High-incidence Regions Research Articles

P11.17 Intensification of a shigellosis epidemic associated with sexual transmission between men: diagnoses ofshigella flexneriands. sonneiin england, 2004 to 2015

Introduction Although Shigellosis is often associated with travel to high incidence regions, outbreaks of Shigella flexneri and S. sonnei associated with sexual transmission between men have been reported in the UK, Australia and elsewhere. We examined national trends in Shigella spp. diagnoses to explore the evidence for on-going sexual transmission of S. flexneri 3a and transmission of other Shigella serotypes or species between men in England. Methods Local hospital laboratories submit presumptive strains of Shigella spp. to the Public Health England national reference laboratory for confirmation and typing. We report trends in diagnoses in men and women aged 16 to 60 years old, excluding cases with recent travel outside the UK. Results Between January 2004 and February 2015, 53% (5,051/9,534) of Shigella spp. diagnoses made in England were not travel-associated, and diagnoses of S. flexneri 3a, S. flexneri 2a, and S. sonnei accounted for 78% of these cases. S. flexneri 3a diagnoses in men increased steadily from 2004 (3 cases) and peaked in 2013 (154 cases). Diagnoses of S. flexneri 2a in men followed a similar pattern, although increases emerged later, rising from 9 cases in 2004 to 220 cases in 2014. In 2010, diagnoses of S. sonnei in men began to exceed those in women (147 compared to 133 cases), and have since risen steadily in men (267 cases in 2014). Diagnoses in women remained low/stable throughout the study period, and the male to female gender ratios increased substantially, peaking in 2014 at 59:1, 17:1 and 3:1 for S. flexneri 3a, S. flexneri 2a, and S. sonnei . Conclusion Surveillance data suggest an intensification of the shigellosis epidemic associated with sex between men in England. The timing and heterogeneity in species and serotypes implies separate introductions into the population. These data raise the possibility of new shigellosis outbreaks occurring elsewhere. Disclosure of interest statement No pharmaceutical grants were received in the development of this study.

Abstract 4630: Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese

Abstract Nasopharyngeal carcinoma (NPC) is an epithelial malignancy highly prevalent in Southern China with varying incidence rates among Han Chinese in different geographic regions. Recently, three independent genome-wide association studies (GWAS) confirmed that the HLA-A was the main risk gene of NPC. However, studies from regions with different incidence rates led to contradictory claims regarding whether HLA-A was the sole risk gene and the association of rs29232 was independent from the HLA-A effect in chromosome 6p21.3 region. To explore whether the differences were caused by genetic factors underlying the varying incidence rates by region in NPC incidence, we performed a meta-analysis by selecting 5 single-nucleotide polymorphisms (SNPs) in chromosome 6p21.3 from 3 published GWAS studies and 3 published case-control studies from Southern China (Taiwan, Guangdong and Guangxi) involving 7 828 NPC patients and 8 813 healthy controls from Han Chinese. The rs29232 SNP exhibited a moderate level of heterogeneity (I2 = 43%) that disappeared (I2 = 0% and 4%) after stratifying the studies according to moderate- and high-incidence NPC regions. The estimated odds ratio (OR) of rs29232 (OR: 1.70, 95% confidence interval [CI]: 1.47-1.95) was higher in the moderate-incidence region than in the high-incidence region (OR: 1.42, 95% CI: 1.30-1.56). The heterogeneity revealed by meta-analysis of rs29232 might be associated with differences in NPC incidence in Han Chinese between geographic regions. Therefore, we postulate that moderate heterogeneity in rs29232 might contribute to the varying incidence rates between regions due to a genetic cause in NPC incidence. The higher OR of rs29232 and the fact that it was independent of the HLA-A effect in the moderate-incidence population suggested that rs29232 might have greater relevance to NPC in a moderate-incidence population than to a high-incidence population. To our knowledge, this is the first study to demonstrate that genetic factors might involve in the varying disease incidence rates by region. This further suggests that the disease incidence rate should be considered as a potential confounding factor when conducting large, cross-region meta-analysis in NPC. Citation Format: Wen-Hui Su, Chi-Cking Chiu, Yin Yao Shugart. Heterogeneity revealed through meta-analysis might link geographical differences with nasopharyngeal carcinoma incidence in Han Chinese. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4630. doi:10.1158/1538-7445.AM2015-4630

Association of genetic polymorphisms in PRKDC and XRCC4 with risk of ESCC in a high-incidence region of North China.

