There is uncertainty around whether the risks of pelvic inflammatory disease (PID) differ following Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoeae (gonorrhea) infection. We quantified ...the risk of PID associated with chlamydia and gonorrhea infection and subsequent repeat infections in a whole-population cohort.
A cohort of 315123 Western Australian women, born during 1974-1995, was probabilistically linked to chlamydia and gonorrhea testing records and to hospitalizations and emergency department presentations for PID from 2002 to 2013. Time-updated survival analysis was used to investigate the association between chlamydia and gonorrhea testing, and positivity, and risk of PID.
Over 3199135 person-years, 120748 women had pathology test records for both chlamydia and gonorrhea, 10745 chlamydia only, and 653 gonorrhea only. Among those tested, 16778 (12.8%) had ≥1 positive chlamydia test, 3195 (2.6%) ≥1 positive gonorrhea test, and 1874 (1.6%) were positive for both. There were 4819 PID presentations (2222 hospitalizations, 2597 emergency presentations). Adjusting for age, Aboriginality, year of follow-up, health area, and socioeconomic status, compared to women negative for chlamydia and gonorrhea, the relative risk (adjusted incidence rate ratio) of PID was 4.29 (95% confidence interval CI, 3.66-5.03) in women who were both chlamydia and gonorrhea positive; 4.54 (95% CI, 3.87-5.33) in those only gonorrhea positive; and 1.77 (95% CI, 1.61-1.94) in those only chlamydia positive.
Gonorrhea infection conferred a substantially higher risk than chlamydia of hospitalization or emergency department presentation for PID. The emergence of gonorrhea antimicrobial resistance may have a serious impact on rates of PID and its associated reproductive health sequelae.
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BFBNIB, NUK, PNG, UL, UM, UPUK
Abstract
SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a ...fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.
Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.
LP ...was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm(3) or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio aOR 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio aIRR 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43).
LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chlamydia trachomatis is one of the most commonly diagnosed sexually transmitted infections worldwide, but reports in the medical literature of an association between genital chlamydia infection and ...adverse obstetric outcomes are inconsistent.
The Western Australia Data Linkage Branch created a cohort of women of reproductive age by linking records of birth registrations with the electoral roll for women in Western Australia who were born from 1974 to 1995. The cohort was then linked to both chlamydia testing records and the state perinatal registry for data on preterm births and other adverse obstetric outcomes. We determined associations between chlamydia testing, test positivity, and adverse obstetric outcomes using multivariate logistic regression analyses.
From 2001 to 2012, 101 558 women aged 15 to 38 years had a singleton birth. Of these women, 3921 (3·9%) had a spontaneous preterm birth, 9762 (9·6% of 101 371 women with available data) had a baby who was small for gestational age, and 682 (0·7%) had a stillbirth. During their pregnancy, 21 267 (20·9%) of these women had at least one chlamydia test record, and 1365 (6·4%) of those tested were positive. Before pregnancy, 19 157 (18·9%) of these women were tested for chlamydia, of whom 1595 (8·3%) tested positive for chlamydia. Among all women with a test record, after adjusting for age, ethnicity, maternal smoking, and history of other infections, we found no significant association between a positive test for chlamydia and spontaneous preterm birth (adjusted odds ratio 1·08 95% CI 0·91–1·28; p=0·37), a baby who was small for gestational age (0·95 0·85–1·07; p=0·39), or stillbirth (0·93 0·61–1·42; p=0·74).
A genital chlamydia infection that is diagnosed and, presumably, treated either during or before pregnancy does not substantially increase a woman's risk of having a spontaneous preterm birth, having a baby who is small for gestational age, or having a stillbirth.
Australian National Health and Medical Research Council.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals ...presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% 95% CI: 1.42-2.34; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
T-cell receptor (TCR) γδ cells are perceived as innate-like effector cells with the possibility of mediating graft-vs. -tumor (GVT) without causing graft-vs.-host disease (GVHD) in the setting of ...hematopoietic allogeneic stem cell transplantation (HSCT). We conducted a prospective study to assess the clinical impact of TCR γδ cell immune reconstitution on overall survival, relapse-free-survival, relapse and GVHD. The impact of CD3, CD4, and CD8 T cells together with NK cells including subtypes were analyzed in parallel. A total of 108 patients with hematological malignancies transplanted with HLA-matched, T cell replete stem cell grafts were included for analyses of absolute concentrations of CD3, CD4, and CD8 positive T cells and NK cells together with a multi-color flow cytometry panel with staining for TCRαβ, TCRγδ, Vδ1, Vδ2, CD3, CD4, CD8, HLA-DR, CD196, CD45RO, CD45RA, CD16, CD56, CD337, and CD314 at 28, 56, 91, 180, and 365 days after transplantation. Immune reconstitution data including subsets and differentiation markers of T and NK cells during the first year after transplantation was provided. Patients with TCR γδ cell concentrations above the median value of 21 (0-416) × 10
cells/L 56 days after transplantation had significantly improved overall survival (
= 0.001) and relapse-free survival (
= 0.007) compared to patients with concentrations below this value. When day 56 cell subset concentrations were included as continuous variables, TCR γδ cells were the only T cell subsets with a significant impact on OS and RFS; the impact of TCR γδ cells remained statistically significant in multivariate analyses adjusted for pre-transplant risk factors. The risk of death from relapse was significantly decreased in patients with high concentrations of TCR γδ cells 56 days after transplantation (
= 0.003). Also, the risk of acute GVHD was significantly lower in patients with day 28 TCR γδ cell concentrations above the median of 18 × 10
cells/L compared to patients with low concentrations (
= 0.01). These results suggest a protective role of TCR γδ cells in relapse and GVHD and encourage further research in developing adaptive TCR γδ cell therapy for improving outcomes after HSCT.
