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Background: Clade Ib, a new strain of clade I monkeypox virus, emerged in eastern DR Congo, sparking an international outbreak. Comprehensive studies are needed to assess its transmission dynamics and clinical presentation., Methods: We did a prospective observational cohort study at Kamituga General Hospital in South Kivu, DR Congo, between May 2 and Oct 9, 2024. Sociodemographic, exposure, and clinical data were collected from mpox-suspected cases. Cases were confirmed by Xpert Mpox PCR and followed through hospitalisation and on days 29 and 59 after diagnosis., Findings: Of the 510 suspected cases included, 407 (80%) tested positive via PCR. Among the 407 confirmed cases, 196 (48%) were women. Age distribution was bimodal, with 58 (14%) children younger than 5 years, and 267 (66%) individuals aged 15-34 years. Most cases (237 [58%] of 406) reported contact with a suspected or confirmed mpox case; primarily colleagues, spouses or sexual partners in adults, and parents or siblings in children. Self-reported comorbidities were rare (18 [5%] of 400), including 6 (2%) people infected with HIV. Prodromal symptoms were present in 331 (88%) of 375 patients, active skin lesions in 394 (97%) of 407 patients, mucosal lesions in 324 (82%) of 394 patients, and lymphadenopathy in 288 (73%) of 394 patients. In adults, 280 (89%) of 314 had genital skin lesions and mean lesion density was highest in the genital area. In contrast, only 35 (42%) of 84 children had genital lesions, as part of a more uniform rash. Among 403 hospitalised patients, two (<1%) deaths occurred. Among 296 patients with detailed hospital follow-up, complications were primarily genito-urinary (169 [57%]) or cutaneous (121 [41%]). Four (67%) of six pregnant women with recorded outcome had adverse pregnancy outcomes. On days 29 and 59, few sequelae were reported other than scars., Interpretation: Clade Ib infections in Kamituga showed distinct clinical patterns compared with clade Ia outbreaks elsewhere in the country and the global clade IIb outbreak. In adults, the disease primarily affected the genito-urinary system, compatible with sexual transmission, whereas children mostly manifested extragenital lesions. These findings highlight the need for updated case definitions and targeted public health interventions to address evolving transmission dynamics and mitigate risks for vulnerable groups, including pregnant women and young children., Funding: European & Developing Countries Clinical Trials Partnership (EDCTP2 and EDCTP3); Belgian Directorate-General Development Cooperation and Humanitarian Aid; Research Foundation-Flanders., Competing Interests: Declaration of interests LL has received institutional consultancy fees from BioNtech and institutional research funding from Sanofi; both not relevant for this work. JK has provided expert witness reports for the Treasury Board of Canada not relevant to this work. JK has also received mpox research funding from the Canadian Institutes of Health Research and the International Development Research Centre in open funding competitions. All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: DR Congo has the highest global burden of mpox, a disease caused by infection with the monkeypox virus. The incidence has risen since 1980, but recent analyses of epidemiological trends are lacking. We aimed to describe trends in suspected and confirmed mpox cases in DR Congo using epidemiological and laboratory mpox surveillance data collected from 2010 to 2023, and provide insights that can better inform the targeting and monitoring of control strategies., Methods: We analysed aggregated national epidemiological surveillance data and individual-level laboratory data from 2010 to 2023. We calculated incidence based on suspected cases, case-fatality ratios, and percentage of laboratory-confirmed cases and assessed geospatial trends. Demographic and seasonal trends were investigated using generalised additive mixed models., Findings: Between Jan 1, 2010, and Dec 31, 2023, a total of 60 967 suspected cases and 1798 suspected deaths from mpox were reported in DR Congo (case-fatality ratio 2·9%). The number of reporting provinces increased from 18 of 26 provinces in 2010 to 24 of 26 provinces in 2023. The annual incidence increased from 2·97 per 100 000 in 2010 to 11·46 per 100 000 in 2023. The highest incidence (46·38 per 100 000) and case-fatality ratio (6·0%) were observed in children younger than 5 years. Incidence was higher in rural compared with urban areas. PCR testing was performed for 7438 suspected cases (12·2%), with 4248 (57·1%) of 7438 samples testing positive. Median age of confirmed cases (13·0 years [IQR 6·0-25·0]) remained stable, although the 95th percentile of age increased over time., Interpretation: The incidence and geographical distribution of suspected mpox cases have increased substantially since 2010. Improvements in surveillance and decentralised testing are essential to monitor mpox trends and direct interventions effectively, to address the public health emergency declarations issued in August, 2024., Funding: Belgian Directorate-General Development Cooperation and Humanitarian Aid; European and Developing Countries Clinical Trials Partnership; Research Foundation-Flanders; European Civil Protection and Humanitarian Aid Operations; Department of Economy, Science, and Innovation of the Flemish Government; Canadian Institutes of Health Research; and the International Development Research Centre., Competing Interests: Declaration of interests LL has received institutional consultancy fees from BioNtech and institutional research