Taking the National Plan of Action a Step Forward program Egypt’s Viral Hepatitis Program Taking the National Plan of Action a Step Forward 2017 This report is developed as part of the World Bank’s Technical Assistance on Strengthening Egypt’s Response to Viral Hepatitis. Comments and suggestions concerning the report contents are encouraged and could be sent to emassiah@worldbank.org 2 © 2017 International Bank for Reconstruction and Development / The World Bank 1818 H Street NW Washington DC 20433 Telephone: 202 473 1000 Internet: www.worldbank.org This work is a product of the staff of The World Bank with external contributions. The findings, interpretations, and conclusions expressed in this work do not necessarily reflect the views of The World Bank, its Board of Executive Directors, or the governments they represent. The World Bank does not guarantee the accuracy of the data included in this work. The boundaries, colors, denominations, and other information shown on any map in this work do not imply any judgment on the part of The World Bank concerning the legal status of any territory or the endorsement or acceptance of such boundaries. Rights and Permissions The material in this work is subject to copyright. Because The World Bank encourages dissemination of its knowledge, this work may be reproduced, in whole or in part, for noncommercial purposes as long as full attribution to this work is given. Any queries on rights and licenses, including subsidiary rights, should be addressed to the Office of the Publisher, The World Bank, 1818 H Street NW, Washington, DC 20433, USA; fax: 202 522 2422; e-mail: pubrights@worldbank.org. 3 Table of Contents Table of Contents 4 List of tables 5 Acknowledgement 6 I. Introduction 7 II. Background and Objectives 8 1. Transmission routes of Hepatitis C virus 9 a. Unsafe medical practices 10 b. Family members of HCV patients (intrafamilial transmission) 14 III. Economic and Health impact of various Prevention strategies 17 1. The economic and health impact of infection control measures on 17 Hep C incidence: patients on renal dialysis. 2. The economic and health impact of surveillance on prevalence of 23 Hep C in multi-transfused patients: case of thalassemia patients 3. The economic and health impact of using safety engineered devices 25 on the incidence of HCV infections: Healthcare workers 4. The economic and health impact of hepatitis B vaccination: 29 Healthcare workers IV. Study’s Limitations 31 V. Summary and Conclusion 32 Appendix 34 National Plan-Costing 36 References 53 4 List of tables Table 1: Infection Control Measures-Model Input Parameters 18 Table 2: Assumptions on Unit Costs 19 Table 3: QALY per disease stage (Leidner et al., 2015) 20 Table 4: Cumulative costs and health impacts of infection control 22 and isolation policies in 200 000 HD patients Table 5: Model Input Parameters 23 Table 6: Cumulative costs and health impacts of supplying blood 25 banks with modern blood analysis tools in 100 000 TM patients Table 7: Model input parameters 26 Table 8: Safety engineered devices Model output 28 Table 9: HBV Model Input Parameters 29 Table 10: Cumulative costs and health impacts of providing Hep B 30 vaccine to 200 000 Healthcare Workers (HCW) Table 11: Return to investment in various prevention strategies 33 5 Acknowledgement This paper was co-authored by Omneya Mohamed Darwish and Amr Elshalakani (Health Specialist). We are grateful for the leadership, guidance and encouragement from Ernest Massiah (Practice Manager for the Middle East, North Africa). We are also thankful for the operational and leadership support provided by Asad Alam (World Bank Director for Egypt, Yemen & Djibouti). We gratefully acknowledge the support received from the incumbent Minister of Health and Population, His Excellency Dr. Ahmed Emad Rady This report was written at their direct request and we greatly valued their continuous support, input, and leadership. The content of the four reports series was enriched by discussions with Ministry of Health and Population (MOHP) leadership and staff, whom we thank for their time and expertise. These include: i) the honorable Leadership and staff of the Preventive Sector, MOHP; ii) the honorable members of the national committee for combating Viral Hepatitis; iii) the team of the Viral Hepatitis Unit, MOHP and iv) the team of the Loans and Grants Administration (MOHP). This appreciation is extended to the leadership and staff at the Regional Health Directorates, especially to the viral hepatitis teams working in the field to combat the disease. We thank health experts in Egypt who shared their candid views to help strengthen the format and recommendations of the paper through multiple engagements. This includes but is not restricted to a spectrum of academicians, senior health professionals, policymakers, and representatives of professional associations. We appreciate the inputs of our World Bank colleagues: Patrick Osewe (Lead Health Specialist) and Andreas Seiter (Lead Health Specialist) for their insightful views, and for their overall support of the activities culminating in this paper. Very warm thanks go to Mohammed Duban and Mirna Mehrez who assisted with typesetting of this document, and to Rana Elgazzaz for doing a meticulous graphics job in a very expedient time frame. 6 I. Introduction To inform policy makers and donors on the most efficient management strategies to control viral hepatitis infections in Egypt, this report assesses the returns to investment of prevention strategies addressing various routes of transmission. The National Plan of Action developed by the Ministry of Health and Population in 2014 set a framework for combating a disease that affects the lives of at least one member in every Egyptian family. The plan was unanimously well received by all pertinent entities, but it also had some shortcomings, most importantly that no costing was done for the various activities listed under it, hence no proper prioritization was given to those activities based on a sound cost-effectiveness study. This has resulted in the Ministry of Finance and interested development partners becoming reluctant towards pledging support to the said activities. Therefore, it was the aim of this report (and sister reports in the same series) to unlock the potential of the National Plan of Action through complementary work that would enable Egypt to make the best use of fully implementing the plan. The assessment started with a costing study of the different pillars of the Plan of Action, which focuses on treatment, prevention, and care of HCV. Then, economic analyses were conducted to assess the returns to investment of the three primary prevention measures listed in the plan, specifically blood safety, infection control, and vaccination. Cost-effectiveness implications of other important measures, namely treatment and screening, are discussed in details in another sister report. 7 II. Background and Objectives Worldwide there are 118.9 million HCV RNA positive cases (Petruzziello, Marigliano, Loquercio, Cozzolino, & Cacciapuoti, 2016). According to the latest Egyptian Health Survey (2015), Egypt has 4.5 million cases of chronic HCV infections (HCV RNA positive cases) aged 15 to 59 years old, representing 7% of the Egyptian population (MOHP, El Zanaty Associates, & ICF, 2015). The estimated national incidence ranged between 0.8 and 6.8 per 1000 person-years (Benova, Awad, Miller, & Abu-Raddad, 2015). Around 7 million Egyptian adults are chronically infected with Hepatitis C, with an estimated 130,000-500,000 new people infected annually and about 40,000 dying every year. The Government of Egypt (GOE) has recently increased its commitment to prevent, contain and treat the HCV epidemic in the country with an explicit vow from its political leadership to reduce viral hepatitis prevalence to <1% by 2030. A National Plan of Action for the Prevention, Care and Treatment of Viral Hepatitis was developed for 2014 to 2018, covering a comprehensive set of actions to control the epidemic of Hepatitis C. Those actions included the treatment of 500,000 CHC patients a year in addition to surveillance and prevention programs for a faster elimination of the virus reservoir and savings in long-term treatment costs. In 2016, MOHP has started its own program of treating patients using direct acting antivirals (DAA). According to the current estimates of the National Committee for the Control of Viral Hepatitis, at least 800,000 patients received treatment in 2016 (after 200,000 in 2015). These figures represent approximatively all those currently diagnosed with chronic hepatitis C. To inform policy makers and donors on the most efficient management strategies to control viral hepatitis, an economic analysis was conducted to assess the returns to investment of the demand driven treatment program and demand creating measures (screening) (for more details please refer to Markus, 2016). For a complete appraisal of the national response to Hepatitis C epidemic, this report assessed the returns to investment of key prevention strategies addressing various routes of transmission. Owing to the limitations of the studies that assess the current national incidence (for more details please refer to Markus, 2016) 8 and the scarcity of studies which assessed incidence among various population groups, this report assessed the returns to investment in three primary prevention measures listed in the National Plan of Action—blood safety, infection control and vaccination—using the characteristics of three different high risk population groups—Hemodialysis (HD) patients, Thalassemia major (TM) patients and health care workers (HCW)—who were sufficiently studied in the current literature on Hepatitis C transmission in Egypt. The report starts with a review of the main routes of transmission and the incidence and prevalence of Hepatitis C (HCV) and Hepatitis B (HBV) in population groups affected by each route of transmission. Section 2 discusses the economic and health impacts of infection control, surveillance and vaccination using model based estimates. Section 3 summarizes the report findings and concludes. 