Epidemiology of Hepatitis C Virus and Norovirus: August 2006

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Epidemiology of Hepatitis C Virus and Norovirus: August 2006

G. Bartlett, MD

Medscape Infectious Diseases. 2006;8(2) ©2006 Medscape

Posted 08/25/2006

Hepatitis C Virus

Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The

prevalence of hepatitis C virus infection in the United States, 1999

through 2002. Ann Intern Med. 2006;144:705-714. An attempt was made to

determine the hepatitis C virus (HCV)-infected population in the United

States with data from the Third National Health and Nutrition Examination

Survey (NHANES III), which was conducted in 1988-1994. That study showed

that about 1.8% of the US population had anti-HCV antibody, indicating

that a total of 3.9 million persons had prior HCV infection and

approximately 2.7 million had chronic infection. Most of the seropositive

persons were between 30 and 49 years of age and had been infected for less

than 20 years. The pattern of age-specific prevalence suggested that the

incidence of infection increased substantially in the 1960s and 1970s, and

peaked in the 1980s. The present study used survey data from 1999 to 2002

to determine the more contemporary prevalence of HCV infection.

Methods: The study was again done with survey results from NHANES III,

which is a nationally representative household survey of the US civilian,

noninstitutionalized population. The survey included 15,079 persons who

provided a blood sample and were over 6 years of age. These participants

were interviewed for relevant information and blood was tested for HCV

antibody; those who were positive were also tested for HCV RNA.

Results: Results were based on an analysis of 15,079 participants. The

overall prevalence of anti-HCV was 1.6%; this extrapolates to an estimated

4 million persons who are seropositive for HCV, and the HCV RNA data

suggested that the total number with chronic HCV infection is

approximately 3.2 million. The peak age of high prevalence was 40-49

years, 10 years greater than with the 1988-1994 survey. The comparative

data for these 2 sequential analyses that were separated by approximately

10 years are shown in Table 1 .

Table 2 shows the anti-HCV distribution by sex, income, receipt of blood

transfusions before 1992, injection drug use history, herpes simplex virus

(HSV) as a surrogate for sexually transmitted disease, age associations,

and alanine aminotransferase (ALT) levels as an indication of liver

disease. Table 2 also shows the prevalence of HCV and the total number of

cases expected in that defined population when extrapolated to the total

US population.

Conclusion: The study authors conclude that the prevalence of HCV is

relatively high and stable at about 1.6% to 1.8%. The great majority of

these patients were 20-59 years of age. Of these, 48% reported a history

of injection drug use, which was clearly the strongest risk factor; other

important risk factors were over 20 lifetime sex partners or blood

transfusions before 1992. Thus, despite a decrease in new HCV infections,

the prevalence in a population-based study has remained relatively stable

due primarily to aging of persons who acquired this infection many years

ago.

Comment: In the accompanying editorial,[1] Jules Dienstag notes that,

despite a dramatic 80% decrease in the annual incidence of acute HCV

infection in the 1990s,[2,3] the recent survey summarized above showed

that the prevalence of HCV has remained relatively constant; the most

remarkable change is a 10-year increase in the age of those infected.

Injection drug use accounted for approximately half of the patients in the

category 20-59 years of age, and much of this infection was apparently

remote rather than recent. This risk was about 150-fold higher than for

persons who did not report use of injected drugs. Of interest, there are

data supporting the role of sexual transmission of HCV, although rates are

a small fraction of the risk associated with injecting drug use.

Norovirus Gastroenteritis

Turcios RM, Widdowson MA, Sulka AC, Mead PS, Glass RI. Reevaluation of

epidemiological criteria for identifying outbreaks of acute

gastroenteritis due to norovirus: United States, 1998-2000. Clin Infect

Dis. 2006;42:964-969. Noroviruses appear to be the most common cause of

foodborne outbreaks of gastroenteritis, but diagnostic tests are not

generally available. In 1982 Kaplan and colleagues[4] authored what has

become the standard criteria for identifying outbreaks of norovirus

gastroenteritis The purpose of the present report from the US Centers for

Disease Control and Prevention (CDC) was to evaluate the Kaplan criteria.

