[Malaria vaccines: a new tool for elimination?] / Vaccins contre le paludisme : un nouvel outil pour l'élimination ?

A malaria vaccine represents an essential complementary tool to curb the stagnation, or even increase, in malaria cases observed over the last decade due to the emergence of resistance to insecticides impregnated on mosquito nets, wars and internal conflicts, as well as global warming. In October 2021, WHO recommended the use of the RTS,S/ASO1 vaccine for children aged 5-17 months in areas of moderate to high transmission. In October 2023, a second vaccine received WHO approval for deployment in the same population, following demonstration of around 70 % efficacy in protecting young children against malaria for one year. Given their partial efficacy, however, these vaccines are not generally recommended for travelers to endemic countries.

Un vaccin contre le paludisme représente une mesure complémentaire essentielle pour juguler la stagnation, voire l'augmentation des cas de paludisme observée durant cette dernière décade en raison de l'émergence de la résistance aux insecticides imprégnés sur les moustiquaires, des guerres et conflits internes ainsi que du réchauffement climatique. En octobre 2021, l'OMS a recommandé l'emploi du vaccin RTS,S/ASO1 pour les enfants de 5 à 17 mois dans les zones de transmission modérée à forte. En octobre 2023, un second vaccin a reçu l'aval de l'OMS pour son déploiement dans la même population, suite à la démonstration d'une efficacité d'environ 70 % pour protéger les jeunes enfants contre le paludisme pendant une année. Vu leur efficacité partielle, ces vaccins ne sont cependant généralement pas recommandés pour les voyageurs se rendant dans les pays d'endémie.

Prevalence and predictors of residual antibiotics in children's blood in community settings in Tanzania.

OBJECTIVE: Children account for a significant proportion of antibiotic consumption in low- and middle-income countries, with overuse occurring in formal and informal health sectors. This study assessed the prevalence and predictors of residual antibiotics in the blood of children in Mbeya and Morogoro regions of Tanzania. METHODS: The cross-sectional community-based survey used two-stage cluster sampling to include children aged under 15 years. For each child, information on recent illness, healthcare-seeking behavior, and use of antibiotics, as well as a dried blood spot sample, were collected. The samples underwent tandem mass spectrometry analysis to quantify the concentrations of 15 common antibiotics. Associations between survey variables and presence of residual antibiotics were assessed using mixed-effects logistic regression. RESULTS: In total, 1742 children were surveyed, and 1699 analyzed. The overall prevalence of residual antibiotics in the blood samples was 17.4% (296/1699), the highest among children under the age of five years. The most frequently detected antibiotics were trimethoprim (144/1699; 8.5%), sulfamethoxazole (102/1699; 6.0%), metronidazole (61/1699; 3.6%) and amoxicillin (43/1699; 2.5%). The strongest predictors of residual antibiotics in the blood were observed presence of antibiotics at home (aOR=2.9; 95% CI: 2.0-4.1) and reported consumption of antibiotics in the last two weeks (aOR=2.5; 95% CI: 1.6-3.9). However, half (145/296) of the children who had residual antibiotics in their blood, some with multiple antibiotics, had no reported history of illness or antibiotic consumption in the last two weeks, and antibiotics were not found at home. DISCUSSION: This study demonstrated a high prevalence of antibiotic exposure among children in Tanzanian communities, albeit likely underestimated, especially for compounds with short half-lives. A significant proportion of antibiotic exposure was unexplained and may have been due to unreported self-medication or environmental pathways. Incorporating biomonitoring into surveillance strategies can help better understand exposure patterns and design antibiotic stewardship interventions.

MALrisk: a machne-learning based tool to predict imported malaria in returned travellers with fever.

