The koala (Phascolarctos cinereus) is recognised as a threatened wildlife species in various parts of Australia. A major contributing factor to the decline and long-term viability of affected ...populations is disease caused by the obligate intracellular bacteria, Chlamydia. Two chlamydial species infect the koala, Chlamydia pecorum and Chlamydia pneumoniae, and have been reported in nearly all mainland koala populations. Chlamydial infections of koalas are associated with ocular infections leading to blindness and genital tract infections linked to infertility, among other serious clinical manifestations. Diagnosis can be based on clinical presentation alone, however, it is complicated by the observation that many koala chlamydial infections occur with no overt signs of clinical disease. Instead, accurate diagnosis requires detailed clinical assessment and confirmatory testing by a range of PCR-based assays. Antibiotic treatment for koala chlamydial infection is possible, however, results on its success are mixed. A more practical solution for the protection of diseased populations is the application of a koala Chlamydia vaccine, with recent trials indicating promising results. Interestingly, molecular epidemiology studies of koala C. pecorum infections and recent comparative genomic analyses of koala C. pneumoniae have revealed potential differences in their origin that will have wider ramifications for our understanding of human chlamydial infections and host adaptation of the chlamydiae. This review summarises changes to the taxonomy of koala chlamydial infections and recent advances in our understanding of the epidemiology, diagnosis, treatment, control and evolution of Chlamydia infections in this iconic wildlife species.
Update of previous U.S. Preventive Services Task Force (USPSTF) recommendations on screening for chlamydia (2007) and gonorrhea (2005).
The USPSTF reviewed the evidence on screening for chlamydial ...and gonococcal infections in asymptomatic patients from studies published since its last reviews. The USPSTF also considered evidence from its previous recommendations and reviews.
This recommendation applies to all sexually active adolescents and adults, including pregnant women.
The USPSTF recommends screening for chlamydia in sexually active females aged 24 years or younger and in older women who are at increased risk for infection. (B recommendation) The USPSTF recommends screening for gonorrhea in sexually active females aged 24 years or younger and in older women who are at increased risk for infection. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for chlamydia and gonorrhea in men. (I statement).
Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large ...arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens.
Expedited partner therapy (EPT), the practice of treating the sex partners of persons with sexually transmitted infections without their medical evaluation, increases partner treatment and decreases ...gonorrhea and chlamydia reinfection rates. We conducted a stepped-wedge, community-level randomized trial to determine whether a public health intervention promoting EPT could increase its use and decrease chlamydia test positivity and gonorrhea incidence in women.
The trial randomly assigned local health jurisdictions (LHJs) in Washington State, US, into four study waves. Waves instituted the intervention in randomly assigned order at intervals of 6-8 mo. Of the state's 25 LHJs, 24 were eligible and 23 participated. Heterosexual individuals with gonorrhea or chlamydial infection were eligible for the intervention. The study made free patient-delivered partner therapy (PDPT) available to clinicians, and provided public health partner services based on clinician referral. The main study outcomes were chlamydia test positivity among women ages 14-25 y in 219 sentinel clinics, and incidence of reported gonorrhea in women, both measured at the community level. Receipt of PDPT from clinicians was evaluated among randomly selected patients. 23 and 22 LHJs provided data on gonorrhea and chlamydia outcomes, respectively. The intervention increased the percentage of persons receiving PDPT from clinicians (from 18% to 34%, p < 0.001) and the percentage receiving partner services (from 25% to 45%, p < 0.001). Chlamydia test positivity and gonorrhea incidence in women decreased over the study period, from 8.2% to 6.5% and from 59.6 to 26.4 per 100,000, respectively. After adjusting for temporal trends, the intervention was associated with an approximately 10% reduction in both chlamydia positivity and gonorrhea incidence, though the confidence bounds on these outcomes both crossed one (chlamydia positivity prevalence ratio = 0.89, 95% CI 0.77-1.04, p = 0.15; gonorrhea incidence rate ratio = 0.91, 95% CI .71-1.16, p = 0.45). Study findings were potentially limited by inadequate statistical power, by the institution of some aspects of the study intervention outside of the research randomization sequence, and by the fact that LHJs did not constitute truly isolated sexual networks.
