Opportunistic and systematic screening for chlamydia: a study of consultations by young adults in general practice

BACKGROUND: Opportunistic screening for genital chlamydia infection is being introduced in England, but evidence for the effectiveness of this approach is lacking. There are insufficient data about young peoples' use of primary care services to determine the potential coverage of opportunistic screening in comparison with a systematic population-based approach. AIM: To estimate use of primary care services by young men and women; to compare potential coverage of opportunistic chlamydia screening with a systematic postal approach. DESIGN OF STUDY: Population based cross-sectional study. SETTING: Twenty-seven general practices around Bristol and Birmingham. METHOD: A random sample of patients aged 16-24 years were posted a chlamydia screening pack. We collected details of face-to-face consultations from general practice records. Survival and person-time methods were used to estimate the cumulative probability of attending general practice in 1 year and the coverage achieved by opportunistic and systematic postal chlamydia screening. RESULTS: Of 12 973 eligible patients, an estimated 60.4% (95% confidence interval [CI] = 58.3 to 62.5%) of men and 75.3% (73.7 to 76.9%) of women aged 16-24 years attended their practice at least once in a 1-year period. During this period, an estimated 21.3% of patients would not attend their general practice but would be reached by postal screening, 9.2% would not receive a postal invitation but would attend their practice, and 11.8% would be missed by both methods. CONCLUSIONS: Opportunistic and population-based approaches to chlamydia screening would both fail to contact a substantial minority of the target group, if used alone. A pragmatic approach combining both strategies might achieve higher coverage.

Silhouettella loricatula (Arachnida, Araneae, Oonopidae): a Haplogyne spider with complex female genitalia

The female genital system of the oonopid Silhouettella loricatula is astonishingly complex. The genital opening is situated medially and leads into an oval receptaculum that is heavily sclerotized except for the ventral half of the posterior wall that appears chitinized only. A large striking sclerite lying in the posterior wall of the uterus externus is attached anteriorly to the receptaculum and continues dorsally into a globular appendix that bears a furrow. The uterus externus shows a peculiar modification in its anterior wall: a paddle-like sclerite with a nail-like posterior process. This sclerite lies opposite to the furrow proceeding in the globular appendix and may serve females to lock the uterus externus by muscle contractions. Massive muscles connect the sclerite with the anterior scutum of the opisthosoma and with two other sclerites that are attached to the receptaculum and serve as attachments for further muscles. Gland cells extend around a pore field of the receptaculum. They produce secretion that encloses spermatozoa in a discrete package (secretory sac) inside the receptaculum. In this way, the mixing of sperm from different males and thus sperm competition may be severely limited or completely prevented. During a copulation in the laboratory the ejection of a secretory sac that most probably contained spermatozoa was observed, indicating sperm dumping in S. loricatula. The ejection of the secretory sac may be caused by female muscle contractions or by male pedipalp movements. The majority of the investigated females have microorganisms in the receptacula that could represent symbionts or infectious agents. The microorganisms can be identified partly as bacteria. They are enclosed in secretion and are always found in the same position inside the receptaculum.

Sperm-binding fibronectin type II-module proteins are genetically linked and functionally related

Fibronectin type II (Fn2) module-containing proteins in the male genital tract are characterized by different numbers of Fn2 modules. Predominantly two classes exist which are distinct by having either two or four Fn2 modules. Minor variants with three Fn2 modules were also found in the human and the porcine epididymis. To reveal their relationship, mRNAs and proteins of representatives of these classes were studied in human, in Sus scrofa, and in rodents. Adult boars expressed members of both classes, i.e. ELSPBP1 and pB1, in subsequent regions of the epididymis, and both were under androgenic control. Human and rodent epididymides, on the other hand, alternatively contained only representatives of one of these two classes, i.e. ELSPBP1 in the human and two different pB1-related counterparts in rodents. ELSPBP1 and pB1-related genomic sequences were closely linked in chromosomal regions HSA 19q and SSC 6 q11-q21; conserved synteny between these regions is well established. On the other hand, in a syntenic region on mouse chromosome 7, ELSPBP1-related sequences were lacking. Tight binding to the sperm membrane via a choline-mediated mechanism was a common feature of the two classes of Fn2-module proteins, suggesting related function(s). However, differences in their regionalized expression patterns along the male genital tract as well as in association sites on the sperm surface suggested a species-specific sequential order in sperm binding.

