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Hearing From the Silent Epidemic - Hepatitis C Virus Infection Among Reproductive-Aged Women and Children in the United States, 2006 to 2014 - 'screening of pregnant women needed & newborns of infected mothers' needed
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"The data from this study may inform ongoing discussions ofHCV screening for all pregnant women to protect theirhealth and that of their offspring..... However, recommendations forscreening in pregnant women and clearer testing guidelines for infants born to HCV-infected mothers do not exist at this time"
"Another silent epidemic of HCV has been occurring as a syndemic within the outbreak of opioid and injection drug use..... The consequences of this epidemic in a younger generation are more challenging than in baby boomers because transmission of the virus is ongoing;..... the population is hard to reach and has less access to, or interaction with, health care; and the demand for substance use treatment and associated services is great, although the supply is limited. The benefits of prevention, medical care, and treatment for the individual and society are evident. HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women.......How to institute them effectively is not known...... Unlike the almost 2:1 ratio of men to women among baby boomers with HCV infection, cases in younger people occur with closer gender parity....... Thus, more children are being born to HCV-infected mothers than at any time since HCV became detectable...... Ly and colleagues, in their current Annals report (8), used data from national surveillance and a large diagnostic testing laboratory to explore the implications of the current epidemic in reproductive-aged women and their babies. They estimate that approximately 29000 women with HCV infection give birth each year, resulting in approximately 1700 infected infants. They note that only 200 infections in children aged 2 to 13 years are reported to public health surveillance each year, so many cases go unrecognized. Although the rate ascribed to vertical transmission of HCV (5.8%) is much lower than the 90% for hepatitis B virus (HBV), the number of children with chronic HCV infection may now be greater than that of children with chronic HBV infection because of the lack of recognition and prevention of maternal HCV infection, as well as the effectiveness of public health programs to control perinatal HBV with vaccine and immune globulin...... Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers......A population-based study in Philadelphia revealed that among 537 babies born to HCV-infected mothers in 2011 through 2013, only 84 (16%) had HCV laboratory results reported by at least 20 months of age (9)."
"The number ofHCV cases in reproductive-aged women reported tothe NNDSS essentially doubled from 2006 to 2014...... an estimated 1700 infants(CI, 1200 to 2200 infants) are infected by this routeeach year..... Strategies to effectively prevent or cure infection in reproductive-aged women and their sexual and needle-sharing partners are critical. The public will be best protected from the consequences of HCV infection only if accurate surveillance data are available to guide prevention and care, innovative and effective treatment and medical care for substance use disorder are delivered to an often marginalized population, and evidence-based harm reduction interventions are deployed."
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Editorials |9 May 2017 - Annals of Internal Medicine May 9 2017
Hearing From the Silent Epidemic
⇒ "The consequences of this epidemic in a younger generation are more challenging than in baby boomers because transmission of the virus is ongoing....more children are being born to HCV-infected mothers than at any time since HCV became detectable.....HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women....At the very least, screening of pregnant women for HCV infection risk factors, as well as risk-based testing, requires more emphasis. Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers"
⇒"Although HIV-HCV co-infection was not determined in this analysis,about 5% to 8% of persons with HCV infection are estimatedto have HIV co-infection (23, 24).
⇒To our knowledge, this is the first national analysisto estimate numbers of HCV-infected pregnant womenand their infants in the United States. The number ofHCV cases in reproductive-aged women reported tothe NNDSS essentially doubled from 2006 to 2014. The Quest Diagnostics data analysis further refines this pictureby suggesting that about 0.73% of the 3.9 millionwomen who give birth each year (19)-that is, about29 000 women (CI, 27 400 to 30 900 women)-haveHCV infection; by extension, an estimated 1700 infants(CI, 1200 to 2200 infants) are infected by this routeeach year. In contrast, only about 200 childhood casesper year are reported to the NNDSS, which may suggesta need for wider screening for HCV in pregnantwomen and their infants, as is recommended for HIVand hepatitis B virus. However, recommendations forscreening in pregnant women and clearer testingguidelines for infants born to HCV-infected mothers do not exist at this time (21).
