A Discovery-Based Metabolomic Approach Using UPLC-Q-TOF-MS/MS Reveals Potential Antimalarial Compounds Present in Artemisia annua L.

In 1972, Nobel laureate Youyou Tu's research team conducted clinical trials on the dried material of Artemisia annua L. from Beijing extracted by ether and then treated with alkali (called "ether neutral dry"), which showed that artemisinin was not the only antimalarial component contained. The biosynthesis of sesquiterpenoids in A. annua has increased exponentially after unremitting cultivation efforts, and the plant resources are now quite different from those in the 1970s. In consideration of emerging artemisinin resistance, it is of great theoretical and practical value to further study the antimalarial activity of A. annua and explore its causes. The purpose of this study is to clarify scientific questions, such as "What ingredients are synergistic with artemisinin in A. annua?", and "Are there non-artemisinin antimalarial ingredients in A. annua?". In this paper, Beijing wild A. annua was used as a control and two representative cultivation species of A. annua were selected to evaluate the antimalarial activity of the herbal medicine. The antimalarial activity of different extracts on mice was studied using the Peters' four-day suppressive test. UPLC-Q-TOF-MS was used to obtain mass spectrum data for all samples, and a UNIFI platform was used for identification. A multivariate statistical method was used to screen the different compounds with positive correlations. The antimalarial activity of different components from the ether extract and alkali treatments was determined and antimalarial components other than artemisinin were obtained. A total of 24 flavonoids, 68 sesquiterpenoids and 21 other compounds were identified. Compounds associated with differential antimalarial activity were identified. The material basis for the antimalarial activity of A. annua was clarified. The antimalarial components of A. annua include two categories: first, artemisinin and non-artemisinin antimalarial active components, of which the non-artemisinin antimalarial active components may include 5α-hydroperoxy-eudesma-4(15),11-diene; second, several antimalarial synergistic ingredients in A. annua, including arteanniun B, arteanniun B analogues and polymethoxy flavonoids.

A New Strategy to Fight Metallodrug Resistance: Mitochondria-Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells.

Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein-based cyclometalated IrIII complex, Ir-Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir-Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death. Moreover, Ir-Rhein can overcome cisplatin resistance. Co-incubation experiment, 3D tumor spheroids experiment and transcriptome analysis reveal that Ir-Rhein shows promising antiproliferation performance for cisplatin-resistant cancer cells with the regulation of platinum resistance-related transporters. To our knowledge, this is a new strategy to overcome metallodrug resistance with a mitochondria-relevant treatment.

Hepatitis A Outbreaks in Developed Countries: Detection, Control, and Prevention.

The incidence of hepatitis A virus (HAV) infection has been low in developed countries for decades; however, many adults in these countries are susceptible to HAV infection. In recent years, the global trade of food products originating from HAV-endemic countries resulted in HAV outbreaks associated with imported foods in developed countries. This article aims to review the characteristics of selected HAV outbreaks associated with imported food in developed countries during 2012-2018, and discusses improvements in global public health capabilities and new tools for effective detection, control, and prevention of HAV outbreaks.

A Point System to Forecast Hepatocellular Carcinoma Risk Before and After Treatment Among Persons with Chronic Hepatitis C.

BACKGROUND: Risk of hepatocellular carcinoma (HCC) may be difficult to determine in the clinical setting. AIM: Develop a scoring system to forecast HCC risk among patients with chronic hepatitis C. METHODS: Using data from the Chronic Hepatitis Cohort Study collected during 2005-2014, we derived HCC risk scores for males and females using an extended Cox model with aspartate aminotransferase-to-platelet ratio index (APRI) as a time-dependent variables and mean Kaplan-Meier survival functions from patient data at two study sites, and used data collected at two separate sites for external validation. For model calibration, we used the Greenwood-Nam-D'Agostino goodness-of-fit statistic to examine differences between predicted and observed risk. RESULTS: Of 12,469 patients (1628 with a history of sustained viral response [SVR]), 504 developed HCC; median follow-up was 6 years. Final predictors in the model included age, alcohol abuse, interferon-based treatment response, and APRI. Point values, ranging from -3 to 14 (males) and -3 to 12 (females), were established using hazard ratios of the predictors aligned with 1-, 3-, and 5-year Kaplan-Meier survival probabilities of HCC. Discriminatory capacity was high (c-index 0.82 males and 0.84 females) and external calibration demonstrated no differences between predicted and observed HCC risk for 1-, 3-, and 5-year forecasts among males (all p values >0.97) and for 3- and 5-year risk among females (all p values >0.87). CONCLUSION: This scoring system, based on age, alcohol abuse history, treatment response, and APRI, can be used to forecast up to a 5-year risk of HCC among hepatitis C patients before and after SVR.

