Participation, retention, and associated factors of women in a prospective multicenter study on Chlamydia trachomatis infections (FemCure).

Prospective studies are key study designs when attempting to unravel health mechanisms that are widely applicable. Understanding the internal validity of a prospective study is essential to judge a study's quality. Moreover, insights in possible sampling bias and the external validity of a prospective study are useful to judge the applicability of a study's findings. We evaluated participation, retention, and associated factors of women in a multicenter prospective cohort (FemCure) to understand the study's validity.Chlamydia trachomatis (CT) infected adult women, negative for HIV, syphilis, and Neisseria gonorrhoeae were eligible to be preselected and included at three sexually transmitted infection (STI) clinics in the Netherlands (2016-2017). The planned follow-up for participants was 3 months, with two weekly rectal and vaginal CT self-sampling and online questionnaires administered at home and at the clinic. We calculated the proportions of preselected, included, and retained (completed follow-up) women. Associations with non-preselection, noninclusion, and non-retention (called attrition) were assessed (logistic and Cox regression).Among the 4,916 women, 1,763 (35.9%) were preselected, of whom 560 (31.8%) were included. The study population had diverse baseline characteristics: study site, migration background, high education, and no STI history were associated with non-preselection and noninclusion. Retention was 76.3% (n = 427). Attrition was 10.71/100 person/month (95% confidence interval 9.97, 12.69) and was associated with young age and low education. In an outpatient clinical setting, it proved feasible to include and retain women in an intensive prospective cohort. External validity was limited as the study population was not representative (sampling bias), but this did not affect the internal validity. Selective attrition, however (potential selection bias), should be accounted for when interpreting the study results.

Therapeutic Impact of Initial Treatment for Chlamydia trachomatis Among Patients With Pelvic Inflammatory Disease: A Retrospective Cohort Study Using a National Inpatient Database in Japan.

BACKGROUND: Pelvic inflammatory disease (PID) is common among women of reproductive age and can be complicated by tuboovarian abscess (TOA), which is a serious and potentially life-threatening disease. However, recent mortality rates from PID on hospital admission and the short-term therapeutic usefulness of initial treatment for Chlamydia trachomatis remain unknown. METHODS: Using the Diagnosis Procedure Combination database, we identified patients who were diagnosed with PID on admission from July 2010 to March 2016 in Japan. We excluded patients who were pregnant, had cancer, or had missing data. Propensity score-adjusted analyses were performed to compare short-term outcomes between patients administered initial treatment for C. trachomatis and those without this treatment. The primary outcome was surgical intervention (laparotomy, laparoscopic surgery, and/or drainage procedure) during hospitalization. RESULTS: In total, 27841 eligible patients were identified. Of these patients, 2463 (8.8%) had TOA on admission. Mortality during hospitalization was 0.56% and 0.28% in the groups without and with TOA, respectively. Propensity score matching created 6149 pairs. A significant difference was observed in the primary outcome between those receiving initial treatment for C. trachomatis and the control group after propensity score matching (11.5% vs 13.4%; risk difference, -1.9%; 95% confidence interval, -3.1 to -0.7). The group that received initial treatment for C. trachomatis also had a significantly lower mortality rate. CONCLUSIONS: In this retrospective nationwide study, initial treatment for C. trachomatis among hospitalized patients diagnosed with PID had clinical benefits in terms of improved short-term outcomes.

T Cell-Independent Gamma Interferon and B Cells Cooperate To Prevent Mortality Associated with Disseminated Chlamydia muridarum Genital Tract Infection.

