Open Forum Infectious Diseases MAJOR ARTICLE Aiming at the Global Elimination of Viral Hepatitis: Challenges Along the Care Continuum 1 2,3 4 5 6 2 7 Alastair Heffernan, Ella Barber, Nicola A. Cook, Asmaa I. Gomaa, Yolande X. Harley, Christopher R. Jones, Aaron G. Lim, 4,8 1,4 4,9 10 11 11 5 Zameer Mohamed, Shevanthi Nayagam, Gibril Ndow, Rajiv Shah, Mark W. Sonderup, C. Wendy Spearman, Imam Waked, 2,12,13 4 Robert J. Wilkinson, and Simon D. Taylor-Robinson 1 2 Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK; Division of Infectious Diseases, Faculty of Medicine, Imperial College London, London, 3 4 5 UK; Médecins Sans Frontières, London, UK; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Hepatology Department, National Liver Institute, 6 7 Menoufiya University, Shebeen El-Kom, Egypt; Research Office, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Population Health Sciences, Bristol Medical 8 9 School, University of Bristol, Bristol, UK; Liver and Antiviral Unit, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, London, UK; Hepatitis Unit, Disease Control and Elimination, MRC 10 11 Unit, Banjul, The Gambia; Infectious Diseases Department, Nottingham University Hospitals NHS Trust, Nottingham, UK; Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Tuberculosis Laboratory, The Francis Crick Institute, London, UK A recent international workshop, organized by the authors, analyzed the obstacles facing the ambitious goal of eliminating viral hepatitis globally. We identified several policy areas critical to reaching elimination targets. These include providing hepatitis B birth- dose vaccination to all infants within 24 hours of birth, preventing the transmission of blood-borne viruses through the expansion of national hemovigilance schemes, implementing the lessons learned from the HIV epidemic regarding safe medical practices to elim- inate iatrogenic infection, adopting point-of-care testing to improve coverage of diagnosis, and providing free or ao ff rdable hepatitis C treatment to all. We introduce Egypt as a case study for rapid testing and treatment scale-up: this country oer ff s valuable insights to policy makers internationally, not only regarding how hepatitis C interventions can be expeditiously scaled-up, but also as a guide for how to tackle the problems encountered with such ambitious testing and treatment programs. Keywords. elimination; hepatitis care continuum; policy; viral hepatitis. Viral hepatitis was responsible for 1.3 million deaths globally in before elimination will be reached. We focused on those areas in 2015 and is now the seventh leading cause of mortality, rising which improvements are possible (using tools currently avail- from the 10th cause in 1990 [1, 2]. The full burden of disease able) and on those aspects of treatment and care where the encompasses not only mortality, but also reduced quality of life impact of changes in policy or strategy is potentially greatest. for patients (through cirrhosis and associated complications), This viewpoint is a distillation of these discussions and is written financial costs of care for individuals and health care systems with the aim of informing policy at this critical moment in the alike, and economic costs to society as a whole. Despite this formation of national and international viral hepatitis programs. burden, viral hepatitis has only in recent years received the HBV BIRTH-DOSE VACCINATION: CONFRONTING attention it merits. Now, with a World Health Organization LOST OPPORTUNITIES (WHO) elimination strategy published , the international Scaling-up of infant vaccination has already had demonstrable community is at last focused on tackling the twin epidemics of impacts on global HBV prevalence . Infant vaccination hepatitis B virus (HBV) and hepatitis C virus (HCV). alone, however, does not prevent mother-to-child transmission At a recent conference (the first “Chronic Viral Hepatitis in (PMTCT). As the risk of chronic hepatitis B (CHB) infection is Africa” conference, Egypt), clinicians and researchers from across as high as 90% if infected perinatally , effective PMTCT is the globe discussed the challenges of reaching WHO elimination crucial to reducing incidence. targets. Considering the hepatitis care continuum (Figure 1) [3, 4], A key component of a comprehensive PMTCT strategy is we identified several key areas in which progress must be made birth-dose vaccination. Modeling studies have suggested that an 80% global scale-up of birth-dose vaccination plus infant Received 6 September 2017; editorial decision 2 November 2017; accepted 16 November 2017. vaccination, compared with scaling-up of infant vaccination Correspondence: C. W. Spearman, Division of Hepatology, Department of Medicine, Faculty alone, could avert 18.7 million new chronic infections over the of Health Sciences, University of K Floor, Old Main Main Building, Groote Schuur Hospital, Observatory, Cape Town, 7925, South Africa (email@example.com). next 15 years, highlighting its importance as a PMTCT tool . Open Forum Infectious Diseases Monovalent HBV vaccine is inexpensive (US$0.20 per dose), © The Author(s) 2017. Published by Oxford University Press on behalf of Infectious Diseases and birth-dose vaccination is likely to be cost-effective . Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits Despite such evidence, global HBV birth-dose vaccine cover- unrestricted reuse, distribution, and reproduction in any medium, provided the original work age remains low, at 39% . Moreover, vaccines are oen admini ft s- is properly cited. DOI: 10.1093/ofid/ofx252 tered beyond 24 hours of birth , when they are less effective in Aiming at Elimination of Viral Hepatitis • OFID • 1 Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018 Reached by prevention services Tested Aware of status Populations Enrolled in care within the care Initiated continuum for treatment viral hepatitis Treatment completed (HCV) or maintained (HBV) Achieved cure (HCV) or viral suppression (HBV) Care continuum Prevention Screening and Linkage to Care Treatments for viral hepatitis Current challenges 1) Provision of HBV birth-dose 3) Adoption of point-of-care testing 5) Maintenance of treatment for all vaccination within 24 hours of to expand diagnostic coverage cirrhotic HBV-infected patients within the care birth to prevent mother-tochild and strengthen linkage to care. indeﬁnitely to minimize risk of continuum for transmission. disease progression. viral hepatitis, 4) Integration of screening into with reference to existing care delivery models for 6) Procurement of aˆordable 2) Expansion of hemovigilance achieving WHO schemes and safe injection at-risk populations to increase directacting antiviral agents to elimination practices to reduce iatrogenic their access to and engagement enable universal access to with viral hepatitis care. treatment for HCV. targets transmission. Figure 1. Overview of the WHO care continuum for viral hepatitis and the associated challenges encountered when aiming toward WHO elimination targets, adapted fromn Zhou et al. . Populations within the care continuum for viral hepatitis are as defined within the Global Health Sector Strategy on Viral Hepatitis . Abbreviations: HBV = hepatitis B virus; HCV = hepatitis C virus; WHO = World Health Organization. PMTCT [11, 12]. There are several reasons for this low coverage: the HCV from blood is 2.5 per 1000 units transfused, compared with monovalent vaccine is not funded by agencies like GAVI, as the cost 1 per 2–3 million units in high-income countries . In add- of the vaccine falls below their funding threshold ; there are sig- ition, the reuse of injection equipment, inadequate sterilization nificant costs for vaccine delivery ; cultural factors may reduce procedures, lack of universal precautions, sharps injuries, and access to health care by women in the postpartum period ; and inadequate medical waste management systems all contribute hepatitis B interventions are rarely a public health priority , with to the burden of viral hepatitis. To reach WHO targets by 2030, only 9 countries in sub-Saharan Africa, for example, incorporating all blood donations should be screened for HIV, HCV, HBV, birth-dose vaccination into their national policies by 2015 [10, 17]. and syphilis in a quality-assured manner, and 90% of injections Innovative approaches exist to improve timely birth-dose should be administered using a safety-engineered device . vaccination administration, including increasing the number er Th e are several options for reducing risk of transfu- of health staff–attended births , ensuring coordination sion-transmissible infections (TTIs). Centralized blood trans- between immunization and maternal health services , fusion services targeting low-risk, regular, voluntary blood expanding vaccine management systems , using prefilled donors should be developed and integrated into health care sys- injectable vaccines for home births , promoting awareness tems . Although more expensive than replacement donor of the need for timely HBV vaccination , and simplifying systems , voluntary blood donors represent a safer, more the supply chain by, for example, using heat-sensitive labels to sustainable approach  and should contribute at least 80% of allow storage of vaccine outside the cold chain [22, 23]. all donations to transfusion services . All donations should A substantial scale-up in birth-dose vaccination coverage is be screened for TTIs, with external quality assurance, using pivotal to reaching WHO 2030 elimination targets . This is highly sensitive and specific assays [30, 31]. National hemovigi- long overdue, and acceleration of efforts requires a combination lance systems supported by local transfusion committees enable of political engagement by governments, financial commit- ongoing surveillance for transfusion-related complications , ment, and strategic planning to help countries reach these goals. but in low- and middle-income countries (LMICs), only 28% operate hemovigilance systems . Blood safety programs IATROGENIC TRANSMISSION: A COST -EFFECTIVE can be cost-effective , but cost-effectiveness varies, and APPROACH TO CURBING TRANSMISSION this should inform program design: adding antigen-antibody Blood and injection safety are fundamental to national viral hep- combination tests to reduce the serologically negative window atitis programs . In Africa, for example, the risk of acquiring period can be cost-effective , whereas TTI predonation 2 • OFID • Heffernan et al Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018 screening using rapid diagnostic tests (RDTs) is not considered suggest a role for DBS testing in marginalized populations un- to be cost-effective . likely to present at centralized testing facilities . Improving injection safety is also key to reducing iatrogenic e de Th velopment and validation of RDTs has become a transmission: in 2010, approximately 1.7 million new cases of HBV research priority. The WHO has prequalified 2 HCV RDTs: and up to 315 000 new cases of HCV were attributable to unsafe SDBioline (SDBioline, Gyeonggi-do, Republic of Korea) and injections . Such infections can be avoided through the use of Oraquick (OraSure Technologies Inc., Bethlehem, PA) [55, 56], safety-engineered devices that protect health care workers from an oral fluid-based point-of-care (POC) test with a comparable hazardous occupational exposures to bodily fluids , needle/ performance to third-generation enzyme immunoassays (EIAs) sharps hygiene and safe disposal, and a ban on needle reuse . . POC testing has been shown to improve HIV linkage to Such measures must be delivered alongside education of health care in LMIC and to be cost-effective [58-60, S61]. Combination care workers in universal precautions and safe waste management RDTs for HIV, HBV, and HCV have also been shown to increase systems. National policies for safe and appropriate use of injec- uptake and receipt of results relative to laboratory testing [S62]. tions are, furthermore, highly cost-effective . Global bodies Finally, the adoption of pangenotypic DAA regimens may must take the lead in promoting and financing blood screening eliminate the requirement for genotype testing entirely . All and injection safety initiatives to ensure that these cheap and ef- such developments can simplify and strengthen the diagnosis fective interventions are implemented worldwide. and treatment cascade, removing potential causes of LTFU, and will be crucial in reaching diagnosis and treatment targets. DIAGNOSTICS FOR HCV: TACKLING THE Active implementation of ao ff rdable POC testing at the primary BOTTLENECK care level will be essential to upscale identification and linkage The advent of highly efficacious direct-acting antiviral (DAA) to care of infected individuals. treatment has revolutionized the therapeutic landscape for PROVIDING CARE: ACCESSING HARD-TO-REACH chronic HCV infection, but less attention has been paid to screen- HCV-INFECTED POPULATIONS ing and diagnosis. Given the nature of the infection, asymptom- atic HCV-infected individuals are unlikely to seek health care In most countries, anti-HCV prevalence is well below 10% in the . Consequently, WHO targets of 90% of active infections general population [S63] but significantly greater in high-risk pop- diagnosed by 2030  are aspirational, outstripping the diagnosis ulations. The most studied population is PWID, in which anti-HCV coverage achieved even in those countries that have been most prevalence can exceed 90% [S64], but men who have sex with men successful in identifying infected individuals, such as France, (MSM) and other recreational drug users are increasingly being Australia, and Sweden . Currently, a 2-step process for diag- recognized as significant at-risk populations [S65, S66]. Such popu- nosing active HCV infection is usually required: a serological test lations are often difficult to reach for a variety of reasons, including to screen for exposure, followed by an HCV RNA nucleic acid stigma and the possibility of prosecution [S67, S68]. Programs spe- test (NAT) to confirm viremia . This 2-step process inevitably cifically designed to address epidemics within these populations are leads to patient loss to follow-up (LTFU) [44–46]. Furthermore, critical to the success of disease burden reduction efforts. in LMIC, NAT is economically challenging, and the specialized Qualitative [S69, S70] and quantitative [S71–S73] research laboratory staff and equipment are often not available [47, 48]. has shown that PWID are interested in engaging with health care Alternatively, serum HCV core antigen quantification services for HCV testing and treatment; there is clear evidence of (HCVcAg) can be used as a surrogate marker for HCV viremia. successful treatment outcomes in this group [S74], yet treatment Testing HCVcAg is a relatively low cost (as low as US$10 per in PWID remains suboptimal [S75,S76]. Health care provider sample ), fully automated, and a commercially available assay