Trends in Poliovirus Seroprevalence in Kano State, Northern Nigeria.

Background: Kano state has been a protracted reservoir of poliovirus in Nigeria. Immunity trends have been monitored through seroprevalence surveys since 2011. The survey in 2015 was, in addition, intended to assess the impact of use of inactivated poliovirus vaccine (IPV). Methods: It was a health facility based seroprevalence survey. Eligible children aged 6-9, 12-15 and 19-22 months of age brought to the paediatrics outpatient department of Murtala Mohammad Specialist Hospital between 19 October and 6 November 2015, were screened for eligibility. Eligible children were enrolled after parental consent, history taken, physical examination conducted, and a blood sample collected to test for neutralizing antibody titres against the three poliovirus serotypes. Results: Overall, 365 results were available in the three age groups. In the 6-9-month-old age group, the seroprevalence was 73% (95% confidence interval [CI] 64-80%), 83% (95% CI 75-88%), and 66% (95% CI 57-73%) for serotypes 1, 2, and 3, respectively. In the 12-15- and 19-22-month-old age groups, seroprevalence was higher but still remained <90% across serotypes. Seroprevalence to serotypes 1 and 3 in 2015 was similar to 2014; however, for serotype 2 there was a significant improvement. IPV received in supplemental immunization activities was found to be a significant predictor of seropositivity among 6-9-month-old infants for serotypes 1 and 2. Conclusions: Seroprevalence for serotypes 1 and 3 remains low (<80%) in 6-9-month-olds. This poses a significant risk for poliovirus spread if reintroduced into the population. Efforts to strengthen immunization coverage are imperative to secure and sustain high population immunity.

Type 2 Poliovirus Detection after Global Withdrawal of Trivalent Oral Vaccine.

BACKGROUND: Mass campaigns with oral poliovirus vaccine (OPV) have brought the world close to the eradication of wild poliovirus. However, to complete eradication, OPV must itself be withdrawn to prevent outbreaks of vaccine-derived poliovirus (VDPV). Synchronized global withdrawal of OPV began with serotype 2 OPV (OPV2) in April 2016, which presented the first test of the feasibility of eradicating all polioviruses. METHODS: We analyzed global surveillance data on the detection of serotype 2 Sabin vaccine (Sabin-2) poliovirus and serotype 2 vaccine-derived poliovirus (VDPV2, defined as vaccine strains that are at least 0.6% divergent from Sabin-2 poliovirus in the viral protein 1 genomic region) in stool samples from 495,035 children with acute flaccid paralysis in 118 countries and in 8528 sewage samples from four countries at high risk for transmission; the samples were collected from January 1, 2013, through July 11, 2018. We used Bayesian spatiotemporal smoothing and logistic regression to identify and map risk factors for persistent detection of Sabin-2 poliovirus and VDPV2. RESULTS: The prevalence of Sabin-2 poliovirus in stool samples declined from 3.9% (95% confidence interval [CI], 3.5 to 4.3) at the time of OPV2 withdrawal to 0.2% (95% CI, 0.1 to 2.7) at 2 months after withdrawal, and the detection rate in sewage samples declined from 71.0% (95% CI, 61.0 to 80.0) to 13.0% (95% CI, 8.0 to 20.0) during the same period. However, 12 months after OPV2 withdrawal, Sabin-2 poliovirus continued to be detected in stool samples (<0.1%; 95% CI, <0.1 to 0.1) and sewage samples (8.0%; 95% CI, 5.0 to 13.0) because of the use of OPV2 in response to VDPV2 outbreaks. Nine outbreaks were reported after OPV2 withdrawal and were associated with low coverage of routine immunization (odds ratio, 1.64 [95% CI, 1.14 to 2.54] per 10% absolute decrease) and low levels of population immunity (odds ratio, 2.60 [95% CI, 1.35 to 5.59] per 10% absolute decrease) within affected countries. CONCLUSIONS: High population immunity has facilitated the decline in the prevalence of Sabin-2 poliovirus after OPV2 withdrawal and restricted the circulation of VDPV2 to areas known to be at high risk for transmission. The prevention of VDPV2 outbreaks in these known areas before the accumulation of substantial cohorts of children susceptible to type 2 poliovirus remains a high priority. (Funded by the Bill and Melinda Gates Foundation and the World Health Organization.).

