Papers by M. Van Esbroeck
Introduction An automated and accurate laboratory assay would be of considerable utility to the d... more Introduction An automated and accurate laboratory assay would be of considerable utility to the diagnosis of syphilis and treatment follow-up. We compared the Sekure RPR (Rapid Plasma Reagin) test performed on the SK500 Clinical Chemistry System to RPR card test results. Methods Serum samples were collected in the context of a 2 year observational cohort study of syphilis infected patients and controls. Syphilis was diagnosed using non-treponemal and treponemal testing. Sera collected at the time of diagnosis (M0) and at 3, 6, 9 and 12 months post-treatment were tested by a Macro-Vue RPR card test (RPR-C) (Becton Dickinson) and a Sekure RPR test (RPR-S) (Sekisui Diagnostics). RPR-S results are expressed in RPR units (R.U.), whereby 1 R.U. equals a 1-fold change in RPR-C titre. The agreement, linearity and reportable ranges were determined using RPR-C results as the gold standard. Linear regression was used to assess correlations from before and after implementation of an extra dilution step for samples with a strong suspicion of prozone effect. Results In total, 451 samples from 150 participants were tested, including 120 new syphilis cases and 30 controls. All 30 controls tested negative. Initially there was a weak correlation between RPR-C and RPR-S values (r=0.15). Further analyses identified 72 RPR-S samples with a strong suspicion of prozone effect. We therefore included an extra dilution step (10x) and retested 60/72 samples; values within the expected range were obtained for 58 of them. After implementing the extra dilution step the correlation was moderate (r=0.61), increasing further to r=0.91 for samples with RPR-C titres£128. Of the 92 samples that tested RPR-C positive and RPR-S negative, 8 were from M0 (RPR-C: 1-4), which would have led to missed diagnoses. Conclusion A reasonable correlation was found between the tested methods for mid-range RPR-C results (titre £128). However, prozone may occur in samples with high antibody concentrations. More investigation is required to elucidate the false negative RPR-S results.
Journal of Travel Medicine, Mar 10, 2023
Highlight We describe a patient presenting with eosinophilia and liver lesions. A juvenile Fascio... more Highlight We describe a patient presenting with eosinophilia and liver lesions. A juvenile Fasciola gigantica emerged through the skin, an occurrence which has been only described in 2 patients so far. Ectopic manifestations usually appear shortly after infection, whereas the time before emergence was more than 1 year in our patient.
Journal of Travel Medicine, Apr 13, 2022
Background: Infection with Mansonella perstans is a neglected filariasis, widely distributed in s... more Background: Infection with Mansonella perstans is a neglected filariasis, widely distributed in sub-Saharan Africa, characterized by an elusive clinical picture; treatment for mansonellosis is not standardized. This retrospective study aimed to describe the clinical features, treatment schemes and evolution, of a large cohort of imported cases of M. perstans infection seen in four European centres for tropical diseases. Methods: Mansonella perstans infections, diagnosed by identification of blood microfilariae in migrants, expatriates and travellers, collected between 1994 and 2018, were retrospectively analysed. Data concerning demographics, clinical history and laboratory examinations at diagnosis and at follow-up time points were retrieved. Results: A total of 392 patients were included in the study. Of the 281 patients for whom information on symptoms could be retrieved, 150 (53.4%) reported symptoms, abdominal pain and itching being the most frequent. Positive serology and eosinophilia were present in 84.4% and 66.1%, respectively, of those patients for whom these data were available. Concomitant parasitic infections were reported in 23.5% of patients. Treatment, administered to 325 patients (82.9%), was extremely heterogeneous between and within centres; the most commonly used regimen was mebendazole 100 mg twice a day for 1 month. A total of 256 (65.3%) patients attended a first follow-up, median 3 months (interquartile range 2-12) after the first visit; 83.1% of patients having received treatment based on mebendazole and/or doxycycline, targeting Wolbachia, became amicrofilaremic, 41.1-78.4% of whom within 12 months from single treatment. Conclusions: Lack of specific symptoms, together with the inconstant positivity of parasitological and antibodybased assays in the infected population, makes the clinical suspicion and screening for mansonellosis particularly difficult. Prospective studies evaluating prevalence of infection in migrants from endemic areas, infection-specific morbidity, presence of Wolbachia endosymbionts in M. perstans populations from different geographical areas and efficacy of treatment regimens are absolutely needed to optimize the clinical management of infection.