The nonhomologous end-joining (NHEJ) pathway is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. This research was designed to study the association between selected variants in NHEJ members and esophageal squamous cell carcinoma (ESCC). Two single nucleotide polymorphisms (SNPs), PRKDC (rs7003908) and X-ray repair cross complementing group 4 (XRCC4; rs1805377), were genotyped in a total of 189 patients with ESCC and 189 unrelated control individuals in a high-risk area for ESCC in North China, and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied. A significantly different distribution was found in the frequency of PRKDC (rs7003908) genotype between the ESCC group and controls. Individuals homozygous for the C allele had a significant (3.185-fold) increased risk of ESCC. As for XRCC4 (rs1805377) polymorphism, no difference was found in distribution between the ESCC and control groups. Our results suggest that variation in DNA repair genes may be associated with risk of ESCC.

Influence of carbapenem resistance on mortality of patients with Pseudomonas aeruginosa infection: a meta-analysis

Treatment of infectious diseases caused by the carbapenem-resistant Pseudomonas aeruginosa (CRPA) is becoming more challenging with each passing year. We conducted a meta-analysis to assess the impact of carbapenem resistance on mortality of patients with P. aeruginosa infection. We searched PUBMED, Web of science, EMBASE, Google Scholar and the Cochrane Library up to December 25, 2014, to identify published cohort or case-control studies. 17 studies, including 6660 patients carrying P. aeruginosa, were identified. The pooling analysis indicated that patients infected with CRPA had significantly higher mortality than those infected with carbapenem-susceptible P. aeruginosa (CSPA) (crude OR = 1.64; 95%CI = 1.40, 1.93; adjusted OR = 2.38; 95%CI = 1.53, 3.69). The elevated risk of mortality in patients with CRPA infection was not lessened when stratified by study design, sites of infection, or type of carbapenem, except that the estimate effect vanished in CRPA high-incidence region, South America (crude OR = 1.12; 95%CI = 0.64, 1.99). Begg’s (z = 0.95, p = 0.34) and Egger’s test (t = 1.23, p = 0.24) showed no evidence of publication bias. Our results suggest that carbapenem resistance may increase the mortality of patients with P. aeruginosa infection, whether under univariate or multivariate analysis.

Long-term trends in invasive Haemophilus influenzae type B disease among indigenous Australian children following use of PRP-OMP and PRP-T vaccines.

Among indigenous populations with high incidence and early onset of invasive Haemophilus influenzae type b (Hib) disease, PRP-OMP vaccines are used in the United States and PRP-T vaccines in Canada. In Australia, PRP-OMP vaccines were exclusively used in indigenous children from 1993 until they were replaced by PRP-T between late 2005 and 2009. Analytic descriptive study of 20 years of enhanced surveillance data (1993-2013) for invasive Hib disease in Australian children <10 years of age was conducted. Of 579 Hib cases under 10 years of age reported from vaccine introduction in 1993 to 2013, 78 (13%) were in indigenous children, 47 (60%) of whom lived in regions with high prevaccine incidence. In this population, incidence per 100,000 declined from 18.1 (95% confidence interval [CI]: 10.4, 29.4) in the early PRP-OMP period (1993-1996) to 6.2 (95% CI: 4.0, 9.2) and 4.7 (95% CI: 1.7, 10.3) in the later PRP-OMP (1996-2009) and PRP-T periods (2009-2013), respectively. The indigenous:nonindigenous incidence rate ratio increased to 43 (95% CI: 16, 145) and 58 (95% CI: 7, 2660) in the later PRP-OMP and PRP-T periods, respectively, more than 10-fold higher than in lesser-incidence Australian regions. We found no change in Hib incidence among indigenous Australian children living in high-incidence regions in the first 4 years following a change to PRP-T-containing combination vaccines. This may be of relevance to North American indigenous populations characterized by suboptimal living conditions and young age of onset for whom PRP-OMP continues to be recommended, such as Alaska Natives.

Human papillomavirus tumor infection in esophageal squamous cell carcinoma.

