Periportal fibrosis, liver and spleen sizes among S. mansoni mono or co-infected individuals with human immunodeficiency virus-1 in fishing villages along Lake Victoria shores, North-Western, Tanzania

Mazigo et al. Parasites & Vectors Periportal fibrosis, liver and spleen sizes among S. mansoni mono or co-infected individuals with human immunodeficiency virus-1 in fishing villages along Lake Victoria shores, North-Western, Tanzania Humphrey D Mazigo 0 1 David W Dunne Domenica Morona 1 Therese E Lutufyo 1 Safari M Kinung'hi Geofrey Kaatano Fred Nuwaha 0 0 Department of Disease Control and Environmental Health, School of Public Health, College of Health Sciences, Makerere University , P.O. Box 7072, Kampala , Uganda 1 Department of Medical Parasitology and Entomology, School of Medicine, Catholic University of Health and Allied Sciences , P.O. Box 1464, Mwanza , Tanzania Background: The pathogenesis of S. mansoni infection involves chronic inflammatory responses to parasite eggs which can be associated with a characteristic periportal fibrosis (PPF) and the progression to severe hepatosplenic disease. The effects of HIV-1 co-infection and the influence of CD4+ cell numbers on these clinical manifestations of chronic S. mansoni are not known. To understand the effects of HIV-1 co-infection on these morbidities, we examined S. mansoni ultrasound-detectable morbidities in relation to HIV-1 infection and CD4+ cell counts, and other factors in fishing communities where the two infections are present. Methods: Ultrasonographical examination was conducted during a cross-sectional study of 1,671 (aged 21-55 years) individuals in North-Western Tanzania. Blood samples were obtained for HIV-1 screening and CD4+ cell quantification. A single stool sample was examined for S. mansoni eggs using the Kato-Katz technique. A questionnaire was used to collect socio-demographic-economic information. Results: The prevalence of PPF (grade C-F) was 13.79% and 15.01% for the HIV-1 infected and non-infected individuals (P = 0.72). Male gender (P< 0.001), age group 21-30 years (P< 0.028) and, residential time of 11-20 (P< 0.01) and 21 years (P< 0.01) were associated with PPF in S. mansoni infected individuals. The height-adjusted measurements of the left liver lobe were significantly larger in HIV-1/S. mansoni co-infected compared to S. mansoni only-infected individuals (t = 2.0702, P< 0.039). Predictors of the height-adjusted measurements of the left liver lobe and spleen were age, male gender, malaria infection, fishing occupation, village of residence and heavy intensity of S. mansoni infection. After accounting for these factors, neither HIV-1 infection nor CD4+ cell counts predicted PPF, hepatosplenomegaly, measurements of the liver or spleen. Height-adjusted ultrasound measurements of the left liver lobe did not correlate with the CD4+ cells counts in co-infected individuals (r = 0.16, P = 0.084). (Continued on next page) - (Continued from previous page) Conclusion: S. mansoni-related PPF, liver and spleen enlargement are prevalent in the study population. The intensity of S. mansoni infection was associated with the enlargement of liver, spleen and hepatosplenomegaly. The PPF grades observed were similar in both HIV-1/S. mansoni co-infected and in those only infected with S. mansoni. There was no evidence that HIV-1 infection or CD4+ cells counts were associated with these S. mansoni morbidities. Background Chronic S. mansoni infection can result in severe complications and life-threatening hepatosplenic disease [1,2]. The pathogenesis of the hepatosplenic form of the disease is a result of the chronic immunological responses mediated by CD4+ T-lymphocytes directed against S. mansoni eggs which are trapped within the host body tissues including the liver [2,3]. Immunological responses against the eggs of the parasite trapped in the liver are responsible for the development of periova granulomas, chronic exposure to which can be associated with the development of fibrosis of the liver portal tracts and associated morbidities [4,5]. Experimental murine model studies suggest that granuloma formation in S. mansoni infection is a CD4+ T-cells dependent process [3,5-7]. The CD4+ cells are predominantly associated with the secretion of Th2 cytokines which contributes to the development of hepatic fibrosis [8,9]. Evidence from immunodeficient mice (nude, T-cell depleted and severe combined immunodeficiency (SCID) mice characterized by the absence of CD4+ T-lymphocytes and egg antibodies response) [10-13], indicate that these animals suffer exacerbated severe hepatic parenchyma damage with reduced granulomatous responses [10-13]. However, there are differences between liver morbidity in S. mansoni infected humans and mice; for example, infected mice do not develop the PPF seen in human infections [8,14]. In human hosts, hepatosplenic disease is often accompanied by hepatic and splenic enlargement; progressive periportal fibrosis (PPF) can lead to portal hypertension and its sequelae [1-3,6,8,9], including ascites, liver surface irregularities and portal-systemic venous shunts, with the risk of oesophageal varices and haematemesis [1-3,8,9]. Many of these manifestations of chronic morbidity can be detected and measured by ultrasonography and the degree of PPF severity is classified using a recommended World Health Organization grading scale, agreed under the Niamey protocol [15-17]. Although immunological responses play a crucial role in the development of hepatosplenic disease, epidemiological [18] and demographic factors are also very important, including the duration of residence in schistosomiasis endemic areas [16,19,20], socio-economic factors such as the involvement in fishing activities [16], as well as environmental [18], genetical [21], parasitological factors [18,20-22] and co-infection with other tropical diseases such as malaria [23,24]. Hepatomegaly or splenomegaly associated with malaria infection is mainly a result of repeated inflammatory responses characterized by hyperplasia of reticuloendothelial and lymphoid tissues [25], which can be exacerbated by chronic S. mansoni infection [23-25]. Any study of the relationship between S. mansoni infection, HIV-1 infection, hepatosplenic disease and its squelae, has to take account of the effects of such factors. The overall pathogenesis of HIV-1 infection is triggered by the destruction or depletion of CD4+ T-lymphocytes which consequently lead to the loss of immune competence [26,27] and an increase in the susceptibility of the infected individuals to other infectious diseases [26]. It has been hypothesized that the destructions of CD4+ Tlymphocytes by HIV-1 infection may alter the sizes of the left liver lobe and the patterns of hepatic fibrosis. This, in turn, may increase the risk of hepatic parenchymal damage due to an insufficient production of the Th2 cytokines which are responsible for fibrogenesis [28,29]. In-vitro studies have shown that T-cells from individuals coinfected with HIV-1 and S. mansoni produced lower IL-4 and IL-10 and IFN- [28]. The inability to stimulate these cells may lead to the development of a sever (...truncated)