viernes, 23 de marzo de 2018

Ahead of Print -Second Human Pegivirus in Hepatitis C Virus–Infected and Hepatitis C Virus/HIV-1–Co-infected Persons Who Inject Drugs, China - Volume 24, Number 5—May 2018 - Emerging Infectious Disease journal - CDC

Ahead of Print -Second Human Pegivirus in Hepatitis C Virus–Infected and Hepatitis C Virus/HIV-1–Co-infected Persons Who Inject Drugs, China - Volume 24, Number 5—May 2018 - Emerging Infectious Disease journal - CDC

Volume 24, Number 5—May 2018


Second Human Pegivirus in Hepatitis C Virus–Infected and Hepatitis C Virus/HIV-1–Co-infected Persons Who Inject Drugs, China

Haiying Wang1, Zhengwei Wan1, Qiang Sun1, Nalin Zhu, Tianyi Li, Xuqi Ren, Xiaoping An, Shuyun Deng, Yue Wu, Xiufen Li, Lin Li, Jingyun Li, Yigang Tong, and Shixing TangComments to Author 
Author affiliations: Southern Medical University, Guangzhou, China (H. Wang, Z. Wan, N. Zhu, Y. Wu, X. Li, S. Tang)Guangdong Provincial Key Laboratory of Tropical Disease Research, Guangzhou (H. Wang, Z. Wan, N. Zhu, Y. Wu, X. Li, S. Tang)Beijing Institute of Microbiology and Epidemiology, Beijing, China (Q. Sun, T. Li, X. An, L. Li, J. Li, Y. Tong)Guangdong Provincial Dermatology Hospital, Guangzhou (X. Ren)Nanfang Hospital, Guangzhou (S. Deng)


We report the presence of the second human pegivirus (HPgV-2) in the Guangdong and Sichuan provinces in China. The prevalence of HPgV-2 in hepatitis C virus/HIV-1–co-infected persons who inject drugs was 12.9% in Guangdong and 15.9% in Sichuan. This population is at high risk for HPgV-2 infection.
In 2015, the second human pegivirus (HPgV-2) was independently reported by 2 groups in the United States (1,2). Previous reports have indicated that HPgV-2 (also known as HHpgV-1) is a transfusion-transmitted virus and is associated with hepatitis C virus (HCV) infection (15). The distribution and prevalence of HPgV-2 infection worldwide are of great importance but remain to be determined. In this study, we demonstrate the existence of HPgV-2 in the southern province of Guangdong and southwestern province of Sichuan in China. We have also identified HCV-infected persons, in particular HCV/HIV-1 co-infected persons who inject drugs (PWID), as populations at high risk for HPgV-2 infection. In addition, our work reveals the difference in the prevalence, distribution, and phylogeny between the first human pegivirus (HPgV; formerly GB virus C or hepatitis G virus) (6,7) and HPgV-2.

The Study

Thumbnail of Detection of second human pegivirus (HPgV-2) antibodies in different samples in Guangdong and Sichuan Provinces, China. Serum or plasma samples from 86 HCV-infected patients, 70 PWID, 122 MSM, and 102 blood donors (100 samples that were negative for HPgV-2 antibodies plus 2 positive samples) are included. The antibody titers from each sample are plotted on the y-axis. HPgV-2 RNA–positive samples are shown in red. HCV, hepatitis C virus; MSM, men who have sex with men; OD450, optical

Figure 1. Detection of second human pegivirus (HPgV-2) antibodies in different samples in Guangdong and Sichuan Provinces, China. Serum or plasma samples from 86 HCV-infected patients, 70 PWID, 122 MSM, and 102 blood...
In our initial investigation of HPgV-2, we screened a total of 367 delinked serum or plasma samples from high-risk groups for infection with HCV and HIV-1 and 500 healthy volunteer blood donors from Guangdong Province, China, by using ELISA (2,5), and a nested reverse transcription PCR targeting both the 5′ untranslated region and nonstructural protein 3 regions of HPgV-2 (3,5). We observed a low frequency (0.4%) of HPgV-2 antibody detection and the absence of HPgV-2 viremia in healthy blood donors tested in our study. Out of 86 HCV-infected patients, 1 (1.2%) was positive for both HPgV-2 antibodies and viral RNA (Table 1). Furthermore, we did not detect HPgV-2 RNA in men who have sex with men (MSM), although 1 (0.5%) of the 211 MSM was weakly positive for HPgV-2 antibodies and negative for HPgV-2 RNA (Table 1Figure 1).

