Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Hu DJ[original query] |
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Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age.
Crider KS , Quinlivan EP , Berry RJ , Hao L , Li Z , Maneval D , Yang TP , Rasmussen SA , Yang Q , Zhu JH , Hu DJ , Bailey LB . PLoS One 2011 6 (12) e28144 ![]() Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (-14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation. |
Invasive Streptococcus pneumoniae infection among hospitalized patients in Jingzhou city, China, 2010-2012
Jiang H , Huai Y , Chen H , Uyeki TM , Chen M , Guan X , Liu S , Peng Y , Yang H , Luo J , Zheng J , Huang J , Peng Z , Xiang N , Zhang Y , Klena JD , Hu DJ , Rainey JJ , Huo X , Xiao L , Xing X , Zhan F , Yu H , Varma JK . PLoS One 2018 13 (8) e0201312 BACKGROUND: Streptococcus pneumoniae (Sp) is a leading cause of bacterial pneumonia, meningitis, and sepsis and a major source of morbidity and mortality worldwide. Invasive pneumococcal disease (IPD) is defined as isolation of Sp from a normally sterile site, including blood or cerebrospinal fluid. The aim of this study is to describe outcomes as well as clinical and epidemiological characteristics of hospitalized IPD case patients in central China. METHODS: We conducted surveillance for IPD among children and adults from April 5, 2010 to September 30, 2012, in four major hospitals in Jingzhou City, Hubei Province. We collected demographic, clinical, and outcome data for all enrolled hospitalized patients with severe acute respiratory infection (SARI) or meningitis, and collected blood, urine, and cerebrospinal fluid (CSF) for laboratory testing for Sp infections. Collected data were entered into Epidata software and imported into SPSS for analysis. RESULTS: We enrolled 22,375 patients, including 22,202 (99%) with SARI and 173 (1%) with meningitis. One hundred and eighteen (118, 3%) with either SARI or meningitis were Sp positive, 32 (0.8%) from blood/CSF culture, and 87 (5%) from urine antigen testing. Of those 118 patients, 57% were aged >/=65 years and nearly 100% received antibiotics during hospitalization. None were previously vaccinated with 7-valent pneumococcal conjugate vaccine (PCV 7), 23-valent pneumococcal polysaccharide vaccine, or seasonal influenza vaccine. The main serotypes identified were 14, 12, 3, 1, 19F, 4, 5, 9V, 15 and 18C, corresponding to serotype coverage rates of 42%, 63%, and 77% for PCV7, PCV10, and PCV13, respectively. CONCLUSIONS: Further work is needed to expand access to pneumococcal vaccination in China, both among children and potentially among the elderly, and inappropriate use of antibiotics is a widespread and serious problem in China. |
Clinical characteristics and factors associated with severe acute respiratory infection and influenza among children in Jingzhou, China
Huai Y , Guan X , Liu S , Uyeki TM , Jiang H , Klena J , Huang J , Chen M , Peng Y , Yang H , Luo J , Zheng J , Peng Z , Huo X , Xiao L , Chen H , Zhang Y , Xing X , Feng L , Hu DJ , Yu H , Zhan F , Varma JK . Influenza Other Respir Viruses 2016 11 (2) 148-156 BACKGROUND: Influenza is an important cause of respiratory illness in children, but data are limited on hospitalized children with laboratory-confirmed influenza in China. METHODS: We conducted active surveillance for severe acute respiratory infection (SARI) (fever and at least one sign or symptom of acute respiratory illness) among hospitalized pediatric patients in Jingzhou, Hubei province from April 2010 to April 2012. Data were collected from enrolled SARI patients on demographics, underlying health conditions, clinical course of illness, and outcomes. Nasal swabs were collected and tested for influenza viruses by RT-PCR. We described the clinical and epidemiological characteristics of children with influenza, and analyzed the association between potential risk factors and SARI patients with influenza. RESULTS: During the study period, 15,354 children aged <15 years with signs and symptoms of SARI were enrolled at hospital admission.. SARI patients aged 5-15 years with confirmed influenza (H3N2) infection were more likely than children without influenza to have radiographic diagnosis of pneumonia (11/31, 36% vs 15/105, 14%. p-value<0.05). Only 16% (1,116/7,145) of enrolled patients had received seasonal trivalent influenza vaccination within 12 months of hospital admission.Non-vaccinated influenza cases were more likely than vaccinated influenza cases to have pneumonia (31/133, 23% vs 37/256, 15%, p-value<0.05). SARI cases aged 5-15 years diagnosed with influenza were also more likely to have a household member who smoked cigarettes compared to SARI cases without a smoking household member (54/208, 26% vs 158/960, 16%, p-value<0.05) CONCLUSIONS: Influenza A (H3N2) virus infection was an important contributor to pneumonia requiring hospitalization. Our results highlight the importance of surveillance in identifying factors for influenza hospitalization, monitoring adherence to influenza prevention and treatment strategies, and evaluating the disease burden among hospitalized pediatric SARI patients. Influenza vaccination promotion should target children. |
Epidemiology, seasonality and treatment of hospitalized adults and adolescents with influenza in Jingzhou, China, 2010-2012