A public health intervention promoting the use of free PDPT substantially increased its use and may have resulted in decreased chlamydial and gonococcal infections at the population level.
ClinicalTrials.gov NCT01665690.
This prospective study aimed to study the composition and structure of the vaginal microbiota prior to
infection.
A nested case-control study was performed in 122 women, half of which acquired
within ...a year after their first visit. At the first visit, the composition and structure of vaginal microbial communities were analysed using 16S rRNA sequencing in the context of the sociodemographic and sexual risk behaviour information using logistic regression.
Five vaginal community state types (CSTs) were identified. Four CSTs were dominated by
spp., of which
(37%) and
(33%) were the most common. One CST was characterised by the absence of
spp. (25%) and the presence of an array of strict and facultative anaerobes. Multivariate logistic regression analysis revealed that women with a
dominated CST had an increased risk of
infection (p=0.04; OR: 2.6, 95% CI 1.0 to 6.6).
The distribution of CSTs dominated by
spp. agreed with previous studies. However, the frequency of dysbiosis among Caucasian women was relatively high (24%). Having vaginal microbiota dominated by
was associated with an increased risk for
infection. Therefore, we hypothesise that specific signatures of vaginal microbiota are indicative of increased host predisposition to acquiring STIs.
ABSTRACT
Chlamydiae are pathogenic intracellular bacteria that cause a wide variety of diseases throughout the globe, affecting the eye, lung, coronary arteries and female genital tract. Rather than ...by direct cellular toxicity, Chlamydia infection generally causes pathology by inducing fibrosis and scarring that is largely mediated by host inflammation. While a robust immune response is required for clearance of the infection, certain elements of that immune response may also damage infected tissue, leading to, in the case of female genital infection, disease sequelae such as pelvic inflammatory disease, infertility and ectopic pregnancy. It has become increasingly clear that the components of the immune system that destroy bacteria and those that cause pathology only partially overlap. In the ongoing quest for a vaccine that prevents Chlamydia-induced disease, it is important to target mechanisms that can achieve protective immunity while preventing mechanisms that damage tissue. This review focuses on mouse models of genital Chlamydia infection and synthesizes recent studies to generate a comprehensive model for immunity in the murine female genital tract, clarifying the respective contributions of various branches of innate and adaptive immunity to both host protection and pathogenic genital scarring.
This review summarizes mouse model studies that significantly contributed to our current understanding of the protective and pathogenic immune responses taking place during genital Chlamydia infections.
Interferon (IFN)-inducible guanylate binding proteins (GBPs) mediate cell-autonomous host resistance to bacterial pathogens and promote inflammasome activation. The prevailing model postulates that ...these two GBP-controlled activities are directly linked through GBP-dependent vacuolar lysis. It was proposed that the rupture of pathogen-containing vacuoles (PVs) by GBPs destroyed the microbial refuge and simultaneously contaminated the host cell cytosol with microbial activators of inflammasomes. Here, we demonstrate that GBP-mediated host resistance and GBP-mediated inflammatory responses can be uncoupled. We show that PVs formed by the rodent pathogen Chlamydia muridarum, so-called inclusions, remain free of GBPs and that C. muridarum is impervious to GBP-mediated restrictions on bacterial growth. Although GBPs neither bind to C. muridarum inclusions nor restrict C. muridarum growth, we find that GBPs promote inflammasome activation in C. muridarum-infected macrophages. We demonstrate that C. muridarum infections induce GBP-dependent pyroptosis through both caspase-11-dependent noncanonical and caspase-1-dependent canonical inflammasomes. Among canonical inflammasomes, we find that C. muridarum and the human pathogen Chlamydia trachomatis activate not only NLRP3 but also AIM2. Our data show that GBPs support fast-kinetics processing and secretion of interleukin-1β (IL-1β) and IL-18 by the NLRP3 inflammasome but are dispensable for the secretion of the same cytokines at later times postinfection. Because IFN-γ fails to induce IL-1β transcription, GBP-dependent fast-kinetics inflammasome activation can drive the preferential processing of constitutively expressed IL-18 in IFN-γ-primed macrophages in the absence of prior Toll-like receptor stimulation. Together, our results reveal that GBPs control the kinetics of inflammasome activation and thereby shape macrophage responses to Chlamydia infections.
