Hepatosplenomegaly associated with chronic malaria exposure: evidence for a pro-inflammatory mechanism exacerbated by schistosomiasis.

In sub-Saharan Africa, chronic hepatosplenomegaly, with palpable firm/hard organ consistency, is common, particularly among school-aged children. This morbidity can be caused by long-term exposure to malaria, or by Schistosoma mansoni, and it is exacerbated when these two occur together. Although immunological mechanisms probably underlie the pathogenic process, these mechanisms have not been identified, nor is it known whether the two parasites augment the same mechanisms or induce unrelated processes that nonetheless have additive or synergistic effects. Kenyan primary schoolchildren, living in a malaria/schistosomiasis co-transmission area, participated in cross-sectional parasitological and clinical studies in which circulating immune modulator levels were also measured. Plasma IL-12p70, sTNF-RII, IL-10 and IL-13 levels correlated with relative exposure to malaria, and with hepatosplenomegaly. Soluble-TNF-RII and IL-10 were higher in children infected with S. mansoni. Hepatosplenomegaly caused by chronic exposure to malaria was clearly associated with increased circulating levels of pro-inflammatory mediators, with higher levels of regulatory modulators, and with tissue repair cytokines, perhaps being required to control the inflammatory response. The higher levels of regulatory modulators amongst S. mansoni infected children, compared to those without detectable S. mansoni and malarial infections, but exposed to malaria, suggest that S. mansoni infection may augment the underlying inflammatory reaction.

Intestinal polyparasitism in a rural Kenyan community.

BACKGROUND: Polyparasitism seems to be a common feature in human populations in sub-Saharan Africa. However, very little is known about its epidemiological significance, its long term impact on human health or the types of interactions that occur between the different parasite species involved. OBJECTIVES: To determine the prevalence and co-occurrence of intestinal parasites in a rural community in the Kibwezi, Makueni district, Kenya. DESIGN: A cross sectional study. SETTING: Kiteng'ei village, Kibwezi, Makueni district, between May and September 2006. SUBJECTS: One thousand and forty five who comprised of 263 adult males, 271 adult females > 15 years of age and 232 boys, and 279 girls <15 years of age. INTERVENTIONS: All infected members of the community were offered Praziquantel (at dosages of 40 mg/kg body weight) for Schistosomiasis and Albendazole (600 mg) for soil transmitted helminths. RESULTS: A total of ten intestinal parasite species (five protozoan and five helminth parasite species) were present in this community and polyparasitsm was common in individuals 5-24 years of age with no gendar related differences. Most of the infections were mild. The protozoan parasites of public health significance present were Entamoeba histolytica and Giardia lamblia with prevalence of 12.6% and 4.2%, respectively. The helminth parasites of public health significance in the locality were Schistosoma mansoni with a prevalence of 28%, and hookworms prevalence of 10%. About 53% of the study population harboured intestinal parasite infections, with 31% of the infected population carrying single parasite species infections, and 22% harbouring two or more intestinal parasite species per individual. Significant positive associations (p values <0.05) were observed between S. mansoni and hookworms, hookworms and Hymenolepis. nana and Entamoeba histolytica and Entamoeba coli. CONCLUSION: Intestinal polyparasitism was common in the Kiteng'ei community, particularly in individuals aged of 5-24 years old. An integrated control programme of approach would be recommended for the control of S. mansoni, hookworms and Entamoeba histolytica for this community.

Schistosomiasis mansoni in Kenya: relationship between infection and anaemia in schoolchildren at the community level.

Haematological surveys were carried out in 3 schools in 2 areas where Schistosoma mansoni is endemic in Machakos District, Kenya, before and after a treatment campaign using praziquantel. Earlier clinical impressions of differences in the levels of anaemia between the 2 areas were not confirmed. Although individual haemoglobin levels and haematocrits often fell below international norms, significant anaemia with abnormal red blood cell morphology was rare (< 5%), but varied between schools. Altitude could have accounted for some of these differences, but other factors, including diet and parasitism, were involved. Anaemia was associated with splenomegaly and, to a lesser extent, hepatosplenomegaly. Epidemic malaria (mainly Plasmodium falciparum) appeared to be the main cause of parasite-induced anaemia. There was no significant association with the scarce hookworm infections (mainly Necator americanus); nor did the much commoner S. mansoni cause severe anaemia at the community level, but haemoglobin levels dropped as its intensity increased. Treatment with praziquantel eliminated this trend except in a few subjects with splenomegaly alone (probably due to malaria) or with schistosomal hepatosplenic disease. Possible pathogenic mechanisms are reviewed, including the consumption of red blood cells by adult schistosomes as a possible cause of anaemia.

