The Southern Hemisphere contains approximately 10 to 12% of the world's human population and has a lower overall level of industrialization than the Northern Hemisphere. Seroprevalence studies based on detection of IgG antibodies against hepatitis A virus (HAV) are still valid in the Southern Hemisphere because until now there have been no established large-scale anti-HAV vaccination strategies in most countries of that part of the world.
The reported seroprevalence of HAV in the Southern Hemisphere has a wide range, varying from approximately 10 to 70%, depending mainly on sanitation standards and living conditions in the area studied [1-8]. This large variability in infection rates occurs not only between countries but also between regions of the same country, according to the level of economic development in the area [1,9-11]. Recent studies suggest a changing epidemiological pattern in HAV infection throughout the Southern Hemisphere, with a shift from high- to intermediate-prevalence patterns of HAV infection observed in most countries [1,2,7,8].
Data on prevalence patterns of HAV infection in South American countries, stratified by age, socioeconomic conditions, and social categories, are scarce and scattered .
Tapia-Conyer et al, in a multicenter study published in 1999, surveyed the HAV seroprevalence in 6 countries in Latin America . Approximately 12,000 subjects were stratified for age in Mexico (n = 5262), Chile (n = 496), Dominican Republic (n = 478), Brazil (n = 3879), Venezuela (n = 495), and Argentina (n = 1475). The highest rates of seroprevalence were recorded in the Dominican Republic (89%) and Mexico (81%), with lower rates in Brazil (64.7%), Chile (58.1%), Venezuela (55.7%), and Argentina (55%). Remarkably, this study showed that the seroprevalence of HAV in children from South American countries was under 40% in the age group of 1 to 5 years old and under 60% in the age group of 5 to 10 years old (Table 1). These results are significantly different from data generated during the 1980s, when the prevalence of anti-HAV in children under 10 years old approached a mean of 75% in Latin America [12-14]. In 1992, for example, the World Health Organization (WHO) estimated that over 90% of the Brazilian population over age 20 had already been exposed to HAV infection . However, more recent data have shown a reduction of seroprevalence to around 75% in the same age group, indicating a shift from high to intermediate patterns of epidemiology .
| ||TABLE 1. HAV seroprevalence (%) in South American countries by age group |
Similar data were found by Fix et al  in Chile, where HAV had been proven endemic in the past, with a high seroprevalence of anti-HAV antibodies [12,17]. The authors of this more recent study, published in 2002, demonstrated a marked change in the country's epidemiological pattern of HAV, with decreasing prevalence among children . The study showed that the age-standardized prevalence of anti-HAV among residents of the city of Santiago younger than 20 years old and of lower socioeconomic status declined from 54% in 1990 to 41% in 1998. In the agestratified analyses, use of potable water, a sewage system, toilets, and refrigerators were all significantly associated with anti-HAV serological status.
Zacarias et al, in a study published in 2004, surveyed the prevalence of anti-HAV antibodies among a population of medium and high socioeconomic status in a metropolitan area in Chile, with ages ranging from 20 to 49 years . The authors showed susceptibility to HAV infection in 75% of those aged 20 to 29, 54% of those aged 30 to 39, and 28% of those aged 40 to 49, further indicating a shift to an intermediate pattern of seroprevalence, similar to the pattern in other countries in the region.
In the year 2000, Costa-Clemens et al published a Brazilian study of the seroprevalence of IgG anti-HAV antibodies in 3653 subjects across 4 regions of the country: north (n = 569), northeast (n = 374), southeast (n = 1164), and south (n = 257) . The overall prevalence of anti-HAV was 65%, with a highly heterogeneous distribution. There was a higher prevalence in the north (93%) and northeast (76.5%) than in the south (56%) and southeast (56%), probably reflecting the gap in levels of socioeconomic development among these regions. HAV seroprevalence in children was low in this study, except among those who endured poor living conditions. In contrast, among older age groups the prevalence was high irrespective of socioeconomic status (Table 2). Vitral et al also demonstrated a change over time in the prevalence of hepatitis A in the city of Rio de Janeiro, Brazil . They determined the age-specific prevalence of anti-HAV IgG antibodies in 2 different population groups with low socioeconomic status whose serum samples were collected 17 years apart (1978 and 1995). The overall prevalence rate was 66% in 1978 but only 32% in 1995. In children up to the age of 3 the seroprevalence was 88% in 1978, whereas in 1995 it was only 4.5%, increasing to 66% in the group over age 14. Vitral et al concluded that the lower exposure to HAV infection in younger children in the 1995 population was a result of improved environmental hygiene and sanitation. Similarly, Villar et al analyzed sera from 299 school children between 5 to 15 years of age and from 25 school staff members, collected during an outbreak of HAV that occurred in the year 2000 at a rural public school in Rio de Janeiro state . Results showed that more than 60% of the 5-year-old children were still susceptible to HAV. Molecular characterization of hepatitis A virus in this population found HAV strains with genotypes IA and IB. These findings, combined with those of other reports, indicate that some strains have been circulating endemically in Brazil for more than 12 years [20-22].
| ||TABLE 2. Seroprevalence of anti-HAV IgG antibodies in 4 Brazilian regions |
Costa-Mattioli et al also studied the genotypes of HAV strains isolated in Uruguay, Argentina, Chile, and Brazil . Phylogenetic analysis revealed that all strains developed initially from HAV genotype IA. Interestingly, the degree of genetic variability found among the strains isolated in this region seems to be higher in comparison with strains isolated in other parts of the world .