⇒ we performedan ancillary analysis of the CDC National Healthand Nutrition Examination Survey (NHANES) for 2003through 2012. The NHANES interviews and tests about5000 randomly selected U.S. residents each year to detectvarious diseases and conditions. Because the overallprevalence of HCV infection is only 1% (1), too fewcases are identified in any year for yearly trends to beestimated, and HCV prevalence is analyzed by combiningdata from several years (3). Given these caveats, wefound that of 7904 women aged 15 to 44 years testedin NHANES from 2003 to 2012, 33 (0.5% [CI, 0.3% to0.7%]) had HCV RNA. This percentage aligns bothwiththe 0.4% positivity in 598 819 women tested in obstetricians'offices and the 0.73% HCV infection rate in the581 255 pregnant women in the Quest data from 2011to 2014 (Table 2), a period overlapping the NHANESdata we analyzed (from 2003 to 2012) by only 2 years-that is, before the HCV incidence increased in youngwomen (3)."
Alfred DeMaria Jr., MD
Hepatitis C virus (HCV) infection has been called a "silent epidemic" (1). Millions of Americans infected with HCV during the 1960s through 1980s were not recognized as such until after 1989, when diagnostic tests became available. The baby-boom generation's high prevalence of infection led to recommendations for universal screening for everyone born between 1945 and 1965 (2). Although these recommendations are 5 years old, we still have a long way to go before all those infected are identified and presented with the option of curative, albeit expensive, therapy. Moreover, surveys on which prevalence estimates were based, such as NHANES (National Health and Nutrition Examination Survey) (3), included only persons willing to respond and participate and left out a growing population at risk for more recent infection (4).
Another silent epidemic of HCV has been occurring as a syndemic within the outbreak of opioid and injection drug use. The lack of diagnostic tests does not account for the silence associated with this epidemic, although underresourced public health surveillance explains much of the delayed recognition. The consequences of this epidemic in a younger generation are more challenging than in baby boomers because transmission of the virus is ongoing; the population is hard to reach and has less access to, or interaction with, health care; and the demand for substance use treatment and associated services is great, although the supply is limited. The benefits of prevention, medical care, and treatment for the individual and society are evident. How to institute them effectively is not.
The ongoing HCV epidemic in persons younger than 30 years was first identified primarily through public health surveillance (5-7). Unlike the almost 2:1 ratio of men to women among baby boomers with HCV infection, cases in younger people occur with closer gender parity. Thus, more children are being born to HCV-infected mothers than at any time since HCV became detectable. Ly and colleagues, in their current Annals report (8), used data from national surveillance and a large diagnostic testing laboratory to explore the implications of the current epidemic in reproductive-aged women and their babies. They estimate that approximately 29000 women with HCV infection give birth each year, resulting in approximately 1700 infected infants. They note that only 200 infections in children aged 2 to 13 years are reported to public health surveillance each year, so many cases go unrecognized. Although the rate ascribed to vertical transmission of HCV (5.8%) is much lower than the 90% for hepatitis B virus (HBV), the number of children with chronic HCV infection may now be greater than that of children with chronic HBV infection because of the lack of recognition and prevention of maternal HCV infection, as well as the effectiveness of public health programs to control perinatal HBV with vaccine and immune globulin.
Of course, babies were born to women with HCV infection in the 1960s through 1980s, but no tests were available to diagnose those cases. Presumably, the children of that era in whom the infection did not clear are now among the adults whose ages fall between the 2 epidemic age cohorts. Today, however, recognizing the infection in pregnant women and neonates is possible, and clinical trials of antiviral therapy may show safety and efficacy in pregnant women and in children. Rather than silence, HCV infection calls out for public health action directed at all aspects of the epidemic, including consideration of screening pregnant women. At the very least, screening of pregnant women for HCV infection risk factors, as well as risk-based testing, requires more emphasis. Another issue in need of attention is the lack of authoritative, consensus-based recommendations for the identification, testing, and case management of newborns of infected mothers. A population-based study in Philadelphia revealed that among 537 babies born to HCV-infected mothers in 2011 through 2013, only 84 (16%) had HCV laboratory results reported by at least 20 months of age (9).