We observed a relatively high prevalence of HPgV-2 infection in HCV/HIV-1 co-infected PWID in the Guangdong Province; 12.9% (9/70) were positive for HPgV-2 antibodies and 5.7% (4/70) for HPgV-2 RNA (Table 1). We obtained similar results from 270 PWID from Sichuan Province; 15.9% (43/270) were positive for HPgV-2 antibodies and 3.0% (8/270) for HPgV-2 RNA (Table 1). Using Fisher exact test, we observed a statistically significant difference between HCV-positive and HCV-negative patients in prevalence of having HPgV-2 antibodies (6.2% vs. 0; p<0.001) and prevalence of having HPgV-2 RNA (5% vs. 0; p = 0.026). Similarly, we observed a statistically significant difference between HIV-1–positive/HCV-positive patients and HIV-1–positive/HCV-negative patients in prevalence of having HPgV-2 antibodies (10% vs. 0; p<0.001) and prevalence of having HPgV-2 RNA (4% vs. 0; p = 0.040) (Table 2). These findings indicate a close association between HPgV-2 and HCV infection and synergy between HIV-1 and HCV infection with respect to HPgV-2 infections (5).
Thumbnail of Phylogenetic analysis of second human pegivirus (HPgV-2) isolates identified in our study (China) and abroad (UK and US). Phylogenetic trees of nucleotide sequences from complete sequences of HPgV-2 strains isolated in our study and elsewhere as well as hepatitis C virus and pegivirus strains from humans, simians, equids, bats, and rodents are included. The phylogenetic trees were constructed with the neighbor-joining tree method using MEGA6 software ( B

Figure 2. Phylogenetic analysis of second human pegivirus (HPgV-2) isolates identified in our study (China) and abroad (UK and US). Phylogenetic trees of nucleotide sequences from complete sequences of HPgV-2 strains isolated in...
Furthermore, we obtained 6 near full-length genome sequences of HPgV-2 by using next-generation sequencing or sequencing of PCR products (5). These strains from China, which included 2 from PWID (IDU31 and SC-LS-01), 2 from HCV-infected patients (HCV-121 and C346), and 2 from HCV-infected blood donors (HCV1241 and HCV1563), exhibited an identity of 93.6%–97.8% at the whole-genome level. Compared with other HPgV-2 strains from the United States and United Kingdom, the nucleotide sequence identity was 93.7%–96.2%. Sequence divergence was greatest at synonymous sites, with ratios of nonsynonymous to synonymous nucleotide substitutions of 0.125–0.150, which are consistent with other reports (13). Phylogenetic analysis indicated that HPgV-2 strains from China, United States, and United Kingdom clustered together to form a separate branch and fell into group 1 with the closely related pegiviruses from bats and rodents (Figure 2). Other pegiviruses from human, simian, and equine sources formed group 2, in which the variants of HPgV fell into a separate clade. These results illustrate the difference between the 2 human pegiviruses (1,2,8) and the low level of genetic diversity of HPgV-2 strains (13).

In contrast to the data on HPgV-2 infection, we observed a high frequency of HPgV infection across all 3 populations tested (HCV-infected patients, PWID, and MSM) (Tables 12). The percentage of HPgV viremia was 14.0% (14/86) in HCV-infected patients, 19.0% (40/211) in MSM, and 40.0% (28/70) in PWID (Table 1). Among MSM, prevalence of HPgV RNA was 28.0% (28/100) in those who were infected with HIV-1 alone and 33.3% (4/12) in those who were HIV-1/HCV co-infected (Table 1). For MSMs who were negative for both HIV-1 and HCV, 7.9% (7/89) were positive for HPgV RNA (Table 1).


