The increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses... Show moreThe increasing number of refugees coming from or passing through Schistosoma-endemic areas and arriving in Europe highlights the importance of screening for schistosomiasis on arrival, and focuses attention on the choice of diagnostic test. We evaluate the diagnostic performance of circulating anodic antigen (CAA) detection in 92 asymptomatic refugees from Eritrea. Results were compared with already-available stool microscopy, serology, and urine point-of-care circulating cathodic antigen (POC-CCA) data. For a full diagnostic comparison, real-time polymerase chain reaction (PCR) and the POC-CCA were included. All outcomes were compared against a composite reference standard. Urine and serum samples were subjected to the ultra-sensitive and highly specific up-converting particle lateral flow CAA test, Schistosoma spp. real-time PCR was performed on urine and stool, and the POC-CCA was used on urine using the G-score method. CAA was detected in 43% of urine and in 40% of serum samples. Urine PCR was negative in all 92 individuals, whereas 25% showed Schistosoma DNA in stool. POC-CCA was positive in 30% of individuals. The CAA test confirmed all microscopy positives, except for two cases that were also negative by all other diagnostic procedures. Post-treatment, a significant reduction in the number of positives and infection intensity was observed, in particular regarding CAA levels. Our findings confirm that microscopy, serology, and POC-CCA lack the sensitivity to detect all active Schistosoma infections. Accuracy of stool PCR was similar to microscopy, indicating that this method also lacks sensitivity. The CAA test appeared to be the most accurate method for screening active Schistosoma infections and for monitoring treatment efficacy. Show less
Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We... Show moreLung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity. Show less
In low-endemicity settings, current tools for the diagnosis and surveillance of schistosomiasis are often inaccurate in detecting true infection. We assessed the accuracy of an up-converting... Show moreIn low-endemicity settings, current tools for the diagnosis and surveillance of schistosomiasis are often inaccurate in detecting true infection. We assessed the accuracy of an up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) test and a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for the diagnosis of Schistosoma mansoni. Our study was conducted in eight schools of western Co<^>te d'Ivoire. Fifty children, aged 9-12 years, were enrolled per school. From each child, a single urine specimen and two stool specimens were collected over consecutive days for diagnostic work-up. Urine samples were subjected to UCP-LF CAA and POC-CCA tests. From each stool sample, triplicate Kato-Katz thick smears were examined. Overall, 378 children had complete data records. The prevalence of S. mansoni, as assessed by six Kato-Katz thick smears, was 4.0%. The UCP-LF CAA and POC-CCA tests revealed S. mansoni prevalence of 25.4% and 30.7%, respectively, when considering trace results as positive, and prevalence of 23.3% and 10.9% when considering trace results as negative. In the latter case, based on a composite "gold" standard, the sensitivity of UCP-LF CAA (80.7%) was considerably higher than that of POC-CCA (37.6%) and six Kato-Katz thick smears (13.8%). The negative predictive value of UCP-LF CAA, POC-CCA, and six Kato-Katz thick smears was 92.8%, 79.8%, and 74.1%, respectively. Our results confirm that UCP-LF CAA is more accurate than Kato-Katz and POC-CCA for the diagnosis of S. mansoni in low-endemicity settings. Show less
Lindert, L. te; Deijl, M. van der; Elirehema, A.; Elteren-Jansen, M. van; Chitanda, R.; Akker, T. van den 2021
High prevalence of teenage pregnancy in low-income countries impacts health, social, economic, and educational situations of teenage girls. To acquire better understanding of factors leading to... Show moreHigh prevalence of teenage pregnancy in low-income countries impacts health, social, economic, and educational situations of teenage girls. To acquire better understanding of factors leading to high prevalence of teenage pregnancy in rural Lindi region, Tanzania, we explored perspectives of girls and key informants by conducting a facilitybased explorative qualitative study according to the grounded theory approach. Participants were recruited from Mnero Diocesan Hospital using snowball sampling, between June and September 2018. Eleven pregnant teenagers, two girls without a teenage pregnancy, and eight other key informants were included. In-depth interviews (including photovoice) and field observations were conducted. Analysis of participant perspectives revealed five main themes: 1) lack of individual agency (peer pressure, limited decision-making power, and sexual coercion); 2) desire to earn money and get out of poverty; 3) dropping out of school contributing to becoming pregnant; 4) absence of financial, material, psychological, or emotional support from the environment; and 5) limited access to contraception. A majority of girls reported the pregnancy to be unplanned, whereas some girls purposely planned it. Our findings and the resulting conceptual framework contribute to a new social theory and may inform national and international policies to consider the needs and perspectives of teenagers in delaying pregnancy and promoting sexual and reproductive health in Tanzania and beyond. Show less
The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis... Show moreThe Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite eggdetection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications. Show less
The field standard for the detection of Schistosoma mansoni infection is Kato-Katz (KK), although it misses many active infections, especially light infections. In 2014, a reassessment of S.... Show moreThe field standard for the detection of Schistosoma mansoni infection is Kato-Katz (KK), although it misses many active infections, especially light infections. In 2014, a reassessment of S. mansoni prevalence was conducted in Rwanda using the more sensitive point-of-care circulating cathodic antigen (POC-CCA) rapid assay. A total of 19,371 children from 399 schools were selected for testing for single urine CCA. Of these, 8,697 children from 175 schools were also tested with single stool double-slide KK. Samples from eight of these 175 schools were tested again with CCA and additionally with the highly specific and sensitive up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay. Latent class analysis was applied to all four test results to assess sensitivity and specificity of POC-CCA and estimate the proportion of trace results from Rwanda likely to be true infections. The overall prevalence of S. mansoni infection in Rwanda when CCA trace results were considered negative was 7.4% (school interquartile range [IQR] 0-8%) and 36.1 % (school IQR 20-47%) when trace was considered positive. Prevalence by KK was 2.0% with a mean intensity of infection of 1.66 eggs per gram. The proportion of active infections among children diagnosed with CCA trace was estimated by statistical analysis at 61 % (Bayesian credibility interval: 50-72%). These results indicate that S. mansoni infection is still widespread in Rwanda and prevalence is much underestimated by KK testing. Circulating cathodic antigen is an affordable alternative to KK and more suitable for measuring S. mansoni prevalence in low-intensity regions. Show less
Elevated circulating endotoxin levels in the plasma of patients with advanced hepatosplenic schistosomiasis caused by Schistosoma mansoni have been reported, possibly caused by parasite egg-induced... Show moreElevated circulating endotoxin levels in the plasma of patients with advanced hepatosplenic schistosomiasis caused by Schistosoma mansoni have been reported, possibly caused by parasite egg-induced intestinal mucosal breaches facilitating bacterial access to the bloodstream. Neither endotoxin levels in people with S. mansoni but without hepatosplenic disease nor the impact of treatment on endotoxin levels have been described. We used a methodically optimized Limulus amebocyte lysate assay to measure plasma endotoxin in community-dwelling women from an S. mansoni-endemic area without clinical hepatosplenic disease. We found no difference in baseline mean plasma endotoxin levels between those with (n = 22) and without (n = 31) infection (1.001 versus 0.949 EU/mL, P= 0.61). Endotoxin levels did not change in schistosome-infected women after successful treatment (1.001 versus 1.093 EU/mL, P = 0.45) and were not correlated with circulating anodic antigen or stool egg burden. Our findings do not support the hypothesis that translocating eggs in S. mansoni infection introduce bacterial sources of endotoxin to the circulation. Show less
Saint Lucia at one time had levels of schistosomiasis prevalence and morbidity as high as many countries in Africa. However, as a result of control efforts and economic development, including more... Show moreSaint Lucia at one time had levels of schistosomiasis prevalence and morbidity as high as many countries in Africa. However, as a result of control efforts and economic development, including more widespread access to sanitation and safe water, schistosomiasis on the island has practically disappeared. To evaluate the current status of schistosomiasis in Saint Lucia, we conducted a nationally representative school-based survey of 8-11-year-old children for prevalence of Schistosoma mansoni infections using circulating antigen and specific antibody detection methods. We also conducted a questionnaire about available water sources, sanitation, and contact with fresh water. The total population of 8-11-year-old children on Saint Lucia was 8,985; of these, 1,487 (16.5%) provided urine for antigen testing, 1,455 (16.2%) provided fingerstick blood for antibody testing, and 1,536 (17.1%) answered the questionnaire. Although a few children were initially low positives by antigen or antibody detection methods, none could be confirmed positive by follow-up testing. Most children reported access to clean water and sanitary facilities in or near their homes and 48% of the children reported contact with fresh water. Together, these data suggest that schistosomiasis transmission has been interrupted on Saint Lucia. Additional surveys of adults, snails, and a repeat survey among school-age children will be necessary to verify these findings. However, in the same way that research on Saint Lucia generated the data leading to use of mass drug administration for schistosomiasis control, the island may also provide the information needed for guidelines to verify interruption of schistosomiasis transmission. Show less
Zijlstra, E.E.; Hellemond, J.J. van; Moes, A.D.; Boer, C. de; Boeschoten, S.A.; Blijswijk, C.E.M. van; ... ; Rothe, C. 2020
Nontraumatic myelopathy causes severe morbidity and is not uncommon in Africa. Clinically, patients often present with paraplegia, and extrinsic cord compression and transverse myelitis are most... Show moreNontraumatic myelopathy causes severe morbidity and is not uncommon in Africa. Clinically, patients often present with paraplegia, and extrinsic cord compression and transverse myelitis are most common causes. Data on exact pathogenesis are scanty because of limitations in diagnostic methods. In Queen Elizabeth Central Hospital, Blantyre, Malawi, we recorded consecutive patients presenting with nontraumatic paraplegia for maximally 6 months between January and July 2010 and from March to December 2011. The diagnostic workup included imaging and examining blood, stool, urine, sputum, and cerebrospinal fluid (CSF) samples for infection. After discharge, additional diagnostic tests, including screening for virus infections, borreliosis, syphilis, and schistosomiasis, were carried out in the Netherlands. The clinical diagnosis was, thus, revised in retrospect with a more accurate final differential diagnosis. Of 58 patients included, the mean age was 41 years (range, 12-83 years) and the median time between onset and presentation was 18 days (range, 0-121 days), and of 55 patients tested, 23 (42%) were HIV positive. Spinal tuberculosis (n = 24, 41%), tumors (n = 16, 28%), and transverse myelitis (n = 6, 10%) were most common; in sixcases (10%), no diagnosis could be made. The additional tests yielded evidence for CSF infection with Schistosoma, Treponema pallidum, Epstein-Barr virus (EBV), HHV-6, HIV, as well as a novel cyclo virus. The diagnosis of the cause of paraplegia is complex and requires access to an magnetic resonance imaging (MRI) scan and other diagnostic (molecular) tools to demonstrate infection. The major challenge is to confirm the role of detected pathogens in the pathophysiology and to design an effective and affordable diagnostic approach. Show less
Forty-four Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low-positive (trace or 1+) children in three districts of very low prevalence in Egypt were given three sequential... Show moreForty-four Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low-positive (trace or 1+) children in three districts of very low prevalence in Egypt were given three sequential praziquantel (PZQ) treatments. Stool and urine specimens were collected 3 months following the initial treatment, and 3 weeks following the second and following the third PZQ treatments, which were conducted 5 weeks apart. Stool specimens were examined by Kato–Katz (four slides/stool sample) and all S. mansoni egg-negative stools were further tested by the “miracidia hatching test” (MHT). Urine samples were examined by the point-of-care CCA assay (POC-CCA). Over the study period, all stool samples from study subjects remained S. mansoni egg negative and MHT negative. Of the POC-CCA test results, in the first day of the study 3 months following the initial treatment, 29.5% were negative, 61.4% CCA trace positives, and 9.1% CCA 1+ positives. Following each PZQ treatment, the test results fluctuated between 1+, trace, and negative, but did not consistently decrease. The proportions of POC-CCA–positive results obtained in the first day (70.5%) as compared with the last day of the study (72.7%) in all of the three districts were very similar. We conclude that CCA trace and 1+ readings, in Kato–Katz S. mansoni egg-negative children in this area with very low levels of intestinal schistosomiasis, are not consistently altered or rendered consistently negative following repeated PZQ treatments and are therefore likely to represent false-positive readings. This finding is of critical importance for countries such as Egypt as they approach elimination. Show less
Hoekstra, P.T.; Partal, M.C.; Amoah, A.S.; Lieshout, L. van; Corstjens, P.L.; Tsonaka, R.; ... ; Dam, G.J. van 2018