The association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) has been recognized for over three decades. Recently, multiple meta-analyses have drawn upon existing literature to assess the strength of the HPV-ESCC linkage. Here, we review these analyses and attempt to provide a clinically-relevant overview of HPV infection in ESCC. HPV-ESCC detection rates are highly variable across studies. Geographic location likely accounts for a majority of the variation in HPV prevalence, with high-incidence regions including Asia reporting significantly higher HPV-ESCC infection rates compared with low-incidence regions such as Europe, North America, and Oceania. Based on our examination of existing data, the current literature does not support the notion that HPV is a prominent carcinogen in ESCC. We conclude that there is no basis to change the current clinical approach to ESCC patients with respect to tumor HPV status.

Predicting cytotoxicity of complex mixtures in high cancer incidence regions of the Huai River Basin based on GC–MS spectrum with partial least squares regression

Complex mixture exposures, such as those associated with water sources, are an important issue in health risk assessment. This study assessed the cytotoxicity of chemical mixtures extracted from water sources in regions of the Huai River Basin with high cancer incidences and built statistical models of cytotoxicity based on pollution profiles that were measured with gas chromatography–mass spectrometry (GC–MS). Both surface and ground waters were collected from rural water sources of Shenqiu County, Henan Province of China from 2008 to 2011 and extracted with XAD-2 resigns. Cytotoxicity was evaluated with Chinese hamster ovary K1 (CHO-K1) cells and compared against the pollution profiles of the extracts. IC50 of water samples ranged from 0.023 to 0.338L-eq/mL. The pollutants in waters determined by GC–MS are complex and some of the compounds that contributed to cytotoxicity lack toxicity data. A partial least squares (PLS) regression model of cytotoxicity was built based on linear aggregation of predictor variables (i.e., peaks for single compounds in the gas chromatograms). The PLS model contains 2 PLS factors extracted from 141 variables. The model was validated internally with training data permutation and externally with a test sample. The model explained 92% of the cytotoxicity in the training samples and 40% in the test sample. This approach provides a general, rapid method for relating water toxicity to GC–MS chromatograms and for predicting the compounds that contribute most to toxicity.

Cervical cancer screening coverage in a high-incidence region.

OBJECTIVE To analyze the coverage of a cervical cancer screening program in a city with a high incidence of the disease in addition to the factors associated with non-adherence to the current preventive program.METHODS A cross-sectional study based on household surveys was conducted. The sample was composed of women between 25 and 59 years of age of the city of Boa Vista, RR, Northern Brazil who were covered by the cervical cancer screening program. The cluster sampling method was used. The dependent variable was participation in a women’s health program, defined as undergoing at least one Pap smear in the 36 months prior to the interview; the explanatory variables were extracted from individual data. A generalized linear model was used.RESULTS 603 women were analyzed, with an mean age of 38.2 years (SD = 10.2). Five hundred and seventeen women underwent the screening test, and the prevalence of adherence in the last three years was up to 85.7% (95%CI 82.5;88.5). A high per capita household income and recent medical consultation were associated with the lower rate of not being tested in multivariate analysis. Disease ignorance, causes, and prevention methods were correlated with chances of non-adherence to the screening system; 20.0% of the women were reported to have undergone opportunistic and non-routine screening.CONCLUSIONS The informed level of coverage is high, exceeding the level recommended for the control of cervical cancer. The preventive program appears to be opportunistic in nature, particularly for the most vulnerable women (with low income and little information on the disease). Studies on the diagnostic quality of cervicovaginal cytology and therapeutic schedules for positive cases are necessary for understanding the barriers to the control of cervical cancer.

Spatio-Temporal Distribution of Malaria in Perak, Malaysia

Malaria incidence in Perak, Malaysia has generally declined, but there remain regions of high incidence. The spatio-temporal distribution pattern of malaria in Perak was studied using Geographical Information Systems (GIS) and spatial statistical tools. Malaria data cases at the subdistrict level in Perak from 2007 to 2011 were analysed to determine the spatial and temporal distribution patterns of malaria incidence. Geographical Information Systems (GIS) and spatial statistical tools were used to identify spatial correlation in the data and malaria hot-spots. Spatial correlation was tested by using an autocorrelation method called Moran’s I. Hot spot analysis was done using Getis-Ord G* statistic technique. Malaria incidence rates were categorized into 3 classes to map the spatial distribution. Malaria cases in Perak were geo-spatially clustered. Most of the hot spots locations were in Kenering, Ulu Kinta, Gerik and Kampar sub-districts. The prevalence of malaria among foreigners was noticeably higher than Malaysians. Improved surveillance of foreign workers can prevent outbreaks and identify high risk areas. This study implies that geographic-based mapping and information system are needed for an effective malaria control.

