Pasteur Institute Research Articles

Symptomatology of COVID-19 - Lessons from a meta-analysis across 13 countries

Background: COVID-19 pandemic has resulted in varying clinical manifestations and mortality rates. There is no consensus on the symptomatology that would guide researchers and clinicians. Aims and Objectives: The objective was to identify symptoms and their frequencies of COVID-19 with a meta-analysis of studies from several countries. Materials and Methods: Data sources: A systematic review using PubMed and Google Scholar data sources and reference tracing were used to identify 7176 articles. Eligibility criteria: Suitable articles were selected manually with selection criteria and 14 original articles included in meta-analysis. Data abstraction and analysis: PRISMA guidelines used for data abstraction and a table was generated by feeding it with numbers and proportions of each symptom described. A meta-analysis was carried out using random effect models on each symptom separately across the studies and their prevalence rates and 95% confident intervals were calculated. Results: Selected 14 studies, either cross-sectional or cohort studies are analyzed. There were 2,660 confirmed cases of COVID-19. The majority were from China (n=2,439, 91.7%) and remainder from the Netherlands, Italy, Korea, and India and one article from Europe. There were a total of 32 symptoms identified from the meta-analysis and additional 7 symptoms were identified from reference searching. The most common symptoms were (prevalence >50%): fever (79.56%, 95% CI: 72.17–86.09%), malaise (63.3%, 95% CI: 53.1–73.0%), cough (56.7%, 95% CI: 48.6–64.6%), and cold (55.6%, 95% CI: 45.2–65.7%). Symptoms of intermediate incidence (5–49%) were anosmia, sneezing, ocular pain, fatigue, sputum production, arthralgia, tachypnea, palpitation, headache, chest tightness, shortness of breath, chills, myalgia, sore throat, anorexia, weakness, diarrhea, rhinorrhea, dizziness, nausea, altered level of consciousness, vomiting, and abdominal pain. Rare symptoms (<5%): tonsil swelling, hemoptysis, conjunctival injection, lymphadenopathy, and rash. Conclusion: We found (25/32, from meta-analysis) symptoms to be present in ≥5% of cases which could be considered as “typical” symptoms of COVID-19. The list of symptoms we identified is different from those documents released by the WHO, CDC, NHS, Chinese CDC, Institute Pasteur and Mayo Clinic. The compiled list would be useful for future researchers to document a comprehensive picture of the illness.

An in Vitro Study of Molecular Effects of a Combination Treatment with Antibiotics and Nanofluid Containing Carbon Nano-tubes on Klebsiella pneumoniae.

Background:We aimed to prepare a nanofluid, containing f-MWCNTs, and investigate the antibacterial efficacy of f-MWCNTs+ ciprofloxacin (cip) on Klebsiella pneumoniae by evaluating the virulence gene expression.Methods:This study was carried out from 2019 to 2020, in the Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran. The nanofluid containing antibiotic and f-MWCNTs were prepared by the ultrasonic method. The minimum inhibitory concentrations (MICs) of ciprofloxacin and f-MWCNTs were determined using the broth micro dilution MIC tests. For examining the antibacterial effects, the expression level of virulence genes, under the influence of f-MWCNTs, was evaluated by a real-time PCR.Results:The effect of 8 μg/ml ciprofloxacin + 400 μg/ml f-MWCNTs, completely inhibited the growth of the resistant isolate of K. pneumoniae, while, in the ATCC 700,603 isolate, 2 μg/ml ciprofloxacin with 100 μg/ml f-MWCNT could inhibit a bacterial growth. In the resistant K. pneumoniae clinical isolate, after f-MWCNT+cip treatment, the expression of fimA, fimD, wza, and wzi genes was significantly downregulated, compared to the ciprofloxacin treatment, and upregulated, compared to the negative control. For the ATCC 700,603 isolate treated with f-MWCNT+cip, the expression of fimA, fimD and wza virulence genes showed upregulation, compared to the negative control and downregulated in comparison with the ciprofloxacin treatment.Conclusion:Simultaneous treatment of resistant isolate of K. pneumoniae with f-MWCNTs +antibiotic could improve the effectiveness of antibiotic at lower doses, due to the reduced expression of virulence genes in comparison with antibiotic treatment, besides the increased cell wall permeability to antibiotics.

