the two surveys provide estimates of hcv prevalence in egypt for the country as a whole and broken down for the major administrative regions ( urban governorates , lower egypt , upper egypt and the frontier governorates ) . in both edhs 2008 and ehis 2015 ,
those aged 1559 years were invited to participate , however , in ehis 2015 , children aged 6 months to 14 years were also included 4 , 5 .
basic demographic information was collected , including : age , gender , marital status , place of residence , level of education , work status and wealth status .
the laboratory procedures applied in 2015 were similar to those in 2008 4 , 5 .
in 2015 , consented individuals provided 7 ml of venous blood added to an edta vacutainer tube . in the field laboratory ,
the 2015 ehis biomarker staff centrifuged the blood and transferred the serum to five microvials that were stored in liquid nitrogen tanks before being transferred to the central public health laboratory ( cphl ) in cairo . a hepatitis c testing algorithm
used thirdgeneration enzyme immunoassay ( elisa ) to determine the presence of hcv antibodies . a more specific assay ,
the chemiluminescent microplate immunoassay ( cia ) was used to confirm hcv antibody status for elisapositive samples and 5% of the elisanegative samples .
quantitative realtime pcr was used to test for hcv rna in hcv antibodypositive samples to confirm active infections . a quality control procedure of retesting of approximately 10% of all samples
was undertaken at the cphl and a further external quality control was done at the theodor bilharz research institute , in cairo , by retesting approximately 5% of the samples tested at the cphl 5 . the only key difference between this procedure and that of the previous survey is that , in 2008 , the quality control measure ( 10% of samples retested ) at cphl was not carried out .
comparisons were carried out for hcv antibody and hcv rnapositive tests , by estimating the absolute and relative risk reductions between the two surveys in comparable age groups . to calculate the 95% confidence interval for the risk difference , newcombe 
wilson 's method without continuity correction was applied 6 . in order to estimate confidence intervals for the relative risk
the level of significance ( pvalue ) was inferred to be less than 0.05 if the corresponding 95% confidence intervals for the relative and absolute effect measures were devoid of 
hcv virus clearance was estimated by finding the absolute difference between the proportion of hcv antibody and hcv rnapositive participants , and dividing this by the proportion of hcv antibodypositive participants .
comparisons of hcv clearance between combined age groups in 2008 and 2015 were done using the chisquare test . in order to demonstrate the cohort effect ,
the 2008 dhs data were shifted forward ; 7 years were added to each participant 's age from the 2008 dhs survey and the hcv antibody and hcv rna prevalence estimates were recalculated using the new numerator and denominator in each age category .
the estimated number of population positive for hcv antibodies and hcv rna was calculated by multiplying the age and genderspecific prevalence of 2015 by the population census of january 2015 categorised by age and gender .
no ethical approval was needed for the data analysis presented in this paper ; the anonymised data is publically available online .
elzanaty and co is the responsible party for the ethical considerations of the edhs 2008 and ehis 2015 ; verbal informed consent was obtained from all individuals aged 18 years and older and from married minors aged 1517 years . for children less than 18 years
we obtained data from the edhs 2008 4 and ehis 2015 5 , both of which were conducted by elzanaty and associates with support from the united states aid of international developmentsponsored dhs7 project .
the national surveys in 2008 and 2015 were crosssectional household surveys , where sampling weights were used to provide estimates considered representative of the egyptian population on the basis of a complex , threestage probability sampling approach .
the two surveys provide estimates of hcv prevalence in egypt for the country as a whole and broken down for the major administrative regions ( urban governorates , lower egypt , upper egypt and the frontier governorates ) . in both edhs 2008 and ehis 2015 ,
those aged 1559 years were invited to participate , however , in ehis 2015 , children aged 6 months to 14 years were also included 4 , 5 .
basic demographic information was collected , including : age , gender , marital status , place of residence , level of education , work status and wealth status .