All-Cause Mortality and Progression Risks to Hepatic Decompensation and Hepatocellular Carcinoma in Patients Infected With Hepatitis C Virus.

BACKGROUND: A key question in care of patients with chronic hepatitis C virus (HCV) infection is beginning treatment immediately vs delaying treatment. Risks of mortality and disease progression in "real world" settings are important to assess the implications of delaying HCV treatment. METHODS: This was a cohort study of HCV patients identified from 4 integrated health systems in the United States who had liver biopsies during 2001-2012. The probabilities of death and progression to hepatocellular carcinoma, hepatic decompensation (hepatic encephalopathy, esophageal varices, ascites, or portal hypertension) or liver transplant were estimated over 1, 2, or 5 years by fibrosis stage (Metavir F0-F4) determined by biopsy at beginning of observation. RESULTS: Among 2799 HCV-monoinfected patients who had a qualifying liver biopsy, the mean age at the time of biopsy was 50.7 years. The majority were male (58.9%) and non-Hispanic white (66.9%). Over a mean observation of 5.0 years, 261 (9.3%) patients died and 34 (1.2%) received liver transplants. At 5 years after biopsy, the estimated risk of progression to hepatic decompensation or hepatocellular carcinoma was 37.2% in stage F4, 19.6% in F3, 4.7% in F2, and 2.3% in F0-F1 patients. Baseline biopsy stage F3 or F4 and platelet count below normal were the strongest predictors of progression to hepatic decompensation or hepatocellular carcinoma. CONCLUSIONS: The risks of death and progression to liver failure varied greatly by fibrosis stage. Clinicians and policy makers could use these progression risk data in prioritization and in determining the timing of treatment for patients in early stages of liver disease.

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection.

BACKGROUND & AIMS: Sustained virological response (SVR) to antiviral therapy for hepatitis C virus (HCV) correlates with changes in biochemical measures of liver function. However, little is known about the long-term effects of SVR on liver fibrosis. We investigated the effects of HCV therapy on fibrosis, based on the Fibrosis-4 (FIB4) score, over a 10-year period. METHODS: We collected data from participants in the Chronic Hepatitis Cohort Study-a large observational multicenter study of patients with hepatitis at 4 US health systems-from January 1, 2006, through December 31, 2013. We calculated patients' FIB4 score and the aminotransferase-to-platelet ratio index (APRI) score over a 10-year period. Of 4731 patients with HCV infection, 1657 (35%) were treated and 755 (46%) of these patients achieved SVR. RESULTS: In propensity score-adjusted analyses, we observed significant longitudinal changes in FIB4 score that varied with treatment and response to treatment. In patients achieving SVR, FIB4 scores decreased sharply, remaining significantly lower over the 10-year period than in untreated patients or patients with treatment failure (P < .001). In independent analyses, men and patients with HCV genotype 1 or 3 infections had higher FIB4 scores than women or patients with HCV genotype 2 infections (P < .01 for both). Findings were similar in a sensitivity analysis that substituted the APRI as the marker of fibrosis instead of the FIB4 score. CONCLUSIONS: SVR to HCV treatment appears to induce long-term regression of fibrosis based on FIB4 scores collected over 10 years from a large observational study of US hepatitis patients. Patients receiving no treatment or with treatment failure had progressive increases in FIB4 scores.

Hepatitis A hospitalizations in the United States, 2002-2011.