Hepatitis С in Russia and the Northwest federal region of Russia: results of the first stage the global programme of infection elimination

The objective. To assess the dynamics of the epidemic process of chronic hepatitis C (CHC) in Russia and the Northwest Federal Region for the period 2015–2020. Materials and methods. The article analyzes the data from the state statistical reporting of infectious diseases in the Russian Federation (RF), from the reference-center for the monitoring of viral hepatitis, from statistical tables compiled at Methodological and Research Center for Epidemiological Surveillance of Viral Hepatitis under Pasteur Institute of Epidemiology and Microbiology. The data from the Federal register of patients with viral hepatitis were used.Results. The epidemiological indicators for 2020 should be interpreted taking into account the implementation of anti-epidemic measures for COVID-19 in the context of a pandemic. In 2015–2019, CHC incidence in the RF decreased by 18% (from 38o⁄oooo to 30,9o⁄oooo). For 2020 — by 46% (up to 16,7o⁄oooo). The total number of people with CHC is increasing (in 2015 — 562 622 people, in 2019 — 635 372). There is no clear downward trend in the dynamics of changes in the mortality rate from causes associated with HCV in the RF and the Northwestern Federal Region. The impact of the pandemic on mortality in HCV infection remains to be assessed. In 2019 in Russia, only 8,6% of patients on the register are covered by treatment. In 2020, according to preliminary data, treatment coverage was less than 1% of the estimated number of people with HCV infection (3 million). СHC incidence in the Northwest Federal Region decreased by less than 15% (48o⁄oooo — in 2019, 56,2o⁄oooo — in 2015), for 2020 — by 41% (up to 28,2o⁄oooo). Incidence is 1,5 times higher than in the RF on average. The total number of people with СHC is increasing (in 2015 — 92 780, in 2020 — 106 052). Few people with viral hepatitis know about their diagnosis (35% HCV-infected persons). Government funding for treatment has increased, but only 3% is covered by therapy. In the Northwestern Federal Region, as in the RF, the WHO strategy targets have not been achieved by 2020. The sharp decline in basic epidemiological indicators for 2020 is most likely due to a decrease in the number of patients seeking outpatient care and screening during the implementation of anti-epidemic measures for COVID-19.

Virulence and antibiotic resistance of Klebsiella pneumoniae strains isolated from wastewater

Abstract Background Multidrug-resistant Klebsiella pneumoniae (Kp) strains are considered a global public health threat. The aim of the present study was to assess the occurrence of resistant and virulent Kp in Italian environmental wastewater, in order to evaluate the contribution of wastewater as reservoir of virulent and multidrug-resistant bacteria. Methods Forty samples of wastewater were collected in six sampling sessions from June to November 2018 in Central Italy and processed to detect Kp. All the presumptive Kp colonies isolated were identified by MALDI-TOF MS (Bruker Daltonics, Germany), then the genome sequences of all the confirmed Kp were obtained using Illumina Sequencing. Finally, characterization of virulence and resistance genes was performed in silico using the BIGSdb-Kp database provided by the Institut Pasteur (http://bigsdb.web.pasteur.fr). Results Kp was detected in 32 out of 40 samples (80%) and all strains were confirmed as Kp by MALDI-TOF MS. Genotyping analysis showed that besides the native bla-SHV, bla-LEN, bla-OKP genes linked to β-lactams resistance, gyr and par genes, involved in quinolone resistance, and no other resistance genes were detected. Regarding virulence, all strains carried the fimbriae encoding gene mrk, associated with adhesion and biofilm formation. The ferric aerobactin receptor iutA was harbored by 3 strains (9.4%). The siderophore Yersiniabactin locus (ybtS, ybtX, ybtQ, ybtP, ybtA, irp2 irp1, ybtU, ybtT, ybtE, fyuA), essential for iron scavenging, is carried by 7 out of 32 strains (21.9%). Conclusions Our results showed a high prevalence of Kp in wastewater that also harbored several resistance and virulence genes. These results make interesting to investigate more about wastewater as hot spots of enrichment, recombination, genetic exchange and selection of antibiotic resistant “super-bugs” that persisting and surviving in the environment could be a health risk for humans and animals. Key messages Wastewater could play a role as Klebsiella pneumoniae reservoir of virulence and resistance genes that can disseminate into wildlife and reach humans. It’s necessary a “one health” approach to deeply investigate about the presence of superbugs bacteria in the environment and the possible risks for human health.