Zheng J , Huo X , Huai Y , Xiao L , Jiang H , Klena J , Greene CM , Xing X , Huang J , Liu S , Peng Y , Yang H , Luo J , Peng Z , Liu L , Chen M , Chen H , Zhang Y , Huang D , Guan X , Feng L , Zhan F , Hu DJ , Varma JK , Yu H . PLoS One 2016 11 (3) e0150713 BACKGROUND: After the 2009 influenza A (H1N1) pandemic, we conducted hospital-based severe acute respiratory infection (SARI) surveillance in one central Chinese city to assess disease burden attributable to influenza among adults and adolescents. METHODS: We defined an adult SARI case as a hospitalized patient aged ≥ 15 years with temperature ≥38.0 degrees C and at least one of the following: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. For each enrolled SARI case-patient, we completed a standardized case report form, and collected a nasopharyngeal swab within 24 hours of admission. Specimens were tested for influenza viruses by real-time reverse transcription polymerase chain reaction (rRT-PCR). We analyzed data from adult SARI cases in four hospitals in Jingzhou, China from April 2010 to April 2012. RESULTS: Of 1,790 adult SARI patients enrolled, 40% were aged ≥ 65 years old. The median duration of hospitalization was 9 days. Nearly all were prescribed antibiotics during their hospitalization, less than 1% were prescribed oseltamivir, and 28% were prescribed corticosteroids. Only 0.1% reported receiving influenza vaccination in the past year. Of 1,704 samples tested, 16% were positive for influenza. Influenza activity in all age groups showed winter-spring and summer peaks. Influenza-positive patients had a longer duration from illness onset to hospitalization and a shorter duration from hospital admission to discharge or death compared to influenza negative SARI patients. CONCLUSIONS: There is substantial burden of influenza-associated SARI hospitalizations in Jingzhou, China, especially among older adults. More effective promotion of annual seasonal influenza vaccination and timely oseltamivir treatment among high risk groups may improve influenza prevention and control in China. |
Response to challenge dose among young adults vaccinated for hepatitis B as infants: importance of detectable residual antibody to hepatitis B surface antigen
Spradling PR , Kamili S , Xing J , Drobeniuc J , Hu DJ , Middleman AB . Infect Control Hosp Epidemiol 2015 36 (5) 1-5 OBJECTIVE: To determine whether a difference in antibody to hepatitis B surface antigen (anti-HBs) response to a hepatitis B vaccine challenge dose existed among persons with a baseline anti-HBs level of 0 mIU/mL (group 1) and those with "non-zero" levels of 0.1-4.9 (group 2) and 5.0-9.9 (group 3) mIU/mL, according to the VITROS ECi anti-HBs assay. DESIGN: Subanalysis of randomized clinical trial. Response was defined as a postchallenge anti-HBs level of at least 10 mIU/mL and 4-fold rise in anti-HBs level 2 weeks after a single challenge dose of 10 vs 20 microg Engerix-B. Baseline was defined as the anti-HBs level immediately before administration of the challenge dose. SETTING: Pediatric integrated healthcare system near Houston, Texas. PARTICIPANTS: Three hundred nineteen US-born 16-19-year-olds who completed the hepatitis B vaccine series during the first year of life. RESULTS: One hundred seventy-eight persons had zero (group 1) and 141 (114 group 2 and 27 group 3) had non-zero anti-HBs levels at baseline. Response to the challenge dose was significantly higher among those with non-zero vs zero anti-HBs levels, irrespective of challenge dosage; only 1 person with a non-zero anti-HBs level failed to respond to the challenge dose (group 3, 27/27 [100%] vs group 2, 113/114 [99%] vs group 1, 145/178 [82%]; P<.0001). CONCLUSIONS: Among participants with residual anti-HBs levels less than 10 mIU/mL 16-19 years after primary hepatitis B vaccination during infancy, non-zero anti-HBs levels, with rare exception, indicated persistence of immune memory to HBsAg. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01341275. |
Duration of protection after infant hepatitis B vaccination series
Middleman AB , Baker CJ , Kozinetz CA , Kamili S , Nguyen C , Hu DJ , Spradling PR . Pediatrics 2014 133 (6) e1500-7 BACKGROUND: Little is known about duration of protection after the infant primary series of hepatitis B (HB) vaccine in settings of low HB endemicity. This study sought to determine the proportion of adolescents immunized as infants who had protective titers of antibody to hepatitis B surface antigen (anti-HBs) before and after a challenge dose of vaccine. METHODS: US-born 16- through 19-year-olds who received a recombinant HB vaccine 3-dose series initiated within 7 days of birth (group 1) or at ≥4 weeks of age (group 2) and completed by 12 months of age were enrolled. Participants had serologic testing before and 2 weeks after randomization to receive a challenge dose of 10 microg or 20 microg of Engerix-B. Baseline and postchallenge levels of anti-HBs were compared by group, challenge dosage, and demographic and behavioral characteristics. RESULTS: At baseline, 24% had protective anti-HBs levels of ≥10 IU/mL; 92% achieved protective levels after challenge dose. Although group 1 had a lower proportion of seroprotection at baseline, group and challenge dosage were not associated with postchallenge proportion of seroprotection. Being in group 2, higher test dosage, higher baseline geometric mean titer, and nonwhite race were associated with significantly higher geometric mean titer after challenge dose. CONCLUSIONS: More than 90% of study participants immunized against HB as infants exhibited a seroprotective response to a challenge dose of vaccine. Duration of protection from the primary infant HB vaccine series extended through the adolescent years in the setting of low HB endemicity. |
Viral hepatitis C gets personal--the value of human genomics to public health.
Zhang L , Gwinn M , Hu DJ . Public Health Genomics 2013 16 (4) 192-7 ![]() About 180 million people worldwide are chronically infected with hepatitis C virus (HCV), with 3-4 million newly infected each year. Only 15-25% of acute HCV infections clear spontaneously, and the remainder persists as chronic HCV infection. More than 350,000 people die every year from hepatitis C-related liver failure and cancer. There is currently no vaccine and the standard-of-care therapies - peg-interferon alpha (pegIFN) plus ribavirin (RBV) - are expensive and have serious side effects. Also, they may be effective in only 40-50% of patients infected with HCV genotype 1, the most common HCV genotype in the US. Interleukin 28B (IL28B) genotype was recently and convincingly associated with response to pegIFN and RBV therapy. It has emerged as a robust pretreatment predictor of sustained virological response (SVR, i.e. virologic clearance) to pegIFN and RBV as well as to new triple therapy regimens that include a direct-acting antiviral agent with pegIFN and RBV and increase SVR rates as much as 75% in patients infected with HCV genotype 1. Testing for IL28B genotype may contribute to clinical decision-making and could inform clinical guidelines and public health policies. |
Investigation of hepatitis B virus and human immunodeficiency virus transmission among severely mentally ill residents at a long term care facility
Jasuja S , Thompson ND , Peters PJ , Khudyakov YE , Patel MT , Linchangco P , Thai HT , Switzer WM , Shankar A , Heneine W , Hu DJ , Moorman AC , Gerber SI . PLoS One 2012 7 (8) e43252 BACKGROUND: A high prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections have been reported among persons with severe mental illness. In October, 2009, the Cook County Department of Public Health (CCDPH) initiated an investigation following notification of a cluster of HBV infections among mentally ill residents at a long term care facility (LTCF). METHODS: LTCF staff were interviewed and resident medical records were reviewed. Residents were offered testing for HBV, HCV, and HIV. Serum specimens from residents diagnosed with HBV or HIV infection were sent to the Centers for Disease Control and Prevention (CDC) for analysis. RESULTS: Eleven newly diagnosed HBV infections were identified among mentally ill residents at the LTCF. Of these 11 infections, 4 serum specimens were available for complete HBV genome sequencing; all 4 genomes were found to be closely related. Four newly diagnosed HIV infections were identified within this same population. Upon molecular analysis, 2 of 4 HIV sequences from these new infections were found to be nearly identical and formed a tight phylogenetic cluster. CONCLUSIONS: HBV and HIV transmission was identified among mentally ill residents of this LTCF. Continued efforts are needed to prevent bloodborne pathogen transmission among mentally ill residents in LTCFs. |
Prevalence of hepatitis B virus infection among persons with diagnosed diabetes mellitus in the United States, 1999-2010
Schillie SF , Xing J , Murphy TV , Hu DJ . J Viral Hepat 2012 19 (9) 674-6 SUMMARY: The prevalence of hepatitis B virus (HBV) infection among persons with diabetes has not been assessed among the US population, despite increasing reports of HBV transmission in institutional care settings. Using national survey data, we found a 60% higher prevalence of HBV infection among persons with (vs without) diagnosed diabetes. |
Evolving epidemiology of hepatitis C virus in the United States
Klevens RM , Hu DJ , Jiles R , Holmberg SD . Clin Infect Dis 2012 55 Suppl 1 S3-9 The impact of hepatitis C virus (HCV) infection on health and medical care in the United States is a major problem for infectious disease physicians. Although the incidence of HCV infection has declined markedly in the past 2 decades, chronic infection in 3 million or more residents now accounts for more disease and death in the United States than does human immunodeficiency virus (HIV)/AIDS. Current trends in the epidemiology of HCV infection include an apparent increase in young, often suburban heroin injection drug users who initiate use with oral prescription opioid drugs; infections in nonhospital healthcare (clinic) settings; and sexual transmission among HIV-infected persons. Infectious disease physicians will increasingly have the responsibility of diagnosing and treating HCV patients. An understanding of how these patients were infected is important for determining whom to screen and treat. |
HIV-1 and breastfeeding in the United States
Little KM , Hu DJ , Dominguez KL . Adv Exp Med Biol 2012 743 261-70 While breastfeeding remains a significant source of mother-to-child HIV transmission (MTCT) globally, it is the recommended infant feeding option for HIV-infected women in resource-limited settings. However, HIV-infected women in the USA-where breast milk alternatives are acceptable, feasible, affordable, sustainable, and safe-have been counseled to avoid all breastfeeding since 1985. A number of studies have found that despite such recommendations against breastfeeding by HIV-infected women, a very small proportion of HIV-infected women in the USA continue to breastfeed their infants for various reasons. Many of these women received late or no prenatal care, inadequate antiretroviral (ARV) prophylaxis, or were not diagnosed with HIV until at or after labor and delivery. While breastfeeding has never been a major source of perinatal HIV infections in the USA, studies have identified the practice as a risk factor for MTCT in the USA. Complete avoidance remains the only sure way to prevent late postnatal HIV transmission through breastfeeding. (2012 Springer Science+Business Media New York.) |