A relationship between HAV seroprevalence and socioeconomic status has been clearly demonstrated in several Brazilian studies. In 1996 in Porto Alegre, southern Brazil, Ferreira et al studied 387 individuals between 1 and 20 years of age, from low (n = 199) and high (n = 188) socioeconomic groups, showing a seroprevalence of anti-HAV IgG antibodies of 51% and 11% respectively (p < .01) .
Similar data were also reported by Gomes in 2004 . Among 462 children in northeast Brazil aged 7 to 14 years, it was observed that those who attended public schools had IgG anti-HAV seroprevalence of 71.5% versus 36.5% observed among those who attended private schools.
Other studies from Brazil also report high rates of HAV seroprevalence associated with low socioeconomic status. Indeed, in 2002 Santos et al, analyzing the pattern of HAV infection in a low-income area of Rio de Janeiro, showed a high overall seroprevalence of anti-HAV IgG antibodies (87%), although almost 50% of subjects under the age of 10 were still susceptible to the infection . In 2006, Almeida et al analyzed the seroprevalence of HAV infection in 891 individuals between the ages of 7 days and 95 years from a community of low socioeconomic status in Bahia state, northeast Brazil . Overall, anti-HAV seropositivity was 86%, ranging from as low as 15.9% under age 4 to 100% over age 70, with intermediate prevalence in other age groups: 5 to 10 years old, 60.8%; 11 to 20 years old, 86%; 21 to 30 years old, 95.5%; 31 to 50 years old, 97.5%; 51 to 70 years old, 98.5%.
In Argentina, the overall prevalence of antibodies against HAV in 3699 children was 52%, with this infection accounting for 93% of cases of acute hepatitis and 20% of liver transplants [28,29]. The impact of socioeconomic status on HAV seroprevalence was also demonstrated in Argentina by Lopez et al . These authors studied 360 middle-class subjects between 10 and 89 years old from Buenos Aires, Argentina, reporting anti-HAV IgG antibodies in 42%. Notably, more than 50% of individuals under 30 years of age were found to be susceptible to HAV infection. The highest percentage of anti-HAV seronegativity (87%) was found in the subgroup of younger people without a history of symptomatic hepatitis and living in houses with more than one bathroom.
In a large population-based study also conducted in Argentina, Gonzalez et al recorded 61,845 and 50,399 new cases of acute hepatitis A during the years 2003 and 2004 respectively . These data indicate an incidence of clinically apparent disease between 139 and 171 per 100,000 persons per year in this country. As expected, there was a high variation of disease frequency among regions with different sanitary and socioeconomic conditions. Thus, in children between 0 and 14 years of age, anti-HAV IgG antibodies were found in 81% of the samples from Tucuman, 64.5% from San Justo, 46.5% from Rosario, and 29% from Buenos Aires.
Montano et al have studied the seroprevalence of HAV infection in 989 children (2 to 14 years of age) and in 1198 adults (18 to 49 years of age) in the city of Montevideo, Uruguay, reporting rates of 27% and 61% respectively . A relationship between anti-HAV seropositivity, deficient socioeconomic conditions, and increasing age was observed.
Although data are scant, HAV infection still appears to be highly endemic throughout Africa except among subpopulations in some areas, such as white people in South Africa . Studies generally show very high prevalence rates, with most people becoming infected in early childhood and with a strong correlation to low socioeconomic status [8,33-36] (Table 3).
| ||TABLE 3. HAV seroprevalence in African countries |
In 1984, Werner et al conducted a study in a rural area of the Democratic Republic of the Congo (formerly known as Zaire) that showed that 90% of all children had antibodies to HAV by the age of 10 . This is probably generally true throughout Africa, again with the exception of South Africa because the levels of prevalence of hepatitis A seem to differ there between black and white populations .
In this regard, Abdool et al reported a community-based HAV sero-epidemiological survey in 1993 with a sample of 782 urban black children from South Africa, aged from newborn to 13 years . By the age of 2 years, 51.2% had anti-HAV IgG antibodies, and by the age of 6, prevalence was almost 100%. In contrast, another study, published by Martin et al in 1994, showed that while almost 100% of black adults in South Africa had anti-HAV antibodies before the age of 20, only 30 to 40% of white adults (individuals working in a virological laboratory and medical students) were anti-HAV-positive by the age of 20, with prevalence rising to about 60% by age 40 to 49 . Thus, for the white population of South Africa, the endemicity is intermediate to low, comparable to that of some countries in South America and even in the developed world.