Klebsiella pneumoniae in vegetable products: antimicrobial resistance and consumer health risk

Abstract Background Klebsiella pneumoniae (Kp) is considered one of the major causes of human hospital infections. Moreover, Kp is often present in several food products and it could be a potential health hazard for the consumers through the increase of Kp antimicrobial resistance (AMR) to the main routinely used antibiotics classes. The aim of this study was to evaluate the AMR profile of Kp strains isolated from vegetable food products. Methods The whole genome sequences of 10 Kp strains, previously isolated from carrots (n. 4), salads (n. 3), tomatoes (n. 2) and pumpkin (n. 1) samples, were obtained by next generation sequencing technique, using Illumina platform. Phenotypic and genotypic AMR profiles, with particular attention to β-lactams, quinolones and aminoglycosides resistances, were acquired by both agar diffusion and micro-dilution susceptibility testing and uploading the Kp sequences to Institut Pasteur platform (https://bigsdb.pasteur.fr/), respectively. Results Most of Kp strains (9 of 10) resulted susceptible to the main antibiotics tested and few AMR genes were detected in silico besides the native blaSHV, blaOKP and blaLEN. Only one Kp harboured blaAMPC and blaCMY, showing resistance to 5 β-lactams (amoxicillin/clavulanate, cefoxitin, cefpodoxime, cefpodoxime/clavulanate, ceftobiprole). Regarding the quinolone resistances, all the Kp strains carried gyr and par genes. No aminoglycoside resistance genes were highlighted in the 10 Kp strains studied. Conclusions These preliminary results showed the presence, in vegetable foods, mainly in ready to eat raw products, of Kp strains, harbouring no or few AMR genes. Good hygiene practices should be properly applied during the entire food processing chain, to avoid hazardous implications for the consumer. Further studies are needed in order to: analyse more vegetable samples, deeply evaluate the phenotypic and genotypic AMR profile of the Kp strains and their possible transmission from food products to consumer. Key messages Klebsiella pneumoniae is often isolated in food, as ready to eat vegetables, and it could be a potential public health risk due to the antimicrobial resistance increase to main antibiotics. The presence of Klebsiella pneumoniae in food implies the correct application of good hygiene practices in the entire food processing chain, in order to avoid dangerous effects for consumers.

Release of infectious virus and cytokines in nasopharyngeal swabs from individuals infected with non-alpha or alpha SARS-CoV-2 variants: an observational retrospective study.

BackgroundThe dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised.MethodsWe measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants.FindingsWith both lineages, viral titers were variable, ranging from 0 to >106 infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10).InterpretationThe alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection.FundingThis retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale.

Effect of change in vaccine schedule on pertussis epidemiology in France: a modelling and serological study