1. Transmission routes of Hepatitis C virus The latest Egyptian Health Issues Survey (2015) assessed the history of medical procedures and hospitalization among HCV and HBV positive interviewees. In addition to a history of parenteral treatment for schistosomiasis, the results showed that certain invasive medical procedures were associated with higher frequencies of viral hepatic infections, including endoscopy, blood transfusion, a history of urinary catheter, suture or intravenous line, and dental treatment. To identify the incidence rates of Hepatitis C and Hepatitis B per risk factor, PubMed database was searched using the following Mesh terms: hepatitis C, Egypt, incidence, transmission and epidemiology with no languages restrictions. We limited the review to the studies conducted from 2000 through 2017. Thirty- four studies were included in the review. The literature review showed that most studies focused on two main categories of risk factors: unsafe medical practices in inpatient and outpatient settings (Kandeel et al., 2012; Miller, Elzalabany, Hassani, & Cuadros, 2015; Reker & Islam, 2014), and familial contacts (Reker & Islam, 2014). The impact of unsafe medical practices were studied in specific population groups such as multi-transfused patients such as hemophiliacs and thalassemics, dialysis patients, and healthcare workers (Mahmoud, El-Mazary, & Khodeary, 2016). The impact of intrafamilial 9 transmission were studied in spouses and offspring of HCV and HBV positive patients (Mahmoud et al., 2016). This section has two parts. Part 1 summarizes the prevalence and incidence in population groups at risk of acquiring HCV via unsafe medical practices. Part 2 summarizes the prevalence and seroconversion rates in family members of HCV and HBV positive patients. At the end of each subsection, we discuss the most appropriate prevention strategy to reduce viral hepatitis transmission in the specific population group. a. Unsafe medical practices Few epidemiological studies assess HCV incidence rates (IR) among population groups at risk of acquiring HCV via unsafe medical practices. The majority of studies focus on HCV incidence in hemodialysis patients, pregnant women, patients with schistosomiasis and health care workers. In this section, we review the incidence and prevalence of HCV in hemodialysis patients and healthcare workers and HCV and HBV prevalence in multitransfused children. 1. Incidence of HCV in hemodialysis patients In Egypt, the estimated total prevalence of patients on dialysis (HD) is 264 per million, as most patients receive dialysis 3 times per week (Allam et al., 2010). The prevalence of HCV among this population group ranges from 50% to 90% (Kamal, Farres, Eissa, Arafa, & Abdel-Reheem, 2017). Studies show that the seroconversion rates in HCV negative HD patients ranges from 1.6% to 48%, with the wide variation related to adherence to control measures in various healthcare settings. A study of isolation policies on seroconversion rates in 4 dialysis units in 3 different governorates (Soliman, Momtaz Abd Elaziz, & El Lawindi, 2013) found a lower seroconversion rate in HD units which implemented strict isolation policies compared with HD units that did not implement isolation polices (14.8% and 42.9%, respectively). Another study conducted in a large public hospital in the Delta, which implemented strict infection control measures and isolation policies, reported an even lower seroconversion rate of 1.6% (0.676/100 person- years) (Kamal et al., 2017). 10 Proposed prevention strategy A thorough implementation of infection control measures and isolation policies is necessary to prevent patient-to-patient transmission of HCV in renal dialysis healthcare facilities (Nguyen et al., 2016). 2. Healthcare workers According to the 2016 statistical yearbook, the Egyptian ministry of Health and Population (MOHP) employs 201,560 full time healthcare workers (HCWs). HCWs are frequently exposed to needle stick injuries in settings where infection control measures are not routinely practiced; therefore, high level of viremia incidence was noticed in this subpopulation. Egyptian healthcare workers experiences a high rate of needle-stick injuries— an average of 4.9 annually according to one study (Talaat et al., 2003). Those occupational blood exposures put HCWs at risk of acquiring blood borne diseases such as hepatitis B1 and C, although one study concluded that HCWs were more likely to acquire HCV in the community than occupationally (Abdelwahab S et al., 2012). Other studies showed that the safe disposal of sharp items was not practiced routinely. These studies also report low HBV vaccination coverage among HCWs and a HCV prevalence similar to the general population (8.1%), yet they also find a significant incidence of viremia (7.3 per 1000 person-years) due to HCWs’ frequent exposure to viremic patients’ blood or body fluids. Talaat et al. (2003) explored the frequency of exposure to needlestick injuries and the hepatitis B vaccination coverage among HCWs in a random sample of different types of health care facilities in the Nile Delta and Upper Egypt. 35.6% of the HCW were exposed to at least 1 needlestick injury during the past 3 months with an estimated annual number of 4.9 needlesticks per worker. Overall, 64% of HCWs disposed of needles unsafely in non-puncture-proof containers. Only 15.8% of interviewed HCWs reported receiving 3 doses of the Hepatitis B vaccine. Vaccination coverage was highest among professional staff (38%) and lowest among housekeeping staff (3.5%). Using Kane’s model to predict infections after needlestick exposures, the authors estimated 24,004 Hepatitis C (1) The prevalence of HBsAg in Egypt is of intermediate endemicity (2–8%) (El-Zayadi, 2007) 11 virus and 8617 Hepatitis B virus infections occurring each year in Egypt as a result of occupational exposure to patient blood. A prospective study of the transient viremia rate in HCW at Cairo’s Ain Shams University Hospital found that at baseline, HCV prevalence in HCWs was not different from HCV in the general population of Cairo (8.1%) and that HCWs were exposed to a highly viremic population (37% of index patients were RNA positive). Transient viremia, without established infection, occurred in 12% of exposed HCWs, particularly those in early stages of training (Munier et al., 2013). Another prospective cohort study conducted by Okasha et al. (2015) assessed the background prevalence and incidence of HCV infection among HCWs in Ain Shams University Hospital and the risk factors associated with HCV seropositivity. Similar to Munier et al. (2013) study, the seroprevalence among HCW was comparable to that of the general population in Cairo (8.1%) yet with a considerable ongoing transmission of 7.3 per 1000 person-years. The authors concluded that the high incidence may be explained by the high number of sharps injuries among HCWs. Proposed prevention strategies Hepatitis B vaccination of HCWs and training of HCWs on safe handling and collection of needles and sharps and infection control measures are required to reduce the risk of HBV and HCV transmission among HCWs. 3. Blood donors (seroconversion in multi transfused patients and HCV and HBV prevalence in blood donors) Several studies assessed HCV and HBV prevalence among blood donors. A review in 2013 showed a decreasing trend in HCV and HBV prevalence among donated blood beginning around early 2000s. Pre-2001, HCV prevalence among blood donors ranged from 5%-35% (Mohamoud, Mumtaz, Riome, Miller, & Abu- Raddad, 2013). Post-2001, following the implementation of infection control measures, stricter donor selection criteria, and the prohibition of payment for blood donation, HCV and HBV prevalence in donated blood decreased to < 5%. In 2013, a review of blood donor recruitment strategies from 2006 through 2013 at Cairo University blood bank found that the overall prevalence of HCV 12 antibodies and Hepatitis B surface antigen were 4.3% and 1.22%, respectively. It is worth mentioning that the routine blood screening preformed in Egyptian blood banks checks for HBV antigens and not for core antibodies or ALT; thus it might not reveal occult HBV infections, which pose a considerable risk for HBV infections in multi-transfused patients (Omran D, Hussein EA, & Nagib M, 2013). Similar results were found in studies conducted in Minya and Alexandria governorates (Khattab, Eslam, Sharwae, & Hamdy, 2010; Wasfi & Sadek, 2011). Worldwide, it is estimated that 100 000 children are born yearly with thalassemia major. The largest numbers are in South East Asia, Sri Lanka, Bangladesh, North West India, Pakistan, Middle East Countries, Greece, and Italy (Ujjwal Bandyopadhyay et al., 2013). In Egypt, the carrier rate is around (9%-10%) which is considered a major health problem (Atwaa & Wahed, 2017). Despite improvements in donated blood screening, multi-transfused patients are at high risk of acquiring transfusion transmitted infections (TTI). Among multi-transfused children, studies found that HCV prevalence ranged from 24% to 51%, whereas HBV prevalence ranged from 0% to 12% . Older age was significantly associated with infectious diseases markers. A study in 2011 from Pediatric Hospital in Cairo University found that HCV and HBV prevalence in hemolytic anemia patients were 51.7% and 0% respectively (Omar et al., 2011). Another study in the same hospital a few years later found a lower HCV prevalence rate (24%) and a higher HBV prevalence (3%) (Hussein, 2014). The inconsistency was likely related to the variation in inclusion criteria in each study. In the study conducted by Omar et al. (2011), patients were included only if they were vaccinated against HBV and had more than 20 blood transfusions. Another study conducted in Qena to estimate the prevalence of Hepatitis C and Hepatitis B among children with thalassemia and hemophilia found that 45% of patients were HCV positive and 12% were either acutely or chronically infected with HBV(El-Faramawy, El-Rashidy, Tawfik, & Hussein, 2012). Similarly, a more recent study of multi-transfused children with thalassemia conducted in Upper Egypt’s universities (Sohag and Mina) found even higher rates of HCV and HBV infections: 37.11% and 4.12%, respectively (Mahmoud et al., 2016). 