BACKGROUND: Early diagnosis is key to reducing the morbi-mortality associated with P. falciparum malaria among international travellers. However, access to microbiological tests can be challenging for some healthcare settings. Artificial Intelligence could improve the management of febrile travellers. METHODS: Data from a multicentric prospective study of febrile travellers was obtained to build a machine-learning model to predict malaria cases among travellers presenting with fever. Demographic characteristics, clinical and laboratory variables were leveraged as features. Eleven machine-learning classification models were evaluated by 50-fold cross-validation in a Training set. Then, the model with the best performance, defined by the Area Under the Curve (AUC), was chosen for parameter optimization and evaluation in the Test set. Finally, a reduced model was elaborated with those features that contributed most to the model. RESULTS: Out of eleven machine-learning models, XGBoost presented the best performance (mean AUC of 0.98 and a mean F1 score of 0.78). A reduced model (MALrisk) was developed using only six features: Africa as a travel destination, platelet count, rash, respiratory symptoms, hyperbilirubinemia and chemoprophylaxis intake. MALrisk predicted malaria cases with 100% (95%CI 96-100) sensitivity and 72% (95%CI 68-75) specificity. CONCLUSIONS: The MALrisk can aid in the timely identification of malaria in non-endemic settings, allowing the initiation of empiric antimalarials and reinforcing the need for urgent transfer in healthcare facilities with no access to malaria diagnostic tests. This resource could be easily scalable to a digital application and could reduce the morbidity associated with late diagnosis.

Assessing viral metagenomics for the diagnosis of acute undifferentiated fever in returned travellers: a multicenter cohort study.

BACKGROUND: Up to 45% of febrile returning travellers remain undiagnosed after a thorough diagnostic work-up, even at referral centres. Although metagenomic next-generation sequencing (mNGS) has emerged as a promising tool, evidence of its usefulness in imported fever is very limited. METHODS: Travellers returning with fever were prospectively recruited in three referral clinics from November 2017 to November 2019. Unbiased mNGS optimised for virus detection was performed on serum samples of participants with acute undifferentiated febrile illness (AUFI), and results were compared to those obtained by reference diagnostic methods (RDM). RESULTS: Among 507 returned febrile travellers, 433(85.4%) presented with AUFI. Dengue virus (n = 86) and Plasmodium spp. (n = 83) were the most common causes of fever. 103/433(23.8%) AUFI remained undiagnosed at the end of the follow-up.Metagenomic next-generation sequencing unveiled potentially pathogenic microorganisms in 196/433(38.7%) AUFI. mNGS identifications were more common in patients with a shorter duration of fever (42.3% in ≤5 days vs 28.7% in >5 days, P = 0.005). Potential causes of fever were revealed in 25/103(24.2%) undiagnosed AUFI and 5/23(21.7%) travellers with severe undiagnosed AUFI. Missed severe aetiologies included eight bacterial identifications and one co-infection of B19 parvovirus and Aspergillus spp.Additional identifications indicating possible co-infections occurred in 29/316(9.2%) travellers with AUFI, and in 11/128(8.6%) travellers with severe AUFI, who had received a diagnosis through RDM. The most common co-infections detected in severe AUFI were caused by Gram-negative bacteria. Serum mNGS was unable to detect >50% of infectious diagnoses achieved by RDM and also yielded 607 non-pathogenic identifications. DISCUSSION: mNGS of serum can be a valuable diagnostic tool for selected travellers with undiagnosed AUFI or severe disease in addition to reference diagnostic techniques, especially during the first days of symptoms. Nevertheless, mNGS results interpretation presents a great challenge. Further studies evaluating the performance of mNGS using different sample types and protocols tailored to non-viral agents are needed.

Injuries and medical emergencies among international travellers.

BACKGROUND: Tropical infectious diseases and vaccine-preventable emergencies are the mainstay of pre-travel consultations. However, non-communicable diseases, injuries and accidents that occur during travel are not emphasized enough in these settings. METHODS: We performed a narrative review based on a literature search of PubMed, Google Scholar, UpToDate, DynaMed and LiSSa and on reference textbooks and medical journals dedicated to travel, emergency and wilderness medicine. Relevant secondary references were extracted. We also aimed to discuss newer or neglected issues, such as medical tourism, Coronavirus Disease 2019, exacerbations of co-morbidities associated with international travel, insurance coverage, health care seeking abroad, medical evacuation or repatriation and tips for different types of travellers' emergency medical kits (personal, group, physician handled). RESULTS: All sources reviewed led to the selection of >170 references. Among epidemiological data on morbidity and deaths while abroad, only retrospective data are available. Deaths are estimated to occur in 1 in 100 000 travellers, with 40% caused by trauma and 60% by diseases, and <3% linked to infectious diseases. Trauma and other injuries acquired during travel, such as traffic accidents and drowning, can be reduced by up to 85% with simple preventive recommendations such as avoiding simultaneous alcohol intake. In-flight emergencies occur on 1 in 604 flights on average. Thrombosis risk is two to three times greater for travellers than for non-travellers. Fever during or after travel can occur in 2-4% of travellers, but in up to 25-30% in tertiary centres. Traveller's diarrhoea, although rarely severe, is the most common disease associated with travel. Autochthonous emergencies (acute appendicitis, ectopic pregnancy, dental abscess) can also occur. CONCLUSIONS: Pre-travel medicine encounters must include the topic of injuries and medical emergencies, such as the risk-taking behaviours and foster better planning in a comprehensive approach along with vaccines and infectious diseases advices.

Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 study.

BACKGROUND: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. METHODS: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18-45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. FINDINGS: 26 participants were enrolled (August-September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088-0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively). INTERPRETATION: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. FUNDING: Emergex Vaccines Holding Limited.

Clinical evaluation of BioFire® multiplex-PCR panel for acute undifferentiated febrile illnesses in travellers: a prospective multicentre study.

BACKGROUND: Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever. METHODS: Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017-November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology). FINDINGS: Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology. INTERPRETATION: The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections.

Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

BACKGROUND: Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. METHODS: In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. RESULTS: Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. CONCLUSIONS: RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Should we treat Blastocystis sp.? A double-blind placebo-controlled randomized pilot trial.

BACKGROUND: Blastocystis sp. is a worldwide-distributed protist colonizing the guts of humans and a great variety of animals. It is unclear whether it is just a commensal or an infectious parasite that prompts eradication.The main objective of this study was to evaluate the usefulness of metronidazole in patients with gastrointestinal symptoms harbouring only Blastocystis sp. In addition, we explored whether Blastocystis subtype or concomitant parasitic infection detected by polymerase chain reaction (PCR) may influence treatment outcome. METHODS: We included adults with persistent gastrointestinal symptoms (>14 days) visiting a primary care physician and in whom stool microscopy revealed only Blastocystis sp. Eligible patients were randomized to receive 10 days of metronidazole or placebo, followed by a crossover if still symptomatic. The primary outcome was normal stool consistency. Secondary outcomes were the changes in other abdominal symptoms (bloating, flatulence, abdominal pain, number of daily bowel movements) and general wellbeing. After the clinical phase of the study, Blastocystis subtypes were determined by PCR sequencing and stool samples were tested for 11 other protozoa with an in-house PCR. RESULTS: We screened 581 outpatients for inclusion, of which 50 met the eligibility criteria. There was no difference in the primary outcome, nor any of the secondary outcomes between the subjects treated with metronidazole and placebo.The most frequent Blastocystis subtypes were ST4 (11/36) and ST2 (10/36). The in-house PCR was positive for other protozoa in 25% (10/40) of the patients. We identified Dientamoeba fragilis in 5, Entamoeba dispar in 3 and Cyclospora cayetanensis in 2 patients. Stratified analysis according to Blastocystis subtype or the presence of other protozoa showed no significant difference in treatment outcome with metronidazole or placebo. CONCLUSIONS: Among patients infected with Blastocystis sp., metronidazole, compared with placebo, was not better in improving gastrointestinal symptoms, irrespective of subtype or microscopically undetected coinfection with other protozoa.