Discovery of insertion element ISCfe1: a new tool for Campylobacter fetus subspecies differentiation

The species Campylobacter fetus is divided into the subspecies C. fetus subsp. venerealis (CFV) and C. fetus subsp. fetus (CFF). CFV is the causative agent of bovine genital campylobacteriosis, a highly contagious venereal disease that may lead to serious reproductive problems, including sterility and abortion. In contrast, CFF can be isolated from the gastrointestinal tract of a wide range of host species, is associated with abortion in sheep and cattle, and can also be isolated from local and systemic infections in humans. Despite differences in host and niche preferences, microbiological differentiation of the two subspecies of C. fetus is extremely difficult. This study describes the identification of a new insertion element, ISCfe1, which is present exclusively in CFV strains, with highly conserved specific ISCfe1 insertion sites. The results are useful for identification and differentiation of the two C. fetus subspecies and will help in understanding the evolution and pathogenesis of C. fetus.

Pollakisuria in a dwarf goat due to pathologic enlargement of the uterus

Pollakisuria in adult goats can be caused by diseases of the urinary tract and by distension of parts of the genital tract leading to irritation of the bladder. Hydrometra is the most common cause of uterine distension in goats and usually can be resolved by prostaglandin injections. But other pathologies of the uterus can generate a similar syndrome. A dwarf goat was presented at the clinic with a history of chronic pollakisuria and tenesm. An initial ultrasonographic examination of the abdomen led to the suspicion of hydrometra, but treatment with injections of prostaglandin were not successful. Blood samples revealed low progesterone and high oestrogen values. A laparotomy was performed and an enlarged uterus with 1.5 L of mucous content and cystic ovaries were found and partially removed. A single solid leiomyoma was diagnosed histologically in the uterine wall. Two months later the goat's condition had deteriorated and therefore she was euthanized. Necropsy and pathohistological examination revealed the presence of a metastasized adenocarcinoma of the uterus. In this case, the pollakisuria provoqued by distension of the uterus was not caused by hydrometra, but by neoplasia. The syndrome and the pathogenesis of the adenocarcinoma in consideration of the hormonal status of the patient is discussed.

Characterization of the first FGFRL1 mutation identified in a craniosynostosis patient

Fibroblast growth factor receptor-like 1 (FGFRL1) is a recently discovered transmembrane protein whose functions remain unclear. Since mutations in the related receptors FGFR1-3 cause skeletal malformations, DNA samples from 55 patients suffering from congenital skeletal malformations and 109 controls were searched for mutations in FGFRL1. One patient was identified harboring a frameshift mutation in the intracellular domain of this novel receptor. The patient showed craniosynostosis, radio-ulnar synostosis and genital abnormalities and had previously been diagnosed with Antley-Bixler syndrome. The effect of the FGFRL1 mutation was studied in vitro. In a reporter gene assay, the wild-type as well as the mutant receptor inhibited FGF signaling. However, the mutant protein differed from the wild-type protein in its subcellular localization. Mutant FGFRL1 was mainly found at the plasma membrane where it interacted with FGF ligands, while the wild-type protein was preferentially located in vesicular structures and the Golgi complex. Two motifs from the intracellular domain of FGFRL1 appeared to be responsible for this differential distribution, a tandem tyrosine based motif and a histidine-rich sequence. Deletion of either one led to the preferential redistribution of FGFRL1 to the plasma membrane. It is therefore likely that mutant FGFRL1 contributes to the skeletal malformations of the patient.