13 Proposed prevention strategies Despite the decreasing presence of HCV and HBV antibodies in donated blood and the inclusion of HBV vaccines in childhood vaccination programs, the prevalence of HBV and HCV in multi-transfused patients is still high. Owing to the lack of HCV treatment for those less than 12 years old (Egypt will soon approve DAAs for children aged 12 years old and older). More sensitive screening techniques should be implemented to detect low levels of HCV antibodies during the window period and HBV occult infections in donated blood, and more rigorous infection control methods should be implemented within healthcare settings to avoid patient-to-patient transmission of HCV and HBV. b. Family members of HCV patients (intrafamilial transmission) Intrafamilial transmission was reported as another potential route for the transmission of Hepatitis C in Egypt. Studies that assessed incidence of intrafamilial transmission of HCV found that a family member living with a HCV- positive patient was at higher risk for acquiring HCV than if living with a family free of HCV, and that the risk of wife-to-husband transmission was higher than husband-to-wife transmission (horizontal transmission). Young children whose mothers were HCV positive were at higher risk for intrafamilial transmission of HCV than children of HCV negative mothers (vertical Transmission). 1. Horizontal transmission A study assessing the prevalence of HCV in thalassemia patients and the risk for horizontal transmission found that 34.4% of thalassemia patients were HCV positive and that family members of HCV-positive thalassemia patients were 5 times more likely to be infected than family members of HCV-negative thalassemia patients (19.2% versus 4.5%, respectively) (Said et al., 2013). A prospective study of HCV incidence among family members of HCV patients in two rural villages in the Nile Delta and Upper Egypt found a higher incidence of HCV in families of HCV-positive patients versus HCV-free families (5.8 versus 1.0 per 1000 persons-years, respectively). In addition, the study revealed that a higher baseline prevalence is associated with a higher seroconversion incidence rate and the highest incidence rate occurred in children aged 10 years 14 and younger living with a HCV-positive parent (Mohamed et al., 2005). Another study, which looked at the risk of HCV transmission between spouses, found that the probability of wife-to-husband transmission was higher than husband-to-wife transmission (34% and 3 %, respectively, for those with detectable HCV RNA, and 10% and 0%, respectively, for those without detectable RNA). However, the study could not identify the exact route of transmission among spouses (Magder et al., 2005). Similar patterns for intrafamilial transmission were also found among family members of chronic hepatitis B patients. A study of the transmission rate of Hep B in Northeastern Egypt found that the prevalence of HBV antigen and antibody were 12% and 23% in family members of index cases, and the prevalence of HBV antigen were higher in family members and offspring of female compared with male patients (19.2% and 23% versus 8.6% and 4.3%, respectively) (Ragheb et al., 2012). Proposed prevention Strategies Prevention of HCV and HBV transmission necessitates public campaigns to raise awareness about potential routes for HCV and HBV transmission within households, such as sharing needles, razors, and other sharp items and exposure to the blood of infected family members. In addition, a close monitoring and screening of family members of HCV patients is important for early detection and treatment of Hepatitis C infection. 2. Children of HCV +ve women (Vertical Transmission) Worldwide, vertical transmission is the considered the most important route of acquiring HCV among children (Benova et al., 2015). According to the latest Egyptian Health Issues Survey, the prevalence of HCV among children aged <5 years old was <1% (MOHP et al., 2015). Studies assessing the contribution of vertical transmission to HCV incidence in children aged <5 years old show that around 50% of HCV in this age group was related to mother-to-child transmission of HCV (Benova et al., 2015). According to the reviewed studies, the rate of vertical transmission ranged from 3.1% (Zahran, Badary, Agban, & Abdel Aziz, 2010) to 3.8% (AbdulQawi et al., 2010). The rate of vertical transmission was even higher in newborns whose mothers are seropositive, ranging from 26%-36% (Kassem, el-Nawawy, Massoud, el-Nazar, 15 & Sobhi, 2000). Benova et al. (2015) used a mathematical model to estimate the number of new infections from vertical transmission in a 2008 Egyptian birth cohort, concluding that between 3,080 and 5,167 HCV infections resulted from vertical transmission among children born in 2008, or roughly half of incident cases in the <5-year age group. Vertical transmission was disproportionately higher in Lower and Upper Egypt rural areas as a result of higher HCV prevalence and fertility rates in those areas. The authors concluded that vertical transmission is one of the primary HCV infection routes among children<5 years in Egypt. Another study assessed the rate of vertical transmission of HBV and HCV in Assiut. Of 500 pregnant women, 6.4% were HCV positive, 4% were HBV positive and 1% were both (HCV and HBV positive). The rate of vertical transmission for HCV, HBV and both were 3.1%, 30% and 20% respectively. The authors concluded that both HCV prevalence and vertical transmission were high in Upper Egypt (Zahran et al., 2010). Finally, a prospective study was conducted at Benha University Hospital to estimate HCV prevalence and the vertical transmission rate of Hepatitis C in pregnant women. The authors found that 6.8% of pregnant women were HCV RNA positive and that 13% of their infants were RNA positive at 1month of age. However, at 6 months of age only 3.8% remained HCV RNA positive. The study concluded the rate of vertical transmission is not substantially different from other countries (AbdulQawi et al., 2010). A similar study conducted in Alexandria University Hospital showed that HCV prevalence among healthy women who delivered spontaneously was 19% and that the vertical transmission risk in newborns whose mother were HCV-RNA and HCV-antibody positive were 36% and 26%, respectively (Kassem et al., 2000). Proposed prevention strategy Screening for HCV seropositivity should be included in routine antenatal care tests, specifically in areas with high fertility such as rural areas and upper Egypt. Although DAAs are not indicated for use during pregnancy, a detection of seropostivity will allow prompt treatment after delivery preventing potential infections for future offsprings. In addition, close monitoring of the offsprings of HCV positive women will allow an early detection of seroconversion and an early access to treatment once the child reaches 12 years old (FDA has approved DAAs for children aged 12 years old and older). 16 III. Economic and Health impact of various Prevention strategies The literature review above revealed that the main routes of transmission of viral hepatitis were unsafe medical practices and intrafamilial transmission. In general, studies assessed HBV and HCV prevalence much more frequently than HBV/HCV incidence; therefore, we limited the economic assessment of the prevention strategies listed in the Plan of Action (appendix 1) to three population groups who were both at high risk for acquiring HCV and HBV and adequately studied in the literature. We specifically assessed: 1. The economic and health impact of infection control measures on Hep C incidence in patients on renal dialysis; 2. The economic and health impact of surveillance on prevalence of Hep C in multi-transfused thalassemia patients; 3. The economic and health impact of vaccination on Hep B incidence in Healthcare workers. 1. The economic and health impact of infection control measures on Hep C incidence: patients on renal dialysis. This model assessed the economic and health impacts of safe injection practices in healthcare facilities with an upfront cost of $36,575,450 in the first year (exchange rate $1USD= 18 EGP). For more details on the strategy and overall costs please refer to appendix 1. The characteristics of hemodialysis (HD) patients aged 50-55 were used to model the study population (Ghonemy, Farag, Soliman, El-okely, & El-hendy, 2016). Model Assumptions The model assumes that 2.6 million patients in Egypt have Chronic Kidney Disease (CKD) and that 200,000 of these patients need renal dialysis. We used tree age pro to develop a closed Markov model of 200,000 patients to assess the economic and clinical outcomes of infection control and isolation strategies on HCV transmission in hemodialysis (HD) patients. The cohort was followed from 2017 through 2040. We assumed that cured patients’ deaths were not liver related, 17 that cured patients were not re-infected and that the patients who failed first and second line treatment using DAAs followed the natural history of disease progression for untreated CHC patients as modelled in Mankoula (2015). Table 1 summarizes the model input parameters. A health care funder perspective (third party payer) was used to calculate costs and outcomes. All future costs and outcomes were discounted at 5% rate per year. Table 1: Infection Control Measures-Model Input Parameters Upper Variable Value lower limit Source