Human IgG subclass responses and subclass restriction to Schistosoma mansoni egg antigens.

In areas endemic for schistosomiasis, there is great heterogeneity in antibody isotype responses to parasite antigens amongst infected individuals. At the population level, the isotype composition of antibody responses undergoes dynamic changes which are associated with the age of infected individuals. Here we examine the IgG subclass responses to Schistosoma mansoni eggs (soluble egg antigens; SEA) of infected individuals by immunoblot and ELISA. By controlled treatment of SEA-coated ELISA plates and immunoblot nitrocellular strips with sodium periodate, in order to oxidize terminal carbohydrate residues selectively, we were able to relate individuals subjects' isotype responses to the different antigens that they responded to, and to the presence of putative carbohydrate and peptide epitopes on those antigens. IgG2 responses were restricted strictly to sodium periodate-sensitive carbohydrate epitopes and antigens of relatively high molecular weight. These antigens were not usually recognized by other isotypes and, therefore, they were only recognized by individuals who had high levels of IgG2. IgG1 and IgG3 responses were directed against both carbohydrate and peptide epitopes, whereas IgG4 responses were restricted to periodate-resistant epitopes. This suggests that the fall in IgG2 responses, and reciprocal rise in IgG4 antibodies, seen in young children as their intensities of schistosome infection increase, is not the result of isotype switching, and that, if these two subclasses are involved in blocking immunity to schistosomiasis, they are operating independently.

Observations on the effects of different chemotherapy strategies on the transmission of Schistosoma mansoni in Machakos District, Kenya, measured by long-term snail sampling and cercariometry.

Transmission of Schistosoma mansoni was monitored by routine snail sampling for Biomphalaria pfeifferi and by supplementary cercariometric measurements in 4 neighbouring study areas in Machakos District, Kenya. After 1 year, extensive, population-based chemotherapy with a single dose of praziquantel was given in 3 areas, but only minimal treatment in the fourth. In the year preceding treatment, seasonal transmission of S. mansoni and other non-human trematodes occurred in all 4 areas, despite some ecological differences and the effects of earlier treatment campaigns in 1 of the study areas. After treatment of all infected subjects in one area in which there had been earlier chemotherapy campaigns, S. mansoni transmission remained very low. It was reduced for at least 2 years after chemotherapy targeted at either all heavily infected subjects or all infected school children, but it was unaffected in an area where treatment was restricted to those few very heavily infected cases at risk of developing disease. Nowhere was transmission entirely eliminated by chemotherapy and that of non-human trematodes continued unabated. The snail data correspond well with the human, parasitological data. Targeting school children was as effective as more extensive campaigns, but chemotherapy alone never stopped S. mansoni transmission: reinfection was inevitable, at rates determined by ecological factors affecting snail populations.

Comparison of different chemotherapy strategies against Schistosoma mansoni in Machakos District, Kenya: effects on human infection and morbidity.

A comparison was made of the long-term impact of different methods of administration of chemotherapy (oxamniquine, 30 mg/kg in divided doses; or praziquantel, 40 mg/kg) on prevalence and intensity of Schistosoma mansoni infection in four areas in Kangundo Location, Machakos District, Kenya. In Area A, treatment was offered in October 1983 and again in April 1985 to all infected individuals. In Area H, treatment was offered in April 1985 to individuals excreting greater than or equal to 100 eggs per gram (epg) of faeces. In Area S, treatment was offered in April 1985 to all infected school children, within the framework of the primary schools. In the witness area, Area W, treatment was given in April 1985, for ethical reasons, to a small number of individuals excreting greater than or equal to 800 epg. Prevalence and intensities of infection were subsequently monitored at yearly intervals for three complete post-treatment years. In the Area S schools, clinical examination was also carried out at yearly intervals. Treatment of all infected individuals on two occasions (Area A) was the most effective and long-lasting way of reducing prevalence and intensity of infection. In this area, however, some earlier interventions had been carried out and pre-treatment intensities were lower than in the other areas. Treatment only of infected schoolchildren (Area S) also had a marked and prolonged effect, comparable to or better than treatment of individuals with heavy infections (Area H). Treatment of infected schoolchildren also caused a persistent reduction in the prevalence of hepatomegaly, and there was suggestive evidence from intensities of infection in community stool surveys (but not from incidence rates) of an effect on transmission. In all study areas, reinfection was most rapid and most intense among children. These findings are discussed in the light of theoretical considerations and of results from other studies, both on schistosomiasis and on intestinal helminths. We conclude that, in areas of low morbidity such as Kangundo, chemotherapy of schoolchildren only, at intervals of up to 3 years, is a satisfactory way of producing a long-term reduction in both intensity of infection and morbidity.

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment.

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.