Impact of socio-economic conditions and perinatal factors on risk of becoming a child looked after: a whole population cohort study using routinely collected data in Wales.

OBJECTIVES: Between 1997 and 2021, the number of children looked after (CLA) in Wales, UK, increased steadily, with stark inequalities. We aimed to assess how deprivation and maternal and child perinatal characteristics influence the risk of becoming CLA in Wales. STUDY DESIGN: We constructed a prospective longitudinal cohort of children born in Wales between April 2006 and March 2021 (n = 395,610) using linked administrative records. METHODS: Survival models examined the risk of CLA from birth by small-area deprivation and maternal and child perinatal characteristics. Population attributable fractions quantify the potential impact of action on modifiable risk factors. RESULTS: Children from the most deprived fifth of the population were 3.4 times more likely to enter care than those in the least deprived (demographic adjusted hazard ratios [aHRs] 3.40, 95% confidence interval [CI] 3.08, 3.74). Maternal mental health problems in pregnancy (fully aHR, 2.03, 95% CI 1.88, 2.19) and behavioural factors, such as smoking (aHR 2.46, 95% CI 2.34-2.60), alcohol problems (aHR 2.35, 95% CI 1.70-3.23) and substance use in pregnancy (aHR 5.72, 95% CI 5.03-6.51), as well as child congenital anomalies (aHR 1.46, 95% CI 1.16-1.84), low birth weight (aHR 1.28, 95% CI 1.17, 1.39) and preterm birth (aHR 1.16, 95% CI 1.06, 1.26), were associated with higher risk of CLA status. The risk of CLA in the population may be reduced by 35% (95% CI 0.33, 0.38) if children in the two most deprived fifths of the population experienced the conditions of those in the least deprived. CONCLUSIONS: Deprivation and perinatal maternal health are important modifiable risk factors for children becoming CLA. Our analysis provides insight into the mechanisms of intergenerational transfer of disadvantage in a vulnerable section of the child population and identifies targets for public health action.

Pregnancy rates and outcomes in women with cystic fibrosis in the UK: comparisons with the general population before and after the introduction of disease-modifying treatment, 2003-17.

OBJECTIVE: To compare pregnancy rates and outcomes for women with cystic fibrosis in the UK with those of the general population and assess the effect of the introduction of disease-modifying treatment. DESIGN: A population-based longitudinal study, 2003-17. SETTING: United Kingdom. POPULATION: Women aged 15-44 years in the UK cystic fibrosis (CF) Registry compared with women in England and Wales. METHODS: We calculated pregnancy and live-birth rates for the CF population and the general population of England and Wales. For women with CF we compared pregnancy rates before and after ivacaftor was introduced in 2013. We further used CF registry data to assess pregnancy outcomes for mothers with CF, and to assess the relationship between maternal pre-pregnancy lung function and nutritional status and child gestational age. MAIN OUTCOME MEASURES: Pregnancy and live-birth rates and child gestational age. RESULTS: Of 3831 women with CF, 661 reported 818 pregnancies. Compared with the general population, the pregnancy rate was 3.3 times lower in the CF population (23.5 versus 77.7 per 1000 woman-years); the live-birth rate was 3.5 times lower (17.4 versus 61.4 per 1000 woman-years) with 70% of pregnancies in CF women resulting in live births; termination of pregnancy rates were also lower (9% versus 22%). Pregnancy rates increased post-ivacaftor for eligible women with CF, from 29.7 to 45.7 per 1000 woman-years. There was no association between pre-pregnancy lung function/nutrition status and gestational age. CONCLUSIONS: Pregnancy rates in women with CF are about one-third of the rates in the general population with favourable outcomes, and increased for eligible women post-ivacaftor. TWEETABLE ABSTRACT: Pregnancy rates in women with CF are about a third of the rate in England and Wales with 70% live births. Ivacaftor increases the rate.

Identifying children with Cystic Fibrosis in population-scale routinely collected data in Wales: A Retrospective Review.