Doxycycline responding illnesses in returning travellers with undifferentiated non-malaria fever: a European multicentre prospective cohort study.

BACKGROUND: Diagnosis of undifferentiated non-malaria fevers (NMF) in returning travellers is a great challenge. Currently, there is no consensus about the use of empirical antibiotics in returning travellers with undifferentiated NMF. Although studies in endemic areas showed that a wide range of pathogens implicated in undifferentiated NMF are treatable with doxycycline, the role of doxycycline in returning travellers with fever still has to be explored. METHODS: Prospective European multicentre cohort study of febrile international travellers (November 2017-November 2019). Immunological and molecular diagnostic techniques for doxycycline responding illnesses (DRI) agents such as Anaplasma phagocytophilum, spotted fever group Rickettsia spp., typhus group Rickettsia spp., Coxiella burnetii, Bartonella spp., Orientia tsutsugamushi, Borrelia miyamotoi, Borrelia recurrentis and Leptospira spp. were systematically performed in all patients with undifferentiated NMF. We estimated the prevalence and predictive factors of DRI in returning travellers with undifferentiated NMF. RESULTS: Among 347 travellers with undifferentiated NMF, 106 (30·5%) were finally diagnosed with DRI. Only 57 (53·8%) of the 106 DRI infections were diagnosed by the standard of care. The main causes of DRI were: 55 (51·9%) Rickettsia spp., 16 (15·1%) C. burnetii; 15 (14·2%) Bartonella spp.; 13 (12·3%) Leptospira spp. and 10 (9·5%) A. phagocytophilum. The only predictive factor associated with DRI was presenting an eschar (aOR 39·52, 95%CI 4·85-322·18). Features of dengue such as retro-orbital pain (aOR 0·40, 95%CI 0·21-0·76) and neutropenia (aOR 0·41, 95%CI 0·21-0·79) were negatively associated with DRI. CONCLUSIONS: Although DRI are responsible for 30% of undifferentiated NMF cases in travellers, those are seldom recognized during the first clinical encounter. Empirical treatment with doxycycline should be considered in returning travellers with undifferentiated fever and negative tests for malaria and dengue, particularly when presenting severe illness, predictive factors for rickettsiosis or no features of dengue.

[Eco-tourism: what recommendations?] / Voyager écolo : quelles recommandations ?

Which recommendations family doctors and travel health practitioners can provide to their patients, to reduce their environmental footprint when travelling? Avoiding flying is the biggest action a traveler can take to reduce their greenhouse gas emissions. Staying at eco-lodges, or carbon offsetting, may help, but one must be aware of false or exaggerated claims on their impact. Using UV light, filters, halogens or boiling water, are effective ways to disinfect water and reduce the waste created from plastic water bottles. Given the large carbon footprint of medications and laboratory exams, limiting prescription of antibiotics or antimalarials in pre-travel consultations, or limiting unnecessary laboratory exams in returning travelers by following the latest recommendations, could reduce greenhouse emissions of the medical practice.

Quelles recommandations les généralistes et médecins du voyage peuvent-ils fournir à leur patientèle pour réduire les impacts environnementaux de leurs voyages ? Éviter les trajets en avion est l'action la plus efficace pour réduire ses émissions de gaz à effet de serre. Séjourner dans des éco-lodges ou la compensation carbone financière peuvent être positifs mais leur bénéfice est souvent surestimé. Filtres, UV, halogènes ou cuisson permettent la désinfection efficace de l'eau et la réduction des déchets dus aux bouteilles en plastique. Au vu de l'empreinte carbone des traitements et examens de laboratoire, limiter la prescription d'antibiotiques et d'antimalariques en consultation prévoyage ainsi que les examens inutiles au retour selon les recommandations actuelles réduisent aussi les impacts de la pratique médicale.

[Travel vaccines: what is in the pipeline?] / Vaccins de voyage : quel horizon ?