Survey of poliovirus antibodies in Borno and Yobe States, North-Eastern Nigeria.

BACKGROUND: Nigeria remains one of only three polio-endemic countries in the world. In 2016, after an absence of 2 years, wild poliovirus serotype 1 was again detected in North-Eastern Nigeria. To better guide programmatic action, we assessed the immunity status of infants and children in Borno and Yobe states, and evaluated the impact of recently introduced inactivated poliovirus vaccine (IPV) on antibody seroprevalence. METHODS AND FINDINGS: We conducted a facility-based study of seroprevalence to poliovirus serotypes 1, 2 and 3 among health-seeking patients in two sites each of Borno and Yobe States. Enrolment was conducted amongst children 6-9 and 36-47 months of age attending the paediatrics outpatient department of the selected hospitals in the two states between 11 January and 5 February 2016. Detailed demographic and immunization history of the child was taken and an assessment of the child's health and nutritional state was conducted via physical examination. Blood was collected to test for levels of neutralizing antibody titres against the three poliovirus serotypes. The seroprevalence in the two age groups, potential determinants of seropositivity and the impact of one dose of IPV on humoral immunity were assessed. A total of 583 subjects were enrolled and provided sufficient quantities of serum for testing. Among 6-9-month-old infants, the seroprevalence was 81% (74-87%), 86% (79-91%), and 72% (65-79%) in Borno State, and 75% (67-81%), 74% (66-81%) and 69% (61-76%) in Yobe States, for serotypes-1, 2 and 3, respectively. Among children aged 36-47 months, the seroprevalence was >90% in both states for all three serotypes, with the exception of type 3 seroprevalence in Borno [87% (80-91%)]. Median reciprocal anti-polio neutralizing antibody titers were consistently >900 for serotypes 1 and 2 across age groups and states; with lower estimates for serotype 3, particularly in Borno. IPV received in routine immunization was found to be a significant determinant of seropositivity and anti-polio neutralizing antibodies among 6-9-month-old infants for serotypes 1 and 3, but demonstrated a non-significant positive association for serotype 2. Children receiving IPV through SIAs demonstrated significantly higher anti-polio neutralizing antibodies for serotypes 1 and 3. CONCLUSIONS: The seroprevalence to poliovirus remains suboptimal in both Borno and Yobe States in Nigeria. The low seroprevalence facilitated the continued transmission of both wild serotype 1 and serotype 2 circulating vaccine-derived poliovirus detected in Borno State in 2016. Further efforts are necessary to improve the immunity status of these populations to ensure sufficient population immunity to interrupt transmission.

Risk factors and short-term projections for serotype-1 poliomyelitis incidence in Pakistan: A spatiotemporal analysis.