Limit Age 52.5 50 55 (Ghonemy et al., 2016) HCV 50% 50% 90% (Kamal et al., 2017) Prevalence Seroconversion rates per year* Baseline 1 14.8% 14.8% 42.9% (Soliman et al., 2013) Strict isolation 2% (Kamal et al., 2017) +Infection control Costs and Health Outcomes The costs included in the models consists of the direct costs of treatment in MOHP facilities and the costs of care for various liver disease stages, as mentioned in the economic analysis of treatment and screening scenarios. Table 2 presents assumptions on unit costs and quality adjusted life years (QALYs) per disease status. The health effects of the different interventions were measured in terms of QALYs and number of cases averted. Patient-incurred costs and accrued QALYs annually are presented in Table 3. * The seroconversion over 36 months 18 Table 2: Assumptions on Unit Costs Hepatitis C Treatment US$ 84 (Source: [placeholder, presumed guidance from Ministry of Health]) Hepatitis C RNA Test US$ (Source: [World Bank/guidance from Ministry of Health]) 66.6 Hepatitis C Antibody Test US$ 5.6 (Source: [working assumption]) Hepatitis C testing: Fixed costs per patient, irrespective of progression to RNA test or treatment. US$ 2 (Source: [working assumption]) Compensated cirrhosis (average annual cost per person in health state) US $110 (Based on Estes and others (2015), reflecting a cost per patient of US$ 685, at a coverage rate of 15 percent.) Decompensated cirrhosis (average annual cost per person in health state) US Source: MOHP $1,905 Hepatocellular cancer (average cost per case) (Estes and others (2015) assume an annual cost per patient of US$ 900 US$ 1,225, at a coverage rate of 60 percent. Annual mortality of 80 percent implies average survival of about 1.25 years. Liver transplantation (one-off) US$ Source: Estes and others (2015) 42,500 Post-liver-transplantation (annual) US$ Source: MOHP 5,560 Source: Haacker (2017). Economic Anaylsis of Egpyt’s Response to Hepatitis C 19 Table 3: QALY per disease stage (Leidner et al., 2015) Value QALYs Disease stage (upper-lower limits) F0-F3 0.88 (0.72-1) HCV free population F4 0.73 (0.55-0.89) Multiplier for HCV F0-F3 0.98 (0.72-1.00) infected patients F4 0.98 (0.62-1.00) HCC 0.52 (0.1-0.91) Multiplier for ESLD DC 0.82 (0.51-0.91) LT 0.9 (0.51-0.97) Model outputs The analysis showed that reducing incidence rate in HD units from 17% to 2% via the implementation of strict infection control and isolation policies was both cost saving and cost effective (assuming that GDP per capita is $2500(2)). These policies would avert 35,350 cases of Hepatitis C and 2,030 liver-related deaths (from 2017 through 2040). In addition, they would result in absolute cost savings. Also, a one-way sensitivity analysis showed that at a seroconversion rate of 5%, the strategy is cost effective, averting 18,900 infections and 189 liver-related deaths and yielding an extra 86,064 QALY compared with baseline scenario at an average cost of $368.5 per QALY gained. Table 4 summarizes the cumulative costs and health impacts of the implementation of infection control strategies in renal dialysis units. (2) Egypt GDP Growth Rate found at http://www.tradingeconomics.com/egypt/gdp-growth accessed on 5/3/2017 20 Owing to the scarcity of studies on incidence rate of hepatitis C in healthcare settings, this economic analysis was limited to adult HD patients aged 50-55 years old, a population group studied previously. Due to the advanced age of this theoretical cohort, the impact of these policies might be underestimated. The results show that prevention policies had a greater impact on averted liver-related deaths than on the number of cases averted. That is because at the age of 50-55, the age-specific liver-related deaths and the probabilities to progress to advanced liver disease stages were much higher than for younger age groups. Consequently, the results showed here cannot be generalized to other HD populations or the general population. More epidemiological studies are needed to accurately measure HCV incidence rate in healthcare facilities. 21 Table 4: Cumulative costs and health impacts of infection control and isolation policies in 200 000 HD patients Isolation Base case Isolation and and   Scenario Infection infection (17%) control (2%) control (5%) Cumulative costs $807,990,585.00 $795,507,434.00 $810,017,875.00 in US$ Millions Cumulative 2112118 2240581 2198182 QALYs Hep C free 1680 37028 20603 Infections averted 35348 18923 Hep C related 42979 40951 42790 death Hep C related 2028 189 death averted Cost per infection $480,946.78 $22,505.02 $39,315.53 averted Cost per Death $392,262.05 $4,285,808.86 averted Cost per QALY $382.55 $355.05 $368.49 gained Return per dollar $1.38 $0.76 invested 22 2. The economic and health impact of surveillance on prevalence of Hep C in multi-transfused patients: case of thalassemia patients This model assessed the economic and health impacts of supplying all blood banks with modern tools, equipment, and machines needed for blood testing, separation, preservations, and transportation at an upfront cost of $64,864,900 in year 1 (exchange rate $1USD= 18 EGP). For more details on the strategy and overall costs please refer to appendix 1. The characteristics of Thalassemia major (TM) patients aged 15 to 19 years old were used to model the study population. Model Assumptions We used tree age pro to develop a closed Markov model of 100,000 thalassemia major patients aged 15 to 19 years old. The cohort was followed from 2017 through 2040 (same as Markus 2016 report). We assumed that blood transfusion was the only risk for acquiring HCV. A health care funder perspective (third party payer) was used to calculate costs and outcomes. All future costs and outcomes were discounted at 5% rate per year. Table 5 summarized the model input parameters . Table 5: Model Input Parameters Lower Upper Variable Value Sources Limit Limit (Atwaa & Wahed, Age 17.5 15 20 2017) HCV Prevalence 35% 24% 57% (Mahmoud et al., HCV prevalence in 5% 5% 30% 2016) blood donors Seroconversion rates Baseline 5% Assumption 2 Strict blood (Ujjwal screening 1.75% 1.75% 2.08% Bandyopadhyay et techniques al., 2013) 23 Model outputs The analysis shows that supplying the blood bank with modern tools, equipment, and machines for blood testing, separation, preservation, and transportation is both cost effective (assuming that GDP=$2,500) and cost saving. The output shows that reducing the incidence rate in HD units from 41% to 1.6% via the implementation of strict infection control and isolation policies is both cost effective and cost saving. Reducing the incidence rate from 5% to 1.75% in TM patients aged 15-19 years old by supplying all blood banks with modern tools, equipment, and machines for blood testing, separation, preservations, and transportation averts an additional 21,288 cases of Hepatitis C and 158 liver- related deaths. In addition, the prevention strategy yielded 1,413,859 QALYs (from 2017 through 2040) at an average cost of $344 per QALY gained. Table 4 summarized the cumulative costs and health impacts of supplying blood banks with modern blood analysis tools. This model did not account for the probability of transmission via unsafe medical practice during blood transfusion in the healthcare settings. In addition, it did not account for the dose effect of number of transfused units’ therefore, the results may be under estimated. More epidemiological studies are needed to accurately assess the impact of multiple transfusion on HCV incidence in multi- transfused patients. 24 Table 6: Cumulative costs and health impacts of supplying blood banks with modern blood analysis tools in 100 000 TM patients* Donated blood   Base case scenario screening Cumulative costs in US$ Millions $429,462,194.00 $486,590,058.00 Cumulative QALYs 1,376,258 1,413,859 Hep C free patients 24,031 45,319 Number of infections averted   21,288 Hep C related death 13,484 13,326 Number of death averted   158 Cost per infection averted $17,871 $10,737 Cost per Death averted   $3,079,684 Cost per QALY gained $312 $344 Return per dollar invested   $1.7 3. The economic and health impact of using safety engineered devices on the incidence of HCV infections: Healthcare workers This model assesses the economic and health impacts of training on safety injection practices and the implementation of safety engineered syringes on HCV transmission in HCWs. * We assumed that the seroconversion rate of TM patients equal HCV prevalence in donate blood. Since the implementation of strict selection criteria for blood donors resulted in 83% (from 30% to 5%) decrease in HCV prevalence in donated blood, we assumed that blood screening using kit with higher specificity and sensitivity can further reduce seroconversion by 50% (from 5% to 1.75%, the incidence rate observed in Indian healthcare facilities). 25 Model Assumptions We used tree age pro to develop a closed Markov model of 200,000 HCWs. The cohort was followed from 2017 through 2040 (same as Markus 2016 report). We assumed that needlestick injuries were the only risk for acquiring HCV. At baseline, we assumed that HCV prevalence is 8.1% and that on average a healthcare worker is exposed to 4.9 needle stick injuries per year (Talaat et al, 2003). To estimate the annual probability of needle-injury-related HCV infections, we used Kane’s model as mentioned inTalaat et al. (2003). A health care funder perspective (third party payer) was used to calculate costs and outcomes. All future costs and outcomes were discounted at 5% rate per year. Table 7 summarizes the model input parameters Table 7: Model input parameters Lower Upper Variable Value Source Limit Limit Age 32 30 35 Assumption Talaat et al. HCV Prevalence 8.1% (2003) Average needle stick Talaat et al. 4.9 injury per person (2003) Prevention Scenarios Training on safety 34% injection practices Percent reduction in Implementation of safety number of needle stick (Kanamori et 49% injuries per prevention al., 2016) engineered devices strategy Training + safety 62% engineered devices 26 Model outputs The analysis showed that implementation of any of the mentioned strategies is both cost effective and cost saving. The most cost effective and cost saving strategy is training HCW on safety injection practices and implementing safety devices in different healthcare settings. The implementation of training and safety devices would reduce the average exposure to needle injuries to 1.8 needle stick injury per HCW per year. At that level, 21,563 cases of HCV cases would be averted at an average cost of $3,877 per case averted and $48/QALY. This model assumed that the only risk for Hep C infection in HCWs was occupational exposure to needlestick injuries. In addition, it accounted only for the impact of safety injection on HCV transmission in HCW. The reduction in potential vertical transmission from HCWs to patients was included in the analysis. 