A recent report from the National Academies of Sciences, Engineering, and Medicine proposes eliminating the public health problem of HBV and HCV infection (10). Much work lies ahead to eradicate HCV, starting with resources for public health surveillance to monitor incidence and prevalence, and to fully characterize the infection in the population. Strategies to effectively prevent or cure infection in reproductive-aged women and their sexual and needle-sharing partners are critical. The public will be best protected from the consequences of HCV infection only if accurate surveillance data are available to guide prevention and care, innovative and effective treatment and medical care for substance use disorder are delivered to an often marginalized population, and evidence-based harm reduction interventions are deployed.
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From previous studies reported:
⇒HCV Vertical Transmission Increases
-http://natap.org/2016/HCV/072616_02.htm-
68% Nationally, HCV detection Rate Among Women of Child-Bearing Age in Kentucky Increased >200%....public health policies needed....the proportion of infants born to HCV-infected women increased 124%, from 0.71% to 1.59%....."Transmission of HCV is primarily via parenteral blood exposure, and HCV can be transmitted vertically from mother to child. Vertical transmission occurs in 5.8% (95% confidence interval = 4.2%-7.8%) of infants born to women who are infected only with HCV and in up to twice as many infants born to women who are also infected with human immunodeficiency virus (HIV) (2) or who have high HCV viral loads.... Increased reported incidence of HCV infection among persons aged ≤30 years (5,6) with similar increases among women and men in this age group (6), raises concern about increases in the number of pregnant women with HCV infection, and in the number of infants who could be exposed to HCV at birth......During 2011-2014, commercial laboratory data indicated that national rates of HCV detection (antibody or RNA positivity ) among women of childbearing age increased 22%, and HCV testing (antibody or RNA) among children aged ≤2 years increased 14%; birth certificate data indicated that the proportion of infants born to HCV-infected mothers increased 68%, from 0.19% to 0.32%. During the same time in Kentucky, the HCV detection rate among women of childbearing age increased >200%, HCV testing among children aged ≤2 years increased 151%, and the proportion of infants born to HCV-infected women increased 124%, from 0.71% to 1.59%. Increases in the rate of HCV detection among women of childbearing age suggest a potential risk for vertical transmission of HCV.
Failure to Test and Identify Perinatally Infected Children Born to Hepatitis C-Positive Women- (01/27/16).....8,119 females (12-54 years) were HCV-positive and in the Hepatitis Registry. Of these, 500 (5%) had delivered ≥1 child, accounting for 537 (1%) of the 55,623 children born in Philadelphia during the study period. Eighty-four (16%) of these children had HCV testing.
⇒Women & HCV - Screen & Treat Early / Screen Pregnant Women to Prevent Transmission to Children / Philadelphia Report.....http://www.natap.org/2016/HCV/092316_03.htm
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Hepatitis C Virus Infection Among Reproductive-Aged Women and Children in the United States, 2006 to 2014 - "The number ofHCV cases in reproductive-aged women reported tothe NNDSS essentially doubled from 2006 to 2014"
Annals of Internal Medicine May 9 2017 - Kathleen N. Ly, MPH; Ruth B. Jiles, PhD, MPH; Eyasu H. Teshale, MD; Monique A. Foster, MD, MPH; Rick L. Pesano, MD, PhD; andScott D. Holmberg, MD, MPH
Abstract
Background:In the United States, hepatitis C virus (HCV) infection has increased among young persons who inject drugs, but the extent of this epidemic among reproductive-aged women and their children is unknown.
Objective:To estimate numbers and describe characteristics of reproductive-aged women with HCV infection and of their offspring.
Design:Analysis of the National Notifiable Diseases Surveillance System (NNDSS) from 2006 to 2014 and the Quest Diagnostics Health Trends national database from 2011 to 2014.