We report the detection of the second human pegivirus, HPgV-2, in HCV-infected (in particular HCV/HIV-1 co-infected) persons in Guangdong and Sichuan Provinces, China (Table 1). Our results and those from previous studies demonstrate that the virus occurs in several geographically distinct regions in the world (14,9,10).
HPgV and HPgV-2 are the only known human pegiviruses (8), and comparing their association with HCV and HIV-1 infection is of great interest. Consistent with previous reports, we found that the prevalence of HPgV viremia was 7.9% in HCV and HIV-1–negative MSM and 33.3%–40% in HCV/HIV-1 co-infected MSM and PWID (Table 1). In contrast, only 0.5% of MSM and 0.4% of healthy blood donors were positive for HPgV-2 antibodies, but all were negative for HPgV-2 RNA (Table 1). These results indicate that HPgV-2 infection might be much less frequent than HPgV infection, possibly because of its low transmissibility or high clearance rate (24). The dramatic difference of distribution and prevalence between HPgV and HPgV-2 infections in different populations provides a clue for investigation of disease association with HPgV-2. HPgV does not cause human diseases (11) and can inhibit HIV-1 replication as well as prolong survival of HIV-1–infected and Ebola virus–infected patients (1214). However, possible pathogenicity and disease association of HPgV-2 remain to be elucidated.
The high-risk population susceptible to HPgV-2 infection includes HCV-infected patients and, in particular, HCV/HIV-1 co-infected PWID. Most (93.3%) of HPgV-2 infected patients were also co-infected with HCV (14). Notably, the relatively high frequency of HPgV-2 RNA detection was observed in HCV/HIV-1 co-infected PWID in the Guangdong (5.7%) and Sichuan (3.0%) Provinces of China (Table 1) and in the United States (10.9%) (9). In contrast, a somewhat lower percentage (1.7%) of HCV-positive PWID in the United Kingdom were reported to be HPgV-2 RNA positive, whereas none of the 30 HIV-1 singly infected and 36 HCV/HIV-1 co-infected PWID were positive for HPgV-2 RNA (3). These discordant results warrant more studies in different countries to address the association between HPgV-2 and HCV/HIV-1 co-infection.
Our findings are subject to 2 limitations. First, because a limited number of samples from only 2 provinces of China were tested, the results might not represent overall prevalence of HPgV-2 infection throughout all of China. Second, this study was a cross-sectional rather than a longitudinal study and therefore the proportion of persistent infection and natural history of HPgV-2 infection remain to be determined.
Future studies should address several questions: whether the close association between HPgV-2 and HCV infection represents a biologic dependence of these 2 viruses; how HCV/HIV-1 co-infection facilitates HPgV-2 infection; and whether HCV or HIV-1 viral proteins enhance the transmissibility or infectivity of HPgV-2. In addition, because the rarity of HPgV-2 detection in MSM could be a result of the low frequency of HCV or HIV-1 infection or the transmission route of HPgV-2, further research should aim to determine if is HPgV-2 more like a transfusion-transmitted virus rather than a sexually transmitted virus.
Dr. Wang is a postdoctoral fellow at School of Public Health of Southern Medical University in Guangzhou. Her research interests include identification and diagnosis of viral pathogens and investigation of viral pathogenesis.


This work was supported by the Bureau of Science and Information Technology of Guangzhou Municipality (grant nos. 201604020011, 2014Y2-00550, and 201704020219) and the Beijing Municipal Science and Technology Project (grant no. D141100000314001).


