Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Xia GL[original query] |
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Coordinated evolution among hepatitis C virus genomic sites is coupled to host factors and resistance to interferon.
Lara J , Tavis JE , Donlin MJ , Lee WM , Yuan HJ , Pearlman BL , Vaughan G , Forbi JC , Xia GL , Khudyakov YE . In Silico Biol 2011 11 213-24 Machine-learning methods in the form of Bayesian networks (BN), linear projection (LP) and self-organizing tree (SOT) models were used to explore association among polymorphic sites within the HVR1 and NS5a regions of the HCV genome, host demographic factors (ethnicity, gender and age) and response to the combined interferon (IFN) and ribavirin (RBV) therapy. The BN models predicted therapy outcomes, gender and ethnicity with accuracy of 90%, 90% and 88.9%, respectively. The LP and SOT models strongly confirmed associations of the HVR1 and NS5A structures with response to therapy and demographic host factors identified by BN. The data indicate host specificity of HCV evolution and suggest the application of these models to predict outcomes of IFN/RBV therapy. |
A 2019 Outbreak Investigation of Hepatitis A Virus Infections in the United States Linked to Imported Fresh Blackberries.
McClure M , Nsubuga J , Montgomery MP , Jenkins E , Crosby A , Schoelen D , Basler C , Ramachandran S , Lin Y , Xia GL , Khudaykov Y , Suktankar V , Wagley A , Thomas V , Woods J , Hintz L , Oliveira J , Sandoval AL , Frederick J , Hendrickson B , Gieraltowski L , Viazis S . Food Environ Virol 2022 14 (3) 236-245 Globally, hepatitis A virus (HAV) is one of the most common agents of acute viral hepatitis and causes approximately 1.4 million cases and 90,000 deaths annually despite the existence of an effective vaccine. In 2019, federal, state, and local partners investigated a multi-state outbreak of HAV infections linked to fresh blackberries sourced from multiple suppliers in Michoacn, Mexico. A total of 20 individuals with outbreak-related HAV infection were reported in seven states, including 11 hospitalizations, and no deaths. The Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and Nebraska State and Douglas County Health Departments conducted a traceback investigation for fresh blackberries reportedly purchased by 16 ill persons. These individuals reported purchasing fresh blackberries from 11 points of service from September 16 through 29, 2019 and their clinical isolates assessed through next-generation sequencing and phylogenetic analysis were genetically similar. The traceback investigation did not reveal convergence on a common grower or packing house within Mexico, but all of the blackberries were harvested from growers in Michoacn, Mexico. FDA did not detect the pathogen after analyzing fresh blackberry samples from four distributors, one consumer, and from nine importers at the port of entry as a result of increased screening. Challenges included gaps in traceability practices and the inability to recover the pathogen from sample testing, which prohibited investigators from determining the source of the implicated blackberries. This multi-state outbreak illustrated the importance of food safety practices for fresh produce that may contribute to foodborne illness outbreaks. |
Hepatitis C virus transmission cluster among injection drug users in Pakistan
Sahibzada KI , Ganova-Raeva L , Dimitrova Z , Ramachandran S , Lin Y , Longmire G , Arthur L , Xia GL , Khudyakov Y , Khan I , Sadaf S . PLoS One 2022 17 (7) e0270910 Hepatitis C virus (HCV) infections are public health problem across the globe, particularly in developing countries. Pakistan has the second highest prevalence of HCV infection worldwide. Limited data exist from Pakistan about persons who inject drugs (PWID) and are at significant risk of exposure to HCV infection and transmission. Serum specimens (n = 110) collected from PWID residing in four provinces were tested for molecular markers of HCV infection. Next generation sequencing (NGS) of the hypervariable region (HVR1) of HCV and Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to determine HCV genotype, genetic heterogeneity, and construct transmission networks. Among tested specimens, 47.3% were found anti-HCV positive and 34.6% were HCV RNA-positive and belonged to four genotypes, with 3a most prevalent followed by 1a, 1b and 4a. Variants sampled from five cases formed phylogenetic cluster and a transmission network. One case harbored infection with two different genotypes. High prevalence of infections and presence of various genotypes indicate frequent introduction and transmission of HCV among PWID in Pakistan. Identification of a transmission cluster across three provinces, involving 20% of all cases, suggests the existence of a countrywide transmission network among PWIDs. Understanding the structure of this network should assist in devising effective public health strategies to eliminate HCV infection in Pakistan. |
Changing Molecular Epidemiology of Hepatitis A Virus Infection, United States, 1996-2019.
Ramachandran S , Xia GL , Dimitrova Z , Lin Y , Montgomery M , Augustine R , Kamili S , Khudyakov Y . Emerg Infect Dis 2021 27 (6) 1742-1745 Hepatitis A virus (HAV) genotype IA was most common among strains tested in US outbreak investigations and surveillance during 1996-2015. However, HAV genotype IB gained prominence during 2016-2019 person-to-person multistate outbreaks. Detection of previously uncommon strains highlights the changing molecular epidemiology of HAV infection in the United States. |
Outbreak of hepatitis B and hepatitis C virus infections associated with a cardiology clinic, West Virginia, 2012-2014.
Tressler SR , Del Rosario MC , Kirby MD , Simmons AN , Scott MA , Ibrahim S , Forbi JC , Thai H , Xia GL , Lyman M , Collier MG , Patel PR , Bixler D . Infect Control Hosp Epidemiol 2021 42 (12) 1-6 OBJECTIVE: To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic. DESIGN: Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome. SETTING: Outpatient cardiology clinic. PATIENTS: Patients undergoing MPI. METHODS: Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed. RESULTS: During 2012-2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%-99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified. CONCLUSIONS: This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings. |
Complex genetic encoding of the hepatitis B virus on-drug persistence.