While no vaccine is on the horizon to prevent traveler's diarrhea, progress has been made in the field of malaria and dengue fever. In both cases, the objective is not primarily the prevention among travelers but rather the reduction of morbidity and mortality in populations living in endemic areas. The immune mechanisms protecting against parasitosis are not well understood, which further complicates vaccine development. The fact that veterinary vaccines against the parasites causing cysticercosis and echinococcosis are available for animals, justifies a certain optimism that vaccines against parasitosis will also be available for humans in the future. We report on recent developments in dengue, malaria, schistosomiasis, and hookworm vaccines.

Si aucun vaccin ne pointe à l'horizon pour prévenir la diarrhée des voyageurs, des progrès ont été faits dans le domaine de la malaria et de la dengue. Dans les deux cas, l'objectif n'est pas prioritairement la prévention chez les voyageurs mais plutôt la diminution de la morbidité et mortalité dans les populations vivant en zone d'endémie. Les mécanismes immunitaires protégeant contre les parasitoses ne sont pas bien connus, ce qui complique encore le développement vaccinal. Le fait que des vaccins vétérinaires contre les parasites causant la cysticercose et l'échinococcose soient disponibles pour les animaux justifie un certain optimisme de voir à l'avenir aussi chez l'humain des vaccins contre des parasitoses. Nous faisons le point sur les développements récents des vaccins contre la dengue, la malaria, la schistosomiase et l'ankylostomiase.

[Covid-19 crisis: testing and vaccination in the light of diminishing returns]. / Crise du Covid-19 : le testing et la vaccination à l'aune des rendements décroissants.

At the time of the assessment of the sanitary measures taken to fight the crisis, we have analysed the testing and vaccination following the grid well known in health economics: the law of diminishing returns. In the first phase, the returns are positive and increasing, the increase in benefits being faster than the increase in costs. In the second phase, returns are still positive but decreasing, with costs increasing faster than benefits. In the third and last phase, the returns become negative, with benefits decreasing despite an increase in costs. Both testing and vaccination, which were very beneficial at the beginning of the crisis, progressively followed a trajectory of diminishing returns with the extension of the measures to wider populations (asymptomatic or young persons), or for example with the emergence of the Omicron variant.

À l'heure du bilan des mesures sanitaires prises pour juguler la crise, nous avons soumis le testing et la vaccination à la grille d'analyse connue en économie de la santé : la loi des rendements décroissants. Dans une première phase, les rendements sont positifs et croissants, l'augmentation des bénéfices étant plus rapide que celle des coûts. Dans une deuxième phase, les rendements sont toujours positifs mais décroissants, l'augmentation des coûts étant plus rapide que celle des bénéfices. Dans une troisième et dernière phase, les rendements deviennent négatifs, les bénéfices diminuant malgré une augmentation des coûts. Tant le testing que la vaccination, très bénéfiques au début de la crise, ont progressivement suivi une trajectoire de rendements décroissants avec l'extension des mesures à des populations plus larges (asymptomatiques ou jeunes), ou par exemple avec l'apparition du variant Omicron.

[Pharmacovigilance - mRNA COVID-19 vaccines : current state of knowledge on their adverse effects]. / Pharmacovigilance - Vaccins à ARNm contre le Covid-19 : le point sur les effets indésirables.

The COVID-19 pandemic has stimulated the rapid development and large-scale use of technologically innovative vaccines, such as the mRNA vaccines Spikevax (Moderna) and Comirnaty (Pfizer-BioNTech). This unprecedented deployment has challenged pharmacovigilance, requiring combined skills in safety monitoring, prompt data analysis and continuous dissemination of knowledge. Main recognised adverse events of these vaccines are moderate and transient, linked to their significant reactogenicity. Active post-marketing surveillance has identified rare adverse events such as myopericarditis and a variety of skin reactions. A number of potential rare adverse events are being evaluated and could be retained at the individual level, but do not question the overall safety of these vaccines.