In April-May, 2013, France modified its pertussis vaccination schedule, which uses the acellular pertussis vaccine, from three primary doses at 2, 3, and 4 months of age and a first booster at 16-18 months of age (former schedule) to two primary doses at 2 and 4 months of age and a first booster at 11 months of age (new schedule). We aimed to assess the subsequent effect of the vaccine schedule change on pertussis epidemiology in France. In this modelling study, using data collected between Jan 1, 2012, and Dec 31, 2019, from French national surveillance sources, we analysed the PCR test results of nasopharyngeal swabs collected from symptomatic outpatients aged 2-20 years with suspected pertussis. We developed a negative binomial regression model for the number of confirmed pertussis cases by year and age to assess the relative risks of pertussis depending on vaccine schedule. The linear predictor included the year, the age group, the population size, and a proxy of waning immunity. We tested different models in which waning immunity could vary with vaccine schedule and type of primary vaccine. The models were fitted to the 2012-18 data via Bayesian Markov chain Monte Carlo sampling, and the 2019 data were left out for external model validation. We also compared the anti-pertussis toxin (PT) antibody concentrations in leftover sera from children not tested for pertussis or recent respiratory tract infection aged 2-5 years born before and after the vaccine schedule change. We collected data on 7493 confirmed cases of pertussis. The model that best fitted the 2012-18 epidemiological data supported a faster waning of immunity following vaccination with the new vaccine schedule. 3 years after vaccination, the risk of developing pertussis was 1·7 (95% CI 1·4-2·0) times higher for children vaccinated according to the new schedule than those vaccinated according to the former schedule. The model correctly predicted the age distribution of cases in 2019. Geometric mean concentrations (GMC) of anti-PT IgG were 50% lower in children aged 2 years vaccinated with the new schedule (GMC=5·85 IU/mL [95% CI 4·08-8·39]) than in children of the same age vaccinated with the former schedule (GMC=11·62 IU/mL [95% CI 9·05-14·92]; p=0·0016), and 43% lower in children aged 3 years vaccinated with the new schedule (GMC=3·88 IU/mL [95% CI 2·82-5·34]) than those with the former schedule (GMC=6·80 IU/mL [95% CI 4·77-9·70]; p=0·026). A shorter-lived protection induced by the new vaccine schedule recommended in France since 2013 is associated with an increase of pertussis cases in children aged 2-5 years. If similar findings are observed in other countries and clinical trials, these findings should be considered in future pertussis vaccination policies. INCEPTION, Labex-IBEID, Institut Pasteur, and Santé Publique France.

Performance of GeneXpert MTB/RIF in the diagnosis of extrapulmonary tuberculosis in Morocco

Tuberculosis (TB), a chronic bacterial disease caused by Mycobacterium tuberculosis, commonly affects the lung but can also affect other parts of the body (extrapulmonary tuberculosis, EPT). A rapid diagnosis is essential to initiate a specific and effective treatment. Although mycobacterial culture remains the gold standard for EPT diagnosis, molecular tools are attracting increasing interest. GeneXpert MTB/RIF, a rapid automated diagnostic test, allows the detection of Mycobacterium tuberculosis as well as mutations in the hot-spot region of the rpoB gene associated with Rifampicin resistance. The present study was performed to evaluate the performance of the GeneXpert MTB/RIF test for the diagnosis of EPT compared to the standard method. This prospective study was conducted on 304 clinical samples collected from 192 patients attending the Laboratory of Mycobacteria and Tuberculosis of Pasteur Institute of Morocco, between 2016 and 2017. Out of the 304 samples, 113 were pleural f luids decontaminated using the Petroff method and 191 were biopsies (78 lymph nodes and 113 pleural biopsies) decontaminated using the Löwenstein method. Mycobacterium tuberculosis detection and identification were performed on all samples using smear microscopy, Löwenstein–Jensen medium culture and the GeneXpert MTB/RIF test. Our results showed that 54.5 (103/189) were men and 45.5% (86/189) were women. The age of patients ranged from 2–78 years and the majority of patients was in the age group 25–45 years. Extrapulmonary samples were derived from lymph nodes, pleural f luids and pleural tissues, with a percentage of 25.66, 37.17 and 37.17%, respectively. Interestingly, the sensitivity of the GeneXpert was 51.4 for all samples and 83.3% for lymph nodes. In conclusion, the present study revealed that the performance of the GeneXpert test depends highly on the type of sample, with a high sensitivity observed for lymph nodes. Additionally, we clearly showed that the GeneXpert MTB/RIF test presents limitations in the diagnosis of pleural TB. Thus, we recommend the coupled use of the GeneXpert MTB/RIF and the conventional techniques for EPT diagnosis.

Herd immunity to SARS-CoV-2 among the population of the Republic of Belarus amid the COVID-19 pandemic

Objective was to investigate the SARS-CoV-2 collective immunity status of the population of Belarus within the context of the COVID-19 pandemic. Materials and methods. The work was carried out according to the methodology for assessing SARS-CoV-2 population immunity, developed by Rospotrebnadzor Russia and the Ministry of Health of Belarus with the participation of the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The Bioethics Committee of Belarus and the local ethics committee of the St. Petersburg Pasteur Institute approved the study. Selection of participants was carried out using a questionnaire method and online technology (internet, cloud server). Volunteers were randomized into seven age groups (years of age): 1–17; 18–29; 30–39; 40–49; 50–59; 60–69; and 70+. Regional randomization ensured proportional representation of volunteers from each region, and no more than 30 people were included from one enterprise. In accordance with manufacturer instructions, blood plasma samples were analyzed for: IgG antibodies (Abs) to the SARS-CoV-2 nucleocapsid (Nc) using a quantitative ELISA test system; and IgG Abs to the receptor binding domain (RBD) of the SARS-CoV-2 S (spike) surface glycoprotein using a qualitative ELISA test system. Statistical processing was carried out using Excel 2010 and other software. Statistical differences were designated as significant when p 0.05, unless otherwise indicated. Results. The level of seroprevalence, in terms of Abs to Nc among the Belarusian population, was 38.4% (95% CI 37.6–45.4). The highest Ab levels were found among individuals in older age groups (50-70+ years old). The lowest were found in children 1–17 years old and in young people 18–39 years old The distribution of seroprevalence across Belarusian regions was relatively homogeneous, with the exception of the Minsk Region, where a statistically significant decrease in the indicator was noted. In terms of profession, the largest share of seropositive individuals was found among transportation workers; the smallest was found in business. The moderate COVID-19 incidence has not led to a dramatic increase in the number of contacts. The base reproduction number (R0) was 1.3. In the Republic of Belarus, there was a moderate level of asymptomatic COVID-19 among seropositive individuals (45.3% [95% CI 44.0–46.7]). This form of infection was observed most often among children aged 1–17 years old (65.0% [95% CI 61.3–68.6]). In parallel with seroprevalence assessment, SARS-CoV-2 vaccination was carried out. We used two vaccines: Gam-COVID-Vac (also known as Sputnik V, developed by Gamaleya National Center for Epidemiology and Microbiology, Russia); and BBIBP-CorV (Sinopharm, PRC). Vaccination against SARS-CoV-2 was accompanied by an increase in the level of anti-RBD Abs (95% [95% CI 94.7–96.7]). Taking into account the vaccination of a subset of the population with BBIBP-CorV, the overall herd immunity, inferred from the analyzed indicators (presence of anti-Nc or anti-RBD Abs), was 47.1% (95% CI 46.3–48.0). Conclusion. COVID-19 in Belarus was characterized by a moderately pronounced course of the epidemic process. The threshold level of herd immunity to SARS-CoV-2 has not yet been reached, as a result of which the conditions for progression of the epidemic remain.

English

Some Candida species are considered as human opportunistic pathogens and can play an important role in spontaneous fermentations, but also as beverage-spoiling microorganisms. The aim of this pioneering study was to investigate Candida spp. in hot beverages, which is consumed mostly on the streets in Côte d’Ivoire. Yeast strains were isolated from 400 hot beverages of tea (200) and coffee (200) samples. Yeast cultures were identified at genus and species level by MALDI-TOF mass spectrometry at the biobank laboratory of the Pasteur Institute of Côte d’Ivoire. A total of 37 Candida isolates were clearly identified by MALDI-TOF (MS) and revealed 11 species of Candida: C. krusei (21.6%), C. tropicalis (18.9%), C. parapsilosis (16.2%), C. guilliermondii (16.2%), C. pelliculosa (8.1%), C. dubliniensis (5.4%), C. rugosa (2.7%), C. kefyr (2.7%), C. silvicola (2.7%), C. lusitaniae (2.7%) and C. orthopsilosis (2.7%). The results showed that C. krusei and C. tropicalis were the dominant yeasts in hot beverages from street vendors. Candida species were more isolated in tea (10%) than in coffee (8.5%). C. tropicalis, C. pelliculosa and C. krusei were more isolated in Cocody. C. guilliermondii and C. parapsilosis were more isolated in Port-Bouët. C. dubliniensis was only isolated in Yopougon town. The presence of Candida spp. in street hot beverages could cause a sanitary risk to consumers or be used as a novel source for biotechnological uses to be explored in future work.   Key words: Street hot beverages, Candida spp., coffee, tea, food safety.