Thai H , Lara J , Xu X , Kitrinos K , Gaggar A , Chan HLY , Xia GL , Ganova-Raeva L , Khudyakov Y . Sci Rep 2020 10 (1) 15574 Tenofovir disoproxil fumarate (TDF) is one of the nucleotide analogs capable of inhibiting the reverse transcriptase (RT) activity of HIV and hepatitis B virus (HBV). There is no known HBV resistance to TDF. However, detectable variation in duration of HBV persistence in patients on TDF therapy suggests the existence of genetic mechanisms of on-drug persistence that reduce TDF efficacy for some HBV strains without affording actual resistance. Here, the whole genome of intra-host HBV variants (N = 1,288) was sequenced from patients with rapid (RR, N = 5) and slow response (SR, N = 5) to TDF. Association of HBV genomic and protein polymorphic sites to RR and SR was assessed using phylogenetic analysis and Bayesian network methods. We show that, in difference to resistance to nucleotide analogs, which is mainly associated with few specific mutations in RT, the HBV on-TDF persistence is defined by genetic variations across the entire HBV genome. Analysis of the inferred 3D-structures indicates no difference in affinity of TDF binding by RT encoded by intra-host HBV variants that rapidly decline or persist in presence of TDF. This finding suggests that effectiveness of TDF recognition and binding does not contribute significantly to on-drug persistence. Differences in patterns of genetic associations to TDF response between HBV genotypes B and C and lack of a single pattern of mutations among intra-host variants sensitive to TDF indicate a complex genetic encoding of the trait. We hypothesize that there are many genetic mechanisms of on-drug persistence, which are differentially available to HBV strains. These pervasive mechanisms are insufficient to prevent viral inhibition completely but may contribute significantly to robustness of actual resistance. On-drug persistence may reduce the overall effectiveness of therapy and should be considered for development of more potent drugs. |
High prevalence of Hepatitis C Virus infection among people who use crack cocaine in an important international drug trafficking route in Central-West Region Brazil.
Castro VOL , Kamili S , Forbi JC , Stabile AC , da Silva EF , do Valle Leone de Oliveira SM , de Carvalho PRT , Puga MAM , Tanaka TSO , do Lago BV , Ibanhes ML , Araujo A , Tejada-Strop A , Lin Y , Xia GL , Sue A , Teles SA , Motta-Castro ARC . Infect Genet Evol 2020 85 104488 In this study, the prevalence rate, associated risk factors and genetic diversity of hepatitis C virus (HCV) infection were determined among people who use crack from an international drug trafficking route in Central-West, Brazil. Blood samples were collected from 700 users of crack from Campo Grande and two border cities of Mato Grosso do Sul State and tested for HCV infection using serological and molecular testing methodologies. Anti-HCV was detected in 31/700 (4.5%, 95% CI: 2.9-6.0%) and HCV RNA in 26/31 (83.9%) of anti-HCV positive samples. Phylogenetic analysis of three HCV sub-genomic regions (5'UTR, NS5B and HVR-1) revealed the circulation of 1a (73.9%), 1b (8.7%) and 3a (17.4%) genotypes. Next-generation sequencing and phylogenetic analysis of intra-host viral populations of HCV HVR-1 showed a significant variation in intra-host genetic diversity among infected individuals, with 58.8% composed of more than one sub-population. Bayesian analysis estimated that the most recent common HCV ancestor for strains identified here was introduced to this region after 1975 following expansion of intravenous drug use in Brazil. Multivariate analyses showed that only 'ever having injected drugs' was independently associated with HCV infection. These results indicate an increasing spread of multiple HCV strains requiring public health intervention, such as harm reduction, testing services and treatment among crack users in this important border region of Central Brazil. |
Integrated HIV surveillance finds recent adult hepatitis B virus (HBV) transmission and intermediate HBV prevalence among military in uncharacterized Caribbean country
O'Connor SM , Mixson-Hayden T , Ganova-Raeva L , Djibo DA , Brown M , Xia GL , Kamili S , Jacobs M , Dong M , Thomas AG , Bulterys M , Hale B . PLoS One 2019 14 (10) e0222835 BACKGROUND: Guyana expanded its HIV response in 2005 but the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has not been characterized. METHODS: The 2011 Seroprevalence and Behavioral Epidemiology Risk Survey for HIV and STIs collected biologic specimens with demographic and behavioral data from a representative sample of Guyana military personnel. Diagnostics included commercial serum: HIV antibody; total antibody to hepatitis B core (anti-HBc); IgM anti-HBc; hepatitis B surface antigen (HBsAg); anti-HBs; antibody to HCV with confirmatory testing; and HBV DNA sequencing with S gene fragment phylogenetic analysis. Chi-square, p-values and prevalence ratios determined statistical significance. RESULTS: Among 480 participants providing serologic specimens, 176 (36.7%) tested anti-HBc-positive. Overall, 19 (4.0%) participants tested HBsAg-positive; 17 (89.5%) of the HBsAg-positive participants also had detectable anti-HBc, including 1 (5.3%) IgM anti-HBc-positive male. Four (6.8%) females with available HBV testing were HBsAg-positive, all aged 23-29 years. Sixteen (16, 84.2%) HBsAg-positive participants had sufficient specimen for DNA testing. All 16 had detectable HBV DNA, 4 with viral load >2x104IU/ml. Sequencing found: 12 genotype (gt) A1 with 99.9% genetic identity between 1 IgM anti-HBc-positive and 1 anti-HBc-negative; 2 gtD1; and 2 with insufficient specimen. No statistically significant associations between risk factors and HBV infection were identified. CONCLUSIONS: Integrated HIV surveillance identified likely recent adult HBV transmission, current HBV infection among females of reproductive age, moderate HBV infection prevalence (all gtA1 and D1), no HCV infections and low HIV frequency among Guyana military personnel. Integrated HIV surveillance helped characterize HBV and HCV epidemiology, including probable recent transmission, prompting targeted responses to control ongoing HBV transmission and examination of hepatitis B vaccine policies. |
Increase in hepatitis A virus infections - United States, 2013-2018
Foster MA , Hofmeister MG , Kupronis BA , Lin Y , Xia GL , Yin S , Teshale E . MMWR Morb Mortal Wkly Rep 2019 68 (18) 413-415 Hepatitis A virus (HAV) is primarily transmitted fecal-orally after close contact with an infected person (1); it is the most common cause of viral hepatitis worldwide, typically causing acute and self-limited symptoms, although rarely liver failure and death can occur (1). Rates of hepatitis A had declined by approximately 95% during 1996-2011; however, during 2016-2018, CDC received approximately 15,000 reports of HAV infections from U.S. states and territories, indicating a recent increase in transmission (2,3). Since 2017, the vast majority of these reports were related to multiple outbreaks of infections among persons reporting drug use or homelessness (4). In addition, increases of HAV infections have also occurred among men who have sex with men (MSM) and, to a much lesser degree, in association with consumption of imported HAV-contaminated food (5,6). Overall, reports of hepatitis A cases increased 294% during 2016-2018 compared with 2013-2015. During 2016-2018, CDC tested 4,282 specimens, of which 3,877 (91%) had detectable HAV RNA; 565 (15%), 3,255 (84%), and 57 (<1%) of these specimens were genotype IA, IB, or IIIA, respectively. Adherence to the Advisory Committee on Immunization Practices (ACIP) recommendations to vaccinate populations at risk can help control the current increases and prevent future outbreaks of hepatitis A in the United States (7). |
HCV transmission in high-risk communities in Bulgaria.
Ganova-Raeva L , Dimitrova Z , Alexiev I , Punkova L , Sue A , Xia GL , Gancheva A , Dimitrova R , Kostadinova A , Golkocheva-Markova E , Khudyakov Y . PLoS One 2019 14 (3) e0212350 BACKGROUND: The rate of HIV infection in Bulgaria is low. However, the rate of HCV-HIV-coinfection and HCV infection is high, especially among high-risk communities. The molecular epidemiology of those infections has not been studied before. METHODS: Consensus Sanger sequences of HVR1 and NS5B from 125 cases of HIV/HCV coinfections, collected during 2010-2014 in 15 different Bulgarian cities, were used for preliminary phylogenetic evaluation. Next-generation sequencing (NGS) data of the hypervariable region 1 (HVR1) analyzed via the Global Hepatitis Outbreak and Surveillance Technology (GHOST) were used to evaluate genetic heterogeneity and possible transmission linkages. Links between pairs that were below and above the established genetic distance threshold, indicative of transmission, were further examined by generating k-step networks. RESULTS: Preliminary genetic analyses showed predominance of HCV genotype 1a (54%), followed by 1b (20.8%), 2a (1.4%), 3a (22.3%) and 4a (1.4%), indicating ongoing transmission of many HCV strains of different genotypes. NGS of HVR1 from 72 cases showed significant genetic heterogeneity of intra-host HCV populations, with 5 cases being infected with 2 different genotypes or subtypes and 6 cases being infected with 2 strains of same subtype. GHOST revealed 8 transmission clusters involving 30 cases (41.7%), indicating a high rate of transmission. Four transmission clusters were found in Sofia, three in Plovdiv, and one in Peshtera. The main risk factor for the clusters was injection drug use. Close genetic proximity among HCV strains from the 3 Sofia clusters, and between HCV strains from Peshtera and one of the two Plovdiv clusters confirms a long and extensive transmission history of these strains in Bulgaria. CONCLUSIONS: Identification of several HCV genotypes and many HCV strains suggests a frequent introduction of HCV to the studied high-risk communities. GHOST detected a broad transmission network, which sustains circulation of several HCV strains since their early introduction in the 3 cities. This is the first report on the molecular epidemiology of HIV/HCV coinfections in Bulgaria. |
Recent and occult hepatitis B virus infections among blood donors in the United States
Ramachandran S , Groves JA , Xia GL , Saa P , Notari EP , Drobeniuc J , Poe A , Khudyakov N , Schillie SF , Murphy TV , Kamili S , Teo CG , Dodd RY , Khudyakov YE , Stramer SL . Transfusion 2018 59 (2) 601-611 BACKGROUND: Characteristics of US blood donors with recent (RBI) or occult (OBI) hepatitis B virus (HBV) infection are not well defined. METHODS: Donors with RBI and OBI were identified by nucleic acid and serologic testing among 34.4 million donations during 2009-2015. Consenting donors were interviewed and their HBV S-gene sequenced. RESULTS: The overall rate of HBV-infected donors was 7.95 per 100,000; of these, 0.35 per 100,000 and 1.70 per 100,000 were RBI and OBI, respectively. RBI (n = 120) and OBI (n = 583) donors constituted 26% of all HBV-infected (n = 2735) donors. Detection of HBV DNA in 92% of OBI donors required individual donation nucleic acid testing. Donors with OBI compared to RBI were older (mean age, 48 vs 39 years; p < 0.0001) with lower median viral loads (9 vs. 529 IU/mL; p < 0.0001). A higher proportion of OBI than RBI donors were born or resided in an endemic country (39% vs. 5%; p = 0.0078). Seventy-seven percent of all RBI and OBI donors had multiple sex partners, an HBV-risk factor. Of 40 RBI and 10 OBI donors whose S gene was sequenced, 33 (83%) and 6 (60%), respectively, carried HBV subgenotype A2; 18 (55%) and 2 (33%), respectively, shared an identical sequence. Infection with 1 or more putative HBV-immune-escape mutants was identified in 5 (50%) of OBI but no RBI donors. CONCLUSION: RBI and OBI continue to be identified at low rates, confirming the importance of comprehensive HBV DNA screening of US blood donations. HBV-infected donors require referral for care and evaluation and contact tracing; their HBV strains may provide important information on emergent genotypes. |
A large HCV transmission network enabled a fast-growing HIV outbreak in rural Indiana, 2015.
Ramachandran S , Thai H , Forbi JC , Galang RR , Dimitrova Z , Xia GL , Lin Y , Punkova LT , Pontones PR , Gentry J , Blosser SJ , Lovchik J , Switzer WM , Teshale E , Peters P , Ward J , Khudyakov Y . EBioMedicine 2018 37 374-381 BACKGROUND: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains. METHODS: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST). FINDINGS: Results from the 492 samples indicate predominance of HCV genotypes 1a (72.2%) and 3a (20.4%), and existence of 2 major endemic NS5B clusters involving 49.8% of the sequenced strains. Among 76 HIV co-infected patients, 60.5% segregated into 2 endemic clusters. NGS analyses of 281 cases identified 826,917 unique HVR1 sequences and 51 cases of mixed subtype/genotype infections. GHOST mapped 23 transmission clusters. One large cluster (n=130) included 50 cases infected with >/=2 subtypes/genotypes and 43 cases co-infected with HIV. Rapid strain replacement and superinfection with different strains were found among 7 of 12 cases who were followed up. INTERPRETATION: GHOST enabled mapping of HCV transmission networks among persons who inject drugs (PWID). Findings of numerous transmission clusters, mixed-genotype infections and rapid succession of infections with different HCV strains indicate a high rate of HCV spread. Co-localization of HIV co-infected patients in the major HCV clusters suggests that HIV dissemination was enabled by existing HCV transmission networks that likely perpetuated HCV in the community for years. Identification of transmission networks is an important step to guiding efficient public health interventions for preventing and interrupting HCV and HIV transmission among PWID. FUND: US Centers for Disease Control and Prevention, and US state and local public health departments. |
HCV adaptation to HIV coinfection.
Lara J , Teka MA , Sims S , Xia GL , Ramachandran S , Khudyakov Y . Infect Genet Evol 2018 65 216-225 Human immunodeficiency virus (HIV) infection is rising as a leading cause of morbidity and mortality among hepatitis C virus (HCV)-infected patients. Both viruses interact in co-infected hosts, which may affect their intra-host evolution, potentially leading to differing genetic composition of viral populations in co-infected (CIP) and mono-infected (MIP) patients. Here, we investigate genetic differences between intra-host variants of the HCV hypervariable region 1 (HVR1) sampled from CIP and MIP. Nucleotide (nt) sequences of intra-host HCV HVR1 variants (N=28,622) obtained from CIP (N=112) and MIP (n=176) were represented using 148 physical-chemical (PhyChem) indexes of DNA nt dimers. Significant (p<.0001) differences in the means and frequency distributions of 7 PhyChem properties were found between HVR1 variants from both groups. Linear projection analysis of 29 PhyChem features extracted from such PhyChem properties showed that the CIP and MIP HVR1 variants have a distinct distribution in the modeled 2D-space, with only ~1.3% of PhyChem profiles (N=6782), shared by all HVR1 variants, being found in both groups. Probabilistic neural network (PNN) and naive Bayesian (NB) classifiers trained on the PhyChem features accurately classified HVR1 variants by the group in cross-validation experiments (AUROC>/=0.96). Similarly, both models showed a high accuracy (AUROC>/=0.95) when evaluated on a test dataset of HVR1 sequences obtained from 10 patients, data from whom were not used for model building. Both models performed at the expected lower accuracy on randomly labeled datasets in cross-validation experiments (AUROC=0.50). The random-label trained PNN showed a similar drop in accuracy on the test dataset (AUROC=0.48), indicating that the detected associations were unlikely due to random correlations. Marked differences in genetic composition of HCV HVR1 variants sampled from CIP and MIP suggest differing intra-host HCV evolution in the presence of HIV infection. PhyChem features identified here may be used for detection of HIV infection from intra-host HCV variants alone in co-infected patients, thus facilitating monitoring for HIV introduction to high-risk populations with high HCV prevalence. |
Large Outbreak of Hepatitis C Virus Associated With Drug Diversion by a Healthcare Technician.
Alroy-Preis S , Daly ER , Adamski C , Dionne-Odom J , Talbot EA , Gao F , Cavallo SJ , Hansen K , Mahoney JC , Metcalf E , Loring C , Bean C , Drobeniuc J , Xia GL , Kamili S , Montero JT . Clin Infect Dis 2018 67 (6) 845-853 Background: In May 2012, the New Hampshire (NH) Division of Public Health Services (DPHS) was notified of 4 persons with newly diagnosed hepatitis C virus (HCV) infection at hospital X. Initial investigation suggested a common link to the hospital cardiac catheterization laboratory (CCL) because the infected persons included 3 CCL patients and a CCL technician. NH DPHS initiated an investigation to determine the source and control the outbreak. Methods: NH DPHS conducted site visits, case patient and employee interviews, medical record and medication use review, and employee and patient HCV testing using enzyme immunoassay for anti-HCV, reverse-transcription polymerase chain reaction for HCV RNA, nonstructural 5B (NS5B) and hypervariable region 1 (HVR1) sequencing, and quasispecies analysis. Results: HCV HVR1 analysis of the first 4 cases confirmed a common source of infection. HCV testing identified 32 of 1074 CCL patients infected with the outbreak strain, including 3 patients coinfected with >1 HCV strain. The epidemiologic investigation revealed evidence of drug diversion by the HCV-infected technician, evidenced by gaps in controlled medication control, higher fentanyl use during procedures for confirmed cases, and building card key access records documenting the presence of the technician during days when transmission occurred. The employee's status as a traveling technician led to a multistate investigation, which identified additional cases at prior employment sites. Conclusions: This is the largest laboratory-confirmed drug diversion-associated HCV outbreak published to date. Recommendations to reduce drug diversion risk and to conduct outbreak investigations are provided. |
QUENTIN: reconstruction of disease transmissions from viral quasispecies genomic data.
Skums P , Zelikovsky A , Singh R , Gussler W , Dimitrova Z , Knyazev S , Mandric I , Ramachandran S , Campo D , Jha D , Bunimovich L , Costenbader E , Sexton C , O'Connor S , Xia GL , Khudyakov Y . Bioinformatics 2018 34 (1) 163-170 Motivation: Genomic analysis has become one of the major tools for disease outbreak investigations. However, existing computational frameworks for inference of transmission history from viral genomic data often do not consider intra-host diversity of pathogens and heavily rely on additional epidemiological data, such as sampling times and exposure intervals. This impedes genomic analysis of outbreaks of highly mutable viruses associated with chronic infections, such as human immunodeficiency virus and hepatitis C virus, whose transmissions are often carried out through minor intra-host variants, while the additional epidemiological information often is either unavailable or has a limited use. Results: The proposed framework QUasispecies Evolution, Network-based Transmission INference (QUENTIN) addresses the above challenges by evolutionary analysis of intra-host viral populations sampled by deep sequencing and Bayesian inference using general properties of social networks relevant to infection dissemination. This method allows inference of transmission direction even without the supporting case-specific epidemiological information, identify transmission clusters and reconstruct transmission history. QUENTIN was validated on experimental and simulated data, and applied to investigate HCV transmission within a community of hosts with high-risk behavior. It is available at https://github.com/skumsp/QUENTIN. Contact: pskums@gsu.edu or alexz@cs.gsu.edu or rahul@sfsu.edu or yek0@cdc.gov. Supplementary information: Supplementary data are available at Bioinformatics online. |
Notes from the field: Increase in reported hepatitis A infections among men who have sex with men - New York City, January-August 2017
Latash J , Dorsinville M , Del Rosso P , Antwi M , Reddy V , Waechter H , Lawler J , Boss H , Kurpiel P , Backenson PB , Gonzalez C , Rowe S , Poissant T , Lin Y , Xia GL , Balter S . MMWR Morb Mortal Wkly Rep 2017 66 (37) 999-1000 Since 2011, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has typically been notified of three or fewer cases of hepatitis A virus (HAV) infection each year among men who have sex with men (MSM) who reported no travel to countries where HAV is endemic. This year, DOHMH noted an increase in HAV infections among MSM with onsets in January-March 2017, and notified other public health jurisdictions via Epi-X, CDC's communication exchange network. As a result, 51 patients with HAV infection involving MSM were linked to the increase in NYC. |
Eradicating hepatitis B virus: The critical role of preventing perinatal transmission
Stevens CE , Toy P , Kamili S , Taylor PE , Tong MJ , Xia GL , Vyas GN . Biologicals 2017 50 3-19 Prevention of hepatitis B virus (HBV) transmission from infected mothers to their newborns is critical to HBV control and eventual eradication. Mother-to-child perinatal transmission causes the highest chronic carrier rate (>85%) with a high rate of subsequent chronic liver disease and hepatocellular carcinoma. This risk is reduced by 90% with HBV vaccine given along with hepatitis B immune globulin (HBIG) starting at birth. New analyses of our data from US trials of HBIG and HBV vaccine in high-risk infants revealed better efficacy with yeast-recombinant vaccine than plasma-derived vaccine, especially in preventing late onset infections, with evidence that vaccine prevented transmission of maternal HBV infection with the glycine to arginine mutation in surface antigen codon 145 (sG145R). Most late infections with sG145R were in vaccine non-responders, suggesting escape from HBIG rather than from vaccine-induced antibody. Our findings also help explain survey results from Taiwan following universal childhood immunization implemented in the mid-1980s. We conclude that current vaccines will remain effective against surface antigen mutants. Anti-viral drugs in high-risk pregnant women, in combination with newborn HBIG and vaccine, show promise for eliminating residual breakthrough neonatal infections, critical to meeting WHO 2030 goals and for eradicating HBV. |
Molecular epidemiology of hepatitis B virus infection in Tanzania.
Forbi JC , Dillon M , Purdy MA , Drammeh BS , Tejada-Strop A , McGovern D , Xia GL , Lin Y , Ganova-Raeva LM , Campo DS , Thai H , Vaughan G , Haule D , Kutaga RP , Basavaraju SV , Kamili S , Khudyakov YE . J Gen Virol 2017 98 (5) 1048-1057 Despite the significant public health problems associated with hepatitis B virus (HBV) in sub-Saharan Africa, many countries in this region do not have systematic HBV surveillance or genetic information on HBV circulating locally. Here, we report on the genetic characterization of 772 HBV strains from Tanzania. Phylogenetic analysis of the S-gene sequences showed prevalence of HBV genotype A (HBV/A, n=671, 86.9 %), followed by genotypes D (HBV/D, n=95, 12.3 %) and E (HBV/E, n=6, 0.8 %). All HBV/A sequences were further classified into subtype A1, while the HBV/D sequences were assigned to a new cluster. Among the Tanzanian sequences, 84 % of HBV/A1 and 94 % of HBV/D were unique. The Tanzanian and global HBV/A1 sequences were compared and were completely intermixed in the phylogenetic tree, with the Tanzanian sequences frequently generating long terminal branches, indicating a long history of HBV/A1 infections in the country. The time to the most recent common ancestor was estimated to be 188 years ago [95 % highest posterior density (HPD): 132 to 265 years] for HBV/A1 and 127 years ago (95 % HPD: 79 to 192 years) for HBV/D. The Bayesian skyline plot showed that the number of transmissions 'exploded' exponentially between 1960-1970 for HBV/A1 and 1970-1990 for HBV/D, with the effective population of HBV/A1 having expanded twice as much as that of HBV/D. The data suggest that Tanzania is at least a part of the geographic origin of the HBV/A1 subtype. A recent increase in the transmission rate and significant HBV genetic diversity should be taken into consideration when devising public health interventions to control HBV infections in Tanzania. |
High hepatitis C virus (HCV) prevalence among men who have sex with men (MSM) in Vietnam and associated risk factors: 2010 Vietnam Integrated Behavioural and Biologic Cross-Sectional Survey
Nadol P , O'Connor S , Duong H , Mixson-Hayden T , Tram TH , Xia GL , Kaldor J , Law M , Nguyen T . Sex Transm Infect 2016 92 (7) 542-549 BACKGROUND: Hepatitis C virus (HCV) is an increasing health issue among key populations such as men who have sex with men (MSM). We sought to assess the burden of and risk factors for HCV among MSM in Vietnam. METHODS: We analysed behavioural and demographic data and stored specimens from MSM surveyed in four provinces through Vietnam's 2009-2010 Integrated Biologic and Behavioural Survey, which used probability-based, respondent-driven sampling. Commercial hepatitis B surface antigen (HBsAg) and HCV/antibody (HCV Ag/Ab) testing were performed on archived sera with follow-up PCR for HCV RNA and genotype determination. RESULTS: Among the 1588 MSM surveyed, the median (range) frequency, by province, of HCV Ag/Ab detection was 28.4% (13.7%-38.8%); 84.5% (83.1%-100%) among HIV-infected and 21.9% (8.9%-28.2%) among HIV-uninfected. HCV prevalence was higher in northern Hanoi and Hai Phong provinces than in southern Ho Chi Minh City and Chan Tho provinces. Among a convenience sample of 67 HCV Ag/Ab+ MSM, 67.2% were HCV RNA+; of 41 genotyped, 73.2% were genotype 1. HBsAg prevalence varied from 8.5% to 27.4%. In the multivariable logistic regression analysis, being HIV-infected (adjusted OR (aOR) 19.0; 7.0-51.9), ever having used injected drugs (aOR 4.4; 1.6-12.4) and age >25 years were significant risk factors for testing HCV Ag/Ab+. CONCLUSIONS: HCV infection in Vietnam appears to be high among MSM, particularly among HIV-infected MSM, with a north-south gradient. Given overlapping risk behaviours and associations between HCV and HIV, integrating HIV and HCV programme services to prevent both HIV and HCV transmission among MSM is indicated. |
Next-Generation Sequencing Reveals Frequent Opportunities for Exposure to Hepatitis C Virus in Ghana.
Forbi JC , Layden JE , Phillips RO , Mora N , Xia GL , Campo DS , Purdy MA , Dimitrova ZE , Owusu DO , Punkova LT , Skums P , Owusu-Ofori S , Sarfo FS , Vaughan G , Roh H , Opare-Sem OK , Cooper RS , Khudyakov YE . PLoS One 2015 10 (12) e0145530 Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana. |
A Large Outbreak of Hepatitis C Virus Infections in a Hemodialysis Clinic.
Nguyen DB , Gutowski J , Ghiselli M , Cheng T , Bel Hamdounia S , Suryaprasad A , Xu F , Moulton-Meissner H , Hayden T , Forbi JC , Xia GL , Arduino MJ , Patel A , Patel PR . Infect Control Hosp Epidemiol 2015 37 (2) 1-9 BACKGROUND: In November and December 2012, 6 patients at a hemodialysis clinic were given a diagnosis of new hepatitis C virus (HCV) infection. OBJECTIVE: To investigate the outbreak to identify risk factors for transmission. METHODS: A case patient was defined as a patient who was HCV-antibody negative on clinic admission but subsequently was found to be HCV-antibody positive from January 1, 2008, through April 30, 2013. Patient charts were reviewed to identify and describe case patients. The hypervariable region 1 of HCV from infected patients was tested to assess viral genetic relatedness. Infection control practices were evaluated via observations. A forensic chemiluminescent agent was used to identify blood contamination on environmental surfaces after cleaning. RESULTS: Eighteen case patients were identified at the clinic from January 1, 2008, through April 30, 2013, resulting in an estimated 16.7% attack rate. Analysis of HCV quasispecies identified 4 separate clusters of transmission involving 11 case patients. The case patients and previously infected patients in each cluster were treated in neighboring dialysis stations during the same shift, or at the same dialysis station on 2 consecutive shifts. Lapses in infection control were identified. Visible and invisible blood was identified on multiple surfaces at the clinic. CONCLUSIONS: Epidemiologic and laboratory data confirmed transmission of HCV among numerous patients at the dialysis clinic over 6 years. Infection control breaches were likely responsible. This outbreak highlights the importance of rigorous adherence to recommended infection control practices in dialysis settings. |
Accurate genetic detection of hepatitis C virus transmissions in outbreak settings.
Campo DS , Xia GL , Dimitrova Z , Lin Y , Forbi JC , Ganova-Raeva L , Punkova L , Ramachandran S , Thai H , Skums P , Sims S , Rytsareva I , Vaughan G , Roh HJ , Purdy MA , Sue A , Khudyakov Y . J Infect Dis 2015 213 (6) 957-65 Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood, being difficult to detect and investigate. Here, we developed and validated a simple approach for molecular detection of HCV transmissions in outbreak settings. We obtained sequences from the HCV hypervariable region 1 (HVR1) using End-Point Limiting-Dilution (EPLD) from 127 cases involved in 32 epidemiologically defined HCV outbreaks and 193 individuals with unrelated HCV strains. We compared several types of genetic distances and calculated a threshold using minimal Hamming distances that identifies transmission clusters in all tested outbreaks with 100% accuracy. The approach was also validated on sequences from 239 individuals obtained using next-generation sequencing, showing the same accuracy as EPLD. In average, nucleotide diversity of the intra-host population was 6.2-times greater in the source than in any incident case, allowing the correct detection of transmission direction in 8 outbreaks for which source cases were known. A simple and accurate distance-based approach for detecting HCV transmissions developed here streamlines molecular investigation of outbreaks, thus improving the public health capacity for rapid and effective control of hepatitis C. |
The epidemiology of acute hepatitis B in the United States from population-based surveillance, 2006-2011
Iqbal K , Klevens RM , Kainer MA , Baumgartner J , Gerard K , Poissant T , Sweet K , Vonderwahl C , Knickerbocker T , Khudyakov Y , Xia GL , Roberts H , Teshale E . Clin Infect Dis 2015 61 (4) 584-92 BACKGROUND: An estimated 20,000 new hepatitis B virus (HBV) infections occur each year in the United States. We describe the results of enhanced surveillance for acute hepatitis B at seven federally funded sites over a six-year period. METHODS: Health departments in Colorado, Connecticut, Minnesota, Oregon, Tennessee, 34 counties in New York state, and New York City were supported to conduct enhanced, population-based surveillance for acute HBV from 2006 through 2011. Demographic and risk factor data were collected on symptomatic cases using a standardized form. Sera from a subset of cases were also obtained for molecular analysis. RESULTS: In the six-year period, 2,220 acute hepatitis B cases were reported from the seven sites. For all sites combined, the incidence rate of HBV infection declined by 19%, but in Tennessee incidence increased by 90%, mainly among persons of white race/ethnicity and those aged 40-49 years. Of all reported cases, 66.1% were male, 57.1% were white, 58.4% were aged 30-49 years, and 60.1% were born in the United States. The most common risk factor identified was any drug use, notably in Tennessee; healthcare exposure was also frequently reported. The most common genotype for all reported cases was HBV genotype A (82%). CONCLUSIONS: Despite an overall decline in HBV infection, attributable to successful vaccination programs, a rise in incident HBV infection related to drug use is an increasing concern in some localities. |
Recent population expansions of hepatitis B virus in the United States.
Ramachandran S , Purdy MA , Xia GL , Campo DS , Dimitrova ZE , Teshale EH , Teo CG , Khudyakov YE . J Virol 2014 88 (24) 13971-80 The recent epidemic history of hepatitis B virus (HBV) infections in the United States is complex, as indicated by current disparity in HBV genotype distribution between acute and chronic hepatitis B cases and rapid decline in hepatitis B incidence since the 1990s. We report temporal changes in genetic composition of the HBV population using whole-genome sequences (n=179) from acute hepatitis B cases (n=1206) identified through the Sentinel County Surveillance for Acute Hepatitis (1998-2006). HBV belonged mainly to subtypes A2 (75%) and D3 (18%), with times of their most recent common ancestors being, respectively, 1979 and 1987, respectively. A2 underwent rapid population expansions in ca. 1995 and ca. 2002, coinciding with transient rises in acute hepatitis B notification rates among adults; D3 underwent expansion in ca. 1998. A2 strains from cases identified after 2002, compared to those before 2002, tended to cluster phylogenetically, indicating selective expansion of specific strains, and were significantly reduced in genetic diversity (p = 0.001) and frequency of drug-resistance mutations (p = 0.001). The expansion of genetically close HBV A2 strains was associated with risk of infection among male homosexuals (p = 0.03). Incident HBV strains circulating in the US were recent in origin, and restricted in genetic diversity. Disparate transmission dynamics among phylogenetic lineages affected the genetic composition of HBV populations and their capacity to maintain drug-resistance mutations. The tendency of selectively expanding HBV strains to be transmitted among male homosexuals highlights the need to improve hepatitis B vaccination coverage among at-risk adults. IMPORTANCE: Hepatitis B virus (HBV) remains an important cause of acute and chronic liver disease globally, and in the United States. Genetic analysis of HBV whole genomes from cases of acute hepatitis B identified from 1998-2006 in the United States showed dominance of genotype A2 (75%), followed by D3 (18%). Strains of both subtypes were recent in origin and underwent rapid population expansions from 1995-2000, indicating increase in transmission rate for certain HBV strains during a period of decline in the reported incidence of acute hepatitis B in the US. HBV A2 strains from a particular cluster that experienced the most recent population expansion were more commonly detected among men who have sex with men. Vaccination needs to be stepped up to protect persons who remain at risk of HBV infection. |
Genetic history of hepatitis C virus in Pakistan.
Ur Rehman I , Vaughan G , Purdy MA , Xia GL , Forbi JC , Rossi LM , Butt S , Idrees M , Khudyakov YE . Infect Genet Evol 2014 27 318-24 Hepatitis C virus (HCV) genotype 3a accounts for approximately 80% of HCV infections in Pakistan, where approximately 10 million people are HCV-infected. Here, we report analysis of the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani genotype 3a variants were as genetically diverse as global variants, with extensive intermixing. Bayesian estimates showed that the most recent ancestor for genotype 3a in Pakistan was last extant in approximately 1896-1914 C.E. (range: 1851-1932). This genotype experienced a population expansion starting from approximately 1905 to approximately 1970 after which the effective population leveled. Death/birth models suggest that HCV 3a has reached saturating diversity with decreasing turnover rate and positive extinction. Taken together, these observations are consistent with a long and complex history of HCV 3a infection in Pakistan. |
Intra-host diversity and evolution of hepatitis C virus endemic to Côte d'Ivoire.
Forbi JC , Campo DS , Purdy MA , Dimitrova ZE , Skums P , Xia GL , Punkova LT , Ganova-Raeva LM , Vaughan G , Ben-Ayed Y , Switzer WM , Khudyakov YE . J Med Virol 2014 86 (5) 765-71 Hepatitis C virus (HCV) infection presents an important, but underappreciated public health problem in Africa. In Cote d'Ivoire, very little is known about the molecular dynamics of HCV infection. Plasma samples (n = 608) from pregnant women collected in 1995 from Cote d'Ivoire were analyzed in this study. Only 18 specimens ( approximately 3%) were found to be HCV PCR-positive. Phylogenetic analysis of the HCV NS5b sequences showed that the HCV variants belong to genotype 1 (HCV1) (n = 12, 67%) and genotype 2 (HCV2) (n = 6, 33%), with a maximum genetic diversity among HCV variants in each genotype being 20.7% and 24.0%, respectively. Although all HCV2 variants were genetically distant from each other, six HCV1 variants formed two tight sub-clusters belonging to HCV1a and HCV1b. Analysis of molecular variance (AMOVA) showed that the genetic structure of HCV isolates from West Africa with Cote d'Ivoire included were significantly different from Central African strains (P = 0.0001). Examination of intra-host viral populations using next-generation sequencing of the HCV HVR1 showed a significant variation in intra-host genetic diversity among infected individuals, with some strains composed of sub-populations as distant from each other as viral populations from different hosts. Collectively, the results indicate a complex HCV evolution in Cote d'Ivoire, similar to the rest of West Africa, and suggest a unique HCV epidemic history in the country. |
Full-length genome characterization and genetic relatedness analysis of hepatitis A virus outbreak strains associated with acute liver failure among children.
Vaughan G , Forbi JC , Xia GL , Fonseca-Ford M , Vazquez R , Khudyakov YE , Montiel S , Waterman S , Alpuche C , Goncalves Rossi LM , Luna N . J Med Virol 2014 86 (2) 202-8 Clinical infection by hepatitis A virus (HAV) is generally self-limited but in some cases can progress to liver failure. Here, an HAV outbreak investigation among children with acute liver failure in a highly endemic country is presented. In addition, a sensitive method for HAV whole genome amplification and sequencing suitable for analysis of clinical samples is described. In this setting, two fatal cases attributed to acute liver failure and two asymptomatic cases living in the same household were identified. In a second household, one HAV case was observed with jaundice which resolved spontaneously. Partial molecular characterization showed that both households were infected by HAV subtype IA; however, the infecting strains in the two households were different. The HAV outbreak strains recovered from all cases grouped together within cluster IA1, which contains closely related HAV strains from the United States commonly associated with international travelers. Full-genome HAV sequences obtained from the household with the acute liver failure cases were related (genetic distances ranging from 0.01% to 0.04%), indicating a common-source infection. Interestingly, the strain recovered from the asymptomatic household contact was nearly identical to the strain causing acute liver failure. The whole genome sequence from the case in the second household was distinctly different from the strains associated with acute liver failure. Thus, infection with almost identical HAV strains resulted in drastically different clinical outcomes. |
Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries.
Forbi JC , Ben-Ayed Y , Xia GL , Vaughan G , Drobeniuc J , Switzer WM , Khudyakov YE . J Clin Virol 2013 58 (1) 59-66 BACKGROUND: Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Cote d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]). STUDY DESIGN/RESULTS: Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Cote d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Cote d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape. CONCLUSIONS: The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa. |
Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010
Sena AC , Moorman A , Njord L , Williams RE , Colborn J , Khudyakov Y , Drobenuic J , Xia GL , Wood H , Moore Z . Infect Control Hosp Epidemiol 2013 34 (7) 709-16 OBJECTIVE: Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. DESIGN: Outbreak investigation with case-control studies. SETTING: Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. PATIENTS: Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. METHODS: After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. RESULTS: Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. CONCLUSIONS: These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission. |
An evaluation of hepatitis B virus diagnostic methods and responses to antiretroviral therapy among HIV-infected women in Thailand
Peters PJ , McNicholl JM , Raengsakulrach B , Wasinrapee P , Mueanpai F , Ratanasuwan W , Intalapaporn P , Drobeniuc J , Ramachandran S , Thai H , Xia GL , Kamili S , Khudyakov Y , Weidle PJ , Teo CG , McConnell MS . J Int Assoc Provid AIDS Care 2013 12 (5) 349-53 Coinfection with HIV and hepatitis B virus (HBV) is common in resource-limited settings but is frequently not diagnosed. The authors retrospectively tested specimens for HBV in HIV-infected Thai women who had participated in an antiretroviral therapy (ART) clinical study. A substantial proportion (27 of 211; 13%) of HIV-infected women were HBV coinfected. Among HIV/HBV-coinfected women, the authors observed similar rates of antiretroviral-associated liver toxicity (despite nevirapine [NVP] use) and CD4 count reconstitution as observed in HIV-monoinfected women. Hepatitis B surface antigen (HBsAg) screening detected the majority (81%) of HBV coinfections, including all 5 HBV-coinfected women who did not suppress HBV despite 48 weeks of lamivudine (3TC)-containing ART and could be used to tailor ART for patients diagnosed with HBV coinfection in accordance with World Health Organization guidelines. Although HBsAg screening did not diagnose 5 occult HBV coinfections, these women achieved HBV suppression on 3TC-containing ART, suggesting that not detecting occult HBV coinfection would have limited clinical impact. |
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