Kaplan criteria:

Vomiting in more than half of the affected persons;

Mean or median incubation period of 24-48 hours;

Mean or median duration of illness of 12-60 hours; and

No bacterial pathogen in stool culture.

Methods: The CDC has maintained a Foodborne Outbreak Reporting System with

a computerized database since 1973. This study analyzed reports between

1998 and 2000 according to identified etiologic agents and again outbreaks

that had complete information that would fit the Kaplan criteria in terms

of incubation period, mean duration of illness, and proportion of

vomiting.

Results: The analysis included 4050 outbreaks of gastroenteritis. Of

these, norovirus was suspected or confirmed in 549 (14%); bacteria were

suspected or confirmed in 1084 (27%); and no etiologic agent was suspected

or confirmed in 2108 (52%). Table 3 summarizes results for evaluation of

the Kaplan criteria in terms of sensitivity, specificity, positive

predictive value, negative predictive value, and odds ratio.

Conclusion: The study authors concluded that the criteria of Kaplan and

coworkers[4] remained the most useful and discriminating diagnostic aid to

identify foodborne outbreaks of gastroenteritis due to norovirus.

Comment: Multiple studies have shown the important role of norovirus in

outbreaks of gastroenteritis. The major limitation in detection has been

the lack of a sensitive assay. Enzyme-linked immunoassays (EIAs) have

limited value due to genetic diversity.[5] Polymerase chain reaction

(PCR)-based assays are considered optimal and are available at the CDC[6]

and some public health laboratories, but they are not available in

commercial or hospital laboratories. It is emphasized that the Kaplan

criteria require assessment of all components rather than any individual

component. It was the composite evaluation that provided the 99%

specificity. It was noted in the editorial comment[7] that noroviruses " do

not get the respect that norovirologists think they deserve. " He notes

that, although these viruses cause a substantial burden of disease,

and Gerber[8] found that only 4% of US public health staff rank them in

the top 3 agents causing foodborne illnesses. In defense of the norovirus,

it was noted that the illness in some populations can be severe[9,10]; the

duration of shedding can be very long; genetic factors moderate

immunity[11]; and the economic impact can be " huge.[12] "

Table 1. Hepatitis C Virus Results of National Health and Nutrition

Examination Survey (NHANES) 1988-1994 and 1999-2002

Hepatitis C Virus 1988-1994 1999-2002

Prevalence in US adults 1.8% 1.6%

Seropositive adults 4.0 million persons 4.0 million persons

Chronic hepatitis C virus infection 2.7 million persons 3.2 million

persons

Peak prevalence age 30-39 years of age 40-49 years of age

Table 2. Anti-HCV Prevalence and Distribution by Demographics and

Potential Risk Factors

Characteristic HCV Seroprevalence (%) Total With Characteristic (x 1

Million) Total With Anti-HCV (x 1000)