27 Table 8: Safety engineered devices Model output Training Using safety Baseline Training on safety engineered Scenario +Safety devices practices devices Injuries per person per 4.9 3.234 2.499 1.862 year Cumulative costs in US$ 158,379,454.00 150,144,799.00 145,629,220.00 141,644,412.00 Millions Cumulative 3,082,407 3,121,618 3,143,422 3,162,832 QALYs Hep C free 81,916 103,479 116,202 127,934 Infections 21,563 34,286 46,018 averted Hep C related 4,253 4,074 3,971 3,877 death Hep C related 179 282 376 death averted Cost per infection $6,963.08 $4,247.48 $3,078.02 averted Cost per Death $838,797.76 $516,415.67 $376,713.86 averted Cost per $51.38 $48.10 $46.33 $44.78 QALY gained 28 4. The economic and health impact of hepatitis B vaccination: Healthcare workers This model assessed the economic and health impacts of HBV immunization in Egyptian healthcare workers. Model Assumptions We used tree age pro to develop a closed Markov model of 200,000 HCW. We modeled two coverage levels (50% and 70%). The cohort was followed from 2017 through 2040 (same as Markus 2016 report). We assumed that occupational exposure was the only risk for acquiring HBV. A health care funder perspective (third party payer) was used to calculate costs and outcomes. All future costs and outcomes were discounted at 5% rate per year. Table 9 summarized the model input parameters. Table 9: HBV Model Input Parameters Lower Upper Variable Value Source Limit Limit Age 32 30 35 Assumption HCB Prevalence 8% 24% 57% (El-Zayadi, 2007) Vaccine Cost $1.2 MOHP source (Hong Anh T. Tu et al., Vaccine efficacy 84% 2012) Coverage levels Base case 15% 3.5% 38% (Talaat et al., 2003) Scenario 1 50% Assumption Scenario 2 70% Assumption 29 Model outputs The analysis showed that increasing the vaccination level to 50% or 70% would be cost saving. A 50% coverage would avert 84,000 cases of hepatitis B and result in 1,203,503 QALY gained over 23 years costing $54/QALY. The 70% would result in more cost saving with an average cost of $21/QALY. The return to investment was highest at 70% coverage with a return of $122 per dollar invested. This model assumed that the only risk for Hep B infection in HCW was occupational exposure. In addition, it accounted only for the direct benefit of HCW immunization. The reduction in potential intrafamilial transmission was not included in the analysis. Table 10 summarized the model output. Table 10: Cumulative costs and health impacts of providing Hep B vaccine to 200000 Healthcare Workers (HCW) Return Liver Cost Coverage Vaccination Cases Total Total Cost/ per related /case level rate averted Cost QALY Mortality QALY dollar averted invested Scenario 103,351,607 4,101 178 9 15% 25,200 580,986 642 1 $ $ $ $ Scenario 60,893,887 725 51 52 50% 84,000 1,203,503 3769 2 $ $ $ $ Scenario 36,632,332 316 21 122 70% 117,600 1,744,655 2261 3 $ $ $ $ 30 IV. Study’s Limitations The methodologies mentioned in this report had few limitations. First, all the models assessed the direct costs and outcomes of HCV infections. For simplicity none of the models accounted for the indirect costs of HCV infections or the synergistic effects of comorbidities specifically in febrile population groups such as hemodialysis patients and thalassemia patients. Second, owing to the lack of recent studies that evaluate the current HCV incidence in the general population and various high risk groups, this report relied on the most recent studies available in the literature to extract disease incidence rates, those published in 2000 and onward. In addition, in cases where incidence estimates could not be identified we relied on incidence rates in countries with comparable contexts such as the incidence rate of HCV among children with thalassemia in India. Another limitation was related to the ongoing rapid changes in Hep C prevalence in Egypt. The massive treatment and screening campaigns currently ongoing should significantly reduce the huge pool of HCV-positive patients, leading to a further reduction in incidence rate that is unrelated to various prevention strategies. Further studies are need for an accurate assessment of the synergetic impact of massive treatment campaigns and other prevention strategies on HCV transmission in Egypt. 31 V. Summary and Conclusion Whereas the high HCV prevalence among certain groups largely reflects historical routes of HCV transmission (schistosomiasis infection or treatment), the incidence rates reflect current transmission routes. The literature review showed that the main routes of HCV transmission today are related to unsafe medical practices and intrafamilial (vertical and horizontal) transmission. HCV and HBV transmission were highest among select groups, such as hospitalized patients with multiple exposures to healthcare (such as renal dialysis patients), multi-transfused patients, partners and offspring of HCV positive patients, and healthcare workers. For an efficient allocation of resources and the highest return to investment, Egypt should adopt targeted prevention strategies tailored to the specificities of each of the high-risk population groups rather than untargeted prevention strategies that address the general population. Nevertheless, more epidemiological studies are needed for an accurate and updated estimation of incidence rate in various risk groups on the national and regional levels. The economic analysis showed that the implementation of targeted prevention strategies in any of the studied high risk population groups is both cost effective and cost saving (i.e. cost effective means that cost incurred per QALY gained is less than the Egyptian GDP/Capita (<$2500)). It is worth mentioning that the implementation of prevention strategies in HCWs (Hep B vaccination and implementation of safety engineered injection devices) would yield the highest return on investment (12069% and 1132%, respectively). The implementation of strict infection control and isolation policies in renal dialysis settings would yield 2,240,581 QALYS at an average cost of $355/QALY. In addition, the return to investment in infection control to reach a transmission as low as 2 % equaled $1.38 per dollar spent with a return on investment (ROI) of 38%. Supplying all blood banks with modern tools, equipment, and machines needed for blood testing, separation, preservations, and transportation would yield 413,859 QALY at an average cost of $344 per QALY gained. The net return to investment in blood testing tools was $1.7 per dollar spent with a return on investment (ROI) of 66%. And providing HBV vaccines for 70% of the Egyptian 32 HCWs would result in 1,744,655 QALY gained at an average cost of $21/QALY. Furthermore, it yielded the highest return to investment at 70% coverage. The net return to investment was $122 per dollar spent with a return on investment (ROI) of 12069%. Finally, the implementation of training and safety engineered devices would avert 21,563 cases of HCV cases at an average cost of $3,877 per case averted. The net return to investment in blood testing tools was $12.3 per dollar spent with a return on investment (ROI) of 1132%. Table 11 presented the return to investment in various prevention strategy. Table 11: Return to investment in various prevention strategies Return Return Strategy Total benefit Total Cost to to Investment Investment infection control and isolation $1,101,457,191.82 $795,507,434 $1.38 38% policies in 200, 000 HD patients supplying blood banks with modern blood $806,974,997 $486,590,058 $1.70 66% analysis tools in 100000 TM patients providing Hep B vaccine to 200000 $4,457,922,758 $36,632,332 $122 12069% Healthcare Workers (HCW) Training + providing 200000 Healthcare $1,744,427,631.62 $141,644,412.00 $12.32 1132% Workers (HCW) with safety engineered devices 33 Appendix Costing of the Egypt National Plan of Action for the Prevention, Care and Treatment of Viral Hepatitis, 2014 Methodology The costing of the various activities listed under the national plan of action was carried out by the World Bank, World Health Organization (WHO), and key stakeholders during the period of April-July 2016. The exercise was done in four phases: Literature and process review: The WB, WHO and MoHP teams carried out a condensed literature review of other country experiences pertaining to costing of national vertical health programs. Similarly, a detailed breakdown mapping of the actual processes that are involved in the respective actions listed in the national plan was done, given the Egyptian context. Unit Cost Data Collection: Actual market-based cost figures were then assigned to the processes where available. New or non-existent processes were assigned a temporary cost allocation with a statistically calculated margin of error. The data were cleaned, aggregated and tabulated using a bottom-up approach to reflect standardized costs. The standard costs were multiplied by the number of each type of interventions to build the total direct costs for an intervention or a group of interventions, to which indirect costs were added. It included a demographic component that allowed the incorporation of projected estimated service utilization and comparison with actual service utilization for different numbers of patients and different service delivery models. Participatory Working Groups: A three-day workshop was convened to revise and deliberate the findings. Seven working groups were formed for each of the respective seven pillars under the national plan of action. Each working group consisted of: i) MoHP technical staff corresponding to their respective pillar; ii) academic capacities in the area; iii) Clinical and technical expertise in the subject; iv) think tanks representing the private and civil society sectors; v) representatives from the general public showing interest in the topic; and vi) WB 34 and WHO technical staff. The costing tables were refined were appropriate based on a participatory and consensual discussions and agreements. Verification of Results and Translation: A final round of verification was done to maintain and preserve the power of data representation. Finally, and owing to the study taking place amid an era of economic reforms in the country and the high level of fluctuation of the local currency, the figures were translated into US Dollar amounts to maintain relevance over the envisaged time of implementation. 