[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.

[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.

[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.

[COVID-19 vaccines: vaccine targets, immunogenicity and allergic reactions]. / Vaccins contre le Covid-19 : cibles vaccinales, immunogénicité et réactions allergiques.

Many vaccine strategies have been developed to control the COVID-19 pandemic. This article presents the mechanisms of action and the efficacy of different vaccines including mRNA- and adenovirus-based vaccines. We will discuss the different vaccine targets, immune responses and allergic reactions which have been reported during the vaccination campaigns. Finally, the latest recommendations for the prevention and management of severe allergic reactions will be summarized.

De nombreuses stratégies vaccinales ont été développées pour tenter de contrôler la pandémie de Covid-19. Cet article présente le fonctionnement et l'efficacité de différents vaccins, en particulier ceux à ARN messager et adénovecteurs. Nous discutons des cibles vaccinales, des véhicules vaccinaux ainsi que de l'immunité qu'ils induisent. Nous nous penchons également sur la question des allergies aux vaccins qui a rapidement été soulevée après le début des campagnes de vaccination à large échelle. Les allergènes potentiellement en cause et les mécanismes impliqués sont discutés. Enfin, nous proposons des recommandations pour la prévention et la prise en charge des réactions allergiques sévères.

[COVID-19 Diagnosis]. / Diagnostic du Covid-19 en milieu ambulatoire.

The need to curb the circulation of SARS-CoV-2 virus in the community and to diagnose those at risk of developing complications implies that an appropriate test should be chosen according to the epidemiological and clinical context. Rapid antigen tests, either nasopharyngeal or nasal, have the advantage of reflecting contagiousness better than PCR and giving an immediate result, reason why they are used as first-line for community diagnosis and screening. A rapid test allows immediate management of outpatients and does not falsely attribute the current acute episode to a previous SARS-CoV-2 infection. PCR, whether nasopharyngeal or buccosalivary, is useful for epidemiological surveillance, including that of new variants, as well as identification of severe COVID in the post-infectious phase.

La nécessité de freiner la circulation du virus SARS-CoV-2 dans la communauté et diagnostiquer les personnes à risque de développer des complications implique de choisir le test approprié selon le contexte épidémiologique et clinique. Les tests antigéniques rapides, soit nasopharyngés, soit nasaux, ont l'avantage de mieux refléter la contagiosité que la PCR et de donner un résultat immédiat, raison pour laquelle ils sont utilisés en première intention pour le diagnostic et le dépistage communautaire. Un test rapide permet d'orienter tout de suite la prise en charge ambulatoire d'un·e patient·e et ne pas attribuer faussement un épisode aigu à une ancienne infection à SARS-CoV-2. La PCR, qu'elle soit nasopharyngée ou buccosalivaire, est utile pour la surveillance épidémiologique, notamment des nouveaux variants, ainsi que pour l'identification d'un Covid sévère dans la phase postinfectieuse.

Vaccine-associated measles in a patient treated with natalizumab: a case report.

BACKGROUND: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. CASE PRESENTATION: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae. CONCLUSION: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

[Long-term travelers to malaria endemic areas†: What prevention strategies†?] / Séjours prolongés en zone endémique de malaria†: quelles stratégies de prévention†?

Long-term travelers are particularly exposed to malaria. It is essential to inform them about this risk, the recognition of the symptoms of the disease and the need for prompt treatment. Addressing any fears of travelers and answering their questions improve therapeutic adherence. Personal protective measures (repellents, mosquito nets) are fundamental and safe to reduce exposure to the vector of the disease. Depending on the individual risk of malaria and the special vulnerability of the traveler, short-term or prolonged chemoprophylaxis and/or emergency self-treatment and a rapid diagnostic test for malaria may be offered.

Les voyageur·euse·s de longue durée sont particulièrement exposé·e·s à la malaria. Il est essentiel de les informer sur ce risque, la reconnaissance des symptômes de la maladie et la nécessité d'un traitement rapide. Aborder les éventuelles craintes des voyageur·euse·s et répondre à leurs interrogations permet d'améliorer l'adhésion thérapeutique. Les mesures de protection personnelles (sprays répulsifs, moustiquaires) sont fondamentales et sûres pour diminuer l'exposition au vecteur de la maladie. Selon le risque individuel de malaria et les facteurs de vulnérabilité du·de la voyageur·euse, une chimioprophylaxie initiale ou prolongée et/ou un autotraitement d'urgence et un test de diagnostic rapide de la malaria peuvent être proposés.