concerns can act as barriers to HCV treatment. Such concerns that can be performed on the Abbott ARCHITECT platform, may include the presence of comorbidities, the belief that there making it an attractive test for resource-limited settings [49, 50]. will be adherence issues, and difficulties managing side effects Employing HCVcAg testing while still dependent on a central- [S77]. From a patient perspective, there are several factors that ized testing facility can “uncouple” the sample collection from the may reduce the likelihood of accessing HCV treatment, includ- testing site through the use of dried blood spot (DBS) samples ing negative experiences within health care systems [S78, S79], [51, 52]: While whole blood and plasma samples require prompt low literacy rates [S80, S81], inadequate communication with transport to the laboratory or refrigeration, DBS samples can be health care providers regarding the nature of the disease and stored at room temperature for several weeks . The robust- treatment options [S79], and social factors such as discrimin- ness of this sample storage technique makes it ideal for decen- ation, the threat of stigmatization, and criminalization [S81]. tralizing testing, which is attractive for resource-limited settings Reviews of treatment models in high-income countries suggest . Though testing DBS samples for HCVcAg has been shown that effective approaches to improving rates of HCV diagnosis to have reduced sensitivity compared with using serum samples and treatment integrate HCV services into addiction care units [52, 54], the low cost and uncoupling of sample and testing site [S82]. Focusing on treatment of addiction [S83] and encouraging Aiming at Elimination of Viral Hepatitis • OFID • 3 Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018 positive feedback between health care staff and PWID [S84] While there is consensus that cirrhotics require lifelong treat- improve outcomes. Such multidisciplinary approaches reduce ment, the safety of stopping therapy in noncirrhotic patients noncompliance even among homeless or active illicit drug users remains less clear. Most international guidelines recommend dis- [S85]. Similar approaches can be utilized in general practitioner continuation of therapy for noncirrhotic HBeAg-positive indi- services; a study in the United Kingdom demonstrated how spe- viduals who show evidence of HBeAg loss and seroconversion cialist nurses seconded to primary care facilities can oer s ff creen- to antibody to HBeAg (anti-HBe), undetectable HBV DNA, and ing to at-risk individuals, considerably improving HCV detection who complete at least 12 months of consolidation therapy [S94]. [S86]. An alternative approach may be treatment as prevention: Discontinuation is only recommended when ALT and HBV Modeling suggests that it may be effective at curbing transmis- DNA levels can be monitored, as a high proportion relapse aer ft sion in both PWID [S87] and MSM [S88]. stopping treatment [S94, S97], placing an additional financial In LMIC, many patients, in addition to those discussed above, strain on health care systems. Antiviral therapy can be stopped in are hard to reach through lack of health care services. In such noncirrhotic HBeAg-negative individuals at least 12 months fol- scenarios, HCV screening could be integrated into existing lowing loss of HBsAg and achieving anti-HBs status [S98]. This care delivery models for HIV and tuberculosis (TB) [S89, S90]. needs to be accompanied by sustained virological suppression and Success of HIV treatment roll-out oer ff s valuable lessons : normalization of ALT, with off-treatment monitoring for relapse. Community-based testing improves uptake among high–CD4 With only a small proportion of patients achieving HBsAg loss, count individuals compared with facility-based approaches and with the need for regular monitoring for reactivation and [S91], and we propose that the impressive improvements in HIV a fl res aer ces ft sation of antiviral therapy in both HBeAg-positive case finding could be replicated for HCV using similar methods. and -negative individuals, we believe it is advisable at present to treat all patients indefinitely [S98]. e Th additional financial bur - TREATING HBV INFECTION: SETTING GLOBAL den that such lifelong treatment imposes, however, as well as STANDARDS TO SIMPLIFY CARE challenges to maintaining people in the cascade of care, must be Achieving ambitious WHO testing and treatment targets for acknowledged when adopting this approach. HBV requires careful consideration of the challenges of scale-up; An additional complication is access to treatment in LMICs: discussion should focus on simplified models of care and meth- despite generic tenofovir costing less than US$50 per annum ods of wide-scale testing and treatment, particularly in LMICs. and being accessible to HIV-HBV co-infected individuals as Treatment for CHB targets individuals with, or at risk for, part of antiretroviral therapy, many HBV-monoinfected indi- advanced