UNLABELLED: Hepatitis A illness severity increases with age. One indicator of hepatitis A illness severity is whether persons are hospitalized. We describe changes in primary hepatitis A hospitalization rates in the United States from 2002-2011, including changes in demographics, secondary discharge diagnoses, and factors affecting hospitalization duration. We describe changes from 2002-2011 among U.S. residents hospitalized with a principal hepatitis A diagnosis and accompanying secondary diagnoses using ICD-9 codes from the National Inpatient Survey discharge data. We calculated rates of hospitalizations with hepatitis A as the principal discharge diagnosis and rates of secondary discharge diagnoses. Using multiple regression, we assessed the effect of secondary diagnoses on hospitalization length of stay for five time intervals: 2002-2003, 2004-2005, 2006-2007, 2008-2009, and 2010-2011. Rates of hospitalization for hepatitis A as a principal diagnosis decreased from 0.72/100,000 to 0.29/100,000 (P < 0.0001) and mean age of those hospitalized increased from 37.6 years to 45.5 years (P < 0.0001) during 2002-2011. The percentage of hepatitis A hospitalizations covered by Medicare increased from 12.4% to 22.7% (P < 0.0001). Secondary comorbid discharge diagnoses increased, including liver disease, hypertension, ischemic heart disease, disorders of lipid metabolism, and chronic kidney disease. No changes in length-of-stay or in-hospital deaths from hepatitis A over time were found, but persons with liver disease were hospitalized longer. CONCLUSION: Hospitalization rates for hepatitis A illness have declined significantly from 2002-2011, but the characteristics of the hospitalized population also changed. Persons hospitalized for hepatitis A in recent years are older and more likely to have liver diseases and other comorbid medical conditions. Hepatitis A disease and resulting hospitalizations could be prevented through adult vaccination.

Cost-effectiveness of hepatitis C treatment for patients in early stages of liver disease.

UNLABELLED: New treatments for hepatitis C virus (HCV) may be highly effective but are associated with substantial costs that may compel clinicians and patients to consider delaying treatment. This study investigated the cost-effectiveness of these treatments with a focus on patients in early stages of liver disease. We developed a state-transition (or Markov) model to calculate costs incurred and quality-adjusted life-years (QALYs) gained following HCV treatment, and we computed incremental cost-effectiveness ratios (cost per QALY gained, in 2012 US dollars) for treatment at different stages of liver disease versus delaying treatment until the subsequent liver disease stage. Our analysis did not include the potential treatment benefits associated with reduced non-liver-related mortality or preventing HCV transmission. All parameter values, particularly treatment cost, were varied in sensitivity analyses. The base case scenario represented a 55-year-old patient with genotype 1 HCV infection with a treatment cost of $100,000 and treatment effectiveness of 90%. In this scenario, for a 55-year-old patient with moderate liver fibrosis (Metavir stage F2), the cost-effectiveness of immediately initiating treatment at F2 (versus delaying treatment until F3) was $37,300/QALY. For patients immediately treated at F0 (versus delaying treatment until F1), the threshold of treatment costs that yielded $50,000/QALY and $100,000/QALY cost-effectiveness ratios were $22,200 and $42,400, respectively. CONCLUSION: Immediate treatment of HCV-infected patients with moderate and advanced fibrosis appears to be cost-effective, and immediate treatment of patients with minimal or no fibrosis can be cost-effective as well, particularly when lower treatment costs are assumed.

Late diagnosis of hepatitis C virus infection in the Chronic Hepatitis Cohort Study (CHeCS): Missed opportunities for intervention.

UNLABELLED: To determine the stage of liver disease at initial diagnosis of hepatitis C virus (HCV) infection, we analyzed data from the Chronic Hepatitis Cohort Study (CHeCS), a large U.S. observational study. We examined the temporal relationships of initial HCV infection diagnosis with cirrhosis-defined by liver biopsy or mean FIB-4 score >5.88-and time to onset of cirrhotic decompensation in electronic medical records. We determined time in the health system prior to HCV diagnosis and rates of hospitalization and death following HCV diagnosis. Of 14,717 patients with chronic HCV seen during 2006-2011, 6,166 (42%) had a definable time of initial HCV diagnosis. Of these, 1,056 (17%) patients met our definition for "late diagnosis" with either cirrhosis concurrent with initial HCV diagnosis (n = 550), a first diagnosis of hepatic decompensation before or within 12 months after initial HCV diagnosis (n = 506), or both (n = 314). Patients with late diagnosis had an average of 6 years in the health system before their HCV diagnosis. In a comparison with patients without late diagnosis, hospitalization (59% versus 35%) and death (33% versus 9%) were more frequent among patients with late diagnosis. Among all who died, mean (median) time from initial HCV diagnosis to death was 4.8 (4.2) years. CONCLUSION: Many CHeCS patients had advanced liver disease concurrent with their initial HCV diagnosis despite many years of engagement with the healthcare system, and these patients had high rates of hospitalization and mortality.

