Winter 1997-98 Volume 2, Number 4		Drug-linked HAV outbreaks tax health departments March 10 - Public health officials across the nation are worried about a surge in hepatitis A outbreaks associated with illicit street drugs. The outbreaks are responsible for a rising number of U.S. hepatitis A cases, and are straining the resources of health departments in the West and Midwest. Drug-associated outbreaks have hit several states. Oklahoma has suffered a drug-linked epidemic since late 1994 involving more than 5,000 cases, with a peak statewide rate of almost 80 per 100,000 person-years (over eight times the U.S. rate). Oregon experienced a similar epidemic during 1994 to 1996, with almost 5,000 cases reported. Missouri and Arkansas have also seen large drug-linked outbreaks in the past few years, with 3,800 and 1,600 cases reported respectively. Drug-associated outbreaks are now underway in Washington, Iowa, central California, Nevada, and other states. All are occurring mainly in adults. The drug most commonly tied to the outbreaks is methamphetamine. The recurring link between HAV and illicit drugs Hepatitis A has been linked to illicit drug use since the 1970s, when researchers in Sweden began to describe outbreaks in drug addicts. Norkrans and colleagues reported in 1974-76 that a large share of hepatitis A cases in Gothenburg was occurring in intravenous (IV) drug users. Since then, many seroprevalence studies from Europe have shown a higher prevalence of anti-HAV in IV drug users than in controls. In the U.S., drug-associated outbreaks of hepatitis A were first noticed in the mid-1980s. A 1988 article in the Morbidity and Mortality Weekly Report (Hepatitis A among drug abusers, MMWR 1988;259:3235-3241), reported on hepatitis A epidemics among drug abusers in upstate New York and northern California. Both epidemics occurred in young adults with a predominance of cases in males. In the New York report, the drug mentioned was intravenous cocaine. In the northern California report, the drug was IV methamphetamine. In the MMWR report, CDC noted that the proportion of hepatitis A cases admitting to IV drug use had risen steadily from 1982 to 1986. The agency said that this indicated "an increasing association between drug abuse and hepatitis A in the United States." Other U.S. reports linking hepatitis A with drug abuse soon followed. In 1988, Schade, reporting on a huge drug-associated outbreak in the Pacific Northwest in 1983-1989, described a pattern that is now recognized as typical: age-specific attack rates highest in the 20-40 age group, male predominance, and a high proportion of cases admitting to illicit drug abuse. Schade found that, during 1985 in Multnomah County, Oregon, 26% of female cases and 36% of male cases admitted to the use of intravenous drugs. The drug most commonly mentioned was heroin (Schade CP, Komorwska D. Continuing outbreak of hepatitis A linked with intravenous drug abuse in Multnomah County. Public Health Reports 1988;103:452-459). Similar accounts have been filed from other U.S. states. A current example: Spokane, Washington The current outbreak in Spokane, Washington is a classic example of the problem. It began in mid-1997 and escalated quickly in early 1998. Before it began, Spokane County (population 405,000) had experienced no significant incidence of hepatitis A since the big Pacific Northwest outbreak in the 1980s. In January 1998, the County reported 77 cases, higher than any previous month since the beginning of the outbreak. The incidence has now leveled at about 50 cases per month, according to Dr. Paul Stepak, the County Epidemiologist. The age-specific attack rate remains highest in the 19-29 and 30-39 age groups, with relatively little disease in children (see chart). About 60% of the cases are in males. Cases are distributed over a wide geographical area within Spokane County, but are concentrated in areas of lower socio-economic status. In 1997, 28% of cases admitted to using intravenous drugs; this has fallen to 17% in 1998 so far. The drug most commonly mentioned is methamphetamine. The outbreak has strained the capacity of the Spokane County health department. Several HAV-infected foodhandlers have been publicly announced, resulting in the administration of over 11,000 doses of immune globulin to restaurant and grocery store patrons. Nearly 5,000 foodhandlers have been vaccinated against hepatitis A. The County Health Officer, Dr. Kim Thorburn, has requested special funding from the Washington State Legislature for a vaccination program aimed at drug abusers and school children ages 13 to 18. Two hypotheses on viral transmission In the 1988 MMWR article mentioned above, CDC editorialized that "[t]wo possible explanations for the association between hepatitis A and drug use have been proposed: 1 HAV may be transmitted by injection or ingestion of contaminated drugs (common-source spread), or 2 transmission may result from direct person-to-person contact." In the years since the article was published, the mechanism of HAV transmission in drug-associated outbreaks still has not been fully elucidated. A few virologists