Cytokine Response Profiles of School-Aged Children Infected with Schistosomiasis before and after Praziquantel Treatment.

Schistosomiasis is a parasitic disease that affects millions of people in 78 countries globally. Children under the age of 14, who have the chronic disease may suffer from anemia and malnutrition that contribute to lost days at school and pervasive learning disabilities. The infection is prevalent in Kenya, especially in endemic areas, contributing to significant morbidity. The cellular response pattern is associated with both the acute and chronic phases of the disease, in which cytokines play a critical role. The objective of this study was to evaluate the cytokine profiles of IL-4, IL-2, IL-10, IL-5, IFN-γ, and TNF in serum samples of infected school-aged children by using flow cytometry before and after treatment. The analysis indicated a shift in the expression of the cytokines after treatment with all the cytokines being downregulated, except TNF. There was a general trend of decrease in the expression of the cytokines at six and twelve weeks after treatment as compared to the pretreatment levels. There were statistically significant differences in the expression in IL-2 (P=0.001 ∗∗ ), IL-4 (P=0.033 ∗ ), IL-10 (P=0.001 ∗∗∗ ), IFN-γ (P=0.023 ∗ ), and IL-5 (P=0.0001 ∗∗∗ ), except in TNF (P=0.095). The reduction in the cytokine levels can be directly related to the influence of the drug praziquantel, modulating the cytokine response by elimination of adult worms, decline in parasitic load, and reduction of morbidity. Therefore, cytokine response is directly related with the influence of treatment in the variation of the immune response.

Intensity of Nematode Infection in Children Aged 3 to 5 Years Living in Mukuru Kwa Njenga Slum Settlement, Nairobi, Kenya.

BACKGROUND: The burden of nematode infections is high mostly in children below 5 years old, with clinical manifestations ranging from mild to painful symptoms due to severe infections that end up suppressing the immune system of the infected children. The occurrence of these infections is highest in areas of extreme poverty. This study evaluated the intensity of nematode infections and assessed the status of deworming in children aged 3 to 5 years living in Mukuru slum settlement, Nairobi County, Kenya. Methodology. A total of 172 children aged between 3 and 5 years were sampled across the 5 major villages of Mukuru Slum settlement: Kwa Njenga, Vietnum, Wapewape, Kwa Reuben, and Motomoto. Community health workers administered questionnaires on the deworming history of children. Stool samples were collected, macroscopically examined, and microscopically analysed using Kato-Katz technique to assess the intensity of infection. The intensities of nematode infections were expressed as eggs per gram (epg) of faeces. RESULTS: The point prevalence of nematode infection among the 98 children in the 1st sampling was 25.5% with a mean infection intensity of 5424 epg, whereas among the 74 children sampled in 2nd sampling, 47.3% had nematode infection with a mean infection intensity of 12384 epg. The average nematode infection for the 172 participants was 34.9% with a mean intensity of 17808 epg. The highest number of children infected with nematodes was in the village of Wapewape where 34 participants were examined and 36.3% were infected with a mean intensity of 3216 epg. Kwa Reuben and Vietnum villages had the same prevalence values of 32.4% where 34 participants in each village had a mean intensity of 3624 epg and 4512 epg, respectively. In both samplings, more than 80% of children had been dewormed more than 6 months prior to the study. Ascaris lumbricoides was the only species of intestinal nematodes identified to be present in the stool samples of children in this study, whereas Trichuris trichiura and hookworm infections were found to be absent. The intensity of infection was not dependent on age or gender.

Oral administration of Coenzyme Q10 protects mice against oxidative stress and neuro-inflammation during experimental cerebral malaria.

In animal model of experimental cerebral malaria (ECM), the genesis of neuropathology is associated with oxidative stress and inflammatory mediators. There is limited progress in the development of new approaches to the treatment of cerebral malaria. Here, we tested whether oral supplementation of Coenzyme Q10 (CoQ10) would offer protection against oxidative stress and brain associated inflammation following Plasmodium berghei ANKA (PbA) infection in C57BL/6 J mouse model. For this purpose, one group of C57BL/6 mice was used as control; second group of mice were orally supplemented with 200 mg/kg CoQ10 and then infected with PbA and the third group was PbA infected alone. Clinical, biochemical, immunoblot and immunological features of ECM was monitored. We observed that oral administration of CoQ10 for 1 month and after PbA infection was able to improve survival, significantly reduced oedema, TNF-α and MIP-1ß gene expression in brain samples in PbA infected mice. The result also shows the ability of CoQ10 to reduce cholesterol and triglycerides lipids, levels of matrix metalloproteinases-9, angiopoietin-2 and angiopoietin-1 in the brain. In addition, CoQ10 was very effective in decreasing NF-κB phosphorylation. Furthermore, CoQ10 supplementation abrogated Malondialdehyde, and 8-OHDG and restored cellular glutathione. These results constitute the first demonstration that oral supplementation of CoQ10 can protect mice against PbA induced oxidative stress and neuro-inflammation usually observed in ECM. Thus, the need to study CoQ10 as a candidate of antioxidant and immunomodulatory molecule in ECM and testing it in clinical studies either alone or in combination with antimalaria regimens to provide insight into a potential translatable therapy.

Cellular responses against Schistosoma mansoni in immunized Balb/c mice with soluble proteins from intermediate host, Biomphalaria pfeifferi.

Scores of millions of people around the world are infected by Schistosoma mansoni causing considerable morbidity, mortality and loss of productivity. Safe chemotherapeutic agents have been used though there are challenges of re-infection due to resistance. Both epidemiological and experimental data suggest that acquired cell mediated immunity play significant roles in regulating the intensity of S. mansoni infection as well as its patho-physiologic sequelae. Improved control of this trematode parasite may be obtained with immunization to enhance the resistance of individuals to risk of infection. This study investigated the cellular responses of mice immunized with soluble proteins from foot and digestive gland of the vector snail and challenged with S. mansoni. The proteins were used to immunize the experimental groups then challenged with the S. mansoni. The experimental groups were FT (immunized with foot protein) and DG (immunized with digestive gland). The parameters, which were analyzed to demonstrate protection, included; the worm counts and cellular (IFN-γ, IL-5 cytokines) responses. It was observed that, the experimental groups showed significant protection in terms of worm reduction and immune responses. The group vaccinated with foot protein showed higher protection (87.5%) as compared to the group vaccinated with the digestive gland (50%) in terms of worm reduction. Cytokines (IFN-γ and IL-5) production was present in different levels during the assay time points which showed an aspect of protection. The Foot protein of the vector showed more immunizing power than the digestive gland. Research towards utilizing the two proteins as feasible vaccine candidates is encouraged.

Previous or ongoing schistosome infections do not compromise the efficacy of the attenuated cercaria vaccine.

A current or previous schistosome infection might compromise the efficacy of a schistosome vaccine administered to humans. We have therefore investigated the influence of infection on vaccination, using the baboon as the model host and irradiated Schistosoma mansoni cercariae as the vaccine. Protection, determined from worm burdens in test and controls, was not diminished when vaccination was superimposed on a chronic infection, nor was it diminished when it followed a primary infection terminated by chemotherapy. Protection was also assessed indirectly based on fecal egg output and circulating antigen levels, as would be the case in human vaccine trials. In almost all instances, these methods overestimated protection, sometimes with discrepancies of >20%. The overwhelming immune response to egg deposition in infected animals made it difficult to discern a contribution from vaccination. Nevertheless, the well-documented immunomodulation of immune responses that follows egg deposition did not appear to impede the protective mechanisms elicited by vaccination with attenuated cercariae.

Influence of age of mice on the susceptibility to murine schistosomiasis infection.

Intensity of human schistosomiasis infection increases with age, a peak being attained at early puberty. Hormones could be involved in the age-related changes in susceptibility to schistosomiasis. Male BALB / c mice were infected with Schistosoma mansoni either before or after puberty and worm numbers, cellular immune responses, hormonal levels and pathology analysed. Pre-puberty infected mice had a significantly higher number of adult worms (p < 0.05), more severe granulomas, higher mortality rate and higher proliferative responses as compared to post-puberty infected mice. Levels of the hormones were lower in the pre-puberty infected mice as compared to the post-puberty group early in the infection. Plasma levels of testosterone and luteinizing hormones decreased significantly (p < 0.05) in infected mice when compared to controls. Susceptibility to S. mansoni in male BALB / c mice seems to be influenced by levels of testosterone and luteinizing hormone at infection. Albeit, an infection with S. mansoni seems to lower the hormonal levels.

The effect of vaccinating S. mansoni-infected BALB/c mice either before or after treatment.

In Schistosoma mansoni endemic areas, there are people with ongoing S. mansoni infection, others have been infected and treated while others have never been infected. What would happen if these different groups of people were vaccinated against S. mansoni? BALB / c mice were divided into five groups: Infected-Treated-Vaccinated; Infected-Vaccinated-Treated; Vaccinated-Treated Control; Challenge Control and Untreated Challenge Control. Vaccination (500 20krad irradiated S. mansoni cercariae), Treatment (praziquantel), Infection and Challenge (150 S. mansoni cercariae) were carried out at specified times. Proliferation assay, Enzyme linked immunosorbent assay, gross pathology, histopathology and perfusion were performed. High protection levels were obtained in mice treated after vaccination: Vaccinated-Treated control, 96.5 %; Infected-Vaccinated-Treated, 68.9 %; and Infected-Treated-Vaccinated, 41 %. A good correlation was obtained between proliferative responses and protective levels, implying cellular involvement in protection. Although all protected animals had high IgG levels, there was no strong correlation between the two. Specificity rather than amounts of IgG, seem more important in protection. Praziquantel seemed to boost protective immunity when administered after vaccination. Granuloma development and modulation in the two test groups was similar. It seems better to vaccinate infected patients before treatment, the ideal situation being vaccinating people who have not encountered S. mansoni.

Parameters of the attenuated schistosome vaccine evaluated in the olive baboon.

Five exposures of baboons to the attenuated schistosome vaccine gave greater protection than three exposures, but this attenuation was not sustained when challenge was delayed. Within the scope of the data collected, fecal egg counts and circulating antigen levels did not accurately predict the observed worm burdens. Levels of immunoglobulin G at challenge correlated best with protection, but there was little evidence of a recall response.

Morbidity and immune response to natural schistosomiasis in baboons ( Papio anubis).

The morbidity and immunological response to naturally acquired Schistosoma mansoni infection in a population of wild baboons ( n=28) was investigated. Serum obtained from the baboons was assayed for adult worm (SWAP) and schistosome egg (SEA)-specific immunoglobulin (Ig)G and IgM antibodies. The animals were euthanised, perfused to recover adult schistosome worms and schistosome-related pathology was assessed. Nineteen animals (68%) had high serum levels of SWAP-specific IgG antibodies and 15 (54%) had high levels of SEA-specific IgG antibodies. Nine animals (32%) had high levels of SWAP-specific IgM antibodies and six (21%) had high levels of SEA-specific IgM antibodies. Mild schistosome-related pathology was noted in 18 animals (64%). However, adult schistosome worms were recovered from only three animals (10%). The results indicate a high exposure to schistosomiasis for free-ranging baboons inhabiting an endemic area, as evidenced by the high prevalence of parasite-specific humoral antibody response. However, this high exposure is associated with low worm recovery and mild pathology. In addition, parasite-specific IgM antibodies provided a good indicator of an active schistosome infection.

Experimental infection of the olive baboon (Paplio anubis) with Plasmodium knowlesi: severe disease accompanied by cerebral involvement.

Experimental systems that model some of the complex interactions between parasite and host can be extremely valuable in identifying and developing new prophylactics and therapeutics against human diseases. Because primates have similar immune systems to humans, we have characterized a baboon model for understanding host response to Plasmodium knowlesi. Ten intact olive baboons (Papio anubis) of either sex were experimentally infected with P. knowlesi H strain erythrocytic parasites. The infection in these baboons was either acute or chronic. Animals with acute infection developed multiple system organ dysfunction and cerebral involvement. In chronically infected animals, only the spleen was moderately enlarged. The P. knowlesi parasitemia profile in baboons and rhesus monkeys was comparable. However, some clinical symptoms of the baboons and P. falciparum-infected humans were similar. These studies demonstrate for the first time that P. anubis is a suitable host for P. knowlesi for studying clinical symptoms and pathology.