HIV-HBV coinfection--a global challenge
Kourtis AP , Bulterys M , Hu DJ , Jamieson DJ . N Engl J Med 2012 366 (19) 1749-52 Human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) exact a high toll worldwide. Both can lead to chronic disease, cancer, and death, and neither can be eradicated with the use of current therapies. Antiviral drug resistance often develops after patients have received treatment for some time and is usually followed by the loss of clinical benefit. Coinfection with the two viruses exacerbates the negative effects. | Worldwide, HBV is the leading cause of chronic liver disease and a leading cause of death, accounting for up to half of all cases of cirrhosis and hepatocellular carcinoma.1 An estimated 400 million people are infected with HBV,1 with the majority of cases occurring in regions of Asia and Africa where the virus is endemic. There, up to 70% of adults show serologic evidence of current or prior infection, and 8 to 15% have chronic HBV infection.1 | These staggering infection rates largely reflect a failure of maternal and child health programs. The majority of HBV infections in settings where the virus is highly endemic occur through perinatal transmission (predominant in East and Southeast Asia) or in young children, transmitted through close household contact or through medical or traditional scarification procedures (predominant in Africa).1 Perinatal HBV infection is associated with a 90% risk of chronic hepatitis B, as compared with a risk of less than 5% among adults with intact immunity.1 The risk of perinatal transmission is lower in Africa than in Asia, a disparity that could be due to a lower prevalence of hepatitis Be antigen (HBeAg) and other differences in the pathogenic characteristics of circulating HBV genotypes.1 |
Hepatitis B vaccination of susceptible elderly residents of long term care facilities during a hepatitis B outbreak
Williams RE , Sena AC , Moorman AC , Moore ZS , Sharapov UM , Drobenuic J , Hu DJ , Wood HW , Xing J , Spradling PR . Vaccine 2012 30 (21) 3147-50 Protection of older persons, particularly those with diabetes, against hepatitis B virus (HBV) infection is of growing concern because of increased reports of outbreaks among long-term care facility residents receiving assisted blood glucose monitoring. We evaluated hepatitis B vaccine immunogenicity among residents immunized in response to two such outbreaks in skilled nursing facilities during June 2009-July 2010. One hundred forty-eight (71%) of 209 residents were found to be susceptible to HBV infection. Of 105 patients who began a vaccination series with Twinrix((R)) (0-, 1-, 6-month dosing), 86 (82%) completed the series and postvaccination testing. Of these, most were elderly (median age 79.5 years; range 45-101), female (56%), and African-American (51%). Twenty-nine (34%) vaccinated residents had post-vaccination hepatitis B surface antibody levels ≥10mIU/ml. There were no significant differences in vaccine response by age, gender, race, diabetes status, body mass index, or current smoking status. Our findings indicate that a low proportion of skilled nursing facility residents achieved a seroprotective response after hepatitis B vaccination. |
Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up
Sharapov UM , Bulkow LR , Negus SE , Spradling PR , Homan C , Drobeniuc J , Bruce M , Kamili S , Hu DJ , McMahon BJ . Hepatology 2012 56 (2) 516-22 Persistence of seropositivity conferred by hepatitis A vaccine administered to children under 2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. Infants and young children (N=197) were randomized into three groups to receive a two dose hepatitis A vaccine (HAVRIX, GlaxoSmithKline; 720 EL.U. in 0.5 ml): group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age; within each group infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months, and at 3, 5, 7 and 10 years after second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after dose 2. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV negative and anti-HAV positive mothers, respectively and 4% of group 3 children born to anti-HAV negative mothers. At 10 years, children born to anti-HAV-negative mothers in Group 3 had highest geometric mean concentration (GMC) (97 mIU/mL, 95% CI: 71-133) and children born to anti-HAV-positive mothers in Group 1 had lowest GMC (29 mIU/mL, 95% CI: 20, 4052). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after second dose). CONCLUSION: The seropositivity induced by hepatitis A vaccine given to children < 2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV. (HEPATOLOGY 2012.). |
Persistence of long-term immunity to hepatitis B among adolescents immunized at birth
Chaves SS , Fischer G , Groeger J , Patel PR , Thompson ND , Teshale EH , Stevenson K , Yano VM , Armstrong GL , Samandari T , Kamili S , Drobeniuc J , Hu DJ . Vaccine 2012 30 (9) 1644-9 The long-term duration of recombinant hepatitis B vaccine-induced immunity among persons vaccinated starting at birth is still not well understood. Waning of vaccine-induced immunity could leave young adults at risk of hepatitis B virus infection due to behavioral or occupational exposures. We followed a cohort of children immunized starting at birth with a 3-dose regimen of recombinant hepatitis B vaccine (5mcg, 2.5mcg, 2.5mcg). They were challenged with a booster dose of the hepatitis B vaccine 10 and 15 years after vaccination to assess anamnestic response as a measure of persistence of protection. Among 108 participants who had lost protective antibody levels against hepatitis B, the majority (>70%) had an anamnestic response to the booster dose; response rates did not decline significantly between 10 and 15 years follow-up periods. A high antibody concentration following primary vaccination was independently associated with an anamnestic response later on in life. Nonetheless, approximately 20-30% of participants were unable to mount an immune response after boosting. Hepatitis B revaccination might be required for persons vaccinated starting at birth if opportunities for hepatitis B virus exposure exist. Future vaccine recommendations should be based on studies ascertaining protection against clinically significant disease. |