There is evidence indicating that along the northern coast of Africa, the overall epidemiology of acute viral hepatitis infections has been changing over the last 2 decades.
Indeed, a recent study conducted in the city of Cairo, Egypt, compared the viral causes of acute hepatitis at a major urban referral center with results reported from the same center 20 years earlier. The authors found that acute hepatitis A virus infection increased from 2.1% in 1983 to 34% in 2002 (p < 01) and occurred at older ages, suggesting that this increase could be related to improved sanitary conditions that resulted in delayed exposure to the virus .
In Algeria, data from the late 1980s indicate that the region also had very high prevalence of HAV infection, with a seroepidemiological survey showing anti-HAV antibodies in 96% of individuals, the majority before the age of 10 .
Recent data indicate that the same shift of HAV infection observed in other parts of the Southern Hemisphere is also occurring throughout Southeast Asia. Barzaga  has documented the epidemiology of HAV infection over the last 20 years in this region, showing that a number of countries such as Thailand, Singapore, Malaysia, and the Philippines have shifted from high to moderate and from moderate to low endemicity, with a corresponding increase in the age of exposure from childhood to early adulthood, probably associated with improvements in hygiene, sanitation, and the quality of drinking water (Table 4).
| ||TABLE 4. HAV seroprevalence in Southeast Asia |
Studies from Thailand and the Philippines dating from the late 1970s and early 1980s indicate that over 80% of the population were positive for anti-HAV antibodies by the age of 10 to 15 years. However, studies conducted in the early 1990s showed that the infection was occurring later in life, by age 30 to 40 years, probably as a result of improved sanitary conditions .
A similar trend was observed in somewhat more developed countries such as Malaysia and Singapore, where data from the 1980s showed about 50% seropositivity for anti-HAV antibodies in 10- to 15-yearolds, a level of seropositivity that had shifted to those aged 50 years and older by the early 1990s .
The exact scope of Oceania is defined variously, with interpretations normally including Australia, New Zealand, New Guinea, and various islands of the Malay archipelago. Most of the available data of this region are from Australia and New Zealand (Table 5).
| ||TABLE 5. HAV seroprevalence in Oceania |
Amin et al conducted a cross-sectional survey in 2001 of HAV seroprevalence in a total of 3043 subjects from different regions of Australia and found that 41.1% of the serum samples were positive for anti-HAV IgG antibodies . As elsewhere internationally, seroprevalence was significantly associated with increasing age (p < .001). Northern Australia had the highest seroprevalence (68.8%) and higher annual reported rates (48.7 per 100,000 inhabitants). The authors concluded that about half the Australian population was still susceptible to HAV infection.
In another Australian study, Ferson et al undertook in 1998 a surveillance study of hepatitis A among residents of inner suburbs in eastern Sydney and found that the epidemiology of HAV infection in this area was characterized by very few childhood cases . Indeed, the authors reported that the majority of the cases were related to recurrent epidemics among homosexuals in 1991-1992 and again in 1995-1996, with around 400 to 500 new cases per 100,000 per year in males 25 to 34 years old. In 1994-95 another epidemic was detected in association with injection drug use, with peak rates of 200 per 100,000 per year reported among males 25 to 29 years old and of 64 per 100 000 per year among females 20 to 24 years old.
In New Zealand, Tobias et al  studied 2000 sera obtained from children and young people aged 0 to 21 years as part of a national survey in 1978-79. The overall prevalence of anti-HAV IgG antibodies was 15.4%, increasing throughout childhood and adolescence. Notably, the age-standardized rate for Maoris (indigenous people of New Zealand) was 39.5%, compared to only 16.1% for Europeans. Also, there was a higher prevalence of HAV among children from the north of the country than among those of the south (19.8% and 5.2% respectively).
These data, gathered in a number of countries in the Southern Hemisphere, taken together indicate that in most regions of the South there is an increasing proportion of HAV-susceptible individuals at a time when the virus is clearly still prevalent in these communities. Indeed, several South American countries that had a high prevalence of HAV infection in the past have shifted to intermediate or low endemicity over the last few years, with the higher rates now measured among adults rather than children and adolescents [1,2].
This shift has probably occurred as a result of improvements in sanitary and socioeconomic conditions of the population, as observed in some areas of the Northern Hemisphere [41,42]. Paradoxically, under improved sanitation and living conditions, people escape infection in early childhood and are left susceptible in adolescence and adulthood, when risk of severe disease is higher .
Currently, the great challenge for health care services in the Southern Hemisphere is to develop effective surveillance tools for HAV infection and to implement practices for endemic control, with the aim of reducing the burden of this disease through preventive efforts, including better living conditions and vaccination whenever cost-effective.
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