CD4 T cells and antibody are required for optimal acquired immunity to Chlamydia muridarum genital tract infection, and T cell-mediated gamma interferon (IFN-γ) production is necessary to clear infection in the absence of humoral immunity. However, the role of T cell-independent immune responses during primary infection remains unclear. We investigated this question by inoculating wild-type and immune-deficient mice with C. muridarum CM001, a clonal isolate capable of enhanced extragenital replication. Genital inoculation of wild-type mice resulted in transient dissemination to the lungs and spleen that then was rapidly cleared from these organs. However, CM001 genital infection proved lethal for STAT1-/- and IFNG-/- mice, in which IFN-γ signaling was absent, and for Rag1-/- mice, which lacked T and B cells and in which innate IFN-γ signaling was retained. In contrast, B cell-deficient muMT mice, which can generate a Th1 response, and T cell-deficient mice with intact B cell and innate IFN-γ signaling survived. These data collectively indicate that IFN-γ prevents lethal CM001 dissemination in the absence of T cells and suggests a B cell corequirement. Adoptive transfer of convalescent-phase immune serum but not naive IgM to Rag1-/- mice infected with CM001 significantly increased the survival time, while transfer of naive B cells completely rescued Rag1-/- mice from CM001 lethality. Protection was associated with a significant reduction in the lung chlamydial burden of genitally infected mice. These data reveal an important cooperation between T cell-independent B cell responses and innate IFN-γ in chlamydial host defense and suggest that interactions between T cell-independent antibody and IFN-γ are essential for limiting extragenital dissemination.

Chlamydia trachomatis Infection in Pregnancy: The Global Challenge of Preventing Adverse Pregnancy and Infant Outcomes in Sub-Saharan Africa and Asia.

Screening and treatment of sexually transmitted infections (STIs) in pregnancy represents an overlooked opportunity to improve the health outcomes of women and infants worldwide. Although Chlamydia trachomatis is the most common treatable bacterial STI, few countries have routine pregnancy screening and treatment programs. We reviewed the current literature surrounding Chlamydia trachomatis in pregnancy, particularly focusing on countries in sub-Saharan Africa and Asia. We discuss possible chlamydial adverse pregnancy and infant health outcomes (miscarriage, stillbirth, ectopic pregnancy, preterm birth, neonatal conjunctivitis, neonatal pneumonia, and other potential effects including HIV perinatal transmission) and review studies of chlamydial screening and treatment in pregnancy, while simultaneously highlighting research from resource-limited countries in sub-Saharan Africa and Asia.

Reporting detection of Chlamydia trachomatis DNA in tissues of neonatal death cases / Relato de detecção de DNA de Chlamydia trachomatis em tecidos de casos de óbito neonatal

OBJECTIVE: to determine whether C. trachomatis was present in neonates with infection, but without an isolated pathogen, who died during the first week of life. METHODS: early neonatal death cases whose causes of death had been previously adjudicated by the institutional mortality committee were randomly selected. End-point and real-time polymerase chain reaction of the C. trachomatis omp1 gene was used to blindly identify the presence of chlamydial DNA in the paraffinized samples of five organs (from authorized autopsies) of each of the dead neonates. Additionally, differential diagnoses were conducted by amplifying a fragment of the 16S rRNA of Mycoplasma spp. RESULTS: in five cases (35.7%), C. trachomatis DNA was found in one or more organs. Severe neonatal infection was present in three cases; one of them corresponded to genotype D of C. trachomatis. Interestingly, another case fulfilled the same criteria but had a positive polymerase chain reaction for Mycoplasma hominis, a pathogen known to produce sepsis in newborns. CONCLUSION: the use of molecular biology techniques in these cases of early infant mortality demonstrated that C. trachomatis could play a role in the development of severe infection and in early neonatal death, similarly to that observed with Mycoplasma hominis. Further study is required to determine the pathogenesis of this perinatal infection. .

