Journal of Medical Virology 37:127-131 (1992)
Seroprevalence of Hepatitis C Antibody in Peru Kenneth C. Hyams, Irving A. Phillips, Albert0 Yuen Moran, Abelardo Tejada, F. Stephen Wignall, and Joel Escamilla Naval Medical Research Institute, Bethesda, Maryland (K.C.H.); Naval Medical Research Institute Detachment (I.A.P.,J.E.), Hospital Nacional Guillermo A l m n a r a Irigoyen (A.Y.M.), and S a n Marcos Institute of Tropical Medicine (A.T.),Lima,Peru; Navy Environmental and Preventive Medicine Unit No. 6, Pearl Harbor, Hawaii (F.S.W.) The prevalence in Peru of antibody to hepatitis C virus (anti-HCV) was determined i n a survey of populations living in the northern jungle region and in groups at high risk of parenterally and sexually transmitted diseases. All sera were initially screened for anti-HCV using commercial first and second generation ELISAs; repeatedly reactive sera were further verified with a second generation immunoblot assay. Serum samples were also tested by ELISA for HBsAg, anti-HBs, and anti-HBc. None of 2,111 sera obtained in the survey of jungle residents was positive for antiHCV by immunoblot assay. Twelve of 16 HIV-1 antibody positive hemophiliacs, one of 103 HIV-1 antibody positive homosexuals, and three of 602 HIV-1 negative registered female prostitutes were positive for anti-HCV. A high prevalence of total markers of hepatitis B infection was found in all subjects, especially in older subjects and groups at high risk of parenterally and sexually transmitted diseases. The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in high risk groups and suggest that the epidemiology of hepatitis C differs substantially from hepatitis B. 0 1992 Wiley-Liss, Inc.
KEY WORDS: viral hepatitis; non-A, non-B hepatitis; hepatitis C; hepatitis B ____
~~
INTRODUCTION Because of the recent development of serologic assays for hepatitis C virus (HCV), the principal cause of parenterally transmitted non-A, non-B hepatitis, i t is now possible to determine the prevalence and risk factors associated with HCV infection in different populations [Kuo et al., 19891. In developed countries, HCV has been found to be the predominate cause of posttransfusion hepatitis and a common infection in drug abusers and patients with frequent parenteral blood exposure [Alter et al., 1989a; Esteban et al., 1989; van den Hoek et al., 19901. Whether sexual transmission is also a n important route of infection has not been clearly 0 1992 WILEY-LISS, INC.
determined [Alter et al., 1989b; Everhart e t al., 19901. Research in developing countries has found serologic markers of HCV infection much less frequently than markers of hepatitis B infection, although these two viral diseases are thought to share similar modes of transmission [Saeed et al., 1991; Al-Faleh et al., 1991; Jackson et al., 19911. In the current study, the prevalence in Peru of antibody to hepatitis C virus (anti-HCV)was determined in a survey of four populations living in the northern jungle region (an area highly endemic for hepatitis B infection) and in groups a t high risk of parenterally and sexually transmitted diseases.
MATERIALS AND METHODS The study was performed a t the U S . Naval Medical Research Institute Detachment (NAMRID), Lima, Peru, a collaborative Peruvian-United States Navy medical research center. NAMRID and the U S . Naval Medical Research and Development Command's guidelines for the protection of human subjects were followed in the conduct of this study. Survey of Jungle Residents Serum samples obtained between 1986 and 1988 prior to initiating a hepatitis B vaccine program in the northern jungle were tested for anti-HCV. Four male populations were surveyed: 1)361 indigenous villagers living in the Amazonas region of Peru; 2) 411 soldiers and 41 villagers living in the El-Milagro region; 3) 403 persons living in Iquitos (a large urban center); and, 4) 895 oilfield workers who had been born in all regions of Peru but were currently working in the northern jungle. All of these populations were at low risk of malaria infection, mainly Plasmodium v i v a . In each of these surveys of hepatitis B infection, subjects were tested by enzyme-linked immunosorbent assays (ELISA) for HBsAg, anti-HBs, and total anti-HBc; HBsAg positive sera were additionally tested for total antibody to delta virus (Abbott Laboratories, North
Accepted for publication November 29,1991. Address reprint requests to Dr K. Craig Hyams, NMRI, 12300 Washington Avenue, Rockville, MD 20852.