Hepatitis E: epidemiology and prevention
Teshale EH , Hu DJ . World J Hepatol 2011 3 (12) 285-91 ![]() Hepatitis E is caused by the hepatitis E virus (HEV), the major etiologic agent of enterically transmitted non-A hepatitis worldwide. HEV is responsible for major outbreaks of acute hepatitis in developing countries, especially in many parts of Africa and Asia. The HEV is a spherical, non-enveloped, single-stranded, positive sense RNA virus that is approximately 32 nm to 34 nm in diameter and is the only member in the family Hepeviridae and genus Hepevirus. There are four distinct genotypes of HEV (genotypes 1-4). While genotype 1 is predominantly associated with large epidemics in developing countries, genotype 3 has recently emerged as a significant pathogen in developed countries. The clinical manifestations and the laboratory abnormalities of hepatitis E are not distinguishable from that caused by other hepatitis viruses. However, high mortality among pregnant women particularly during the third trimester distinguishes HEV from other causes of acute viral hepatitis. Specific etiologic diagnosis among infected cases can be made by serological testing or detection of viral nucleic acid by reverse transcription polymerase chain reaction. Although there are vaccine candidates that had been shown to be safe and efficacious in clinical trials, none are approved currently for use. There is no specific therapy for acute hepatitis E as treatment remains supportive. |
Variants in ABCB1, TGFB1, and XRCC1 genes and susceptibility to viral hepatitis A infection in Mexican Americans.
Zhang L , Yesupriya A , Hu DJ , Chang MH , Dowling NF , Ned RM , Udhayakumar V , Lindegren ML , Khudyakov Y . Hepatology 2011 55 (4) 1008-18 ![]() Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assess associations between 67 genetic variants (single nucleotide polymorphisms, 'SNPs') among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6779 participants, including 2619 non-Hispanic whites, 2095 non-Hispanic blacks, and 2065 Mexican Americans, enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV (anti-HAV) was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.14-1.68; p-value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR = 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR = 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007). CONCLUSIONS: Genetic variants in ABCB1, TGFB1, and XRCC1 appear to be associated with susceptibility to HAV infection among Mexican Americans. Replication studies involving larger population samples are warranted. (HEPATOLOGY 2011). |
Evaluation of hepatitis B vaccine immunogenicity among older adults during an outbreak response in assisted living facilities
Tohme RA , Awosika-Olumo D , Nielsen C , Khuwaja S , Scott J , Xing J , Drobeniuc J , Hu DJ , Turner C , Wafeeg T , Sharapov U , Spradling PR . Vaccine 2011 29 (50) 9316-20 BACKGROUND: During the past decade, in the United States, an increasing number of hepatitis B outbreaks have been reported in assisted living facilities (ALFs) as a result of breaches in infection control practices. We evaluated the seroprotection rates conferred by hepatitis B vaccine among older adults during a response to an outbreak that occurred in multiple ALFs and assessed the influence of demographic and clinical factors on vaccine response. METHODS: Residents were screened for hepatitis B and C infection prior to vaccination and susceptible residents were vaccinated against hepatitis B with one dose of 20mcg Engerix-B (GSK) given at 0, 1, and 4 months. Blood samples were collected 80-90 days after the third vaccine dose to test for anti-HBs levels. RESULTS: Of the 48 residents who had post-vaccination blood specimens collected after the third vaccine dose, 16 (33.3%) achieved anti-HBs concentration ≥10mIU/mL. Age was a significant determinant of seroprotection with rates decreasing from 88% among persons aged ≤60 years to 12% among persons aged ≥90 years (p=0.001). Geometric mean concentrations were higher among non-diabetic than diabetic residents, however, the difference was not statistically significant (5.1 vs. 3.8mIU/mL, p=0.7). CONCLUSIONS: These findings highlight that hepatitis B vaccination is of limited effectiveness when administered to older adults. Improvements in infection control and vaccination at earlier ages might be necessary to prevent spread of infection in ALFs. |
Acute hepatitis associated with autochthonous hepatitis E virus infection--San Antonio, Texas, 2009
Tohme RA , Drobeniuc J , Sanchez R , Heseltine G , Alsip B , Kamili S , Hu DJ , Guerra F , Teshale EH . Clin Infect Dis 2011 53 (8) 793-6 Locally acquired hepatitis E infection is increasingly being observed in industrialized countries. We report 2 cases of autochthonous acute hepatitis E in the United States. Hepatitis E virus genotype 3a related to US-2 and swine hepatitis E virus strains was isolated from one of the patients, indicating potential food-borne or zoonotic transmission. |
Genotypic distribution of hepatitis B virus (HBV) among acute cases of HBV infection, selected United States counties, 1999-2005.