OBJETIVO: determinar se a C. trachomatis está presente em neonatos com infecção, porém sem patógeno isolado, que morreram durante a primeira semana de vida. MÉTODOS: casos de óbito neonatal precoce cujas causas de óbito haviam sido anteriormente determinadas pelo Comitê de Mortalidade da instituição foram aleatoriamente selecionados. Foram utilizadas as reações em cadeia da polimerase convencional e em tempo real do gene omp1 da C. trachomatis, para identificar, às cegas, a presença de DNA de clamídia nas amostras desparafinizadas de cinco órgãos (de autópsias autorizadas) de cada um dos neonatos mortos. Além disso, foram realizados diagnósticos diferenciais por amplificação de um fragmento do rRNA 16S de Mycoplasma ssp. RESULTADOS: em cinco casos (35,7%) a presença de DNA de C. trachomatis foi detectada em um ou mais órgãos. Havia infecção neonatal grave em três casos; um deles correspondente ao genótipo D de C. trachomatis. Curiosamente, outro caso preencheu os mesmos critérios, porém possuía uma reação em cadeia da polimerase positiva para Mycoplasma hominis, um patógeno conhecido por causar sepse em recém-nascidos. CONCLUSÃO: a utilização de técnicas de biologia molecular nos casos de mortalidade infantil precoce mostrou que a C. trachomatis poderia desempenhar um papel no desenvolvimento de infecção grave e no óbito neonatal precoce semelhante ao observado com a Mycoplasma hominis. São necessários estudos adicionais para determinar a patogênese dessa infecção perinatal. .

Reporting detection of Chlamydia trachomatis DNA in tissues of neonatal death cases.

OBJECTIVE: to determine whether C. trachomatis was present in neonates with infection, but without an isolated pathogen, who died during the first week of life. METHODS: early neonatal death cases whose causes of death had been previously adjudicated by the institutional mortality committee were randomly selected. End-point and real-time polymerase chain reaction of the C. trachomatis omp1 gene was used to blindly identify the presence of chlamydial DNA in the paraffinized samples of five organs (from authorized autopsies) of each of the dead neonates. Additionally, differential diagnoses were conducted by amplifying a fragment of the 16S rRNA of Mycoplasma spp. RESULTS: in five cases (35.7%), C. trachomatis DNA was found in one or more organs. Severe neonatal infection was present in three cases; one of them corresponded to genotype D of C. trachomatis. Interestingly, another case fulfilled the same criteria but had a positive polymerase chain reaction for Mycoplasma hominis, a pathogen known to produce sepsis in newborns. CONCLUSION: the use of molecular biology techniques in these cases of early infant mortality demonstrated that C. trachomatis could play a role in the development of severe infection and in early neonatal death, similarly to that observed with Mycoplasma hominis. Further study is required to determine the pathogenesis of this perinatal infection.

A retrospective study of admission trends of koalas to a rehabilitation facility over 30 years.

To identify threats to the survival of koalas (Phascolarctos cinereus) in coastal New South Wales, Australia, we compared 3,781 admission records of koalas, admitted between 1 January 1975 and 31 December 2004 to a koala rehabilitation facility on the midnorthern coast of New South Wales, against local wild population demographics, with the use of multinomial logistic regression and chi-square analyses. Trauma, the most frequent reason for admission, affected young and male animals more frequently than other groups. Seasonal differences in the probability of males presenting as trauma cases suggest behavioral factors as an important risk factor for this group. An increasing probability of koalas presenting as a result of motor vehicle accident since 1985 strongly supports the enhanced action of local authorities to pursue traffic-calming strategies if urban koala populations are to be maintained in this area. Koalas with clinical signs of chlamydiosis made up the second most frequent admission group, and these animals were more likely to be aged. This study highlights the potential usefulness of wildlife rehabilitation centers in detailing threats to local wildlife populations, provided record keeping is efficient and focused, and the role of such studies in providing evidence for focusing threat-mitigation efforts. Continual community engagement by koala researchers is important to ensure that maximum benefit is obtained from activities of special interest groups.

Diagnosis, treatment and outcomes for koala chlamydiosis at a rehabilitation facility (1995-2005).