128
Hyams et al.
years), and belonged to Mestizo (81%)or Amerindian (15%)racialiethnic groups. Sixty-seven (3.2%) serum samples were repeatedly reactive by ELISA for anti-HCV (mean optical density ratio, 0.8).However, by immunoblot assay none of these sera tested positive or indeterminate for anti-HCV. In contrast, 34 (1.6%) sera were positive for HBsAg, and High Risk Group Survey 525 (24.9%)were positive for either antigen or antibody markers of hepatitis B infection. Three of 34 HBsAg As part of the Peruvian Ministry of Health's AIDS positive samples were also positive for antibody to delta prevention program, NAMRID has tested serum samvirus. ples from more than 70,000 blood donors and high risk There was a steady rise in the prevalence of total groups for human immunodeficiency virus type 1 (HIV-1)[Phillips et al., 19911. The sera from 305 indi- hepatitis B seropositivity with age; however, the prevaviduals (mean age, 32 years; 86% male) found since lence of HBsAg decreased with increasing age (Table I). 1987 to be HIV-1 antibody positive by Western blot In bivariate analysis, markers of hepatitis B infection were most common in the Amerindian racialiethnic were tested for anti-HCV. Two HIV-1 antibody negative groups were also tested group, in subjects born in jungle regions, and in manual for anti-HCV: 1) 602 registered female prostitutes laborers (Tables I, 11).All three anti-delta positive sub(mean age, 34 years) working in Callao, Peru, and 2) jects were soldiers who had been born in the northern 148 Peruvian Navy Hospital employees. Callao, the jungle region of Peru. Serologic markers of hepatitis B principal port city of Peru, is part of metropolitan Lima. infection were more frequently found in the 188 subSurveyed hospital employees included both profes- jects with a history of acute jaundice than in other sional staff who were exposed to patients and blood study subjects (44.1% vs. 23.76, P < .001). Evaluation of age, racelethnicity, birth location, and products and support personnel without regular blood occupation by multivariate analysis demonstrated a n exposure. independent association between seropositivity for any hepatitis B marker and age, Amerindian racei Hepatitis C Tests ethnicity, birth in jungle regions, and military occupaAll sera, which had been stored at -7O"C, were ini- tion (Table 111). Too few subjects were positive for tially screened for anti-HCV using commercial first HBsAg to evaluate this marker alone in multivariate generation ELISA test kits (Abbott). Sera repeatedly analysis. reactive by ELISA were further verified with a second generation immunoblot assay (CHIRON RIBA HCV High Risk Group Survey TEST SYSTEM; Chiron Corporation; Emeryville, CA) Among 305 HIV-1 antibody positive subjects, 13 [van der Poel et al., 19911. In addition, the 305 HIV-1 (4.3%) were anti-HCV positive by immunoblot assay positive study subjects were screened for anti-HCV and six sera yielded indeterminate results. Anti-HCV with a second generation ELISA assay (Abbott) and was found in 12 of 16 hemophiliacs and in one of 103 reactive samples were again verified by immunoblot male homosexuals (Table IV). The second generation assay (Chiron).The ELISA optical density ratio (mean anti-HCV ELISA assay did not identify any immunotest optical densityicutoff optical density) was calcu- blot positive serum samples not detected using the first lated a s previously described [van der Poel e t al., 19901. generation ELISA assay. Chicago, IL). Standardized questionnaires were administered in these surveys which elicited basic demographic information, including birth location. Birth locations were grouped into the urban area of Lima and three distinctive geographic regions: Pacific coast, mountains, and jungle.