35 National Plan-Costing Budget (USD) Total Plan 533,390,018 Total cost 463,817,407 1- Strengthening surveillance to detect viral hepatitis 1,190,878 transmission and detection 1.1- Strengthen acute viral hepatitis surveillance system to monitor trends of acute disease, assess risk factors, assess 931,869 prevention programs, and detect outbreaks 1.1.1- Continue existing sentinel surveillance systems under 577,140 the direction of the MOHP viral hepatitis Administration. 1.1.1.A- Address policy and regulatory requirements of facilities and participating parties, including the development 11,261.26 of a Memorandum of Understanding (MOU) between all involved parties. 1.1.1.B- Invest in manpower at all levels, by recruiting MOHP 47,297.30 hospital staff for each facility to include field epidemiologists. 1.1.1.C- Add extra 5 sentinel surveillance sites, and add ID 135,135.14 component to avoid duplication. 1.1.1.D- The need for IT supports in all domains hardware, 168,918.92 software, and internet services, etc. 1.1.1.E- The CPHL role should be redefined according to a 1,126.13 new revised protocol. 1.1.1.F- Establish a quality assurance system among 23,648.65 concerned parties and CPHL. 1.1.1.G- Supporting CPHL and the functioning sites with the 114,864.86 required equipment, kits, supplies, and required training. 1.1.1.H- Continuous training of new employees and existing staff. 63,063.06 1.1.1.I- Legislation to ensure maintenance and sustainability 6,756.76 of staff and required equipment. 1.1.1.J- Revise/develop SOPs in all existing sites and future ones. 5,067.57 36 1.1.2- Expand sentinel surveillance to other facilities, including MOHP hospitals, university hospitals, military hospitals, 102,477 private hospitals, and liver institutes in Cairo and Menofia 1.1.2.A- Develop a plan to include other entities such as 21,396.40 universities, private sectors. 1.1.2.B- Strengthen existing routine surveillance (NEDSS) system through raising capacities of fever hospitals (Man 81,081.08 power, Lab. review SOPs, Forms, etc.) 1.1.3- Increase capacity of the MOHP viral hepatitis Administration in the areas of surveillance, epidemiology, 37,162 data analysis and management, and reporting. 1.1.3.A- Develop clear TORs for the Viral Hepatitis Administration and its responsibilities in relation to the 4,504.50 Central Surveillance Unit 1.1.3.B- Increase staff members by providing at least one fulltime qualities epidemiologist, in addition to intensive 32,657.66 training programs on SOPs 1.1.4- Increase the capacity of laboratories throughout Egypt to support outbreak investigations and other surveillance activities, and ensure quality of sentinel sites through laboratories at the Central Public Health Laboratory (CPHL) 85,586 and Viral Hepatitis Research Laboratory (VHRL) within the National Hepatology and Tropical Medicine Research Institute (NHTMRI). 1.1.4.A- External and internal review of laboratory capacities 27,027.03 to identify labs capable of handling viral hepatitis specimens. 1.1.4.B- Identify gaps in laboratory capacity and identify 4,504.50 strategies to address them. 1.1.4.C- Conduct regular training for central laboratories and public health laboratories by conducting viral hepatitis 54,054.05 workshops and hands-on training for laboratory staff and developing SOPs for laboratory diagnosis. 1.1.5- Strengthen existing routine surveillance (NEDSS) 87,838 system. 1.1.5.A- Review attributes of surveillance systems (MMWR 27,027.03 Guidelines) through an evaluation of the NEDSS surveillance system. 37 1.1.5.B- Equip the existing system based on results of - surveillance evaluation. 1.1.5.C- Improve capacity for complete and accurate disease 60,810.81 reporting among laboratories and providers. 1.1.6- Develop supervision, monitoring, and evaluation for 41,667 the sentinel surveillance system. 1.1.6.A- Review current supervisory systems (SOPs), acknowledge gaps, and take measures to strengthen the 3,378.38 system. 1.1.6.B- Situational analysis to identify gaps and defects of 2,252.25 data management system. 1.1.6.C- Conduct regular visits with clear monitoring indicators by an external independent entity for reviewing 36,036.04 and assessment. 1.2- Strengthen chronic viral hepatitis surveillance to monitor trends of acute chronic infection and associated 259,009 disease and to assess prevention programs 1.2.1- Use existing data sources to monitor chronic viral 54,054 hepatitis infection. 1.2.1.A- Identify and assess available data sources (where viral hepatitis testing is currently being conducted) for analysis. Potential data sources include blood donors; hemodialysis 10,135.14 groups; patients in intensive care units; HIV surveillance groups-mobile units “voluntary counselling & testing (VCT) sites;” and visa applicants. 1.2.1.B- Assess available-needed-data and suggesting a proper 3,378.38 reporting mechanism with minimum required data 1.2.1.C- Establishing and ensuring the continuity & quality of data from different sources and their linkage with a relational 22,522.52 database 1.2.1.D- Developing a protocol & SOPs between concerned 6,756.76 decision makers. 1.2.1.E- Integrate viral hepatitis surveillance into the HIV 4,504.50 VCT program 1.2.1.F- Revise DHS protocols to include age groups, 6,756.76 questionnaires, serology, and storage of samples. 38 1.2.2- Establish new surveillance systems for chronic viral 113,739 hepatitis infections. 1.2.2.A- Establish viral hepatitis serologic surveillance among identified groups, such as military recruits, prisoners, drug users, and patients with medical conditions requiring 56,306.31 frequent medical procedures (e.g., blood transfusions, endoscopy, diabetes management, and chemotherapy) 1.2.2.B- Establish viral hepatitis serologic surveillance among 9,009.01 women receiving antenatal care. 1.2.2.C- Establish a system for reporting between private and 48,423.42 other labs to CPHL and central surveillance unit. 1.2.2.D- Establish a system for analysis and reporting of - chronic viral hepatitis surveillance data. 1.2.3- Initiate surveillance programs in hospital dialysis units 56,306 to measure seroconversion of viral hepatitis (HBV and HCV). 1.2.3.A- Establish a system for regular reporting of hemodialysis-related transmissions of viral hepatitis from MOHP and non- MOHP dialysis units to MOHP viral 56,306.31 hepatitis Administration and subsequently to central surveillance unit 1.2.3.B- Disseminate annual reports on district governorate - and national levels of seroconversion in hemodialysis patients 1.2.4- Monitor mortality and morbidity related to viral 34,910 hepatitis. 1.2.4.A- Review various institute registries (e.g., health insurance organizations [HIOs], liver treatment centers, and Program of Treatment at the Expense of State [PTES]) to 6,756.76 determine suitability as a source of data concerning care and treatment of acute and chronic liver disease 1.2.4.B- Linkage to the death certificate through the National 22,522.52 Health Information System 1.2.4.C- Collaborate with liver cancer registries 5,630.63 2- Promoting Infection prevention & control practices to 79,297,973 reduce transmission of viral hepatitis 2.1- Establish government commitment and support of policies 42,509,685 that ensure infection prevention & control practices in Egypt 39 2.1.1- Develop /update policies and legislations to enforce the implementation of IPC programs in Egypt, through 73,198 empowering the National Steering committee 2.1.1.A- Enforce the formulation of a national IPC steering committee formed by heads of all IPC department of health - organizations in Egypt and external technical advisors to report directly to the High Health council 2.1.1.B- Develop clear and comprehensive TORs to govern the National Steering Committee’s activities. The TORs should include reviewing membership, convening frequent 22,522.52 meetings at least four times annually, and creating exchange forums 2.1.1.C- Empower the National steering Committee, by 4,504.50 developing/ updating policies and legislations 2.1.1.D- IPC practitioners should be included in the free treatment sector to monitor IPC practices performance of the 18,018.02 private health units before initiation or renewal of licensing 2.1.1.E- Promote the implementation of standard IPC protocols in all healthcare settings; those operated by the 28,153.15 government, private sector, or charity organizations including dentistry 2.1.1.F- All sectors such as military, police, and university should communicate with the MoHP to get the latest statistical data regarding infection rates of diseases specially - hepatitis to empower