liver disease, and aims to suppress virus replication, halt viduals cannot access antiviral therapy or have to pay out of disease progression, prevent complications, and avert HBV-related pocket. National health care systems need to ensure funded, deaths [S92–S94]. Several antiviral agents approved for the treat- sustainable access to antiviral therapy for HBV-mono-infected ment of CHB are available in developed countries, with regional individuals, implemented in concert with diagnosis scale-up guidelines outlining a continuum of care and recommendations on strategies. who to treat, how to treat, and when to stop treatment [S95–S96]. Treatment programs need to be accompanied by wide-scale es Th e documents, while based on evidence of drug efficacy and HBV testing, particularly in LMICs, where screening rates are benefits of treatment, are not adapted for use in countries where low. Community-based testing and treatment for chronic HBV CHB is endemic and HBV-related mortality is highest . WHO infection has been shown to be feasible: In The Gambia, the guidelines for the prevention and treatment of CHB attempt to Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) address this unmet need [S94]. Tenofovir is the recommended study showed that POC HBV tests perform well in African com- antiviral in resource-limited settings, with entecavir recommended munity settings [S99], and subsequently demonstrated that com- in children aged 2–11 years. The guidelines encourage the use of munity-based screening could achieve high coverage and good clinical parameters (clinical diagnosis of cirrhosis) and/or nonin- linkage to care [S100] while remaining cost-effective [S101]. vasive tests (APRI score > 2) to assess severity of liver disease. THE COST OF DIRECT-ACTING ANTIVIRALS FOR WHO guidelines suggest that treatment should be targeted at HCV: HOW PROGRESS CAN BE MADE those with the highest risk of disease progression, based on the detection of persistently raised alanine aminotransferase (ALT), A 12-week DAA course costs in excess of US$70 000 in the and HBV DNA levels greater than 20 000 IU/mL in those older United States today [S102]. With an estimated 71 million active than age 30 years [S94]. All cirrhotics should be treated regard- HCV infections globally , such prices render any program less of ALT levels, HBeAg status, or HBV DNA levels. The sim- aimed at global HCV elimination unrealistic. In 2016, the WHO plicity of administration of these antivirals, their tolerability reported a range of approaches adopted by several countries to and safety profiles, and their high barrier to resistance make demonstrate how barriers to treatment can be overcome [S103]. them ideal for long-term use in regions where close monitoring In LMICs where patents have not been filed or remain under and management of adverse effects may not be feasible. examination, a market for low-cost, generic versions of patented 4 • OFID • Heffernan et al Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018 drugs can be created. Sofosbuvir is not patented in Egypt, and a example to policy makers, not only as an exemplar of how viral 28-day supply currently costs under US$30 [S104]. India has used hepatitis interventions can be scaled-up quickly and intensively, this approach to facilitate production of generics, but a recent but also as a guide for how to tackle the problems that may be decision to grant a patent to Gilead for Sofosbuvir may damage faced with such ambitious interventions. India’s role as an HCV generics producer [S105]. Pharmaceutical Recommendations companies have, in places, awarded voluntary license agreements Egypt demonstrates what can be accomplished with regards to to permit local companies to produce generics. As of August 2015, HCV diagnosis and treatment, given sufficient political will, Gilead had 11 such agreements with Indian companies [S106]. state coordination, and investment. Across the world, efforts Additionally, the originator company of Daclatasvir has signed an to address viral hepatitis, both HBV and HCV, should focus agreement with the Medicines Patent Pool to enable sublicensing on providing universal HBV birth-dose vaccination within 24 to multiple generic manufacturers in 112 LMICs [S103]. Many hours of birth, establishing hemovigilance schemes to prevent middle-income countries are viewed as having market potential transmission of blood-borne viruses, providing nonreusable and are excluded from these agreements, including China, Brazil, syringes and educating health staff in injection safety, adopt- and Thailand [S106]. More generally, complexities of volun- ing new diagnostic technologies to expand access to screen- tary licensing fragment the market, ensuring that pricing power ing, specializing intervention efforts for vulnerable high-risk remains in the hands of pharmaceutical companies [S107]. This groups to reduce transmission where it is highest, treating all problem can be circumvented by development of new therapies: HBV-infected