OBJECTIVE: To document the application of diagnostics and treatments at one rehabilitation facility over 10 years and their effects on recovery and post-release survival of 88 koalas treated for chlamydiosis, and to highlight associated wildlife care issues with potential significance to animal welfare and disease ecology. DESIGN: Using a retrospective analysis of medical records, we identified risk factors for successful release using a logistic regression model and descriptive statistics. PROCEDURE: We examined the clinical presentation, signalment, diagnostics, treatments, outcomes and whether released koalas were re-presented by the end of 2008 indicating post-release survival. RESULTS: Records of 88 koalas were included. Treatments and diagnostics were directed at the anatomical site displaying clinical signs. Younger age and use of ancillary treatments were associated with successful release. The type, route and duration of the treatments used were not those theorised to result in microbial cure. Despite this, approximately 50% of koalas were released and many survived in the wild for extended periods. CONCLUSIONS: Wildlife rehabilitators' records can guide research priorities and the development of care facilities and policies. This study identified the need for more accessible chlamydial diagnostic tests and veterinary support of carers, and the need for a more rigorous assessment of novel therapies. Current treatment regimens appear to be moderately successful in terms of clinical improvement, but it is unclear which aspects are responsible for the success or whether microbial cure is achieved. The long-term effect of released koalas on wild populations requires further study to assess its contribution to the conservation of koala populations.

Perinatal morbidity and mortality associated with chlamydial infection: a meta-analysis study

OBJECTIVE: To evaluate the effect of Chlamydia trachomatis infection during pregnancy on perinatal morbidity and mortality. METHODS: Systematic review and meta-analysis in an electronic database and manual, combining high sensitivity specific descriptors seeking to answer the research objective. The articles considered to be of high methodological quality (score above 6 on the Newcastle-Ottawa Scale) were assessed by meta-analysis. RESULTS: Summary estimates of 12 studies were calculated by means of Mantel-Haenszel test with 95 percent confidence interval. It was observed that Chlamydia infection during pregnancy increased risk of preterm labor (relative risk (RR) = 1.35 [1.11, 1.63]), low birth weight (RR = 1.52 [1.24, 1.87]) and perinatal mortality (RR = 1.84 [1.15, 2.94]). No evidence of increased risk was associated with Chlamydia infection in regard to premature rupture of membranes (RR = 1.13 [0.95, 1.34]), abortion and postpartum endometritis (RR = 1.20 [0.65, 2.20] and 0.89 [0.49, 1.61] respectively). CONCLUSION: The diagnosis and treatment of Chlamydia cervicitis during pregnancy can reduce perinatal morbidity and mortality associated with this infection. However, clinical trials are needed to confirm these findings.

Perinatal morbidity and mortality associated with chlamydial infection: a meta-analysis study.

OBJECTIVE: To evaluate the effect of Chlamydia trachomatis infection during pregnancy on perinatal morbidity and mortality. METHODS: Systematic review and meta-analysis in an electronic database and manual, combining high sensitivity specific descriptors seeking to answer the research objective. The articles considered to be of high methodological quality (score above 6 on the Newcastle-Ottawa Scale) were assessed by meta-analysis. RESULTS: Summary estimates of 12 studies were calculated by means of Mantel-Haenszel test with 95% confidence interval. It was observed that Chlamydia infection during pregnancy increased risk of preterm labor (relative risk (RR) = 1.35 [1.11, 1.63]), low birth weight (RR = 1.52 [1.24, 1.87]) and perinatal mortality (RR = 1.84 [1.15, 2.94]). No evidence of increased risk was associated with Chlamydia infection in regard to premature rupture of membranes (RR = 1.13 [0.95, 1.34]), abortion and postpartum endometritis (RR = 1.20 [0.65, 2.20] and 0.89 [0.49, 1.61] respectively). CONCLUSION: The diagnosis and treatment of Chlamydia cervicitis during pregnancy can reduce perinatal morbidity and mortality associated with this infection. However, clinical trials are needed to confirm these findings.