funding from Sanofi, both not relevant for this work. JKi has provided expert witness reports for the Treasury Board of Canada not relevant to this work. JKi has also received mpox research funding from the Canadian Institutes of Health Research and the International Development Research Centre in open funding competitions. All other authors declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: We aimed to determine the timeliness of rabies post-exposure prophylaxis (PEP) and the proportion of individuals with an adequate antibody response post-PEP among those attending the Belgian national reference center., Methods: Retrospective analysis of patient records who attended our center from 2018 to 2023. Delay was defined as rabies immunoglobulin (RIG) and vaccine initiation beyond 2 calendar days after exposure. Antibodies were measured by rapid fluorescent focus inhibition test (RFFIT) after PEP in high-risk exposures. A titer ≥0.5 IU/ml was considered adequate., Results: We reviewed 317 patient records. Among individuals with inland exposure (n = 103), 85 % timely received PEP. Among travelers exposed abroad (n = 214), administration of RIG and vaccine initiation were timely in 30 % and 50 % of cases, respectively. An adequate antibody response was detected in 99.5 % (195/196) individuals., Conclusion: Substantial PEP delays among travelers were observed. The robust antibody responses suggest that routine serological follow-up is not necessary for all patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission., (© 2024. The Author(s).)

Objectives: The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological, behavioral, and immunological factors behind the waning of the epidemic in Belgium., Methods: We investigated temporal evolutions in the characteristics and behavior of mpox patients using national surveillance data and data from a prospective registry of mpox patients in the Institute of Tropical Medicine (Antwerp). We studied behavioral changes in the population at risk using a survey among HIV-preexposure prophylaxis (PrEP) users. We determined the seroprevalence of anti-orthopoxvirus antibodies among HIV-PrEP users across four-time points in 2022., Results: Mpox patients diagnosed at the end of the epidemic had less sexual risk behavior compared to those diagnosed earlier: they engaged less in sex at mass events, had fewer sexual partners, and were less likely to belong to the sexual network's central group. Among HIV-PrEP users there were no notable changes in sexual behavior. Anti-orthopoxvirus seroprevalence did not notably increase before the start of national vaccination campaigns., Conclusion: The observed changes in group immunity and behavior in the population at greater risk of exposure to mpox seem unable to explain the waning of the mpox epidemic. A change in the profile of mpox patients might have contributed to the decline in cases., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021., Methods: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression., Results: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality., Conclusions: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution., (© 2024. The Author(s).)

T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3β TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3β sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/β sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics., Competing Interests: Potential conflicts of interest . B. O., K. L., and P. M. are cofounders, board directors, and shareholders of ImmuneWatch. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Schistosomiasis treatment entirely relies on a single drug, praziquantel, prompting research into alternative therapeutics. Here we evaluated the efficacy and safety of the antimalarial combination artesunate-mefloquine for the treatment of schistosomiasis in a proof-of-concept, pragmatic, open-label, randomized controlled trial in primary schools of six villages endemic for schistosomiasis in northern Senegal. Children (6-14 years) were eligible if Schistosoma eggs were detected by microscopy in urine and/or stool. In total, 726 children were randomized 1:1 to praziquantel (standard care: 40 mg kg -1 single dose; n = 364) or to artesunate-mefloquine (antimalarial dosage: artesunate 4 mg kg -1 and mefloquine 8 mg kg -1 daily for three consecutive days; n = 362). Eight children not meeting the inclusion criteria were excluded from efficacy analysis. Median age of the remaining 718 participants was 9 years; 399 (55.6%) were male, and 319 (44.4%) female; 99.3% were infected with Schistosoma haematobium and 15.2% with S. mansoni. Primary outcomes were cure rate, assessed by microscopy, and frequency of drug-related adverse effects of artesunate-mefloquine versus praziquantel at 4 weeks after treatment. Cure rate was 59.6% (208/349) in the artesunate-mefloquine arm versus 62.1% (211/340) in the praziquantel arm. The difference of -2.5% (95% confidence interval (CI) -9.8 to 4.8) met the predefined criteria of noninferiority (margin set at 10%). All drug-related adverse events were mild or moderate, and reported in 28/361 children receiving artesunate-mefloquine (7.8%; 95% CI 5.4 to 11.0) versus 8/363 (2.2%; 95% CI 1.1 to 4.3) receiving praziquantel (P < 0.001). Artesunate-mefloquine at antimalarial dosage was moderately safe and noninferior to standard-care praziquantel for the treatment of schistosomiasis, predominantly due to S. haematobium. Multicentric trials in different populations and epidemiological settings are needed to confirm these findings. ClinicalTrials.gov identifier: NCT03893097 ., (© 2024. The Author(s).)

