Immuno-epidemiology of Schistosoma haematobium infection in Zimbabwean communities with different infection patterns

This study addressed the immuno-epidemiology of Schistosoma haematobium in people living in communities in Zimbabwe with distinct patterns of prevalence and intensity of infection. The studies were located at three different areas within known endemic regions of the country. The two areas located in The Burma Valley were within 10 km of one another. One was designed a Low Transmission (LT) area and the other a High Transmission (HT) area. In these two localities, the immunological studies were centred on the cellular immune responses. Levels of cellular proliferation of peripheral blood mononuclear cells (PBMC) in response to specific (schistosome) antigen stimulation were measured from both school children and adults (age range 5 - 64) in each area, while cytokine production by PBMC was investigated on a smaller cohort of school children aged 7-16 years from each area. T cell clones were derived from PBMC collected from two infected and two uninfected children from the High Transmission area. This aspect of the study attempted to establish if any T helper cell dichotomy existed during human S. haematobium infection by defining the cytokine phenotypes of the clones derived from the PBMC. The longer term aim was to assess the potential predictive value of T cell clones in determining resistance or susceptibility to infection, and thus contribute towards a rationale strategy for vaccine development. The third area of the study was in an endemic region with very high S. haematobium and low S. mansoni infection. This study focused on pre-school children two to six years old and examined the impact of repeated chemotherapy with praziquantel. The children were followed up for 14 months, with praziquantel treatment at each examination point, every eight weeks. The study reports on the antibody isotype profiles in sera collected at each follow-up point during the 14 months of the study

Multiplex peptide microarray profiling of antibody reactivity against neglected tropical diseases derived B-cell epitopes for serodiagnosis in Zimbabwe

INTRODUCTION: Peptides (B-cell epitopes) have broad applications in disease diagnosis and surveillance of pathogen exposure. In this framework, we present a pilot study to design and produce a peptide microarray for the integrated surveillance of neglected tropical diseases. The peptide microarray was evaluated against peptides derived from Ascaris lumbricoides, Necator americanus, Schistosoma haematobium, Schistosoma mansoni, Trichuris trichiura, Bacillus anthracis, Mycobacterium leprae, Wuchereria bancrofti, Rabies lyssavirus, Chlamydia trachomatis and Trypanosoma brucei. METHODS: S. haematobium was diagnosed using the urine filtration technique. S. mansoni, A. lumbricoides, N. americanus and T. trichiura were diagnosed using the Kato Katz and formal ether concentration techniques. Immunogenic peptides were retrieved from the Tackling Infection to Benefit Africa infectious diseases epitope microarray. Further peptides were predicted using ABCpred. IgG and IgM reactivity against the derived peptides were evaluated using peptide microarray multiplex immunoassays. Positive response was defined as fluorescence intensity ≥ 500 fluorescence units. Immunodominant peptides were identified using color-coded heat maps and bar graphs reflecting the obtained fluorescence signal intensities. Receiver Operating Characteristic analysis and Mann-Whitney-U test were performed to determine the diagnostic validity of the peptides. RESULTS: Species-specific responses with at least one peptide derived from each NTD pathogen were observed. The reactive peptides included; for S. haematobium, XP_035588858.1-206-220 and XP_035588858.1-206-220 immunodominant for IgG and IgM respectively, for S. mansoni, P20287.1-58-72 immunodominant for both antibodies and for T. trichiura, CDW52482.1-326-340 immunodominant for IgG and CDW57769.1-2017-2031 and CDW57769.1-1518-1532 immunodominant for IgM. According to ROC analysis most of the peptides selected were inaccurate; with AUC < 0.5. Some peptides had AUC values ranging from 0.5 to 0.5875 for both IgM and IgG suggesting no discrimination. CONCLUSION: Multiplex peptide microarrays are a valuable tool for integrated NTDs surveillance and for screening parasites exposure in endemic areas. Species sero-reactivity observed in the study maybe indicative of exposure to the different NTDs parasites. However, although peptides with the least cross reactivity were selected there is need to validate the sero-reactivity with recombinant antigens and immune-blotting techniques such as western blotting

Global Control Efforts of Schistosomiasis and Soil-Transmitted Helminthiasis

Schistosomiasis is a waterborne disease whose life cycle involves freshwater sources conducive for the survival and reproduction of aquatic snails that form a connective link between man and water in the life cycle and transmission of schistosomiasis. The African region has network of rivers with freshwater suggesting the presence of schistosomiasis and difficulty to control. Some communities, due to socioeconomic challenges, have inadequate sanitation and water supply; use of bush toilets for excretion is commonly practiced. These conditions in Africa also promote transmission of soil-transmitted helminthiasis. The World Health Organization (WHO), in response to the public health and socioeconomic impact of neglected tropical diseases, is coordinating strategies for the control and elimination of the diseases including schistosomiasis and soil-transmitted helminthiasis. As one of the milestones, mapping of neglected tropical diseases in the African region has been prioritized for the implementation of control strategies. In countries where mapping has been completed, WHO and its partners are supplying medicines required for annual mass treatment for preventive chemotherapy and encourage countries to take ownership in implementing complementary strategies for morbidity control, elimination and eradication of country-specific neglected tropical diseases. The mainstay of helminthiasis control is preventive chemotherapy, targeting school age children to prevent morbidity and development of pathological manifestations, including urogenital schistosomiasis that is understood to contribute to HIV transmission. Vaccines are still to be discovered and designed, with many possible antigen candidates, but however the immune responses are still to be fully understood. There is need to understand the subtle link between each component of the immune responses and the host immunogenetics impacting on the translated immunological response of cytokines that are delicately controlled for cellular immunity and antibody production. Currently, preventive chemotherapy treatment is the only control method in concert with health education in an attempt to cut the helminthiasis life cycle

Association between Micronutrients (Vitamin A, D, Iron) and Schistosome-Specific Cytokine Responses in Zimbabweans Exposed to Schistosoma haematobium

Micronutrients play an important role in the development of effective immune responses. This study characterised a populations exposed to schistosome infections in terms of the relationship between micronutrients and immune responses. Levels of retinol binding protein (RBP; vitamin A marker), vitamin D, ferritin and soluble transferrin receptor (sTfR), and C reactive protein (CRP) were related to levels of schistosome specific cytokines (IFN-γ, IL-4/5/10) in 40 Zimbabweans (7–54 years) exposed to Schistosoma haematobium infection. 67.2% of the participants were deficient in vitamin D. RBP levels were within normal ranges but declined with age. The two indicators of iron levels suggested that although levels of stored iron were within normal levels (normal ferritin levels), levels of functional iron (sTfR levels) were reduced in 28.6% of the population. Schistosome infection alone was not associated with levels of any of the micronutrients, but altered the relationship between parasite-specific IL-4 and IL-5 and levels of ferritin and sTfR

Effect of schistosoma haematobium infection on the cognitive functions of preschool age children and benefits of treatment from an endemic area in Zimbabwe

BACKGROUND: Schistosomiasis is known to affect the cognitive functions of children, however, but there is paucity of information on its impact on early childhood development in developing countries where the disease is endemic. This study aimed at determining the effects of schistosomiasis due to Schistosoma haematobium on early childhood development in children below 5 years old from Murewa District, Zimbabwe, including the benefits of treatment. METHODS: Preschool age children (PSAC) under the age of 5 years were screened at baseline and at 6 months post-treatment for S. haematobium infections diagnosed using the urine filtration method. Cognitive domains were assessed using the Griffith Mental Developmental Scales III on 136 PSAC. Multivariate logistic regression was used to determine the level of association between S. haematobium infection and performance in the cognitive domains adjusting for confounding factors (i.e. nutrition, hemoglobin levels, gender and age). Median Development Quotient scores of each cognitive domain at baseline and at 6 months post-treatment were compared and quantified. RESULTS: After adjusting for confounding factors, PSAC infected with S. haematobium had greater odds of having lower scores in the Foundation of Learning Domain (OR = 3.9, p = 0.008), Language and Communication Domain (OR = 3.2, p = 0.017), Eye-Hand Coordination Domains (OR = 10.7, p = 0.001), Personal-Social-Emotional Domain (19.3, p = 0.001) and in the Overall General Development Domain (7.2, p = 0.011). Improvement of cognitive performance was observed at 6 months post treatment in the following Domains; Language and Communication Domain (p = 0.003), Eye-Hand Coordination Domain (p = 0.02) and General Development Domain (p = 0.006). CONCLUSION: The study showed that S. haematobium infection in PSAC is associated with lower cognitive scores in the Foundation of Learning, Language and Communication, Eye-Hand Coordination, Personal-Social-Emotional and in the Overall General Development domains. Our results strengthen the call for inclusion of PSAC in routine deworming programs for the control of urinary schistosomiasis and the need to develop locally validated tools to monitor early child development in endemic areas where resources are limited

Similar cellular responses after treatment with either praziquantel or oxamniquine in Schistosoma mansoni infection.

The effect of treatment with either oxamniquine or praziquantel on S.mansoni specific IFN-gamma, IL-4, IL-5 and IL-10 was compared on PBMC which were collected pretreatment, 6 and 18 weeks post treatment. Using sandwich ELISA on the supernatants harvested from the PBMC stimulation by crude S. mansoni SEA and SWAP antigens after 5 days the levels of PBMC proliferation and cytokine production were similar according to treatment with either praziquantel or oxamniquine. Before treatment, infected groups showed low ratios, of IL-4:IFN-gamma, IL-5:IFNgamma and IL-10:IFN-gamma, indicating that IFN-gamma was high in the infected individuals. The general increase in immuno-modulation was observed post-treatment with elevated immune reactivity and cytokine production in both treatment groups. Treatment induced significant increases in levels of IL-4 (p < 0.05), IL-5 (p < 0.0001) and IL-10 (p < 0.05) cytokines 6 and 18 weeks after treatment. There were no significant differences in the increase in IL-4, IL-5 and IL-10 between children treated with praziquantel or oxamniquine. Pre-treatment IFN-gamma and IL-5 levels were positively correlated with infection (p < 0.001), while post treatment IL-4 cytokine levels were negatively correlated with baseline infection status (p < 0.001). The results suggest that treatment-induced immune responses are similar for both common anti-schistosome drugs praziquantel or oxamniquine having similar and immunizing effect

Antioxidant properties, protein binding capacity and mineral contents of some plants traditionally used in the management of animal wounds

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