Rabies post-exposure prophylaxis: A retrospective analysis of timing of initiation and antibody responses in a Belgian cohort.

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.

Schistosomiasis in the Military-A Narrative Review.

Schistosomiasis is a parasitosis caused by trematodes of the genus Schistosoma. Humans are infected when coming into contact with freshwater containing the parasites' infective stages, which are amplified through freshwater-dwelling snails acting as intermediate hosts. Schistosomiasis has posed significant problems for troops exposed to freshwater in endemic regions ever since the Napoleonic wars. Schistosomiasis has substantial differences in clinical presentation, depending on the type of parasite, intensity of infection and reinfection, clinical form, and disease stage. It can remain undiagnosed for long periods of time, with well-known long-term morbidity and mortality risks. The diagnosis of schistosomiasis depends on its stage and relays on several tests, all with limitations in sensitivity and specificity. The diagnostic gold standard is the detection of eggs in urine, feces, or tissue biopsies, but this can raise problems in patients such as military personnel, in which the worm burden is usually low. Praziquantel is the drug of choice for schistosomiasis. Currently, there is no available commercial vaccine against any Schistosoma parasite. Avoiding freshwater exposure is the best prevention. Herein, we review the clinical presentation, diagnosis, treatment, and prevention of schistosomiasis in the military. This information may decrease the impact of schistosomiasis on this particular professional group.

Humoral immune response against SARS-CoV-2 after adapted COVID-19 vaccine schedules in healthy adults: The IMCOVAS randomized clinical trial.

BACKGROUND: To overcome supply issues of COVID-19 vaccines, this partially single blind, multi-centric, vaccine trial aimed to evaluate humoral immunogenicity using lower vaccine doses, intradermal vaccination, and heterologous vaccine schedules. Also, the immunity after a booster vaccination was assessed. METHODOLOGY: 566 COVID-19-naïve healthy adults were randomized to 1 of 8 treatment arms consisting of combinations of BNT162b2, mRNA-1273, and ChAdOx1-S. Anti-Receptor-Binding Domain immunoglobulin G (RBD IgG) titers, neutralizing antibody titres, and avidity of the anti-RBD IgGs was assessed up to 1 year after study start. RESULTS: Prolonging the interval between vaccinations from 28 to 84 days and the use of a heterologous BNT162b2 + mRNA-1273 vaccination schedule led to a non-inferior immune response, compared to the reference schedule. A low dose of mRNA-1273 was sufficient to induce non-inferior immunity. Non-inferiority could not be demonstrated for intradermal vaccination. For all adapted vaccination schedules, anti-RBD IgG titres measured after a first booster vaccination were non-inferior to their reference schedule. CONCLUSION: This study suggests that reference vaccine schedules can be adapted without jeopardizing the development of an adequate immune response. Immunity after a booster vaccination did not depend on the dose or brand of the booster vaccine, which is relevant for future booster campaigns. The trial is registered in the European Union Clinical Trials Register (number 2021-001993-52) and on clinicaltrials.gov (NCT06189040).

Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study.

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127-0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 .

COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

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.

Presymptomatic viral shedding in high-risk mpox contacts: A prospective cohort study.

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.

Five accelerated schedules for the tick-borne encephalitis vaccine FSME-Immun® in last-minute travellers: an open-label, single-Centre, randomized controlled pilot trial.

BACKGROUND: The purpose of this exploratory study was to evaluate different accelerated tick-borne encephalitis (TBE) vaccine schedules for last-minute travellers. METHODS: In a single-centre, open-label pilot study, 77 TBE-naïve Belgian soldiers were randomized to one of the following five schedules with FSME-Immun®: group 1 ('classical accelerated' schedule) received one intramuscular (IM) dose at day 0 and day 14, group 2 two IM doses at day 0, group 3 two intradermal (ID) doses at day 0, group 4 two ID doses at day 0 and day 7, group 5 two ID doses at day 0 and day 14. The last dose(s) of the primary vaccination scheme were given after one year: IM (1 dose) or ID (2 doses). TBE virus neutralizing antibodies were measured in a plaque reduction neutralization test (PRNT90 and 50) at day 0, 14, 21, 28, month 3, 6, 12, and 12 + 21 days. Seropositivity was defined as neutralizing antibody titres ≥10. RESULTS: The median age was 19-19.5 years in each group. Median time-to-seropositivity up to day 28 was shortest for PRNT90 in ID-group 4 and for PRNT50 in all ID groups. Seroconversion until day 28 peaked highest for PRNT90 in ID-group 4 (79%) and for PRNT50 in ID-groups 4 and 5 (both 100%). Seropositivity after the last vaccination after 12 months was high in all groups. Previous yellow fever vaccination was reported in 16% and associated with lower GMTs of TBE-specific antibodies at all time points. The vaccine was generally well tolerated. However, mild to moderate local reactions occurred in 73-100% of ID compared to 0-38% of IM vaccinations, persistent discolouration was observed in nine ID vaccinated individuals. CONCLUSION: The accelerated two-visit ID schedules might offer a better immunological alternative to the recommended classical accelerated IM schedule but an aluminium-free vaccine would preferable.

