Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control.... Show moreControl of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits. Show less
Background Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated... Show moreBackground Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated with increased vascularity. If FGS is associated with the presence of hemoglobin in cervicovaginal lavage (CVL), the use of urinary reagent strips to detect hemoglobin in CVL could supplement FGS diagnosis. Methods Nonmenstruating, nonpregnant, sexually active women aged 18-31 participating in the HPTN 071 (PopART) Population-Cohort were invited in 2 Zambian communities. Genital self-swabs and a urine specimen were collected at a home visit, and CVL and hand-held colposcopy were performed at a midwife led clinic visit. Urinary reagent strips were used to identify hemoglobin in CVL. Eggs and circulating anodic antigen (CAA) were detected from urine. Visual-FGS was defined as the presence of sandy patches, rubbery papules, or abnormal blood vessels. Polymerase chain reaction (PCR)-FGS was defined as Schistosoma deoxyribonucleic acid detected by real-time PCR on CVL or cervical or vaginal swab. Results Of 209 women with home genital swabs and companion CVL specimens, 66% (138 of 209) had detectable CVL hemoglobin, 13.4% (28 of 209) had PCR-defined FGS, and 17.2% (36 of 209) had visual-FGS. Active Schistosoma infection, diagnosed by CAA or urine microscopy, was present in 21.0% (44 of 209) participants. Active Schistosoma infection (P = .4), PCR-FGS (P = 0.7), and visual-FGS (P = 0.3) were not associated with CVL hemoglobin presence. Results did not differ in subgroups with high infection burden (cycle threshold < 35 or 2-3 positive genital PCR). Conclusions Polymerase chain reaction-FGS, visual-FGS, and active Schistosoma infection were not associated with the presence of CVL hemoglobin. Further research is needed to establish accessible community-based FGS diagnostics.Urinary reagent strips (URS) are useful for estimating S haematobium prevalence. Female genital schistosomiasis (FGS) occurs as a complication of S haematobium infection and is associated with cervical mucosal changes. This study evaluates URS in cervicovaginal lavage for FGS diagnosis. Show less
Background Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated... Show moreBackground Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated with increased vascularity. If FGS is associated with the presence of hemoglobin in cervicovaginal lavage (CVL), the use of urinary reagent strips to detect hemoglobin in CVL could supplement FGS diagnosis. Methods Nonmenstruating, nonpregnant, sexually active women aged 18-31 participating in the HPTN 071 (PopART) Population-Cohort were invited in 2 Zambian communities. Genital self-swabs and a urine specimen were collected at a home visit, and CVL and hand-held colposcopy were performed at a midwife led clinic visit. Urinary reagent strips were used to identify hemoglobin in CVL. Eggs and circulating anodic antigen (CAA) were detected from urine. Visual-FGS was defined as the presence of sandy patches, rubbery papules, or abnormal blood vessels. Polymerase chain reaction (PCR)-FGS was defined as Schistosoma deoxyribonucleic acid detected by real-time PCR on CVL or cervical or vaginal swab. Results Of 209 women with home genital swabs and companion CVL specimens, 66% (138 of 209) had detectable CVL hemoglobin, 13.4% (28 of 209) had PCR-defined FGS, and 17.2% (36 of 209) had visual-FGS. Active Schistosoma infection, diagnosed by CAA or urine microscopy, was present in 21.0% (44 of 209) participants. Active Schistosoma infection (P = .4), PCR-FGS (P = 0.7), and visual-FGS (P = 0.3) were not associated with CVL hemoglobin presence. Results did not differ in subgroups with high infection burden (cycle threshold < 35 or 2-3 positive genital PCR). Conclusions Polymerase chain reaction-FGS, visual-FGS, and active Schistosoma infection were not associated with the presence of CVL hemoglobin. Further research is needed to establish accessible community-based FGS diagnostics.Urinary reagent strips (URS) are useful for estimating S haematobium prevalence. Female genital schistosomiasis (FGS) occurs as a complication of S haematobium infection and is associated with cervical mucosal changes. This study evaluates URS in cervicovaginal lavage for FGS diagnosis. Show less
BackgroundFemale genital schistosomiasis (FGS) is a neglected and disabling gynecological disease that can result from infection with the parasitic trematode Schistosoma haematobium. Accurate... Show moreBackgroundFemale genital schistosomiasis (FGS) is a neglected and disabling gynecological disease that can result from infection with the parasitic trematode Schistosoma haematobium. Accurate diagnosis of FGS is crucial for effective case management, surveillance and control. However, current methods for diagnosis and morbidity assessment can be inaccessible to those at need, labour intensive, costly and unreliable. Molecular techniques such as PCR can be used to reliably diagnose FGS via the detection of Schistosoma DNA using cervicovaginal lavage (CVL) samples as well as lesser-invasive vaginal self-swab (VSS) and cervical self-swab samples. PCR is, however, currently unsuited for use in most endemic settings. As such, in this study, we assessed the use of a rapid and portable S. haematobium recombinase polymerase amplification (Sh-RPA) isothermal molecular diagnostic assay, coupled with simplified sample preparation methodologies, to detect S. haematobium DNA using CVL and VSS samples provided by patients in Zambia.Methodology/Principal findingsVSS and CVL samples were screened for FGS using a previously developed Sh-RPA assay. DNA was isolated from VSS and CVL samples using the QIAamp Mini kit (n = 603 and 527, respectively). DNA was also isolated from CVL samples using two rapid and portable DNA extraction methods: 1) the SpeedXtract Nucleic Acid Kit (n = 223) and 2) the Extracta DNA Tissue Prep Kit (n = 136). Diagnostic performance of the Sh-RPA using VSS DNA extacts (QIAamp Mini kit) as well as CVL DNA extracts (OIAamp Mini kit, SpeedXtract Nucleic Acid Kit and Extracta DNA Tissue Prep Kit) was then compared to a real-time PCR reference test.Results suggest that optimal performance may be achieved when the Sh-RPA is used with PuVSS samples (sensitivity 93.3%; specificity 96.6%), however no comparisons between different DNA extraction methods using VSS samples could be carried out within this study. When using CVL samples, sensitivity of the Sh-RPA ranged between 71.4 and 85.7 across all three DNA extraction methods when compared to real-time PCR using CVL samples prepared using the QIAamp Mini kit. Interestingly, of these three DNA extraction methods, the rapid and portable SpeedXtract method had the greatest sensitivity and specificity (85.7% and 98.1%, respectively). Specificity of the Sh-RPA was >91% across all comparisons.Conclusions/SignificanceThese results supplement previous findings, highlighting that the use of genital self-swab sampling for diagnosing FGS should be explored further whilst also demonstrating that rapid and portable DNA isolation methods can be used to detect S. haematobium DNA within clinical samples using RPA. Although further development and assessment is needed, it was concluded that the Sh-RPA, coupled with simplified sample preparation, shows excellent promise as a rapid and sensitive diagnostic tool capable of diagnosing FGS at the point-of-care in resource-poor schistosomiasis-endemic settings. Show less
Background. The cervicovaginal microbiota, including sexually transmitted infections (STIs), have not been well described in female genital schistosomiasis (FGS).Methods. Women (aged 18-31,... Show moreBackground. The cervicovaginal microbiota, including sexually transmitted infections (STIs), have not been well described in female genital schistosomiasis (FGS).Methods. Women (aged 18-31, sexually active, nonpregnant) were invited to participate at the final follow-up of the HPTN 071 (PopART) Population Cohort in January-August 2018. We measured key species of the cervicovaginal microbiota (Lactobacillus crispatus, L. iners, Gardnerella vaginalis, Atopobium vaginae, and Candida) and STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) using quantitative PCR (qPCR). We evaluated associations of the microbiota and STI presence and concentration with FGS (qPCR-detected Schistosoma DNA in any of 3 genital specimens).Results. The presence and concentration of key cervicovaginal species did not differ between participants with (n = 30) or without FGS (n = 158). A higher proportion of participants with FGS had T. vaginalis compared with FGS-negative women (P = .08), with further analysis showing that T. vaginalis was more prevalent among women with >= 2 Schistosoma qPCR-positive genital specimens (50.0%, 8/16) than among FGS-negative women (21.5%, 34/158; P = .01).Conclusions. We found weak evidence of an association between the presence of T. vaginalis and FGS, with a stronger association in women with a higher-burden FGS infection. Additional research is needed on potential between-parasite interactions, especially regarding HIV-1 vulnerability. Show less
Koopman, J.P.R.; Lule, S.A.; Zziwa, C.; Akurut, H.; Lubyayi, L.; Nampijja, M.; ... ; Bradley, J. 2021
Background Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium,... Show moreBackground Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. Methods Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. Results VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). Conclusions This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed. Show less
Background. Female genital schistosomiasis (FGS) has been associated with prevalent HIV-1. We estimated the incidence of HIV-1 infection in Zambian women with and without FGS.Methods. Women (aged... Show moreBackground. Female genital schistosomiasis (FGS) has been associated with prevalent HIV-1. We estimated the incidence of HIV-1 infection in Zambian women with and without FGS.Methods. Women (aged 18-31, nonpregnant, sexually active) were invited to participate in this study in January-August 2018 at the final follow-up of the HPTN 071 (PopART) Population Cohort. HIV-1-negative participants at enrollment (n = 492) were included in this analysis, with testing to confirm incident HIV-1 performed in HPTN 071 (PopART). The association of incident HIV-1 infection with FGS (Schistosoma DNA detected by polymerase chain reaction [PCR] in any genital specimen) was assessed with exact Poisson regression.Results. Incident HIV-1 infections were observed in 4.1% (20/492) of participants. Women with FGS were twice as likely to seroconvert as women without FGS but with no statistical evidence for a difference (adjusted rate ratio, 2.16; 95% CI, 0.21-12.30; P = .33). Exploratory analysis suggested an association with HIV-1 acquisition among women with >= 2 positive genital PCR specimens (rate ratio, 6.02; 95% CI, 0.58-34.96; P = .13).Conclusions. Despite higher HIV seroconversion rates in women with FGS, there was no statistical evidence of association, possibly due to low power. Further longitudinal studies should investigate this association in a setting with higher schistosomiasis endemicity. Show less
HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis ... Show moreHIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1 alpha (CCL-3), MIP-1 beta (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18-31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy and Schistosoma circulating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positive Schistosoma PCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negative Schistosoma PCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by >= 2 genital specimens with detectable Schistosoma DNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability. Show less
Background In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also... Show moreBackground In high-income, temperate countries, IgE to allergen extracts is a risk factor for, and mediator of, allergy-related diseases (ARDs). In the tropics, positive IgE tests are also prevalent, but rarely associated with ARD. Instead, IgE responses to ubiquitous cross-reactive carbohydrate determinants (CCDs) on plant, insect and parasite glycoproteins, rather than to established major allergens, are dominant. Because anti-CCD IgE has limited clinical relevance, it may impact ARD phenotyping and assessment of contribution of atopy to ARD. Methods Using an allergen extract-based test, a glycan and an allergen (glyco)protein microarray, we mapped IgE fine specificity among Ugandan ruralSchistosoma mansoni(Sm)-endemic communities, proximate urban communities, and importantly in asthmatic and nonasthmatic schoolchildren. Results Overall, IgE sensitization to extracts was highly prevalent (43%-73%) but allergen arrays indicated that this was not attributable to established major allergenic components of the extracts (0%-36%); instead, over 40% of all participants recognized CCD-bearing components. Using glycan arrays, we dissected IgE responses to specific glycan moieties and found that reactivity to classical CCD epitopes (core beta-1,2-xylose, alpha-1,3-fucose) was positively associated with sensitization to extracts, rural environment andSminfection, but not with skin reactivity to extracts or sensitization to their major allergenic components. Interestingly, we discovered that reactivity to only a subset of core alpha-1,3-fucose-carrying N-glycans was inversely associated with asthma. Conclusions CCD reactivity is not just an epiphenomenon of parasite exposure hampering specificity of allergy diagnostics; mechanistic studies should investigate whether specific CCD moieties identified here are implicated in the protective effect of certain environmental exposures against asthma. Show less
Background Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV ... Show moreBackground Given the potentially causal association of female genital schistosomiasis (FGS) with HIV-1 infection, improved diagnostics are urgently needed to scale-up FGS surveillance. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared to cervicovaginal lavage (CVL) for the detection ofSchistosomaDNA by real-time polymerase chain reaction (PCR). Methods Between January and August 2018, a consecutive series of female participants from the Population-Cohort of the previous HIV prevention trial HPTN 071 (PopART), resident in Livingstone, Zambia were invited to take part in BILHIV if they were 18-31 years old, non-pregnant and sexually active. Genital self-collected swabs and a urine specimen were obtained and a questionnaire completed at home visits. CVL was obtained at clinic follow-up. Results 603 women self-collected genital swabs. Of these, 527 women had CVL performed by a mid-wife during clinic follow-up.SchistosomaDNA was more frequently detected in genital self-collected specimens (24/603, 4.0%) compared to CVL (14/527, 2.7%). Overall, 5.0% (30/603) women had female genital schistosomiasis, defined as a positive PCR by any genital sampling method (cervical swab PCR, vaginal swab PCR, or CVL PCR) and 95% (573/603) did not have a positive genital PCR. The sensitivity of any positive genital self-collected swab against CVL was 57.1% (95% CI 28.9-82.3%), specificity 97.3% (95.5-98.5%). In a subset of participants with active schistosome infection, determined by detectable urine Circulating Anodic Antigen (CAA) (15.1%, 91/601), positive PCR (4.3%, 26/601), or positive microscopy (5.5%, 33/603), the sensitivity of any positive self-collected specimen against CVL was 88.9% (51.8-99.7%). Conclusions Genital self-sampling increased the overall number of PCR-based FGS diagnoses in a field setting, compared with CVL. Home-based sampling may represent a scalable alternative method for FGS community-based diagnosis in endemic resource limited settings.Author summary Female Genital schistosomiasis (FGS) is a neglected and disabling disease that results when eggs from the waterborne parasiteSchistosoma haematobiumare trapped in the human reproductive tract. Current female genital schistosomiasis (FGS) diagnostic strategies are limited because they require expertise and equipment that may not be readily available in low income settings. Improved and accessible diagnostics are urgently needed to scale-up FGS surveillance. This is especially important as FGS has been associated with HIV-1 infection. The BILHIV (bilharzia and HIV) study assessed the performance of home-based self-collection methods (cervical and vaginal swabs) compared with a clinic-based cervicovaginal lavage (CVL) performed by a medical professional. Both methods used real-time polymerase chain reaction (PCR) to detectSchistosomaDNA. We found that, in a field setting, self-collected genital and cervical swabs increased the overall number of PCR-based FGS diagnoses, compared with clinically collected CVL. We report the sensitivity of self-collected swabs for the diagnosis of FGS, compared with CVL. We found that the sensitivity of self-collected genital swabs was high in a subset of women with active schistosome infection. We suggest that home-based self-sampling may represent a scalable community-based sampling platform for FGS community-based diagnosis in endemic resource limited settings. Show less
Background. Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated... Show moreBackground. Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure.Methods. We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants.Results. Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, -13%; 95% CI, -48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA.Conclusions. In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era. Show less
Background: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.Objective:... Show moreBackground: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.Objective: We aimed to assess how helminth exposure influences rural-urban differences in risk factors for allergy-related outcomes in tropical low- and middle-income countries.Methods: In cross-sectional surveys in Ugandan rural Schistosoma mansoni (Sm)-endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen-specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy-related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure.Results: Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma-specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non-Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm- and Schistosoma-specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma-specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural-urban differences in risk factors.Conclusions and clinical relevance: Risk factors for allergy-related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly. Show less
Nkurunungi, G.; Diepen, A. van; Nassuuna, J.; Sanya, R.E.; Nampijja, M.; Nambuya, I.; ... ; Hokke, C.H. 2019
Core beta-1,2-xylose and alpha-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of... Show moreCore beta-1,2-xylose and alpha-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of schistosome infection with responses to these motifs, we assessed plasma IgE and IgG reactivity using microarray technology among Ugandans from rural Schistosoma mansoni (Sm)-endemic islands (n = 209), and from proximate urban communities with lower Sm exposure (n = 62). IgE and IgG responses to core beta-1,2-xylose and alpha-1,3-fucose modified N-glycans were higher in rural versus urban participants. Among rural participants, IgE and IgG to core beta-1,2-xylose were positively associated with Sm infection and concentration peaks coincided with the infection intensity peak in early adolescence. Responses to core alpha-1,3-fucose were elevated regardless of Sm infection status and peaked before the infection peak. Among urban participants, Sm infection intensity was predominantly light and positively associated with responses to both motifs. Principal component and hierarchical cluster analysis reduced the data to a set of variables that captured core beta-1,2-xylose- and alpha-1,3-fucose-specific responses, and confirmed associations with Sm and the rural environment. Responses to core beta-1,2-xylose and alpha-1,3-fucose have distinctive relationships with Sm infection and intensity that should further be explored for associations with protective immunity, and cross-reactivity with other exposures. Show less