Association of the genetic polymorphisms in XRCC6 and XRCC5 with the risk of ESCC in a high-incidence region of North China.

The XRCC6 and XRCC5 genes are part of the nonhomologous end-joining (NHEJ) pathway, which is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. Genetic variations of XRCC6 and XRCC5 might contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. ESCC patients (n = 189) and cancer-free controls (n = 189) were recruited in an ESCC high-risk area of north China. Then the rs2267437 (XRCC6), rs3835 (XRCC5) and rs16855458 (XRCC5) polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A significant difference in genotype distribution and allele frequency of rs2267437 (XRCC6) was observed between the cases and controls. The CG carriers were at higher risk of ESCC (p = 0.001, odds ratio [OR] = 2.040, 95% confidence interval [95% CI], 1.323-3.147). G allele carriers were also associated with an increased ESCC risk (p = 0.003, OR = 1.868, 95% CI, 1.230-2.836). In the 2 polymorphisms of XRCC5, no significant difference was found between both groups in the distribution of either genotype or allelic frequency. But in the haplotypes established by the single nucleotide polymorphisms (SNPs) of XRCC5, the haplotype AT and CC separately increased by 4.28- and 2.31-fold the risk ratio of ESCC (p = 0.01, OR = 4.28, 95% CI, 1.40-13.05; p = 0.03, OR = 2.31, 95% CI, 1.11-4.80, respectively). In addition, gene-smoking or gene-drinking interactions, and their effect on the risk of ESCC were observed, but no significant gene-environment interaction was demonstrated. In conclusion, both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC susceptibility.

State of the art: hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, mainly occurring in cirrhotic livers (in 80–90% of cases) after years of chronic inflammation [1,2]. The pathogenesis of HCC is a multistep process associated with changes in the host gene expression of multiple redundant negative-growth regulatory pathways that protect cells against transformation. An imbalance between the proliferation and apoptosis of liver cells is thought to promote tumor development [3]. Annually, 3–6% of cirrhotic patients will develop HCC, mainly men with advanced liver disease. Recent trends in the USA show that men are affected three-times more frequently than women, Asians are affected twice as often as blacks and Hispanics, and blacks are affected twice as often as whites [4]. One explanation for the disproportionate effects of HCC in men may be due to the higher estrogen concentrations present in women, which suppress IL-6 production and inhibit chemically induced liver carcinogenesis [1]. Epidemiology & etiology HCC is the principal cause of death in patients with compensated cirrhosis worldwide. It is largely a problem of less developed regions, where 83% (50% in China alone) of the estimated 782,000 new cases of liver cell cancer worldwide occur (based on 2012 data) [5]. HCC is the fifth most common cancer in men (554,000 cases; 7.5% of the total) and the ninth in women (228,000 cases; 3.4% of the total) [5]. Regions of high incidence (age adjusted rates per 100,000 inhabitants per year in men) are eastern and south-eastern Asia (31.9 and 22.2, respectively). Intermediate rates occur in southern Europe (9.5) and North America (9.3), and the lowest rates are in northern Europe (4.6) and south-central Asia (3.7) [5]. The global age distribution of HCC cases is related to the dominant viral hepatitis in the underlying population and the age at which it was acquired. For example, the disease burden is highest in areas with endemic hepatitis B virus (HBV) infection, such as in sub-Saharan Africa, where the virus is mainly transmitted at birth (with >90% of these cases becoming chronic HBV carriers). However, the diagnosis of HCC often occurs later in North America and southern Europe, where the most common etiology is HBV or hepatitis C virus (HCV) acquired later in life [2]. Several factors have been reported to increase HCC risk among HBV carriers, including male sex, older age, Asian or African ethnicity, family history of HCC, viral (higher levels of HBV repli cation, HBV genotype, longer duration of infection or coinfection with HCV, HIV or hepatitis D virus), clinical (cirrhosis) and environmental or lifestyle factors (exposure to aflatoxin, chronic excessive alcohol consumption or tobacco smoking). Other risk factors that increase the risk in HCV-infected patients include coinfection with HIV, HBV, HCV genotype 1b, old age, the presence of diabetes and obesity and a high level of chronic alcohol consumption. However, both HBV and HCV are highly amenable to preventive measures with antivirals or vaccination (for HBV). In Italy, for example, the Italian Liver Cancer (ITA.LI.CA) database reveals a decline in HCV infection with a concomitant increase in alcohol consumption as the primary etiology for HCC [6].