BACKGROUND: Pakistan currently provides a substantial challenge to global polio eradication, having contributed to 73% of reported poliomyelitis in 2015 and 54% in 2016. A better understanding of the risk factors and movement patterns that contribute to poliovirus transmission across Pakistan would support evidence-based planning for mass vaccination campaigns. METHODS AND FINDINGS: We fit mixed-effects logistic regression models to routine surveillance data recording the presence of poliomyelitis associated with wild-type 1 poliovirus in districts of Pakistan over 6-month intervals between 2010 to 2016. To accurately capture the force of infection (FOI) between districts, we compared 6 models of population movement (adjacency, gravity, radiation, radiation based on population density, radiation based on travel times, and mobile-phone based). We used the best-fitting model (based on the Akaike Information Criterion [AIC]) to produce 6-month forecasts of poliomyelitis incidence. The odds of observing poliomyelitis decreased with improved routine or supplementary (campaign) immunisation coverage (multivariable odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.67-0.84; and OR = 0.75, 95% CI 0.66-0.85, respectively, for each 10% increase in coverage) and increased with a higher rate of reporting non-polio acute flaccid paralysis (AFP) (OR = 1.13, 95% CI 1.02-1.26 for a 1-unit increase in non-polio AFP per 100,000 persons aged <15 years). Estimated movement of poliovirus-infected individuals was associated with the incidence of poliomyelitis, with the radiation model of movement providing the best fit to the data. Six-month forecasts of poliomyelitis incidence by district for 2013-2016 showed good predictive ability (area under the curve range: 0.76-0.98). However, although the best-fitting movement model (radiation) was a significant determinant of poliomyelitis incidence, it did not improve the predictive ability of the multivariable model. Overall, in Pakistan the risk of polio cases was predicted to reduce between July-December 2016 and January-June 2017. The accuracy of the model may be limited by the small number of AFP cases in some districts. CONCLUSIONS: Spatiotemporal variation in immunization performance and population movement patterns are important determinants of historical poliomyelitis incidence in Pakistan; however, movement dynamics were less influential in predicting future cases, at a time when the polio map is shrinking. Results from the regression models we present are being used to help plan vaccination campaigns and transit vaccination strategies in Pakistan.

An assessment of the geographical risks of wild and vaccine-derived poliomyelitis outbreaks in Africa and Asia.

BACKGROUND: The international spread of wild poliomyelitis outbreaks continues to threaten eradication of poliomyelitis and in 2014 a public health emergency of international concern was declared. Here we describe a risk scoring system that has been used to assess country-level risks of wild poliomyelitis outbreaks, to inform prioritisation of mass vaccination planning, and describe the change in risk from 2014 to 2016. The methods were also used to assess the risk of emergence of vaccine-derived poliomyelitis outbreaks. METHODS: Potential explanatory variables were tested against the reported outbreaks of wild poliomyelitis since 2003 using multivariable regression analysis. The regression analysis was translated to a risk score and used to classify countries as Low, Medium, Medium High and High risk, based on the predictive ability of the score. RESULTS: Indicators of population immunity, population displacement and diarrhoeal disease were associated with an increased risk of both wild and vaccine-derived outbreaks. High migration from countries with wild cases was associated with wild outbreaks. High birth numbers were associated with an increased risk of vaccine-derived outbreaks. CONCLUSIONS: Use of the scoring system is a transparent and rapid approach to assess country risk of wild and vaccine-derived poliomyelitis outbreaks. Since 2008 there has been a steep reduction in the number of wild poliomyelitis outbreaks and the reduction in countries classified as High and Medium High risk has reflected this. The risk of vaccine-derived poliomyelitis outbreaks has varied geographically. These findings highlight that many countries remain susceptible to poliomyelitis outbreaks and maintenance or improvement in routine immunisation is vital.

Immunogenicity to poliovirus type 2 following two doses of fractional intradermal inactivated poliovirus vaccine: A novel dose sparing immunization schedule.

INTRODUCTION: The polio eradication endgame strategic plan calls for the sequential removal of Sabin poliovirus serotypes from the trivalent oral poliovirus vaccine (tOPV), starting with type 2, and the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV), to maintain an immunity base against poliovirus type 2. The global removal of oral poliovirus type 2 was successfully implemented in May 2016. However, IPV supply constraints has prevented introduction in 21 countries and led to complete stock-out in >20 countries. METHODS: We conducted a literature review and contacted corresponding authors of recent studies with fractional-dose IPV (fIPV), one-fifth of intramuscular dose administered intradermally, to conduct additional type 2 immunogenicity analyses of two fIPV doses compared with one full-dose IPV. RESULTS: Four studies were identified that assessed immunogenicity of two fIPV doses compared to one full-dose IPV. Two fractional doses are more immunogenic than 1 full-dose, with type 2 seroconversion rates improving between absolute 19-42% (median: 37%, p<0.001) and relative increase of 53-125% (median: 82%), and antibody titer to type 2 increasing by 2-32-fold (median: 10-fold). Early age of administration and shorter intervals between doses were associated with lower immunogenicity. DISCUSSION: Overall, two fIPV doses are more immunogenic than a single full-dose, associated with significantly increased seroconversion rates and antibody titers. Two fIPV doses together use two-fifth of the vaccine compared to one full-dose IPV. In response to the current IPV shortage, a schedule of two fIPV doses at ages 6 and 14weekshas been endorsed by technical oversight committees and has been introduced in some affected countries.