favor the contaminated-drug hypothesis. The drugs themselves could become contaminated with feces containing HAV during manufacture, handling, transport (such as in rectal condoms), or during the process of snorting or injection. This hypothesis was strengthened recently, when researchers learned that the viremic stage of hepatitis A is much longer than previously thought - perhaps as long as 30 days prior to the onset of symptoms and for a long time afterwards (see Hepatitis Control Notes in this issue of HCR). Most epidemiologists favor the person-to-person hypothesis. The epidemiology of drug-associated outbreaks argues against common-source spread. Moreover, public health workers in several states have observed extremely poor hygiene among users of methamphetamine. One health department investigator in Washington State recently described the scene of a typical methamphetamine party. In a decrepit trailer with no running water or toilet, a dozen young adults smoked and injected methamphetamine repeatedly over several days, often engaging in sex with multiple partners. According to the investigator, the partygoers completely abandoned normal hygienic measures for themselves and for their small children, who wandered about for days with unchanged diapers. Another investigator in Iowa has described the use of common ice buckets during methamphetamine parties, from which thirsty partygoers grab ice with unwashed hands. All these conditions favor high-grade environmental fecal contamination and person-to-person transmission of HAV. Recent research suggests that both the contaminated drug and person-to-person hypotheses may be correct. Hutin and colleagues conducted an interesting case-control study last year during a drug-linked outbreak in Des Moines and Ottumwa, Iowa. The study involved 28 serologically-confirmed cases and 16 susceptible controls, all methamphetamine abusers. Cases were more likely than controls to have injected the drug (OR=10.0, 95% C.I.=2.0-54.5) or to have used the drug with another case (OR=8.6, 95% C.I.=1.5-87.5). The authors noted that "case-patients indicated frequent direct handling of drug with unwashed hands during preparation before injection or ingestion," and concluded that "hepatitis A is transmitted from person to person among methamphetamine users through multiple routes that could include fecal-oral, percutaneous and fecal-percutaneous." They also said that a small common-source outbreak caused by fecally contaminated methamphetamine could have been imbedded in the epidemic (Hutin YJF et al. Multiple modes of hepatitis A virus transmission among methamphetamine users. Presentation at the International Conference on Emerging Infectious Disease, Atlanta, March 8-11, 1998). The problem of control In recognition of the HAV infection risk faced by illicit drug users, the 1996 hepatitis A recommendations of the Advisory Committee on Immunization Practices (ACIP) state that "vaccination is recommended for injecting and noninjecting illegal drug users if local epidemiologic and surveillance data indicate current or past outbreaks among persons with such risk behaviors." The ACIP policy is very clear, but, unfortunately, very difficult to implement. Drug abusers are notoriously difficult to find. Over the years, health departments have despaired in their attempts to deliver hepatitis immunization or other public health services to drug-abusing groups. This is particularly true for methamphetamine abusers, who often belong to alienated or criminal subcultures and may suffer from irritability, depression, and paranoia, three long-term effects of methamphetamine use. On the other hand, everyone knows that it is relatively easy to deliver vaccines to children through school-based programs. Could hepatitis A vaccination of children be used to control drug-linked outbreaks? The answer to this question, of course, depends on the amount of HAV transmission taking place among children during these outbreaks. In traditional communitywide hepatitis A epidemics, the peak attack rate occurs in the 5-9 age group. Epidemiologists interpret this to mean that HAV transmission is occurring mainly in asymptomatic young children - under age 6. But drug-associated outbreaks appear to be different. Only a few cases occur in young children. Most cases appear in adults ages 20 to 40. In the Spokane outbreak, for example, the attack rate in children 5 to 12 years old is only a third of the rate in adults age 30 to 39. This is typical of drug-associated outbreaks, and suggests that young children may not play a major role in viral transmission. This suggestion is supported by a study from Oregon. Researchers there conducted a cohort study during a drug-associated outbreak in 1995. Risk factors for HAV infection were assessed in adults with recent, IgM-seropositive infection (N=27) and compared to seronegative adults (N=1,598). Recently infected adults were no more likely than seronegative adults to be living with, or have any contact with, children less than five years old. The authors concluded that "control strategies targeted primarily at children, including