Statistical Analysis Proportions were compared using the X2 test with Yates' correction or Fisher's exact test. Multiple logistic regression analysis was performed using the SPSSiPC statistical package (SPSSInc., Chicago, IL). A final logistic model was developed using the maximumlikelihood method and a forward selection process. The outcome variable for logistic analysis was the presence or absence of any serologic marker of hepatitis B virus infection. Adjusted odds ratios (OR) were reported with 95% confidence intervals (95% GI). Significance was set a t the ,051level. RESULTS Survey of Jungle Residents There was a total of 2,111 male Peruvians tested for anti-HCV in the survey of jungle residents. Most subjects were adults (mean age, 27 years; range, 14-80
Of 602 HIV-1 negative registered female prostitutes, three (0.5%)were positive for anti-HCV by immunoblot assay and a n indeterminate result was observed for one sample (Table IV). None of 183 hospital employees was positive for anti-HCV. A high prevalence of hepatitis B seropositivity was found in all high risk groups (Table IV).
DISCUSSION The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in groups a t high risk of parenterally and sexually transmitted diseases, particularly hemophiliacs. High levels of anti-HCV have been found in hemophiliacs living in other countries INoel et al., 1989; Rumi et al., 1990; Chen e t al., 19901. Hemophiliacs are at increased risk of infection because they receive blood products derived from multiple donors. In Peru, hemophiliacs are primarily treated with blood transfusions
Hepatitis C in Peru
129
TABLE I. Prevalence of Anti-HCV, HBsAg, and Total Hepatitis B Seropositivity by Age, Race/Ethnicity, and Birth Region in a Survey of 2,111 Male Peruvians Living in the Northern Jungle
Characteristic Age 11-20 years 21-30 years 31-40 years >40 years Race/ethnicity Mestizo Amerindian Caucasian Other Birth Region Jungle Mountain Pacific coast Lima
No.
Percent (number) Dositive Hepatitis B Anti-HCVa HBsAg seropositivity b
1,082 259 497 273
0 0 0 0
2.2 (24) 1.5 (4) 1.0 (5) 0.4 (1)
17.3 (187) 20.5 (53) 34.0 (169) 42.5 (116)
1,706 319 46 18
0 0 0 0
1.5(26) 2.2 (7) 0 5.6 (1)
24.4 (416) 29.5 (94) 17.4 (8) 16.7 (3)
1,220 454 239 198
0 0 0 0
1.4 (17) 2.6 (12) 2.1 (5) 0 (0)
30.2 (369) 13.9 (63) 22.2 (53) 20.2 (40)
"Positive for anti-HCV by immunoblot assay. bPositive for HBsAg, anti-HBs, or anti-HBc.
TABLE 11. Prevalence of Anti-HCV, HBsAg, and Hepatitis B Seropositivity by Occupation in a Survey of 2,111 Male Peruvians Living in the Northern Jungle
Occupation Farmer Oilfield worker Military Unemployed Manual laborer Student
No. 437 427 411 409 352 75
Percent (number) positive Hepatitis B Anti-HCV" HBsAg seropositivityb 0 1.1 (5) 17.6 (77) 0 0.7 (3) 29.5 (126) 0 4.4 (18) 21.2 (87) 0 1.7 (7) 21.8 (89) 0 0.3 (1) 36.6 (129) 0 0 22.7 (17)
"Positive for anti-HCV by immunoblot assay. bPositive for HBsAg, anti-HBs, or anti-HBc.
TABLE 111. Final Multivariate Model With Variables Independently Associated With Seropositivity for Any Hepatitis B Marker* Independent variablesa
OR
95% CI
P-value
Age (by 10-year increments) Race/ethnicity (referent mestizo) Amerindian Birth region (referent Lima) Jungle Occupation (referent unemployed) Military
1.8
1.6-2.1
Seroprevalence of Hepatitis C Antibody in Peru Kenneth C. Hyams, Irving A. Phillips, Albert0 Yuen Moran, Abelardo Tejada, F. Stephen Wignall, and Joel Escamilla Naval Medical Research Institute, Bethesda, Maryland (K.C.H.); Naval Medical Research Institute Detachment (I.A.P.,J.E.), Hospital Nacional Guillermo A l m n a r a Irigoyen (A.Y.M.), and S a n Marcos Institute of Tropical Medicine (A.T.),Lima,Peru; Navy Environmental and Preventive Medicine Unit No. 6, Pearl Harbor, Hawaii (F.S.W.) The prevalence in Peru of antibody to hepatitis C virus (anti-HCV) was determined i n a survey of populations living in the northern jungle region and in groups at high risk of parenterally and sexually transmitted diseases. All sera were initially screened for anti-HCV using commercial first and second generation ELISAs; repeatedly reactive sera were further verified with a second generation immunoblot assay. Serum samples were also tested by ELISA for HBsAg, anti-HBs, and anti-HBc. None of 2,111 sera obtained in the survey of jungle residents was positive for antiHCV by immunoblot assay. Twelve of 16 HIV-1 antibody positive hemophiliacs, one of 103 HIV-1 antibody positive homosexuals, and three of 602 HIV-1 negative registered female prostitutes were positive for anti-HCV. A high prevalence of total markers of hepatitis B infection was found in all subjects, especially in older subjects and groups at high risk of parenterally and sexually transmitted diseases. The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in high risk groups and suggest that the epidemiology of hepatitis C differs substantially from hepatitis B. 0 1992 Wiley-Liss, Inc.
KEY WORDS: viral hepatitis; non-A, non-B hepatitis; hepatitis C; hepatitis B ____
~~
INTRODUCTION Because of the recent development of serologic assays for hepatitis C virus (HCV), the principal cause of parenterally transmitted non-A, non-B hepatitis, i t is now possible to determine the prevalence and risk factors associated with HCV infection in different populations [Kuo et al., 19891. In developed countries, HCV has been found to be the predominate cause of posttransfusion hepatitis and a common infection in drug abusers and patients with frequent parenteral blood exposure [Alter et al., 1989a; Esteban et al., 1989; van den Hoek et al., 19901. Whether sexual transmission is also a n important route of infection has not been clearly 0 1992 WILEY-LISS, INC.
determined [Alter et al., 1989b; Everhart e t al., 19901. Research in developing countries has found serologic markers of HCV infection much less frequently than markers of hepatitis B infection, although these two viral diseases are thought to share similar modes of transmission [Saeed et al., 1991; Al-Faleh et al., 1991; Jackson et al., 19911. In the current study, the prevalence in Peru of antibody to hepatitis C virus (anti-HCV)was determined in a survey of four populations living in the northern jungle region (an area highly endemic for hepatitis B infection) and in groups a t high risk of parenterally and sexually transmitted diseases.
MATERIALS AND METHODS The study was performed a t the U S . Naval Medical Research Institute Detachment (NAMRID), Lima, Peru, a collaborative Peruvian-United States Navy medical research center. NAMRID and the U S . Naval Medical Research and Development Command's guidelines for the protection of human subjects were followed in the conduct of this study. Survey of Jungle Residents Serum samples obtained between 1986 and 1988 prior to initiating a hepatitis B vaccine program in the northern jungle were tested for anti-HCV. Four male populations were surveyed: 1)361 indigenous villagers living in the Amazonas region of Peru; 2) 411 soldiers and 41 villagers living in the El-Milagro region; 3) 403 persons living in Iquitos (a large urban center); and, 4) 895 oilfield workers who had been born in all regions of Peru but were currently working in the northern jungle. All of these populations were at low risk of malaria infection, mainly Plasmodium v i v a . In each of these surveys of hepatitis B infection, subjects were tested by enzyme-linked immunosorbent assays (ELISA) for HBsAg, anti-HBs, and total anti-HBc; HBsAg positive sera were additionally tested for total antibody to delta virus (Abbott Laboratories, North
Accepted for publication November 29,1991. Address reprint requests to Dr K. Craig Hyams, NMRI, 12300 Washington Avenue, Rockville, MD 20852.