Boosting Immune Responses Following Fractional-Dose Inactivated Poliovirus Vaccine: A Randomized, Controlled Trial.

BACKGROUND: Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt. METHODS: We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28; serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion or a ≥4-fold rise in antibody titer. The noninferiority limit was 10%. The secondary end point was safety, assessed by the number and intensity of adverse reactions. RESULTS: A total of 503 of 534 enrolled participants (94.2%) completed all study requirements. Twenty-eight days after the first dose, 94.8%, 98.0%, and 98.0% of fIPV recipients had an immune response to poliovirus types 1, 2, and 3, respectively, compared with 98.1% (P = .06), 98.0% (P = 1.00), and 99.2% (P = .45) in the IPV arm. Noninferiority was achieved on days 7, 28, and 56 for all serotypes. No serious adverse events were reported. CONCLUSION: fIPV induced similar boosting immune responses, compared with full-dose IPV. This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation. CLINICAL TRIALS REGISTRATION: ACTRN12615000305527.

Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data.

BACKGROUND: Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of serotype-2 vaccine-derived polioviruses (VDPV2s). METHODS AND FINDINGS: In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004-30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children <36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity within and among districts. Forward projections of immunity, based on these estimates and planned immunisation activities, were produced through to April 2016 using a cohort model. Estimated population immunity was negatively correlated with the probability of VDPV2 poliomyelitis being reported in a district. In Nigeria and Pakistan, declines in immunity during 2008-2009 and 2012-2013, respectively, were associated with outbreaks of VDPV2. Immunity has since improved in both countries as a result of increased use of trivalent OPV, and projections generally indicated sustained or improved immunity in April 2016, such that the majority of districts (99% [95% uncertainty interval 97%-100%] in Nigeria and 84% [95% uncertainty interval 77%-91%] in Pakistan) had >70% population immunity among children <36 mo old. Districts with lower immunity were clustered in northeastern Nigeria and northwestern Pakistan. The accuracy of immunity estimates was limited by the small numbers of non-polio AFP cases in some districts, which was reflected by large uncertainty intervals. Forecasted improvements in immunity for April 2016 were robust to the uncertainty in estimates of baseline immunity (January-June 2015), vaccine coverage, and vaccine efficacy. CONCLUSIONS: Immunity against serotype-2 poliomyelitis was forecasted to improve in April 2016 compared to the first half of 2015 in Nigeria and Pakistan. These analyses informed the endorsement of OPV2 withdrawal in April 2016 by the WHO Strategic Advisory Group of Experts on Immunization.

Human Circulating Antibody-Producing B Cell as a Predictive Measure of Mucosal Immunity to Poliovirus.

