Investigation of a mpox outbreak in Central African Republic, 2021-2022.

Human monkeypox virus is spreading globally, and more information is required about its epidemiological and clinical disease characteristics in endemic countries. We report the investigation of an outbreak in November 2021 in Central African Republic (CAR). The primary case, a hunter, fell ill after contact with a non-human primate at the frontier between forest and savannah. The ensuing investigation in a small nearby town concerned two families and four waves of inter-human transmission, with 14 confirmed cases, 11 suspected cases and 17 non-infected contacts, and a secondary attack rate of 59.5% (25/42). Complications were observed in 12 of the 19 (63.2%) confirmed and suspected cases with available clinical follow-up data: eight cases of bronchopneumonia, two of severe dehydration, one corneal ulcer, one abscess, two cutaneous superinfections, and six cutaneous sequelae (cheloid scars, or depigmentation). There was one death, giving a case fatality ratio of 1/25 (4.0%) for confirmed and suspected cases. This outbreak, with the largest number of confirmed cases ever described in CAR, confirms the potential severity of the disease associated with clade I monkeypox viruses, and highlights the need for rapid control over virus circulation to prevent the further national and international spread of infection.

Need for integrative thinking to fight against emerging infectious diseases. Proceedings of the 5th seminar on emerging infectious diseases, March 22, 2016 - current trends and proposals.

We present here the proceedings of the 5th seminar on emerging infectious diseases, held in Paris on March 22nd, 2016, with seven priority proposals that can be outlined as follows: encourage research on the prediction, screening and early detection of new risks of infection; develop research and surveillance concerning transmission of pathogens between animals and humans, with their reinforcement in particular in intertropical areas ("hot-spots") via public support; pursue aid development and support in these areas of prevention and training for local health personnel, and foster risk awareness in the population; ensure adapted patient care in order to promote adherence to treatment and to epidemic propagation reduction measures; develop greater awareness and better education among politicians and healthcare providers, in order to ensure more adapted response to new types of crises; modify the logic of governance, drawing from all available modes of communication and incorporating new information-sharing tools; develop economic research on the fight against emerging infectious diseases, taking into account specific driving factors in order to create a balance between preventive and curative approaches.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193.

Interactions of the hemagglutinin (HA) of influenza viruses with sialic acids (SA) are important for host range restriction. Most human H3s have a Ser193, while avian and equine H3s usually have an Asn or a Lys, respectively. To investigate the role of residue 193 in the recognition of SA, substitutions were introduced by mutagenesis within a human H3 and an equine H3. Hemadsorption assays performed on COS-1 cells expressing wt or mutated HAs, showed that a K193S substitution in the context of an equine H3 decreased its ability to bind several animal erythrocytes. Using de- and then alpha2,3 or alpha2,6 re-sialylated chicken erythrocytes we showed that for both human and equine H3s, substitution of a Serine by positively-charged Arginine or Lysine at position 193 increased binding to its preferred receptor, SAalpha2,6Gal and SAalpha2,3Gal, respectively. Moreover, when combined with the L194I substitution, the S193R substitution induced binding of the human H3 to NeuAcalpha2,3Gal.

[Epidemiology of SARS: mission of the emergency medical department of the French Hospital of Hanoi]. / Epidémie de pneumopathie atypique: mission SAMU à l'Hôpital Français de Hanoï.

During the epidemic of severe acute respiratory syndrome (SARS) that occurred in Vietnam in March 2003, the French Ministries of Health and Foreign Affairs dispatched a mission composed of personnel from the emergency medical assistance department (French acronym, SAMU) and one virologist from the Pasteur Institute to the French hospital in Hanoi. The purpose of this mission was to reinforce the local medical staff, to bring medical equipment, and to assist in identifying the cause of the SARS epidemic. Most of the 39 cases observed involved health care personnel working at the hospital. Six including 5 who died presented severe manifestations. Application of strict empirical measures of isolation, hygiene, and personal protection allowed containment of the SARS outbreak in Hanoi.

[Epidemics of acute respiratory infections in Madagascar in 2002: from alert to confirmation]. / Epidémies d'infections respiratoires aiguës à Madagascar en 2002: de l'alerte à la confirmation.

UNLABELLED: An epidemiological investigation (Ministry of Health/Institut Pasteur de Madagascar (IPM)) was conducted in July 2002, in two districts of a same province (Fianarantsoa: Fianarantsoa II and Ikongo) considering the high frequency of deaths linked with acute respiratory infection (ARI). Morbidity and mortality data was collected in the Centre de Santé de Base (CSB) which gave the alert (village of Sahafata, district Fianarantsoa II). Analysis of monthly activity reports (MAR) allowed calculation of incidence rates of ARI/pneumonia in Fianarantsoa province. Virological data was based on the analysis of nasopharyngeal samples collected during the investigations. Clinical symptoms and homogeneity of laboratory results are consistent with an origin of these epidemics being related to the circulation of an influenza virus A subtype H3N2. Attack rates were very high. CFR was significantly higher in individuals of less than 1 year and more than 65 years. This data was confirmed by posterior investigations of teams from MoH/WHO. Surprisingly, this large epidemic was due to a known influenza virus that previously circulated in countries of northern hemisphere (the year before) and even in Antananarivo weeks before. Different hypothesis could be proposed to explain such phenomenon: great restriction of exchanges between different geographical zones, nutritional status.... CONCLUSION: The epidemic episodes of acute respiratory infections in Madagascar in July 2002 were due to an influenza virus A subtype H3N2 without any genotypic or phenotypic features. Various factors, could explain the importance of the epidemic and particular high lethality found in some age groups. This epidemic illustrates the relative incapacity for a developing country, to face and manage a flu epidemic caused by a classical influenza virus.

Hemagglutinin residues of recent human A(H3N2) influenza viruses that contribute to the inability to agglutinate chicken erythrocytes.

To identify the molecular determinants contributing to the inability of recent human influenza A(H3N2) viruses to agglutinate chicken erythrocytes, phenotypic revertants were selected upon passage in eggs or MDCK cells. The Leu194Ile or Val226Ile substitutions were detected in their hemagglutinin (HA) sequence concomitantly with the phenotypic reversion. Remarkably, as little as 3.5% of variants bearing a Val226Ile substitution was found to confer the ability to agglutinate chicken erythrocytes to the virus population. Hemadsorption assays following transient expression of mutated HA proteins showed that the successive Gln226 --> Leu --> Ile --> Val changes observed on natural isolates resulted in a progressive loss of the ability of the HA to bind chicken erythrocytes. The Val226Ile change maintained the preference of the HA for SAalpha2,6Gal over SAalpha2,3Gal and enhanced binding of the HA to alpha2,6Gal receptors present on chicken erythrocytes. In contrast, simultaneous Ser193Arg and Leu194Ile substitutions that were found to confer the ability to agglutinate sheep erythrocytes increased the affinity of the HA for SAalpha2,3Gal.

Monitoring of influenza in the EISS European network member countries from October 2000 to April 2001.

In countries covered by the European Influenza Surveillance Scheme (EISS), the 2000-2001 winter was marked mainly by the spread of influenza A(H1N1) viruses. Influenza B, which globally represented a minority of cases, was common later in the season and predominant in Great Britain, Ireland, and Portugal. Influenza activity was at its maximum during the period of January and February/March 2001 with little time lag between countries (maximum four weeks). Overall, the morbidity rates reported were much lower than for the previous season, illustrating a moderate level of influenza activity.

Evidence for evolutionary stasis and genetic drift by genetic analysis of two equine influenza H3 viruses isolated in France.

The amino acid sequences of the HA(1) portion of the haemagglutinin of two equine A(H3N8) influenza viruses isolated in France in 1993 and 1998 were analysed to determine their evolutionary relationship with 51 other HA(1) amino acid sequences available in databanks. Our data show that the French strain isolated in 1993 belongs to a group of phylogenetically related viruses branched on the main trunk, illustrating the main lineage of evolution of the equine-2 H3 sequences before its split into two distinct lineages in the late 1980s. By contrast, the 1998 French isolate appears to belong to the more recent 'Eurasian' lineage. These data suggest that equine-2 strains antigenically related to old prototype viruses may cocirculate with the more recent 'Eurasian' and 'American' lineages. In conclusion, it may be necessary to include both strains representative of recent equine influenza variants and an older prototype strain in the current equine influenza vaccines.

Surveillance of influenza in Europe from October 1999 to February 2000.

Surveillance of influenza through EISS (European Influenza Surveillance Scheme) during the 1999 to 2000 winter shows that influenza affected most of the 11 participating countries and was particularly active in December 1999 and January 2000. Influenza A(

Production of influenza virus in serum-free mammalian cell cultures.

Human influenza viruses are routinely isolated and grown in a variety of mammalian cell substrates. However, influenza viruses for use as inactivated vaccine are still produced in embryonated eggs. Using a perfusion culture-based bioreactor process using serum-free medium, both human and equine influenza viruses of different types and subtypes could be produced to high titres. Classical DEAE-dextran microcarriers were found to be more suitable than polyester sponge carriers for virus production. In addition, MDCK cells grown in serum-free medium were further validated as the most suitable cell substrate compared to Vero and BHK-21 C13 cells for large scale virus production of influenza virus. Finally, to minimize potential contamination by adventitious agents, it was demonstrated that a new serum-free medium in which all animal-derived products are replaced by a plant extract, efficiently supports the growth of MDCK cells as well as the production of influenza virus in the presence of trypsin when using the perfusion bioreactor process.

Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network.

BACKGROUND: Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables. OBJECTIVE: To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people. METHODS: This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2 x 2 factorial design for 2 years. MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality. RESULTS: Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P = .06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups. CONCLUSIONS: Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.

The new medium MDSS2N, free of any animal protein supports cell growth and production of various viruses.

The development of media free of serum and animal or human proteins is of utmost importance for increasing the safety of biologicals produced for therapy and vaccination. In order to reduce the risk of contamination, we have modified the serum free medium MDSS2, a very efficient serum free medium for the production of various biologicals including experimental vaccines using different cell lines (Merten et al., 1994), by replacing the animal derived products by plant extracts. The new serum and animal protein free medium (MDSS2N) can be efficiently used for biomass production of various cell lines. These cells grow equally well or better in this new serum-free medium than in the old formulation (MDSS2):* BHK-21/BRS cells, adapted to MDSS2N, showed an overall specific growth rate of 0.0197 h-1 (mu_max = 0.0510+/-0.0058 h-1), whereas those cultivated in MDSS2 grew with an average specific growth rate of 0.0179 h-1 (mu_max = 0.0305+/-0.0177 h-1).* Vero cells grew with an average specific growth rate of 0.0159 h-1 and 0.0153 h-1 in MDSS2 and MDSS2N, respectively. Very similar growth rates were obtained in microcarrier cultures in stirred tank reactors: the specific growth rates were 0.0161 h-1 and 0.0166 h-1 for MDSS2 and MDSS2N cultures, respectively.* For MDCK cells, when cultured on microcarriers in bioreactors, a higher average specific growth rate was observed in MDSS2N than in MDSS2; values of 0.0248 h-1 and 0.0168 h-1, respectively, were obtained.The capacity of MDSS2N to support the production of different viruses was equally evaluated and it could be established that for certain viruses there are no or insignificant differences between MDSS2N and MDSS2 (influenza and polio virus), whereas, the production of rabies virus is somewhat reduced in MDSS2N when compared to MDSS2. The use of MDSS2N for cell culture and the production of various viruses is discussed.

European Influenza Surveillance Scheme on the Internet.

In 1995, The European Influenza Surveillance Scheme was created with the participation of eight networks from seven countries. The main objectives were to continue the previous CARE Telematics Network and to adapt the project to the Internet environment as well as to improve substantially the quality of the surveillance according to new epidemiological requirements. Clinical and virological data from the general population and hospitals are collected in an interactive real-time database which can then be used for data entry, queries and consultations. Research programmes have been undertaken in various fields such as standardisation of clinical data and comparability between countries. Validation and security processes guarantee the quality assurance as well as regular assessment by the steering committee. Two additional countries will participate during the next influenza season (1997-98). This will represent an early warning system in a region of approximately 264 million inhabitants.

Study of the O-acetylesterase activity of five influenza C virus strains.

Four influenza C virus strains, isolated in France in 1991, were used as a source for a kinetic study of the enzyme O-acetylesterase (EC 3.1.1.53) related to another strain, C/JHB/1/66, considered as the reference strain. Similarities, but also differences, in their haemagglutination titres were detected. Remarkable differences were found for enzyme activity and the K(m), Vmax, and the Vmax/K(m) ratio between certain strains, as well as for their thermostability at 40 degrees C when methylumbelliferyl acetate was used as substrate. By contrast, their optimum pH, stability at different pH values, and stability at 4 degrees C over 14 days were very similar. The effect of some compounds on O-acetylesterase activity was studied. The peculiarities of these factors are discussed in relation to the functional variation of the virus.

Chimeric peptides: a new approach to enhancing the immunogenicity of peptides with low MHC class I affinity: application in antiviral vaccination.

Recruitment of the CTL repertoire specific for subdominant epitopes that have a low MHC class I-binding affinity could be the way to achieve an efficient protective immunity against spontaneous tumors and viruses with high mutation rate. However, we have reported recently that subdominant peptides of influenza A Puerto Rico/8/34 (flu PR8) nucleoprotein (NP) with low Db affinity are only partially able to protect mice against lethal influenza infection. This seems to be due to their inability to recruit the specific CTL repertoire, and suggests that subdominant peptides could be used for vaccination only if they become highly immunogenic. In this work, we describe an approach that allows enhancement of the immunogenicity of every low affinity peptide presented by the Db molecule. It consists in producing chimeric peptides composed by amino acids from a high Db affinity peptide (NP366) in positions that interact with the MHC, and amino acids from low Db affinity nonimmunogenic influenza NP-derived peptides (NP17, NP97, NP330, and NP469) in positions that are exposed to the TCR. All chimeric peptides tested exhibited a high Db affinity and efficiently recruited the CTL repertoire specific for the corresponding low Db affinity peptide. Furthermore, vaccination with chimeric peptides that corresponded to subdominant NP17 and NP97 peptides induced a very potent anti-flu PR8 protective immunity.

[Influenza: interspecies transmissions and viral rearrangement]. / Grippe: transmissions inter-espèces et réassortiment viral.

Influenza is an infection of humans beings and many animal species. It is caused by viruses which belong to the Orthomyxoviridae family. There are three types of influenza viruses A, B and C. The type A is the most pathogenic of all. The type is determined mainly by the nature of the nucleoprotein (NP), an antigen which does not greatly vary. On the contrary, the surface antigens, among which the haemagglutinin is the most important, are highly variable and their nature determines the sub-type of virus within the type A. The expressed mutations affecting the haemagglutinin are referred as antigenic drift and make virological surveillance necessary in order to annually assess the composition of the vaccine strains. The segmented nature of the genome of influenza viruses, makes possible the genetic reassortment of two different influenza viruses co-infecting one cell and produces a new hybrid virus. When such an event affects the haemagglutinin, the reassortment leads to an antigenic shift. In nature, it most certainly takes place in swine, between human and avian viruses. Whereas antigenic drift is a continuous and progressive phenomenon, antigenic shift occurs occasionally every 10 to 30 years. The emergence of a hybrid virus bearing a new haemagglutinin and thus belonging to a new human subtype, can be the starting point of the genesis of a pandemic, generally associated with a high mortality rate in humans. The participation of the pig is specially mentioned.

Protection against lethal viral infection by vaccination with nonimmunodominant peptides.

CTL response of H-2b mice to influenza PR8 virus is directed against the nucleoprotein (NP)-derived immunodominant 366-374 (NP366PR8) peptide presented by the Db molecule. However, NP has three nonimmunodominant peptides corresponding to the 17-25 (NP17), 55-63 (NP55), and 97-105 (NP97) sequences that have the Db consensus motifs and bind to the Db molecule with an intermediate (NP55) or low (NP17 and NP97) affinity. In a previous report, we have shown that NP55 peptide is naturally processed by infected cells. In the present work, we studied whether nonimmunodominant peptides can protect mice against viral infection. Antiviral protection was evaluated by measuring three parameters: survival after inoculation of a lethal dose of mouse-adapted PR8 virus, percentage of pulmonary lesions in surviving mice, and virus clearance from lungs of infected mice. Our results showed that immunization of B6 mice with nonimmunodominant peptides protected from PR8 virus infection, although less efficiently than immunization with the immunodominant NP366PR8 peptide. Protection was mediated by CD8 T cells. The efficacy of nonimmunodominant peptides correlated with their Db binding affinity; the low affinity binders NP17 and NP97 induced a weaker protection than the intermediate affinity binder NP55. A mixture of NP366PR8 and nonimmunodominant peptides gave a higher protection than NP366PR8 peptide alone. In conclusion, nonimmunodominant peptides protect against a viral infection with an efficacy that is proportional to their affinity for the restricting class I molecule.

Production of influenza virus in cell cultures for vaccine preparation.

Influenza virus strains of different types for use as an inactivated vaccine have been successfully grown in different cell lines. Increasing titres were obtained with BHK-21/BRS, VERO and MDCK cells. Cultures in stationary flasks, in spinner cultures or in large bioreactor systems were tested and the optimal conditions were studied. MDCK cells grown in serum-free medium before and during the virus production phase were found to yield high titres in the presence of trypsin. Satisfactory results were obtained with egg-adapted strains of human and equine origin as well as with strains just isolated from human patients without any further passages in eggs or cell culture.

Modifications of cell surface sialic acids modulate cell adhesion mediated by sialoadhesin and CD22.

An increasing number of mammalian cell adhesion molecules, including sialoadhesion, CD22 and the family of selectins, have been found to bind cell surface glycoconjugates containing sialic acids. Here we describe how the structural diversity of this sugar influences cell adhesion mediated by the related molecules sialoadhesin and CD22 in murine macrophages and B-cells respectively. We show that the 9-O-acetyl group of Neu5,9Ac2 and the N-glycoloyl residue of Neu5Gc interfere with sialoadhesin binding. In contrast, CD22 binds more strongly to Neu5Gc compared to Neu5Ac. Of two synthetic sialic acids tested, only CD22 bound the N-formyl derivative, whereas a N-trifluoroacetyl residue was accepted by sialoadhesin. The potential significance for the regulation of sialic acid dependent cell adhesion phenomena is discussed.