Team experience of nasopharyngeal samples reception, decontamination, and sorting during the COVID-19 pandemic (2020) at Institut Pasteur Côte d’Ivoire

Molecular testing sensitivity, which allows for early diagnosis of the 2019 coronavirus disease (COVID-19), could be affected by sample quality, storage, and transportation timeframe to the laboratory, along with bias related to the pre-analytic phase. The present study reports the selection and decontamination of nasopharyngeal samples during COVID-19 management at the Institut Pasteur Côte d’Ivoire. The objective of this work was to organize sample reception management and report a complete picture of sample selection and decontamination in the context of diagnosis activity decentralization.An administrative note creating the selection and decontamination unit of nasopharyngeal samples initiated activities in May 2020. The required human resources and necessary materials were identified and put in place. Daily activity consisted of receiving, sorting, decontaminating, and sending nasopharyngeal samples to different diagnostic laboratories. Nonconformities were recorded monthly.After a six-month period of activities, from a total amount of 11,401 containers received and decontaminated, 174,085 samples were selected. A proportion of 92.0% of these specimens met the diagnostic standards, while 7.0% that were found acceptable showed minor irregularities. Nevertheless, a rate of 1.0% of samples with major abnormalities could not be used for COVID-19 testing and, therefore, were rejected. Additionally, the non-conformity rate was reduced by 2.4% after the first term activity.Sorting and decontamination of nasopharyngeal samples are crucial steps in biosafety optimization for the technical staff and quality improvement of sample care.

Herd immunity to SARS-CoV-2 in the Novosibirsk Region population amid the COVID-19 pandemic

To determine the level of SARS-CoV-2 seroprevalence among the Novosibirsk Region population against the background of the COVID-19 pandemic. The work was carried out in 2 phases: 1) a cross-sectional cohort study performed 28.06- 15.07.2020; 2) longitudinal cohort 3-stage seromonitoring: 1st stage 28.06-15.07.2020; 2nd 14.09-04.10.2020; 3rd 10-30.12.2020 The work was carried out according to a unified methodology developed by Rospotrebnadzor with the participation of St-Petersburg Pasteur Institute, taking into account the recommendations of the WHO. IgG antibodies to the SARS-CoV-2 nucleocapsid protein were detected by ELISA using a kit of reagents produced by the SRCMSB (Obolensk) according to the manufacturer's instructions. Statistical analysis was performed using Microsoft Excel 2010 and other programs. The seroprevalence in the region's population was 9.1% (95% CI 8.0-10.2): maximum in children 14-17 years old (17.6%, 95% CI 12.3-23.9) and persons over 75 years (14.8%, 95% CI 11.4-18.8), minimum among persons 30-39 years old (4.9%, 95% CI 3.0-8.0). Increased rate was noted among the unemployed (15.4%, 95% CI 9.9-17.1) and other individuals (13.0%, 95% CI 8.6-18.5). Seroprevalence was 33.3% (95% CI 16.3-59.0) in COVID-19 convalescents and 19.0% (95% CI 13.9-25.0) in contact persons. More than 94.7% (95% CI 91.2-97.2) of seropositive individuals were asymptomatic. During the serological monitoring, seroprevalence increased from 7.4% (95% CI 6.2-8.9) at 1st stage 1 to 12.4% (95% CI 10.6-14.3) at 2nd , and 31% (95% CI 28.8-33.3) at 3rd stage. SARS-CoV-2 herd immunity has not reached the threshold level, this does not exclude exacerbation of the epidemic process.

First person – Paola Lepanto and Florencia Levin-Ferreyra

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Paola Lepanto and Florencia Levin-Ferreyra are co-first authors on ‘ Insights into in vivo adipocyte differentiation through cell-specific labeling in zebrafish’, published in BiO. Paola is a research assistant in the lab of José Badano at Institut Pasteur Montevideo, investigating cellular and developmental biology. Florencia conducted the research described in this article while a final dissertation student in José Badano's lab at Institut Pasteur Montevideo. She is now a research associate in the lab of Bruno di Stefano at Baylor College of Medicine, Houston, USA, investigating stem cell potency and cell fate decisions.

