[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.

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.

[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.

[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.

[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.

[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 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.

Clinical relevance of low-density Plasmodium falciparum parasitemia in untreated febrile children: A cohort study.

BACKGROUND: Low-density (LD) Plasmodium infections are missed by standard malaria rapid diagnostic tests (standard mRDT) when the blood antigen concentration is below the detection threshold. The clinical impact of these LD infections is unknown. This study investigates the clinical presentation and outcome of untreated febrile children with LD infections attending primary care facilities in a moderately endemic area of Tanzania. METHODS/FINDINGS: This cohort study includes 2,801 febrile pediatric outpatients (median age 13.5 months [range 2-59], female:male ratio 0.8:1.0) recruited in Dar es Salaam, Tanzania between 01 December 2014 and 28 February 2016. Treatment decisions were guided by a clinical decision support algorithm run on a mobile app, which also collected clinical data. Only standard mRDT+ cases received antimalarials. Outcomes (clinical failure, secondary hospitalization, and death) were collected in follow-up visits or interviews on days 3, 7, and 28. After patient recruitment had ended, frozen blood from all 2,801 patients was tested for Plasmodium falciparum (Pf) by ultrasensitive-quantitative polymerase chain reaction (qPCR), standard mRDT, and "ultrasensitive" mRDT. As the latter did not improve sensitivity beyond standard mRDT, it is hereafter excluded. Clinical features and outcomes in LD patients (standard mRDT-/ultrasensitive-qPCR+, not given antimalarials) were compared with those with no detectable (ND) parasitemia (standard mRDT-/ultrasensitive-qPCR-) or high-density (HD) infections (standard mRDT+/ultrasensitive-qPCR+, antimalarial-treated). Pf positivity rate was 7.1% (n = 199/2,801) and 9.8% (n = 274/2,801) by standard mRDT and ultrasensitive qPCR, respectively. Thus, 28.0% (n = 76/274) of ultrasensitive qPCR+ cases were not detected by standard mRDT and labeled "LD". LD patients were, on average, 10.6 months younger than those with HD infections (95% CI 7.0-14.3 months, p < 0.001). Compared with ND, LD patients more frequently had the diagnosis of undifferentiated fever of presumed viral origin (risk ratio [RR] = 2.0, 95% CI 1.3-3.1, p = 0.003) and were more often suffering from severe malnutrition (RR = 3.2, 95% CI 1.1-7.5, p = 0.03). Despite not receiving antimalarials, outcomes for the LD group did not differ from ND regarding clinical failures (2.6% [n = 2/76] versus 4.0% [n = 101/2,527], RR = 0.7, 95% CI 0.2-3.5, p = 0.7) or secondary hospitalizations (2.6% [n = 2/76] versus 2.8% [n = 72/2,527], RR = 0.7,95% CI 0.2-3.2, p = 0.9), and no deaths were reported in any Pf-positive groups. HD patients experienced more secondary hospitalizations (10.1% [n = 20/198], RR = 0.3, 95% CI 0.1-1.0, p = 0.005) than LD patients. All the patients in this cohort were febrile children; thus, the association between parasitemia and fever cannot be investigated, nor can the conclusions be extrapolated to neonates and adults. CONCLUSIONS: During a 28-day follow-up period, we did not find evidence of a difference in negative outcomes between febrile children with untreated LD Pf parasitemia and those without Pf parasitemia. These findings suggest LD parasitemia may either be a self-resolving fever or an incidental finding in children with other infections, including those of viral origin. These findings do not support a clinical benefit nor additional risk (e.g. because of missed bacterial infections) to using ultrasensitive malaria diagnostics at a primary care level.

Pregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.

BACKGROUND: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. METHODS: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. RESULTS: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). CONCLUSIONS: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.

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.

A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

Diagnostic Performance of Conventional and Ultrasensitive Rapid Diagnostic Tests for Malaria in Febrile Outpatients in Tanzania.

BACKGROUND: A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. METHODS: Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: us-RDT identified few additional P. falciparum-positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. CONCLUSION: There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT.

[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.

[Covid-19 diagnosis†: clinical recommendations and performance of nasopharyngeal swab-PCR]. / Performance du frottis nasopharyngé-PCR pour le diagnostic du Covid-19 - Recommandations pratiques sur la base des premières données scientifiques.

The Covid-19 pandemic imposes new diagnostic strategies in order to optimize the medical care of our patients. The current biblio-graphy, although of low quality, shows a sensitivity of 56 to 83 % for the Covid-19 PCR. Even though one negative test can exclude a Covid-19 in the majority of cases, the NPV (Negative Predictive Value) decreases with increasing prevalence (pre-test probability). This finding suggests the need for strict auto-isolation of patients until the resolution of their symptoms. For patients that present with typical symptoms, who have a presumed Covid-19 prevalence of -40-50 %, a negative test should be interpreted with caution and a repeat test may be needed.

La pandémie actuelle du Covid-19 impose une stratégie diagnostique pour la prise en charge des patients. La performance du frottis nasopharyngé avec analyse par PCR peut être estimée sur la base des premières données bibliographiques. Celles-ci, certes de qualité faible, montrent une sensibilité de 56 à 83 % pour la PCR Covid-19. Un seul test négatif permet d'infirmer un Covid-19 dans la majorité des situations. Cependant, comme la valeur ­prédictive négative du test se situe entre 88 et 95 % en cas de ­probabilité prétest de 30 %, il est indispensable d'assurer le suivi de ces patients. Pour ceux qui présentent des symptômes typiques, qui auraient une probabilité prétest présumée à 40-50 %, un test négatif doit être interprété avec précaution et un deuxième test peut être indiqué.

Safety and Efficacy of C-reactive Protein-guided Antibiotic Use to Treat Acute Respiratory Infections in Tanzanian Children: A Planned Subgroup Analysis of a Randomized Controlled Noninferiority Trial Evaluating a Novel Electronic Clinical Decision Algorithm (ePOCT).

BACKGROUND: The safety and efficacy of using C-reactive protein (CRP) to decide on antibiotic prescription among febrile children at risk of pneumonia has not been tested. METHODS: This was a randomized (1:1) controlled noninferiority trial in 9 primary care centers in Tanzania (substudy of the ePOCT trial evaluating a novel electronic decision algorithm). Children aged 2-59 months with fever and cough and without life-threatening conditions received an antibiotic based on a CRP-informed strategy (combination of CRP ≥80 mg/L plus age/temperature-corrected tachypnea and/or chest indrawing) or current World Health Organization standard (respiratory rate ≥50 breaths/minute). The primary outcome was clinical failure by day (D) 7; the secondary outcomes were antibiotic prescription at D0, secondary hospitalization, or death by D30. RESULTS: A total of 1726 children were included (intervention: 868, control: 858; 0.7% lost to follow-up). The proportion of clinical failure by D7 was 2.9% (25/865) in the intervention arm vs 4.8% (41/854) in the control arm (risk difference, -1.9% [95% confidence interval {CI}, -3.7% to -.1%]; risk ratio [RR], 0.60 [95% CI, .37-.98]). Twenty of 865 (2.3%) children in the intervention arm vs 345 of 854 (40.4%) in the control arm received antibiotics at D0 (RR, 0.06 [95% CI, .04-.09]). There were fewer secondary hospitalizations and deaths in the CRP arm: 0.5% (4/865) vs 1.5% (13/854) (RR, 0.30 [95% CI, .10-.93]). CONCLUSIONS: CRP testing using a cutoff of ≥80 mg/L, integrated into an electronic decision algorithm, was able to improve clinical outcome in children with respiratory infections while substantially reducing antibiotic prescription. CLINICAL TRIALS REGISTRATION: NCT02225769.

The Candidate Blood-stage Malaria Vaccine P27A Induces a Robust Humoral Response in a Fast Track to the Field Phase 1 Trial in Exposed and Nonexposed Volunteers.

Background: P27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults. Methods: This study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 µg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 µg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up. Results: Most AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects. Conclusions: The candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials. Clinical Trials Registration: NCT01949909, PACTR201310000683408.

Performance of prediction rules and guidelines in detecting serious bacterial infections among Tanzanian febrile children.

BACKGROUND: Health-workers in developing countries rely on clinical algorithms, such as the Integrated Management of Childhood Illnesses (IMCI), for the management of patients, including diagnosis of serious bacterial infections (SBI). The diagnostic accuracy of IMCI in detecting children with SBI is unknown. Prediction rules and guidelines for SBI from well-resourced countries at outpatient level may help to improve current guidelines; however, their diagnostic performance has not been evaluated in resource-limited countries, where clinical conditions, access to care, and diagnostic capacity differ. The aim of this study was to estimate the diagnostic accuracy of existing prediction rules and clinical guidelines in identifying children with SBI in a cohort of febrile children attending outpatient health facilities in Tanzania. METHODS: Structured literature review to identify available prediction rules and guidelines aimed at detecting SBI and retrospective, external validation on a dataset containing 1005 febrile Tanzanian children with acute infections. The reference standard, SBI, was established based on rigorous clinical and microbiological criteria. RESULTS: Four prediction rules and five guidelines, including IMCI, could be validated. All examined rules and guidelines had insufficient diagnostic accuracy for ruling-in or ruling-out SBI with positive and negative likelihood ratios ranging from 1.04-1.87 to 0.47-0.92, respectively. IMCI had a sensitivity of 36.7% (95% CI 29.4-44.6%) at a specificity of 70.3% (67.1-73.4%). Rules that use a combination of clinical and laboratory testing had better performance compared to rules and guidelines using only clinical and or laboratory elements. CONCLUSIONS: Currently applied guidelines for managing children with febrile illness have insufficient diagnostic accuracy in detecting children with SBI. Revised clinical algorithms including simple point-of-care tests with improved accuracy for detecting SBI targeting in tropical resource-poor settings are needed. They should undergo careful external validation against clinical outcome before implementation, given the inherent limitations of gold standards for SBI.

[Screening the asymptomatic traveler returning from the tropics]. / Bilan de santé chez le voyageur asymptomatique au retour des tropiques.

When travelling to a tropical country, the tourist can be exposed to different pathogens that can cause symptoms after a long period of latency. The physician should be informed about the geographical distribution of these diseases (schistosomiasis, Chagas disease, strongyloidiasis), the situations in which an exposure can occur and the presentation of an acute or chronic infection, in order to diagnose them in the presence of symptoms. Moreover, a screening should be offered to certain groups of people considered more at risk of contracting a cosmopolitan illness (HIV) whilst travelling. A specific screening in the returning traveler is thus only justified under particular circumstances that are to be determined by a detailed history or specific signs (screening for schistosomiasis when bathing in fresh water in an endemic area).

Lors d'un séjour en région tropicale, le voyageur peut être exposé à divers pathogènes pouvant causer des manifestations tardives après une longue période asymptomatique. Le médecin devrait être informé sur la répartition géographique de ces pathologies (schistosomiase, maladie de Chagas, strongyloïdose), les situations d'exposition à risque ainsi que les manifestations d'une infection aiguë ou chronique, afin de les rechercher si elles devaient apparaître. Pour les maladies cosmopolites dont le risque infectieux est augmenté en voyage (VIH), il est indiqué de les rechercher dans les groupes à risque. Un dépistage spécifique au retour des tropiques n'est justifié que dans des circonstances particulières, qu'une anamnèse ciblée permettra de déterminer (schistosomiase après un bain en eau douce par exemple).

Mass drug administration for malaria elimination: do we understand the settings well enough?

Mass drug administration (MDA) of antimalarials has re-emerged as a recommended tool for interrupting malaria transmission, but evidence from low endemicity settings is scarce. A trial in Zanzibar found that two rounds of MDA made no significant impact on malaria incidence, and many questions on the optimal mode and setting for implementing MDA remain unanswered. A more thorough understanding of local sources and drivers of transmission, and a better toolbox for evaluating interventions in near-elimination settings are essential.Please see related research article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1202-8 .