La pandémie de Covid-19 a conduit au développement rapide de vaccins à la technologie innovante, utilisés à large échelle, dont les vaccins à ARNm Spikevax (Moderna) et Comirnaty (Pfizer-BioNTech). Ce déploiement sans précédent défie la pharmacovigilance, nécessitant d'allier un suivi attentif de la sécurité, une analyse rapide des données et une diffusion continue des connaissances. Les principaux effets indésirables reconnus pour ces vaccins sont modérés et transitoires, liés à leur importante réactogénicité. Une pharmacovigilance active a permis d'identifier des effets indésirables rares, tels que des myopéricardites et diverses réactions cutanées. Un certain nombre d'effets indésirables rares potentiels sont en cours d'évaluation et pourraient être retenus à l'échelle individuelle, mais ne remettent pas en cause la sécurité vaccinale globale.

Causes of fever in returning travelers: a European multicenter prospective cohort study.

BACKGROUND: Etiological diagnosis of febrile illnesses in returning travelers is a great challenge, particularly when presenting with no focal symptoms [acute undifferentiated febrile illnesses (AUFI)], but is crucial to guide clinical decisions and public health policies. In this study, we describe the frequencies and predictors of the main causes of fever in travelers. METHODS: Prospective European multicenter cohort study of febrile international travelers (November 2017-November 2019). A predefined diagnostic algorithm was used ensuring a systematic evaluation of all participants. After ruling out malaria, PCRs and serologies for dengue, chikungunya and Zika viruses were performed in all patients presenting with AUFI ≤ 14 days after return. Clinical suspicion guided further microbiological investigations. RESULTS: Among 765 enrolled participants, 310/765 (40.5%) had a clear source of infection (mainly traveler's diarrhea or respiratory infections), and 455/765 (59.5%) were categorized as AUFI. AUFI presented longer duration of fever (p < 0.001), higher hospitalization (p < 0.001) and ICU admission rates (p < 0.001). Among travelers with AUFI, 132/455 (29.0%) had viral infections, including 108 arboviruses, 96/455 (21.1%) malaria and 82/455 (18.0%) bacterial infections. The majority of arboviral cases (80/108, 74.1%) was diagnosed between May and November. Dengue was the most frequent arbovirosis (92/108, 85.2%). After 1 month of follow-up, 136/455 (29.9%) patients with AUFI remained undiagnosed using standard diagnostic methods. No relevant differences in laboratory presentation were observed between undiagnosed and bacterial AUFI. CONCLUSIONS: Over 40% of returning travelers with AUFI were diagnosed with malaria or dengue, infections that can be easily diagnosed by rapid diagnostic tests. Arboviruses were the most common cause of AUFI (above malaria) and most cases were diagnosed during Aedes spp. high season. This is particularly relevant for those areas at risk of introduction of these pathogens. Empirical antibiotic regimens including doxycycline or azithromycin should be considered in patients with AUFI, after ruling out malaria and arboviruses.

Clinical sign and biomarker-based algorithm to identify bacterial pneumonia among outpatients with lower respiratory tract infection in Tanzania.