Co-infection of ST2IP carbapenem-resistant Acinetobacter baumannii with SARS-CoV-2 in the patients admitted to a Tehran tertiary referral hospital

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is among the most concerning cause of healthcare-associated infections (HAI) due to its high level of antibiotic resistance and high mortality. In the era of the COVID-19 pandemic, the key priority of infection control committees is to contain the dissemination of antibiotic resistant Gram-negative bacteria. Here, we aimed to timely recognize the emergence of CRAB in COVID-19 cases admitted to the wards of a tertiary referral hospital and to identify the genetic relatedness of the isolates.MethodsFrom 30 March to 30 May 2020, a total of 242 clinical samples from COVID-19 cases were screened for CRAB isolates using standard microbiologic and antibiotic susceptibility tests. The PCRs targeting oxa23, oxa24, oxa58, blaTEM and blaNDM-1 genes were performed. Two multiplex PCRs for identifying the global clones (GC) of A. baumannii were also performed. The sequence type of CRABs was determined using Institut Pasteur (IP) multilocus sequence typing (MLST) scheme.ResultsEighteen CRAB isolates were recovered from COVID-19 patients with the mean age of 63.94 ± 13.8 years. All but 4 COVID-19 patients co-infected with CRAB were suffering from an underlying disease. Death was recorded as the outcome in ICUs for 9 (50%) COVID-19 patients co-infected with CRAB. The CRAB isolates belong to GC2 and ST2IP and carried the oxa23 carbapenem resistance gene.ConclusionThis study demonstrated the co-infection of CRAB isolates and SARS-CoV-2 in the patients admitted to different ICUs at a referral hospital in Tehran. The CRAB isolates were found to belong to ST2IP, share the oxa23 gene and to have caused several outbreaks in the wards admitting COVID-19 patients.

Rethinking Collaboration: Medical Research and Working Relationships at the Iranian Pasteur Institute

The Pasteur Institute of Iran underwent a major expansion of its research productivity and international recognition during some of the most significant events of modern Iranian history: the nationalization of the Iranian oil industry, followed by the Anglo-American coup against Prime Minister Mohammad Mosaddegh in 1953. During this period, the institute’s French director, Marcel Baltazard, was embedded in a complex set of working relationships with his Iranian employees, research subjects, and government ministers; American scientists and foreign aid workers; and French Pasteurians and diplomats. Baltazard constantly described these relationships as instances of “collaboration.” The temporal and geographical context demands a critical reading of scientific collaboration alongside the negative implications of political collaboration. Investigating the political commitments and social attitudes of the French director and Iranian staff, this essay demonstrates that scientific collaboration at the institute both reinforced socioeconomic inequalities within Iran and mirrored global Cold War geopolitics that undermined Iranian sovereignty.

An Epidemic for Sale: Observation, Modification, and Commercial Circulation of the Danysz Virus, 1890–1910

This essay tells the story of the “Danysz virus,” a bacterial culture that was designed and deployed to cause epidemics among rodents and was sold globally by the Institut Pasteur from 1900. Jean Danysz (1860–1928) initially identified the culture during his studies of epidemics in population cycles of common voles. His experiments turned to the ambitious goal of increasing the bacteria’s virulence by emulating the rodent’s animal economy in the laboratory in order to mass-produce a culture. The bacterial culture was supposed to bring about a man-made epidemic for sale on the global pest- and plague-control market. The essay considers the Danysz virus as a “cognitive good” and analyzes the material as well as intellectual transfers that shaped its development, supported its international application, and prompted the experimental testing of its promises. While the culture largely failed to bring about the exponential growth of lethal infections in rat populations Danysz promised, the virus did succeed in distributing his theoretical revision of virulence. Through its commercial distribution, his product recast virulence as a function of the relation between bacteria and their milieu and offered a novel concept of mutual pathogenicity that far exceeded deterministic models of infection prevalent at the time.