P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia

Patients with adrenal insufficiency, genital anomalies and bony malformations resembling the Antley- Bixler syndrome (a craniosynostosis syndrome), are likely to have P450 oxidoreductase (POR) deficiency. Since our first report in 2004, about 26 recessive POR mutations have been identified in 50 patients. POR is the obligate electron donor to all microsomal (type II) P450 enzymes, including the steroidogenic enzymes CYP17A1, CYP21A2 and CYP19A1. POR deficiency may cause disordered sexual development manifested as genital undervirilization in 46,XY newborns as well as overvirilization in those who are 46,XX. This may be explained by impaired aromatization of fetal androgens which may also lead to maternal virilization and low urinary estriol levels during pregnancy. A role for the alternate 'backdoor' pathway of androgen biosynthesis, leading to dihydrotestosterone production bypassing androstenedione and testosterone, has been suggested in POR deficiency but remains unclear. POR variants may play an important role in drug metabolism, as most drugs are metabolized by hepatic microsomal P450 enzymes. However, functional assays studying the effects of specific POR mutations on steroidogenesis showed that several POR variants impaired CYP17A1, CYP21A2 and CYP19A1 activities to different degrees, indicating that each POR variant must be studied separately for each potential target P450 enzyme. Thus, the impact of POR mutations on drug metabolism by hepatic P450s requires further investigation.

Effectiveness of chlamydia screening: systematic review

BACKGROUND: Screening programmes are promoted to control transmission of and prevent female reproductive tract morbidity caused by genital chlamydia. The objective of this study was to examine the effectiveness of register-based and opportunistic chlamydia screening interventions. METHODS: We searched seven electronic databases (Cinahl, Cochrane Controlled Trials Register, DARE, Embase, Medline, PsycINFO and SIGLE) without language restrictions from January 1990 to October 2007 and reference lists of retrieved articles to identify studies published before 1990. We included studies examining primary outcomes (pelvic inflammatory disease, ectopic pregnancy, infertility, adverse pregnancy outcomes, neonatal infection, chlamydia prevalence) and harms of chlamydia screening in men and non-pregnant and pregnant women. We extracted data in duplicate and synthesized the data narratively or used random effects meta-analysis, where appropriate. RESULTS: We included six systematic reviews, five randomized trials, one non-randomized comparative study and one time trend study. Five reviews recommended screening of women at high risk of chlamydia. Two randomized trials found that register-based screening of women at high risk of chlamydia and of female and male high school students reduced the incidence of pelvic inflammatory disease in women at 1 year. Methodological inadequacies could have overestimated the observed benefits. One randomized trial showed that opportunistic screening in women undergoing surgical termination of pregnancy reduced post-abortal rates of pelvic inflammatory disease compared with no screening. We found no randomized trials showing a benefit of opportunistic screening in other populations, no trial examining the effects of more than one screening round and no trials examining the harms of chlamydia screening. CONCLUSION: There is an absence of evidence supporting opportunistic chlamydia screening in the general population younger than 25 years, the most commonly recommended approach. Equipoise remains, so high-quality randomized trials of multiple rounds of screening with biological outcome measures are still needed to determine the balance of benefits and harms of chlamydia screening.

[Follow-up after malignant tumours of the uterus (cancer of the uterine corpus / cervical cancer)]

Malignant uterine tumours can affect the corpus or the cervix. The endometrial carcinoma with its different histological subtypes counts for most of the malignomas of the uterine body. But the rare category of uterine sarcomas (carcinosarcomas, leiomyosarcomas as well as endometrial stromal sarcomas) also belongs to this group. Cervical cancer presents an own entitity, regarding both histology and therapeutic options. Endometrial cancer is the most common genital malignoma in Northern Europe and North America. Histologically, the endometrial cancer can be subdivided in two groups: type I is hormonal sensitive and well differentiated, type II represents an undifferenciated aggressive tumour with poor prognosis. In general, the patient is elderly. Due to the main symptom - abnormal vaginal bleeding - endometrial cancer is detected in an early stage in about 75% of all patients. First choice in therapy is stage related surgery. Follow-up schemes have not proved yet to improve survival, therefore clear guidelines are missing. National and international groups recommend regular follow-up visits to detect the early vaginal vault relapse which is curable. Cervical cancer is mainly a squamous cell carcinoma and oncogenic Human Papilloma Virus (HPV) associated. Surgery is only indicated up to stage IIA, advanced stages should be treated by radio-chemotherapy. Several studies have shown that follow-up visits can improve survival rates. Intention is the detection of the curable local relapse.

Mesenteric lymphangitis and sepsis due to RTX toxin-producing Actinobacillus spp in 2 foals with hypothyroidism-dysmaturity syndrome

Actinobacillus suis-like organisms (ASLOs) have been isolated from the genital, respiratory, and digestive tracts of healthy adult horses, horses with respiratory disease, and septic foals. Two foals with congenital hypothyroidism-dysmaturity syndrome from separate farms developed ASLO infection. At necropsy, both had contracted carpal flexor tendons, thyroid hyperplasia, and thrombotic and necrotizing mesenteric lymphangitis and lymphadenitis; one foal also had mandibular prognathism. Numerous ASLOs were isolated from tissues from both foals, including intestine. Biochemical testing and mass spectrometric analysis of the two Actinobacillus isolates did not allow unequivocal identification. Comparative genetic analysis was done on these and similar isolates, including phylogeny based on 16S rRNA, rpoB and recN genes, as well as RTX (repeat in toxin) toxin typing of apxIA-apxIVA and aqxA genes. One isolate was identified as Actinobacillus suis sensu stricto, based on the presence of apxIA and apxIIA but not aqxA, whereas the other isolate had aqxA but neither apxIA nor apxIIA, consistent with A equuli ssp haemolyticus. Based on genotypic analysis of the isolates included for comparison, 3 of 3 equine ASLOs and 2 of 5 A equuli isolates were reclassified as A equuli subsp haemolyticus, emphasizing the importance of toxin genotyping in accurate classification of actinobacilli.

Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study

BACKGROUND Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). METHODS We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. RESULTS The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. CONCLUSIONS This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

Toward global prevention of sexually transmitted infections (STIs): The need for STI vaccines.

An estimated 499 million curable sexually transmitted infections (STIs; gonorrhea, chlamydia, syphilis, and trichomoniasis) occurred globally in 2008. In addition, well over 500 million people are estimated to have a viral STI such as herpes simplex virus type 2 (HSV-2) or human papillomavirus (HPV) at any point in time. STIs result in a large global burden of sexual, reproductive, and maternal-child health consequences, including genital symptoms, pregnancy complications, cancer, infertility, and enhanced HIV transmission, as well as important psychosocial consequences and financial costs. STI control strategies based primarily on behavioral primary prevention and STI case management have had clear successes, but gains have not been universal. Current STI control is hampered or threatened by several behavioral, biological, and implementation challenges, including a large proportion of asymptomatic infections, lack of feasible diagnostic tests globally, antimicrobial resistance, repeat infections, and barriers to intervention access, availability, and scale-up. Vaccines against HPV and hepatitis B virus offer a new paradigm for STI control. Challenges to existing STI prevention efforts provide important reasons for working toward additional STI vaccines. We summarize the global epidemiology of STIs and STI-associated complications, examine challenges to existing STI prevention efforts, and discuss the need for new STI vaccines for future prevention efforts.

Chlamydia prevalence in young attenders of rural and regional primary care services in Australia: a cross-sectional survey.