Traumatic brain injury (TBI) may be a risk factor for criminal behaviour however multiple factors potentially confound the association.
Record linkage and Cox proportional hazards regression analyses ...were used to examine the association between hospital-recorded TBI (n = 7,694) and subsequent first criminal conviction in a retrospective cohort matched 1:3 with 22,905 unaffected community controls and full-sibling controls (n = 2,397). Aboriginality, substance abuse, social disadvantage, and mental illness were included in analyses as potential confounders.
In multivariable models, relative to general population controls, TBI was associated with any conviction (males: Hazard Ratio (HR) = 1.58 (95% CI 1.46 to 1.72); females: HR = 1.52 (95% CI 1.28 to 1.81)); and similar Hazard Ratios were obtained for the sibling analyses in males (HR = 1.68 (95% CI 1.31-2.18)) and females (HR 1.27 (95% CI 0.71-2.29)). TBI was also associated with violent convictions relative to the general population, (males: HR = 1.65 (95% CI 1.42 to 1.92); females HR = 1.73 (95% CI 1.21 to 2.47)), and in analyses with sibling controls in men (HR = 1.89 (95% CI 1.20-3.00)), but not in women (HR 0.73, 95% CI 0.29-1.81)).
The results support a modest causal link between TBI and criminality after comprehensive adjustment for confounding. Reducing the rate of TBI, a major public health imperative, might have benefits in terms of crime reduction.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Monitoring specific underlying causes of death in solid organ transplant (SOT) recipients is important in order to identify emerging trends and health challenges. This retrospective cohort study ...includes all SOT recipients transplanted at Rigshospitalet between January 1st, 2010 and December 31st, 2019. The underlying cause of death was determined using the newly developed Classification of Death Causes after Transplantation (CLASS) method. Cox regression analyses assessed risk factors for all-cause and cause-specific mortality. Of the 1774 SOT recipients included, 299 patients died during a total of 7511 person-years of follow-up (PYFU) with cancer (N = 57, 19%), graft rejection (N = 55, 18%) and infections (N = 52, 17%) being the most frequent causes of death. We observed a lower risk of all-cause death with increasing transplant calendar year (HR 0.91, 95% CI 0.86–0.96 per 1-year increase), alongside death from graft rejection (HR 0.84 per year, 95% CI 0.74–0.95) and death from infections (HR 0.86 per year, 95% CI 0.77–0.97). Further, there was a trend towards lower cumulative incidence of death from cardiovascular disease, graft failure and cancer in more recent years, while death from other organ specific and non-organ specific causes did not decrease. All-cause mortality among SOT recipients has decreased over the past decade, mainly due to a decrease in graft rejection- and infection-related deaths. Conversely, deaths from a broad range of other causes have remained unchanged, suggesting that cause of death among SOT recipients is increasingly diverse and warrants a multidisciplinary effort and attention in the future.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Indonesia has had low uptake of HIV testing and treatment. We did a study to estimate the cascade of HIV care in key populations and identify predictors of outcomes at key cascade steps.
We used an ...observational cohort study design to recruit and follow up men who have sex with men (MSM), female sex workers, transgender women (known as waria in Indonesia), and people who inject drugs (PWID) diagnosed with HIV in four locations in Indonesia: Bali, Bandung, Jakarta, and Yogyakarta. Recruitment, baseline, and follow-up visits were done at collaborating clinical services, including both primary care sites and hospitals. Inclusion criteria for participants included identifying as a member of a key population, age 16 years or older, not previously tested positive for HIV, and HIV positivity at baseline. All participants were offered treatment as per national guidelines, with the addition of viral load testing and completion of study-specific forms. Estimates were calculated of proportions of participants linked to care, commencing treatment, adherent to treatment, and who achieved virological suppression. We used logistic regression to investigate characteristics associated with antiretroviral therapy (ART) initiation and viral suppression and Cox regression to identify factors associated with loss to follow-up. This study is registered with ClinicalTrials.gov, NCT03429842.
Between Sept 15, 2015, and Sept 30, 2016, 831 individuals were enrolled in the study, comprising 637 (77%) MSM, 116 (14%) female sex workers, 27 (3%) waria, and 51 (6%) PWID. Of those enrolled, 703 (84·6%, 95% CI 82·1-87·1) were linked to HIV care and 606 (86·2%, 83·7-88·8) who were linked with care started ART. Among participants who started treatment, 457 (75·4%, 71·8-78·9) were retained in care, of whom 325 (71·1%, 66·7-75·2) had a viral load test about 6 months after enrolment, with 294 (90·5%, 86·7-93·4) of those tested (294 35%, 32·1-38·7 of the original cohort) virally suppressed. 146 (24%) of 606 who started treatment were lost to follow-up. People who enrolled at sites that offered both testing and treatment had a higher likelihood of treatment initiation than those who enrolled at sites offering testing only (p<0·0001 by multivariate analysis), and participants who had been linked to care and had a high school or university education were significantly more likely to achieve viral suppression than those with a primary school or lower level of education (p≤0·029 by mulivariate analysis).
HIV cascade data among key populations in Indonesia show very poor rates of retention in treatment and viral suppression. Site and individual characteristics associated with initiating and continuing treatment suggest an urgent need to develop and implement effective interventions to support patients in achieving viral suppression among all people with HIV.
Australian Government Department of Foreign Affairs and Trade, WHO, and Indonesian Government.
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