Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 33 Records) |
Query Trace: Teo CG[original query] |
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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. |
Risk Factors Associated with Blood Exposure for Sporadic Hepatitis E in Dhaka, Bangladesh.
Sazzad HMS , Luby SP , Labrique AB , Kamili S , Hayden TM , Kamili NA , Teo CG , Gurley ES . Am J Trop Med Hyg 2017 97 (5) 1437-1444 ![]() Fecal contamination of drinking water is associated with large hepatitis E virus (HEV) outbreaks of genotypes 1 and 2 in endemic areas. Sporadic transmission of HEV genotypes 3 and 4 in high-income countries has been associated with exposure to blood and animal contact. The objective of the study was to identify the risk factors for hepatitis E and the genotype(s) causing sporadic hepatitis E in Dhaka, Bangladesh. We selected, from a diagnostic center in Dhaka between November 2008 and November 2009, cases presenting with jaundice and anti-HEV IgM antibodies and age-matched controls were defined as those with no history of jaundice and normal blood test results. Serum samples were tested for HEV RNA using real-time reverse transcriptase polymerase chain reaction followed by a sequencing and phylogenetic analysis. A total of 109 cases and 109 controls were enrolled. The cases were more likely to be male (adjusted matched odds ratios [mOR] 2.2, 95% CI: 1.2-3.9; P = 0.01), or have reported contact with another person's blood or blood product, or contact with blood-contaminated sharp instruments (adjusted mOR 2.1, 95% CI: 1.1-4.1; P = 0.03) than controls. There were no significant differences between the cases and the controls in terms of reported high-risk sexual intercourse, consumption of undercooked meat, or contact or drinking fecally-contaminated water. The sera from three cases carried HEV RNA, all belonging to genotype 1. Findings from this study suggest that contact with human blood and sharing sharp instruments may transmit sporadic hepatitis E in Dhaka, Bangladesh. Efforts to prevent the transmission of blood-borne pathogens may also prevent sporadic HEV transmission in this endemic setting. |
Permissive, in vitro replication of hepatitis B virus genotype E.
Ji X , Zafrullah M , Wiese N , Hayden-Mixon T , Forbi JC , Teo CG , Purdy MA . J Virol Methods 2017 243 20-24 ![]() A cloned stable cell line, HepG2-HBVE6, was established following transfection of HepG2 cells with a retroviral plasmid into which a 1.1-fold genomic construct of hepatitis B virus (HBV) belonging to genotype E (HBV/E) was inserted. The cell line retains the entire HBV/E insert, and produces episomal HBV DNA. It expresses HBV pregenomic, preS1 and preS2/S transcripts, and sheds hepatitis B surface and e antigens as well as structures resembling HBV-subviral and Dane particles. The HepG2-HBVE6 cell line, in permitting recapitulation of the HBV life cycle, may be used for studying viral characteristics, therapeutic and preventative outcomes and for preparing reagents specific to HBV genotype E. |
Hepatitis E in Singapore: A Case-Series and Viral Phylodynamics Study.