128
Hyams et al.
years), and belonged to Mestizo (81%)or Amerindian (15%)racialiethnic groups. Sixty-seven (3.2%) serum samples were repeatedly reactive by ELISA for anti-HCV (mean optical density ratio, 0.8).However, by immunoblot assay none of these sera tested positive or indeterminate for anti-HCV. In contrast, 34 (1.6%) sera were positive for HBsAg, and High Risk Group Survey 525 (24.9%)were positive for either antigen or antibody markers of hepatitis B infection. Three of 34 HBsAg As part of the Peruvian Ministry of Health's AIDS positive samples were also positive for antibody to delta prevention program, NAMRID has tested serum samvirus. ples from more than 70,000 blood donors and high risk There was a steady rise in the prevalence of total groups for human immunodeficiency virus type 1 (HIV-1)[Phillips et al., 19911. The sera from 305 indi- hepatitis B seropositivity with age; however, the prevaviduals (mean age, 32 years; 86% male) found since lence of HBsAg decreased with increasing age (Table I). 1987 to be HIV-1 antibody positive by Western blot In bivariate analysis, markers of hepatitis B infection were most common in the Amerindian racialiethnic were tested for anti-HCV. Two HIV-1 antibody negative groups were also tested group, in subjects born in jungle regions, and in manual for anti-HCV: 1) 602 registered female prostitutes laborers (Tables I, 11).All three anti-delta positive sub(mean age, 34 years) working in Callao, Peru, and 2) jects were soldiers who had been born in the northern 148 Peruvian Navy Hospital employees. Callao, the jungle region of Peru. Serologic markers of hepatitis B principal port city of Peru, is part of metropolitan Lima. infection were more frequently found in the 188 subSurveyed hospital employees included both profes- jects with a history of acute jaundice than in other sional staff who were exposed to patients and blood study subjects (44.1% vs. 23.76, P < .001). Evaluation of age, racelethnicity, birth location, and products and support personnel without regular blood occupation by multivariate analysis demonstrated a n exposure. independent association between seropositivity for any hepatitis B marker and age, Amerindian racei Hepatitis C Tests ethnicity, birth in jungle regions, and military occupaAll sera, which had been stored at -7O"C, were ini- tion (Table 111). Too few subjects were positive for tially screened for anti-HCV using commercial first HBsAg to evaluate this marker alone in multivariate generation ELISA test kits (Abbott). Sera repeatedly analysis. reactive by ELISA were further verified with a second generation immunoblot assay (CHIRON RIBA HCV High Risk Group Survey TEST SYSTEM; Chiron Corporation; Emeryville, CA) Among 305 HIV-1 antibody positive subjects, 13 [van der Poel et al., 19911. In addition, the 305 HIV-1 (4.3%) were anti-HCV positive by immunoblot assay positive study subjects were screened for anti-HCV and six sera yielded indeterminate results. Anti-HCV with a second generation ELISA assay (Abbott) and was found in 12 of 16 hemophiliacs and in one of 103 reactive samples were again verified by immunoblot male homosexuals (Table IV). The second generation assay (Chiron).The ELISA optical density ratio (mean anti-HCV ELISA assay did not identify any immunotest optical densityicutoff optical density) was calcu- blot positive serum samples not detected using the first lated a s previously described [van der Poel e t al., 19901. generation ELISA assay. Chicago, IL). Standardized questionnaires were administered in these surveys which elicited basic demographic information, including birth location. Birth locations were grouped into the urban area of Lima and three distinctive geographic regions: Pacific coast, mountains, and jungle.