patients indefinitely to minimize potential harm e Dr Th ugs for Neglected Diseases Initiative (DNDi) has obtained caused by discontinuation, and collaborating across the contin- the license for a new HCV DAA, ravidasvir. This has allowed it to ent to drive down HCV drug costs to ensure that, once treat- begin production of the drug through an Egyptian firm, Pharco ment has been accessed, it is affordable. Pharmaceuticals, without the need to maximize prot [S108]. fi Supplementary Data High-income countries can bulk purchase to reduce costs; Supplementary materials are available at Open Forum Infectious Diseases online. no country has attempted this more ambitiously than Australia. Consisting of data provided by the authors to benefit the reader, the posted e g Th overnment agreed to a AU$1 billion (US$0.73 billion) materials are not copyedited and are the sole responsibility of the authors, so program to treat 62 000 individuals, corresponding to per-treat- questions or comments should be addressed to the corresponding author. ment costs of around US$12 000 [S109]. The true novelty of the Australian approach is that if expenditure exceeds up-front cost, Acknowledgments e a Th uthors are grateful to the Newton Fund, the British Council, the the price of drugs decreases, potentially to 0 [S109]. Australia Mosharafa Foundation, the Science and Technology Development Fund, has, in effect, created a subscription system, paying a fixed and the South African National Research Foundation for facilitating the amount and treating as many Australians as it can. workshop and for funding the conference at which this work was started. What ultimately unites these approaches is their customized Author contributions. I.W., A.I.G., C.W.S., M.W.S., Y.X.H., R.J.W., N.C., and S.T.R. organized the conference and conceived the article, along with its nature; some countries have had success in reducing prices, but principal themes. A.H., A.G.L., C.R.J., E.B., G.N., I.W ., R.S., S.N., and Z.M. wrote others risk being left behind. A unified approach must be taken the initial draft. All authors critically reviewed the manuscript. A.H., S.T.R., to ensure that high-quality, low-cost drugs are available regard- C.W.S., Y.X.H., R.J.W., and M.W.S. edited and formatted the final submission. Potential conifl cts of interest. All authors: no reported conflicts of less of location. Pooled procurement is one method for achieving interest. All authors have submitted the ICMJE Form for Disclosure of this, an approach pioneered by the Global Fund to tackle the HIV, Potential Conflicts of Interest. Conflicts that the editors consider relevant to malaria, and TB epidemics [S110], and attempts are underway to the content of the manuscript have been disclosed. apply this approach to viral hepatitis [S111]. Such schemes could References be transformative; however, they will rely on capital and political 1. World Health Organization. Global hepatitis report, 2017. 2017. http://apps.who. will to achieve the scale required for the program to be a success. int/iris/bitstream/10665/255016/1/9789241565455-eng.pdf ?ua=1. Accessed 28 April 2017. Egypt as a Case Study 2. Stanaway JD, Flaxman AD, Naghavi M, et al. The global burden of viral hepati- Egypt serves as a model for HCV diagnosis and treatment tis from 1990 to 2013: findings from the Global Burden of Disease study 2013. Lancet 2016; 388:1081–8. scale-up [S104, S112]. This country, with the world’s highest 3. Zhou K, Fitzpatrick T, Walsh N, et al. Interventions to optimise the care con- HCV prevalence, has increased HCV treatment numbers to the tinuum for chronic viral hepatitis: a systematic review and meta-analyses. Lancet Infect Dis 2016; 16:1409–22. hundreds of thousands [S103] and intends to treat 5 million 4. World Health Organization. Global health sector strategy on viral hepatitis 2016– patients by 2030 [S104]. It has achieved this by slashing HCV 2021. 2016. http://apps.who.int/iris/handle/10665/246177. Accessed 1 April 2017. 5. Ni YH, Chang MH, Huang LM, et al. Hepatitis B virus infection in children and treatment costs and empowering dozens of diagnostic facilities. adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Furthermore, by simplifying the diagnostic process through Ann Intern Med 2001; 135:796–800. 6. Edmunds WJ, Medley GF, Nokes DJ, et al. The influence of age on the develop- implementing the first universal test and treat strategy, it has ment of the hepatitis B carrier state. Proc Biol Sci 1993; 253:197–201. reduced the time from initial diagnosis to treatment to as little 7. Nayagam S, Thursz M, Sicuri E, et al. Requirements for global elimination of hep- as one week in some centers . Egypt offers an invaluable atitis B: a modelling study. Lancet Infect Dis 2016; 16:1399–408. Aiming at Elimination of Viral Hepatitis • OFID • 5 Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018 8. Klingler C, Thoumi AI, Mrithinjayam VS. Cost-effectiveness analysis of an add- 36. Shittu AO, Olawumi HO, Adewuyi JO. Pre-donation screening of blood for trans- itional birth dose of hepatitis B vaccine to prevent perinatal transmission in a fusion transmissible infections: the gains and the pains—experience at a resource medical setting in Mozambique. Vaccine 2012; 31:252–9. limited blood bank. Ghana Med J 2014; 48:158–62. 