P16 hypermethylation: a biomarker for increased esophageal cancer susceptibility in high incidence region of North East India.

Esophageal cancer is one of the most common cancers in North East India. The molecular mechanisms of esophageal cancer susceptibility in North East India have not been fully understood. There is a need for identification of biomarkers to identify people at risk of esophageal cancer. p16 is an essential G1 cell cycle regulatory gene whose loss of function is associated with carcinogenesis. Therefore, we conducted this study to determine the prevalence of p16 gene methylation in patients with esophageal cancer to assess the feasibility of using gene methylation as a biomarker. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex, and ethnicity-matched controls were included in this study. Methylation-specific PCR was used to determine the p16 methylation status. Aberrant promoter methylation of the p16 gene was detected in 81 of 100 (81%) esophageal cancer cases. Hypermethylation of p16 gene was found to be influenced by lifestyle factors. Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95% confidence interval (CI) = 1.64-28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95% CI = 1.87-26.38, p = 0.001 for tobacco chewing). Further, intake of green leafy vegetables and fruits lowered the risk of esophageal cancer (adjusted OR = 0.16, 95 % CI = 0.04-0.58, p = 0.05 for green leafy vegetables and adjusted OR = 0.15, 95% CI = 0.04-0.64, p = 0.01 for fruits). Thus, p16 hypermethylation may aid as a biomarker in identifying habitués at greater risk for esophageal cancer susceptibility in high incidence region of North East India.

Higher Rates of Helicobacter pylori Infection and Gastric Intestinal Metaplasia in the Asian Population

Introduction: The rate of Helicobacter pylori (H. pylori) infection is higher in minority patients in the United States. Gastric intestinal metaplasia (IM) is associated with H. pylori infection and increased risk for gastric cancer over time, in particular for patients from regions of high gastric cancer incidence. We aimed to compare the rates of Helicobacter pylori infection and gastric intestinal metaplasia in Asian patients vs. non-Hispanic white (hereafter white) patients at our institution. Methods: After IRB approval, a chart review was performed on Asian and white patients who underwent diagnostic EGD with random stomach biopsies (antrum, body, and incisura) performed by the same endoscopist (YRW) during the study period. Endoscopy and pathology reports were used to identify the presence of peptic ulcer disease, H. pylori infection, and gastric IM. Other variables of interest included patient age and sex. The Student’s t-test, chi-square test, and multivariate logistic regression were used in statistical analysis. Results: Our study sample included 60 Asian patients (35 Korean, 11 Vietnamese, 10 Chinese, and 4 other Asian) and 67 white patients. Compared with white patients, Asian patients were older (mean age [standard deviation]: Asian 56.5 [15.4], white 49.6 [17.1], p<0.05) and similar in percentage of females (Asian 65.0%, white 68.7%). The presence of peptic ulcer disease was similar (Asian 13.3%, white 10.4%), while the rates of H. pylori infection and gastric IM were higher in Asian patients (H. pylori infection: Asian 20.0%, white 6.0%, p<0.05; gastric IM: Asian 40.0%, white 13.4%, p<0.001). Multivariate logistic regression controlling for patient age and sex confirmed Asian patients’ higher risks of H. pylori infection (odds ratio [OR] 3.96; 95% confidence interval [CI] 1.17-13.4) and gastric IM (3.93; 1.62-9.52). Conclusion: The rates of H. pylori infection and gastric IM in Asian patients were similarly 4 times as high as those in white patients, suggestive of the role of (prior or active) H. pylori infection in gastric IM.

Residual disease following conization of women with stage IA-IB1 cervical carcinoma in a high incidence region.

To determine rates of residual disease along with influencing factors in women with stage IA to IB1 cervical carcinoma after conization. A retrospective study was conducted of medical records of 198 stage IA to IB1 cervical carcinoma patients who had undergoing cervical conization followed by primary surgical treatment during 2006-2013. Independent factors correlating with residual carcinoma in subsequent surgical specimens were analyzed by stepwise regression analysis. Mean age was 48.9 years. Cone specimens demonstrated free margins in 36 women (18.8%). In case of having disease at margin, high-grade cervical intraepithelial neoplasia (CIN) and carcinoma were evidenced in 58 and 97 women, respectively. Pathology of subsequent specimens revealed residual carcinoma in 78 women (39.4%), high-grade CIN or adenocarcinoma in situ (AIS) in 45 (22.7%), and no residual pathology in 75 (37.9%). Age more than 35 years, postmenopausal status, having symptoms, diseases or invasive lesions at conization margins or disease on endocervical aspect, and higher stage were significantly correlated with residual cancer in surgical treatment specimens. On regression analysis, postmenopause and stage were independent factors associated with residual carcinoma. Patient and tumor characteristics are predictive factors for residual cancer in the studied group of women.

An investigation into the relationship between region specific quality of life and adverse tuberculosis treatment outcomes in Istanbul, Turkey

Background and objectiveIstanbul has the highest incidence of tuberculosis (TB) in Turkey. It is also the largest city, with considerable differences in quality of life across its urban regions. The aim of this study is to investigate the relationship between (i) the diverse quality of life across specific urban regions, (ii) TB incidence rates, inclusive of demographic and clinical characteristics of TB patients, and (iii) adverse treatment outcomes. MethodsThis retrospective study included 23,845 new TB patients (recorded in the National TB Registry between 2006 and 2010) in Istanbul. Thirty-nine urban districts of Istanbul were ranked into five groups on the basis of an urban quality of life index. Patient data were matched with these groups, and further categorized according to ‘age’, ‘sex’, ‘country of birth’ and ‘antibiotics resistance’. Adverse treatment outcomes and TB incidence rates were extracted from official records. Logistic regression, clustered analyses, 95% CI and p values (STATA) were reported to describe the association between variables. ResultsSix per cent of total cases had ‘at least one adverse treatment outcome’ (default 3.8%, failure 0.5%, death 1.7% in total cases). ‘An adverse treatment outcome’ was found to be associated with age OR (CI 95%) (1.02 (1.01–1.03)); ‘male sex’ 1.65 (1.28–2.12); ‘other country of birth’ 4.82 (3.05–7.62); 100,000 per ‘over 60’ insidence goups 1.61 (1.32-1.97), the lowest quality of life index 0.65 (0.47-0.83). ConclusionsPatients with high tuberculosis risk factors living in high incidence regions need to be closely monitored. Patients living in lower ranking regions are more likely to have ‘poor treatment outcomes’.

Viral hepatitis in Denmark

OZET To provide an overview of the epidemiology and public health strategies concerning viral hepatitis in Denmark. Studies and guidelines in viral hepatitis in Denmark and national surveillance data were reviewed. The incidence of acute hepatitis A has declined since 1980 and was 0.2/105 in 2011. The majority of cases are imported by children of foreign origin. The incidence of acute hepatitis B has also been declining; the prevalence of chronic hepatitis B is estimated to be 0.24% of the adult population and genotype D is the most prevalent. The majority of patients with chronic hepatitis B are immigrants from high incidence regions and co-infection with hepatitis D is rare. The prevalence of hepatitis C is 0.38% of the adult population and the majority has been infected through 4 drug use. Genotype 1 is the most prevalent genotype. Hepatitis E is a rare and imported condition but a high prevalence of anti-HEV among farmers indicates the infection is an asymptomatic zoonotic infection in Denmark. There are national treatment guidelines for hepatitis B and C and the treatment is provided free of charge to all Danish residents. Vaccination against hepatitis A is recommended to persons travelling to high incidence countries and persons with chronic hepatitis C. Vaccination against hepatitis B is recommended and free of charge to all newborns of HBsAg positive mothers and persons specifically assessed to be at an increased risk. Denmark is a low incidence country for viral hepatitis, but continuous attention is required within risk groups. (Viral Hepatitis Journal 2014; 20(2): 43-48)

Estimation of costs caused by cystic echinococcosis

Hydatid disease or cystic echinococcosis, caused by the parasite Echinococcus granulosus, has a worldwide distribution, affecting people of working age and can cause high levels of morbidity and even death. To estimate the economic impact at the human and animal level caused by the disease in Chile. We analyzed information about the disease obtained from reports and publications emanated from the Chilean Ministry of Health, United Nations Food and Agriculture Organization, the U.S. National Institute of Statistics and the National Agricultural Service. Animal derived costs were estimated evaluating the expenses for pharmacological treatment of infected dogs and animal production losses derived from confiscations and reductions in meat production. The total number of patients who underwent surgery to remove a hydatid cyst in Chile during 2012, was estimated as 767 individuals. The annual costs derived only from surgical treatment, were estimated in USD 2.46 million. Summing the costs of sick leaves and loss of productivity, the costs at the human level ascended to USD 3.13 million. Considering human and animal costs, the annual economic burden of the disease was estimated in USD 14.35 million. The Analysis of the regional distribution of human and animal hydatidosis, suggests a significant environmental contamination with parasite eggs in high incidence regions such as Aysén, Araucanía, BioBío and Coquimbo. The efficiency of control programs for the disease would be greatly improved if the causes for these regional contaminations are elucidated.