Teo EC , Tan BH , Purdy MA , Wong PS , Ting PJ , Chang PJ , Oon LL , Sue A , Teo CG , Tan CK . Am J Trop Med Hyg 2017 96 (4) 922-928 ![]() ![]() The incidence of hepatitis E in Singapore appears to be increasing. A retrospective case-series study of patients diagnosed with hepatitis E in a tertiary hospital from 2009 to 2013 was conducted. Of 16 cases, eight (50%) were solid-organ transplant recipients (SOTRs), and 14 (88%) were found infected by genotype 3 hepatitis E virus (HEV-3). Bayesian inferences based on HEV subgenomic sequences from seven cases suggest that HEV-3 strains were introduced to Singapore as two principal lineages. Within limitations of the study, it can be inferred that one lineage, in the 3efg clade, emerged about 83 years ago, probably originating from Japan, whereas the other, in the 3abchij clade, emerged about 40 years ago, from the United States. Establishment and subsequent transmissions of strains from these two lineages likely contribute to the current endemicity of hepatitis E in Singapore. |
Evaluation of potencies of immune globulin products against hepatitis A
Tejada-Strop A , Costafreda MI , Dimitrova Z , Kaplan GG , Teo CG . JAMA Intern Med 2017 177 (3) 430-432 Passive immunization with human immune globulin (IG) is recommended for prophylaxis against hepatitis A and infection with its causative agent, hepatitis A virus (HAV). Immune globulin preparations administered intramuscularly (0.02 mL/kg) may confer protection for up to 3 months.1 Because anti-HAV antibody levels are declining in plasma donors from developed countries,2 we evaluated antibody levels in currently marketed IG products. Several products had lower-than-expected anti-HAV potencies, potentially conferring protection of reduced magnitude or duration against hepatitis A. |
Surveillance at private laboratories identifies small outbreaks of hepatitis E in urban Bangladesh
Sazzad HM , Labrique AB , Teo CG , Luby SP , Gurley ES . Am J Trop Med Hyg 2016 96 (2) 395-399 Although large outbreaks of hepatitis E are regularly identified in south Asia, the majority of south Asian countries lack surveillance systems for this disease, which has hindered burden of disease estimates and prioritization of resources for prevention. Our study aimed to identify small hepatitis E outbreaks through a sentinel private laboratory in Dhaka, Bangladesh. We identified patients with detectable IgM antibody against hepatitis E virus. We defined a small outbreak as at least two laboratory-confirmed cases or ≥ 2 acute jaundice cases from the sentinel cases' family, neighborhood, or workplace. From November 2008 to November 2009, we identified 29 small outbreaks of hepatitis E from one private laboratory. The median number of cases in each outbreak was three. Cases were identified every month. Eighteen outbreaks occurred among families or neighbors, and 11 in the workplace. Among 103 cases identified as part of outbreaks, 31 (30%) sought care for diagnosis. In Bangladesh, collaboration between government public health surveillance and private laboratories can strengthen capacity for outbreak detection and improve estimates of disease burden. |
Reply to Apolipoprotein E polymorphisms and their protective effect on Hepatitis E virus replication
Teo CG , Yesupriya A , Chang MH , Zhang L . Hepatology 2016 We appreciate the attention that Weller et al. have given to our report and findings. Weller et al. used an in vitro system based on Huh-7.5 cells silenced for endogenous apolipoprotein E (apoE) protein expression to investigate if genetic variants of the APOE gene (ϵ2, ϵ3, and ϵ4), when ectopically expressed, influence the production of intracellular hepatitis E virus (HEV) RNA and the expression of HEV open reading frame 2 (ORF2) protein after the cells were transfected with an HEV genotype 3 replicon. Finding that HEV RNA and ORF2 protein production were not affected regardless of which isoforms were expressed, they concluded that APOE polymorphisms do not affect HEV RNA replication and virus production. | HEV RNA quantification was applied by Weller et al. as an index of viral replication, and ORF2 protein quantification was used as a marker of the extent of viral particle assembly. However, HEV RNA measurement shows replication of the viral genome, not productive viral replication. Furthermore, measurement of the ORF2 protein, per se, is inadequate to indicate virion assembly; and other means of verifying if assembly has taken place are needed.(1) |
Chronic Infection With Camelid Hepatitis E Virus in a Liver-transplant Recipient Who Regularly Consumes Camel Meat and Milk.
Lee GH , Tan BH , Teo EC , Lim SG , Dan YY , Wee A , Aw PP , Zhu Y , Hibberd ML , Tan CK , Purdy MA , Teo CG . Gastroenterology 2015 150 (2) 355-7 e3 ![]() There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared these with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, so camelid HEV, which is genotype 7, might infect humans. Our finding links consumption of camel-derived food products to post-transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents. |
Fatal Accelerated Cirrhosis after Imported HEV Genotype 4 Infection.