Bulletin of The World Health Organization, Jul 6, 2016
Interim guidelines to prevent sexual transmission of Zika virus (ZIKV) do not recommend diagnosti... more Interim guidelines to prevent sexual transmission of Zika virus (ZIKV) do not recommend diagnostic testing, because the knowledge of viral kinetics in semen after acute infection is limited. We studied the presence and duration of ZIKV in semen after onset of symptoms. Methods A prospective observational cohort study (NCT 02733796) is ongoing to determine the presence, persistence and kinetics of ZIKV in semen of men with confirmed ZIKV infection after returning from areas with vector-borne transmission. ZIKV RT-PCR is performed in weekly semen samples until ZIKV is no longer detectable. The main endpoint is the proportion of ZIKV positive semen samples over time after acute ZIKV infection. We report preliminary findings after enrolment of the first 4 patients. Findings Semen of two out of four immunocompetent men with symptomatic ZIKV infection tested positive for ZIKV-RNA by RT-PCR. ZIKV levels in semen declined to undetectable after 68 and 56 days respectively, suggesting elimination of the virus. Conclusion Our findings indicate that presence and persistence of ZIKV in semen after acute infection appear common. Algorithms can be developed that incorporate ZIKV-specific molecular and antibody detection assays and subsequent testing for ZIKV in semen of selected men. We suggest that future guidelines to prevent sexual transmission of ZIKV, adopt diagnostic testing of both symptomatic and asymptomatic individuals returning from endemic areas.
Eurosurveillance, Jul 25, 2013
We describe Leishmania species determination on clinical samples on the basis of partial sequenci... more We describe Leishmania species determination on clinical samples on the basis of partial sequencing of the heat-shock protein 70 gene (hsp70), without the need for parasite isolation. The method is especially suited for use in non-endemic infectious disease clinics dealing with relatively few cases on an annual basis, for which no fast high throughput diagnostic tests are needed. We show that the results obtained from this gene are in nearly perfect agreement with those from multilocus enzyme electrophoresis, which is still considered by many clinicians and the World Health Organization (WHO) as the gold standard in Leishmania species typing. Currently, 203 sequences are available that cover the entire hsp70 gene region analysed here, originating from a total of 41 leishmaniasis endemic countries, and representing 15 species and sub-species causing human disease. We also provide a detailed laboratory protocol that includes a step-by-step procedure of the typing methodology, to facilitate implementation in diagnostic laboratories.
Frontiers in Immunology, Jan 26, 2022
In a world with an increasing population at risk of exposure to arthropod-borne flaviviruses, acc... more In a world with an increasing population at risk of exposure to arthropod-borne flaviviruses, access to timely and accurate diagnostic tests would impact profoundly on the management of cases. Twenty peptides previously identified using a flavivirus proteome-wide microarray were evaluated to determine their discriminatory potential to detect dengue virus (DENV) infection. This included nine peptides recognized by IgM antibodies (PM peptides) and 11 peptides recognized by IgG antibodies (PG peptides). A bead-based multiplex peptide immunoassay (MPIA) using the Luminex technology was setup to determine Ab binding levels to each of these peptides in a panel of 323 carefully selected human serum samples. Sera are derived from individuals either infected with different viruses, namely, the four DENV serotypes, Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), West Nile virus (WNV) and Human immunodeficiency virus (HIV), or receiving vaccination against YFV, tick-borne encephalitis (TBEV), and Japanese encephalitis virus (JEV). Additionally, a set of healthy controls were included. We targeted a minimum specificity of 80% for all the analysis. The PG-9 peptide had the best sensitivity (73%) when testing DENV sera from acute patients (A-DENV; <8 days since symptom onset). With sera from convalescent DENV patients (C-DENV; >10 days since symptom onset) the FPG-1 peptide was the best seromarker with a sensitivity of 86%. When combining all A-DENV and C-DENV samples, peptides PM-22 and FPG-1 had the best-diagnostic performance with a sensitivity of 60 and 61.1%, and areas under the curve (AUC) of 0.7865 and 0.8131, respectively. A Random forest (RF) algorithm was used to select the best combination of peptides to classify DENV infection at a targeted specificity >80%. The best RF model for PM peptides that included A-DENV and C-DENV samples, reached a sensitivity of 72.3%, while for PG peptides, the best RF models for A-DENV only, C-DENV only and A-DENV + C-DENV reached a sensitivity of 88.9%, 89.1%, and 88.3%, respectively. In conclusion, the combination of multiple peptides constitutes a founding set of seromarkers for the discrimination of DENV infected individuals from other flavivirus infections.