INTRODUCTION: The challenges in identifying a cohort of people with a rare condition can be addressed by routinely collected, population-scale electronic health record (EHR) data, which provide large volumes of data at a national level. This paper describes the challenges of accurately identifying a cohort of children with Cystic Fibrosis (CF) using EHR and their validation against the UK CF Registry. OBJECTIVES: To establish a proof of principle and provide insight into the merits of linked data in CF research; to identify the benefits of access to multiple data sources, in particular the UK CF Registry data, and to demonstrate the opportunity it represents as a resource for future CF research. METHODS: Three EHR data sources were used to identify children with CF born in Wales between 1st January 1998 and 31st August 2015 within the Secure Anonymised Information Linkage (SAIL) Databank. The UK CF Registry was later acquired by SAIL and linked to the EHR cohort to validate the cases and explore the reasons for misclassifications. RESULTS: We identified 352 children with CF in the three EHR data sources. This was greater than expected based on historical incidence rates in Wales. Subsequent validation using the UK CF Registry found that 257 (73%) of these were true cases. Approximately 98.7% (156/158) of individuals identified as CF cases in all three EHR data sources were confirmed as true cases; but this was only the case for 19.8% (20/101) of all those identified in just a single data source. CONCLUSION: Identifying health conditions in EHR data can be challenging, so data quality assurance and validation is important or the merit of the research is undermined. This retrospective review identifies some of the challenges in identifying CF cases and demonstrates the benefits of linking cases across multiple data sources to improve quality.

Socioeconomic deprivation and the burden of head and neck cancer-Regional variations of incidence and mortality in Merseyside and Cheshire, North West, England.

OBJECTIVES: The aim of this longitudinal study was to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends. DESIGN: We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN) for head and neck cancers. Data from the North West of England and England were used as comparator regions. SETTING: This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The Merseyside and Cheshire region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis. MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age-standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against them and measured by Pearson's correlation coefficients. RESULTS: The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100 000 population. Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION: Our study emphasises notable geographical variations within the region which need to be addressed through public health measures.

Sinus surgery postpones chronic Gram-negative lung infection: cohort study of 106 patients with cystic fibrosis.

BACKGROUND: In patients with cystic fibrosis (CF) the sinuses are a bacterial reservoir for Gram-negative bacteria (GNB). From the sinuses the GNB can repeatedly migrate to the lungs. In a one-year follow-up study, endoscopic sinus surgery (ESS) with adjuvant therapy reduced the frequency of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined by Leeds criteria. RESULTS: One hundred and six CF patients underwent ESS; 27 had improved lung infection status after three years. The prevalence of patients free of lung colonization with GNB significantly increased from 16/106 patients (15%) preoperatively to 35/106 patients (33%) after three years. The total cohort had decreasing lung function during follow-up; however, in 27 patients with improved lung infection status lung function was stable. Revision surgery was performed in 31 patients (28%). CONCLUSION: ESS with adjuvant therapy significantly improves the lung infection status for at least three years in our cohort of patients with CF and may postpone chronic lung infection with GNB and thus stabilize lung function.

Do early-life exposures explain why more advantaged children get eczema? Findings from the U.K. Millennium Cohort Study.

BACKGROUND: Atopic dermatitis (eczema) in childhood is socially patterned, with higher incidence in more advantaged populations. However, it is unclear what factors explain the social differences. OBJECTIVES: To identify early-life risk factors for eczema, and to explore how early-life risk factors explain any differences in eczema. METHODS: We estimated odds ratios (ORs) for ever having had eczema by age 5 years in 14 499 children from the U.K. Millennium Cohort Study (MCS), with a focus on maternal, antenatal and early-life risk factors and socioeconomic circumstances (SECs). Risk factors were explored to assess whether they attenuated associations between SECs and eczema. RESULTS: Overall 35·1% of children had ever had eczema by age 5 years. Children of mothers with degree-level qualifications vs. no educational qualifications were more likely to have eczema (OR 1·52, 95% confidence interval 1·31-1·76), and there was a gradient across the socioeconomic spectrum. Maternal atopy, breastfeeding (1-6 weeks and ≥ 6 months), introduction of solids under 4 months or cow's milk under 9 months, antibiotic exposure in the first year of life and grime exposure were associated with an increased odds of having eczema. Female sex, Pakistani and Bangladeshi ethnicity, smoking during pregnancy, exposure to environmental tobacco smoke and having more siblings were associated with reduced odds for eczema. Controlling for maternal, antenatal and early-life characteristics (particularly maternal smoking during pregnancy, breastfeeding and number of siblings) reduced the OR for eczema to 1·26 (95% confidence interval 1·03-1·50) in the group with the highest educational qualifications compared with the least. CONCLUSIONS: In a representative U.K. child cohort, eczema was more common in more advantaged children. This was explained partially by early-life factors including not smoking during pregnancy, breastfeeding and having fewer siblings.

