Effects of Population Based Screening for Chlamydia Infections in The Netherlands Limited by Declining Participation Rates

Background

A large trial to investigate the effectiveness of population based screening for chlamydia infections was conducted in the Netherlands in 2008–2012. The trial was register based and consisted of four rounds of screening of women and men in the age groups 16–29 years in three regions in the Netherlands. Data were collected on participation rates and positivity rates per round. A modeling study was conducted to project screening effects for various screening strategies into the future.

Methods and Findings

We used a stochastic network simulation model incorporating partnership formation and dissolution, aging and a sexual life course perspective. Trends in baseline rates of chlamydia testing and treatment were used to describe the epidemiological situation before the start of the screening program. Data on participation rates was used to describe screening uptake in rural and urban areas. Simulations were used to project the effectiveness of screening on chlamydia prevalence for a time period of 10 years. In addition, we tested alternative screening strategies, such as including only women, targeting different age groups, and biennial screening. Screening reduced prevalence by about 1% in the first two screening rounds and leveled off after that. Extrapolating observed participation rates into the future indicated very low participation in the long run. Alternative strategies only marginally changed the effectiveness of screening. Higher participation rates as originally foreseen in the program would have succeeded in reducing chlamydia prevalence to very low levels in the long run.

Conclusions

Decreasing participation rates over time profoundly impact the effectiveness of population based screening for chlamydia infections. Using data from several consecutive rounds of screening in a simulation model enabled us to assess the future effectiveness of screening on prevalence. If participation rates cannot be kept at a sufficient level, the effectiveness of screening on prevalence will remain limited.     

Implementation of a Bundle of Care to Reduce Surgical Site Infections in Patients Undergoing Vascular Surgery

Background

Surgical site infections (SSI’s) are associated with severe morbidity, mortality and increased health care costs in vascular surgery.

Objective

To implement a bundle of care in vascular surgery and measure the effects on the overall and deep-SSI’s rates.

Design

Prospective, quasi-experimental, cohort study.

Methods

A prospective surveillance for SSI’s after vascular surgery was performed in the Amphia hospital in Breda, from 2009 through 2011. A bundle developed by the Dutch hospital patient safety program (DHPSP) was introduced in 2009. The elements of the bundle were (1) perioperative normothermia, (2) hair removal before surgery, (3) the use of perioperative antibiotic prophylaxis and (4) discipline in the operating room. Bundle compliance was measured every 3 months in a random sample of surgical procedures and this was used for feedback.

Results

Bundle compliance improved significantly from an average of 10% in 2009 to 60% in 2011. In total, 720 vascular procedures were performed during the study period and 75 (10.4%) SSI were observed. Deep SSI occurred in 25 (3.5%) patients. Patients with SSI’s (28,5±29.3 vs 10.8±11.3, p<0.001) and deep-SSI’s (48.3±39.4 vs 11.4±11.8, p<0.001) had a significantly longer length of hospital stay after surgery than patients without an infection. A significantly higher mortality was observed in patients who developed a deep SSI (Adjusted OR: 2.96, 95% confidence interval 1.32–6.63). Multivariate analysis showed a significant and independent decrease of the SSI-rate over time that paralleled the introduction of the bundle. The SSI-rate was 51% lower in 2011 compared to 2009.

Conclusion

The implementation of the bundle was associated with improved compliance over time and a 51% reduction of the SSI-rate in vascular procedures. The bundle did not require expensive or potentially harmful interventions and is therefore an important tool to improve patient safety and reduce SSI’s in patients undergoing vascular surgery.     

The Easiest Children to Reach Are Most Likely to Be Infected with Ocular Chlamydia trachomatis in Trachoma Endemic Areas of Niger

Background

Control programs for trachoma use mass antibiotic distributions to treat ocular Chlamydia trachomatis in an effort to eliminate this disease worldwide. To determine whether children infected with ocular Chlamydia are more likely to present later for examination than those who are uninfected, we compare the order of presentation for examination of children 0–5 years, and the presence of ocular Chlamydia by PCR in 4 villages in Niger where trachoma is endemic.

Methods

We conducted a cluster-randomized, controlled trial where 48 randomly selected villages in Niger are divided into 4 study arms of different mass treatment strategies. In a substudy of the main trial, we randomly selected 1 village from each of the 4 study arms (4 total villages) and we evaluated the odds of ocular Chlamydia versus the rank order of presentation for examination and laboratory assessment before treatment was offered.

Findings

We found the odds of harboring ocular Chlamydia dropped by more than 70% from the first child examined to the last child examined (OR 0.27, 95% CI 0.13–0.59, P = 0.001) in the 4 randomly selected villages. We found the odds of active trachoma dropped by 80% from the first child examined to the last child examined (OR 0.20, 95% CI 0.10–0.4, P<0.0001) in the 48 villages in the main trial.

Interpretation

This study demonstrates that even if the WHO recommended 80% treatment coverage is not reached in certain settings, children 0–5 years with the greatest probability of ocular Chlamydia have higher odds of receiving attention because they are the first to present. These results suggest there may be diminishing returns when using scarce resources to track down the last few children in a mass treatment program.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00792922","term_id":"NCT00792922"}}NCT00792922     

Wound Edge Protectors in Open Abdominal Surgery to Reduce Surgical Site Infections: A Systematic Review and Meta-Analysis

Importance

Surgical site infections remain one of the most frequent complications following abdominal surgery and cause substantial costs, morbidity and mortality.

Objective

To assess the effectiveness of wound edge protectors in open abdominal surgery in reducing surgical site infections.

Evidence Review

A systematic literature search was conducted according to a prespecified review protocol in a variety of data-bases combined with hand-searches for randomized controlled trials on wound edge protectors in patients undergoing laparotomy. A qualitative and quantitative analysis of included trials was conducted.

Findings

We identified 16 randomized controlled trials including 3695 patients investigating wound edge protectors published between 1972 and 2014. Critical appraisal uncovered a number of methodological flaws, predominantly in the older trials. Wound edge protectors significantly reduced the rate of surgical site infections (risk ratio 0.65; 95%CI, 0.51–0.83; p = 0.0007; I² = 52%). The results were robust in a number of sensitivity analyses. A similar effect size was found in the subgroup of patients undergoing colorectal surgery (risk ratio 0.65; 95%CI, 0.44–0.97; p = 0.04; I² = 56%). Of the two common types of wound protectors double ring devices were found to exhibit a greater protective effect (risk ratio 0.29; 95%CI, 0.15–0.55) than single-ring devices (risk ratio 0.71; 95%CI, 0.54–0.92), but this might largely be due to the lower quality of available data for double-ring devices. Exploratory subgroup analyses for the degree of contamination showed a larger protective effect in contaminated cases (0.44; 95%CI, 0.28–0.67; p = 0.0002, I² = 23%) than in clean-contaminated surgeries (0.72, 95%CI, 0.57–0.91; p = 0.005; I² = 46%) and a strong effect on the reduction of superficial surgical site infections (risk ratio 0.45; 95%CI, 0.24–0.82; p = 0.001; I² = 72%).

Conclusions and Relevance

Wound edge protectors significantly reduce the rate of surgical site infections in open abdominal surgery. Further trials are needed to explore their effectiveness in different risk constellations.     

Epizootic abortion related to infections by Chlamydophila abortus and Chlamydophila pecorum in water buffalo (Bubalus bubalis)

Water buffalo (Bubalus bubalis) are affected by high rates of embryonic mortality and abortion related to infectious diseases and non-infectious factors. A number of viral and bacterial infections have been associated with reproductive failure, but there is limited information on the role of chlamydial infections.

In order to investigate the presence and the role of Chlamydiaceae in water buffalo a retrospective study was performed in a herd with a history of reproductive failure. During an 11-month period, the pregnant heifers suffered an abortion rate of 36.8% between the 3rd and 7th month of pregnancy. Antibodies to Chlamydiaceae were detected in 57% of the aborted cows, and in 0% of the overtly healthy cows used as control. By a nested-PCR assay, three of 14 vaginal swabs from aborted animals tested positive for Chlamydophila agents and, additionally, three out of seven aborted fetuses tested positive for Chlamydophila spp., with two being co-infections by Cp. abortus and Cp. pecorum and one being characterised as Cp. abortus. Sequence analysis of the amplicons confirmed the results of the nested-PCR. The presence of anti-Chlamydiaceae antibodies in more than half of the aborting animals (P < 0.002) and the detection of Chlamydophila agents in several fetal organs and in the vaginal swabs are consistent with the history of abortions observed in the herd and suggest an abortifacient role by Chlamydophila spp. in water buffalo (B. Bubalis) herds.     

Using Fluorescent Proteins to Visualize and Quantitate Chlamydia Vacuole Growth Dynamics in Living Cells

The obligate intracellular bacterium Chlamydia elicits a great burden on global public health. C. trachomatis is the leading bacterial cause of sexually transmitted infection and also the primary cause of preventable blindness in the world. An essential determinant for successful infection of host cells by Chlamydia is the bacterium''s ability to manipulate host cell signaling from within a novel, vacuolar compartment called the inclusion. From within the inclusion, Chlamydia acquire nutrients required for their 2-3 day developmental growth, and they additionally secrete a panel of effector proteins onto the cytosolic face of the vacuole membrane and into the host cytosol. Gaps in our understanding of Chlamydia biology, however, present significant challenges for visualizing and analyzing this intracellular compartment. Recently, a reverse-imaging strategy for visualizing the inclusion using GFP expressing host cells was described. This approach rationally exploits the intrinsic impermeability of the inclusion membrane to large molecules such as GFP. In this work, we describe how GFP- or mCherry-expressing host cells are generated for subsequent visualization of chlamydial inclusions. Furthermore, this method is shown to effectively substitute for costly antibody-based enumeration methods, can be used in tandem with other fluorescent labels, such as GFP-expressing Chlamydia, and can be exploited to derive key quantitative data about inclusion membrane growth from a range of Chlamydia species and strains.     

A Regional Initiative to Reduce Skin Infections amongst Aboriginal Children Living in Remote Communities of the Northern Territory,Australia

Background

Linked to extreme rates of chronic heart and kidney disease, pyoderma is endemic amongst Aboriginal children in Australia''s Northern Territory (NT). Many of those with pyoderma will also have scabies. We report the results of a community-based collaboration within the East Arnhem Region, which aimed to reduce the prevalence of both skin infections in Aboriginal children.

Methodology/Principal Findings

Commencing September 2004, we conducted an ecological study that included active surveillance for skin infections amongst children aged <15 years in five remote East Arnhem communities over a three year period. Screening was undertaken by trained local community workers, usually accompanied by another project team member, using a standard data collection form. Skin infections were diagnosed clinically with the aid of a pictorial flip chart developed for the purpose. Topical 5% permethrin was provided for age-eligible children and all household contacts whenever scabies was diagnosed, whilst those with pyoderma were referred to the clinic for treatment in accordance with current guidelines. In addition, annual mass scabies treatment (5% permethrin cream) was offered to all community residents in accordance with current guidelines but was not directly observed. Pyoderma and scabies prevalence per month was determined from 6038 skin assessments conducted on 2329 children. Pyoderma prevalence dropped from 46.7% at baseline to a median of 32.4% (IQR 28.9%–41.0%) during the follow-up period – an absolute reduction of 14.7% (IQR 4.7%–16.8%). Compared to the first 18 months of observation, there was an absolute reduction in pyoderma prevalence of 18 cases per 100 children (95%CI −21.0, −16.1, p≤0.001) over the last 18 months. Treatment uptake increased over the same period (absolute difference 13.4%, 95%CI 3.3, 23.6). While scabies prevalence was unchanged, the prevalence of infected scabies (that is with superimposed pyoderma) decreased from 3.7% (95%CI 2.4, 4.9) to 1.5% (95%CI 0.7, 2.2), a relative reduction of 59%.

Conclusion

Although pyoderma prevalence remained unacceptably high, there was a substantial reduction overall with improvements in treatment uptake a critical factor. More acceptable alternatives, such as cotrimoxazole for pyoderma and ivermectin as a community-wide scabicide, warrant further investigation in these settings. We are encouraged by progress made through this work, where local action was led by local community members and primary health care providers with external training and support.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00884728","term_id":"NCT00884728"}}NCT00884728     

Increased Classical Endoplasmic Reticulum Stress Is Sufficient to Reduce Chondrocyte Proliferation Rate in the Growth Plate and Decrease Bone Growth

Mutations in genes encoding cartilage oligomeric matrix protein and matrilin-3 cause a spectrum of chondrodysplasias called multiple epiphyseal dysplasia (MED) and pseudoachondroplasia (PSACH). The majority of these diseases feature classical endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) as a result of misfolding of the mutant protein. However, the importance and the pathological contribution of ER stress in the disease pathogenesis are unknown. The aim of this study was to investigate the generic role of ER stress and the UPR in the pathogenesis of these diseases. A transgenic mouse line (ColIITg^cog) was generated using the collagen II promoter to drive expression of an ER stress-inducing protein (Tg^cog) in chondrocytes. The skeletal and histological phenotypes of these ColIITg^cog mice were characterised. The expression and intracellular retention of Tg^cog induced ER stress and activated the UPR as characterised by increased BiP expression, phosphorylation of eIF2α and spliced Xbp1. ColIITg^cog mice exhibited decreased long bone growth and decreased chondrocyte proliferation rate. However, there was no disruption of chondrocyte morphology or growth plate architecture and perturbations in apoptosis were not apparent. Our data demonstrate that the targeted induction of ER stress in chondrocytes was sufficient to reduce the rate of bone growth, a key clinical feature associated with MED and PSACH, in the absence of any growth plate dysplasia. This study establishes that classical ER stress is a pathogenic factor that contributes to the disease mechanism of MED and PSACH. However, not all the pathological features of MED and PSACH were recapitulated, suggesting that a combination of intra- and extra-cellular factors are likely to be responsible for the disease pathology as a whole.     

Changes of Exponential Growth Rates in Relation to Differentiation of Geotrichum candidum in Submerged Culture

Growth and differentiation of the imperfect fungus Geotrichum candidum were followed in submerged cultures containing a simple synthetic glucose salt medium. Uptake of glucose, ammonium and oxygen from the medium were measured during the entire growth perod. In 0.1% glucose the fungus grows with one exponential growth phase until all the glucose has been consumed. The arthrospores are formed in the stationary phase. In 0.5% glucose the growth curve has two exponential growth phases, one with a doubling time of 1.8 h and a second one with a doubling time of 4.9 h. The second exponential growth phase, which starts when less than 15% of the glucose and less than 30% of the ammonium have been consumed, is shown to be the sporulation phase. During this growth phase the oxygen saturation in the culture remained constant at about 50%.     

Estimating the Number of Persons Who Inject Drugs in the United States by Meta-Analysis to Calculate National Rates of HIV and Hepatitis C Virus Infections

Background

Injection drug use provides an efficient mechanism for transmitting bloodborne viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Effective targeting of resources for prevention of HIV and HCV infection among persons who inject drugs (PWID) is based on knowledge of the population size and disparity in disease burden among PWID. This study estimated the number of PWID in the United States to calculate rates of HIV and HCV infection.

Methods

We conducted meta-analysis using data from 4 national probability surveys that measured lifetime (3 surveys) or past-year (3 surveys) injection drug use to estimate the proportion of the United States population that has injected drugs. We then applied these proportions to census data to produce population size estimates. To estimate the disease burden among PWID by calculating rates of disease we used lifetime population size estimates of PWID as denominators and estimates of HIV and HCV infection from national HIV surveillance and survey data, respectively, as numerators. We calculated rates of HIV among PWID by gender-, age-, and race/ethnicity.

Results

Lifetime PWID comprised 2.6% (95% confidence interval: 1.8%–3.3%) of the U.S. population aged 13 years or older, representing approximately 6,612,488 PWID (range: 4,583,188–8,641,788) in 2011. The population estimate of past-year PWID was 0.30% (95% confidence interval: 0.19 %–0.41%) or 774,434 PWID (range: 494,605–1,054,263). Among lifetime PWID, the 2011 HIV diagnosis rate was 55 per 100,000 PWID; the rate of persons living with a diagnosis of HIV infection in 2010 was 2,147 per 100,000 PWID; and the 2011 HCV infection rate was 43,126 per 100,000 PWID.

Conclusion

Estimates of the number of PWID and disease rates among PWID are important for program planning and addressing health inequities.     

The Relative Growth Rates of Three Plankton Diatoms in Relation to Underwater Radiation and Temperature

Relative growth rates of three freshwater plankton diatoms-Asterionellaformosa, Fragilaria crotonensis, and Tabellaria flocculosa var.asterionelloides-are described from cultures suspended at variousdepths and during several seasons in the lake Windermere. Seasonalvariation in rates recorded near the surface (i m. depth) isinterpreted in terms of seasonal changes in temperature anddaylength. Rates recorded for Asterionella and Fragilaria aregenerally similar, but are approximately twice the rates obtainedwith Tabellaria. Depth profiles of relative growth rates areof similar form in all species, and normally show lightsaturationnear the surface. The shape of profiles for Asterionella isin good agreement with estimates of photosynthesis integratedover the growth periods. The parallelism between photosyntheticand relative growth rates of Asterionella is further illustratedfrom laboratory experiments: an approximate interconversion,under certain conditions, is given.     

Regulation of Bacterial Growth Rates by Dissolved Organic Carbon and Temperature in the Equatorial Pacific Ocean

Abstract The effect of dissolved organic matter (DOM) and temperature on bacterial production was examined in the equatorial Pacific Ocean. Addition of glucose, glucose plus ammonium, or free amino acids stimulated bacterial production ([³H]thymidine incorporation), whereas changes in bacterial abundance were either negligible or much less than changes in bacterial production. The average bacterial growth rate also greatly increased following DOM additions, whereas in contrast, addition of ammonium alone never affected production, bacterial abundance, or growth rates. Since the large glucose effect was not observed in previous studies of cold oceanic waters, several experiments were conducted to examine DOM-temperature interactions. These experiments suggest that bacteria respond more quickly and to a greater extent to DOM additions at higher temperatures, which may explain apparently conflicting results from previous studies. We also examined how temperate affects the kinetic parameters of sugar uptake. Maximum uptake rates (V_max) of glucose and mannose increased with temperature (Q₁₀= 2.4), although the half-saturation constant (K_m) was unaffected; K_m+ S was roughly equal to glucose concentrations (S) measured by a high pressure liquid chromographic technique. Bacterial production and growth rates appear to be limited by DOM in the equatorial Pacific, and thus bacterial production follows primary production over large spatial and temporal scales in this oceanic regime, as has been observed in other aquatic systems. Although temperature may not limit bacterial growth rates in the equatorial Pacific and similar warm waters, it could still affect how bacteria respond to changes in DOM supply and help set steady-state DOM concentrations. Received: 26 July 1995; Revised: 19 January 1996     

Measurement of Microbial Activity and Growth in the Ocean by Rates of Stable Ribonucleic Acid Synthesis

A relatively simple and extremely sensitive technique for measuring rates of stable ribonucleic acid (RNA) synthesis was devised and applied to bacterial cultures and seawater samples. The procedure is based upon the uptake and incorporation of exogenous radiolabeled adenine into cellular RNA. To calculate absolute rates of synthesis, measurements of the specific radioactivity of the intracellular adenosine 5′-triphosphate pools (precursor to RNA) and of the total amount of radioactivity incorporated into stable cellular RNA per unit time are required. Since the rate of RNA synthesis is positively correlated with growth rate, measurements of RNA synthesis should be extremely useful for estimating and comparing the productivities of microbial assemblages in nature. Adenosine 5′-triphosphate, adenylate energy charge, and rates of stable RNA synthesis have been measured at a station located in the Columbian Basin of the Caribbean Sea. A subsurface peak in RNA synthesis (and therefore growth) was located within the dissolved oxygen minimum zone (450 m), suggesting in situ microbiological utilization of dissolved molecular oxygen. Calculations of the specific rates of RNA synthesis (i.e., RNA synthesis per unit of biomass) revealed that the middepth maximum corresponded to the highest specific rate of growth (420 pmol of adenine incorporated into RNA·day⁻¹) of all depths sampled, including the euphotic zone. The existence of an intermediate depth zone of active microbial growth may be an important site for nutrient regeneration and may serve as a source of reduced carbon for mesopelagic and deep sea environments.     

Concurrent Rates of N2 Fixation, Nitrate and Ammonium Uptake by White Clover in Response to Growth at Different Root Temperatures

Nodulated white clover plants (Trifolium repens L. cv. Huia)were grown for 71 d in flowing nutrient solutions containingN as 10 mmol m_–3 NH₄NO₃, under artificial illumination,with shoots at 20/15°C day/night temperatures and root temperaturereduced decrementally from 20 to 5°C. Root temperatureswere then changed to 3, 7, 9, 11, 13, 17 or 25°C, and theacquisition of N by N₂ fixation, NH₄+ and NO₃^– uptakewas measured over 14 d. Shoot specific growth rates (d. wt)doubled with increasing temperature between 7 and 17°C,whilst root specific growth rates showed little response; shoot:root ratios increased with root temperature, and over time at11°C. Net uptake of total N per plant (N₂ fixation + NH₄++ NO₃^–) over 14 d increased three-fold between 3 and 17°C.The proportion contributed by N₂ fixation decreased with increasingtemperature from 51% at 5°C to 18% at 25°C. Uptake ofNH₄+ as a proportion of NH₄+ + NO₃^– uptake over 14 d variedlittle (55–62%) with root temperature between 3 and 25°C,although it increased with time at most temperatures. Mean ratesof total N uptake per unit shoot f. wt over 14 d changed littlebetween 9 and 25°C, but decreased progressively with temperaturebelow 9°C, due to the decline in the rates of NH₄+ and NO₃^–uptake, even though N₂ fixation increased. The results suggestthat N₂ fixation in the presence of sustained low concentrationsof NH₄+ and NO₄^– is less sensitive to low root temperaturethan are either NH₄+ or NO₃^– uptake systems. White clover, Trifolium repens L. cv. Huia, root temperature, nitrogen fixation, ammonium, nitrate