Rôle du laboratoire dans le diagnostic virologique de la grippe pandémique A(H1N1)v

La nouvelle grippe pandémique, apparue au mois d’avril 2009 au Mexique est encore appelée grippe porcine. Elle est due à un nouveau virus Influenza A(H1N1)v, totalement inédit, jamais identifié auparavant dans aucune espèce et résulte de réassortiments génétiques complexes. Le rôle du laboratoire est fondamental pour le diagnostic virologique de cette grippe émergente. Il permet d’apporter la certitude du diagnostic chez des patients dont le contexte clinico-épidémiologique est évocateur d’une infection par le virus A(H1N)v. La confirmation virologique d’un cas d’infection due à ce virus est apportée par la positivité des tests de laboratoire suivants: RT-PCR et/ou culture virale et/ou multiplication par quatre du taux des anticorps neutralisants spécifiques dirigés contre le virus A(H1N1)v sur une paire de sérums prélevés à deux semaines d'intervalle. La RT-PCR en temps réel, représente à l’heure actuelle un outil de choix en raison de sa rapidité, sensibilité et spécificité. Les tests immunologiques de diagnostic rapide (TDR) permettent de détecter la présence des antigènes de la nucléoprotéine des virus grippaux saisonniers de type A et B. L’évaluation de ces tests a montré, dans le contexte pandémique actuel, une faible sensibilité ne leur conférant pas une valeur prédictive négative compatible avec une utilisation généralisée. Leurs résultats doivent être interprétés avec prudence et malgré leur bonne valeur prédictive positive, ils ne permettent qu’un diagnostic de présomption, une confirmation par RT-PCR en temps réel sera conduite chaque fois que cela est nécessaire

Emergence d’isolats cliniques de Pseudomonas aeruginosa producteurs de bêta-lactamases à spectre étendu en milieu hospitalier

Les infections nosocomiales dues à des bacilles à Gram négatif producteurs de bêta-lactamases à spectre étendu (BLSE) sont à l’heure actuelle un sujet de préoccupation majeure en milieu hospitalier, en particulier en milieu de réanimation. Les BLSE ne sont plus l’apanage des entérobactéries et leur diffusion est de plus en plus observée parmi de nombreuses espèces de bacilles non fermentant comme Pseudomonas spp et Acinetobacter spp en raison de l’utilisation abusive des bêta-lactamines. La multirésistance développée par les souches sécrétrices de BLSE, responsables d’épidémies nosocomiales conduit le clinicien à un choix très restreint d’antibiotiques encore effcaces dont les carbapénèmes.En microbiologie clinique, la détection des souches productrices de bêta-lactamases à spectre étendu (BLSE) requiert la combinaison de techniques microbiologiques spécifques, phénotypiques (test de synergie) et génotypiques (recherche de gènes de résistance hébergés par ces souches ..). La surveillance des infections par des bacilles à Gram négatif producteurs de BLSE est devenue une nécessité en milieu de réanimation, pourvoyeur d’infections nosocomiales. La maîtrise de la prescription des antibiotiques, l’application des règles élémentaires d’hygiène hospitalière (notamment l’hygiène des mains), le dépistage des patients porteurs de bactéries multirésistantes (BMR) ainsi que le recours aux précautions standard d’isolement technique et géographique sont autant de stratégies à mettre en oeuvre pour limiter la dissémination de ces souches. Nous rapportons pour la première fois, cinq isolats cliniques de Pseudomonas aeruginosa producteurs de bêta-lactamases à spectre étendu (BLSE), phénotype de résistance aux bêta-lactamines rarement observé en pratique de laboratoire au sein de cette espèce

Impact of H1N1 on Socially Disadvantaged Populations: Systematic Review

The burden of H1N1 among socially disadvantaged populations is unclear. We aimed to synthesize hospitalization, severe illness, and mortality data associated with pandemic A/H1N1/2009 among socially disadvantaged populations.Studies were identified through searching MEDLINE, EMBASE, scanning reference lists, and contacting experts. Studies reporting hospitalization, severe illness, and mortality attributable to laboratory-confirmed 2009 H1N1 pandemic among socially disadvantaged populations (e.g., ethnic minorities, low-income or lower-middle-income economy countries [LIC/LMIC]) were included. Two independent reviewers conducted screening, data abstraction, and quality appraisal (Newcastle Ottawa Scale). Random effects meta-analysis was conducted using SAS and Review Manager.Sixty-two studies including 44,777 patients were included after screening 787 citations and 164 full-text articles. The prevalence of hospitalization for H1N1 ranged from 17-87% in high-income economy countries (HIC) and 11-45% in LIC/LMIC. Of those hospitalized, the prevalence of intensive care unit (ICU) admission and mortality was 6-76% and 1-25% in HIC; and 30% and 8-15%, in LIC/LMIC, respectively. There were significantly more hospitalizations among ethnic minorities versus non-ethnic minorities in two studies conducted in North America (1,313 patients, OR 2.26 [95% CI: 1.53-3.32]). There were no differences in ICU admissions (n = 8 studies, 15,352 patients, OR 0.84 [0.69-1.02]) or deaths (n = 6 studies, 14,757 patients, OR 0.85 [95% CI: 0.73-1.01]) among hospitalized patients in HIC. Sub-group analysis indicated that the meta-analysis results were not likely affected by confounding. Overall, the prevalence of hospitalization, severe illness, and mortality due to H1N1 was high for ethnic minorities in HIC and individuals from LIC/LMIC. However, our results suggest that there were little differences in the proportion of hospitalization, severe illness, and mortality between ethnic minorities and non-ethnic minorities living in HIC

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09‐related pneumonia: an individual participant data meta‐analysis

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza‐related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta‐analysis of individual participant data from 20 634 hospitalised patients with laboratory‐confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) ‘pandemic influenza’. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64–1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44–1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71–1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55–0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54–0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: An individual participant data meta-analysis

Background: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. Methods: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. Results: Of 20 634 included participants, 5978 (29\ub70%) had IRP; conversely, 3349 (16\ub72%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0\ub783 (95% CI 0\ub764-1\ub706; P = 0\ub7136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0\ub772 (0\ub744-1\ub717; P = 0\ub7180)] or likelihood of requiring ventilatory support [adj. OR = 1\ub717 (0\ub771-1\ub792; P = 0\ub7537)], but early treatment versus later significantly reduced mortality [adj. OR = 0\ub770 (0\ub755-0\ub788; P = 0\ub7003)] and likelihood of requiring ventilatory support [adj. OR = 0\ub768 (0\ub754-0\ub785; P = 0\ub7001)]. Conclusions: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support