Characteristics of confirmed mpox cases among clinical suspects: A prospective single-centre study in Belgium during the 2022 outbreak.

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.

Persistent morbidity in Clade IIb mpox patients: interim results of a long-term follow-up study, Belgium, June to November 2022.

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.

Alternative sampling specimens for the molecular detection of mpox (formerly monkeypox) virus.

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.

Bacteriophage-antibiotic combination therapy against extensively drug-resistant Pseudomonas aeruginosa infection to allow liver transplantation in a toddler.

Post-operative bacterial infections are a leading cause of mortality and morbidity after ongoing liver transplantation. Bacteria causing these infections in the hospital setting can exhibit high degrees of resistance to multiple types of antibiotics, which leads to major therapeutic hurdles. Alternate ways of treating these antibiotic-resistant infections are thus urgently needed. Phage therapy is one of them and consists in using selected bacteriophage viruses - viruses who specifically prey on bacteria, naturally found in various environmental samples - as bactericidal agents in replacement or in combination with antibiotics. The use of phage therapy raises various research questions to further characterize what determines therapeutic success or failure. In this work, we report the story of a toddler who suffered from extensively drug-resistant Pseudomonas aeruginosa sepsis after liver transplantation. He was treated by a bacteriophage-antibiotic intravenous combination therapy for 86 days. This salvage therapy was well tolerated, without antibody-mediated phage neutralization. It was associated with objective clinical and microbiological improvement, eventually allowing for liver retransplantation and complete resolution of all infections. Clear in vitro phage-antibiotic synergies were observed. The occurrence of bacterial phage resistance did not result in therapeutic failure, possibly due to phage-induced virulence tradeoffs, which we investigated in different experimental models.

Incidence and predictors of severe altitude illness symptoms in Mt. Kilimanjaro hikers: a prospective cohort study.

BACKGROUND: Each year several Mt. Kilimanjaro hikers die due to altitude illness (AI) although urgent descent is technically easily possible. The objectives of this study were to determine the incidence and predictors of severe altitude illness (SAI) symptoms and of summit success in Mt. Kilimanjaro hikers, and the measures taken when AI symptoms develop. METHODS: A prospective observational cohort study in Mt. Kilimanjaro hikers was conducted from December 2019 until March 2020. Participants were asked to complete a questionnaire at the entrance gate and one at the descend gate. A multivariate logistic regression was performed to study the relations between the variables. RESULTS: A total of 1237 recreational hikers and 266 porters or guides were included. The incidence of severe symptoms was 8.6% in recreational hikers and 1.5% in porters and guides. One percent (1.1%) of hikers was hospitalized due to SAI. A history of SAI, young age, summit failure and lack of clear advice predicted the development of severe symptoms. Uhuru peak was reached by 87.9% of the hikers. Absence of severe symptoms, acetazolamide prophylaxis, climbing higher in daytime, young age and climbing in more days predicted summit success. The majority climbed further despite the presence of mild or severe symptoms. The only measure taken in case of mild symptoms that was associated with a lower incidence of severe symptoms was not climbing further. CONCLUSION: The incidence of SAI symptoms in Mt. Kilimanjaro hikers was observed to be high. However, how hikers reacted during symptoms was not appropriate. Therefore, travel health counsellors should emphasize even more that hikers do not ascend higher until mild symptoms have resolved and that it is vital to descend immediately when severe symptoms develop. In addition, they can be informed on the measures, which improved summit success.

A case of Escherichia coli and Peptoniphilus species mixed osteomyelitis successfully identified by MALDI TOF-MS with a review of the literature.

