ABO Blood Groups Do Not Predict Schistosoma mansoni Infection Profiles in Highly Endemic Villages of Uganda

Schistosoma mansoni is a parasite which causes significant public-health issues, with over 240 mil-lion people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the ef-fect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemio-logical link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities

Impacts of host gender on Schistosoma mansoni risk in rural Uganda-A mixed-methods approach

Background The World Health Organization identified Uganda as one of the 10 highly endemic countries for schistosomiasis. Annual mass drug administration (MDA) with praziquantel has led to a decline in intensity of Schistosoma mansoni infections in several areas. However, as hotspots with high (re)infection rates remain, additional research on risk factors and implementing interventions to complement MDA are required to further reduce disease burden in these settings. Through a mixed-methods study we aimed to gain deeper understanding of how gender may impact risk and reinfection in order to inform disease control programmes and ascertain if gender-specific interventions may be beneficial. Methodology/Principal findings In Bugoto, Mayuge District, Eastern Uganda we conducted ethnographic observations (n = 16) and examined epidemiology (n = 55) and parasite population genetics (n = 16) in school-aged children (SAC), alongside a community-wide household survey (n = 130). Water contact was frequent at home, school and in the community and was of domestic, personal care, recreational, religious or commercial nature. Qualitative analysis of type of activity, duration, frequency, level of submersion and water contact sites in children showed only few behavioural differences in water contact between genders. However, survey data revealed that adult women carried out the vast majority of household tasks involving water contact. Reinfection rates (96% overall) and genetic diversity were high in boys (pre-He = 0.66; post-He = 0.67) and girls (pre-He = 0.65; post-He = 0.67), but no differences in reinfection rates (p = 0.62) or genetic diversity by gender before (p = 0.54) or after (p = 0.97) treatment were found. Conclusions/Significance This mixed methods approach showed complementary findings. Frequent water exposure with few differences between boys and girls was mirrored by high reinfection rates and genetic diversity in both genders. Disease control programmes should consider the high reinfection rates among SAC in remaining hotspots of schistosomiasis and the various purposes and settings in which children and adults are exposed to water

ABO Blood Groups Do Not Predict Schistosoma mansoni Infection Profiles in Highly Endemic Villages of Uganda

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-23, pub-electronic 2021-11-27Publication status: PublishedFunder: European Research Council; Grant(s): 680088 SCHISTO_PERSISTFunder: Wellcome Trust; Grant(s): 204820/Z/16/ZFunder: Engineering and Physical Sciences Research Council; Grant(s): EP/T003618/1, EP/R01437X/Funder: Medical Research Council; Grant(s): MR/P025447/1Schistosoma mansoni is a parasite which causes significant public-health issues, with over 240 million people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the effect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemiological link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities

Translating from egg- to antigen-based indicators for Schistosoma mansoni elimination targets: A Bayesian latent class analysis study

This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations

Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test (POC-CCA) in two Schistosoma mansoni endemic areas in Uganda

Over 240 million people are infected with schistosomiasis. Detecting Schistosoma mansoni eggs in stool using Kato–Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’

Translating From Egg- to Antigen-Based Indicators for Schistosoma mansoni Elimination Targets: A Bayesian Latent Class Analysis Study

From Frontiers via Jisc Publications RouterHistory: received 2021-11-30, collection 2022, accepted 2022-01-12, epub 2022-02-18Publication status: PublishedSchistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations

Investigating portable fluorescent microscopy (CyScope®) as an alternative rapid diagnostic test for malaria in children and women of child-bearing age

<p>Abstract</p> <p>Background</p> <p>Prompt and correct diagnosis of malaria is crucial for accurate epidemiological assessment and better case management, and while the gold standard of light microscopy is often available, it requires both expertise and time. Portable fluorescent microscopy using the CyScope^®offers a potentially quicker, easier and more field-applicable alternative. This article reports on the strengths, limitations of this methodology and its diagnostic performance in cross-sectional surveys on young children and women of child-bearing age.</p> <p>Methods</p> <p>552 adults (99% women of child-bearing age) and 980 children (99% ≤ 5 years of age) from rural and peri-urban regions of Ugandan were examined for malaria using light microscopy (Giemsa-stain), a lateral-flow test (Paracheck-Pf^®) and the CyScope^®. Results from the surveys were used to calculate diagnostic performance (sensitivity and specificity) as well as to perform a receiver operating characteristics (ROC) analyses, using light microscopy as the gold-standard.</p> <p>Results</p> <p>Fluorescent microscopy (qualitative reads) showed reduced specificity (<40%), resulting in higher community prevalence levels than those reported by light microscopy, particularly in adults (+180% in adults and +20% in children). Diagnostic sensitivity was 92.1% in adults and 86.7% in children, with an area under the ROC curve of 0.63. Importantly, optimum performance was achieved for higher parasitaemia (>400 parasites/μL blood): sensitivity of 64.2% and specificity of 86.0%. Overall, the diagnostic performance of the CyScope was found inferior to that of Paracheck-Pf^®.</p> <p>Discussion</p> <p>Fluorescent microscopy using the CyScope^®is certainly a field-applicable and relatively affordable solution for malaria diagnoses especially in areas where electrical supplies may be lacking. While it is unlikely to miss higher parasitaemia, its application in cross-sectional community-based studies leads to many false positives (i.e. small fluorescent bodies of presently unknown origin mistaken as malaria parasites). Without recourse to other technologies, arbitration of these false positives is presently equivocal, which could ultimately lead to over-treatment; something that should be further explored in future investigations if the CyScope^®is to be more widely implemented.</p

Anonymised raw Schistosoma mansoni and host ABO blood group data for: Francoeur et al. ABO blood group do not predict Schistosoma mansoni infection profiles in highly endemic villages of Uganda

Raw anonymised Schistosoma mansoni and human host ABO blood group dataset from school-aged children, aged 6-14, from three high endemicity villages in Mayuge District Uganda. Data include age, sex, height, weight, village, date, timepoint pre and post treatment with praziquantel and albendazole, up to three days per timepoint of duplicate Kato-Katz slides with infection intensity data for S. mansoni and soil-transmitted helminth infections, including hookworm, Ascaris lumbricoides, Trichuris trichiura, Hymenolepis nana, and Enterobius vermicularis, recorded, and ABO and Rhesus positive or negative blood group type

ABO Blood Groups Do Not Predict <i>Schistosoma mansoni</i> Infection Profiles in Highly Endemic Villages of Uganda.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-11-01, epub 2021-11-27Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/P025447/1Funder: European Research Council; Grant(s): 680088 SCHISTO_PERSISTFunder: Engineering and Physical Sciences Research Council; Grant(s): EP/R01437X/, EP/T003618/1Funder: Wellcome Trust; Grant(s): 204820/Z/16/ZSchistosoma mansoni is a parasite which causes significant public-health issues, with over 240 million people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the effect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemiological link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities