119 research outputs found
Human Schistosome Infection and Allergic Sensitisation
No full textSeveral field studies have reported an inverse relationship between the prevalence of helminth infections and that of allergic sensitisation/atopy. Recent studies show that immune responses induced by helminth parasites are, to an extent, comparable to allergic sensitisation. However, helminth products induce regulatory responses capable of inhibiting not only antiparasite immune responses, but also allergic sensitisation. The relative effects of this immunomodulation on the development of protective schistosome-specific responses in humans has yet to be demonstrated at population level, and the clinical significance of immunomodulation of allergic disease is still controversial. Nonetheless, similarities in immune responses against helminths and allergens pose interesting mechanistic and evolutionary questions. This paper examines the epidemiology, biology and immunology of allergic sensitisation/atopy, and schistosome infection in human populations
demographic and immunoepidemiology data
No full textIn order to protect health workers from SARS-CoV-2, there is need to characterise the different types of patient-facing health workers. These data were collected to determine both the infection and seroprevalence of SARS-COV-2 in health workers as well as to evaluate the occupational and demographic predictors of seropositivity to inform the country’s infection prevention and control strategy. The data presented here were collected from 651 health workers in Zimbabwe. The participants were recruited through a mixed sampling approach was to allow the study to capture different types of patient-facing worker in different health care settings. Their demographic data (age, sex) and type of health centre, occupation, and station in the health centres is provided. Also collected were health variables which are self-explanatory in the data spread sheet. These include the following; COVID-19 symptoms in the previous 4 months e.g. fever recorded as fever_4months in the spread sheet as well as COVID-19 symptoms at the time of the study recorded as fever, new dry cough etc and, self-reported co-morbidities recorded at the time of collection are also given e.g. diabetes, cancer where yes means co-morbidity or symptom is present and no means the co-morbidity or symptom is not present in the participant. We determined the serological status of the health workers by detecting the presence of SARS CoV-2 antibodies using a rapid chromatographic immunoassay for the qualitative detection of IgG and IgM antibodies (Wuhan UNscience Biotechnology Companies UNICOV-40 test kit) following the manufacturer’s guidelines. The test detects the presence of IgM and IgG antibodies directed against the nucleocapsid and the spike proteins of the virus. The IgM antibody status is recorded in the spreadsheet under the variable SARSCOV2 IgM antibody_result, where negative means no IgM antibodies were detected and positive means IgM antibodies were detected. The IgG antibody status is recorded in the spreadsheet under the variable SARSCOV2 IgG antibody_result, where negative means no IgG antibodies were detected and positive means IgG antibodies were detected.Excel data se
The predicted impact of immunosuppression upon population age-intensity profiles for schistosomiasis.
No full textThe slow development of acquired immunity is thought to be responsible for the characteristic convex age-intensity curve seen in human schistosome infection, which peaks earlier in more heavily infected populations (this is described as a peak shift). Schistosomes are able to suppress protective host responses, and it is hypothesized that this suppression is responsible for the delayed development of protective responses. A deterministic mathematical model is used to describe levels of infection and immunity in an endemic population, incorporating protective immune responses which either reduce adult worm burden or reduce superinfection. Suppression, related to current worm burden, is also included and acts against one or both protective responses. If suppression acts against the entire protective response, it is able to delay the development of protective immunity, and the peak shift is predicted to be reversed at higher infection intensities, with removal of the peaks altogether at the highest levels of infection and/or suppression. If only the anti-adult worm protective immune response is vulnerable to suppression, while the anti-reinfection response remains intact, then suppression does not remove the peak in the age-intensity curve. These findings are discussed in the light of existing field and experimental data
Impact of preventive chemotherapy survey during a national helminth control program dataset: perception, knowledge, attitudes and practices (KAP) outcome data.
No full textThe impact of preventive chemotherapy project was a study to determine the perception and knowledge, attitudes and practices (KAP) on Zimbabwe’s national helminth control programme conducted between 2012 and 2017. It focused on schistosomiasis (a parasitic disease affecting tropical and subtropical communities without access to safe drinking water and adequate sanitation provision) in the school children treated with the antihelminthic drug praziquantel, as well as schoolteachers and village health workers (VHW).
School children (n= 409) from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017 were recruited, in addition to 36 schoolteachers and 22 VHW who were serving the schools. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to all participants. The questions focused on the perceived impact of the preventive chemotherapy programme for schistosomiasis on individual/overall health, school attendance and performance, as well as KAP. Data were captured electronically on android platforms using the Open Data Kit.
Full details are given in Mutapi et al., 2020 (Title: Positive impact of preventative chemotherapy during a national helminth control program: perception and KAP)File name: Impact_survey outcome data.xlsx
Description: This includes the full outcome data for the study.
File name: Impact Survey Data Dictionary.xlsx
Description: This is a data dictionary describing each variable its associated codes and a summary of values for each variabl
Parasite and host factors that drive heterogeneity in human malaria
No full textMalaria affects over half of the world’s population and causes half a million deaths
annually, especially in Sub-Saharan Africa. Four species of the apicomplexan
Plasmodium parasite (P. falciparum, P. ovale, P. malariae and P. vivax) are
responsible for malaria in Africa. Both parasite and host factors contribute to
heterogeneity in the risk of developing malaria, clinical manifestation of the disease as
well as the number of treatments required to clear parasites. The epidemiology of the
different species, and the role of exposure to mixed-species Plasmodium co-infections
in generating heterogeneity remains poorly studied. Being an obligate intracellular
parasite the blood-stage life cycle of the Plasmodium parasite takes place in the
erythrocytes of the human host. The surfaces of these erythrocytes are the medically
important ABO blood group antigens that have been reported to influence the
susceptibility or otherwise of an individual developing severe malaria. In this thesis I
have considered the contributions of the species of Plasmodium parasites and the ABO
blood group of the host in driving heterogeneity in human malaria.
The aims of this thesis were to determine:
(i) the seroepidemiology of the different Plasmodium species in two
mesoendemic African populations (Zimbabwe and Sudan);
(ii) to determine if heterogeneity in clinical presentations of malaria (history
of fever, body temperature and parasitaemia) and response to drug
treatment is related to exposure to single vs. mixed-Plasmodium species
infection;
(iii) the spatial and temporal dynamics of malaria prevalence and Plasmodium
species distribution in a mesoendemic village in eastern Sudan;
(iv) gene expression changes in 3D7 P. falciparum parasites as they infect
erythrocytes of different ABO blood group donors.
For aims (i to iii) I developed an enzyme-linked immunosorbent assay using antigens
derived from Plasmodium merozoite surface protein 1, also known as MSP-119, to
detect IgG antibodies to all four malaria parasite species in Zimbabwean and Sudanese
populations. In the Zimbabwean study, plasma samples from 100 individuals each
(aged 5-18 years) from three villages (Burma Valley, Mutoko and Chiredzi) were
screened for exposure to Plasmodium parasites. In Daraweesh, Sudan, plasma samples
from 333 individuals (aged 1-74 years) who had experienced a first malaria episode
between 1990 and 2000 were recruited into the study. For study aim (iv) I cultured a
single clone of 3D7 P. falciparum parasite using erythrocytes of individuals of
different ABO blood group types, harvested parasite RNA and sequenced it to
determine gene expression changes in the different hosts.
I showed that human IgG antibodies to MSP-119 antigens of the four Plasmodium
species are species-specific and do not cross-react. In both study populations almost
all antibody responses involved P. falciparum, and single-species responses were
almost exclusively directed against P. falciparum antigens. Mixed-species responses
accounted for more than a third of responses, and were associated with chloroquine
treatment failure, with significantly high proportion of individuals with mixed-species
infections requiring repeated treatment with chloroquine/sulfadoxine-pyrimethamine
for parasite clearance. This finding highlights the need for a sensitive method for
detecting mixed-species malaria infections to enable the assessment of the true
prevalence and magnitude of the disease burden caused by the non-falciparum species
in endemic populations. Drug treatment failures associated with mixed species
infections have significant impact on malaria morbidity and mortality. Treatment
failure or partial parasite clearance has the potential to allow dormant liver stages of
P. vivax and P. ovale to become a source of parasite reservoir for onward transmission.
Furthermore, untreated low-grade chronic infections caused by P. malariae have been
reported to cause systemic diseases many years after the primary infection. Spatial
analysis of malaria epidemiology showed that malaria parasite transmission in
Daraweesh was focal, and that infections are not randomly distributed in the village.
Two space-time clusters of significantly increased malaria risk were identified (1993-
1999, and 1998-1999) with marked variations between households, but little or no
variation in the species of Plasmodium over time. Similarly, multiple significant
clusters were identified for the parasite species; three for P. falciparum, two for P.
vivax and P. malariae, and one for P. ovale. These clusters had overlapping time
frames, with some of the species significantly infecting the same households. This
suggests that even in a small geographic area malaria transmission shows
heterogeneity, and that such data can provide useful information to guide malaria
control efforts. Finally, I demonstrated that 3D7 P. falciparum parasite growth was
similar in the erythrocytes of different blood group donors, and provide preliminary
data to show that the non-coding RNA gene, PF3D7_1370800, is differentially
expressed in blood group A donors relative to blood groups B and O donors. Further
research is needed to better understand the role of this gene in malaria pathology.
All together, these findings will aid malaria researchers and other stakeholders in
making informed choices about tools for diagnosing Plasmodium species, and control
programmes targeting eradication of malaria caused by all Plasmodium species, as is
the case of incorporating these findings into current malaria research in Sudan
Systematic review and meta-analysis of the effects of treatment and immunization against schistosomiasis
No full textSchistosomiasis is a water-borne parasitic disease of great public health importance mainly
in sub-Saharan African countries. The majority of current control programmes use the
antihelminthic drug praziquantel to reduce disease burden in endemic areas. Praziquantel
treatment has been reported to accelerate the development of protective immunity against
re-infection that otherwise takes years to develop. To date, there is no licensed vaccine for
schistosomiasis in humans but an attenuated schistosome parasite vaccine has been tested in
animal models.
Employing systematic review and meta-analysis approaches, my PhD research has four main
objectives relating to attenuated schistosome vaccine and praziquantel treatment: 1) to
identify predictors that determine protection levels after treatment with attenuated
Schistosoma mansoni vaccines in the mouse model, 2) to quantify the influence of host and
schistosome parasite species on attenuated parasite vaccine efficacy, 3) to explore the
direction of change (increase/decrease) in schistosome parasite-specific antibody isotypes
after praziquantel treatment in humans, 4) to identify predictors of praziquantel efficacy in
humans.
My analyses revealed three factors that have an influence on the protection levels provided
by attenuated schistosome parasite vaccines: increasing numbers of immunizing parasites
had a positive effect on the levels of protection whereas increasing the radiation dose and the
time to challenge infection had negative effects. Analyses showed that the attenuated
schistosome vaccine has the potential to achieve protection levels as high as 79% after a
single dose in mice. Alongside this, baboon studies consistently reported protective effects of
attenuated schistosome vaccines against re-infection. These results show there is a high
potential for an attenuated schistosome parasite vaccine to be effective in humans.
A meta-analysis of the influence of praziquantel treatment on the direction of change in
schistosome-specific antibody isotypes was conducted. The analysis revealed considerable
variability in the antibodies’ direction of change among populations. The results also
demonstrated an increase of anti-worm IgA and IgE in the majority of studies. These
antibodies have been reported to have a protective effect against re-infection. The
combination of age and infection intensity, and the number of days after treatment were
identified as influential predictors for some antibody isotypes, but there was no single
predictor that consistently affected all antibody isotypes in the same way.
Praziquantel efficacy levels in humans were investigated and the analyses revealed that cure
rates for schistosomiasis increase with praziquantel dose, and were affected by the identity of
the schistosome parasite species (S. mansoni vs. S. haematobium) and the age of the
participants (children: 0-19 years old vs. adults: ≥ 20 years old). There has been no clear
efficacy level reduction over the treatment years (1979-2013) suggesting that praziquantel is
still effective in the treatment of schistosomiasis despite concerns about possible resistance.
The development of a schistosome vaccine will benefit from a closer investigation into the
mechanisms through which protection is acquired in attenuated schistosome parasite vaccine
studies showing high potential efficacy in animal models. Nevertheless, it will take time to
develop a schistosome vaccine for human use. The uptake of the vaccine will be made even
more challenging by the lack of adequate infrastructure in schistosomiasis endemic areas. In
the meantime, close monitoring of praziquantel efficacy levels is necessary to confirm the
effectiveness of schistosomiasis control in endemic areas
Impact of preventive chemotherapy survey during a national helminth control program dataset: perception, knowledge, attitudes and practices (KAP) outcome data.
No full textThe impact of preventive chemotherapy project was a study to determine the perception and knowledge, attitudes and practices (KAP) on Zimbabwe’s national helminth control programme conducted between 2012 and 2017. It focused on schistosomiasis (a parasitic disease affecting tropical and subtropical communities without access to safe drinking water and adequate sanitation provision) in the school children treated with the antihelminthic drug praziquantel, as well as schoolteachers and village health workers (VHW). School children (n= 409) from Grades 6 and 7 who had the full benefit of the 6 years of MDA from 2012 to 2017 were recruited, in addition to 36 schoolteachers and 22 VHW who were serving the schools. A structured questionnaire developed in English, translated into the local language Shona, and validated prior to the study was administered to all participants. The questions focused on the perceived impact of the preventive chemotherapy programme for schistosomiasis on individual/overall health, school attendance and performance, as well as KAP. Data were captured electronically on android platforms using the Open Data Kit. Full details are given in Mutapi et al., 2020 (Title: Positive impact of preventative chemotherapy during a national helminth control program: perception and KAP)Osakunor, D; Mutapi, F. (2020). Impact of preventive chemotherapy survey during a national helminth control program dataset: perception, knowledge, attitudes and practices (KAP) outcome data., [dataset]. University of Edinburgh. School of Biological Sciences. https://doi.org/10.7488/ds/2890
Paediatric schistosomiasis: dynamics and consequences
No full textUrogenital schistosomiasis, caused by the parasite helminth Schistosoma haematobium, is one of the major parasitic diseases affecting millions of preschool-aged children (PSAC), i.e. aged 5 years and below, in sub-Saharan Africa. Diagnosis is via microscopic detection of parasite eggs in urine, and treatment is by administration of the antihelminthic drug of choice, praziquantel. Epidemiological studies show that PSAC are infected as early as a year old, with negative impacts on nutrition, growth, cognition, and overall health. Despite recommendations to treat PSAC with schistosomiasis, this age group is still excluded from treatment programmes for various reasons including: a) the lack of a child-friendly formulation of praziquantel, b) lack of a coherent strategy to access PSAC for screening and treatment, and c) lack of compelling evidence on infection, disease and treatment dynamics. Currently, the global infection and disease burden is not fully known in this age group, and longitudinal studies to describe the incidence of infection and morbidity, especially the early events that occur during the very first infection and treatment in PSAC are lacking. In addition, the mechanistic pathways of disease, treatment, and immunity are poorly understood in this age group. Operational difficulties including obtaining parasitology samples for diagnosis, failure to detect light infections, and inadequate knowledge about risk factors have also contributed to a lower research focus on PSAC, relative to school-aged children and adults.
To address these, I completed a series of studies, based on a larger longitudinal study on paediatric urogenital schistosomiasis (population age range: 6 months–5 years) conducted in the Shamva district of Zimbabwe. The aim was to determine the dynamics of infection, morbidity and treatment of the first S. haematobium infection, and to examine the impact of a regular screening and treatment strategy on (re)infections. I also determined the early host metabolic changes associated with the first S. haematobium infection as well as the impact of schistosome infection on the gut microbiome, and how these relate to disease progression, morbidity and overall health.
I determined that 92% of microhaematuria, 38% of stunting, and between 9%–34% of malnutrition (depending on what index is used) are attributable to S. haematobium infection in PSAC; schistosome-positive children were more likely to present with microhaematuria (25 times) and stunting (2 times), compared to uninfected children. I demonstrated the annual incidence of first schistosome infections (17.4%) and urinary morbidity (microhaematuria; 20.4%), with significant incidences recorded every quarter. I showed that within 3 months of the first infection, a significant amount of urinary morbidity, i.e. microhaematuria (61%) occurs, and is resolved 3 months post-praziquantel treatment.
In PSAC with no history of schistosome infection, regular quarterly screening and treatment of the first S. haematobium infection reduces the actual time at risk of infection in the population, and results in reduced rates of subsequent new infections. A single praziquantel treatment of schistosome infections (upon first infection) was associated with reduced reinfection rates and intensity a year later; an effect comparable to that observed post-treatment in chronically-infected children.
In young children experiencing their first schistosome infection, there are significant increases (≥2-fold) in serum metabolites primarily linked with energy (glycolysis, pentose phosphate pathway, starch, and galactose) and purine metabolism. The observed changes were commensurate with increasing infection intensity and were restored 3 months post-curative antihelminthic treatment. The affected metabolic pathways and its implications on the natural adaptive metabolic responses were consistent with parasite survival and development of schistosome morbidity in PSAC, including malnutrition, stunting and poor physical and cognitive performance.
Metagenomic analysis of the gut microbiota showed that the abundance of bacteria and fungi phyla from Proteobacteria, Ascomycota, and Basidiomycota, differed between schistosome-infected versus uninfected children. Specifically, infection was associated with increases in Pseudomonas, Stenotrophomonas, Derxia, Thalassospira, Aspergillus, Tricholoma, and Periglandula, and a decrease in Azospirillum. I found evidence of 262 antimicrobial resistance genes, from 12 functional drug classes, but these showed no association with individual-specific data, including schistosome infection. This points to microbiome dysbiosis as an additional consequence of schistosome infection, with implications for morbidity, immunity, and overall health.
Taken together, the findings of this thesis show that early in the first S. haematobium infection, PSAC present with significant morbidity, and this resolves quickly with praziquantel treatment. A routine screen-and-treat strategy will optimise the chances of detecting and treating infections early, while reducing the risk of new and reinfections. The findings further highlight microbiome and metabolic alterations during schistosome infection, which may be relevant for disease pathogenesis. This thesis presents an integrative approach to schistosomiasis studies in PSAC, which contributes to evidence on infection/disease burden and dynamics, the applicability of currently available tools in the diagnosis, treatment and control of schistosomiasis, as well as the systemic impacts of infection on the host microbiome, metabolism, and overall health. It also adds to the repository of information, by providing a novel metagenomics and metabolomics dataset of PSAC from Zimbabwe. The findings reaffirm the need for early diagnosis and treatment of schistosome infections in PSAC to avert accumulative morbidity, and will inform stakeholders in providing new and appropriate interventions targeted at reducing schistosome-related pathology in young children
Cytokine responses to <it>Schistosoma haematobium </it>in a Zimbabwean population: contrasting profiles for IFN-γ, IL-4, IL-5 and IL-10 with age
No full textAbstract Background The rate of development of parasite-specific immune responses can be studied by following their age profiles in exposed and infected hosts. This study determined the cytokine-age profiles of Zimbabweans resident in a Schistosoma haematobium endemic area and further investigated the relationship between the cytokine responses and infection intensity. Methods Schistosome adult worm antigen-specific IFN-γ, IL-4, IL-5 and IL-10 cytokine responses elicited from whole blood cultures were studied in 190 Zimbabweans exposed to S. haematobium infection (aged 6 to 40 years old). The cytokines were measured using capture ELISAs and the data thus obtained together with S. haematobium egg count data from urine assays were analysed using a combination of parametric and nonparametric statistical approaches. Results Age profiles of schistosome infection in the study population showed that infection rose to peak in childhood (11–12 years) followed by a sharp decline in infection intensity while prevalence fell more gradually. Mean infection intensity was 37 eggs/10 ml urine (SE 6.19 eggs/10 ml urine) while infection prevalence was 54.7%. Measurements of parasite-specific cytokine responses showed that IL-4, IL-5 and IL-10 but not IFN-γ followed distinct age-profiles. Parasite-specific IL-10 production developed early, peaking in the youngest age group and declining thereafter; while IL-4 and IL-5 responses were slower to develop with a later peak. High IL-10 producers were likely to be egg positive with IL-10 production increasing with increasing infection intensity. Furthermore people producing high levels of IL-10 produced little or no IL-5, suggesting that IL-10 may be involved in the regulation of IL-5 levels. IL-4 and IFN-γ did not show a significant relationship with infection status or intensity and were positively associated with each other. Conclusion Taken together, these results show that the IL-10 responses develop early compared to the IL-5 response and may be down-modulating immunopathological responses that occur during the early phase of infection. The results further support current suggestions that the Th1/Th2 dichotomy does not sufficiently explain susceptibility or resistance to schistosome infection.</p
Differential recognition patterns of Schistosoma haematobium adult worm antigens by the human antibodies IgA, IgE, IgG1 and IgG4
No full textAbstract Schistosoma haematobium antigen recognition profiles of the human isotypes IgA, IgE, IgG1 and IgG4 were compared by image analysis of western blots. Adult worm antigens separated by 2-dimensional gel electrophoresis were probed with pooled sera from Zimbabweans resident in a S. haematobium endemic area, followed by identification of individual antigenic parasite proteins using mass spectrometry. Overall, IgG1 reacted with the largest number of antigens, followed by IgE and IgA which detected the same number, while IgG4 detected the fewest antigens. IgE recognised all the antigens reactive with IgG4 as well as an additional four antigens; an isoform of 28kDaGST, phosphoglycerate kinase, actin 1 and calreticulin. IgG1 additionally recognised fatty acid binding protein, triose-phosphate isomerase, and heat shock protein 70, which were not recognised by IgA. Recognition patterns varied between some isoforms e.g. the 2 fructose 1-6-bis-phosphate aldolase isoforms differentially recognised by IgA and IgG1. Although the majority of S. haematobium adult worm antigens are recognised by all the four isotypes there are clear restrictions in antibody recognition for some antigens. This may partly explain differences observed in isotype dynamics at a population level. Differential recognition patterns for some isoforms indicated in the study have potential importance for vaccine developmen
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