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Hepatitis A shifting epidemiology in Latin America
Vaccine 18 (2000) S57±S60
www.elsevier.com/locate/vaccine
Hepatitis A shifting epidemiology in Latin America Jorge Tanaka Biological Division, SmithKline Beecham Biologicals, Av. Insurgentes sur 1605 Ð Piso 20, Col. San Jose Insurgentes, Delegacion Benito Juarez, Mexico City, C.P. 01020, Mexico
Abstract In the past, Latin America was considered to be an area of high endemicity for hepatitis A virus (HAV) infection, with most people infected in early childhood. A seroepidemiological study was recently undertaken in six countries to determine whether this pattern has changed. The highest seroprevalence of antibodies to HAV (anti-HAV) was found in Mexico and the Dominican Republic. Analysis of the dierent age groups showed that at age 6±10 years, 30% of children in Chile and 54±55% in Brazil, Venezuela and Argentina had been infected, compared with almost 70% in Mexico and 80% in the Dominican Republic. At age 11±15 years, nearly 90% in Mexico and 91% in the Dominican Republic had been infected, compared with 54% in Argentina, 62% in Venezuela, 60% in Brazil and 70% in Chile. By age 31±40 years, over 80% of the populations in all six countries had been exposed to HAV. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was signi®cantly higher in females than in males. In Mexico, Argentina and Brazil, anti-HAV seroprevalence was signi®cantly higher in the low socioeconomic groups than in the middle/high socioeconomic groups. The results show that there has been a shift from high to medium endemicity of HAV infection throughout Latin America, which may result in more clinical cases in adolescents and adults and a greater potential for outbreaks. The vaccination strategy for hepatitis A should thus be reviewed. # 2000 Published by Elsevier Science Ltd. All rights reserved. Keywords: Hepatitis A; Latin America; Endemicity; Epidemiology; Risk factors
The endemicity of hepatitis A virus (HAV) infection can be divided into four groups, which have slightly dierent patterns of transmission and infection. . In the high endemicity areas, the incidence varies from low to high, with a peak age of infection in early childhood. The transmission pattern is from person to person and outbreaks are uncommon. . In moderate endemicity areas, the incidence is high and the peak age of infection is in late childhood/ adolescence or in young adults. The transmission pattern is also from person to person, and by food and water. Outbreaks are common. . In low endemicity areas, the incidence is low, with the peak age of infection in young adulthood. Transmission pattern is from person to person and also by food and water. Outbreaks are common. . Finally, in the very low endemicity areas, the disease rate is very low and the peak age of infection is in
adulthood. The transmission pattern is through travellers in these areas, and outbreaks are uncommon. In the past, Latin America was considered a high endemicity area, in common with South-East Asia, India and Africa. It is important to remember that there is only one serotype of HAV, which produces lifelong immunity after infection. Transmission of HAV is usually through the faecal-oral route to close contacts. This is particularly important among food handlers: eating marketplace food is a common source of infection in Latin America. In Latin America, the data on morbidity and mortality due to hepatitis A are incomplete because of insucient information when the disease is noti®ed. For example, it is common for the virus causing the hepatitis to either not be stated or even for the aetiology of the infection not to be investigated. There are,
0264-410X/00/$ - see front matter # 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 2 6 4 - 4 1 0 X ( 9 9 ) 0 0 4 6 6 - 1
S58
J. Tanaka / Vaccine 18 (2000) S57±S60
55.7
Venezuela
81
Mexico
Dominican Republic 58.1
Chile
64.7
Brazil 55
Venezuela 0
10
20
30
40
50
60
70
80
90
Anti-HAV seroprevalence (%) Fig. 1. Seroprevalence of hepatitis A antibodies in Latin America by age group. Source: Unpublished data.
however, data relating to fulminant hepatitis. In Argentina, hepatitis A was responsible for 64% of 70 cases of fulminant hepatic failure in children [1], and in Brazil HAV was also responsible for 30 per 41 cases of severe hepatic failure [2]. The case fatality rate in this last series was 48.7%. Latin American countries show many of the characteristics of developing countries, with migration from rural communities to cities leading to urban areas of low income and social deprivation. Improvements in public health programmes and sanitary conditions have had an impact on the epidemiological patterns of HAV infection in developing economies, and so previous studies showing Latin America to be an area of high endemicity with almost universal infection before the age of 10 years may no longer be valid. This was the rationale for a seroepidemiological study of HAV,
100
Anti-HAV seroprevalence (%)
90
88
80 70 60 50
40 40.5 35.1 30
68.6 53.9
71.1
which was carried out together with the hepatitis B virus (HBV) seroprevalence study. 1. Methods The seroprevalence of antibodies to HAV (antiHAV) and HBV was investigated in Argentina, in four cities in Brazil (Manaus in the North, Rio de Janeiro in the South, Porto Alegre in the West, and Fortaleza in the East), in Santiago in Chile, in the capital city of the Dominican Republic, in several states in the Republic of Mexico, and in Caracas in Venezuela. In total, 12,085 subjects were included (Argentine, 1475; Brazil, 3879; Chile, 496; Dominican Republic, 478; Mexico, 5262; Venezuela, 495). The presence of antiHAV was determined in the blood samples collected.