vaccination, are unlikely to be effective" (Van Beneden C et al. Epidemic hepatitis A among illicit drug users in Oregon: Evidence for adult-to-adult transmission. Presentation at the International Conference on Emerging Infectious Disease, Atlanta, March 8-11, 1998). Another study, however, supports the possibility of transmission in children. Staes and colleagues studied household contacts of cases with no known risk factors for HAV. The study was conducted in Salt Lake City during a drug-associated outbreak among adults in 1996. They found that, among 390 household contacts, 25% were IgM antibody seropositive, indicating recent infection. Among contacts less than 7 years old, 47% were seropositive. The authors concluded that young children may be the source of infection in a substantial number of cases in which risk factors were not identified (Staes C et al. Sources of infection among persons with acute hepatitis A and no identified risk factors, Salt Lake County, Utah, 1996. Presentation at the IDSA 35th Annual Meeting, San Francisco, 1997). A few health departments have tried to slow drug-linked outbreaks by vaccinating children. Jinadu gave hepatitis A vaccine to schoolchildren ages 2 to 18 in two small towns in Kern County, California during a drug-associated outbreak in adults. He attained very high coverage rates and probably suppressed the outbreak (Jinadu BA et al. Increasing immunization rates for two school-based hepatitis A immunization campaigns in Kern County. Presentation at the 31st National Immunization Conference, May 19-22, 1997, Detroit, Michigan). Currier carried out a similar program in rural Mississippi (Currier M et al. Results of hepatitis A vaccine campaigns in four rural Mississippi outbreaks. Presentation at the 7th Annual Meeting of the Society for Healthcare Epidemiology of America, April 27-29, 1997, St. Louis, Missouri). A handful of jurisdictions, including Missouri and Oklahoma, are currently vaccinating children in drug-associated outbreaks, but the effectiveness of those programs is not yet known. Other halth departments are planning to start vaccination programs soon. Vaccinating children in school is attractive because of the potential for high vaccine coverage and the availability of no-cost hepatitis A vaccine through the federal Vaccines for Children (VFC) entitlement. In outbreak areas, 20%-60% of children may be eligible for the entitlement. For non-eligible children, hepatitis A vaccine can be purchased through health departments for less than $12 per dose. Although the effectiveness of vaccinating children to interrupt drug-linked outbreaks is not yet established, it can offer some benefits to harried health departments. Vaccinating older children may lower the attack rate in the vaccinated cohort, especially if a high coverage rate (>70%) can be attained. At a minimum, vaccinating children (and adults) who abuse drugs can offer individual protection against disease. Some health departments have viewed the vaccination of schoolchildren mainly as a way to prevent future outbreaks. Oklahoma, for example, plans to mandate hepatitis A vaccination for all middle schoolers next year, and for all first graders the following year. CDC has approved the state's use of VFC vaccine for the program. The state is aiming to prevent a recurrence of the severe drug-associated outbreak it has experienced since 1994. Future of the crank connection Methamphetamine (see text box) has replaced opiates as the drug of choice in much of the American drug-abusing subculture. The number of methamphetamine-related visits to hospital emergency rooms more than tripled from 1991 to 1994, from 4,900 to 17,400 (NIDA Notes, November/December, 1996). The highest rates of methamphetamine abuse are in the western and midwestern states. For example, the Drug Enforcement Administration reported that methamphetamine seizures rose 4,000 percent in Des Moines, Iowa from 1993 to 1994. Methamphetamine accounts for 80% of the Des Moines Police Department's drug investigations. In the West, methamphetamine abuse has exploded in Arizona, Colorado, California, Washington, and Oregon. State health departments have wondered what characteristics of methamphetamine cause it to be so closely linked to hepatitis A. Why methamphetamine, more than other drugs? Part of the link may simply be related to the huge increase in methamphetamine abuse in America's youngs. Hutin's study suggests that extensive handling of the drug with contaminated fingers prior to use, plus the absence of any preparation steps that can inactivate HAV, contribute to the link. Others have theorized that methamphetamine bingeing leads to a truly extraordinary deterioration in personal hygiene, a deterioration not seen with other drugs. Methamphetamine's association with sexual promiscuity may also play a role. With no drop in methamphetamine abuse in sight, the HAV connection will continue to vex health departments wherever abuser meets virus. Eventually, programs of universal hepatitis A vaccination, such as the one being pursued by Oklahoma, will prevent coincident epidemics of methamphetamine and hepatitis A.