Stratification for confounding--part 1: the Mantel-Haenszel formula.

Stratification allows to control for confounding by creating two or more categories or subgroups in which the confounding variable either does not vary or does not vary very much. The Mantel-Haenszel formula is applied in cohort and in case-control studies to calculate an overall, unconfounded, effect estimate of a given exposure for a specific outcome by combining stratum-specific relative risks (RR) or odds ratios (OR). Stratum-specific RRs or ORs are calculated within each stratum of the confounding variable and compared with the corresponding effect estimates in the whole group (that is, with the unstratified RR or OR). The use of the Mantel-Haenszel formula presents some limitations: (1) if there is more than a single confounder, the application of this formula is laborious and demands a relatively large sample size, and (2) this method requires continuous confounders to be constrained into a limited number of categories thus potentially generating residual confounding (a phenomenon particularly relevant when the variable is categorized into few strata). In the stratified analysis, residual confounding can be minimized by increasing the number of strata, a possibility strictly dependent on sample size.

[Comparative efficiency of detection of the causative agent of urogenital chlamydiasis by immunofluorescence, polymerase chain reaction, and dot immunoassay].

The diagnostic efficiency of three diagnostic kits--two commercial (for direct immunofluorescent test (DIFT) and polymerase chain reaction (PCR) and one predeveloped experimental dot-ELISA--was compared. For this, specimens (cervical or urethral scrapes) from 225 patients with suspected or verified urogenital chlamydiasis were analyzed. Dot-ELISA was shown to have a higher sensitivity and a higher specificity than both commercial kits. The coincidence of positive and negative results of dot-ELISA with DIFT and PCR was 98.6 +/- 1.4 and 100%, respectively. In addition, dot-ELISA on the "Amersham" membrane could detect cases of the disease by 7 and 1.2 times, as compared with PCR and DIFT, respectively. The prospects of the dot-ELISA kit for the rapid, simple, and cheap diagnosis of urogenital chlamydiasis are discussed.

Chlamydia pneumoniae serology in donors and recipients and the risk of bronchiolitis obliterans syndrome after lung transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a common late complication in lung transplant recipients (LTR). Chlamydia pneumoniae (C. pneumoniae) is a common but difficult to diagnose respiratory pathogen with a propensity to latency. METHODS: We studied the impact of C. pneumoniae on BOS development using donor-recipient serology obtained before transplantation in a cohort of 76 LTR. RESULTS: BOS was present in 29.9% patients (mean follow-up 866 days). High donor C. pneumoniae immunoglobulin (Ig)G titers were associated with BOS in the recipient (area under the curve [AUC] 0.71, 95% confidence interval [CI] 0.52-0.91, P=0.027), whereas high recipient titers were inversely associated with BOS (AUC 0.27, 95% CI 0.11-0.44, P=0.018). The risk of developing BOS was 75.0% in the case of a primary seromismatch for C. pneumoniae (D+/R-), whereas a reverse mismatch had a risk of 4.6% (likelihood ratio 9.8, P=0.02). In a multivariate model that included human leukocyte antigen matching, acute rejection and cytomegalovirus pneumonitis, C. pneumoniae IgG donor 32 or greater and C. pneumoniae IgG recipient 32 or greater remained positive and negative independent risk factors, respectively, for BOS in LTR. In the freedom from BOS analysis, BOS occurred more frequently and earlier in C. pneumoniae seropositive donors, and the reverse was true in seronegative recipients. CONCLUSION: C. pneumoniae serology in donor and recipient is associated with the development of BOS in LTR.

Chlamydia pneumoniae and atherosclerosis following carotid endarterectomy.