Objective: The available epidemiological and clinical evidence from the currently ongoing monkeypox (MPX) outbreak in non-endemic areas suggests an important factor of sexual transmission. However, limited information on the behaviour and experiences of individuals with an MPX infection has to date been provided. We aimed to describe the initial phase of the MPX outbreak in Belgium, and to provide a more in-depth description of sexual behaviour and transmission contexts., Methods: We used routine national surveillance data of 139 confirmed MPX cases with date of symptom onset until 19 June 2022, complemented with 12 semistructured interviews conducted with a subsample of these cases., Results: Sexualised environments, including large festivals and cruising venues for gay men, were the suspected exposure setting for the majority of the cases in the early outbreak phase. In-depth narratives of sexual behaviour support the hypothesis of MPX transmission through close physical contact during sex. Despite awareness of the ongoing MPX outbreak, low self-perceived risk of MPX acquisition and confusing initial signs and symptoms for other STIs or skin conditions delayed early detection of an MPX infection. In addition, we describe relevant contextual factors beyond individual behaviour, related to sexual networks, interpersonal interactions and health systems. Some of these factors may complicate early MPX detection and control efforts., Conclusion: Our results highlight the role of sexual contact and networks in the transmission of MPX during the early phase of the outbreak in Belgium. Risk communication messages should consistently and transparently state the predominant sexual transmission potential of MPX virus, and prevention and control measures must be adapted to reflect multilevel factors contributing to MPX transmission risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite the general agreement on the significance of T cells during SARS-CoV-2 infection, the clinical impact of specific and cross-reactive T-cell responses remains uncertain. Understanding this aspect could provide insights for adjusting vaccines and maintaining robust long-term protection against continuously emerging variants. To characterize CD8+ T-cell response to SARS-CoV-2 epitopes unique to the virus (SC2-unique) or shared with other coronaviruses (CoV-common), we trained a large number of T-cell receptor (TCR) - epitope recognition models for MHC-I-presented SARS-CoV-2 epitopes from publicly available data. These models were then applied to longitudinal CD8+ TCR repertoires from critical and non-critical COVID-19 patients. In spite of comparable initial CoV-common TCR repertoire depth and CD8+ T-cell depletion, the temporal dynamics of SC2-unique TCRs differed depending on the disease severity. Specifically, while non-critical patients demonstrated a large and diverse SC2-unique TCR repertoire by the second week of the disease, critical patients did not. Furthermore, only non-critical patients exhibited redundancy in the CD8+ T-cell response to both groups of epitopes, SC2-unique and CoV-common. These findings indicate a valuable contribution of the SC2-unique CD8+ TCR repertoires. Therefore, a combination of specific and cross-reactive CD8+ T-cell responses may offer a stronger clinical advantage. Besides tracking the specific and cross-reactive SARS-CoV-2 CD8+ T cells in any TCR repertoire, our analytical framework can be expanded to more epitopes and assist in the assessment and monitoring of CD8+ T-cell response to other infections., Competing Interests: BO, KL, and PM are co-founders, board directors and shareholders of ImmuneWatch™. None of the work presented here was influenced in any way by this. ImmuneWatch™ had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Postovskaya, Vujkovic, de Block, van Petersen, van Frankenhuijsen, Brosius, Bottieau, Van Dijck, Theunissen, van Ierssel, Vlieghe, Bartholomeus, Mullan, Adriaensen, Vanham, Ogunjimi, Laukens, Vercauteren and Meysman.)