the laboratory procedures applied in 2015 were similar to those in 2008 4 , 5 . in 2015 , consented individuals provided 7 ml of venous blood added to an edta vacutainer tube . in the field laboratory ,
the 2015 ehis biomarker staff centrifuged the blood and transferred the serum to five microvials that were stored in liquid nitrogen tanks before being transferred to the central public health laboratory ( cphl ) in cairo . a hepatitis c testing algorithm
used thirdgeneration enzyme immunoassay ( elisa ) to determine the presence of hcv antibodies . a more specific assay ,
the chemiluminescent microplate immunoassay ( cia ) was used to confirm hcv antibody status for elisapositive samples and 5% of the elisanegative samples .
quantitative realtime pcr was used to test for hcv rna in hcv antibodypositive samples to confirm active infections . a quality control procedure of retesting of approximately 10% of all samples
was undertaken at the cphl and a further external quality control was done at the theodor bilharz research institute , in cairo , by retesting approximately 5% of the samples tested at the cphl 5 . the only key difference between this procedure and that of the previous survey is that , in 2008 , the quality control measure ( 10% of samples retested ) at cphl was not carried out .
comparisons were carried out for hcv antibody and hcv rnapositive tests , by estimating the absolute and relative risk reductions between the two surveys in comparable age groups . to calculate the 95% confidence interval for the risk difference , newcombe 
wilson 's method without continuity correction was applied 6 . in order to estimate confidence intervals for the relative risk
the level of significance ( pvalue ) was inferred to be less than 0.05 if the corresponding 95% confidence intervals for the relative and absolute effect measures were devoid of 
hcv virus clearance was estimated by finding the absolute difference between the proportion of hcv antibody and hcv rnapositive participants , and dividing this by the proportion of hcv antibodypositive participants .
comparisons of hcv clearance between combined age groups in 2008 and 2015 were done using the chisquare test . in order to demonstrate the cohort effect ,
the 2008 dhs data were shifted forward ; 7 years were added to each participant 's age from the 2008 dhs survey and the hcv antibody and hcv rna prevalence estimates were recalculated using the new numerator and denominator in each age category .
the estimated number of population positive for hcv antibodies and hcv rna was calculated by multiplying the age and genderspecific prevalence of 2015 by the population census of january 2015 categorised by age and gender .
no ethical approval was needed for the data analysis presented in this paper ; the anonymised data is publically available online .
elzanaty and co is the responsible party for the ethical considerations of the edhs 2008 and ehis 2015 ; verbal informed consent was obtained from all individuals aged 18 years and older and from married minors aged 1517 years . for children less than 18 years , consent was obtained from the parent or child caretaker .
in edhs 2008 , 4757 households including 12 780 individuals aged 1559 years were identified for interview and blood testing .
a total of 4662 households complied ( 98% ) , 12 008 persons were interviewed ( 93.9% ) and out of these , 11 126 persons provided blood samples for testing ( 92.7% ) . in ehis 2015 ,
a total of 7516 households complied ( 98.3% ) , and 27 549 persons ( age : 159 years ) were interviewed ( 98.1% ) . of the total 28 079 persons
identified , 17 182 were aged 1559 years , of which 16 671 were interviewed ( 97.0% ) and out of these , 16 003 provided blood samples for testing ( 96.0% ) .
the remaining 10 897 persons identified were children aged 114 years , and of these , 10 878 ( 99.8% ) were interviewed through their caregivers and 10 044 ( 92.3% ) children provided blood samples for testing .
children therefore represented 39.5% of the total study population ( those interviewed ) in ehis 2015 .
the characteristics of the two populations surveyed in edhs 2008 and ehis 2015 are presented in table 1 . for comparison purposes ,
participant characteristics of egyptian demographic health surveys in 2008 compared to ehis 2015 there was an overall significant reduction of 32 and 29% in the prevalence of hcv antibody and hcv rnapositive individuals , respectively , between the dhs in 2008 and the ehis in 2015 ( table 2 ) .
the agespecific prevalence of hcv antibody and hcv rnapositive individuals in 2008 and 2015 is presented in table 2 and fig .
the pattern of increased prevalence of hcv antibody and hcv rnapositive persons with age was observed in both the 2008 and the 2015 survey .
a statistically significant reduction in hcv antibody prevalence was observed in all age groups , and the greatest relative prevalence reduction ( 75% ) was observed among those aged 1519 years .
a statistically significant reduction in hcv rnapositive individuals was observed in all except the two age groups encompassing those 2029 years of age .
the agespecific prevalence of hcv antibody and hcv rnapositive individuals from 2008 shifted forward by 7 years is presented alongside the 2015 prevalence estimates ( fig .