Perumpail RB , Ahmed A , Higgins JP , So SK , Cochran JL , Drobeniuc J , Mixson-Hayden TR , Teo CG . Emerg Infect Dis 2015 21 (9) 1679-81 ![]() Hepatitis E is a viral hepatitide that is endemic in many developing countries. In its classic form, it results from ingesting fecally contaminated water that carries hepatitis E virus (HEV), and it frequently resolves without treatment. When hepatitis E is imported to the United States, it originates mainly from persons who have acquired HEV genotype 1 infection from South Asia (1). We report imported HEV genotype 4 infection (Technical Appendix Figure, panel A) in a patient during which cirrhosis and fatal hepatic decompensation ensued. | The patient was a 68-year-old man of Chinese ethnicity who had been a California resident since 1985. He sought treatment for mild jaundice in April 2013 in Hong Kong, where he had been staying for 7 weeks. Sixteen years before, he had undergone orthotopic liver transplantation at Stanford University Medical Center (Palo Alto, California, USA) for hepatitis B cirrhosis. Since then, he had received entecavir and tacrolimus for maintenance and had been vaccinated against hepatitis A virus. Until his current illness, routine liver function tests had not indicated hepatic dysfunction (values in November 2012: alanine aminotransferase 2 IU/L, aspartate aminotransferase 24 IU/L, alkaline phosphatase 67 IU/L, total bilirubin 0.5 mg/dL). |
Cost-effectiveness of strategies for testing current hepatitis C virus infection
Chapko MK , Dufour DR , Hatia R , Drobeniuc J , Ward JW , Teo CG . Hepatology 2015 62 (5) 1396-404 OBJECTIVE: Six strategies for identifying hepatitis C virus (HCV) viremia, involving testing for HCV antibody (HCVAb) followed by a nucleic acid test (NAT) for HCV RNA when the antibody test is positive, are compared. METHODS: Decision analysis was used to determine mean relative cost per person tested and outcomes of HCV viremia detection. Parameters included proportions of test population with HCV antibody and viremia, plus specificity, sensitivity and cost of individual tests. RESULTS: For testing a population with an HCVAb seroprevalence of 3.25%, all strategies when adopting quantitative NAT vary little in cost (range: $29.50-$30.70) and are highly viremia-specific (≥ 0.9997). Four of the strategies using venipuncture blood for HCVAb testing (whether laboratory-conducted or employing a rapid, point-of-care assay) and for NAT (whether done by reflex or using separately-drawn blood) achieve the highest viremia-sensitivities (range: 0.9950-0.9954). Point-of-care HCVAb testing in fingerstick blood followed by NAT in venipuncture blood yields relatively lower viremia sensitivity (0.9301). The strategy that requires returning for NAT is even less viremia-sensitive (<0.9000) because of follow-up loss. Strategies adopting qualitative rather than quantitative NAT are slightly cheaper (range: $28.90-$29.99), similarly viremia-specific (≥ 0.9997), but less viremia-sensitive (≤ 0.9456). Viremia-sensitivity and specificity remain the same regardless of the proportion of HCVAb-seropositive persons in the cohort being tested. CONCLUSIONS: Strategies involving HCVAb testing in venipuncture blood, whether laboratory-conducted or using a point-of-care assay, when followed by quantitative NAT done reflexively or in separately-drawn blood, are comparably economical and suitably viremia-sensitive. Less cost-effective is point-of-care HCVAb testing in fingerstick blood followed by NAT in venipuncture blood. Least cost-effective is the strategy requiring the tested person to return for NAT. |
Apolipoprotein E and protection against hepatitis E virus infection in American, non-Hispanic blacks.