Setting:United States.
Participants:171801 women (aged 15 to 44 years) and 1859 children (aged 2 and 13 years) with HCV infection reported to the NNDSS; 2.1 million reproductive-aged women and 56684 children who had HCV testing by Quest Diagnostics.
Measurements:NNDSS HCV case reports and Quest laboratory data regarding unique reproductive-aged women and children who were tested for HCV infection.
Results:The number of reproductive-aged women with acute and past or present HCV infection in the NNDSS doubled, from 15550 in 2006 to 31039 in 2014. Of 581255 pregnant women tested by Quest from 2011 to 2014, 4232 (0.73% [95% CI, 0.71% to 0.75%]) had HCV infection. Of children tested by Quest, 0.76% (CI, 0.69% to 0.83%) had HCV infection, but the percentage was 3.2-fold higher among children aged 2 to 3 years (1.62% [CI, 1.34% to 1.96%]) than those aged 12 to 13 years (0.50% [CI, 0.41% to 0.62%]). Applying the Quest HCV infection rate to annual live births from 2011 to 2014 resulted in an estimated average of 29000 women (CI, 27400 to 30900 women) with HCV infection, who gave birth to 1700 infants (CI, 1200 to 2200 infants) with the infection each year.
Limitations:Only a fraction of HCV infections is detected and reported to the NNDSS. Quest data are potentially biased, because women who are asymptomatic, do not access health care, or have unreported risks may be less likely to be tested for HCV infection.
Conclusion:These data suggest a recent increase in HCV infection among reproductive-aged women and may inform deliberations regarding a role for routine HCV screening during pregnancy.
Primary Funding Source:
Centers for Disease Control and Prevention.
RESULTS
HCV in Reproductive-Aged Women
Of 425 322 women with confirmed HCV infectionreported to the NNDSS from 2006 to 2014, 171 801(40.4%) were of reproductive age (15 to 44 years) (Table1). The reported number of acute cases in thesewomen increased 3.4-fold, and the reported number ofpast or present cases doubled from 2006 to 2014 (Table1); by 2012, the total number of cases reported inreproductive-aged women surpassed that of womenaged 45 to 64 years (Figure). Non-Hispanic whitewomen accounted for about half (2342 [57%]) of allacute infections; for the 2069 women with available riskinformation, 1310 (63%) acknowledged injection druguse (Table 1). Among reproductive-aged women withHCV infection, the median age was 28 years (IQR, 23 to34 years) for those with acute infection and 31 years (IQR,25 to 39 years) for those with past or present infection.
From 2011 to 2014, Quest performed approximately10.6 million HCV diagnostic tests, 3.3 million(31.3%) of which were done in 2.1 million uniquereproductive-aged women (that is, those with individualidentifiers). Of these women, 51 117 (2.39% [CI,2.37% to 2.41%]) had past or present HCV infection and28 693 (1.34% [CI, 1.32% to 1.36%]) had current HCVinfection (Table 2), as determined by the following:
28 646 (93.56% [CI, 93.27% to 93.84%]) had a positiveHCV RNA result, 15 123 (52.71% [CI, 52.13% to53.29%]) had an HCV genotype identified, and 13 276(46.27% [CI, 45.69% to 46.85%]) had both a positiveHCV RNA result and a genotype identified (data notshown). Of the women who had HCV genotyping,70.81% (CI, 70.08% to 71.54%) had genotype 1,10.41% (CI, 9.93% to 10.91%) genotype 2, 17.27% (CI,16.67% to 17.88%) genotype 3, and 1.51% (CI, 1.32%to 1.71%) genotypes 4 through 6. The median age ofreproductive-aged women was 32 years (IQR, 26 to 39years) for those who had current HCV infection and 29years (IQR, 24 to 36 years) for those who did not. Withregard to regions where HCV testing was done inreproductive-aged women, the greatest concentrationsof both HCV testing and current HCV infection were inthe South, followed by the Northeast (Table 2). Womenwith HCV infection had their testing reimbursed bypublic insurance (Medicare or Medicaid) more frequentlythan other types of coverage. Providers from awide range of specialties ordered HCV testing (Table2). Of almost 600 000 women who were tested for HCVinfection in their obstetrician's office, 0.37% (CI, 0.36%to 0.39%) had HCV RNA positivity (indicating current[active] HCV infection).