Prevalence of Renal Impairment and Associated Conditions Among HCV-Infected Persons in the Chronic Hepatitis Cohort Study (CHeCS).

BACKGROUND: Guidelines for the treatment of HCV-infected persons were updated in August 2015 with new recommendations for patients with renal impairment. Treatment is imperative for patients with severe, renal-associated extrahepatic manifestations of HCV infection. AIMS: We sought to describe the prevalence of these conditions among current HCV-infected patients in a population-based prospective, observational cohort study at four large US health systems. METHODS: Data from cohort patients with chronic HCV infection during 2012 were analyzed for the period from 2006 to 2013. We determined the prevalence of mild to moderately impaired renal function defined as having the most recent estimated glomerular filtration rate [eGFR] ≤ 80 ml/min/1.73 m(2), with severe impairment defined as eGFR < 30 ml/min/1.73 m(2), based on the treatment guidelines. Prevalence of extrahepatic conditions was ascertained using ICD9-codes. RESULTS: Among 5772 persons, the prevalence of eGFR ≤ 80 was 33 % and eGFR < 30 was 2 %, including among patients with hepatic fibrosis. Diagnosed extrahepatic renal manifestations were rare: vasculitis- 0.2 %, nephrotic syndrome- 0.3 %, and cryoglobulinemia- 0.9 %. CONCLUSIONS: While the prevalence of severe renal impairment and diagnosed extrahepatic manifestations was low, mild-to-moderate renal impairment was common in HCV patients, including those with advanced liver fibrosis for whom the need for treatment is urgent.

Frequency of and Factors Associated with Receipt of Liver-Related Specialty Care Among Patients with Hepatitis C in the Chronic Hepatitis Cohort Study.

BACKGROUND: Linking persons with hepatitis C virus (HCV) to care and treatment is critical to reduction in disease burden; typically, this entailed referral to a specialist. However, data regarding the frequency and factors associated with referral among patients in healthcare organizations (HCOs) are lacking. METHODS: Among persons in four US HCOs with newly diagnosed HCV during 2006-2011, we determined the frequency of liver-related specialist care after diagnosis. We also identified sociodemographic and clinical characteristics associated with such care by multivariate analysis, adjusted for all variables. RESULTS: Among 3592 patients with newly diagnosed HCV, 57 % (range among sites 45-90 %) received specialist care; of these, 57 % received care within 90 days of diagnosis. Patient characteristics associated with receipt of specialist care included: affiliation with one of the study sites [adjusted odds ratio (aOR) 4.8 vs. the referent site); having Medicare plus private insurance (aOR 1.6 vs. Medicaid); and having elevated alanine aminotransferase (ALT) (aOR 1.6 vs. normal ALT) or lower platelet values (aOR 1.4 vs. normal platelet level). Specialist care within 90 days of diagnosis was associated with private insurance (aOR 1.5 vs. Medicaid), elevated ALT levels (aOR 1.3-2.3 vs. normal), and having ≥2 comorbid conditions (aOR 1.4 vs. no comorbid conditions). Compared to patients not referred, those referred were more likely to be treated (aOR 3.5). CONCLUSIONS: Receipt of specialist care among persons with newly diagnosed HCV varied among HCOs. Clinical evidence of liver disease and having private insurance were associated with prompt receipt of specialist care and HCV treatment.

Increased incidence of cancer and cancer-related mortality among persons with chronic hepatitis C infection, 2006-2010.

