Prevalence of hepatitis A virus infection: the paradoxical example of isolated communities in the western Brazilian Amazon region.

This study evaluated the prevalence of hepatitis A virus infection in the rural area of Lábrea, in the western Brazilian Amazon region. Communities and households were selected randomly. Serum samples were analyzed by means of the immunoenzymatic method for the presence of total antibodies against HAV. The study included 1,499 individuals. The prevalence of anti-HAV was 74.6% (95% CI 72.3-76.8). Univariate analysis showed associations with age (chi-square for linear trend = 496.003, p < 0.001), presence of outside toilet (p < 0.001), history of hepatitis (p < 0.001) and family history of hepatitis (p = 0.05). After adjusting for age, HAV infection also showed an association with the number of people in the family (p = 0.03). The overall prevalence rates were high, but not more than 60% of the children under the age of ten years had already been infected. Very high prevalence was detected only within older cohorts, thus paradoxically defining this as a region with intermediate endemicity, even under the conditions of poverty encountered.

Prevalence of hepatitis A virus infection: the paradoxical example of isolated communities in the western Brazilian Amazon region / Prevalência da infecção pelo vírus da hepatite A: o exemplo paradoxal de comunidades isoladas na região Amazônica Ocidental Brasileira

This study evaluated the prevalence of hepatitis A virus infection in the rural area of Lábrea, in the western Brazilian Amazon region. Communities and households were selected randomly. Serum samples were analyzed by means of the immunoenzymatic method for the presence of total antibodies against HAV. The study included 1,499 individuals. The prevalence of anti-HAV was 74.6 percent (95 percent CI 72.3-76.8). Univariate analysis showed associations with age (chi-square for linear trend = 496.003, p < 0.001), presence of outside toilet (p < 0.001), history of hepatitis (p < 0.001) and family history of hepatitis (p = 0.05). After adjusting for age, HAV infection also showed an association with the number of people in the family (p = 0.03). The overall prevalence rates were high, but not more than 60 percent of the children under the age of ten years had already been infected. Very high prevalence was detected only within older cohorts, thus paradoxically defining this as a region with intermediate endemicity, even under the conditions of poverty encountered.

Este estudo avaliou a prevalência de infecção pelo vírus da hepatite A na área rural de Lábrea, Amazônia Ocidental Brasileira. Comunidades e domicílios foram selecionados aleatoriamente. Amostras de soro foram analisadas pelo método imunoenzimático para os anticorpos totais contra o vírus da hepatite A. O estudo incluiu 1.499 indivíduos. A prevalência do anti-HAV foi 74,6 por cento (IC 95 por cento 72,3 a 76,8). Análise univariada mostrou associação com idade (qui-quadrado de tendência linear = 496,003, p<0,001), presença de sanitário fora do domicílio (p<0,001), passado de hepatite (p<0,001) e história familiar de hepatite (p=0,05). Depois de controlado por idade, a infecção pelo VHA mostrou também associação com o número de pessoas na família (p=0,03). A prevalência global mostra taxas elevadas, entretanto não mais do que 60 por cento dos menores de 10 anos, já são infectados, e prevalências elevadas são detectadas em coortes de mais idade, mostrando paradoxalmente uma definição de região de endemicidade intermediária, mesmo nas condições de pobreza encontradas.

ATP-induced apoptosis involves a Ca2+-independent phospholipase A2 and 5-lipoxygenase in macrophages.

Macrophages express P2X(7) and other nucleotide (P2) receptors, and display the phenomena of extracellular ATP (ATP(e))-induced P2X(7)-dependent membrane permeabilization and cell death by apoptosis and necrosis. P2X(7) receptors also cooperate with toll-like receptors (TLRs) to induce inflammasome activation and IL-1beta secretion. We investigated signaling pathways involved in the induction of cell death by ATP(e) in intraperitoneal murine macrophages. Apoptosis (hypodiploid nuclei) and necrosis (LDH release) were detected 6h after an induction period of 20 min in the presence of ATP. Apoptosis was blocked by caspase 3 and caspase 9 inhibitors and by cyclosporin A. The MAPK inhibitors PD-98059, SB-203580 and SB-202190 provoked no significant effect on apoptosis, but SB-203580 blocked LDH release. Neither apoptosis nor necrosis was inhibited when both intra- and extracellular Ca(2+) were chelated during the induction period. Mepacrine, a generic PLA(2) inhibitor and BEL, an inhibitor of Ca(2+)-independent PLA(2) (iPLA(2)) blocked apoptosis, while pBPB and AACOOPF(3), inhibitors of secretory and Ca(2+)-dependent PLA(2) respectively, had no significant effect. Cycloxygenase inhibitors had no effect on apoptosis, while the inhibitors of lipoxygenase (LOX) and leukotriene biosynthesis nordihydroguaiaretic acid (NDGA), zileuton, AA-861, and MK-886 significantly decreased apoptosis. Neither NDGA nor MK-886 blocked apoptosis of 5-LOX(-/-) macrophages. CP-105696 and MK-571, antagonists of leukotriene receptors, had no significant effect on apoptosis. None of the inhibitors of PLA(2) and LOX/leukotriene pathway had a significant inhibitory effect on LDH release. Our results indicate that a Ca(2+)-independent step involving an iPLA(2) and 5-LOX are involved in the triggering of apoptosis but not necrosis by P2X(7) in macrophages.