BACKGROUND: Peptoniphilus species are Gram-positive anaerobic cocci that are commensals of the human vagina and gut. METHODS AND RESULTS: We describe a case of mixed Escherichia coli and Peptoniphilus spp. osteomyelitis identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry as Peptoniphilus harei and present a short literature review. CONCLUSION: To our knowledge, only six cases of P. harei osteomyelitis have been reported to date.

Human Filariasis in Travelers and Migrants: A Retrospective 25-year Analysis at the Institute of Tropical Medicine, Antwerp, Belgium.

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.

Epidemiology and etiology of blood stream infections in a Belgian burn wound center.

BACKGROUND: Infections are a major cause of morbidity in burn patients. We aimed to investigate the epidemiology and antibiotic susceptibility of blood stream infections in order to gain a better understanding of their role and burden in our Burn Wound Center. METHODS: This retrospective epidemiological investigation analyzed data derived from medical files of patients admitted to our Burn Wound Center having had at least one positive blood culture between 1 January and 31 December 2018. We focused on the prevalence of causative agents in blood stream infections in function of the time after injury and on their drug sensitivity. RESULTS: Among the 363 patients admitted to our Burn Wound Center during the study period, 29 had at least one episode of blood stream infection. Gram-negative organisms accounted for 56,36% of the pathogens in blood stream infections, Gram-positives for 38,17%, and yeasts for 5,45%. Pseudomonas aeruginosa was the most common bacterium (20%), followed by Staphylococcus epidermidis (16.36%), Escherichia coli and Klebsiella pneumoniae (9,09% each). A third of the Gram-negative isolates were multidrug resistant. Gram-positive cocci were isolated from blood cultures at a median of 9 days after the injury, earlier than Gram-negative rods (median 15 days). The main sources of blood stream infections were the burn wounds, followed by infected catheters. CONCLUSIONS: Multidrug resistant bacteria must be considered when selecting empirical antibiotic therapy in septic burn patients. In our center, we need to update our antibiotic guidelines, to review the hospital infection control measures and to introduce routine typing technology.

Severe mpox (formerly monkeypox) disease in five patients after recent vaccination with MVA-BN vaccine, Belgium, July to October 2022.

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.

A case of Flavonifractor plautii blood stream infection in a severe burn patient and a review of the literature.

BACKGROUND: Flavonifractor plautii is a strictly anaerobic rod shaped bacterium belonging to the family of Clostridiales. It is a commensal of the human intestinal microbiota which was seldom isolated from clinical samples, therefore clinical data are scarce. To date, only four cases of F. plautii infections were described, all occurring in immunosuppressed patients. CASE PRESENTATION: We report a case where F. plautii was isolated from the blood culture of a severe burn victim and identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. DISCUSSION: To the best of our knowledge, this is the first case of F. plautii blood stream infection described in a burn patient.

Evaluating Diagnostic Accuracy of Saliva Sampling Methods for Severe Acute Respiratory Syndrome Coronavirus 2 Reveals Differential Sensitivity and Association with Viral Load.

Nasopharyngeal swabs are considered the preferential collection method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Less invasive and simpler alternative sampling procedures, such as saliva collection, are desirable. We compared saliva specimens and nasopharyngeal (NP) swabs with respect to sensitivity in detecting SARS-CoV-2. A nasopharyngeal and two saliva specimens (collected by spitting or oral swabbing) were obtained from >2500 individuals. All samples were tested by RT-qPCR, detecting RNA of SARS-CoV-2. The test sensitivity was compared on the two saliva collections with the nasopharyngeal specimen for all subjects and stratified by symptom status and viral load. Of the 2850 patients for whom all three samples were available, 105 were positive on NP swab, whereas 32 and 23 were also positive on saliva spitting and saliva swabbing samples, respectively. The sensitivity of the RT-qPCR to detect SARS-CoV-2 among NP-positive patients was 30.5% (95% CI, 1.9%-40.2%) for saliva spitting and 21.9% (95% CI, 14.4%-31.0%) for saliva swabbing. However, when focusing on subjects with medium to high viral load, sensitivity on saliva increased substantially: 93.9% (95% CI, 79.8%-99.3%) and 76.9% (95% CI, 56.4%-91.0%) for spitting and swabbing, respectively, regardless of symptomatic status. Our results suggest that saliva cannot readily replace nasopharyngeal sampling for SARS-CoV-2 diagnostics but may enable identification of the most contagious cases with medium to high viral loads.