Penetrating assaults in children: often non-fatal near-miss events with opportunities for prevention in the UK.

INTRODUCTION: Media reports portray a growing problem of gun and stab assaults amongst UK children. Recent legislative changes aim to increase integration between services and protect children better. Child victims of gun or stab assaults are at increased risk of reinjury and are therefore vital targets for interventions shown to be effective at preventing violent injury. There is currently a paucity of data with which to inform public debate, guide policy and develop prevention strategies. We therefore aimed to provide contemporary data on the epidemiology and clinical outcomes for intentional gun and stab injuries in children, using a large UK city as a model environment and also to ascertain whether interventions to prevent violent injury are currently in routine use in a sample of UK urban paediatric EDs. METHODS: A retrospective case series analysis was performed of children (<16 years) attending Emergency Departments (EDs) in a typical major UK city with high levels of deprivation. In addition, we undertook a qualitative survey of a sample of UK urban paediatric EDs regarding their use of violent injury prevention strategies in children. RESULTS: Contrary to media reports and data from London, rates of gun and stab assault remained unchanged through the study (2003-2008). Although tragic fatal injury can occur, the majority of injuries were minor, with most children not requiring admission. Of those admitted, a minority needed surgery (mainly wound debridement and closure). Socioeconomically deprived, adolescent boys appear to be particularly at risk, with attacks at weekends and in public spaces beyond home and school being more common. Interventions to prevent violent reinjury are not currently employed in paediatric EDs in the 15 most populated urban areas of the UK. CONCLUSIONS: Patient safety literature emphasises the need to identify near miss events. Media reports of tragic child deaths due to gunshot and stabbing are actually accompanied by large numbers of minor wounds that we should see as near miss events. Measures shown to reduce reinjury in these high-risk groups could now be pursued in the UK for patient safety and child protection purposes.

Difficulties experienced in defining the microbial cause of pelvic inflammatory disease.

Clinical assessment of women with pelvic pain was a poor indicator of disease seen at laparoscopy. Thus, of 109 women, 22 at laparoscopy had salpingitis, 19 had adhesions without salpingitis, 20 had endometriosis or ovarian pathology and 48 no observable abnormality. In all laparoscopic categories, Ureaplasma spp. and Mycoplasma hominis, but not Mycoplasma genitalium, were at least as common in the cervix/vagina as Chlamydia trachomatis and equally frequent in the endometrium. However, C. trachomatis had the greatest propensity for spread to the Fallopian tubes. Thus, of 28 women who had C. trachomatis organisms in the vagina/cervix, 13 had them in a Fallopian tube (ratio 2.2:1); the ratio was 6:1 for Neisseria gonorrhoeae, 8:1 for M. genitalium, 21:1 for M. hominis and 31:1 for Ureaplasma spp. M. hominis organisms in a large number were detected most often in women with salpingitis. The likelihood of spread of Ureaplasma urealyticum and U. parvum from the lower to the upper genital tract was about the same and they were detected only once each in a tube, which was not inflamed in either case. Multiple bacteria were often detected at a single site, making it difficult to establish the exact cause of disease. However N. gonorrhoeae was considered to be the sole cause of salpingitis in one woman and the primary or equal primary contributor in four others; C. trachomatis was involved in at least 11 women, mostly as the sole cause or as the primary contributor; M. genitalium was considered the cause in one woman and had possible involvement in three others; and M. hominis was a questionable sole cause in one woman and the primary or equal primary contributor in three. Serologically, C. trachomatis was related to adhesions, without salpingitis, more often (63%) than any other micro-organism. M. genitalium may have been implicated in one case. Serologically, a previous C. trachomatis infection was indicated in 40% of women without an observable laparoscopic abnormality. C. trachomatis in the endometrium and tubes of women without any laparoscopic abnormality suggests subclinical disease, endometritis or endosalpingitis. There was evidence for a smaller proportion (19%) of women without an abnormality having been infected previously with M. genitalium. To some extent this is consistent with the infrequency of acute M. genitalium infections in this cohort of women.

