1 Hepatitis Branch, Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA.
2 Statistics and Epidemiology Branch, Division of Prevention Research and Analytic Methods, Epidemiology Program Office, Centers for Disease Control and Prevention, Atlanta, GA.
3 Iowa Department of Public Health, Des Moines, IA.
4 Polk County Department of Public Health, Des Moines, IA.
5 Wapello County Department of Public Health, Ottumwa, IA.
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ABSTRACT |
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case-control studies; disease outbreaks; epidemiologic methods; equipment contamination; hepatitis A; methamphetamine; substance abuse, intravenous
Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; OR, odds ratio
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INTRODUCTION |
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Most hepatitis A cases occur during communitywide outbreaks that are often prolonged and difficult to control (1). In published reports of several of these outbreaks (4
6
), a high proportion of case-patients reported use of illicit drugs, mostly injected. An association between hepatitis A and injecting drug use has also been reported from other countries (7
12
). In the United States, methamphetamine, a drug also known as "speed," "crystal," "crank," and "ice," which can be swallowed, smoked, snorted, or injected, has been commonly reported to be associated with hepatitis A outbreaks (4
, 5
, 13
).
Among illicit drug users, hepatitis A virus could be transmitted from person to person or acquired during common source outbreaks caused by fecally contaminated batches of drug (14). The route of transmission from person to person could be fecal-oral, facilitated by poor hygienic practices (4
). Among injectors, transmission could also occur through the percutaneous route (2
, 15
). Identification of modes of transmission among illicit drug users would help in formulating recommendations for the prevention of hepatitis A in this population.
Between December 1, 1996, and July 31, 1997, 158 hepatitis A cases were reported in Marion, Monroe, Polk, and Wapello counties in Iowa, compared with two cases during the same time period in 1995 and 1996. Similar to an outbreak that occurred the previous year in western Iowa, a high proportion of cases (26.1 percent) occurred among persons who reported injecting drugs, mostly methamphetamine (13). On June 4, 1997, an investigation was initiated to identify modes of hepatitis A virus transmission among persons using methamphetamine and to formulate recommendations to control the outbreak.
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MATERIALS AND METHODS |
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Pilot study among case-patients
A convenience sample of case-patients was enrolled in a pilot study to generate hypotheses about potential modes of transmission. Data were collected on a questionnaire containing both open-ended and close-ended questions about demographic characteristics, use of health care and social services, methamphetamine use, practices associated with methamphetamine consumption, paraphernalia use, and injection practices.
Case-control study
A case-control study was conducted to identify risk factors for hepatitis A among residents of Polk and Wapello counties. Reported laboratory-confirmed hepatitis A cases with onset dates between April 1 and July 24, 1997, and a reported methamphetamine use in the 26 weeks prior to onset were included in the study. Cases reported before June 15, 1997 (date of the initiation of the case-control study), were included retrospectively while cases reported from June 15 were included prospectively.
Of the 13 case-patients who used methamphetamine included in the pilot study, 10 (76.9 percent) reported using the emergency room more than any other health care facility. Potential controls were therefore identified prospectively from patients seeking medical care at two emergency rooms in the area (one in each county) and at a public clinic adjacent to the emergency room of Polk County. During the study period, the triage nurse in each facility asked all patients between 15 and 45 years of age about methamphetamine use in the last 12 months. Patients who reported methamphetamine use during this time period were identified as potential controls.
The referent exposure period for cases was defined as the 26 weeks before illness onset, the incubation period of hepatitis A virus infection. Referent exposure periods of the controls were 4-week time periods chosen to match the distribution of the cases' referent exposure periods.
Trained interviewers administered a questionnaire directly to case-patients and potential controls to collect data on demographic characteristics; education; living conditions; use of social and public assistance services; exposure to a day care center; contact with a hepatitis A case-patient; international travel; sexual activity; history of substance abuse; behaviors associated with methamphetamine usage; type, quantity, and route of administration of methamphetamine; and injection practices. Potential controls were asked to give a blood sample for serologic testing.
Potential controls who did not report methamphetamine usage during the referent exposure period or who were positive or not tested for total antibody to hepatitis A virus were excluded from the study.
Associations between potential exposures and hepatitis A were measured by the calculation of odds ratios. The Kruskall-Wallis nonparametric test was used to test the significance of the differences for quantitative variables, and confidence intervals for odds ratios were calculated using the exact method (crude analyses) or the method of Robins, Greenland, and Breslow (adjusted analyses) using Epi-Info, version 6 (17). Variables for which the p value in stratified analysis was 0.2 or less were tested in a stepwise forward logistic regression model using EGRET software (SERC, Seattle, Washington). For study participants who reported methamphetamine injection during the referent exposure period, the association between the circumstances of the injection events and hepatitis A was measured using generalized estimating equations (18
), using SAS software (SAS Institute, Cary, North Carolina). For this purpose, the data were transposed to represent repeated measures on individuals where each injection was considered as an incident without an underlying distribution.