Zhang L , Yesupriya A , Chang MH , Teshale E , Teo CG . Hepatology 2015 62 (5) 1346-52 ![]() Hepatitis E virus (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks address environmental and host behavioral/lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between anti-HEV IgG seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non-Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms (SNPs) across 190 genes (particularly those associated with lipid metabolism). Genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV IgG (15.3%; 95% confidence interval [CI], 12.3%-19.0%), compared with non-Hispanic whites (22.3%; 95% CI, 19.1%-25.7%), and Mexican Americans (21.8%; 95% CI, 19.0%-25.3%) (P < 0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional epsilon3 and epsilon4 alleles of apolipoprotein E (APOE) gene, encoding apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE epsilon4 (odds ratio [OR], 0.5; 95%CI, 0.4-0.7; P = 0.00004) and epsilon3 (OR, 0.6; 95%CI, 0.4-0.8; P = 0.001) compared to those carrying APOE epsilon2. No significant associations were observed between other SNPs and anti-HEV seropositivity in non-Hispanic blacks or between any SNPs and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans. CONCLUSION: APOE epsilon3 and epsilon4 are significantly associated with protection against HEV infection in non-Hispanic blacks. Additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons. |
Nosocomial hepatitis C virus transmission from tampering with injectable anesthetic opioids
Hatia RI , Dimitrova Z , Skums P , Teo EY , Teo CG . Hepatology 2015 62 (1) 101-10 The extent of provider-to-patient hepatitis C virus (HCV) transmission from diversion, self-injection and substitution ("tampering") of anesthetic opioids is unknown. To quantify the contribution of opioid tampering to nosocomial hepatitis C outbreaks, data from healthcare-related hepatitis C outbreaks occurring in developed countries from 1990-2012 were collated, grouped and compared. Tampering was associated with 17% (8/46) of outbreaks but 53% (438/833) of cases. Of the tampering outbreaks, 6 (75%) involved fentanyl, 5 (63%) occurred in the United States, and one each in Australia, Israel and Spain. Case counts ranged from 5-275 in the tampering outbreaks (mean, 54.8; median, 25), and 1-99 in the non-tampering outbreaks (mean, 10.4; median, 5); between them, the difference in mean ranks of counts was significant (p<0.01). To estimate HCV transmission risks from tampering, risk-assessment models were constructed, and these risks compared with those from surgery. The HCV transmission risk from exposure to an opioid preparation tampered by a provider of unknown HCV-infection status who is a person who injects drugs (PWID) (0.62%; standard error [e]=0.38%) exceeds 16,757 times the risk from surgery by a surgeon of unknown HCV-infection status (0.000037%; e=0.000029%), and 135 times by an HCV-infected surgeon (0.0046%; e=0.0033%). To pose a 50% patient transmission risk, an infected surgeon may take 30 years, compared to <1 year for a PWID-tamperer, and weeks or days for a PWID-tamperer who intensifies access to opioids. CONCLUSION: Disproportionately many cases of HCV infection from nosocomial outbreaks were attributable to provider tampering of anesthetic opioids. The transmission risk from tampering is substantially higher than from surgery. |
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. |
Decline in hepatitis E virus antibody prevalence in the United States from 1988-1994 to 2009-2010
Teshale EH , Denniston MM , Drobeniuc J , Kamili S , Teo CG , Holmberg SD . J Infect Dis 2014 211 (3) 366-73 BACKGROUND: Previous population-based estimates in the United States have shown a relatively high prevalence of hepatitis E virus (HEV) antibody. We sought to determine whether changes in the prevalence of HEV antibody have occurred over time. METHODS: We analyzed data from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) and NHANES III (1988-1994). Using the same serologic assay, we compared the estimated anti-HEV-IgG prevalence and risk factors for antibody positivity for the two time periods. RESULTS: The prevalence of HEV antibody among those aged>6 years declined from 10.2% (95% CI 9.1-11.4) during 1988-1994 to 6.0% (5.2-6.8%) during 2009-2010, and for those of US birth, from 9.6% (8.4-10.9) to 5.2% (4.4-6.2). Among US-born persons, the estimated HEV-antibody prevalence declined significantly for all subgroups of age , sex, region of residence, and number of persons per room in the household; significant declines also were observed for persons at or above poverty level, and persons of non-Hispanic white, non-Hispanic black and Mexican-American race/ethnicity. No clear associations with food consumption were found. CONCLUSION: Anti-HEV prevalence is declining in the US. Although the decline suggests a decrease in exposure to HEV over time, the risks associated with exposure remain unknown. |
Next-generation sequencing reveals large connected networks of intra-host HCV variants.