Teshale EH , Ramachandran S , Xia GL , Roberts H , Groeger J , Barry V , Hu DJ , Holmberg SD , Holtzman D , Ward JW , Teo CG , Khudyakov Y . Clin Infect Dis 2011 53 (8) 751-6 ![]() BACKGROUND: Knowledge of the genotypic distribution of hepatitis B virus (HBV) facilitates epidemiologic tracking and surveillance of HBV infection as well as prediction of its disease burden. In the United States, HBV genotyping studies have been conducted for chronic but not acute hepatitis B. METHODS: Serum samples were collected from patients with acute hepatitis B cases reported from the 6 counties that participated in the Sentinel Counties Study of Acute Viral Hepatitis from 1999 through 2005. Polymerase chain reaction followed by nucleotide sequencing of a 435-base pair segment of the HBV S gene was performed, and the sequences were phylogenetically analyzed. RESULTS: Of 614 patients identified with available serum samples, 75% were infected with genotype A HBV and 18% were infected with genotype D HBV. Thirty-two percent of genotype A sequences constituted a single subgenotype A2 cluster. The odds of infection with genotype A (vs with genotype D) were 5 times greater among black individuals than among Hispanic individuals (odds ratio [OR], 5; 95% confidence interval [CI], 2.3-10.7). The odds of infection with genotype A were 49, 8, and 4 times greater among patients from Jefferson County (Alabama), Pinellas County (Florida), and San Francisco (California), respectively, than among those living in Denver County (Colorado). Genotype A was less common among recent injection drug users than it was among non-injection drug users (OR, 0.2; 95% CI, 0.1-0.4). CONCLUSIONS: HBV genotype distribution was significantly associated with ethnicity, place of residence, and risk behavior. |
Outbreak of acute hepatitis B virus infections associated with podiatric care at a psychiatric long-term care facility
Wise ME , Marquez P , Sharapov U , Hathaway S , Katz K , Tolan S , Beaton A , Drobeniuc J , Khudyakov Y , Hu DJ , Perz J , Thompson ND , Bancroft E . Am J Infect Control 2011 40 (1) 16-21 BACKGROUND: Effective measures exist to prevent health care-associated hepatitis B virus (HBV) transmission, yet outbreaks continue to occur. In 2008, the Los Angeles County Department of Public Health identified an outbreak of HBV infections among psychiatric long-term care facility residents. METHODS: Residents underwent HBV serologic testing and were classified as acutely infected, chronically infected, susceptible, or immune. Persons residing in the facility during 2008 were enrolled in a retrospective cohort study to identify risk factors for acute HBV infection. We assessed infection control practices at the facility. RESULTS: Nine of 81 residents (11%) enrolled in the cohort study had acute HBV infection. Five of 15 residents (33%) undergoing podiatric care on a single day subsequently developed acute infection (rate ratio, 4.33; 95% confidence interval, 1.18-15.92). Infection control observations of the consulting podiatrist revealed opportunities for cross-contamination of instruments with blood. Other potential health care and behavioral modes of transmission were identified as well. Residents were offered HBV vaccination, and infection control recommendations were implemented by the podiatrist and facility. CONCLUSIONS: Of the multiple potential transmission modes identified, exposure to HBV during podiatry was likely the dominant mode in this outbreak. Long-term care facilities should ensure compliance with infection control standards among staff and consulting health care providers. |
Preparing for the availability of a partially effective HIV vaccine: lessons from other licensed vaccines
Chen RT , Hu DJ , Dunne E , Shaw M , Mullins J , Rerks-Ngarm S . Vaccine 2011 29 (36) 6072-8 The 2009 RV144 trial in Thailand shows that a partially effective vaccine against human immunodeficiency virus (HIV) acquisition is possible (1). Past mathematical models have shown HIV vaccines with partial effectiveness (assuming availability and no compensatory risk behavior) may have important public health impact (2). While we are still many years away from a licensed HIV vaccine, what might be some of the “downstream” considerations for the implementation of a partially effective HIV vaccine in the developed and developing world in the current era? Are there any changes since the HIV domain last considered this issue in anticipation of the results of the first Phase III trials of HIV vaccine (Vaxgen gp120) a decade earlier? (3, 4). | During the Acquired Immunodeficiency Disease Syndrome (AIDS) Vaccine 2010 Conference, a satellite symposium cosponsored by AIDS Vaccine Advocacy Coalition (AVAC), the U. S. Centers for Disease Control and Prevention (CDC), Gates Foundation, the Joint United Nations Programme on HIV/AIDS (UNAIDS), US Agency for International Development (USAID), US Military HIV Research Program (USMHRP), World Health Organization (WHO) took advantage of the conference location in Atlanta to draw upon some of the experience of CDC and its associated partners in preparing for the availability and implementation of newly licensed vaccines to further this dialogue. This paper summarizes the presentations on some lessons for future HIV vaccine implementation from the introduction of hepatitis B vaccine, human papillomavirus (HPV) vaccine, the annual influenza virus vaccine strain selection, a potential annual HIV vaccine strain selection, as well as planning for next steps in Thailand in response to the RV144 trial, and highlights from the moderated discussions with the audience on issues relevant to low/middle income countries and developed countries (Table 1). Hopefully these ideas will facilitate preparations for the introduction of a future licensed HIV vaccine. |
Assessment of BED HIV-1 incidence assay in seroconverter cohorts: effect of individuals with long-term infection and importance of stable incidence
McNicholl JM , McDougal JS , Wasinrapee P , Branson BM , Martin M , Tappero JW , Mock PA , Green TA , Hu DJ , Parekh B . PLoS One 2011 6 (3) e14748 BACKGROUND: Performance of the BED assay in estimating HIV-1 incidence has previously been evaluated by using longitudinal specimens from persons with incident HIV infections, but questions remain about its accuracy. We sought to assess its performance in three longitudinal cohorts from Thailand where HIV-1 CRF01_AE and subtype B' dominate the epidemic. DESIGN: BED testing was conducted in two longitudinal cohorts with only incident infections (a military conscript cohort and an injection drug user cohort) and in one longitudinal cohort (an HIV-1 vaccine efficacy trial cohort) that also included long-term infections. METHODS: Incidence estimates were generated conventionally (based on the number of annual serocoversions) and by using BED test results in the three cohorts. Adjusted incidence was calculated where appropriate. RESULTS: For each longitudinal cohort the BED incidence estimates and the conventional incidence estimates were similar when only newly infected persons were tested, whether infected with CRF01_AE or subtype B'. When the analysis included persons with long-term infections (to mimic a true cross-sectional cohort), BED incidence estimates were higher, although not significantly, than the conventional incidence estimates. After adjustment, the BED incidence estimates were closer to the conventional incidence estimates. When the conventional incidence varied over time, as in the early phase of the injection drug user cohort, the difference between the two estimates increased, but not significantly. CONCLUSIONS: Evaluation of the performance of incidence assays requires the inclusion of a substantial number of cohort-derived specimens from individuals with long-term HIV infection and, ideally, the use of cohorts in which incidence remained stable. Appropriate adjustments of the BED incidence estimates generate estimates similar to those generated conventionally. |
An outbreak of hepatitis A among primary and secondary contacts of an international adoptee
Pelletier AR , Mehta PJ , Burgess DR , Bondeson LM , Carson PJ , Rea VE , Sharapov UM , Hu DJ . Public Health Rep 2010 125 (5) 642-6 The Advisory Committee on Immunization Practices recommends that susceptible people traveling to developing countries receive hepatitis A vaccine or immune globulin prior to departure. Until 2009, the recommendations did not address non-traveling family members or other close contacts of international adoptees. We report an outbreak of hepatitis A in 2008 that occurred in Maine. Eight members of an extended family developed hepatitis A following the arrival of an asymptomatic infant from Ethiopia who was brought to the United States by an adoption agency. Two children in the family attended an elementary school where five additional cases of hepatitis A were subsequently identified. Only three (1%) of 208 students at the school had previously been immunized against hepatitis A. This outbreak highlights the need to immunize household members and other close contacts of families adopting children from countries where hepatitis A is endemic, as well as all children at one year of age. |
The two faces of Hepatitis E virus
Teshale EH , Hu DJ , Holmberg SD . Clin Infect Dis 2010 51 (3) 328-34 Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%-21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration-approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world. |
Transforming strategies for the prevention of chronic HBV and HCV infections