surveillance as a part of the national action plan 2.1.2- Ensure establishment of regulations relevant to waste 42,436,486 management 2.1.2.A- Activate regulatory mechanisms governing waste - management 2.1.2.B- Develop educational materials on waste management 168,918.92 to be distributed to all healthcare facilities 2.1.2.C- Training environmental health providers on waste 206,756.76 management regulations 2.1.2.D- Include waste management staff in the hepatitis B - vaccination program 40 2.1.2.E- Monitoring and management of medical waste centrally by MoHP to ensure proper disposal and 10,529,279.28 management of medical waste 2.1.2.F- Building new incinerators to ensure covering all 31,531,531.53 health units in Egypt to secure proper safe waste disposal 2.2- Reduce occupational transmission of viral hepatitis 109,234 2.2.1- Promote the prevention and management of 109,234 occupational exposure to HBV, HCV , and other BBPs 2.2.1.A- Teaching and training undergraduate medical students the basic IPC guidelines before starting their clinical 28,153.15 practice 2.2.1.B- Assessment of the HCWM system in Egypt through 29,279.28 meeting and visits to some facilities from different health sectors 2.2.1.C- Update and disseminate the MoHP IPC training 6,756.76 curriculum 2.2.1.D- Advocate the vaccination of HCWs against vaccine 16,891.89 preventable diseases including HBV 2.2.1.E- Promote safe disposal of sharps - 2.2.1.F- Develop and distribute a specific manual for 28,153.15 management of occupational exposure to BBPs 2.3- Promote safe injection practices in healthcare 36,575,450 2.3.1- Ensure the implementation of safe injection practices 36,575,450 2.3.1.A- Assessment of injection practice in health sectors and among communities where information is missing 56,306.31 (University hospitals, private sector, pharmacies, dentists, Health Insurance hospitals, households, etc.) 2.3.1.B- Formulate and disseminate clear, applicable, and credible SOPs on safe injection for both healthcare and 112,612.61 community settings 2.3.1.C- Inventory of policies around safe injections and gaps 3,378.38 in policy content 2.3.1.D- Assessment of the procurement and supply management areas (incl. Healthcare waste management 112,612.61 supplies) relevant to injection safety commodities using a standardized tool 41 2.3.1.E- Provide standardized safe injection training for 168,918.92 injection providers 2.3.1.F- Encourage the use of safety-engineered syringes for 6,756.76 curative purposes 2.3.1.G- Safe injection devices and safe disposal equipment should be supplied and controlled by criteria set by the 35,990,990.99 MoHP 2.3.1.H- Encourage national factories o start investing in 33,783.78 safety engineered syringes production 2.3.1.I- Develop innovative communication means/ system 22,522.52 for raising public awareness 2.3.1.J- Facilitation of technology transfer in the country, and acquiring the WHO prequalification for safety engineered - devices 2.3.1.K- Study the health impact and economic costs associated with unsafe and unnecessary injections and impact from reduction of unsafe injections (including baseline data 67,567.57 collection on costs of infections, disabilities, and deaths due to unsafe injections 2.4- Strengthen monitoring and evaluation programs for ensuring implementation of infection prevention and control 103,604 programs 2.4.1- Develop critical indicators to measure processes of IPC 103,604 (process indicators). 2.4.1.A- Develop a multi-disciplinary taskforce to revise and validate current monitoring tools, including the “scoring 13,513.51 system” developed by MoHP, and validate those tools 2.4.1.B- Develop and validate a monitoring tool specific to viral Hepatitis (including BBPs exposure, injection safety 6,756.76 elements, etc.) in primary healthcare settings 2.4.1.C- Conduct regular supervision and monitoring of all 56,306.31 healthcare settings using an updated, revised scoring system. 2.4.1.D- Disseminate the monitoring results through a web- 27,027.03 based platform 3- Improving blood safety to reduce transmission of viral 14,550,676 hepatitis 42 3.1- Establish government commitment and support of policies 270,270 that ensure the safety and adequacy of national blood supply 3.1.1- Develop an independent National Blood Authority 270,270 (NBA) with representation by all stakeholders 3.1.1.A- Establishment of a road map of administrative, legal, 5,630.63 and financial, aspects needed to found a NBA 3.1.1.B- Assign responsibility for regulating and licensing blood - banks and conducting compliance inspections to the NBA. 3.1.1.C- Standardise the National Blood Policy and quality control of screening tests to be followed by all blood banks 3,378.38 throughout Egypt 3.1.1.D- Review and standardize the National Blood Law (NBL) according to the new centralisation policy put by 2,252.25 parliamentary legislation 3.1.1.E- Commission the NRA to re-evaluate the current legislation that governs the importation/ exportation of - human blood products 3.1.1.F- Build capacity of Blood-bank staff to ensure - compliance to that standardized policies and procedures 3.1.1.G- Build a strategy for training/ awareness to decrease usage of blood and/ or blood components transfusion aiming 259,009.01 to decrease abuse or unnecessary transfusions 3.2- Build a sustainable base of safe blood donors to maintain 14,280,405 adequate and safe national blood supplies 3.2.1- Expand the pool of appropriate volunteer blood donors 10,613,739 3.2.1.A- Review current volunteer blood-donor system and 5,630.63 recruitment strategies across all sectors 3.2.1.B- Conduct quantitative/ qualitative research to study 22,522.52 the motivations and barriers of blood donations in Egypt 3.2.1.C- Create a pool of voluntary blood donors, in - collaboration with the civil society 3.2.1.D- Increase public awareness regarding need for 1,126,126.13 donated blood through promoting it as a healthy practice 3.2.1.E- Reaching out for donors through increasing access to 9,459,459.46 safe and trusted facilities/mobile units for blood donations 43 3.2.2- Improve selection and management of all blood donors 41,667 (both volunteer and family donors 3.2.2.A- Assessment of current selection criteria for blood 36,036.04 banks’ sectors (MOH, NBTS, MOE, etc.). 3.2.2.B- Revise donor selection criteria based on the most recent data, taking into consideration the epidemiological / - demographic background of donors 3.2.2.C- Develop a national database for voluntary donors to support donation campaigns and increase safety and - efficiency of blood donation 3.2.2.D- Establish a counselling and medical referral process for transfusion-transmissible infections (TTIs) from blood 5,630.63 banks and hospitals as needed 3.2.3- Conduct surveillance on the prevalence and incidence 3,625,000 of HCV, HBV, and other BBPs in blood donors 3.2.3.A- Establish a blood safety network with central management and expand it to include all the other blood 21,396.40 banks, university, HIO, Police and Army hospitals 3.2.3.B- Supply all blood banks with modern tools, equipment, and machines needed for blood testing, 3,603,603.60 separation, preservations, and transportation 3.2.3.C- Merging blood safety network with surveillance data - 3.2.3.D- Establish a monitoring system with clear KPIs - 4- Eliminating transmission of vaccine-preventable viral 1,436,632 hepatitis 4.1- Achieve universal hepatitis B vaccination for populations 464,099 at high risk for infection or complications 4.1.1- Ensure all HCWs are vaccinated against hepatitis B 251,261 4.1.1.A- Promote legislation requiring completion and documentation of hepatitis B vaccination for all HCWs as a - condition for licensing. 44 4.1.1.B- Establish a system for HCWs vaccination that includes HBV, and expanding MOHP database to include 11,261.26 other sectors through engaging the National Immunization Technical Advisory Group (NITAG). 4.1.1.C- Vaccine cost ($0.4) 240,000 4.1.2- : Ensure hepatitis B vaccination for persons at high risk for infection from non-medical sources (e.g. Family members of HBV infection patients, street children, incarcerated 212,838 persons, PWID, men who have sex with men [MSM], and patients of sexually transmitted infections [STO] clinics). 4.1.2.A- Create a policy paper describing the current status and gaps in hepatitis B vaccination among people in non- 11,261.26 medical high-risk groups, and resources need for vaccination 4.1.2.B- Conduct media campaigns to reach high risk 168,918.92 populations 4.1.2.C- Engage appropriate NGOs and social entrepreneurs 22,522.52 providing services to high-risk groups 4.1.2.D- Promote coordination between MOHP programs 10,135.14 (Viral hepatitis unit, EPI, and HIV 4.2- Ensure all newborns receive hepatitis B birth dose as 972,533 soon as possible following birth (<24 hours) 4.2.1- Ensure that all hospitals and birthing centers administer a birth dose of hepatitis B vaccine to all newborns 865,551 during the first 24 hours after birth 4.2.1.A- Train all relevant hospitals staff on SOPs of hepatitis 31,193.69 B birth dose. 4.2.1.B- Support logistics of data collection and analysis from all hospitals to insure acquiring valid data for informed 12,820.95 decision making 4.2.1.C- Ensure continuous monitoring of birth dose administration at hospitals by district, governorate, and EPI 50,139.64 staff. 45 4.2.1.D- Advocate for the importance of birth dose of hepatitis B vaccine targeting physicians and health care 101,351.35 workers 4.2.1.E- Ensure availability of the vaccine, cold chain, 50,675.68 logistics, and dry supplies for hospitals 4.2.1.F- Update neonates’ care protocol at MOHP and 11,261.26 Teaching Hospitals 4.2.1.G- Social mobilization to communicate and emphasise 608,108.11 the importance of Hepatitis B birth dose 4.2.2- Ensure that all newborns being delivered outside hospitals receive a birth dose of hepatitis B vaccine within 24 106,982 hours of delivery 4.2.2.A- Preparation of all Primary Health Care units to 67,567.57 administer the birth dose 4.2.2.B- Support data collection from all Primary Health Care units, districts, and governorates to be analysed in order to 39,414.41 support informed decision making. 