  1. Kapoor AKumar ASimmonds PBhuva NSingh Chauhan LLee Bet al. Virome analysis of transfusion recipients reveals a novel human virus that shares genomic features with hepaciviruses and pegiviruses. MBio2015;6:e0146615DOIPubMed
  2. Berg MGLee DColler KFrankel MAronsohn ACheng Ket al. Discovery of a novel human pegivirus in blood associated with hepatitis C virus co-infection. PLoS Pathog2015;11:e1005325DOIPubMed
  3. Bonsall DGregory WFIp CLDonfield SIles JAnsari MAet al. Evaluation of viremia frequencies of a novel human pegivirus by using bioinformatic screening and PCR. Emerg Infect Dis2016;22:6718DOIPubMed
  4. Coller KEBerg MGFrankel MForberg KSurani RChiu CYet al. Antibodies to the novel human pegivirus 2 are associated with active and resolved infections. J Clin Microbiol2016;54:202330DOIPubMed
  5. Wang HWan ZXu RGuan YZhu NLi Jet al. A novel human pegivirus, HPgV-2 (HHpgV-1), is tightly associated with hepatitis C virus (HCV) infection and HCV/human immunodeficiency virus type 1 coinfection. Clin Infect Dis2018;66:2935DOIPubMed
  6. Simons JNLeary TPDawson GJPilot-Matias TJMuerhoff ASSchlauder GGet al. Isolation of novel virus-like sequences associated with human hepatitis. Nat Med1995;1:5649DOIPubMed
  7. Linnen JWages J JrZhang-Keck ZYFry KEKrawczynski KZAlter Het al. Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science1996;271:5058DOIPubMed
  8. Smith DBBecher PBukh JGould EAMeyers GMonath Tet al. Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family. J Gen Virol2016;97:2894907DOIPubMed
  9. Kandathil AJBreitwieser FPSachithanandham JRobinson MMehta SHTimp Wet al. Presence of human hepegivirus-1 in a cohort of people who inject drugs. Ann Intern Med2017;167:17DOIPubMed
  10. Frankel MForberg KColler KEBerg MGHackett J JrCloherty Get al. Development of a high-throughput multiplexed real time RT-PCR assay for detection of human pegivirus 1 and 2. J Virol Methods2017;241:3440DOIPubMed
  11. Mohr ELStapleton JTGB virus type C interactions with HIV: the role of envelope glycoproteins. J Viral Hepat2009;16:75768DOIPubMed
  12. Vahidnia FPetersen MStapleton JTRutherford GWBusch MCuster BAcquisition of GB virus type C and lower mortality in patients with advanced HIV disease. Clin Infect Dis2012;55:10129DOIPubMed
  13. Zhang WChaloner KTillmann HLWilliams CFStapleton JTEffect of early and late GB virus C viraemia on survival of HIV-infected individuals: a meta-analysis. HIV Med2006;7:17380DOIPubMed
  14. Lauck MBailey ALAndersen KGGoldberg TLSabeti PCO’Connor DHGB virus C coinfections in west African Ebola patients. J Virol2015;89:24259DOIPubMed



Suggested citation for this article: Wang H, Wan Z, Sun Q, Zhu N, Li T, Ren X, et al. Second human pegivirus in hepatitis C virus–infected and hepatitis C virus/HIV-1–co-infected persons who inject drugs, China. Emerg Infect Dis. 2018 May [date cited].
DOI: 10.3201/eid2405.161162

1These authors contributed equally to this article.

jueves, 22 de marzo de 2018

TB Notes 2, 2018 - Updates from CDC’s Division of Tuberculosis Elimination

Table of Contents

Notes from the Director

Dear Colleague:
One of the most important events for people working in tuberculosis (TB) elimination is World TB Day. World TB Day is observed annually on March 24, to commemorate Dr. Robert Koch’s announcement of his discovery of Mycobacterium tuberculosis, the bacillus that causes TB. On March 24, and the days leading up to it, CDC and many others share successes in TB prevention and control and raise awareness of the challenges that hinder our progress. The U.S. theme for World TB Day 2018 is “Wanted: Leaders for a TB Free United States. We can make history. End TB.” The Division of Tuberculosis Elimination (DTBE) World TB Day activities highlight our past achievements, present efforts, and future aspirations.
A total of 9,093 TB cases were reported in the United States in 2017 according to preliminary data from the CDC National TB Surveillance System. This 2017 provisional case count is the lowest number of TB cases on record in the United States; however, our current strategies will not be sufficient to reach the goal of TB elimination in the United States. Eliminating TB in the United States will require a sustained effort to control TB disease, and expanding testing and treatment of latent TB infection to prevent the development of TB disease.
Achieving TB elimination will also require the continued hard work and dedication from those working on the state and local levels. One of the goals of this year’s World TB Day campaign is to highlight this great work through the 2018 CDC U.S TB Elimination Champions project. In keeping with this year’s theme, we are highlighting organizations and individuals who are leading the effort to collaborate with public health partners, health care providers, and community organizations. We encourage you to read and share their stories with your partners and colleagues. Additional CDC resources are available in English and Spanish, including up-to-date information on TB, promotional materials, and other tools you can use as part of your World TB Day events and activities.
I hope all of you will have a chance to plan or take part in your own World TB Day activities. Thank you for your work and commitment to eliminate TB in the United States.
Philip LoBue, MD, FACP, FCCP
Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Communications, Education, and Behavioral Studies Branch Updates

March 24 is World TB Day and this year’s theme is “Wanted: Leaders for a TB-Free United States. We can make history. End TB.” CDC’s World TB Day website is a one-stop-shop for resources and information. U.S. World TB Day posters are available in two different sizes (8.5x11 and 11x17) to download and print. Graphics in a variety of sizes are also available for use in digital and print materials. Check out all the activities happening across the United States on the World TB Day Activities Map.

Surveillance, Epidemiology, and Outbreak Investigations Branch Updates

In recognition of World TB Day, DTBE has published preliminary TB surveillance data for 2017, documenting 9,093 new cases of TB in the United States in 2017. This is the lowest case count on record and corresponds with a TB rate of 2.8 per 100,000 persons, a rate 2.5% lower than reported in 2016. Read More

Laboratory Branch Updates

TB Laboratory Services in Puerto Rico After Hurricane Maria
On September 20, 2017, Hurricane Maria made landfall in Puerto Rico, as a Category 4 storm, with sustained winds of 155 mph and gusts up to 190 mph destroying roads and bridges, causing flooding and landslides, and destroying the island’s power grid and telecommunication system. Hurricane Maria was the strongest hurricane in PR in 80 years, with estimated losses of more than 95 billion dollars. Read More

Clinical Research Branch Updates

The Latest News from the TB Trials Consortium (TBTC)
TBTC Study 31 (also known as ACTG A5349; “Rifapentine-containing treatment shortening regimens for pulmonary tuberculosis: A randomized, open-label, controlled phase 3 clinical trial”) continues to enroll. As of December 7, 2017, the study had 1,522 participants, 61% of target enrollment.  The AIDS Clinical Trials Group (ACTG) network is collaborating with TBTC, contributing substantially to enrollment. Read More

Data Management and Statistics Branch

TB Education and Training Network (TB ETN)/ Program Evaluators Network (PEN) Webinar Summary
Meet the DMSEB Program Evaluation and Health Economics Team!
The Mission of the DTBE Program Evaluation and Health Economics Team is to collaborate with internal and external partners to identify and promote the use of the best available evidence for the planning and implementation of TB elimination strategies.Read More

New CDC Publications

January 2018
Click ES, Murithi W, Ouma GS, McCarthy K, Willby M, Musau S, Alexander H, Pevzner E, Posey J, Cain KP. Detection of Apparent Cell-free M. tuberculosis DNA from Plasma. Sci Rep 2018 Jan 12; 8(1):645. doi: 10.1038/s41598-017-17683-6. PMID: 29330384.Read More