Ward JW , Hu DJ , Alter MJ , Kanwal F , Taylor C , Block JM , Caballero JB , Chase D , Saly M , Sandt L , Swan T . J Fam Pract 2010 59 S23-8 The article focuses on the prevention of chronic hepatitis B and C virus (HBV and HCV) infections in the U.S. It discusses the global implication of the pandemic chronic viral infections, prevention strategies for HBV infection using the framework of the Centers for Disease Control and Prevention (CDC), and the HCV in quality indicators which include confirmation of HCV viremia, hepatitis A and HBV vaccinations, counseling, and treatment with the Department of Health and Human Services Centers. |
Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in northern Uganda
Teshale EH , Grytdal SP , Howard C , Barry V , Kamili S , Drobeniuc J , Hill VR , Okware S , Hu DJ , Holmberg SD . Clin Infect Dis 2010 50 (7) 1006-10 BACKGROUND: Outbreaks of infection with hepatitis E virus (HEV) are frequently attributed to contaminated drinking water, even if direct evidence for this is lacking. METHODS: We conducted several epidemiologic investigations during a large HEV infection outbreak in Uganda. RESULTS: Of 10,535 residents, 3218 had HEV infection; of these, 2531 lived in households with >1 case. HEV was not detected in drinking water or zoonotic sources. Twenty-five percent of cases occurred 8 weeks after onset of hepatitis in an index case in the household. Households with 2 cases were more likely to have a member(s) who attended a funeral, had close contact with a jaundiced person, or washed hands in a common basin with others (P < .05 for all). CONCLUSIONS: A high attack rate in households, lack of a common source of infection, and poor hygienic practices in households with 2 cases suggest person-to-person transmission of HEV during this outbreak. |
Improved anamnestic response among adolescents boosted with a higher dose of the hepatitis B vaccine
Chaves SS , Groeger J , Helgenberger L , Auerbach SB , Bialek S , Hu DJ , Drobeniuc J . Vaccine 2010 28 (16) 2860-4 Some hepatitis B vaccine booster studies have suggested waning of vaccine-induced immunity in adolescents vaccinated starting at birth. Those studies, however, used a pediatric formulation of the hepatitis B vaccine as a booster to detect anamnestic response. We compared adolescents boosted with an adult dose of hepatitis B vaccine with those boosted with a pediatric dose. Among adolescents who had lost protective antibody levels against hepatitis B, a higher proportion had an anamnestic response when boosted with the adult dose (60.0% vs. 43.8%). Thus, higher antigen concentrations may be required to elicit an adequate immune memory response. Despite improved anamnestic response, our study still raises concerns about whether children immunized in early infancy will remain protected from hepatitis B as they age into adulthood. |
Development of two avidity-based assays to detect recent HIV type 1 seroconversion using a multisubtype gp41 recombinant protein
Wei X , Liu X , Dobbs T , Kuehl D , Nkengasong JN , Hu DJ , Parekh BS . AIDS Res Hum Retroviruses 2010 26 (1) 61-71 Current laboratory methods to detect recent HIV-1 infection for the estimation of incidence have various limitations, including varying performance in different subtypes or populations. Therefore, new methods are needed to detect recent infections with increased specificity. We developed a recombinant protein, rIDR-M, that covered divergent sequences from the immunodominant region (IDR) of gp41 from all major subtypes and recombinants of HIV-1 group M and expressed in Escherichia coli. The rIDR-M protein was highly reactive with HIV antibodies in sera from different subtypes and equivalently detected antibodies to divergent subtypes B and AE from Thailand, in contrast to individual gp41 peptides derived from respective subtypes, suggesting that it can be used for incidence assays. The protein was used in two different assay formats to measure antibody avidity: (1) a two-well avidity index assay (AI-EIA) and (2) a new one-well limiting antigen avidity assay (LAg-avidity EIA), both with a pH 3.0 buffer to dissociate low-avidity antibodies present during early infection. Limiting the amount of antigen allowed detection of recent HIV-1 infection, with or without dissociation buffer, but the detection was most efficient when the pH 3.0 dissociation buffer was included. When a well-characterized 41-member seroincidence panel (20 recent and 21 long-term) was used, both the two-well AI-EIA and one-well LAg-avidity EIA efficiently distinguished recent and long-term infections. The new avidity-based assays using rIDR-M antigen may improve the accuracy of detecting recent HIV-1 infection and allow a better estimation of incidence in diverse HIV-1 subtypes. |
Hepatitis E epidemic, Uganda
Teshale EH , Howard CM , Grytdal SP , Handzel TR , Barry V , Kamili S , Drobeniuc J , Okware S , Downing R , Tappero JW , Bakamutumaho B , Teo CG , Ward JW , Holmberg SD , Hu DJ . Emerg Infect Dis 2010 16 (1) 126-9 In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths. |
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