OBJECTIVE To estimate chlamydia prevalence among 16-29-year-olds attending general practice clinics in Australia. DESIGN, PARTICIPANTS AND SETTING A cross-sectional survey was conducted from May 2010 to December 2012. Sexually experienced 16-29-year-olds were recruited from 134 general practice clinics in 54 rural and regional towns in four states and in nine metropolitan clinics (consecutive patients were invited to participate). Participants completed a questionnaire and were tested for chlamydia. MAIN OUTCOME MEASURE Chlamydia prevalence. RESULTS Of 4284 participants, 197 tested positive for chlamydia (4.6%; 95% CI, 3.9%-5.3%). Prevalence was similar in men (5.2% [65/1257]; 95% CI, 3.9%-6.4%) and women (4.4% [132/3027]; 95% CI, 3.5%-5.2%) (P = 0.25) and high in those reporting genital symptoms or a partner with a sexually transmissible infection (STI) - 17.0% in men (8/47; 95% CI, 2.8%-31.2%); 9.5% in women (16/169; 95% CI, 5.1%-13.8%). Nearly three-quarters of cases (73.4% [130/177]) were diagnosed in asymptomatic patients attending for non-sexual health reasons, and 83.8% of all participants (3258/3890) had attended for non-sexual health reasons. Prevalence was slightly higher in participants from rural and regional areas (4.8% [179/3724]; 95% CI, 4.0%-5.6%) than those from metropolitan areas (3.1% [17/548]; 95% CI, 1.5%-4.7%) (P = 0.08). In multivariable analysis, increasing partner numbers in previous 12 months (adjusted odds ratio [AOR] for three or more partners, 5.11 [95% CI, 2.35-11.08]), chlamydia diagnosis in previous 12 months (AOR, 4.35 [95% CI, 1.52-12.41]) and inconsistent condom use with most recent partner (AOR, 2.90 [95% CI, 1.31-6.40]) were significantly associated with chlamydia in men. In women, increasing partner numbers in previous 12 months (AOR for two partners, 2.59 [95% CI, 1.59-4.23]; AOR for three or more partners, 3.58 [95% CI, 2.26-5.68]), chlamydia diagnosis in previous 12 months (AOR, 3.13 [95% CI, 1.62-6.06]) and age (AOR for 25-29-year-olds, 0.23 [95% CI, 0.12-0.44]) were associated with chlamydia. CONCLUSIONS Chlamydia prevalence is similar in young men and women attending general practice. Testing only those with genital symptoms or a partner with an STI would have missed three-quarters of cases. Most men and women are amenable to being tested in general practice, even in rural and regional areas.

Chronic bovine besnoitiosis: intra-organ parasite distribution, parasite loads and parasite-associated lesions in subclinical cases.

Bovine besnoitiosis caused by Besnoitia besnoiti is a chronic and debilitating disease. The most characteristic clinical signs of chronic besnoitiosis are visible tissue cysts in the scleral conjunctiva and the vagina, thickened skin and a generally poor body condition. However, many seropositive animals remain subclinically infected, and the role that these animals may play in spreading the disease is not known. The aim of the present study was to assess the intra-organ parasite distribution, the parasite load and the parasite-associated lesions in seropositive but subclinically infected animals. These animals were seropositive at the time of several consecutive samplings, had visible tissue cysts in the past and, at time of slaughter, had detectable specific anti-Besnoitia spp. antibody levels, but they did not show evident clinical signs at culling. Thus, histopathological, immunohistochemical and molecular analyses of several samples from the respiratory tract, reproductive tract, other internal organs and skin from six cows were performed. The tissue cysts were located primarily in the upper respiratory tract, i.e., in the rhinarium and larynx/pharynx (four cows), followed by the distal genital tract (vulva/vagina) and the skin of the neck (three and two cows, respectively, out of the four cows with cysts in the respiratory tract). We were unable to detect any parasites in the two remaining cows. Cysts were associated with a significant non-purulent inflammatory infiltrate consisting predominantly of T lymphocytes and activated monocytes/macrophages in two cows. The parasite burden, estimated by quantitative real-time PCR, was very low. It is noteworthy that the only animal that showed a recent increase in the antibody titre had the highest parasite burden and the most conspicuous inflammatory reaction against the cysts. In conclusion, although these cows no longer displayed any visible signs of besnoitiosis, they remained infected. Therefore, cows without visible signs of disease may still be able to transmit the parasite.

Spider Ecophysiology

With over 43,000 species, spiders are the largest predacious arthropod group. They have developed key characteristics such as multi-purpose silk types, venoms consisting of hundreds of components, locomotion driven by muscles and hydraulic pressure, a highly evolved key-lock mechanism between the complex genital structures, and many more unique features. After 300 million years of evolutionary refinement, spiders are present in all land habitats and represent one of the most successful groups of terrestrial organisms. Ecophysiology combines functional and evolutionary aspects of morphology, physiology, biochemistry and molecular biology with ecology. Cutting-edge science in spiders focuses on the circulatory and respiratory system, locomotion and dispersal abilities, the immune system, endosymbionts and pathogens, chemical communication, gland secretions, venom components, silk structure, structure and perception of colours as well as nutritional requirements. Spiders are valuable indicator species in agroecosystems and for conservation biology. Modern transfer and application technologies research spiders and their products with respect to their value for biomimetics, material sciences, and the agrochemical and pharmaceutical industries.