In emergency departments (EDs), diagnosis and treatment of Chlamydia trachomatis and Neisseria gonorrhoeae are challenging. We conducted a randomized clinical trial to assess rapid C trachomatis and ...N gonorrhoeae testing on overtreatment and undertreatment of women evaluated for C trachomatis and N gonorrhoeae.
Women undergoing pelvic examinations and C trachomatis and N gonorrhoeae testing (n=254) were randomized to control or rapid test groups. The control group received standard-of-care C trachomatis and N gonorrhoeae nucleic acid amplification tests of endocervical specimens, with 2- to 3-day turnaround times. For the rapid test group, clinicians collected an extra endocervical swab for GeneXpert C trachomatis and N gonorrhoeae rapid testing, in addition to the standard-of-care nucleic acid amplification test swab. Rapid results were immediately provided, and all patients were treated according to providers’ clinical judgment.
In the rapid test group, 7.9% of patients had positive test results for C trachomatis; 3.9% had positive test results for N gonorrhoeae. In the control standard-of-care group, 10.2% of patients had positive nucleic acid amplification test results for C trachomatis; 5.5% had positive results for N gonorrhoeae. Undertreatment for both C trachomatis and N gonorrhoeae in the ED was 0% for the rapid test group and 43.8% for the control standard-of-care group. Clinicians overtreated 46.5% of uninfected standard-of-care control patients for C trachomatis compared with 23.1% of uninfected rapid test patients. For patients uninfected with N gonorrhoeae, clinicians overtreated 46.7% of standard-of-care control patients compared with 25.4% of rapid test patients. The length of stay did not differ significantly between groups.
Rapid C trachomatis and N gonorrhoeae testing in the ED led to a significant reduction in overtreatment for women without infections compared with the standard-of-care control group. Additionally, in the rapid test group there was significant improvement in appropriate treatment for patients with infections.
ABSTRACT
The iconic Australian marsupial, the koala (Phascolarctos cinereus), has suffered dramatic population declines as a result of habitat loss and fragmentation, disease, vehicle collision ...mortality, dog attacks, bushfires and climate change. In 2012, koalas were officially declared vulnerable by the Australian government and listed as a threatened species. In response, research into diseases affecting koalas has expanded rapidly. The two major pathogens affecting koalas are Chlamydia pecorum, leading to chlamydial disease and koala retrovirus (KoRV). In the last eight years, these pathogens and their diseases have received focused study regarding their sources, genetics, prevalence, disease presentation and transmission. This has led to vast improvements in pathogen detection and treatment, including the ongoing development of vaccines for each as a management and control strategy. This review will summarize and highlight the important advances made in understanding and combating C. pecorum and KoRV in koalas, since they were declared a threatened species. With complementary advances having also been made from the koala genome sequence and in our understanding of the koala immune system, we are primed to make a significant positive impact on koala health into the future.
Recent advances in understanding the two major pathogens of koalas, Chlamydia pecorum and koala retrovirus (KoRV), have benefited both koala conservation and general chlamydial and retroviral research fields.
The natural history of chlamydia is variable and may include persisting asymptomatic infection, complications, or spontaneous resolution before treatment. Reinfection is common. We evaluated whether ...spontaneous resolution was associated with decreased reinfection in women returning for treatment of a positive chlamydia screening test. At enrollment, participants were tested for chlamydia, treated with azithromycin, and scheduled for a 6-month follow-up visit for repeat testing. Two hundred participants returned 1 to 12 months after treatment. Spontaneous resolution at enrollment was demonstrated in 44 (22.0%). Reinfection at follow-up occurred in 33 (16.5%), being more frequent in those with persisting infection at enrollment versus spontaneous resolution (31 of 156 19.9% vs 2 of 44 4.5%; P = .016). Adjusting for age, the odds of reinfection was 4 times higher for participants with persisting infection at enrollment (odds ratio 4.0, 95% confidence interval, 1.1—25.6; P = .034). Chlamydia treatment may attenuate protective immunity in some patients.
PDF