5- Role of care and treatment in reducing transmission of 362,389,672 viral hepatitis 5.1- Provide safe, effective, and affordable treatment to patients with 362,389,672 chronic hepatitis B and C 5.1.1- Optimize treatment management for chronic hepatitis B and C patients in existing treatment facilities in a cost- 361,770,302 effective manner. 5.1.1.A- Develop a standardized audit tool to assess treatment 3,378.38 centre efficiency. 5.1.1.B- Conduct an independent audit of treatment centres 563,063.06 to ensure efficiency 5.1.1.C- Revise hepatitis B national treatment guidelines 40,540.54 according to the latest research 5.1.1.D- Establish a collaboration between Pharmaco- vigilance units and the National Committee of Control f viral 22,522.52 Hepatitis (NCCVH). 46 5.1.1.E- Conduct cost-effectiveness studies on the new 11,261.26 treatments before establishing treatment guidelines 5.1.1.F- Increase the number of treatment facilities providing 12,105,855.86 HCV and HBV treatment to 100 centres by the end of 2017 5.1.1.G- Build capacities and provide necessary equipment to conduct Resistant Associated Variants (RAVs ) analysis for 1,126,126.13 patients with past treatment failures at an affordable prices 5.1.1.H- Expand the use of electronic medical records from 27 to 100 medical facilities, and link those records to a 1,126,126.13 centralized database 5.1.1.I- Treatment of 500000 patients per year 105,000,000.00 5.1.1.I- Screening cost assuming 7% prevalence of CHC 241,771,428.57 5.1.2- Increase the capacity for treatment of chronic hepatitis 619,369 B and C patients at the national level 5.1.2.A- Build capacity of local healthcare staff (e.g., doctors 563,063.06 and nurses) to implement revised guidelines. 5.1.2.B- Create distance tools for clinicians to obtain advice on patient management from senior hepatologists; conduct 56,306.31 pilot testing of distance tools to include monitoring and evaluation 6- Educating providers and communities to reduce 4,951,577 transmission of Viral Hepatitis 6.1- Increase the inter-sectorial coordination for effective 33,784 public awareness in viral hepatitis 6.1.1- Increase policymakers’ commitment to supporting the policy change necessary to prevent viral hepatitis 33,784 transmission 6.1.1.A- Include all stakeholders in policy discussions 5,630.63 6.1.1.B- Hold annual workshops to provide professional associations and NGOs with information about viral hepatitis 16,891.89 epidemiology 47 6.1.1.C- Designing and launching an online platform for EIC on viral hepatitis control to be reference for all the partners 11,261.26 and stakeholders for educating on viral hepatitis in Egypt 6.2- Educate healthcare workers to increase awareness about 36,599 transmission of viral hepatitis in Egypt 6.2.1- Determine HCWs existing beliefs, knowledge, and 19,707 practices regarding viral hepatitis 6.2.1.A- Conduct extensive review of available data (literature 4,504.50 review/ partner outreach). 6.2.1.B- Identify partners capable of developing an electronic and in-person infection prevention and control curriculum for healthcare professional and those capable of building - a database to track completion of learning activities in collaboration with the IPC steering committee 6.2.1.C- Expand training campaigns through a “train of trainer” program or volunteer program in facilities that lack 15,202.70 internet access 6.2.2- Develop continuous medical education (CME) focused 16,892 on viral hepatitis infection prevention and control 6.2.2.A- Meet with relevant professional associations (e.g., dentistry, nursing, and medical) to garner support for CME 5,630.63 development 6.2.2.B- Pilot curriculum and educational material before 11,261.26 widespread distribution 6.3- Increase public awareness in viral hepatitis control 4,881,194 6.3.1- Develop scientific materials and messages 3,378 6.3.1.A- Build a team with representation from diverse disciplines (e.g., epidemiologists, hepatitis, specialists, and communications experts and communications experts) 3,378.38 to review existing materials on hepatitis; revise as needed; develop scientific materials and messages 48 6.3.2- Determine the impact of stigma associated with viral 9,009 hepatitis infection 6.3.2.A- Conduct literature review and studies to better understand the magnitude of stigma against people with viral 9,009.01 hepatitis 6.3.3- Increase awareness among different age groups, each 4,582,207 through their appropriate channel 6.3.3.A- Increase awareness among school aged children through reviewing existing school-based infectious disease 15,765.77 curriculum, and partner with the Ministry of Education to update materials to include viral hepatitis 6.3.3.B- Increase awareness among university aged students through partnerships with the Ministry of higher education, 16,891.89 supreme council of universities and the universities 6.3.3.C- Empowering youth (age 15-25) to raise awareness as 45,045.05 advocates for viral hepatitis prevention 6.3.3.D- Launch regular on-going national awareness 4,504,504.50 campaigns for controlling the viral hepatitis in Egypt 6.3.4- Improve counselling services for patients identified with hepatitis, and their families, in order to reduce risk of 28,716 infection 6.3.4.A- Identify catchment areas (e.g., visa applicants, blood 2,252.25 banks, liver institutes, hospitals…etc. 6.3.4.B- Coordinate and train viral hepatitis counsellors 15,202.70 6.3.4.C- Develop appropriate counselling materials 11,261.26 6.3.5- Develop partnerships based on social responsibility with media organization (traditional and social) and other 5,631 CSOs civil society organizations 6.3.5.A- Identify partners (e.g. NGOs, commercial companies, - media organizations). 6.3.5.B- Involve media in all stages of viral hepatitis planning 5,630.63 and implementation 49 6.3.6- Initiate and promote a viral hepatitis specific hotline 252,252 that operates 24 hours a day/ 7 days a week 6.3.6.A- Prepare site with needed infrastructures 78,828.83 6.3.6.B- Review materials 4,504.50 6.3.6.C- Provide training and resources for hotline staff 45,045.05 6.3.6.D- Install hardware and software 123,873.87 6.3.6.E- Include hotline number in media materials. (Hotline would be used by both patients and their families for referral - and vaccination). 7- Strategy for promoting viral hepatitis Health Research and 69,572,611.08 information technology 7.1- Define a participatory Viral Hepatitis Health Research plan 9,740,165.55 7.1.1- Viral Hepatitis Health Research priorities will be defined based on research plan to be developed through the 4,870,082.78 taskforce activities 7.1.1.A- Revise currently proposed Viral Hepatitis research 1,461,024.83 priorities after their discussion with the taskforce for approval 7.1.1.B- Conducting gap analysis through reviewing current 1,461,024.83 research database 7.1.1.C- Define roles in each approved research project 487,008.28 7.1.1.D- Establish a research protocol checklist 487,008.28 7.1.1.E- Work on a detailed national plan for viral hepatitis 974,016.56 health research in Egypt 7.1.2- Conduct regular monitoring of the Viral Hepatitis 4,870,082.78 Health research plan 7.1.2.A- Define a monitoring body 487,008.28 7.1.2.B- Set SOPs for monitoring the Viral Hepatitis health 4,383,074.50 research plan 7.2- Building capacities in research. 24,350,413.88 50 7.2.1- Develop research capacities to conduct Viral Hepatitis research projects following ethical guidelines for research on human subjects, translate research results into the public 24,350,413.88 health practice. Through developing briefs and sharing results with the scientific community and policy-makers 7.2.1.A- Facilitate developing/ participating in courses on research methodologies (quantitative/ qualitative) and ethics 2,435,041.39 in health research 7.2.1.B- Linking research methods courses to funding opportunities, which would facilitate application of 1,948,033.11 theoretical concepts and methods. 7.3- Develop central research warehouse concerning viral 10,435,891.66 hepatitis in Egypt. 7.3.1- Establish a central research warehouse for each 1,043,589.17 component to facilitate viral hepatitis research projects 7.3.1.A- Index studies about viral hepatitis through literature 939,230.25 research 7.3.1.B- Communicate with network bodies/ custodians of databases to share/ provide access to relevant literature 104,358.92 (published and grey literature) on viral hepatitis in Egypt. 7.3.2- Establish a wide research network gathering all bodies which may contribute to/ benefit from viral hepatitis research 9,392,302.50 data 7.3.2.A- Define network bodies 469,615.12 7.3.2.B- Establish and sign a memorandum or collaboration 469,615.12 with each 7.3.2.C- Compile central research database for viral hepatitis 3,756,921.00 7.3.2.D- Design a system for disseminating / sharing 3,756,921.00 information 51 7.3.2.E- Assign roles of networks as applicable 939,230.25 7.4- Establish collaboration between different stakeholders with vested interest in prevention, treatment and control of 695,726.11 viral hepatitis in Egypt. 7.4.1- Establish a taskforce consisting of relevant stakeholders, responsible for research decisions related to viral hepatitis in 695,726.11 Egypt 7.4.1.A- Identify stakeholders 556,580.89 7.4.1.B- Sign a memorandum of understanding (MOU), and define clear TORs for collaboration with each of the 139,145.22 stakeholders 7.4.1.C- Define leadership and hierarchy of command 139,145.22 7.5- Support the conduction experimental studies (e.g. clinical trials and community intervention studies) 24,350,413.88 reinforcing Viral hepatitis prevention and control in Egypt 52 References - Abdelwahab S, Rewisha E, Hashem M, Sobhy M, Galal I, Allam WR, . . . 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