Seroprevalence of Trypanosoma cruzi infection in three rural communities in Guatemala.

A systematic, house-based serological survey for Trypanosoma cruzi seroreactivity was conducted in three contiguous communities in Olopa municipality, Chiquimula Department, Guatemala. Blood samples from a total of 292 individuals in 63 households were examined by enzyme-linked immunosorbent assay. The seropositive rate ranged from 0% to 20.8% for the three communities, with a mean of 15.1%. Log-linear models showed that seroprevalence was significantly related to age (P < 0.005) but not to sex. However, when the age group with the lowest prevalence (1-9 years) was excluded from the analysis, age was not a significant factor (P = 0.55). Data from a stratified sample collected at the same time were combined with those of the systematic sample to analyze the relationship between seropositivity and possible explanatory variables. Log-linear models, based on 586 individuals in 129 households from the two surveys, revealed a significant positive association between seropositivity and thatched roofs (P = 0.01).

Schistosoma mansoni: relationship of tumor necrosis factor-alpha to morbidity and collagen deposition in chronic experimental infection.

Chronic (20-week) Schistosoma mansoni infections in male CBA/J mice present as one of two pathophysiologic forms: severe hypersplenomegaly syndrome (HSS) or a less severe, moderate splenomegaly syndrome (MSS). HSS mice are cachectic (including anemia and hypertriglyceridemia) and exhibit high levels of periportal and perioval fibrosis. Because tumor necrosis factor-alpha (TNF-alpha) is associated with the symptoms of cachexia, we measured TNF-alpha protein and mRNA levels in the livers of infected and uninfected animals. TNF-alpha levels in liver homogenates from mice with acute infections (8-week) were high (mean +/- SEM; 41.0 +/- 1.6 ng/g tissue) and remained high in livers of HSS mice (41.8 +/- 3.0 ng/g tissue) while TNF-alpha levels in liver homogenates of MSS mice were significantly lower (27.9 +/- 2.0 ng/g tissue). Similarly, hepatic TNF-alpha mRNA levels from HSS mice were two- to threefold higher than those from MSS mice. Hydroxyproline levels in these animals were determined as a measure of collagen deposition and fibrosis and showed increased overall levels in the livers of HSS animals. To investigate the progression of HSS development, hematocrit and serum triglyceride levels were followed over a 20-week period after infection. In mice that developed HSS, hematocrit levels decreased significantly and progressively from Weeks 10 through 20. These same animals showed significant increases in serum triglycerides compared to 8-week-infected mice or the mice which developed MSS over the same time period. These results suggest that failure to downregulate hepatic production of TNF-alpha correlates with, and may contribute to, the development of liver fibrosis and HSS in experimental schistosomiasis.

Early development and progression of lymphocyte-stimulatory cross-reactive idiotypes expressed on antibodies to soluble egg antigens during Schistosoma mansoni infection of mice.

Idiotypes (Id) that stimulate immunoregulatory anti-Id T lymphocyte proliferation are expressed on murine and human antibodies (Ab) to soluble egg antigens (SEA) of Schistosoma mansoni. Kinetics of early expression of these stimulatory Id have now been studied using immunoaffinity-purified serum anti-SEA Ab from mice infected with S. mansoni for 6, 7, 8, 12, or 16 weeks. Rabbit anti-Id Ab specific for mouse anti-SEA Id expressed at 8 weeks post-infection (anti-8WkId) demonstrated the strongest interactions with Id present at 7 and 8 weeks post-infection by competitive enzyme-linked immunosorbent assay. Anti-8WkId Ab reacted progressively less well with 12 WkId, 6WkId, and 16WkId. Splenocytes from mice infected for 8 weeks demonstrated the highest blast transformation responses in vitro to anti-SEA Id from mice infected for 6 weeks, while 7, 8, 12, and 16 weeks post-infection Id preparations stimulated progressively less proliferation. These data indicate that although eventual Id-associated immunoregulatory events contribute to chronicity in this disease, production of anti-SEA Ab that express stimulatory cross-reactive immunoregulatory Id comprises a substantial portion of the initial, acute anti-SEA response in mice infected with Schistosoma mansoni. Furthermore, either this particular Id-expressing response is not maintained, or its proportional presence is greatly diminished by the cumulative production of other multiple anti-SEA Ab during the establishment of chronicity, perhaps in response to its immunoregulatory influence very early in infection.

Two distinct pathological syndromes in male CBA/J inbred mice with chronic Schistosoma mansoni infections.

Humans chronically infected with Schistosoma mansoni most commonly present with the relatively asymptomatic intestinal form of the disease, whereas a small minority develop hepatosplenism characterized by severe hepatic disease with portal hypertension. Investigation of hypotheses describing the pathogenic mechanisms underlying the clinical forms of the human disease has been limited by the absence of an animal model that predictably develops such a spectrum of disease. We report that inbred male CBA/J mice that are chronically infected with S. mansoni develop two distinct syndromes, hypersplenomegaly syndrome (HSS) and moderate splenomegaly syndrome (MSS). Pathologically and immunologically, MSS and HSS remarkably parallel the intestinal and hepatosplenic clinical forms, respectively, in humans. HSS affects approximately 20% of these mice and consists of massive splenomegaly, ascites, thymic atrophy, severe anemia, and cachexia. The remaining majority of mice with MSS develop moderate splenomegaly only. Histopathological features of HSS include 1) relatively extensive hepatic fibrosis and granulomatous inflammation, 2) splenic congestion, 3) lymph node plasmacytosis, and 4) worms and eggs in the pulmonary vasculature. Immunologically, the idiotypes present on antisoluble egg antigen antibodies from HSS mice are distinct from those from mice with acute infections or the chronic MSS infection. These idiotypic differences are similar to those observed in patients with intestinal and hepatosplenic forms of the disease and may have regulatory importance. Investigation of the cellular and molecular events that lead to the development of MSS and HSS may advance current understanding of the pathogenesis of the clinical forms of chronic schistosomiasis in humans.