All participants 1.6 255.4 4060

Male 2.1 123.9 2570

Female 1.1 131.5 1490

Income

? 2 times the poverty threshold 1.0 145.0 1410

Below poverty threshold 3.2 35.6 1240

Blood transfusion prior to 1992

Yes; age 20-59 5.8 8.8 510240.0

Yes; age > 60 3.2 7.4 2900190.0

No; age 20-59 2.0 143.1

No; age > 60 0.5 35.5

Lifetime drug use, age 20-59

None or marijuana 0.7 112.3 770960.0

Drug use not marijuana 3.5 27.6 1620

Injection drug use 57.5 2.8

HSV seropositive, age 18-49

Negative 1.7 103.1 1750

Positive 5.2 24.5 1280

HIV, age 18-49

Negative 2.3 128.8 3020

Positive 13.8 600.0 80

ALT levels

< 40 U/L 0.9 207.4 1860

> 120 U/L 24.0 1.4 340.0

ALT = alanine aminotransferase; HCV = hepatitis C virus; HIV = human

immunodeficiency virus; HSV= herpes simplex virus; U/L = units per liter

Table 3. Evaluation of Kaplan Criteria for Identifying Outbreaks of Acute

Gastroenteritis Due to Norovirus

Characteristic Norovirus Bacteria Sen Spec OR PPV NPV

Kaplan criteria

Fit 101 3 68% 99% 49 97% 82%

Do not fit 47 211

Percentage of patients with vomiting

> 50% 131 84 89% 61% 2.2 61% 88%

< 50% 17 130

Duration

12-60 hr 127 75 86% 65% 2.4 63% 87%

< 12 or > 60 hr 21 139

Incubation period

24-48 hr 132 65 89% 70% 2.9 67% 90%

< 24 or > 48 hr 16 149

Fever:vomiting ratio*

? 1 127 101 90% 47% 1.7 56% 86%

> 1 14 88

Diarrhea:vomiting ratio†

< 2.5 143 116 97% 45% 67 55% 95%

? 2.5 5 93

*Fever:vomiting ratio = proportion of persons with fever to proportion

with vomiting

†Diarrhea:vomiting ratio = proportion of persons with diarrhea to

proportion with vomiting

NPV = negative predictive value; OR = odds ratio; PPV = positive

predictive value; Sen = sensitivity; Spec = specificity

References

Dienstag J. Hepatitis C: a bitter harvest. Ann Intern Med.

2006;144:770-771. Abstract

Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non-A, non-B

hepatitis in the United States and association with hepatitis C virus

infection. JAMA. 1990;264:2231-2235. Abstract

Tanaka Y, Hanada K, Mizokami M, et al. Inaugural article: a comparison of

the molecular clock of hepatitis C virus in the United States and Japan

predicts that hepatocellular carcinoma incidence in the United States will

increase over the next two decades. Proc Natl Acad Sci U S A.

2002;99:15584-15589. Abstract

Kaplan JE, GW, Baron RC, et al. Epidemiology of Norwalk

gastroenteritis and the role of Norwalk virus in outbreaks of acute

nonbacterial gastroenteritis. Ann Intern Med. 1982;96:756-761. Abstract

TF, Gerber DE. Perceived etiology of foodborne illness among public

health personnel. Emerg Infect Dis. 2001;7:904-905. Abstract

Parashar U. " Norwalk-like viruses " public health consequences and outbreak

management. MMWR Recomm Rep. 2001;50:1-18.

Lopman B. Noroviruses: simple detection for complex epidemiology. Clin

Infect Dis. 2006;42:970-971. Abstract

TF, Gerber DE. Perceived etiology of foodborne illness among public

health personnel. Emerg Infect Dis. 2001;7:904-905. Abstract

Rockx B, De Wit M, Vennema H, et al. Natural history of human calicivirus

infection: a prospective cohort study. Clin Infect Dis. 2002;35:246-253.

Abstract

Lopman BA, Reacher MH, Vipond IB, Sarangi J, Brown DW. Clinical

manifestation of norovirus gastroenteritis in health care settings. Clin

Infect Dis. 2004;39:318-324. Abstract

AM, Atmar RL, Graham DY, Estes MK. Norwalk virus infection and

disease is associated with ABO histo-blood group type. J Infect Dis.

2002;185:1335-1337. Abstract

Widdowson MA, Cramer EH, Hadley L, et al. Outbreaks of acute

gastroenteritis on cruise ships and on land: identification of a

predominant circulating strain of norovirus -- United States, 2002. J

Infect Dis. 2004;190:27-36. Abstract

G. Bartlett, MD, Professor of Medicine; Chief, Division of Infectious

Diseases, s Hopkins University School of Medicine, Baltimore, land

Disclosure: G. Bartlett, MD, has disclosed that he has served on the

HIV advisory board for Bristol-Myers Squibb, Abbott, and GlaxoKline.

" and the beat goes on....... " Sonny Bono " It's not the years in your life that

count. It's the life in your years. " Abraham Lincoln

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