Statistical Analysis Proportions were compared using the X2 test with Yates' correction or Fisher's exact test. Multiple logistic regression analysis was performed using the SPSSiPC statistical package (SPSSInc., Chicago, IL). A final logistic model was developed using the maximumlikelihood method and a forward selection process. The outcome variable for logistic analysis was the presence or absence of any serologic marker of hepatitis B virus infection. Adjusted odds ratios (OR) were reported with 95% confidence intervals (95% GI). Significance was set a t the ,051level. RESULTS Survey of Jungle Residents There was a total of 2,111 male Peruvians tested for anti-HCV in the survey of jungle residents. Most subjects were adults (mean age, 27 years; range, 14-80
Of 602 HIV-1 negative registered female prostitutes, three (0.5%)were positive for anti-HCV by immunoblot assay and a n indeterminate result was observed for one sample (Table IV). None of 183 hospital employees was positive for anti-HCV. A high prevalence of hepatitis B seropositivity was found in all high risk groups (Table IV).
DISCUSSION The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in groups a t high risk of parenterally and sexually transmitted diseases, particularly hemophiliacs. High levels of anti-HCV have been found in hemophiliacs living in other countries INoel et al., 1989; Rumi et al., 1990; Chen e t al., 19901. Hemophiliacs are at increased risk of infection because they receive blood products derived from multiple donors. In Peru, hemophiliacs are primarily treated with blood transfusions
Hepatitis C in Peru
129
TABLE I. Prevalence of Anti-HCV, HBsAg, and Total Hepatitis B Seropositivity by Age, Race/Ethnicity, and Birth Region in a Survey of 2,111 Male Peruvians Living in the Northern Jungle
Characteristic Age 11-20 years 21-30 years 31-40 years >40 years Race/ethnicity Mestizo Amerindian Caucasian Other Birth Region Jungle Mountain Pacific coast Lima
No.
Percent (number) Dositive Hepatitis B Anti-HCVa HBsAg seropositivity b
1,082 259 497 273
0 0 0 0
2.2 (24) 1.5 (4) 1.0 (5) 0.4 (1)
17.3 (187) 20.5 (53) 34.0 (169) 42.5 (116)
1,706 319 46 18
0 0 0 0
1.5(26) 2.2 (7) 0 5.6 (1)
24.4 (416) 29.5 (94) 17.4 (8) 16.7 (3)
1,220 454 239 198
0 0 0 0
1.4 (17) 2.6 (12) 2.1 (5) 0 (0)
30.2 (369) 13.9 (63) 22.2 (53) 20.2 (40)
"Positive for anti-HCV by immunoblot assay. bPositive for HBsAg, anti-HBs, or anti-HBc.
TABLE 11. Prevalence of Anti-HCV, HBsAg, and Hepatitis B Seropositivity by Occupation in a Survey of 2,111 Male Peruvians Living in the Northern Jungle
Occupation Farmer Oilfield worker Military Unemployed Manual laborer Student
No. 437 427 411 409 352 75
Percent (number) positive Hepatitis B Anti-HCV" HBsAg seropositivityb 0 1.1 (5) 17.6 (77) 0 0.7 (3) 29.5 (126) 0 4.4 (18) 21.2 (87) 0 1.7 (7) 21.8 (89) 0 0.3 (1) 36.6 (129) 0 0 22.7 (17)
"Positive for anti-HCV by immunoblot assay. bPositive for HBsAg, anti-HBs, or anti-HBc.
TABLE 111. Final Multivariate Model With Variables Independently Associated With Seropositivity for Any Hepatitis B Marker* Independent variablesa
OR
95% CI
P-value
Age (by 10-year increments) Race/ethnicity (referent mestizo) Amerindian Birth region (referent Lima) Jungle Occupation (referent unemployed) Military
1.8
1.6-2.1