Further observations, mainly serological, on a cohort of women with or without pelvic inflammatory disease.

An analysis was undertaken of data pertaining to over 100 women with lower abdominal pain who were laparoscoped. Prior to laparoscopy, 11 of the women were considered to almost certainly have salpingitis, of whom six (55%) had salpingitis at laparoscopy; 17 to probably have salpingitis, of whom six (35%) did; 28 to possibly have salpingitis, of whom five (18%) did; and 56 to be very unlikely to have salpingitis, of whom five (9%) did. Of the 22 women who had salpingitis at laparoscopy, 14 (64%) had a Chlamydia trachomatis IgG antibody titre of >or=1:128 and might reasonably be regarded as having chlamydial disease on this basis; six without such a titre probably did not have chlamydial disease as C. trachomatis could not be detected at any genital site. At laparoscopy, 18 women had adhesions without obvious tubal inflammation; clinically, 15 of them had been regarded as possibly having salpingitis or unlikely to have it, with 12 having chronic pelvic pain. Twelve (67%) of the 18 women had a chlamydial IgG antibody titre of >or=1:128. IgM antibody was also detected most often in the 'salpingitis' group. Of 49 women without any abnormality detected at laparoscopy, nine (18%) had a high chlamydial IgG antibody titre. Overall, a woman who had a high titre of chlamydial IgG antibody and acute pelvic pain, together with a clinical picture of pelvic inflammation, was more likely to have salpingitis than adhesions alone. Likewise, a woman who had a high titre of chlamydial IgG antibody and chronic pelvic pain, together with a clinical picture suggesting that salpingitis was unlikely, was more likely to have adhesions alone than acute chlamydial salpingitis. However, while antibody measurement and seeking cervical C. trachomatis may help in formulating a diagnosis, there seems no simple way of detecting the small proportion of women who are infected by C. trachomatis in the upper genital tract but whose laparoscopic findings indicate normality. So far as patient care is concerned, the only way of preventing damage to the upper genital tract is to treat early on the basis of suspicion.

A trial of the validity of genital smears and cultures with gonococcal vaccine provocation in diagnosing genital gonorrhoea in women.

In Russia the diagnosis of gonorrhoea in women relied on microscopy, justified by the hypothesis that sensitivity increases using 'provocation' techniques. The aim was to test the value of Gonovaccine as provocation in women who would have received it normally. Cervical specimens from 204 women were tested by culture and a ligase chain reaction (LCR) assay before the women were randomized to receive provocation or not. Further cervical specimens were obtained 24, 48 and 72 hours later for microscopy, culture and LCR tests. In both provocation and non-provocation arms, 24 women were positive for gonorrhoea by the LCR assay. Test-by-test, sensitivity of microscopy was 30% in the provocation arm and 13% in the control arm (P = 0.0407, Fisher's exact test). Patient-by-patient, sensitivity of microscopy was 50% in the provocation arm, but only 25% in the control arm (P = 0.0675, Fisher's exact test). The cost per case was greater ($214) using provocation with microscopy than culture and microscopy at the first visit ($150). Thus, although Gonovaccine provocation doubled the sensitivity of microscopy in detecting gonococci, the internationally recommended protocol of microscopy and culture at first visit should be adopted as routine practice in Russia. The findings raise questions about the pathogenesis and natural history of gonorrhoea.