92.9 79.4 72.8
96.5 85.9
100 97.8 95.3
60.7
Mexico Chile Brazil
31
20
10 11 0 1 5
6 10
11 15
16 20
Age group (years)
21 30
31 40
Fig. 2. Seroprevalence of hepatitis A antibodies in Mexico, Chile and Brazil by age group. Source: Unpublished data.
J. Tanaka / Vaccine 18 (2000) S57±S60 100
98.5
Anti-HAV seroprevalence (%)
90
72 63
50
30
54
6—10
11—15
Dominican Republic Venezuela
70.5 66
62 55 54
98 89 82
82
70
40
97
91
80
60
S59
55
Argentina
39.5 27.3 27.3
20 10 0 1—5
16—20
21—30
31—40
Age group (years) Fig. 3. Seroprevalence of anti-HAV in the Dominican Republic, Venezuela and Argentina by age group. Source: Unpublished data.
2. Results 2.1. Seroprevalence Overall, the highest anti-HAV seroprevalence rates were found in Mexico and the Dominican Republic, with the other four countries' studies all being very similar (Fig. 1). This was re¯ected in the anti-HAV seroprevalence in dierent age groups. Thus, at age 6±10 years, only 30% of the population of Chile had been in contact with HAV, compared with 54% in Brazil. In Mexico, almost 70% of this age group had had contact with the virus (Fig. 2). Nearly 90% of 11±15-year-olds in Mexico had been in contact with the virus, compared with 60% in Brazil and 70% in Chile. In the Dominican Republic, 80% of those aged 6±10 years had been in contact with HAV, compared with just over 50% in Venezuela and Argentina
(Fig. 3). At 11±15 years of age, these proportions had changed little in Venezuela and Argentina, but had risen to over 90% in the Dominican Republic. By the age of 31±40 years, over 80% of the populations in all six countries had been exposed to HAV, rising to 98% in the Dominican Republic. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was signi®cantly higher in females than in males. In Mexico and Argentina, the seroprevalence of anti-HAV was signi®cantly higher in the low socioeconomic groups compared with the middle and high socioeconomic groups (P < 0.001), though in Argentina the dierence between the low and middle group was only marginally signi®cant (P = 0.062). In Brazil, there was a signi®cant dierence in anti-HAV seroprevalence between the low socioeconomic group and the middle/high group (P < 0.001). 2.2. Risk factors
Table 1 Risk factors for HAV infection in Latin America Odds ratio Argentina Drinking outdoor tap water Drinking indoor tap water Brazil Drinking well water Eating marketplace food Chile Eating outdoor meals Mexico Drinking tap water Eating marketplace meals Venezuela Eating food from street vendors Drinking tap water
1.49 1.39 4.64 5.07 2.17 1.04 1.06 1.68 2.65
The strongest risk factors for HAV infection in Latin America were related to water and food (Table 1). In several of these countries, marketplace or street vendors were strongly associated with the risk of HAV infection.
3. Conclusions The ®ndings of this study clearly suggest that the endemicity pattern of HAV infection in Latin America is changing. Comparison with results from about 15 years ago show that the peak of infection now occurs in later childhood or adolescence, rather than in early childhood [3], indicating a shift towards med-
S60
J. Tanaka / Vaccine 18 (2000) S57±S60
ium endemicity. It is not yet clear whether the increasing numbers of cases in adolescents and adults will produce an increase in mortality or an increase in the frequency of outbreaks, but these are dangers that must be borne in mind because of their potentially high social and economic impact. The dierences in seroprevalence of anti-HAV between the lower and higher socioeconomic groups may also increase the potential for outbreaks in some areas. For these reasons, the vaccination strategy for hepatitis A should be reviewed.