The risk of infection after exposure to clade IIb mpox virus (MPXV) is unknown, and potential presymptomatic shedding of MPXV remains to be demonstrated. High-risk contacts of mpox patients were followed-up in a prospective longitudinal cohort study. Individuals reporting sexual contact, >15 min skin-to-skin contact, or living in the same household with an mpox patient were recruited in a sexual health clinic in Antwerp, Belgium. Participants kept a symptom diary, performed daily self-sampling (anorectal, genital, and saliva), and presented for weekly clinic visits for physical examination and sampling (blood and oropharyngeal). Samples were tested for MPXV by PCR. Between June 24 and July 31, 2022, 25 contacts were included, of which 12/18 (66.0%) sexual and 1/7 (14.0%) nonsexual contacts showed evidence of infection by MPXV-PCR. Six cases had typical mpox symptoms. Viral DNA was detected as early as 4 days before symptom onset in 5 of them. In 3 of these cases, replication-competent virus was demonstrated in the presymptomatic phase. These findings confirm the existence of presymptomatic shedding of replication-competent MPXV and emphasize the high risk of transmission during sexual contact. Sexual contacts of mpox cases should abstain from sex during the incubation period, irrespective of symptoms., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The presentation of mpox clade IIb during the 2022 outbreak overlaps with a range of other diseases. Understanding the factors associated with mpox is important for clinical decision making., Methods: We described the characteristics of mpox patients who sought care at Belgian sexual health clinic. Furthermore we compared their characteristics to those of patients with a clinical suspicion of mpox but who tested negative on polymerase chain reaction., Results: Between May 23 and September 20, 2022, 155 patients were diagnosed with mpox, and 51 patients with suspected symptoms tested negative. All mpox patients self-identified as men and 148/155 (95.5%) as gay or bisexual MSM. Systemic symptoms were present in 116/155 (74.8%) patients. All but 10 patients (145/155, 93.5%) presented with skin lesions. Other manifestations were lymphadenopathy (72/155, 46.5%), proctitis (50/155, 32.3%), urethritis (12/155, 7.7%), tonsillitis (2/155, 1.3%). Complications involved bacterial skin infection (13/155, 8.4%) and penile oedema with or without paraphimosis (4/155, 2.6%). In multivariable logistic regression models, the presence of lymphadenopathy (OR 3.79 95% CI 1.44-11.49), skin lesions (OR 4.35 95% CI 1.15-17.57) and proctitis (OR 9.41 95% CI 2.72-47.07) were associated with the diagnosis of mpox. There were no associations with age, HIV status, childhood smallpox vaccination, number of sexual partners and international travel., Conclusions: The presence of proctitis, lymphadenopathies and skin lesions should increase clinical suspicion of mpox in patients with compatible symptoms., (© 2023 The Authors.)

While mpox was well characterised during the 2022 global Clade IIb outbreak, little is known about persistent morbidity. We present interim results of a prospective cohort study of 95 mpox patients assessed 3-20 weeks post-symptom onset. Two-thirds of participants had residual morbidity, including 25 with persistent anorectal and 18 with genital symptoms. Loss of physical fitness, new-onset/worsened fatigue and mental health problems were reported in 36, 19 and 11 patients, respectively. These findings require attention by healthcare providers.

Background: Mpox (formerly monkeypox) is a viral disease caused by the mpox virus (MPXV), endemic in Central and West Africa and currently causing a global outbreak of international concern. Much remains unknown about sample types most suited for mpox laboratory diagnosis. While it is established that high viral loads can be found in active skin lesions (currently the recommended mpox laboratory confirmation specimen type), WHO mpox testing guidelines encourage the use of oropharyngeal swabs as an additional sample type for mpox diagnosis and suggest investigating the value of other specimens like blood samples., Objective: In this study, we verified the value of select alternative specimen types for mpox laboratory confirmation., Methods: We included 25 patients with MPXV-confirmed skin lesions to compare diagnostic sensitivity of MPXV PCR testing on EDTA plasma and two upper respiratory specimens: oropharyngeal swabs and saliva., Results: In our patient cohort with MPXV-confirmed skin lesions, diagnostic sensitivity of MPXV PCR was 80% in EDTA plasma, 64% in oropharyngeal swabs, and 88% in saliva. MPXV viral loads were significantly higher in saliva compared to oropharyngeal swabs and EDTA plasma., Discussion: The WHO recommendation to collect oropharyngeal swabs as an additional specimen for mpox diagnosis might need to be revised to include saliva wherever feasible. We suggest investigating saliva as a diagnostic specimen in the absence of active skin lesions or during the phase preceding skin manifestations. Moreover, the relatively high MPXV DNA content of saliva warrants elucidating its potential role in disease transmission., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Vaccination is important in containing the 2022 mpox (formerly monkeypox) epidemic. We describe five Belgian patients with localised severe symptoms of proctitis and penile oedema, occurring between 4 and 35 days after post-exposure preventive vaccination or after one- or two-dose off-label pre-exposure preventive vaccination with MVA-BN vaccine. Genome sequencing did not reveal evidence for immune escape variants. Healthcare workers and those at risk should be aware of possible infections occurring shortly after vaccination and the need for other preventive measures.

The magnitude of the 2022 multi-country monkeypox virus (MPXV) outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. In this study, we aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhea and chlamydia testing using an MPXV PCR assay and identified MPXV-DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21-37 days later, these three men were free of clinical signs, and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak., (© 2022. The Author(s).)

Background: Following an outbreak of cases of vesicular-pustular rash with fever, evocative of human monkeypox, in Bas-Uélé province, Democratic Republic of Congo, surveillance was strengthened., Methods: Households with at least one active generalized vesicular-pustular rash case were visited, and contact and clinical history information were collected from all household members. Whenever possible, skin lesions were screened by polymerase chain reaction for the monkeypox virus, followed by the varicella-zoster virus, when negative for the former., Results: Polymerase chain reaction results were obtained for 77 suspected cases, distributed in 138 households, of which 27.3% were positive for monkeypox, 58.4% positive for chickenpox, and 14.3% negative for both. Confirmed monkeypox cases presented more often with monomorphic skin lesions on the palms of the hands and on the soles of the feet. Integrating these three features into the case definition raised the specificity to 85% but would miss 50% of true monkeypox cases. A predictive model fit on patient demographics and symptoms had 97% specificity and 80% sensitivity but only 80% and 33% in predicting out-of-sample cases., Conclusion: Few discriminating features were identified and the performance of clinical case definitions was suboptimal. Rapid field diagnostics are needed to optimize worldwide early detection and surveillance of monkeypox., (Published by Elsevier Ltd.)

Background: Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades., Methods: We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3-12 months., Results: A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively)., Conclusions: The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: COVID-19 patients experience several features of dysregulated immune system observed in sepsis. We previously showed a dysregulation of several proline-selective peptidases such as dipeptidyl peptidase 4 (DPP4), fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP) and prolylcarboxypeptidase (PRCP) in sepsis. In this study, we investigated whether these peptidases are similarly dysregulated in hospitalized COVID-19 patients., Methods: Fifty-six hospitalized COVID-19 patients and 32 healthy controls were included. Enzymatic activities of DPP4, FAP, PREP and PRCP were measured in samples collected shortly after hospital admission and in longitudinal follow-up samples., Results: Compared to healthy controls, both DPP4 and FAP activities were significantly lower in COVID-19 patients at hospital admission and FAP activity further decreased significantly in the first week of hospitalization. While PRCP activity remained unchanged, PREP activity was significantly increased in COVID-19 patients at hospitalization and further increased during hospital stay and stayed elevated until the day of discharge., Conclusion: The changes in activities of proline-selective peptidases in plasma are very similar in COVID-19 and septic shock patients. The pronounced decrease in FAP activity deserves further investigation, both from a pathophysiological viewpoint and as its utility as a part of a biomarker panel., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is a viral lower respiratory tract infection caused by the highly transmissible and pathogenic SARS-CoV-2 (severe acute respiratory-syndrome coronavirus-2). Besides respiratory failure, systemic thromboembolic complications are frequent in COVID-19 patients and suggested to be the result of a dysregulation of the hemostatic balance. Although several markers of coagulation and fibrinolysis have been studied extensively, little is known about the effect of SARS-CoV-2 infection on the potent antifibrinolytic enzyme carboxypeptidase U (CPU). Blood was collected longitudinally from 56 hospitalized COVID-19 patients and 32 healthy controls. Procarboxypeptidase U (proCPU) levels and total active and inactivated CPU (CPU+CPUi) antigen levels were measured. At study inclusion (shortly after hospital admission), proCPU levels were significantly lower and CPU+CPUi antigen levels significantly higher in COVID-19 patients compared to controls. Both proCPU and CPU+CPUi antigen levels showed a subsequent progressive increase in these patients. Hereafter, proCPU levels decreased and patients were, at discharge, comparable to the controls. CPU+CPUi antigen levels at discharge were still higher compared to controls. Baseline CPU+CPUi antigen levels (shortly after hospital admission) correlated with disease severity and the duration of hospitalization. In conclusion, CPU generation with concomitant proCPU consumption during early SARS-CoV-2 infection will (at least partly) contribute to the hypofibrinolytic state observed in COVID-19 patients, thus enlarging their risk for thrombosis. Moreover, given the association between CPU+CPUi antigen levels and both disease severity and duration of hospitalization, this parameter may be a potential biomarker with prognostic value in SARS-CoV-2 infection.

COVID-19 Antibody Detecting Rapid Diagnostic Tests (COVID-19 Ab RDTs) are the preferred tool for SARS-CoV-2 seroprevalence studies, particularly in low- and middle-income countries. The present study challenged COVID-19 Ab RDTs with pre-pandemic samples of patients exposed to tropical pathogens. A retrospective study was performed on archived serum ( n = 94) and EDTA whole blood ( n = 126) samples obtained during 2010-2018 from 196 travelers with malaria ( n = 170), schistosomiasis ( n = 25) and dengue ( n = 25). COVID-19 Ab RDTs were selected based on regulatory approval status, independent evaluation results and detecting antigens. Among 13 COVID-19 Ab RDT products, overall cross-reactivity was 18.5%; cross-reactivity for malaria, schistosomiasis and dengue was 20.3%, 18.1% and 7.5%, respectively. Cross-reactivity for current and recent malaria, malaria antibodies, Plasmodium species and parasite densities was similar. Cross-reactivity among the different RDT products ranged from 2.7% to 48.9% (median value 14.5%). IgM represented 67.9% of cross-reactive test lines. Cross-reactivity was not associated with detecting antigens, patient categories or disease (sub)groups, except for schistosomiasis (two products with ≥60% cross-reactivity). The high cross-reactivity for malaria, schistosomiasis and-to a lesser extent-dengue calls for risk mitigation when using COVID-19 Ab RDTs in co-endemic regions.

Introduction: Alternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity against Schistosoma larvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response., Methods and Analysis: The SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic for Schistosoma mansoni and Schistosoma haematobium , are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial's primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated., Ethics and Dissemination: Ethics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences., Trial Registration Number: NCT03893097; pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bacterial sexually transmitted infections (STIs) are highly prevalent among men who have sex with men who use HIV pre-exposure prophylaxis (PrEP), which leads to antimicrobial consumption linked to the emergence of antimicrobial resistance. We aimed to assess use of an antiseptic mouthwash as an antibiotic sparing approach to prevent STIs., Methods: We invited people using PrEP who had an STI in the past 24 months to participate in this single-centre, randomised, double-blind, placebo-controlled, AB/BA crossover superiority trial at the Institute of Tropical Medicine in Antwerp, Belgium. Using block randomisation (block size eight), participants were assigned (1:1) to first receive Listerine Cool Mint or a placebo mouthwash. They were required to use the study mouthwashes daily and before and after sex for 3 months each and to ask their sexual partners to use the mouthwash before and after sex. Participants were screened every 3 months for syphilis, chlamydia, and gonorrhoea at the oropharynx, anorectum, and urethra. The primary outcome was combined incidence of these STIs during each 3-month period, assessed in the intention-to-treat population, which included all participants who completed at least the first 3-month period. Safety was assessed as a secondary outcome. This trial is registered with Clinicaltrials.gov, NCT03881007., Findings: Between April 2, 2019, and March 13, 2020, 343 participants were enrolled: 172 in the Listerine followed by placebo (Listerine-placebo) group and 171 in the placebo followed by Listerine (placebo-Listerine) group. The trial was terminated prematurely because of the COVID-19 pandemic. 151 participants completed the entire study, and 89 completed only the first 3-month period. 31 participants withdrew consent, ten were lost to follow-up, and one acquired HIV. In the Listerine-placebo group, the STI incidence rate was 140·4 per 100 person-years during the Listerine period, and 102·6 per 100 person-years during the placebo period. In the placebo-Listerine arm, the STI incidence rate was 133·9 per 100 person-years during the placebo period, and 147·5 per 100 person-years during the Listerine period. We did not find that Listerine significantly reduced STI incidence (IRR 1·17, 95% CI 0·84-1·64). Numbers of adverse events were not significantly higher than at baseline and were similar while using Listerine and placebo. Four serious adverse events (one HIV-infection, one severe depression, one Ludwig's angina, and one testicular carcinoma) were not considered to be related to use of mouthwash., Interpretation: Our findings do not support the use of Listerine Cool Mint as a way to prevent STI acquisition among high-risk populations., Funding: Belgian Research Foundation - Flanders (FWO 121·00)., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background : Data on rabies post-exposure prophylaxis (PEP) and the use of human rabies immunoglobulins (HRIG) in Belgium are scarce. The main objective of this study was to evaluate the timely administration of HRIG after rabies exposure. The secondary objective was to evaluate the adequate antibody response following PEP. Methods : We reviewed all medical records from July 2017 to June 2018 of patients seeking care at, or referred to, the Institute of Tropical Medicine and the University Hospital, Antwerp for the administration of human rabies immunoglobulins following potential rabies exposure abroad or in Belgium.A timely response was defined as starting HRIG with a delay of ≤48 h and rabies vaccination in the first 7 days after exposure.Adequate antibody response was defined as a titer of >5.0 IU/mL in case of bat-related exposure and >3.0 IU/mL in case of exposure to other animals. Titers were measured 10 days after the last PEP vaccine dose, using the rapid fluorescent focus inhibition test (RFFIT). Results : Of the 92 cases treated with HRIG, 75 were evaluated.The majority of injuries were acquired in Asia (n = 26,34%) and in Western Europe (n = 18, 24%), of which 17 in Belgium. The five most frequently recorded countries overseas were Indonesia (n = 13), Thailand (n = 7), Morocco (n = 4), Peru (n = 3) and Costa Rica (n = 3). Administration of immunoglobulins was related to injuries by dogs (36%), monkeys (25%) or bats (22%).A timely response was observed in 16 (21,33%) and in 55 (73,33%) of subjects receiving HRIG (≤48 h) or rabies vaccine (<7days) respectively. The mean time between exposure and the first administered dose of rabies vaccine and HRIG was 7.7 and 8.7 days, respectively. The mean delay for HRIG administration was 9.6 days and 6 days for abroad and inland risks, respectively.In 15 of 16 (94%) bat-related cases the antibody titer after full PEP was >5.0 IU/ml. In 38 of 47 (81%) cases related to other animals the RFFIT titer was >3.0 IU/ml. All low-responders received additional rabies injections. Conclusion : This study showed a substantial time delay between the animal-related risk and the administration of HRIG, in particular when the injury occurred abroad. More targeted communication about the risks of rabies and preventable measures may reduce this delay.Furthermore, the antibody response was inadequate in some cases following full PEP administration according to the Belgian recommendation.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown. This study investigates systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet, inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic measurements, aortic contractility studies, and in situ liver perfusion experiments were performed. The mean arterial blood pressure was lower and portal blood pressure was higher in steatosis compared to controls. The maximal contraction force in aortic rings from steatotic rats was markedly reduced compared to controls. While blockade of nitric oxide (NO) production did not reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity in both controls and steatosis, whereas effects were more pronounced in controls. Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation and endothelin-1 induced a significantly more pronounced increase in THPG in steatosis compared to controls. Our results demonstrate that severe steatosis, without inflammation or fibrosis, induces portal hypertension and signs of a hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO-independent, but appears to be mediated by specific COX-2-related mechanisms. Besides, the increased intrahepatic vascular resistance in steatosis appears not to be NO-related but rather to vasoconstrictor hyperreactivity.