Performance of direct fluorescent antibody tests for routine diagnosis of Chlamydia trachomatis in Russian sexually transmitted disease clinics.

SUMMARY: Testing for Chlamydia trachomatis in Russia is usually done by microscopic examination of genital smears stained with fluorescent antibody provided in locally produced kits. The aim was to assess the sensitivity and specificity of such direct fluorescent antibody (DFA) tests compared with a nucleic acid amplification test (NAAT) (ligase chain reaction) to detect C. trachomatis in 171 cervical smears and 201 urethral smears from men. The patients were at high risk of chlamydial infection and had been recruited at three sexually transmitted disease clinics in Moscow. Among women, DFA test sensitivity was 6% (95% CI 0-14) and the specificity was 92% (95% CI 88-97). Among men, the sensitivity was 9% (95% CI 2-16) and the specificity was 90% (95% CI 83-94). Poor DFA test performance was probably due to poor antibody quality and such tests are not adequate for routine examination of populations with either low or high chlamydial prevalence. As there may remain a place for DFA testing where few patients are seen, the Russian Ministry of Health should enforce registration of diagnostic tests, and Russian manufacturers should seek ways of improving DFA test performance. However, the mainstay of testing should depend on NAATs.

David Arthur John Tyrrell CBE: 19 June 1925 - 2 May 2005.

David Tyrrell is remembered by physicians and scientists principally for his discovery of the common cold viruses and elucidation of their pathogenesis, but also for his work in various other areas, including influenza, bovine spongiform encephalopathy (BSE) and chronic fatigue syndrome (CFS). David possessed a deep humanity, honesty, perseverance and a vision of collaboration as a means of making discoveries that would contribute meaningfully to the alleviation of human suffering. He also had a warmth and a mischievous sense of humour that was frequently directed at bureaucracy, which he thoroughly disliked.

Relation between Gram-stain and clinical criteria for diagnosing bacterial vaginosis with special reference to Gram grade II evaluation.

The aim of this study was to analyse how the results of Gram-staining vaginal smears correlated with the clinical criteria for determining the existence of bacterial vaginosis (BV) and, in particular, how the category defined as 'intermediate' or Gram grade II did so and its significance. Women attending an antenatal clinic with an abnormal vaginal flora, that is those who had Gram-stains of grades II or III, the latter considered to equate with BV, were given clindamycin or a placebo intravaginally and examined again on up to three occasions. Gram-stain readings of grade III correlated with the clinical criteria for BV on 356 (91.7%) of 388 occasions. Grade II readings covered the spectrum of clinical criteria and correlated with those for BV on 35 (37.2%) of 94 occasions. Grade I, recorded 231 times and seen usually after clindamycin treatment, was associated with BV only once. The sensitivity, specificity, positive predictive value and negative predictive value of the Gram stain for the diagnosis of BV, based on a combination of grades II and III, were 99.7%, 71.6%, 81% and 99.6%, respectively; based on grade III only, the values were 99.7%, 87.7%, 91.6% and 99.6%, respectively. Women reported a malodorous vaginal discharge on 49.2% of the occasions a grade III flora was seen and 13.3% of the times grade II was recorded. It was not associated with grade I and would seem a useful adjunct to the accepted clinical criteria for diagnosing BV. Each of the clinical criteria was found in about equal proportions (87%-91%) for women whose Gram grade was III. For grade II, an increased discharge was noted most often (76.5%) and 'clue' cells least often (24.5%). A positive amine test was the most specific, being associated with <1% of grade I smears. Of women with grade III status, 91% reverted to grade I after treatment with clindamycin for three days. In contrast, of women with grade II status, 53% reverted to grade I, as did 47% of those who were given a placebo. The 'intermediate' (grade II) category is a Gram-stain diagnosis and not one that can be made clinically. It is important to recognize as a distinct entity not only because amalgamation with grade III diminishes the specificity and positive predictive value of the Gram-stain for diagnosing BV, but also because women of grade II status usually fail to respond to clindamycin treatment, whereas those of grade III do not.