BACKGROUND & AIMS: Persons chronically infected with the hepatitis C virus (HCV) may be at higher risk for developing and dying from non-liver cancers than the general population. METHODS: 12,126 chronic HCV-infected persons in the Chronic Hepatitis Cohort Study (CHeCS) contributed 39,984 person-years of follow-up from 2006 to 2010 and were compared to 133,795,010 records from 13 Surveillance, Epidemiology and End Results Program (SEER) cancer registries, and approximately 12 million U.S. death certificates from Multiple Cause of Death (MCOD) data. Measurements included standardized rate ratios (SRR) and relative risk (RR). RESULTS: The incidence of the following cancers was significantly higher among patients with chronic HCV infection: liver (SRR, 48.6 [95% CI, 44.4-52.7]), pancreas (2.5 [1.7-3.2]), rectum (2.1 [1.3-2.8]), kidney (1.7 [1.1-2.2]), non-Hodgkin lymphoma (NHL) (1.6 [1.2-2.1]), and lung (1.6 [1.3-1.9]). Age-adjusted mortality was significantly higher among patients with: liver (RR, 29.6 [95% CI, 29.1-30.1]), oral (5.2 [5.1-5.4]), rectum (2.6 [2.5-2.7]), NHL (2.3 [2.2-2.31]), and pancreatic (1.63 [1.6-1.7]) cancers. The mean ages of cancer diagnosis and cancer-related death were significantly younger among CHeCS HCV cohort patients compared to the general population for many cancers. CONCLUSIONS: Incidence and mortality of many types of non-liver cancers were higher, and age at diagnosis and death younger, in patients with chronic HCV infection compared to the general population.

Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort Study (CHeCS): a retrospective and prospective observational study.

OBJECTIVES: The severity of liver disease in the hepatitis C virus (HCV)-infected population in the United States remains uncertain. We estimated the prevalence of cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters including liver biopsy, diagnosis/procedure codes, and a biomarker. METHODS: Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received health services during 2006-2010 were included. Cirrhosis was identified through liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic decompensation, and Fibrosis-4 (FIB-4) scores ≥5.88. Demographic and clinical characteristics associated with cirrhosis were identified through multivariable logistic modeling. RESULTS: Among 9,783 patients, 2,788 (28.5%) were cirrhotic by at least one method. Biopsy identified cirrhosis in only 661 (7%) patients, whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%) patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only 356 (54%) had an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender, Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes, history of antiviral therapy, and history of alcohol abuse were independently associated with higher odds of cirrhosis (all, P<0.05). Conversely, private health insurance coverage, black race, and HCV genotype 2 were associated with lower odds of cirrhosis. CONCLUSIONS: A high proportion of patients with biopsy-confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD-9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis in cohort studies. Use of additional parameters suggests a fourfold higher prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest that cirrhosis in CHC patients may be significantly underdocumented and underdiagnosed.

Estimating the Number of Patients Infected With Chronic HCV in the United States Who Meet Highest or High-Priority Treatment Criteria.

We estimated the number of people infected with HCV in the United States who would qualify for immediate treatment according to the 2014 guidance. We based fibrosis stage on biopsy results, when available, or on FIB-4 scores. We used laboratory tests and International Classification of Diseases, Ninth Revision, Clinical Modification codes to determine if patients had any qualifying comorbidities. Of the 2.7 million people with HCV infection, we assumed that 1.35 million (50%) had been diagnosed. We estimated 457, 000 met the highest and 356, 000 the high-priority criteria for treatment, indicating that as many as 813,000 people could be treated immediately with new therapies. These estimates can inform planning efforts to address clinical capacity constraints and treatment costs.

Mortality among persons in care with hepatitis C virus infection: the Chronic Hepatitis Cohort Study (CHeCS), 2006-2010.

BACKGROUND: The number of deaths in hepatitis C virus (HCV)-infected persons recorded on US death certificates has been increasing, but actual rates and causes of death in these individuals have not been well elucidated. METHODS: Disease-specific, liver-related, and non-liver-related mortality data for HCV-infected patients in an observational cohort study, the Chronic Hepatitis Cohort Study (CHeCS) at 4 US healthcare systems, were compared with multiple cause of death (MCOD) data in 12 million death certificates in 2006-2010. Premortem diagnoses, liver biopsies, and FIB-4 scores (a noninvasive measure of liver damage) were examined. RESULTS: Of 2 143 369 adult patients seen at CHeCS sites in 2006-2010, 11 703 (0.5%) had diagnosed chronic HCV infection, and 1590 (14%) died. The majority of CHeCS decedents were born from 1945 to 1965 (75%), white (50%), and male (68%); mean age of death was 59 years, 15 years younger than MCOD deaths. The age-adjusted mortality rate for liver disease in CHeCS was 12 times higher than the MCOD rate. Before death, 63% of decedents had medical record evidence of chronic liver disease, 76% had elevated FIB-4 scores, and, among those biopsied, 70% had moderate or worse liver fibrosis. However, only 19% of all CHeCS decedents and only 30% of those with recorded liver disease had HCV listed on their death certificates. CONCLUSIONS: HCV infection is greatly underdocumented on death certificates. The 16 622 persons with HCV listed in 2010 may represent only one-fifth of about 80 000 HCV-infected persons dying that year, at least two-thirds of whom (53 000 patients) would have had premortem indications of chronic liver disease.

Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012.

BACKGROUND: Reports of acute hepatitis C in young persons in the United States have increased. We examined data from national surveillance and supplemental case follow-up at selected jurisdictions to describe the US epidemiology of hepatitis C virus (HCV) infection among young persons (aged ≤30 years). METHODS: We examined trends in incidence of acute hepatitis C among young persons reported to the Centers for Disease Control and Prevention (CDC) during 2006-2012 by state, county, and urbanicity. Sociodemographic and behavioral characteristics of HCV-infected young persons newly reported from 2011 to 2012 were analyzed from case interviews and provider follow-up at 6 jurisdictions. RESULTS: From 2006 to 2012, reported incidence of acute hepatitis C increased significantly in young persons-13% annually in nonurban counties (P = .003) vs 5% annually in urban counties (P = .028). Thirty (88%) of 34 reporting states observed higher incidence in 2012 than 2006, most noticeably in nonurban counties east of the Mississippi River. Of 1202 newly reported HCV-infected young persons, 52% were female and 85% were white. In 635 interviews, 75% of respondents reported injection drug use. Of respondents reporting drug use, 75% had abused prescription opioids, with first use on average 2.0 years before heroin. CONCLUSIONS: These data indicate an emerging US epidemic of HCV infection among young nonurban persons of predominantly white race. Reported incidence was higher in 2012 than 2006 in at least 30 states, with largest increases in nonurban counties east of the Mississippi River. Prescription opioid abuse at an early age was commonly reported and should be a focus for medical and public health intervention.

Prevalence of HIV, sexually transmitted infections, and viral hepatitis by Urbanicity, among men who have sex with men, injection drug users, and heterosexuals in the United States.

BACKGROUND: Men who have sex with men (MSM), injection drug users (IDUs), and certain subgroups of heterosexuals are disproportionately affected by the syndemics of HIV, other sexually transmitted infections, and viral hepatitis. Although understanding the burden of these infections in these populations by urbanicity (the degree to which a geographic area is urban) is critical to targeting prevention programs, few studies have done so. METHODS: We analyzed nationally representative 1999 to 2010 data from the National Health and Nutrition Examination Survey on persons aged 18 to 59 years. We estimated the weighted prevalence of HIV, herpes simplex virus type 2 (HSV-2), human papillomavirus, chlamydia, hepatitis B, and hepatitis C, stratified by urbanicity level, for the overall sample, MSM, IDUs, and heterosexuals. Geographic areas with population at least million are classified into large central and large fringe metropolitan counties. RESULTS: Overall, large central metropolitan areas had a higher prevalence of HIV, HSV-2, and hepatitis B. HIV prevalence among MSM was elevated in large central and large fringe metro areas (14.5% and 16.9%, respectively). Among heterosexuals, large central metropolitan areas had elevated prevalence of HSV-2, chlamydia, and hepatitis B. Human papillomavirus and hepatitis C prevalence did not vary significantly by urbanicity for any population, including IDUs. CONCLUSIONS: Infections with higher prevalence in urban areas merit a geographically focused approach to screening and prevention programs, whereas those with uniform prevalence across levels of urbanicity would benefit from a generalized prevention approach. These nationally representative, population-based data allow for more effective planning for prevention programs.

Racial disparities in the proportion of current, unresolved hepatitis C virus infections in the United States, 2003-2010.