Helicobacter pylori and Gastric Cancer

Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the ‘point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations.

An investigation into the relationship between region specific quality of life and adverse tuberculosis treatment outcomes in Istanbul, Turkey

Background and objectiveIstanbul has the highest incidence of tuberculosis (TB) in Turkey. It is also the largest city, with considerable differences in quality of life across its urban regions. The aim of this study is to investigate the relationship between (i) the diverse quality of life across specific urban regions, (ii) TB incidence rates, inclusive of demographic and clinical characteristics of TB patients, and (iii) adverse treatment outcomes. MethodsThis retrospective study included 23,845 new TB patients (recorded in the National TB Registry between 2006 and 2010) in Istanbul. Thirty-nine urban districts of Istanbul were ranked into five groups on the basis of an urban quality of life index. Patient data were matched with these groups, and further categorized according to ‘age’, ‘sex’, ‘country of birth’ and ‘antibiotics resistance’. Adverse treatment outcomes and TB incidence rates were extracted from official records. Logistic regression, clustered analyses, 95% CI and p values (STATA) were reported to describe the association between variables. ResultsSix per cent of total cases had ‘at least one adverse treatment outcome’ (default 3.8%, failure 0.5%, death 1.7% in total cases). ‘An adverse treatment outcome’ was found to be associated with age OR (CI 95%) (1.02 (1.01–1.03)); ‘male sex’ 1.65 (1.28–2.12); ‘other country of birth’ 4.82 (3.05–7.62); 100,000 per ‘over 60’ insidence goups 1.61 (1.32-1.97), the lowest quality of life index 0.65 (0.47-0.83). ConclusionsPatients with high tuberculosis risk factors living in high incidence regions need to be closely monitored. Patients living in lower ranking regions are more likely to have ‘poor treatment outcomes’.

Use of a Recombinant Cysteine Proteinase from Leishmania (Leishmania) infantum chagasi for the Immunotherapy of Canine Visceral Leishmaniasis

BackgroundA recombinant cysteine proteinase from Leishmania (Leishmania) infantum chagasi (rLdccys1) was previously shown to induce protective immune responses against murine and canine visceral leishmaniasis. These findings encouraged us to use rLdccys1 in the immunotherapy of naturally infected dogs from Teresina, Piauí, a region of high incidence of visceral leishmaniasis in Brazil.Methodology/Principal FindingsThirty naturally infected mongrel dogs displaying clinical signs of visceral leishmaniasis were randomly divided in three groups: one group received three doses of rLdccys1 in combination with the adjuvant Propionibacterium acnes at one month interval between each dose; a second group received three doses of P. acnes alone; a third group received saline. The main findings were: 1) dogs that received rLdccys1 with P. acnes did not display increase of the following clinical signs: weight loss, alopecia, onychogryphosis, cachexia, anorexia, apathy, skin lesions, hyperkeratosis, ocular secretion, and enlarged lymph nodes; they also exhibited a significant reduction in the spleen parasite load in comparison to the control dogs; 2) rLdccys1-treated dogs exhibited a significant delayed type cutaneous hypersensitivity elicited by the recombinant antigen, as well as high IgG2 serum titers and low IgG1 serum titers; sera from rLdccys1-treated dogs also contained high IFN-γ and low IL-10 concentrations; 3) control dogs exhibited all of the clinical signs of visceral leishmaniasis and had low serum IgG2 and IFN-γ levels and high concentrations of IgG1 and IL-10; 4) all of the dogs treated with rLdccys1 were alive 12 months after treatment, whereas dogs which received either saline or P. acnes alone died within 3 to 7 months.Conclusions/SignificanceThese findings illustrate the potential use of rLdccys1 as an additional tool for the immunotherapy of canine visceral leishmaniasis and support further studies designed to improve the efficacy of this recombinant antigen for the treatment of this neglected disease.