Observations on experimental colonisation of mice by ureaplasmas of human origin.

Three serovars (5, 8 and 10) of Ureaplasma urealyticum were inoculated intravaginally into groups of oestradiol-treated young adult BALB/c strain mice. Hormone treatment was essential for vaginal colonisation. The proportion of mice colonised initially and the persistence of colonisation were different with the three serovars; half of those given serovar 8 were still colonised after 84 days. A strain of serovar 5 after a further 50 subcultures in vitro was a little less persistent than it was before such subculture, but not in a way to suggest that subculturing was the main reason for differences in the behaviour of the serovars. At autopsy of six mice that were still colonised vaginally 158 days after inoculation of serovar 8, spread to the upper genital tract was shown to have occurred in three of them and dissemination to the liver and kidney in one. Compared with immunocompetent mice of strain CB20, such dissemination was not a feature in genetically related mice with severe combined immunodeficiency. This is not in keeping with the situation in hypogammaglobulinaemic patients in whom ureaplasmas and other mycoplasmas are known to disseminate. However, differences in the proportion of immunocompetent mice colonised or in ureaplasmal persistence with different serovars may act as a marker for differences in human pathogenicity and is worthy of further study.

Do all men attending departments of genitourinary medicine need to be screened for non-gonococcal urethritis?

We investigated the influence of symptoms and signs on the detection of Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum organisms (ureaplasmas) in men with non-gonococcal urethritis (NGU). Two hundred and forty-two men attending the Jefferiss Wing at St Mary's Hospital for a sexual health assessment were evaluated, of whom 169 had NGU. Urethral inflammation was diagnosed if there were either > or =5 polymorphonuclear leucocytes (PMNLs) per high-power field (HPF) in five or more microscope fields of a Gram-stained urethral smear, or > or =10 PMNLs per HPF in five or more fields of a Gram-stained thread from 15-20 mL of a first-passed urine (FPU) specimen. C. trachomatis was diagnosed by direct immunofluoresence, M. genitalium by a polymerase chain reaction assay and ureaplasmas by culture. On multivariate analysis, to control for potential confounding by age, ethnicity, sexual lifestyle and co-infection, an urethral discharge remained significantly associated with the detection of C. trachomatis and M. genitalium in men with acute urethritis [OR 12.3, 95% CI (2.39-63.5) and OR 35.2, 95% CI (3.9-319.6), respectively], but dysuria or penile irritation did not. The detection of ureaplasmas was not associated with any clinical feature. In addition, on multivariate analysis men with NGU who were either symptomatic or had an observable discharge were more likely to have C. trachomatis or M. genitalium detected [(OR 6.92, 95% CI 1.41-33.9) and (OR 5.18, 95% CI 0.99-27.1), respectively], but not ureaplasmas (OR 1.19, 95% CI 0.33-4.35). The findings suggest that in men with acute NGU, symptoms or signs, and in particular a urethral discharge, are associated with the detection of C. trachomatis and M. genitalium, but not ureaplasmas. Currently, there is no precise answer to the question of whether all men attending a GUM clinic need to be screened for NGU, but if clinically asymptomatic NGU is found not to be associated with a sexually transmitted pathogen, the UK clinical guidelines requiring the preparation of a urethral smear from such men would need to be revised.

Chlamydia pneumoniae in infrequently examined blood vessels.

AIM: To determine the prevalence of Chlamydia pneumoniae DNA in infrequently examined blood vessels. METHODS: Vessels obtained from 15 men and six women at coronary artery bypass surgery were tested by a nested polymerase chain reaction (PCR) assay for C pneumoniae DNA. RESULTS: Chlamydia pneumoniae DNA was detected in four of six atheromatous ascending aorta specimens but in none of eight non-atheromatous aorta specimens, in six of 11 atheromatous internal mammary artery specimens but in none of seven non-atheromatous internal mammary artery specimens, in five of seven long saphenous vein specimens showing evidence of disease but in none of 12 specimens without evidence of disease, and in two of three previously grafted veins. Overall, C pneumoniae occurred significantly more often in diseased than in normal vessels (p = < 0.00001). CONCLUSIONS: Chlamydia pneumoniae is often present in diseased areas of arteries, including the internal mammary arteries, and even in diseased areas of veins. It is not present in apparently healthy areas of either type of vessel.