Evaluation of the prevalence of Mycobacterium tuberculosis strains isolated from tuberculosis patients referred to Pasteur Institute of Iran

Evaluation of the prevalence of Mycobacterium tuberculosis strains isolated from tuberculosis patients referred to Pasteur Institute of Iran

Effective Biosecurity measures during the Diagnosis of COVID-19 at the Pasteur Institute from the Perspective of Hazardous Hospital Waste Management

BACKGROUND AND AIM: Waste is a daily health hazard that must be addressed through appropriate management. The Institut Pasteur of Côte d'Ivoire (IPCI) produces waste that is generally infectious waste and waste assimilated to household waste. The presence of this mostly infectious waste can create a risk for staff. Thus, since March 11, 2020, the date of the first case of COVID-19, a rigorous health management policy has been taken to protect health workers. METHODS: Diagnosis of the COVID-19 pandemic in Côte d'Ivoire is mainly done at the Institut Pasteur of Côte d’Ivoire (IPCI). Thus, the waste produced in the various laboratories is disinfected, then sorted, packaged in 5 to 10 liter bags, transported in dedicated bins to final storage. The waste is weighed under biosafety conditions before being incinerated in an ATI Environment CP100 incinerator. RESULTS:Waste management at IPCI in 2020 during COVID-19 resulted in biosafety training for staff, collection, packaging, transportation, storage and incineration of 26.4 tons of waste. It should be noted that no waste management personnel were infected during the entire period from March to December 2020 CONCLUSIONS:During the year 2020 and mainly from March 11, 2020 to December 31, 2020, waste management increased significantly from 12.2 tons in 2019 during the same period to 26.4 tons in 2020 and was related to COVID-19. This shows that waste has more than doubled and requires rigorous management. It would therefore be imperative to properly manage waste in order to protect health care personnel. Also, this study showed one aspect of the environmental impact of COVID-19 that needs further research. KEYWORDS: COVID-19, Waste management, incineration

A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis.MethodsTo better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels.FindingsThe most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling.ConclusionsThese results provide potential for a better understanding of disease pathophysiology.FundingAgence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d’Excellence ‘‘Milieu Intérieur,” grant ANR-10-LABX-69-01; ANR-flash Covid19 “AIROCovid” and “CoVarImm”), Institut National de la Santé et de la Recherche Médicale (INSERM), and the “URGENCE COVID-19” fundraising campaign of Institut Pasteur.

Analysis of clinical and multi antigenic aspects of malaria serodiagnosis tests prescribed to patients at Institut Pasteur de Cte dIvoire from 2016 to 2019

Malaria is the world's leading parasitic endemic and the major cause of morbidity and mortality in Cote d'Ivoire. The aim of this study was to analyse the clinical aspects and evaluate a kit’s performance (NovaLisa® Malaria) against a panel of antigens (AMA1, GLURP, CSP and Schizont Extract) to determine the antigen used in diagnosing malaria serology in Cote d’Ivoire. A retrospective study was carried out on patients requesting malaria serological test. The ELISA technique and an antigen panel was respectively used for the multi-antigen approach and to measure the proportion of responders from 28 samples. 345 samples were assayed, with a positive rate of 92.49% (319/345) revealed by the malaria serology test with a mean concentration of 50.1 NTU, 6.38% (22/345) of negativity with a mean concentration of 5.96 NTU and 1.16% (4/345) in the doubtful zone (16.26 NTU). Mean concentration of prescriptions for cervical adenopathy was 73.12 NTU. The antigen panel seroprevalence was 35.72; 50; 64.28 and 78.5% respectively for AMA1, CSP, GLURP and schizont extract for negative samples and the proportion of responders was significant (p = 0.003) for schizont extract. The seroprevalence for the 28 samples was 60.7% for AMA1 and 89.29% for schizont extract. The proportions of responders to CSP (p = 0.008), GLURP (p < 0.001) and schizont extract (p < 0.001) antigens were significantly higher than those of non-responders. GLURP antigen and schizont extract could be used for diagnosing malaria serology in Cote d'Ivoire. Key words: Malaria, Plasmodium falciparum, antigen, serodiagnosis.