Pathogens, Aug 22, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Background Pathogens causing acute fever, with the exception of malaria, remain largely unidentif... more Background Pathogens causing acute fever, with the exception of malaria, remain largely unidentified in sub-Saharan Africa, given the local unavailability of diagnostic tests and the broad differential diagnosis. Methodology/Principal Findings We conducted a cross-sectional study including outpatient acute febrile syndromes in both children and adults, between November 2015 and June 2016 in Kinshasa, Democratic Republic of Congo. Serological and molecular diagnostic tests for arboviral infections were performed on blood, including PCR and NS1-RDT for acute, and ELISA and IFAT for past infections. Conclusions/Significance Among 342 patients, aged 2 to 68 years, 45.3% tested positive on malaria Rapid Diagnostic Test. However, 87.7% received antimalarial and 64.3% antibacterial treatment. Further investigation among 235 fever cases revealed 19 (8.1%) acute dengue and 2 (0.9%) acute chikungunya infections, with an important proportion of participants already exposed to flaviviridae (possibly dengue) and alphaviridae (possibly chikungunya) in the past, namely 30.2 % and 26.4% respectively. We found no evidence of exposure to Zika nor yellow fever virus. .
Travel Medicine and Infectious Disease, 2021
Background: Many tropical clinics offer post-travel screening for parasitic infections in asympto... more Background: Many tropical clinics offer post-travel screening for parasitic infections in asymptomatic travellers. However, literature on attack rates and incidence rates of parasitic infections is scarce. Method: All military personnel returning from a tropical region during the year 2018 were tested for the presence of antibodies against Strongyloides stercoralis, Schistosoma and Entamoeba histolytica. Test results were compared with previous results if available to distinguish recent and old infection. Results: In total, 949 soldiers were included in the study. The median age was years 31 (IQR: 26-41), 96.3% were male. The median duration of stay in the tropics was 35 days (IQR: 14-90). The destination was predominantly central Africa. Serological tests were positive for S. stercoralis in 10 patients (1.1%), Schistosoma in 3 (0.3%), and E. histolytica in 16 (1.7%). The attack rates were 0.84, 0.32 and 1.69 respectively. The incidence rates were 3.99, 1.49 and 7.97 respectively. Conclusions: The risk for parasitic infection in the asymptomatic returning soldiers is low. However, the potentially serious complications of unrecognised parasitic infection can legitimise systematic screening.
Journal of Clinical Pathology
We report on a Pashtun family affected by haemoglobin D-Punjab/β+-thalassemia to increase the awa... more We report on a Pashtun family affected by haemoglobin D-Punjab/β+-thalassemia to increase the awareness of the increasing prevalence of haemoglobinopathies among primary care physicians. We highlight the diagnostic approach of these conditions and the benefits of genetic counselling.
Travel Medicine and Infectious Disease, 2021
Background: Many tropical clinics offer post-travel screening for parasitic infections in asympto... more Background: Many tropical clinics offer post-travel screening for parasitic infections in asymptomatic travellers. However, literature on attack rates and incidence rates of parasitic infections is scarce. Method: All military personnel returning from a tropical region during the year 2018 were tested for the presence of antibodies against Strongyloides stercoralis, Schistosoma and Entamoeba histolytica. Test results were compared with previous results if available to distinguish recent and old infection. Results: In total, 949 soldiers were included in the study. The median age was years 31 (IQR: 26-41), 96.3% were male. The median duration of stay in the tropics was 35 days (IQR: 14-90). The destination was predominantly central Africa. Serological tests were positive for S. stercoralis in 10 patients (1.1%), Schistosoma in 3 (0.3%), and E. histolytica in 16 (1.7%). The attack rates were 0.84, 0.32 and 1.69 respectively. The incidence rates were 3.99, 1.49 and 7.97 respectively. Conclusions: The risk for parasitic infection in the asymptomatic returning soldiers is low. However, the potentially serious complications of unrecognised parasitic infection can legitimise systematic screening.
Frontiers in Immunology, 2022
In a world with an increasing population at risk of exposure to arthropod-borne flaviviruses, acc... more In a world with an increasing population at risk of exposure to arthropod-borne flaviviruses, access to timely and accurate diagnostic tests would impact profoundly on the management of cases. Twenty peptides previously identified using a flavivirus proteome-wide microarray were evaluated to determine their discriminatory potential to detect dengue virus (DENV) infection. This included nine peptides recognized by IgM antibodies (PM peptides) and 11 peptides recognized by IgG antibodies (PG peptides). A bead-based multiplex peptide immunoassay (MPIA) using the Luminex technology was set-up to determine Ab binding levels to each of these peptides in a panel of 323 carefully selected human serum samples. Sera are derived from individuals either infected with different viruses, namely, the four DENV serotypes, Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), West Nile virus (WNV) and Human immunodeficiency virus (HIV), or receiving vaccination against YFV, tick-bo...
Frontiers in Immunology, 2021
Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the... more Dengue is a major public health problem in tropical and sub-tropical regions worldwide. Since the Zika epidemic and the increased co-circulation of other arboviruses, the serology-based diagnosis of dengue has become more problematic due to the high antigenic resemblance, especially among the flavivirus family. Therefore, a more comprehensive understanding of the diversity, specificity and temporal evolution of the antibody response following dengue infection is needed. In order to close this knowledge gap, we used a high-density peptide microarray of 9,072 linear peptides covering the entire proteome diversity of dengue, Zika, yellow fever and chikungunya viruses. The IgM and IgG antibody responses were measured against the designed microarray in symptomatic dengue infected individuals from an arbovirus endemic area in Peru and in overseas travelers returning to Belgium, as representatives of multiple-exposed and primary infections, respectively. Serum samples were collected longit...
Virology Journal, 2020
Background: Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Cen... more Background: Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Central/South African (ECSA), West African (WA), and Asian. Previously, a rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity for certain ECSA-genotype viruses, but this test showed poor performance against the Asian-genotype virus that is spreading in the American continents. We found that the reactivity of one monoclonal antibody (MAb) used in the IC rapid diagnostic test (RDT) is affected by a single amino acid substitution in E1. Therefore, we developed new MAbs that exhibited specific recognition of all three genotypes of CHIKV. Methods: Using a combination of the newly generated MAbs, we developed a novel version of the IC RDT with improved sensitivity to Asian-genotype CHIKV. To evaluate the sensitivity, specificity, and cross-reactivity of the new version of the IC RDT, we first used CHIKV isolates and E1-pseudotyped lentiviral vectors. We then used clinical specimens obtained in Aruba in 2015 and in Bangladesh in 2017 for further evaluation of RDT sensitivity and specificity. Another alphavirus, sindbis virus (SINV), was used to test RDT cross-reactivity. Results: The new version of the RDT detected Asian-genotype CHIKV at titers as low as 10^4 plaque-forming units per mL, a concentration that was below the limit of detection of the old version. The new RDT had sensitivity to the ECSA genotype that was comparable with that of the old version, yielding 92% (92 out of 100) sensitivity (95% confidence interval 85.0-95.9) and 100% (100 out of 100) specificity against a panel of 100 CHIKV-positive and 100 CHIKV-negative patient sera obtained in the 2017 outbreak in Bangladesh.
Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)... more Large-scale serosurveillance of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) will only be possible if serological tests are sufficiently reliable, rapid and inexpensive. Current assays are either labour-intensive and require specialised facilities (e.g. virus neutralization assays), or expensive with suboptimal specificity (e.g. commercial ELISAs). Bead-based assays offer a cost-effective alternative and allow for multiplexing to test for antibodies of other pathogens. Here, we compare the performance of four antigens for the detection of SARS-CoV-2 specific IgG antibodies in a panel of sera that includes both severe (n=40) and mild (n=52) cases, using a neutralization and a Luminex bead-based assay. While we show that neutralising antibody levels are significantly lower in mild than in severe cases, we demonstrate that a combination of recombinant nucleocapsid protein (NP), receptor-binding domain (RBD) and the whole spike protein (S1S2) results in a highly sen...
Eurosurveillance, 2020
We illustrate the potential for specialist laboratory networks to be used as preparedness and res... more We illustrate the potential for specialist laboratory networks to be used as preparedness and response tool through rapid collection and sharing of data. Here, the Emerging Viral Diseases-Expert Laboratory Network (EVD-LabNet) and a laboratory assessment of chikungunya virus (CHIKV) in returning European travellers related to an ongoing outbreak in Thailand was used for this purpose. EVD-LabNet rapidly collected data on laboratory requests, diagnosed CHIKV imported cases and sequences generated, and shared among its members and with the European Centre for Disease Prevention and Control. Data across the network showed an increase in CHIKV imported cases during 1 October 2018–30 April 2019 vs the same period in 2018 (172 vs 50), particularly an increase in cases known to be related to travel to Thailand (72 vs 1). Moreover, EVD-LabNet showed that strains were imported from Thailand that cluster with strains of the ECSA-IOL E1 A226 variant emerging in Pakistan in 2016 and involved in ...
PLOS ONE, 2018
Introduction In non-endemic settings, expertise in malaria microscopy is limited and rapid diagno... more Introduction In non-endemic settings, expertise in malaria microscopy is limited and rapid diagnostic tests (RDTs) are an adjunct to malaria diagnosis. Aim We performed an External Quality Assessment (EQA) on reading and interpretation of malaria RDTs in a non-endemic setting. Methods Participants were medical laboratories in Belgium and the Grand Duchy of Luxembourg using malaria RDTs; they received (i) 10 high-resolution photographs presenting test line combinations of RDTs with interpretations listed in a multiple choice format and (ii) a questionnaire about their practices of malaria diagnosis. Results Among 135 subscribing laboratories, 134 (99.3%) used 139 RDT products (11 different products from 8 brands). After exclusion of the results of one laboratory, analysis was done for 133 laboratories using 137 RDT products. Scores of 10/10, 9/10 and 8/10 were achieved for 58.4%, 13.1% and 8.0% of 137 RDT products respectively. For three-band P. falciparum-pan-Plasmodium RDTs (113 (82.5%) products, 6 brands), most frequent errors were (1) disregarding faint test lines (18.6%), (2) reporting invalid instead of P. falciparum (16.8%) and (3) reporting "Plasmodium spp., no further differentiation possible" without mentioning the presence or absence of P. falciparum (11.5%). For four-band RDTs (21 (15.3%) products, 1 brand), errors were (4) disregarding faint P. vivax test lines (47.6%) and (5) reporting "Plasmodium spp., no further differentiation possible" without mentioning the presence of P. falciparum and P. vivax (28.6%). Instructions for use (IFU) of only 4 out of 10 RDT products mentioned to interpret faint-intensity test lines as positive (conducive to errors PLOS ONE |
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Papers by M. Van Esbroeck