Campo DS , Dimitrova Z , Yamasaki L , Skums P , Lau DT , Vaughan G , Forbi JC , Teo CG , Khudyakov Y . BMC Genomics 2014 15 Suppl 5 S4 ![]() BACKGROUND: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host. RESULTS: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient. CONCLUSIONS: Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance. |
Discrepant hepatitis B surface antigen results in pregnant women screened to identify hepatitis B virus infection
Veselsky SL , Walker TY , Fenlon N , Teo CG , Murphy TV . J Pediatr 2014 165 (4) 773-8 OBJECTIVE: To resolve discrepant hepatitis B surface antigen (HBsAg) results for pregnant women screened for hepatitis B virus (HBV) infection. STUDY DESIGN: A case was defined as discrepant HBsAg (reactive followed by non-reactive) result during the same pregnancy. The Centers for Disease Control and Prevention examined a convenience sample of cases passively reported by US Perinatal Hepatitis B Prevention Programs. Using a standard form, available results were obtained for hepatitis B tests and vaccination histories. Results were independently reviewed by 3 viral hepatitis experts and a clinical virologist to resolve discrepancies. The initial HBsAg result was classified as probable true positive, probable false positive, or unresolved. RESULTS: From April 2009-December 2011, 142 (75.9%) of 187 reported discrepant cases met the case definition. Of the 142 initial reactive HBsAg results, 113 (79.5%) were laboratory-confirmed, and 89 (62.7%) were resolved. Among these 89 cases, the initial test was a probable true positive in 14 (15.7%), and a false positive in 75 (84.3%). Total antibody to hepatitis B core antigen was positive for 11 (78.6%) of the true positive cases and negative for 67 (89.3%) of the false positive cases. True positives included 2 cases of resolving acute HBV infection and one case recently given hepatitis B vaccination. CONCLUSIONS: In this retrospective analysis of discrepant HBsAg-reactive screening results from pregnant women, the majority were false positives, but true positives occurred. Testing for total hepatitis B core antigen, an indicator of past or current HBV infection, was useful for resolving discrepancies. |
HIV and HCV infection in the United States: whom and how to test
Panneer N , Lontok E , Branson BM , Teo CG , Dan C , Parker M , Stekler JD , DeMaria A Jr , Miller V . Clin Infect Dis 2014 59 (6) 875-82 In the United States, of the 1.1 million persons infected with human immunodeficiency virus (HIV) and the 2.7 million infected with hepatitis C virus (HCV), approximately 16% and 50%, respectively, are unaware of their infection. Highly effective treatments have turned both diseases into manageable conditions, and in the case of hepatitis C, a disease that can be cured. Early diagnosis is imperative so infected persons can take measures to stay healthy, get into care, benefit from therapy, and reduce the risk of transmission. In this report, we review current recommendations provided by the Centers for Disease Control and Prevention (CDC) and the United States Preventive Services Task Force on whom to screen for HIV and HCV infections, and recommendations from the CDC, the Association of Public Health Laboratories, and the Clinical and Laboratory Standards Institute on how to test for these infections. |
The legacies of Eugene Jamot and La Jamotique
Mbopi-Keou FX , Belec L , Milleliri JM , Teo CG . PLoS Negl Trop Dis 2014 8 (4) e2635 Who remembers “l'éveilleur” (“the awakener”), Colonel Eugène Jamot (1879–1937) [2]? Many still, it would seem, judging from the constant stream of biographies and articles that have appeared over the century, commemorating his contributions to the control of sleeping sickness, otherwise known as human African trypanosomiasis (HAT) [1], [3]. There is even an association that has been established and dedicated to his life and achievements [4]. |
Hepatitis B virus infection among HIV-infected pregnant women in Malawi and transmission to infants
Chasela CS , Kourtis AP , Wall P , Drobeniuc J , King CC , Thai H , Teshale EH , Hosseinipour M , Ellington S , Codd MB , Jamieson DJ , Knight R , Fitzpatrick P , Kamili S , Hoffman I , Kayira D , Mumba N , Kamwendo DD , Martinson F , Powderly W , Teo CG , van der Horst C . J Hepatol 2014 60 (3) 508-14 BACKGROUND & AIMS: The extent of HBV infection to infants of HBV/HIV-coinfected pregnant women in sub-Saharan Africa is unknown. The aim of this study was to assess prevalence of HBV infection among antiretroviral-naive, HIV-infected pregnant women in Malawi and examine HBV transmission to their infants. METHODS: Plasma from 2048 HIV-infected, Malawian women and their infants were tested for markers of HBV infection. Study participants were provided standard-of-care health services, which included administration of pentavalent vaccine to infants at 6, 10, and 14weeks of age. RESULTS: One-hundred and three women (5%) were HBsAg-positive; 70 of these HBsAg-positive women were also HBV-DNA-positive. Sixteen women (0.8%) were HBV-DNA-positive but HBsAg-negative. Five of 51 infants (9.8%) born to HBsAg-positive and/or HBV-DNA-positive women were HBV-DNA-positive by 48weeks of age.HBV DNA concentrations of two infants of mothers who received extended lamivudine-containing anti-HIV prophylaxis were <4 log10 IU/ml compared to 8 log10 IU/ml in three infants of mothers who did not. CONCLUSIONS: HBV DNA was detected in nearly 10% of infants born to HBV/HIV-coinfected women. Antenatal testing for HIV and HBV, if instituted, can facilitate implementation of prophylactic measures against infant infection by both viruses. |
Drug-resistance of a viral population and its individual intra-host variants during the first 48 hours of therapy
Campo DS , Skums P , Dimitrova Z , Vaughan G , Forbi JC , Teo CG , Khudyakov Y , Lau DT . Clin Pharmacol Ther 2014 95 (6) 627-35 ![]() Using HCV and IFN-resistance as a proof of concept, we have devised a new methodology for calculating the effect of a drug over a viral population and the resistance of its individual intra-host variants. By means of next-generation sequencing, HCV variants were obtained from sera collected at 9 time-points from 16 patients during the first 48 hours after injection of IFN-a. IFN-resistance coefficients were calculated for individual variants using changes in their relative frequencies, and for the entire intra-host viral population using changes in viral titer during the initial 48 hours. Population-wide resistance and presence of IFN-resistant variants were highly associated with pegIFN-a2a/RBV treatment outcome at week 12 (p = 3.78x10-5 and 0.0114, respectively). This new method allows an accurate measurement of resistance based solely on changes in viral titer or the relative frequency of intra-host viral variants during a short observation time. |
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. |
Laboratory-based surveillance for hepatitis E virus infection, United States, 2005-2012
Drobeniuc J , Greene-Montfort T , Le NT , Mixson-Hayden TR , Ganova-Raeva L , Dong C , Novak RT , Sharapov UM , Tohme RA , Teshale E , Kamili S , Teo CG . Emerg Infect Dis 2013 19 (2) 218-22 ![]() To investigate characteristics of hepatitis E cases in the United States, we tested samples from persons seronegative for acute hepatitis A and B whose clinical specimens were referred to the Centers for Disease Control and Prevention during June 2005-March 2012 for hepatitis E virus (HEV) testing. We found that 26 (17%) of 154 persons tested had hepatitis E. Of these, 15 had not recently traveled abroad (nontravelers), and 11 had (travelers). Compared with travelers, nontravelers were older (median 61 vs. 32 years of age) and more likely to be anicteric (53% vs. 8%); the nontraveler group also had fewer persons of South Asian ethnicity (7% vs. 73%) and more solid-organ transplant recipients (47% vs. 0). HEV genotype 3 was characterized from 8 nontravelers and genotypes 1 or 4 from 4 travelers. Clinicians should consider HEV infection in the differential diagnosis of hepatitis, regardless of patient travel history. |
Changing strategies for hepatitis C testing
Teo CG . Antivir Ther 2012 17 1391-5 ![]() Recent approvals of direct-acting, orally delivered pharmaceuticals for the treatment of patients with infection by HCV and of a point-of-care assay for community screening of HCV infection have generated impetus to widen the identification of HCV-infected individuals. Diagnosis of HCV infection is, however, still based on the detection of anti-HCV immunoglobulin G. As treatment is intended for individuals with current infection, testing for evidence of infection would need to centre on the detection of HCV viraemia. Minimizing the complexity and costs associated with HCV nucleic acid testing and speeding the development and validation of HCV antigen assays expedite the identification of HCV-viraemic individuals. Establishing means to diagnose recent HCV infection and to engage in surveillance of drug-resistant HCV are also apposite. Successful implementation of these various measures brightens prospects for the eventual elimination of HCV. |
Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965
Smith BD , Morgan RL , Beckett GA , Falck-Ytter Y , Holtzman D , Teo CG , Jewett A , Baack B , Rein DB , Patel N , Alter M , Yartel A , Ward JW . MMWR Recomm Rep 2012 61 1-32 Hepatitis C virus (HCV) is an increasing cause of morbidity and mortality in the United States. Many of the 2.7-3.9 million persons living with HCV infection are unaware they are infected and do not receive care (e.g., education, counseling, and medical monitoring) and treatment. CDC estimates that although persons born during 1945-1965 comprise an estimated 27% of the population, they account for approximately three fourths of all HCV infections in the United States, 73% of HCV-associated mortality, and are at greatest risk for hepatocellular carcinoma and other HCV-related liver disease. With the advent of new therapies that can halt disease progression and provide a virologic cure (i.e., sustained viral clearance following completion of treatment) in most persons, targeted testing and linkage to care for infected persons in this birth cohort is expected to reduce HCV-related morbidity and mortality. CDC is augmenting previous recommendations for HCV testing (CDC. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47[No. RR-19]) to recommend one-time testing without prior ascertainment of HCV risk for persons born during 1945-1965, a population with a disproportionately high prevalence of HCV infection and related disease. Persons identified as having HCV infection should receive a brief screening for alcohol use and intervention as clinically indicated, followed by referral to appropriate care for HCV infection and related conditions. These recommendations do not replace previous guidelines for HCV testing that are based on known risk factors and clinical indications. Rather, they define an additional target population for testing: persons born during 1945-1965. CDC developed these recommendations with the assistance of a work group representing diverse expertise and perspectives. The recommendations are informed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, an approach that provides guidance and tools to define the research questions, conduct the systematic review, assess the overall quality of the evidence, and determine strength of the recommendations. This report is intended to serve as a resource for health-care professionals, public health officials, and organizations involved in the development, implementation, and evaluation of prevention and clinical services. These recommendations will be reviewed every 5 years and updated to include advances in the published evidence. |
Convergence and coevolution of hepatitis B virus drug resistance.
Thai H , Campo DS , Lara J , Dimitrova Z , Ramachandran S , Xia G , Ganova-Raeva L , Teo CG , Lok A , Khudyakov Y . Nat Commun 2012 3 789 ![]() ![]() Treatment with lamivudine of patients infected with hepatitis B virus (HBV) results in a high rate of drug resistance, which is primarily associated with the rtM204I/V substitution in the HBV reverse transcriptase domain. Here we show that the rtM204I/V substitution, although essential, is insufficient for establishing resistance against lamivudine. The analysis of 639 HBV whole-genome sequences obtained from 11 patients shows that rtM204I/V is independently acquired by more than one intra-host HBV variant, indicating the convergent nature of lamivudine resistance. The differential capacity of HBV variants to develop drug resistance suggests that fitness effects of drug-resistance mutations depend on the genetic structure of the HBV genome. An analysis of Bayesian networks that connect rtM204I/V to many sites of HBV proteins confirms that lamivudine resistance is a complex trait encoded by the entire HBV genome rather than by a single mutation. These findings have implications for public health and offer a more general framework for understanding drug resistance. |
Fatal outbreaks of jaundice in pregnancy and the epidemic history of hepatitis E
Teo CG . Epidemiol Infect 2012 140 (5) 1-21 SUMMARY: Space-time clustering of people who fall acutely ill with jaundice, then slip into coma and death, is an alarming phenomenon, more markedly so when the victims are mostly or exclusively pregnant. Documentation of the peculiar, fatal predisposition of pregnant women during outbreaks of jaundice identifies hepatitis E and enables construction of its epidemic history. Between the last decade of the 18th century and the early decades of the 20th century, hepatitis E-like outbreaks were reported mainly from Western Europe and several of its colonies. During the latter half of the 20th century, reports of these epidemics, including those that became serologically confirmed as hepatitis E, emanated from, first, the eastern and southern Mediterranean littoral and, thereafter, Southern and Central Asia, Eastern Europe, and the rest of Africa. The dispersal has been accompanied by a trend towards more frequent and larger-scale occurrences. Epidemic and endemic hepatitis E still beset people inhabiting Asia and Africa, especially pregnant women and their fetuses and infants. Their relief necessitates not only accelerated access to potable water and sanitation but also vaccination against hepatitis E. |
Restricted enzooticity of hepatitis E virus genotypes 1 to 4 in the United States.