9. Casey RM, Dumolard L, Danovaro-Holliday MC, et al. Global routine vaccina- 37. Pépin J, Abou Chakra CN, Pépin E, et al. Evolution of the global burden of tion coverage, 2015. MMWR Morb Mortal Wkly Rep 2016; 65;1270–3. viral infections from unsafe medical injections, 2000–2010. PLoS One 2014; 10. Miyahara R, Jasseh M, Gomez P, et al. Barriers to timely administration of birth 9:e99677. dose vaccines in The Gambia, West Africa. Vaccine 2016; 34:3335–41. 38. Kanamori H, Weber DJ, DiBiase LM, et al. Impact of safety-engineered devices 11. Marion SA, Tomm Pastore M, Pi DW, Mathias RG. Long-term follow-up of hep- on the incidence of occupational blood and body fluid exposures among health- atitis B vaccine in infants of carrier mothers. Am J Epidemiol 1994; 140:734–46. care personnel in an academic facility, 2000–2014. Infect Control Hosp Epidemiol 12. World Health Organization. Hepatitis B vaccines: WHO position paper—recom- 2016; 37:497–504. mendations. Vaccine 2010; 28:589–90. 39. World Health Organization. WHO guideline on the use of safety-engineered 13. GAVI: The Vaccine Alliance. Hepatitis B vaccine at birth – GAVI responds to syringes for intramuscular, intradermal and subcutaneous injections in health- MSF. 2014. http://www.gavi.org/library/news/statements/2014/hepatitis-b-vac- care settings. 2015. http://apps.who.int/iris/bitstream/10665/250144/1/97892415 cine-at-birth-gavi-responds-to-msf/. Accessed 5 January 2017. 49820-eng.pdf. Accessed 11 April 2017. 14. Lydon P, Gandhi G, Vandelaer J, Okwo-Bele JM. Health system cost of delivering 40. Dziekan G, Chisholm D, Johns B, et al. The cost-effectiveness of policies for the routine vaccination in low- and lower-middle income countries: what is needed safe and appropriate use of injection in healthcare settings. Bull World Health over the next decade? Bull World Health Organ 2014; 92:382–4. Organ 2003; 81:277–85. 15. World Health Organization. Addressing the challenge of women’s health in 41. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014; Africa: report of the Commission on Women’s Health in the African Region. 61:S58–68. 2012. http://www.afro.who.int/index.php?option=com_docman&task=doc_ 42. Dore GJ, Ward J, Thursz M. Hepatitis C disease burden and strategies to manage download&gid=8196&Itemid=2593. Accessed 10 July 2017. the burden (Guest Editors Mark Thursz, Gregory Dore and John Ward). J Viral 16. Cowie BC, Carville KS, MacLachlan JH. Mortality due to viral hepatitis in the Hepat 2014; 21(Suppl 1):1–4. Global Burden of Disease Study 2010: new evidence of an urgent global public 43. Easterbrook PJ; WHO Guidelines Development Group. Who to test and how to health priority demanding action. Antivir Ther 2013; 18:953–4. test for chronic hepatitis C infection—2016 WHO testing guidance for low- and 17. Tamandjou CR, Maponga TG, Chotun N, et al. Is hepatitis B birth dose vaccine middle-income countries. J Hepatol 2016; 65:46–66. needed in Africa? Pan Afr Med J 2017; 27(Supp 3):18. 44. Papadopoulos N, Manolakopoulos S, Deutsch M, et al. Frequency and predictors 18. Cui F, Li L, Hadler SC, et al. Factors associated with effectiveness of the first dose of no treatment in anti-hepatitis C virus-positive patients at tertiary liver centers of hepatitis B vaccine in China: 1992–2005. Vaccine 2010; 28:5973–8. in Greece. Eur J Gastroenterol Hepatol 2013; 25:587–93. 19. World Health Organization. Practices to improve coverage of the hepatitis B birth 45. Rongey CA, Kanwal F, Hoang T, et al. Viral RNA testing in hepatitis C dose vaccine. 2012. http://apps.who.int/iris/bitstream/10665/78616/1/WHO_ antibody-positive veterans. Am J Prev Med 2009; 36:235–8. IVB_12.11_eng.pdf ?ua=1. Accessed 11 April 2017. 46. Mendes L, Ralla S, Vigani A. Loss to follow-up in anti-HCV-positive patients in a 20. Sutanto A, Suarnawa IM, Nelson CM, et al. Home delivery of heat-stable vaccines Brazilian regional outpatient clinic. Braz J Med Biol Res 2016; 49(10):e5455. in Indonesia: outreach immunization with a prefilled, single-use injection device. 47. McNerney R. Diagnostics for developing countries. Diagnostics (Basel) 2015; Bull World Health Organ 1999; 77:119–26. 5:200–9. 21. World Health Organization. Preventing perinatal hepatitis B virus transmission: a 48. Hans R, Marwaha N. Nucleic acid testing-benefits and constraints. Asian J guide for introducing and strengthening hepatitis B birth dose vaccination. 2015. Transfus Sci 2014; 8:2–3. http://apps.who.int/iris/bitstream/10665/208278/1/9789241509831_eng.pdf. 49. Freiman JM, Tran TM, Schumacher SG, et al. Hepatitis C core antigen testing for Accessed 7 July 2017. diagnosis of hepatitis C virus infection: a systematic review and meta-analysis. 