BACKGROUND: The hepatitis C virus (HCV) antibody test alone does not distinguish current from resolved infections. AIM: The study aimed to describe the percentage of current HCV infection, defined by HCV RNA positivity, among those tested positive for anti-HCV, and to examine characteristics of those with current infection. METHODS: Using nationally representative data from the 2003 to 2010 National Health and Nutrition Examination Surveys, descriptive analyses and regressions were performed on data from anti-HCV-positive adults aged ≥ 40 years. RESULTS: Of 13,909 participants examined, 304 were anti-HCV-positive. Of these, 238 or 75.3% [95% confidence interval (CI) 67.5-81.8%] had detectable viral RNA. The percentage of current, unresolved HCV infection was highest among non-Hispanic Blacks (91.1%) and lowest among those with a college education (57.3%). In multivariate analyses, non-Hispanic Blacks were more likely to have current HCV infection compared to non-Hispanic Whites (adjusted odds ratio 3.9, 95% CI 1.6-9.2). Among persons with current HCV infection, most had elevated alanine aminotransferase (56.5%) or aspartate aminotransferase (71.8%) levels, but only 35.3% reported having been diagnosed with any abnormal liver conditions. Excessive alcohol drinking was reported by 27.3% of participants with current HCV infection. CONCLUSIONS: Among adults aged ≥ 40 years who had ever been infected with HCV, approximately three-quarters had current, unresolved HCV infection. Non-Hispanic Blacks were more likely to have current infection than non-Hispanic Whites. The majority of those with current infection had abnormal liver function tests but had not received appropriate diagnoses. Many currently infected persons would benefit from lifestyle modifications to avoid the multiplicative effect of alcohol on HCV infection.

Safety and effectiveness of a 2009 H1N1 vaccine in Beijing.

BACKGROUND: After the first monovalent 2009 pandemic influenza A (H1N1) vaccine became available in September 2009, Chinese officials conducted a mass vaccination program in Beijing. We evaluated the safety and effectiveness of the vaccine. METHODS: During a 5-day period in September 2009, a total of 95,244 children and adults received the PANFLU.1 vaccine (Sinovac Biotech), a monovalent split-virion vaccine of 15 µg of hemagglutinin antigen without adjuvant. We assessed adverse events after immunization through an enhanced passive-surveillance system and through active surveillance, using diary cards and telephone interviews. Active surveillance for neurologic diseases was implemented in hospitals citywide. To assess vaccine effectiveness, we compared the rates of reported laboratory-confirmed cases of 2009 H1N1 virus infection in students who received the vaccine with the rates in those who did not receive the vaccine, starting 2 weeks after the mass vaccination. RESULTS: As of December 31, 2009, adverse events were reported by 193 vaccine recipients. Through hospital-based active surveillance, 362 cases of incident neurologic diseases were identified within 10 weeks after the mass vaccination, including 27 cases of the Guillain-Barré syndrome. None of the neurologic conditions occurred among vaccine recipients. From 245 schools, 25,037 students participated in the mass vaccination and 244,091 did not. During the period from October 9 through November 15, 2009, the incidence of confirmed cases of 2009 H1N1 virus infection per 100,000 students was 35.9 (9 of 25,037) among vaccinated students and 281.4 (687 of 244,091) among unvaccinated students. Thus, the estimated vaccine effectiveness was 87.3% (95% confidence interval, 75.4 to 93.4). CONCLUSIONS: Among 95,244 children and adults in Beijing, the PANFLU.1 vaccine had a safety profile similar to those of seasonal influenza vaccines and appeared to be effective against confirmed H1N1 virus infection in school-age children. (Funded by the Beijing Municipal Health Bureau.).

Screening and treating Chlamydia trachomatis genital infection to prevent pelvic inflammatory disease: interpretation of findings from randomized controlled trials.

We critically reviewed randomized controlled trials evaluating chlamydia screening to prevent pelvic inflammatory disease (PID) and explored factors affecting interpretation and translation of trial data into public health prevention. Taken together, data from these trials offer evidence that chlamydia screening and treatment is an important and useful intervention to reduce the risk of PID among young women. However, the magnitude of benefit to be expected from screening may have been overestimated based on the earliest trials. It is likely that chlamydia screening programs have contributed to declines in PID incidence through shortening prevalent infections, although the magnitude of their contribution remains unclear. Program factors such as screening coverage as well as natural history factors such as risk of PID after repeat chlamydia infection can be important in determining the impact of chlamydia screening on PID incidence in a population. Uptake of chlamydia screening is currently suboptimal, and expansion of screening among young, sexually active women remains a priority. To reduce transmission and repeat infections, implementation of efficient strategies to treat partners of infected women is also essential. Results of ongoing randomized evaluations of the effect of screening on community-wide chlamydia prevalence and PID will also be valuable.