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RESULTS |
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While methamphetamine can be swallowed, snorted, or smoked, a high proportion of the case-patients (n = 11; 84.6 percent) who used it reported injecting it. A common setting for injecting methamphetamine was a small group gathering (two or three people), with one person preparing for the others. Hand washing before preparation was reported to be uncommon. First, methamphetamine was diluted with tap water in a drug-mixing container (a spoon or a cup) and stirred with the tip of a needle. No heating was needed because methamphetamine dissolves well in water. Second, the solution was aspirated with the syringe through a cigarette filter (a "cotton"). Sharing of drug-mixing containers or "cottons" among patients was common. Eight (80 percent) of the 10 injecting case-patients for whom the information was available reported buying their syringes and needles without prescription from pharmacies. The same proportion of these case-patients (80 percent) reported reusing needles and syringes for themselves, but none reported sharing syringes and needles with other people.
Eating food, sharing a bowl of ice cubes, or having sex while gathered to use methamphetamine was reported by 20 percent, 33 percent, and 30 percent of case-patients who used methamphetamine, respectively. Drinking sodas while using methamphetamine was reported by 80 percent of case-patients. Two case-patients reported believing that brown methamphetamine was the source of their infection.
Case-control study
Of the 95 patients reported with laboratory-confirmed hepatitis A with onset dates after April 1, 1997, 19 could not be located, one refused to participate, and 75 (78.9 percent) were interviewed. Of the 75 interviewed, 40 (54.1 percent) reported methamphetamine use in the last 12 months, and 28 (37.3 percent) who reported methamphetamine use during the referent exposure period were included in the case-control study. Of the 62 potential controls who had used methamphetamine in the last 12 months, 34 (54.8 percent) reported methamphetamine use during the referent exposure period. Serum was available from 24 (70.6 percent) of these 34 controls. Of these, 18 (75 percent) were negative for anti-hepatitis A virus and were included in the analysis.
All 18 controls and 14 (50.0 percent) cases were recruited prospectively, while the remaining 14 cases were included retrospectively. The proportion of case-patients who had sought medical care in the emergency room for their hepatitis symptoms did not differ from the proportion of controls recruited in the emergency room (table 2). Cases and controls did not differ with respect to age, sex, county of residence, and many indicators of socioeconomic status; however, case-patients were more likely than controls to have less than 12 years of schooling and to receive food stamps. A majority of case-patients and controls had attended a drug treatment center (table 2).
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In an analysis restricted to the 24 study participants who reported injecting methamphetamine during the referent exposure period, there was no difference in the median number of methamphetamine doses injected (48 vs. 47, p = 0.84). Ten of the 20 case-patients who had injected had used needles or syringes previously used by others (i.e., receptive needle sharing) versus none of the four injecting controls (OR undefined, exact lower limit of the CI: 0.51). When injection events of cases and controls were compared, injection events of cases were less likely to have occurred with a new syringe and needle (OR = 0.16, 95 percent CI: 0.01, 0.7). No other characteristics of injection events differed between cases and controls.
Case-patients were more likely than controls to have used methamphetamine during the referent exposure period with someone who currently had hepatitis A. This association persisted when the analysis was restricted to study participants who had not injected during that time (OR = 17, 95 percent CI: 1.0, 920) or to study participants who did not have household or sexual contact with a case-patient (OR = undefined, lower limit of the 95 percent CI: 1.1).
Case-patients were more likely than controls to have used brown methamphetamine (table 2), even when adjusted for recent methamphetamine use with a case-patient (adjusted OR = 9.5, 95 percent CI: 0.96, 95). Illness onset dates for case-patients who reported use of brown methamphetamine were clustered around the 19th and 20th week of 1997 (figure 2). Use of other specific colors of methamphetamine was not associated with illness.
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DISCUSSION |
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During communitywide outbreaks of hepatitis A, transmission by the fecal-oral route between household or sexual contacts is a major mode of transmission (1). In addition, facilitation of person-to-person transmission of hepatitis A virus via the fecal-oral route by social and environmental conditions associated with lower socioeconomic status has been hypothesized (4
, 19
, 20
). Compared with controls, case-patients more frequently reported household or sexual contact with a case-patient, although these associations were not statistically significant, and by some indicators (e.g., level of education and receiving food stamps), case-patients were of lower socioeconomic status than controls. Using methamphet-amine with a case-patient was associated with an increased risk of hepatitis A, even among users who did not report injections during the referent exposure period. This indicates that transmission by the fecal-oral route may also occur when people gather to swallow, smoke, or snort methamphetamine together.