References [1] Ramonet M, Ciocca M, Haydee Nunez M, Afazani A, Arusa O, Planes N. Etiology of acute viral hepatitis in a pediatric population. Medicina (B Aires) 1985;45:273±8. [2] Moreira-Silva SF, Frauches DO, Pereira PEL. Hepatite fulminante em crianc° as em vitoÂria, es: observac° aÁo em hospital pediaÂtrico no periodo 1992±97. Rev Soc Bras Med Trop 1998;31(Suppl):S87. [3] Kumate J, Alvizouri AM, Isibasi A. Serologic survey of hepatitis A antibodies in Mexican children. Bull Pan Am Health Organ 1982;16:156±60.
www.elsevier.com/locate/vaccine
Hepatitis A shifting epidemiology in Latin America Jorge Tanaka Biological Division, SmithKline Beecham Biologicals, Av. Insurgentes sur 1605 Ð Piso 20, Col. San Jose Insurgentes, Delegacion Benito Juarez, Mexico City, C.P. 01020, Mexico
Abstract In the past, Latin America was considered to be an area of high endemicity for hepatitis A virus (HAV) infection, with most people infected in early childhood. A seroepidemiological study was recently undertaken in six countries to determine whether this pattern has changed. The highest seroprevalence of antibodies to HAV (anti-HAV) was found in Mexico and the Dominican Republic. Analysis of the dierent age groups showed that at age 6±10 years, 30% of children in Chile and 54±55% in Brazil, Venezuela and Argentina had been infected, compared with almost 70% in Mexico and 80% in the Dominican Republic. At age 11±15 years, nearly 90% in Mexico and 91% in the Dominican Republic had been infected, compared with 54% in Argentina, 62% in Venezuela, 60% in Brazil and 70% in Chile. By age 31±40 years, over 80% of the populations in all six countries had been exposed to HAV. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was signi®cantly higher in females than in males. In Mexico, Argentina and Brazil, anti-HAV seroprevalence was signi®cantly higher in the low socioeconomic groups than in the middle/high socioeconomic groups. The results show that there has been a shift from high to medium endemicity of HAV infection throughout Latin America, which may result in more clinical cases in adolescents and adults and a greater potential for outbreaks. The vaccination strategy for hepatitis A should thus be reviewed. # 2000 Published by Elsevier Science Ltd. All rights reserved. Keywords: Hepatitis A; Latin America; Endemicity; Epidemiology; Risk factors
The endemicity of hepatitis A virus (HAV) infection can be divided into four groups, which have slightly dierent patterns of transmission and infection. . In the high endemicity areas, the incidence varies from low to high, with a peak age of infection in early childhood. The transmission pattern is from person to person and outbreaks are uncommon. . In moderate endemicity areas, the incidence is high and the peak age of infection is in late childhood/ adolescence or in young adults. The transmission pattern is also from person to person, and by food and water. Outbreaks are common. . In low endemicity areas, the incidence is low, with the peak age of infection in young adulthood. Transmission pattern is from person to person and also by food and water. Outbreaks are common. . Finally, in the very low endemicity areas, the disease rate is very low and the peak age of infection is in
adulthood. The transmission pattern is through travellers in these areas, and outbreaks are uncommon. In the past, Latin America was considered a high endemicity area, in common with South-East Asia, India and Africa. It is important to remember that there is only one serotype of HAV, which produces lifelong immunity after infection. Transmission of HAV is usually through the faecal-oral route to close contacts. This is particularly important among food handlers: eating marketplace food is a common source of infection in Latin America. In Latin America, the data on morbidity and mortality due to hepatitis A are incomplete because of insucient information when the disease is noti®ed. For example, it is common for the virus causing the hepatitis to either not be stated or even for the aetiology of the infection not to be investigated. There are,
0264-410X/00/$ - see front matter # 2000 Published by Elsevier Science Ltd. All rights reserved. PII: S 0 2 6 4 - 4 1 0 X ( 9 9 ) 0 0 4 6 6 - 1
S58
J. Tanaka / Vaccine 18 (2000) S57±S60
55.7
Venezuela
81
Mexico
Dominican Republic 58.1
Chile
64.7
Brazil 55
Venezuela 0
10
20
30
40
50
60
70
80
90
Anti-HAV seroprevalence (%) Fig. 1. Seroprevalence of hepatitis A antibodies in Latin America by age group. Source: Unpublished data.
however, data relating to fulminant hepatitis. In Argentina, hepatitis A was responsible for 64% of 70 cases of fulminant hepatic failure in children [1], and in Brazil HAV was also responsible for 30 per 41 cases of severe hepatic failure [2]. The case fatality rate in this last series was 48.7%. Latin American countries show many of the characteristics of developing countries, with migration from rural communities to cities leading to urban areas of low income and social deprivation. Improvements in public health programmes and sanitary conditions have had an impact on the epidemiological patterns of HAV infection in developing economies, and so previous studies showing Latin America to be an area of high endemicity with almost universal infection before the age of 10 years may no longer be valid. This was the rationale for a seroepidemiological study of HAV,
100
Anti-HAV seroprevalence (%)
90
88
80 70 60 50
40 40.5 35.1 30
68.6 53.9
71.1
which was carried out together with the hepatitis B virus (HBV) seroprevalence study. 1. Methods The seroprevalence of antibodies to HAV (antiHAV) and HBV was investigated in Argentina, in four cities in Brazil (Manaus in the North, Rio de Janeiro in the South, Porto Alegre in the West, and Fortaleza in the East), in Santiago in Chile, in the capital city of the Dominican Republic, in several states in the Republic of Mexico, and in Caracas in Venezuela. In total, 12,085 subjects were included (Argentine, 1475; Brazil, 3879; Chile, 496; Dominican Republic, 478; Mexico, 5262; Venezuela, 495). The presence of antiHAV was determined in the blood samples collected.
92.9 79.4 72.8
96.5 85.9
100 97.8 95.3
60.7
Mexico Chile Brazil
31
20
10 11 0 1 5
6 10
11 15
16 20
Age group (years)
21 30
31 40
Fig. 2. Seroprevalence of hepatitis A antibodies in Mexico, Chile and Brazil by age group. Source: Unpublished data.
J. Tanaka / Vaccine 18 (2000) S57±S60 100
98.5
Anti-HAV seroprevalence (%)
90
72 63
50
30
54
6—10
11—15
Dominican Republic Venezuela
70.5 66
62 55 54
98 89 82
82
70
40
97
91
80
60
S59
55
Argentina
39.5 27.3 27.3
20 10 0 1—5
16—20
21—30
31—40
Age group (years) Fig. 3. Seroprevalence of anti-HAV in the Dominican Republic, Venezuela and Argentina by age group. Source: Unpublished data.
2. Results 2.1. Seroprevalence Overall, the highest anti-HAV seroprevalence rates were found in Mexico and the Dominican Republic, with the other four countries' studies all being very similar (Fig. 1). This was re¯ected in the anti-HAV seroprevalence in dierent age groups. Thus, at age 6±10 years, only 30% of the population of Chile had been in contact with HAV, compared with 54% in Brazil. In Mexico, almost 70% of this age group had had contact with the virus (Fig. 2). Nearly 90% of 11±15-year-olds in Mexico had been in contact with the virus, compared with 60% in Brazil and 70% in Chile. In the Dominican Republic, 80% of those aged 6±10 years had been in contact with HAV, compared with just over 50% in Venezuela and Argentina
(Fig. 3). At 11±15 years of age, these proportions had changed little in Venezuela and Argentina, but had risen to over 90% in the Dominican Republic. By the age of 31±40 years, over 80% of the populations in all six countries had been exposed to HAV, rising to 98% in the Dominican Republic. In all of the countries except Brazil and Venezuela, the seroprevalence of anti-HAV was signi®cantly higher in females than in males. In Mexico and Argentina, the seroprevalence of anti-HAV was signi®cantly higher in the low socioeconomic groups compared with the middle and high socioeconomic groups (P < 0.001), though in Argentina the dierence between the low and middle group was only marginally signi®cant (P = 0.062). In Brazil, there was a signi®cant dierence in anti-HAV seroprevalence between the low socioeconomic group and the middle/high group (P < 0.001). 2.2. Risk factors
Table 1 Risk factors for HAV infection in Latin America Odds ratio Argentina Drinking outdoor tap water Drinking indoor tap water Brazil Drinking well water Eating marketplace food Chile Eating outdoor meals Mexico Drinking tap water Eating marketplace meals Venezuela Eating food from street vendors Drinking tap water
1.49 1.39 4.64 5.07 2.17 1.04 1.06 1.68 2.65
The strongest risk factors for HAV infection in Latin America were related to water and food (Table 1). In several of these countries, marketplace or street vendors were strongly associated with the risk of HAV infection.
3. Conclusions The ®ndings of this study clearly suggest that the endemicity pattern of HAV infection in Latin America is changing. Comparison with results from about 15 years ago show that the peak of infection now occurs in later childhood or adolescence, rather than in early childhood [3], indicating a shift towards med-
S60
J. Tanaka / Vaccine 18 (2000) S57±S60
ium endemicity. It is not yet clear whether the increasing numbers of cases in adolescents and adults will produce an increase in mortality or an increase in the frequency of outbreaks, but these are dangers that must be borne in mind because of their potentially high social and economic impact. The dierences in seroprevalence of anti-HAV between the lower and higher socioeconomic groups may also increase the potential for outbreaks in some areas. For these reasons, the vaccination strategy for hepatitis A should be reviewed.
References [1] Ramonet M, Ciocca M, Haydee Nunez M, Afazani A, Arusa O, Planes N. Etiology of acute viral hepatitis in a pediatric population. Medicina (B Aires) 1985;45:273±8. [2] Moreira-Silva SF, Frauches DO, Pereira PEL. Hepatite fulminante em crianc° as em vitoÂria, es: observac° aÁo em hospital pediaÂtrico no periodo 1992±97. Rev Soc Bras Med Trop 1998;31(Suppl):S87. [3] Kumate J, Alvizouri AM, Isibasi A. Serologic survey of hepatitis A antibodies in Mexican children. Bull Pan Am Health Organ 1982;16:156±60.