Qualitative and quantitative aspects of the ligase chain reaction assay for Chlamydia trachomatis in genital tract samples and urines.

The performance of the ligase chain reaction (LCR) assay for Chlamydia trachomatis was evaluated in a genitourinary medicine (GUM) clinic population. Its sensitivity was 100%, 91% and 95%, respectively, for cervical, vaginal and urine samples from 417 women, when compared with direct fluorescent antibody (DFA) staining of cervical samples, and 100% and 91%, respectively, for urethral and urine samples from 317 men, when compared with DFA staining of urethral smears. An enzyme immunoassay (EIA) was only 65% sensitive for cervical samples. Urethral swabs from a number of treated men remained LCR-positive when antigen was no longer detectable by DFA staining. An association between quantitative data from the LCR assay (i.e. the optical density of samples, measured in relation to internal controls and calibrators) and the antigen load of the samples, measured by DFA staining, indicated a lack of significant inhibition in the LCR assay in this study. This was probably due to freezing of the samples before testing. Diluting 20 LCR-positive urines with a range of antigen loads resulted in loss of positivity in 3, and a reduction in the signal in 13. The implications of the antigen load on the performance of detection assays for chlamydia-positive patients are discussed.

An association of disseminated Mycoplasma fermentans in HIV-1 positive patients with non-Hodgkin's lymphoma.

We examined the relationship between the haematogenous dissemination of Mycoplasma fermentans and non-Hodgkin's lymphoma (NHL) in 265 HIV-1 positive patients. A polymerase chain reaction (PCR) assay was used to detect M. fermentans in peripheral blood mononuclear cells (PBMCs) from 50 patients enrolled consecutively from an HIV outpatient clinic in 1991 (cohort 1), 56 patients with lower respiratory tract infection who underwent bronchoscopy in 1992 (cohort 2), and 159 patients who were enrolled into a natural history cohort study in 1994 (cohort 3). The incidence of NHL among the patients was determined in 1998. The PBMCs of 29 patients (10.9%) were positive for M. fermentans (8 in cohort 1, 13 in cohort 2 and 8 in cohort 3) and 11 patients (4.2%) developed NHL which was confirmed histologically (3 in cohort 1, 4 in cohort 2 and 4 in cohort 3). We found a statistically significant association between the presence of M. fermentans and the development of NHL in the combined cohort (risk ratio [RR]=6.78 [95% confidence interval (CI) 2.21--20.84], P=0.003 Fisher's exact test [FET]). This association remained significant even after adjustment in a multivariate analysis for CD4 cell count and HIV disease status at the time of M. fermentans testing (RR=7.97 [95% CI=2.16--29.47], P=0.002).

Disseminated Mycoplasma fermentans in AIDS patients: several case reports.

We describe the clinical course of 2 HIV-positive patients in whom Mycoplasma fermentans was disseminated and persistent. We identified individuals in whom M. fermentans had been detected in a peripheral blood mononuclear cell (PBMC) or bronchoalveolar lavage (BAL) specimen. Of this group a number had archival specimens of interest: liver and/or bone marrow, taken to investigate a systemic illness, and a few had M. fermentans positive tissues. Two patients, NC and DP, had recurrent episodes of lower respiratory tract infection and fever and both had been investigated by bronchoscopy on 4 occasions. M. fermentans was detected in specimens taken 18 and 27 months apart for NC and DP respectively, and in between, and repeatedly in respiratory tract tissues of DP. Granuloma were identified in the liver of NC that was M. fermentans positive but no further evidence of opportunistic infection was found during his illness. Both patients had M. fermentans positive bone marrow specimens. Assessment of the patients' records suggested that in one patient M. fermentans may have contributed to the respiratory disease and in the other to the systemic disease.