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.

COVID-19 Vaccination Program for Undocumented Migrants: Notes from the Field of a Regional Center of General Medicine and Public Health, Canton of Vaud, Switzerland.

The COVID-19 pandemic highlighted health inequities for vulnerable populations and the need for more equitable care and access to vaccination. This article described the implementation of a COVID-19 vaccination program for undocumented migrants in a regional academic center of general medicine and public health (Unisanté). The vaccination program's specific components included: triple coordination between the health authorities, the regional center and community partners, a walk-in and free service, no health insurance required, qualified nursing and administrative staff with previous experience with vulnerable populations, translated information materials and interpreters, a guarantee of confidentiality and a widespread communication campaign within the communities. In total, 2'351 undocumented migrants from 97 nationalities received at least one dose of mRNA COVID-19 vaccine (Spikevax) and 2242 were considered fully vaccinated. Although it was hard to assess its global effectiveness, the program vaccinated a significant number of undocumented adult migrants in the Canton of Vaud. The difficulties linked to the pandemic context, the heavy workload for healthcare staff and the limited resources were overcome by strong collaborations between the different actors involved throughout the program. Targeted public health policies, such as vaccination programs for undocumented migrants, are essential to guarantee equitable care, especially in pandemic times.

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).

Intradermal Testing With COVID-19 mRNA Vaccines Predicts Tolerance.

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy or with a suspected allergic reaction after the first dose remains to be defined. Methods: In this real-life study, we defined two cohorts of individuals: one pre-vaccination including 187 individuals with high-risk profiles for developing anaphylaxis and a second post-vaccination including 87 individuals with suspected allergic reactions after the COVID-19 mRNA vaccine. Upon negative skin test with an mRNA vaccine, a two-step (10-90%) vaccination protocol was performed. Positive skin tests were confirmed with the basophil activation test (BAT). Results: Among 604,267 doses of vaccine, 87 suspected allergic reactions (5 after the booster) were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% of the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced isolated asthmatic reactions during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Conclusion: Sensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10-90%-vaccination protocol can be safely administered upon negative skin testing.

Performance of RT-PCR on Saliva Specimens Compared With Nasopharyngeal Swabs for the Detection of SARS-CoV-2 in Children: A Prospective Comparative Clinical Trial.

BACKGROUND: Saliva reverse transcriptase-Polymerase chain reaction (RT-PCR) is an attractive alternative for the detection of severe acute respiratory syndrome coronavirus 2 in adults with less known in children. METHODS: Children with coronavirus disease 2019 symptoms were prospectively enrolled in a 1-month comparative clinical trial of saliva and nasopharyngeal (NP) RT-PCR. Detection rates and sensitivities of saliva and NP RT-PCR were compared as well as discordant NP and saliva RT-PCR findings including viral loads (VLs). RESULTS: Of 405 patients enrolled, 397 patients had 2 tests performed. Mean age was 12.7 years (range, 1.2-17.9). Sensitivity of saliva was 85.2% (95% confidence interval: 78.2%-92.1%) when using NP as the standard; sensitivity of NP was 94.5% (89.8%-99.2%) when saliva was considered as the standard. For a NP RT-PCR VL threshold of ≥103 and ≥104 copies/mL, sensitivity of saliva increases to 88.7% and 95.2%, respectively. Sensitivity of saliva and NP swabs was, respectively, 89.5% and 95.3% in patient with symptoms less than 4 days (P = 0.249) and 70.0% and 95.0% in those with symptoms ≥4-7 days (P = 0.096). The 15 patients who had an isolated positive NP RT-PCR were younger (P = 0.034), had lower NP VL (median 5.6 × 103 vs. 3.9 × 107, P < 0.001), and could not drool saliva at the end of the sampling (P = 0.002). VLs were lower with saliva than with NP RT-PCR (median 8.7 cp/mL × 104; interquartile range 1.2 × 104-5.2 × 105; vs. median 4.0 × 107 cp/mL; interquartile range, 8.6 × 105-1 × 108; P < 0.001). CONCLUSIONS: While RT-PCR testing on saliva performed more poorly in younger children and likely after longer duration of symptoms, saliva remains an attractive alternative to NP swabs in children.