1 ) . the current data ( ehis 2015 ) for the three oldest age groups ( 4559 years ) show a similar hcv clearance percentage when compared to the same age groups in the shiftedforward 2008 data ( 31.2% in 2015 , 32.0% in the shifted 2008 , p = 0.756 ) . for the cohort of children aged 114 years in 2015 ,
the overall prevalence of hcv antibody and hcv rnapositive individuals was 0.4% ( 95% ci 0.30.5 ) and 0.2% ( 95% ci 0.10.3 ) respectively ( table 3 ) .
prevalence of hepatitis c virus ( hcv ) antibody and hcv rna positive persons ( age 1559 years ) by age , gender and region ( edhs 2008 and ehis 2015 surveys ) statistically significant ( p < 0.05 ) .
( a ) agespecific prevalence of hepatitis c virus ( hcv ) antibodypositive persons in 2008 and 2015 ( left ) , then shifted ( by 7 years ) 2008 and 2015 ( right ) .
( b ) agespecific prevalence of hcv rnapositive persons in 2008 and 2015 ( left ) , then shifted ( by 7 years ) 2008 and 2015 ( right ) .
estimated population numbers who are hepatitis c virus ( hcv ) antibody and hcv rna positive ( ehis 2015 ) a significant reduction of hcv antibody and hcv rnapositive individuals was observed when looking at the overall prevalence in the urban governorates and , and for lower and upper egypt governorates ( fig .
2 ) . no significant change in prevalence of either hcv antibody or hcv rna positivity was observed in the frontier governorates .
prevalence of hepatitis c virus antibody in the 2008 and 2015 egyptian demographic and health surveys .
table 3 shows the age and genderspecific prevalence of hcv antibody and hcv rnapositive persons in 2015 , as well as the estimated total number of persons positive for hcv antibody and hcv rna in egypt at this time . in the population aged 059 years
, we estimated a total of 3 693 180 persons with chronic hcv infection ( hcv rna positive ) , and 5 309 555 persons with hcv antibodies .
in 2015 , hcv still affects a substantial proportion of the egyptian population , where it is estimated that , in the 159year age group , 5.3 million persons are positive for hcv antibodies and , of these , approximately 3.7 million ( 69.5% ) are hcv rna positive .
this is an underestimate of the total human hcv reservoir in egypt because older age groups ( > 59 years ) were not included in the ehis 2015 .
this recent survey shows a similar epidemiological pattern of increased hcv antibody prevalence with age as did the edhs 2008 .
this phenomenon was described in many studies 9 , 10 and is because of the continuing exposure and risk of infection with age 11 , while the proportion of persons with hcv infection who go on to develop severe disease and die of it remains low until 30 years after infection ; the rate of progression to cirrhosis is estimated at 7% after 20 years of being infected 12 .
the increase in hcv antibody prevalence with age is therefore demonstrating the cumulative hcv incidence over time until hcvrelated mortality becomes manifest .
this study shows a significant reduction in the overall prevalence of hcv antibody from 14.7 to 10.0% , and hcv rna from 9.9 to 7.0% , between 2008 and 2015 among those aged 1559 years .
the main explanation for this marked reduction in hcv prevalence is the disappearance of the group infected during the mass schistosomiasis treatment campaign with reused syringes ( 1960s through early 1980s ) to outside the age range covered by the survey ( i.e. those older than 59 years ) 13 , 14 . indeed , as demonstrated in fig .
1 , the agespecific hcv antibody and hcv rna prevalence for 2015 matches well with the 2008 prevalence estimates shifted by 7 years , suggesting that the ageing of the infected cohort , the socalled  cohort effect , is the driving mechanism underlying the hcv age distribution ; this was also demonstrated in the earlier reduction of hcv antibody prevalence from 30% in 1996 14 to 14.7% in 2008 4 . in order to see whether or not a decrease in hcv incidence may have also been a contributor to the reduction in hcv prevalence , the most interesting age groups to look at are those less than 20 years of age ; persons who were not affected by the mass treatment campaigns and for whom hcvrelated mortality remains low .
if we assume that mothertochild hcv transmission is a negligible source of infant infection , as suggested by the < 0.5% hcv antibody prevalence in the 14year age group , then the hcv antibody prevalence at age 19 indicates the cumulative incidence over the past 20 years . in 2008 and 2015 , the prevalence of hcv antibodies in those aged 1519 years was 4.1 and 1.0% , respectively ; the percentage of relative risk reduction was 75% ( 95% ci 6485 ) , implying a very substantial reduction in hcv incidence in the past 20 years in this age group .
furthermore , the prevalence of hcv antibody ( 0.4% ) and hcv rnapositive persons ( 0.2% ) observed in ehis 2015 among the age group 114 years is low compared to several studies conducted in early 2000s , which described the hcv antibody prevalence to be ranging from 2 to 7% in children under 10 years in rural areas of the nile delta 15 , 16 , 17 .
this change in incidence in the younger age groups could possibly be because of the various public health interventions implemented by the ministry of health and population and its partners since 2008 . in this time
, several efforts have been made to promote and expand the infection prevention and control programmes beyond ministry of health and population hospitals , particularly to the university hospitals .
auto disabled syringes were introduced to the routine immunisation sector in 2008 in order to promote safe injection practices among children .
safe blood transfusion activities , including policies and guidelines , have been intensified since 2009 .
raising the awareness of the public , by targeting universities and schools to improve their understanding on the epidemiology and prevention of viral hepatitis , was also carried out .
preservice education targeting healthcare staff has been carried out since 2008 to enforce the concepts of safe healthcare and prevention of bloodborne pathogens .
one may question whether the national treatment programme , which managed to treat more than 350 000 persons in the past 7 years 18 using pegylated interferon and ribavirin 19 , has had an impact on hcv prevalence figures .
in such a case , it would be expected that cured patients would have cleared hcv rna , but kept hcv antibodies .
therefore , the impact would be seen through an increase in hcv clearance percentage in the age groups most targeted by the national treatment programme .
owing to established approximate 50% cure rates of the combination of pegylated interferon and ribavirin 20 , only half of these persons ( i.e. 175 000 ) would have cleared their hcv infection after treatment .
the national treatment programme prioritises persons with more advanced forms of liver disease , and therefore , at least half of the beneficiaries of this service are in their 40s or 50s .
indeed , in a group of 3235 patients treated for hcv in a hospital run by the ministry of health in cairo , between 2007 and 2011 , the mean age was 41 years with a standard deviation of approximately 10 years 21 . in order to see whether or not treatment has , as of yet , had an impact on lowering the prevalence of persons with hcv rna in egypt , we can see whether or not there has been increased clearance in the four older age groups ( i.e. encompassing 4059 years ) over the past 7 years .
if we assume that around half ( 87 500 ) of the total persons cured was in the 4059year age group , and considering that we have estimated 2.87 million persons with hcv antibodies in the same age group in 2015 ( table 3 ) , we would have expected to see around a 3% higher clearance percentage in this group , in comparison with 2008 .
however , an increase in clearance in these older age groups was not observed when comparing data from 2015 and the shiftedforward 2008 data .
indeed , it would require around 4000 antihcvpositive persons in this age group , in each data set , in order to have enough power to demonstrate this expected 3% difference ; unfortunately , the antihcv population examined in this survey was much lower than that .
treatment may show a larger impact in the near future as it is expected that emphasis will be put on an upscale of treatment of infected persons to prevent longterm complications 22 , particularly considering that new directacting antiviral ( daa ) drugs were approved for the treatment of hcv by the u.s . food and drug administration ( fda ) in late 2013 , and then introduced into egypt in late 2014 .
these new treatment regimens have reduced treatment duration to 1224 weeks , decreased side effects and improved outcomes , with cure rates of 8595% across all patient populations 23 , 24 .
finally , differential migration and mortality of persons infected with hcv could have contributed to the reduced prevalence of both hcv antibody and hcv rnapositive persons in 2015 , as long as these rates are higher than infection incidence 25 , 26 , 27 ; these topics needs to be explored further . the prevalence of hcv antibody and hcv rnapositive individuals varied among governorates and was reduced in several geographical regions .
lower egypt governorates , which are mostly rural in nature , still show a higher prevalence of hcv antibodies and hcv rna when compared to urban governorates .
this pattern of high hcv prevalence in rural areas is similar to previous multiple studies conducted in rural lower egypt governorates which showed a prevalence ranging from 14.4 to 18.5% 28 , 29 , 30 .
the frontier governorates did not show any significant change , however , this is possibly owing to the fact that the sample size was very low ( n < 200 ) , in both the 2008 and 2015 surveys . based on our findings in this study , we recommend the expansion of national health surveys in egypt in order to include older age groups and allow further followup of elderly persons who have been
the most affected by hcv and who , by the cohort effect , are being pushed out of view .
furthermore , there should be continued prioritisation of prevention programmes to increase the effects we are seeing in incidence in young age groups , with a focus on interventions which promote injection safety by reducing the frequency of unnecessary injections and syringe reuse .
interventions could include introduction of singleuse materials and engineered safety devices , such as autodisabled or autodestructive syringes into the curative sector .
expansion of infection prevention and control programmes are of utmost importance , along with development of elaborate systems for delivering and renewing licenses of healthcare facilities to ensure continuity of safe procedures and application of standard precautions
. other analyses of the ehis data should be done , using tools such as mathematical modelling , in order to properly estimate and explain changes in hcv incidence in egypt ; this could lead to further evidencebased recommendations related to prevention and control efforts .
finally , access to treatment should be a priority , and although economic constraints are faced by the country , treatment has been shown to be costeffective in this context 31 , 32 and focused , early treatment strategies may be effective in supporting prevention measures and reducing transmission 33 .
 abstractbackground & aimsin 2015 , a national egyptian health issue survey was conducted to describe the prevalence of hepatitis c virus ( hcv ) infection . in this paper 
 , we describe the hcv burden in 2015 , compare the results with the national survey conducted in 2008 , and discuss the implications of the new findings on prevention of hcv in egypt.methodsa multistage probability sampling approach was used , similar to the national demographic survey conducted in 2008 . 
 more than 90% of sampled individuals complied with the interview and provided blood samples.resultsin the 1559year age groups , the prevalence of hcv antibody was found to be 10.0% ( 95% ci 9.510.5 ) and that of hcv rna to be 7.0% ( 95% ci 6.67.4 ) . in children , 114 years old , the prevalence of hcv antibody and hcv rna were 0.4% ( 95% ci 0.30.5 ) and 0.2% ( 95% ci 0.10.3 ) respectively . 
 approximately , 3.7 million persons have chronic hcv infection in the age group 1559 in 2015 . 
 an estimated 29% reduction in hcv rna prevalence has been seen since 2008 , which is largely attributable to the ageing of the group infected 4050 years ago during the mass schistosomiasis treatment campaigns . 
 prevention efforts may have also contributed to this decline , with an estimated 75% ( 95% ci 645 ) decrease in hcv incidence in the 019 year age groups over the past 20 years.conclusionsthese findings can be used to shape future hcv prevention policies in egypt . 
Materials and methods
Source of data
Sampling strategy
Data collection
Laboratory procedures
Statistical analysis
Ethical considerations
Results
Discussion