BACKGROUND: The "gold standard" for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore evaluated circulating antibody-secreting cells (ASCs) as a potential means to evaluate mucosal immunity to poliovirus vaccine. METHODS: 199 subjects, aged 10 years, and previously immunized repeatedly with OPV, were selected. Subjects were assigned to receive either a booster dose of inactivated poliovirus vaccine (IPV), bivalent OPV (bOPV), or no vaccine. Using a micro-modified whole blood-based ELISPOT assay designed for field setting, circulating poliovirus type-specific IgA- and IgG-ASCs, including gut homing α4ß7+ ASCs, were enumerated on days 0 and 7 after booster immunization. In addition, serum samples collected on days 0, 28 and 56 were tested for neutralizing antibody titers against poliovirus types 1, 2, and 3. Stool specimens were collected on day 28 (day of bOPV challenge), and on days 31, 35 and 42 and processed for poliovirus isolation. RESULTS: An IPV dose elicited blood IgA- and IgG-ASC responses in 84.8 to 94.9% of subjects, respectively. In comparison, a bOPV dose evoked corresponding blood ASC responses in 20.0 to 48.6% of subjects. A significant association was found between IgA- and IgG-ASC responses and serum neutralizing antibody titers for poliovirus type 1, 2, 3 (p<0.001). In the IPV group, α4ß7+ ASCs accounted for a substantial proportion of IgA-ASCs and the proportion of subjects with a positive α4ß7+ IgA-ASC response to poliovirus types 1, 2 and 3 was 62.7%, 89.8% and 45.8%, respectively. A significant association was observed between virus excretion and α4ß7+ IgA- and/or IgG-ASC responses to poliovirus type 3 among immunized children; however, only a weak association was found for type 1 poliovirus. DISCUSSION: Our results suggest that virus-specific blood ASCs, especially for type 3 poliovirus, can serve as surrogate of mucosal immunity after vaccination. Further studies are needed to evaluate the duration of such memory responses and to assess the programmatic utility of this whole blood-based mucosal ASC testing for the polio eradication program.

Impact of inactivated poliovirus vaccine on mucosal immunity: implications for the polio eradication endgame.

The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio.

Polio eradication. Efficacy of inactivated poliovirus vaccine in India.

Inactivated poliovirus vaccine (IPV) is efficacious against paralytic disease, but its effect on mucosal immunity is debated. We assessed the efficacy of IPV in boosting mucosal immunity. Participants received IPV, bivalent 1 and 3 oral poliovirus vaccine (bOPV), or no vaccine. A bOPV challenge was administered 4 weeks later, and excretion was assessed 3, 7, and 14 days later. Nine hundred and fifty-four participants completed the study. Any fecal shedding of poliovirus type 1 was 8.8, 9.1, and 13.5% in the IPV group and 14.4, 24.1, and 52.4% in the control group by 6- to 11-month, 5-year, and 10-year groups, respectively (IPV versus control: Fisher's exact test P < 0.001). IPV reduced excretion for poliovirus types 1 and 3 between 38.9 and 74.2% and 52.8 and 75.7%, respectively. Thus, IPV in OPV-vaccinated individuals boosts intestinal mucosal immunity.

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). METHODS: A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. RESULTS: The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. CONCLUSIONS: A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.

Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review.

BACKGROUND & AIMS: We conducted a systematic review to determine changes in the worldwide incidence and prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in different regions and with time. METHODS: We performed a systematic literature search of MEDLINE (1950-2010; 8103 citations) and EMBASE (1980-2010; 4975 citations) to identify studies that were population based, included data that could be used to calculate incidence and prevalence, and reported separate data on UC and/or CD in full manuscripts (n = 260). We evaluated data from 167 studies from Europe (1930-2008), 52 studies from Asia and the Middle East (1950-2008), and 27 studies from North America (1920-2004). Maps were used to present worldwide differences in the incidence and prevalence of inflammatory bowel diseases (IBDs); time trends were determined using joinpoint regression. RESULTS: The highest annual incidence of UC was 24.3 per 100,000 person-years in Europe, 6.3 per 100,000 person-years in Asia and the Middle East, and 19.2 per 100,000 person-years in North America. The highest annual incidence of CD was 12.7 per 100,000 person-years in Europe, 5.0 person-years in Asia and the Middle East, and 20.2 per 100,000 person-years in North America. The highest reported prevalence values for IBD were in Europe (UC, 505 per 100,000 persons; CD, 322 per 100,000 persons) and North America (UC, 249 per 100,000 persons; CD, 319 per 100,000 persons). In time-trend analyses, 75% of CD studies and 60% of UC studies had an increasing incidence of statistical significance (P < .05). CONCLUSIONS: Although there are few epidemiologic data from developing countries, the incidence and prevalence of IBD are increasing with time and in different regions around the world, indicating its emergence as a global disease.

Challenges associated with identifying the environmental determinants of the inflammatory bowel diseases.

In the last several years there has been an explosion in the discovery of inflammatory bowel disease (IBD) susceptibility genes; however, similar advances in identifying and defining environmental risk factors associated with IBD have lagged behind. Moreover, many studies that have explored the same or similar environmental risk factors of IBD have demonstrated disparate results and come to conflicting conclusions. In order for the field to move forward, it is important to understand and resolve why these differences exist. This significant heterogeneity has blurred the identification of the fundamental environmental determinants of IBD. The purpose of this review article is to explore the factors that have likely contributed to the heterogeneity among observational studies of environmental risk factors in IBD. In doing so, it is hoped that methodological standardization may lead to consistent environmental associations.

Validity of administrative data for the diagnosis of primary sclerosing cholangitis: a population-based study.

BACKGROUND/AIMS: Administrative databases could be useful in studying the epidemiology of primary sclerosing cholangitis (PSC); however, there is no information regarding the validity of the diagnostic code in administrative databases. The aims of this study were to determine the validity of administrative data for a diagnosis of PSC and generate algorithms for the identification of PSC patients. METHODS: The sensitivity (Se) and positive predictive value (PPV) of a PSC diagnosis based on administrative data from 2000 to 2003 were determined through chart review data. Algorithms were developed by considering variables associated with PSC and coding details. A logistic regression model was constructed using covariates associated with PSC. Based on this model, each subject was assigned a probability of having PSC. A cutoff value was selected that maximized the Se and specificity (Sp) of correctly predicting PSC cases. RESULTS: In the administrative data, the initial Se and PPV were 83.7 and 7.2% respectively. The optimal algorithm included one PSC code and one inflammatory bowel disease code and had Se 56% and PPV 59%. Overall, the algorithms yielded inadequate PPV and Se estimates to identify a cohort of true PSC cases. The predictive model was constructed using six covariates. For this model, the area under the receiver operating characteristic curve was 93.5%. A cutoff of 0.0729 was used, which maximized the Se 81.9% and Sp 90.7%; however, the PPV was 41.0%. CONCLUSION: An algorithm for the identification of true PSC cases from administrative data was not possible. We recommend that PSC receives a distinct ICD code from ascending cholangitis.

Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis.

UNLABELLED: Incidence studies of primary sclerosing cholangitis (PSC) are important for describing the disease's burden and for shedding light on the disease's etiology. The purposes of this study were to conduct a systematic review of the incidence studies of PSC with a meta-analysis and to investigate possible geographic variations and temporal trends in the incidence of the disease. A systematic literature search of MEDLINE (1950-2010) and Embase (1980-2010) was conducted to identify studies investigating the incidence of PSC. The incidence of PSC was summarized with an incidence rate (IR) and 95% confidence intervals. The test of heterogeneity was performed with the Q statistic. Secondary variables extracted from the articles included the following: the method of case ascertainment, the country, the time period, the age, the male/female incidence rate ratio (IRR), and the incidence of PSC subtypes (small-duct or large-duct PSC and inflammatory bowel disease). Stratified and sensitivity analyses were performed to explore heterogeneity between studies and to assess effects of study quality. Time trends were used to explore differences in the incidence across time. The search retrieved 1669 potentially eligible citations; 8 studies met the inclusion criteria. According to a random-effects model, the pooled IR was 0.77 (0.45-1.09) per 100,000 person-years. However, significant heterogeneity was observed between studies (P < 0.001). Sensitivity analyses excluding non-population-based studies increased the overall IR to 1.00 (0.82-1.17) and eliminated the heterogeneity between studies (P = 0.08). The IRR for males versus females was 1.70 (1.34-2.07), and the median age was 41 years (35-47 years). All studies investigating time trends reported an overall increase in the incidence of PSC. CONCLUSION: The incidence of PSC is similar in North American and European countries and continues to increase over time. Incidence data from developing countries are lacking, and this limits our understanding of the global incidence of PSC.

Environmental risk factors for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD.