Understanding tuberculosis epidemiology using structured statistical models

Molecular epidemiological studies can provide novel insights into the transmission of infectious diseases such as tuberculosis. Typically, risk factors for transmission are identified using traditional hypothesis-driven statistical methods such as logistic regression. However, limitations become apparent in these approaches as the scope of these studies expand to include additional epidemiological and bacterial genomic data. Here we examine the use of Bayesian models to analyze tuberculosis epidemiology. We begin by exploring the use of Bayesian networks (BNs) to identify the distribution of tuberculosis patient attributes (including demographic and clinical attributes). Using existing algorithms for constructing BNs from observational data, we learned a BN from data about tuberculosis patients collected in San Francisco from 1991 to 1999. We verified that the resulting probabilistic models did in fact capture known statistical relationships. Next, we examine the use of newly introduced methods for representing and automatically constructing probabilistic models in structured domains. We use statistical relational models (SRMs) to model distributions over relational domains. SRMs are ideally suited to richly structured epidemiological data. We use a data-driven method to construct a statistical relational model directly from data stored in a relational database. The resulting model reveals the relationships between variables in the data and describes their distribution. We applied this procedure to the data on tuberculosis patients in San Francisco from 1991 to 1999, their Mycobacterium tuberculosis strains, and data on contact investigations. The resulting statistical relational model corroborated previously reported findings and revealed several novel associations. These models illustrate the potential for this approach to reveal relationships within richly structured data that may not be apparent using conventional statistical approaches. We show that Bayesian methods, in particular statistical relational models, are an important tool for understanding infectious disease epidemiology.     

Ixodes ricinus density, and distribution and prevalence of Borrelia burgdorferi sensu lato infection along an altitudinal gradient

In this study, we measured the phenology of Ixodes ricinus ticks and their infection with Borrelia burgdorferi sensu lato (sl) simultaneously along an altitudinal gradient to assess the impact of climate on the phenology of ticks and on their infection with B. burgdorferi sl. From 1999 to 2001, free-living I. ricinus ticks were collected monthly by flagging vegetation at three different altitudes (620, 740, and 900 m above sea level) on the slope of a mountain in Chaumont (Neuchatel, Switzerland). I. ricinus ticks were examined for the presence of B. burgdorferi sl by using direct fluorescent antibody assay and isolation of spirochetes. Borrelia species were characterized by polymerase chain reaction followed by restriction fragment-length polymorphism. Tick density and tick phenology varied with altitude. Although the peak tick density decreased and the onset of ticks was delayed with altitude, the phenology was much more stable among years at the highest altitudes than at the lowest. The prevalence of B. burgdorferi infection in nymphs and adults decreased with altitude. The prevalence of infection differed significantly among years, and it was significantly higher in adults (30%) than in nymphs (21%). B. burgdorferi infection in adults was positively related with adult density, but this was not observed for nymphs. Five B. burgdorferi sl genospecies were successfully isolated: B. garinii, B. burgdorferi sensu stricto, B. afzelii, B. valaisiana, and B. lusitaniae. Mixed infections were obtained from five of 140 infected ticks. The greatest diversity in Borrelia species was observed at the lowest altitude where all five Borrelia species were present, whereas at the two highest altitudes, B. lusitaniae was not observed.     

Immigrant status, antenatal depressive symptoms, and frequency and source of violence: what's the relationship?

This study describes the prevalence of violence during pregnancy and examines the association between the experience of violence since the beginning of pregnancy and the prevalence of antenatal depressive symptoms while taking into account immigrant status. Cross-sectional study including 5,162 pregnant women attending Montreal hospitals for antenatal care was conducted, with 1,400 being born outside of Canada. CES-D scale was used to evaluate depression at 24-26?weeks of pregnancy. The Abuse Assessment Screen scale was used to determine the frequency and severity of violence since the beginning of pregnancy. Relationship with abuser was also considered. All modeling was done using logistic regressions. Threats were the most frequent type of violence, with 63?% happening more than once. Long-term immigrant women reported the highest prevalence of all types of violence (7.7?%). Intimate partner violence (IPV) (15?%) was most frequently reported among the poorest pregnant women. Strong associations exist between more than one episode of abuse and depression (POR?=?5.21 [3.73; 7.23], and IPV and depression [POR?=?5.81 [4.19; 8.08]. Immigrant status did not change the associations between violence and depression. Violence against pregnant women is not rare in Canada, and it is associated with antenatal depressive symptoms. These findings support future development of perinatal screening for violence, follow-up, and a culturally sensitive referral system.     

Clostridium difficile infection after allogeneic hematopoietic stem cell transplantation: incidence, risk factors, and outcome

Clostridium difficile (C. difficile) infection was observed in 13% of recipients after hematopoietic stem cell transplantation (HSCT), mainly in the first month posttransplantation. Risk factors were cord blood as the source of stem cells, acute graft-versus-host disease (GVHD), and total body irradiation (TBI). No association was found with an increased risk of mortality. The purpose of this study was to evaluate the incidence, risk factors, and outcome of C. difficile infection (CDI) after HSCT. We conducted a single-center, retrospective, cohort study on all patients who received an allogeneic HSCT from January 2004 to December 2007. All patients with diarrhea in the first year after HSCT were tested for the presence of C. difficile in stools. Among the 407 assessable patients, 53 presented at least 1 CDI in the first year post-HSCT. The total incidence rate?was 5.6 cases of CDI per 10,000 patient-days. Fifty percent of cases were diagnosed in the first month after HSCT, and 95% occurred during the first 6 months. Fewer than 5% of patients with CDI had severe diarrhea and severe complications were never observed. TBI in the conditioning regimen, cord blood as the source of stem cells, and acute graft-versus-host disease (aGVHD) were independently associated with CDI. Six patients (11%) had a recurrence of CDI. Four patients required second-line treatment with vancomycin. With a median follow-up of 22 months, the 2-year overall survival rates were similar between patients who presented a CDI and those who did not. CDI was observed in approximately 13% of recipients after HSCT, mainly in the first month posttransplantation and was associated with CB, aGVHD, and TBI. CDI was not associated either with severe complications or with an increased risk of mortality in this large cohort of patients.     

Functional polymorphisms in the LTF gene and risk of coronary artery stenosis

Plasma lactoferrin concentrations are increased in patients with coronary artery stenosis. We investigated the effects of LTF gene polymorphisms in 305 healthy blood donors and their associations with coronary artery stenosis in 236 patients admitted for coronary angiography. Lactoferrin concentrations were determined by enzyme immunoassay. Genotyping was performed by polymerase chain reaction and DNA sequencing of LTF exons 2 and 4. In the blood donors, the deletion variant of rs10662431 and the G allele of rs1126478 were associated with higher plasma lactoferrin concentrations. The G allele of rs1126478 was more frequent in patients with significant coronary artery stenosis (p = 0.018, p value limit for significance by permutation = 0.030). The association remained significant in logistic regression with adjustment for clinical risk factors (odds ratio 2.485 [95% confidence interval 1.116-5.536], p = 0.026), but was weakened upon the inclusion of plasma lactoferrin (odds ratio 2.295 [0.949-5.550], p = 0.064). Current evidence indicates that rs1126478 affects the antibacterial effect of lactoferrin and that lactoferrin is involved in lipid metabolism. The relationships among lactoferrin genotypes, lactoferrin concentrations, and clinical factors on the risk for atherosclerosis are not fully understood, but the G allele of rs1126478 seems to have a detrimental effect in a European population.     

Immunoglobulin G antibody profiles against Anopheles salivary proteins in domestic animals in Senegal

Although domestic animals may not be permissive for Plasmodium, they could nevertheless play a role in the epidemiology of malaria by attracting Anopheles away from humans. To investigate interactions between domestic animals and mosquitoes, we assayed immunoglobulin G (IgG) antibodies directed against the salivary proteins of Anopheles gambiae in domestic animals living in Senegalese villages where malaria is endemic. By Western blotting, sera from bovines (n=6), ovines (n=36), and caprines (n=36) did not react with Anopheles whole saliva. In contrast, equine sera recognized proteins in both saliva and salivary gland extracts. Two of the major immunogens (32 and 72 kDa) were also reactive in extracts from other major mosquito genera (Aedes and Culex), but reactions toAnopheles-specific antigens were detected in 12 of 17 horses. These data suggest that horses strongly react to Anopheles bites, and further experiments on horses are warranted to investigate the impact of this domestic animal species on the transmission of human malaria.     

Randomized Study Comparing a Reusable Morcellator with a Resectoscope in the Hysteroscopic Treatment of Uterine Polyps: The RESMO Study

Study ObjectiveTo compare a reusable hysteroscopic morcellator and standard resectoscopes in the hysteroscopic management of uterine polyps.DesignSingle-center randomized prospective single-blind trial (resectoscope-morcellator study).SettingCentre Médico-chirurgical Obstétrique teaching hospital, Strasbourg University Hospitals, France.PatientsAll patients presenting with a single endometrial polyp of size 1 cm or larger.InterventionsAfter consent, the patients were randomized into 2 groups: hysteroscopic morcellation (HM) group or standard resection (SR) group. Office-based review hysteroscopy was performed 6 weeks to 8 weeks after surgery. Primary end point: time of morcellation or resection. Secondary outcomes: total operating time (minutes), volume of fluid used (mL), fluid deficit (mL), number of morcellator or resectoscope insertions, operator comfort (visual analog scale: 0 to 10) and quality of vision (0 to 5), perioperative complications, completeness of resection, need to convert to another technique, pain assessment (visual analog scale), and length of hospitalization. At review hysteroscopy, we noted whether the resection or morcellation had been effective and if synechiae were present or absent. Statistical analyses followed Bayesian methods.Measurements and Main ResultsNinety patients were randomized: 45 in the HM group and 45 in the SR group. The average size of polyps at hysteroscopy was 13.3 mm. Morcellation time was lower than resection time (6.1 minutes vs 9 minutes; p [HM < SR] = .996). This also applied to total operating time (12.7 minutes vs 15.6 minutes; p [HM < SR] = .985), number of device insertions (1.50 vs 6; p [HM < SR] > .999), volume of fluid used (766.9 mL vs 1118.9 mL; p [HM < SR] = .994), and fluid deficit (60.2 mL vs 169.8 mL; p [HM < SR] = .989). Operator comfort was better in the HM group (8.4 vs 7.4; p [HM > SR] = .999) as was visualization (4 vs 3.7; p [HM > SR] = .911, highly probable). Operative complications were higher in the SR group (5 vs 0; p [HM < SR] = .989]. One patient in the SR group died after surgery owing to an anesthetic complication (anaphylactic shock complicated by pulmonary embolism). No differences were noted between the groups for pain assessment, length of hospitalization, and outcome on review hysteroscopy.ConclusionThe reusable morcellator is quicker, uses less fluid with less deficit and fewer introductory maneuvers, and offers better comfort and visualization than the resectoscope while being as effective for the hysteroscopic treatment of uterine polyps.     

Postoperative Outcomes after Surgery for Deep Endometriosis of the Sacral Plexus and Sciatic Nerve: A 52-patient Consecutive Series

Study ObjectiveTo assess 1-year postoperative outcomes of surgery for deep endometriosis involving the sacral roots and sciatic nerve.DesignRetrospective case series.SettingThree referral centers.PatientsFifty-two women.InterventionsSurgery for deep endometriosis involving the sacral roots and sciatic nerve.Measurements and Main ResultsDeep endometriosis involved the sacral roots in 49 women (94.2%) and the sciatic nerve in 3 cases (5.8%). Sciatic pain (buttock or leg) was recorded in 43 women (82.7%), pudendal neuralgia in 11 women (21.2%), and leg motor weakness in 14 cases (27%). The surgical procedures carried out on the pelvic nerves included complete release and decompression (92.3%), excision of the epineurium by shaving (5.8%), and intraneural excision (1.9%). Additional major surgical procedures involved the digestive tract in 82.7% of the cases and the urinary tract in 46.2%. Rectovaginal fistula occurred in 13.5% of the cases. Self-catheterization was required in 14 cases (27%) at 3 weeks after surgery and in 3 women (5.8%) 12 months later. One-year follow-up showed significant improvement in quality of life measured using the Short-Form 36 questionnaire and standardized gastrointestinal scores. De novo hypoesthesia, hyperesthesia, or allodynia were recorded in 9 women (17.2%). The cumulative pregnancy rate was 77.2%% after natural conception in 47%.ConclusionLaparoscopic management of deep endometriosis involving the sacral roots and sciatic nerve improves patients’ symptoms and overall quality of life. Although pain reduction may be rapid after surgery, other sensory or motor complaints, including bladder dysfunction, may be recorded over months or years.     

Immunohistological expression of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 in consecutive biopsies during chemoradiotherapy in patients with rectal cancer

The aim of this study was to describe the dynamics of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 during chemoradiotherapy (CRT) of rectal cancer, and to investigate the fluctuation of these biomarkers in relation to pathological response to CRT. The study included 86 patients with rectal adenocarcinoma receiving preoperative CRT (>50.4 Gy and Uracil/Tegafur). Immunohistological expressions of HIF‐1α, GLUT‐1, Bcl‐2 and Ki‐67 were investigated in biopsies taken before treatment, after 2, 4 and 6 weeks of CRT and in specimens from the operation. Decreasing expressions of HIF‐1α, Bcl‐2 and Ki‐67 were observed during CRT, whereas GLUT‐1 overall was unchanged. No significant changes of the markers were observed in the interval between CRT and surgery. A significant association was observed between the presence of residual carcinoma after 6 weeks of treatment and pathological response to CRT, but no association was seen between the fluctuations of any of the markers and response to CRT. This unique material containing specimens before, after and during CRT for rectal cancer demonstrated biological dynamics in HIF‐1α, Bcl‐2 and Ki‐67, but not GLUT‐1, expression during CRT, and a significant association was seen between the presence of residual carcinoma after 6 weeks of treatment and pathological response to CRT.