BACKGROUND: Seroepidemiological studies have shown an association between raised antibody titres against Chlamydia pneumoniae, and carotid atherosclerosis or stroke. However, direct evidence for a causal link between arterial infection with C. pneumoniae and carotid disease remains weak. We hypothesized that long-term follow-up of patients with pathologically-proven arterial C. pneumoniae infection might provide further insight into the role of C. pneumoniae in carotid atherosclerosis. METHODS: We followed a cohort of 70 carotid endarterectomy patients for ipsilateral restenosis, contralateral progression, and all-cause mortality (four year median follow-up period). All patients had presence or absence of C. pneumoniae in their carotid plaques documented by immunohistochemistry after endarterectomy. A survival function was generated and the log-rank test was used to assess the difference in survival between subjects with and without documented chlamydial infection in their plaque. RESULTS: Baseline demographic and cardiovascular risk factors were similar between the two groups, and survival analysis demonstrated no difference (p>0.05) in all-cause mortality, or all-cause mortality combined with restenosis and progression. CONCLUSIONS: Our data finds no causal role for C. pneumoniae in restenosis or progression of carotid disease or mortality in this patient population with advanced carotid atherosclerosis.

[Establishment and experimental study on mouse model of Chlamydia pneumoniae pneumonitis].

OBJECTIVE: To evaluate mice as experimental animals for Chlamydia pneumoniae (C. Pneumoniae) infection and investigate the pathogenesis of C. pneumoniae pneumonitis. METHODS: The Icr mice were inoculated with C. pneumoniae, strain CWL-029, by the intranasal or intravenous routes. After a single inoculation, mice were killed on the 1st, 3rd, 7th, 15th, 21th, 28th and 60th day separately. The pathological changes of lung tissue were analyzed. RESULTS: The Icr mice were shown to be susceptible to C. pneumoniae. Inoculation of mice with C. pneumoniae induced a prolonged course of lung infection, as demonstrated by persistence of lung pathology (60 days). In the intranasal inoculation of mice, the lung pathology was characterized by patchy interstitial pneumonitis with predominately neutrophil leukocyte infiltration in the early(7 days) and lyphocytes infiltration in the later stages(14 days later) of infection. After i.v. inoculation, a similarly interstitial pneumonitis was seen, but it was milder and more patchy, especially in the early stage. C. pneumoniae DNA was detected by polymerase chain reaction(PCR) intermittently in the lung tissue. Inoculated mice developed serum IgG antibody responses. CONCLUSIONS: The Icr mice were shown to be susceptible to C. pneumoniae and the pulmonary infection was characterized by interstitial pneumonitis, especially in mice of intranasal inoculation.

Chlamydia pneumoniae serology, lung function decline, and treatment for respiratory disease.

Associations have been reported between Chlamydia pneumoniae seropositivity and both acute and chronic obstructive airway diseases. Plasma specimens collected between 1979 and 1983 from 1, 773 men 45 to 59 yr of age in Caerphilly, South Wales, were tested for IgG and IgA antibodies to C. pneumoniae (TW183) by microimmunofluorescence. Subsequent mortality and medication for obstructive airway disease were ascertained at 5-yr follow-up examinations. Spirometry was performed at the first and second examinations and analyzed both cross-sectionally and longitudinally; 642 men (36%) had IgG antibodies at a titer of 1:16 or above, of whom 362 also had detectable IgA antibodies. No statistically significant associations were found between either IgG titer or IgA titer and any of the outcome measures: inhaler therapy at entry; commencement of inhalers during follow-up; death from respiratory causes; baseline FEV(1), FVC, and FEV(1)/FVC ratio; and decline in FEV(1) (p > 0.1 throughout). Men with high IgG titers (>/= 1:64) had a slower rate of decline of FEV(1) than did seronegative subjects (adjusted mean difference in 5-yr change in FEV(1): +22 ml, 95% confidence interval: -31 ml to +76 ml). Men with high IgA titers (>/= 1:16) had a slightly faster rate of decline (-12 ml, - 96 ml to +71 ml). This first prospective assessment suggests that chronic C. pneumoniae infection is not a major risk factor for progressive airflow obstruction.

Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study.

OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.