Dong C , Meng J , Dai X , Liang JH , Feagins AR , Meng XJ , Belfiore NM , Bradford C , Corn JL , Cray C , Glass GE , Gordon ML , Hesse RA , Montgomery DL , Nicholson WL , Pilny AA , Ramamoorthy S , Shaver DD , Drobeniuc J , Purdy MA , Fields HA , Kamili S , Teo CG . J Clin Microbiol 2011 49 (12) 4164-72 ![]() Hepatitis E is recognized as a zoonosis, and swine are known reservoirs, but how broadly enzootic its causative agent, hepatitis E virus (HEV), is remains controversial. To determine the prevalence of HEV infection in animals, a serological assay with capability to detect anti-HEV-antibody across a wide variety of animal species was devised. Recombinant antigens comprising truncated capsid proteins generated from HEV-subgenomic constructs that represent all four viral genotypes were used to capture anti-HEV in the test sample and as an analyte reporter. To facilitate development and validation of the assay, serum samples were assembled from blood donors (n = 372), acute hepatitis E patients (n = 94), five laboratory animals (rhesus monkey, pig, New Zealand rabbit, Wistar rat, and BALB/c mouse) immunized with HEV antigens, and four pigs experimentally infected with HEV. The assay was then applied to 4,936 sera collected from 35 genera of animals that were wild, feral, domesticated, or otherwise held captive in the United States. Test positivity was determined in 457 samples (9.3%). These originated from: bison (3/65, 4.6%), cattle (174/1,156, 15%), dogs (2/212, 0.9%), Norway rats (2/318, 0.6%), farmed swine (267/648, 41.2%), and feral swine (9/306, 2.9%). Only the porcine samples yielded the highest reactivities. HEV RNA was amplified from one farmed pig and two feral pigs and characterized by nucleotide sequencing to belong to genotype 3. HEV infected farmed swine primarily, and the role of other animals as reservoirs of its zoonotic spread appears to be limited. |
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. |
Transmission of human immunodeficiency virus and hepatitis C virus from an organ donor to four transplant recipients
Ison MG , Llata E , Conover CS , Friedewald JJ , Gerber SI , Grigoryan A , Heneine W , Millis JM , Simon DM , Teo CG , Kuehnert MJ . Am J Transplant 2011 11 (6) 1218-1225 ![]() In 2007, a previously uninfected kidney transplant recipient tested positive for human immunodeficiency virus type 1 (HIV) and hepatitis C virus (HCV) infection. Clinical information of the organ donor and the recipients was collected by medical record review. Sera from recipients and donor were tested for serologic and nucleic acid-based markers of HIV and HCV infection, and isolates were compared for genetic relatedness. Routine donor serologic screening for HIV and HCV infection was negative; the donor's only known risk factor for HIV was having sex with another man. Four organs (two kidneys, liver and heart) were transplanted to four recipients. Nucleic acid testing (NAT) of donor sera and posttransplant sera from all recipients were positive for HIV and HCV. HIV nucleotide sequences were indistinguishable between the donor and four recipients, and HCV subgenomic sequences clustered closely together. Two patients subsequently died and the transplanted organs failed in the other two patients. This is the first recognized cotransmission of HIV and HCV from an organ donor to transplant recipients. Routine posttransplant HIV and HCV serological testing and NAT of recipients of organs from donors with suspected risk factors should be considered as routine practice. |
Serologic assays specific to immunoglobulin M antibodies against hepatitis E virus: pangenotypic evaluation of performances
Drobeniuc J , Meng J , Reuter G , Greene-Montfort T , Khudyakova N , Dimitrova Z , Kamili S , Teo CG . Clin Infect Dis 2010 51 (3) e24-7 ![]() Six immunoassays for detecting immunoglobulin M antibodies to hepatitis E virus were evaluated. Serum samples representing acute infection by each of the 4 viral genotypes as well as nonacute hepatitis E virus infection constituted the test panels. Diagnostic sensitivities and specificities as well as interassay agreement varied widely. Analytical sensitivity limits also were determined and were found to be particularly disparate. |
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