BACKGROUND: Inappropriate antibiotics use in lower respiratory tract infections (LRTI) is a major contributor to resistance. We aimed to design an algorithm based on clinical signs and host biomarkers to identify bacterial community-acquired pneumonia (CAP) among patients with LRTI. METHODS: Participants with LRTI were selected in a prospective cohort of febrile (≥ 38 °C) adults presenting to outpatient clinics in Dar es Salaam. Participants underwent chest X-ray, multiplex PCR for respiratory pathogens, and measurements of 13 biomarkers. We evaluated the predictive accuracy of clinical signs and biomarkers using logistic regression and classification and regression tree analysis. RESULTS: Of 110 patients with LRTI, 17 had bacterial CAP. Procalcitonin (PCT), interleukin-6 (IL-6) and soluble triggering receptor expressed by myeloid cells-1 (sTREM-1) showed an excellent predictive accuracy to identify bacterial CAP (AUROC 0.88, 95%CI 0.78-0.98; 0.84, 0.72-0.99; 0.83, 0.74-0.92, respectively). Combining respiratory rate with PCT or IL-6 significantly improved the model compared to respiratory rate alone (p = 0.006, p = 0.033, respectively). An algorithm with respiratory rate (≥ 32/min) and PCT (≥ 0.25 µg/L) had 94% sensitivity and 82% specificity. CONCLUSIONS: PCT, IL-6 and sTREM-1 had an excellent predictive accuracy in differentiating bacterial CAP from other LRTIs. An algorithm combining respiratory rate and PCT displayed even better performance in this sub-Sahara African setting.

[mRNA Covid vaccines: What do we know eight months after deployment]. / Vaccins à ARN messager contre le Covid-19 : piqûre de rappel.

This paper summarizes the main knowledge on mRNA vaccines in September 2021. The only contraindication for a 1st dose of vaccine is an allergy to one of the components of the vaccine, but a specialized consultation is possible for an eventual split vaccination under medical supervision. Serious side effects are rare and consist mainly of myocarditis, shingles and appendicitis, but the risk/benefit ratio is always favorable for vaccination. Efficacy against severe COVID-19 is > 90 % after 6 months, and this against all variants. It is recommended to vaccinate pregnant women. A 3rd dose is not recommended at this time, except for immunosuppressed individuals without detectable antibodies after 2 doses. Vaccine mixing is possible, including with a viral vector vaccine.

Cet article résume les connaissances principales sur les vaccins à ARN messager en septembre 2021. La seule contre-indication pour une 1re dose de vaccin est une allergie à l'un des composants du vaccin, mais une consultation spécialisée est possible pour une éventuelle vaccination fractionnée sous surveillance médicale. Les effets secondaires graves sont rares et consistent principalement en myocardite, zona et appendicite, mais le rapport risques/bénéfices est toujours favorable pour la vaccination. L'efficacité contre le Covid-19 sévère est supérieure à 90 % après 6 mois, et cela contre tous les variants. Il est recommandé de vacciner les femmes enceintes. Une 3e dose n'est pas recommandée pour l'instant, sauf pour les personnes immunosupprimées sans anticorps détectables après 2 doses. Les mélanges de vaccins sont possibles, y compris avec un vaccin à vecteur viral.

Which strategy for using medical and community masks? A prospective analysis of their environmental impact.

INTRODUCTION: The use of personal protective equipment, especially medical masks, increased dramatically during the COVID-19 crisis. Medical masks are made of synthetic materials, mainly polypropylene, and a majority of them are produced in China and imported to the European market. The urgency of the need has so far prevailed over environmental considerations. OBJECTIVE: Assess the environmental impact of different strategies for the use of face mask. METHOD: A prospective analysis was conducted to assess the environmental impact of different strategies for the use of medical and community masks. Eight scenarios, differentiating the typologies of masks and the modes of reuse are compared using three environmental impact indicators: the Global Warming Potential (GWP100), the ecological scarcity (UBP method, from German 'Umweltbelastungpunkte') and the plastic leakage (PL). This study attempts to provide clear recommendations that consider both the environmental impact and the protective effectiveness of face masks used in the community. RESULTS: The environmental impact of single-use masks is the most unfavourable, with a GWP of 0.4-1.3 kg CO2 eq., depending on the transport scenario, and a PL of 1.8 g, for a 1 month protection against COVID-19. The use of home-made cotton masks and prolonged use of medical masks through wait-and-reuse are the scenarios with the lowest impact. CONCLUSION: The use of medical masks with a wait and reuse strategy seems to be the most appropriate when considering both environmental impact and effectiveness. Our results also highlight the need to develop procedures and the legal/operational framework to extend the use of protective equipment during a pandemic.