Percutaneous transmission of hepatitis A virus has been reported among persons who received contaminated clotting factor concentrates or blood units (2, 21
, 22
). This mode of transmission has also been hypothesized to occur among injecting drug users who share needles (2
), but it has been considered to be uncommon because of the short duration of the viremia during hepatitis A virus infection. In this study, 74.1 percent of the case-patients reported injecting methamphetamine during the referent exposure period, and there was a strong association between hepatitis A and methamphetamine injection compared with other routes of administration. In addition, injection events of cases were less likely to have occurred with a new syringe and needle. Thus, for the 10 injectors (50 percent) who reported receptive needle sharing, the source of the percutaneous transmission may have been contamination of the syringe or the needle by the blood of a viremic patient. For the 10 injectors (50 percent) who did not report receptive needle sharing, this source is unlikely. Five of these case-patients reported sharing drug-mixing containers, and five reported sharing of "cottons." These practices, referred to as "indirect sharing" (23
), are more common among injecting drug users than receptive needle sharing and are suspected to lead to transmission of bloodborne pathogens (24
26
). In addition, in the absence of hand washing, sharing of drug-mixing containers and "cottons" may have facilitated fecal contamination of methamphetamine during the manipulation that preceded injection.
There was an association in univariate analysis between using brown methamphetamine and hepatitis A, and the onset dates of case-patients who reported using this product were clustered. These findings suggested that a small common source outbreak associated with a batch of brown methamphetamine contaminated with hepatitis A virus may have occurred. However, in multivariate analysis, this association was not statistically significant. One published report from Sweden is compatible with the occurrence of such a cluster (14). No information was available on the manufacturing process used for the brown methamphetamine, and no information was available to suggest a relation between the brown color of the methamphetamine and a hypothetical fecal contamination. An infected manufacturer could have contaminated a batch of methamphetamine through manipulation of the product during packing or distribution, after the manufacturing process, which would have inactivated hepatitis A virus. However, if a common source cluster associated with brown methamphetamine indeed occurred, the distribution of cases over time and the limited number of case-patients exposed to brown methamphetamine indicate that exposure to this contaminated drug could not have accounted for the majority of cases during the outbreak.
In addition to hepatitis A virus infection, injecting drug users are also at increased risk for infection with human immunodeficiency, hepatitis B, hepatitis C, and hepatitis D viruses (27, 28
). Vaccines effective against hepatitis A and hepatitis B are available. The Advisory Committee on Immunization Practices has recommended hepatitis B vaccination for injecting drug users since 1982 and, since 1996, hepatitis A vaccination for users of illicit drugs (1
, 29
, 30
). However, vaccination programs targeting these populations have encountered barriers, including the cost of vaccine and the difficulties in accessing injecting drug users (31
, 32
). The high proportion of case-patients and controls who had ever attended a drug treatment center in our study suggests that these facilities could be access points to methamphetamine users for long-term vaccination programs.
Our study had limitations. First, because of our small sample size, we had limited statistical power to find statistically significant associations between certain exposures, including brown methamphetamine and household contact with a case-patient. Second, the small number of susceptible controls who had injected methamphetamine limited our ability to study specific risk factors among injectors, such as different injection practices. Third, because controls were recruited among patients visiting certain health care facilities, the control group may not have been representative of all methamphetamine users in the study area. However, cases and controls were recruited from similar health care facilities, and their similarity with respect to demographic characteristics, total number of methamphetamine doses used, and duration of methamphetamine use suggests that they were recruited from the same secondary study base (33). Fourth, because they had hepatitis A, case-patients might have been more likely to recall using methamphetamine with someone who had hepatitis A at the time that they were likely to have been infected. Finally, potential controls who used methamphetamine may have denied it during the interview by the triage nurse. However, case-patients may also have denied methamphetamine use, and the failure to report methamphetamine use probably affected the recruitment of cases and controls in a nondifferential way, so that case-patients and controls were comparable in that they all admitted methamphetamine use.
In addition to the recommended vaccination of illicit drug users against hepatitis A (1, 13
), other measures to prevent hepatitis A virus transmission among methamphetamine users can be proposed. Since transmission occurred from person to person among people who used drugs together, consideration should be given to recommending immune globulin in addition to hepatitis A vaccine for people who used methamphetamine in the previous 2 weeks with hepatitis A patients. Persons who intend to continue using methamphetamine should also be educated about the risk of hepatitis A associated with using drugs with other people. Hands should be washed before drug preparation, and drug-mixing containers, "cottons," syringes, needles, and other injection works should not be shared. Although the effectiveness of needle exchange programs is unclear for the prevention of hepatitis B and C virus infection, they might provide useful settings for provision of safe equipment and education of injecting drug users about the dangers associated with direct and indirect sharing (26
).
In many communitywide outbreaks, a high proportion of case-patients report illicit use of drugs (13). During such outbreaks, reducing hepatitis A virus transmission among drug users through behavior modification and vaccination early in the outbreak may prevent the extension to broader segments of the community (34
). Routine vaccination of methamphetamine users may also help to prevent outbreaks and reduce the overall burden of hepatitis A. However, it is unlikely that sustained nationwide reductions in hepatitis A incidence will occur through short-term programs to control individual communitywide epidemics or vaccination of selected high-risk groups. The initiation of programs of routine vaccination of young children in states and communities with consistently elevated rates of hepatitis A as recommended in 1999 by the Advisory Committee on Immunization Practices will create a high level of population immunity that should produce sustained reductions of hepatitis A incidence over time (30
).
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ACKNOWLEDGMENTS |
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NOTES |
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REFERENCES |
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