Of the 581 255 pregnant women aged 15 to 44years tested by Quest from 2011 to 2014, 4232 (0.73%[CI, 0.71% to 0.75%]) had HCV infection (Table 2). Themedian age of reproductive-aged women with HCV infectionwas 27 years (IQR, 24 to 31 years) for those whowere pregnant and 34 years (IQR, 27 to 40) for thosewho were not.
HCV in Children
Of the 1 149 646 confirmed cases of HCV infectionreported to the NNDSS from 2006 to 2014, 1859 (0.2%)were in children aged 2 to 13 years (Table 1). Most ofthese cases were reported as past or present HCV infection(n = 1846) in children aged 2 to 5 years from thenortheastern and southern regions. Cases were distributedapproximately evenly by sex and year of report,with an average of 207 cases reported each year.
From 2011 to 2014, Quest performed 86 783 HCVtests in 57 136 children aged 2 to 13 years. Of thesechildren, 882 (1.54% [CI, 1.44% to 1.65%]) had past orpresent HCV infection, 432 (0.76% [CI, 0.69% to0.83%]) had current infection, and 56 252 (98.45% [CI,98.35% to 98.55%]) were not currently infected (Table2). For the remaining 452 children, current HCV infectionstatus could not be established because of indeterminateor missing test results for HCV antibody,RNA, or genotype. Of the children with current HCVinfection, 413 (95.60% [CI, 93.22% to 97.33%]) had apositive HCV RNA result, 145 (33.56% [CI, 29.12% to38.23%]) had an HCV genotype reported, and 126(29.17% [CI, 24.92% to 33.70%]) had both. Of the childrenwho had HCV genotyping, 69.66% (CI, 61.48% to77.01%) had genotype 1.
Among children, HCV testing was ordered mostfrequently for those living in the South, those aged 8 to12 years, those with private insurance, and those seenin physician or pediatrician offices (Table 2). Amongchildren with current HCV infection, the following characteristicswere reported most frequently: age 2 to 3years, coverage by private health insurance, HCV testingordered by a physician's office, and HCV testingordered by a pediatrician (Table 2). The median agewas 7 years (IQR, 4 to 11 years) for children who hadHCV infection and 9 years (IQR, 6 to 12 years) for thosewho did not.
The proportion of children with current HCV infectionin the Quest database was 3.2-fold higher amongthose aged 2 to 3 years (1.62% [CI, 1.34% to 1.96%])than those aged 12 to 13 years (0.50% [CI, 0.41% to0.62%]) (Table 2).
Estimated Number of HCV-Infected WomenWho Gave Birth and of HCV-Infected Infants
Because 0.73% (CI, 0.69% to 0.78%) of pregnantwomen tested for HCV infection from 2011 to 2014were found to have the infection and approximately 3.9million live births occurred each year from 2011 to2014 (19), it may be estimated that an average of29 000 women (CI, 27 400 to 30 900 women) with HCVinfection gave birth during that period. A recent systematicreview and meta-analysis found a likely rate ofmother-to-infant transmission of 5.8 in 100 live births(CI, 4.2 to 7.8 in 100 live births) (20), suggesting that anestimated 1700 infants (CI, 1200 to 2200 infants) wereborn with HCV infection each year from 2011 to 2014.
DISCUSSION
To our knowledge, this is the first national analysisto estimate numbers of HCV-infected pregnant womenand their infants in the United States. The number ofHCV cases in reproductive-aged women reported tothe NNDSS essentially doubled from 2006 to 2014. The
Quest Diagnostics data analysis further refines this pictureby suggesting that about 0.73% of the 3.9 millionwomen who give birth each year (19)-that is, about29 000 women (CI, 27 400 to 30 900 women)-haveHCV infection; by extension, an estimated 1700 infants
(CI, 1200 to 2200 infants) are infected by this routeeach year. In contrast, only about 200 childhood casesper year are reported to the NNDSS, which may suggesta need for wider screening for HCV in pregnantwomen and their infants, as is recommended for HIV
and hepatitis B virus. However, recommendations forscreening in pregnant women and clearer testingguidelines for infants born to HCV-infected mothers donot exist at this time (21).
The HCV infection rate was 3.2-fold higher amongchildren in the youngest than the oldest age group inthe Quest data analysis: 1.62% (CI, 1.34% to 1.96%) inthose aged 2 to 3 years and 0.50% (CI, 0.41% to 0.62%)in those aged 12 to 13 years. This difference may bethe result of a decrease in testing over time in childrenwho already are known to have chronic HCV infectionor of spontaneous resolution of HCV infection, whichoccurs more often in infants and children (25% to 50%of those infected) than adults (12, 22). Treatment is consideredon an individual basis but generally is recommendedonly in the rare instance of severe liver diseasein children younger than 18 years; therefore, it likelyhas not contributed to the decline.
These data have several limitations. Data from boththe NNDSS and Quest may be affected by ascertainmentbias. For NNDSS data, increases in testing by providersor changes in case definition may have resultedin more cases being reported, thus showing a spuriousincrease in cases over time. However, federal fundingfor 7 to 10 "sentinel" surveillance sites has not changedduring the past 20 years (3), and the case definitionshave not changed substantially during that periodeither.
In the case of Quest data, the percentage of pregnantwomen with HCV infection may be inflated becauseproviders are more likely to screen women theyknow or suspect are at risk, such as injection drug users,or who reside in areas with a high HCV incidence orprevalence. To explore this possibility further, we performedan ancillary analysis of the CDC National Healthand Nutrition Examination Survey (NHANES) for 2003through 2012. The NHANES interviews and tests about5000 randomly selected U.S. residents each year to detectvarious diseases and conditions. Because the overallprevalence of HCV infection is only 1% (1), too fewcases are identified in any year for yearly trends to beestimated, and HCV prevalence is analyzed by combiningdata from several years (3). Given these caveats, wefound that of 7904 women aged 15 to 44 years testedin NHANES from 2003 to 2012, 33 (0.5% [CI, 0.3% to0.7%]) had HCV RNA. This percentage aligns both withthe 0.4% positivity in 598 819 women tested in obstetricians'offices and the 0.73% HCV infection rate in the581 255 pregnant women in the Quest data from 2011to 2014 (Table 2), a period overlapping the NHANESdata we analyzed (from 2003 to 2012) by only 2 years-that is, before the HCV incidence increased in youngwomen (3).
Although Quest provided laboratory services forapproximately half of all U.S. physicians and hospitals during the period of study, we cannot verify that Questdid half of all HCV tests in the United States during that time. However, Quest laboratories performed HCV testing
in more than 2 million reproductive-aged women, as reported here, and are located throughout the country. The reasons and motivations for testing also cannot be determined from these data, but the testing locations (Table 2) indicate that women were tested by providers from various specialties and children mainly byprimary care and pediatric clinicians. Although HIV-HCV co-infection was not determined in this analysis, about 5% to 8% of persons with HCV infection are estimated to have HIV co-infection (23, 24).
In conclusion, these data suggest that the numberof U.S. reproductive-aged women with HCV infectionhas increased substantially in recent years. Although no HCV treatments have been approved by the U.S. Foodand Drug Administration for use in pregnant women,clinical trials of promising drugs are under way. Pregnancymay be the only time a young woman is seen by a clinician, so some clinicians already are screeningpregnant women known or suspected to be at risk for HCV infection according to current guidelines (21).
The data from this study may inform ongoing discussions of HCV screening for all pregnant women to protect theirhealth and that of their offspring.
From Centers for Disease Control and Prevention, Atlanta,Georgia, and Quest Diagnostics Nichols Institute, San JuanCapistrano, California.
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