22. Hipgrave DB, Maynard JE, Biggs BA. Improving birth dose coverage of hepatitis Ann Intern Med 2016; 165:345–55. B vaccine. Bull World Health Organ 2006; 84:65–71. 50. Roberts T. Simplified HCV diagnostics. 2016. https://www.eiseverywhere.com/ 23. Wang L, Li J, Chen H, et al. Hepatitis B vaccination of newborn infants in rural file_uploads/5f481231a53e90f6169771d5346c53d1_INHSU16_TeriRoberts_ China: evaluation of a village-based, out-of-cold-chain delivery strategy. Bull Abstract.pdf. Accessed 27 October 2017. World Health Organ 2007; 85:688–94. 51. Thursz M, Lacombe K. Breaking down barriers to care in hepatitis C virus infec- 24. Marcucci C, Madjdpour C, Spahn DR. Allogeneic blood transfusions: benefit, tion. J Infect Dis 2016; 213:1055–6. risks and clinical indications in countries with a low or high human development 52. Soulier A, Poiteau L, Rosa I, et al. Dried blood spots: a tool to ensure broad access index. Br Med Bull 2004; 70:15–28. to hepatitis C screening, diagnosis, and treatment monitoring. J Infect Dis 2016; 25. World Health Organization. Combating hepatitis B and C to reach elimination 213:1087–95. by 2030: advocacy brief. 2016. http://apps.who.int/iris/handle/10665/206453. 53. MSF. A product guide for point-of-care and laboratory-based HIV and HCV Accessed 9 January 2017. tests. 2015. https://www.msf.org.za/about-us/publications/briefing-documents/ 26. Bloch EM, Vermeulen M, Murphy E. Blood transfusion safety in Africa: a litera- putting-hiv-and-hcv-test. Accessed 11 April 2017. ture review of infectious disease and organizational challenges. Transfus Med Rev 54. Mohamed Z, Mbwambo J, Shimakawa Y, et al. Clinical utility of HCV core anti- 2012; 26:164–80. gen detection and quantification using serum samples and dried blood spots 27. Lara AM, Kandulu J, Chisuwo L, et al. Laboratory costs of a hospital-based blood in people who inject drugs in Dar-es-Salaam, Tanzania. J Int AIDS Soc 2017; transfusion service in Malawi. J Clin Pathol 2007; 60:1117–20. 20:21856. 28. Hussein E. Blood donor recruitment strategies and their impact on blood safety in 55. US Food and Drug Administration. Press announcements - FDA approves Egypt. Transfus Apher Sci 2014; 50:63–7. rapid test for antibodies to hepatitis C virus. 2010. http://www.fda.gov/ 29. World Health Organization. Screening donated blood for transfusion-trans- NewsEvents/Newsroom/PressAnnouncements/ucm217318.htm. Accessed 10 missible infections: recommendations. 2010. http://www.who.int/bloodsafety/ February 2017. ScreeningTTI.pdf. Accessed 11 April 2017. 56. World Health Organization. WHO prequalification of in vitro diagnostics public 30. Bloch EM, Shah A, Kaidarova Z, et al; Anglophone Africa Transfusion Research report product: SD BIOLINE HCV . 2016. http://www.who.int/diagnostics_labora- Group. A pilot external quality assurance study of transfusion screening for HIV, tory/evaluations/pq-list/hcv/161129_final_public_report_0257_012_00_v3.pdf. HCV and HBsAG in 12 African countries. Vox Sang 2014; 107:333–42. Accessed 2 October 2016. 31. Laperche S; Francophone African Group for Research in Blood Transfusion. 57. Khuroo MS, Khuroo NS, Khuroo MS. Diagnostic accuracy of point-of-care tests Multinational assessment of blood-borne virus testing and transfusion safety on for hepatitis C virus infection: a systematic review and meta-analysis. PLoS One the African continent. Transfusion 2013; 53:816–26. 2015; 10:e0121450. 32. World Health Organization. A guide to establishing a national haemovigilance 58. Govindasamy D, Meghij J, Negussi EK, et al. Interventions to improve or system. 2016. http://apps.who.int/iris/bitstream/10665/250233/1/978924154984 facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART 4-eng.pdf ?ua=1. Accessed 5 January 2017. in low- and middle-income settings—a systematic review. J Int AIDS Soc 33. World Health Organization. Blood safety and availability. 2016. http://www.who. 2014; 17:19032. int/mediacentre/factsheets/fs279/en/. Accessed 5 January 2017. 59. Heffernan A, Barber E, Thomas R, et al. Impact and cost-effectiveness of point- 34. van Hulst M, Smit Sibinga CT, Postma MJ. Health economics of blood transfusion of-care CD4 testing on the HIV epidemic in South Africa. PLoS One 2016; safety–focus on sub-Saharan Africa. Biologicals 2010; 38:53–8. 11:e0158303. 35. van Hulst M, Hubben GA, Sagoe KW , et al. Web interface-supported transmission risk 60. Patten GE, Wilkinson L, Conradie K, et al. Impact on ART initiation of point- assessment and cost-effectiveness analysis of postdonation screening: a global model of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha, applied to Ghana, Thailand, and the Netherlands. Transfusion 2009; 49:2729–42. South Africa. J Int AIDS Soc 2013; 16:18518. 6 • OFID • Heffernan et al Downloaded from https://academic.oup.com/ofid/article-abstract/5/1/ofx252/4638518 by Ed 'DeepDyve' Gillespie user on 16 March 2018
Open Forum Infectious Diseases – Oxford University Press
Published: Jan 1, 2018
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera