of bacteria-bacteria and bacteria-monolayer interactions and indicated similarities with the aggregative adherence patterns of the Enterobacteriaceae. The presence of extracellular bacterial appendages and their correlation with increased adhesive capacity may indicate a role in the process of adherence.

Inhibition of chemotaxis by organic acids from anaerobes may prevent a purulent response in bacterial vaginosis.

It has been postulated that certain organic acids produced by the anaerobes associated with bacterial vaginosis (BV) could prevent a purulent response in this infection. Varying concentrations of pure succinic, acetic and lactic acids were incubated in vitro with a monocytic cell line (MonoMac 6). High inhibition of chemotaxis was produced by succinic acid; lower inhibition and no inhibition was shown by acetic acid and lactic acid respectively. Succinic and acetic acids were detected in high concentrations in the vaginal fluid of women with BV and in culture supernates of Prevotella and Mobiluncus spp.; these acids impaired chemotaxis of MonoMac 6 cells in vitro. The vaginal fluids of normal women and the culture supernates of Lactobacillus spp. had no effect on chemotaxis.

Comparative in vitro activities of cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency.

Cefotaxime and its desacetoxymethyl derivative, ceftizoxime (previously known as FK749), are both extremely active against a wide spectrum of bacteria. In the present comparative study, the activity of ceftizoxime exceeded that of cefotaxime by a factor of four or more for strains of Klebsiella, Enterobacter, Providencia, Serratia, and Bacteroides; the only species for which the activity of cefotaxime exceeded that of ceftizoxime by a factor of four was Vibrio cholerae. Against other species, the activity of the two drugs was roughly comparable. Both showed outstanding activity against Haemophilus influenzae and Neisseria gonorrhoeae. Comparative turbidimetric and morphological studies revealed that ceftizoxime was able to induce spheroplast formation and rapid lysis in Escherichia coli strains at lower concentrations than cefotaxime. This difference was not found, however, when E. coli strains resistant to ampicillin by an intrinsic (nonenzymic) mechanism were tested.

Real-time polymerase chain reaction shows that density centrifugation does not always remove Chlamydia trachomatis from human semen

OBJECTIVE To evaluate the efficiency of sperm washing procedures to remove Chlamydia trachomatis from semen both in clinical samples and experimental inoculations. DESIGN Laboratory-based study. SETTING Research laboratory in a university hospital. PATIENT(S) One hundred men attending for diagnostic semen analysis as part of infertility investigations and three sperm donors providing ejaculates for research purposes. MAIN OUTCOME MEASURE(S) Number of DNA copies of C. trachomatis, infectivity in an HeLa cell monolayer, and immunofluorescence. RESULT(S) Of the 100 semen samples examined, 13 contained detectable levels of C. trachomatis DNA (675-15,920 copies/mL) and in only 7 was this completely removed after sperm washing. In the remaining six DNA-positive samples, the number of copies in the postwash preparation ranged from 36-455 per mL. Experimental inoculations found that postwash preparations containing C. trachomatis DNA as low as 61 copies/mL were able to establish an infection in vitro. CONCLUSION(S) Undiagnosed C. trachomatis infections in men attending for assisted conception could potentially lead to infection or contamination of the IVF culture system as sperm washing methods are not 100% effective.