The Wood equation allows consistent fitting of individual antibody-response profiles of Zika virus or SARS-CoV-2 infected patients.

Antibody kinetic curves obtained during a viral infection are often fitted using aggregated patient data, hiding the heterogeneity of individual humoral immune responses. Individual antibody responses can be modeled using the Wood equation and grouped according to their profile. Such modeling takes into account several important kinetic parameters, such as the day when antibody detection becomes positive [daypos], the day of the maximal response [daymax], the maximum antibody level [levelmax], and the day when antibody detection becomes negative [dayneg]. Potential associations between these profiles and studied factors can then be tested.

[Management of the COVID-19 epidemic in the carrier battle group (January-April 2020) by the Armed Forces Epidemiology and Public Health Center]. / Gestion de l'épidémie de COVID-19 au sein du groupe aéronaval (janvier­avril 2020) par le Centre d'épidémiologie et de santé publique des armées.

Objectives: Faced with the COVID-19 epidemic that occurred within the naval air group and the nuclear aircraft carrier Charles de Gaulle, the French Armed Forces Epidemiology and Public Health Center (CESPA) carried out an investigation (January - April 2020) whose objectives were: to identify the possible routes of introduction of the virus ; to describe the characteristics of the epidemic and to describe and model the dynamics of the epidemic's spread. Methods: A telephone survey was conducted. The biological diagnoses were transmitted by the medical antennas. A time/place/population analysis was carried out, as well as the description of the clinical pictures with their exposure factors. The instantaneous reproduction rate Rt of the epidemic was modeled. A spatial analysis of the epidemic on board was carried out. Forty-three viral genomes were sequenced and compared to the reference bases. Results: 0f 1767 sailors, 1568 (89%) participated in the telephone survey and 1064 (67.9%) were confirmed cases. Four patient profiles have been described: asymptomatic (13.0%); non-specific symptomatic (8.1%); specific symptomatic (76.3%); severe cases (2.6%). In univariate and multivariate analysis, age, overweight and obesity were significantly associated with the risk of having a severe form. Smoking was a protective factor. The evolution kinetics of Rt was in favor of an introduction of the virus at the end of February with a reintroduction during the stopover in Brest. Analysis of viral genomes ruled out introduction and spread of a single strain. Conclusion: Despite the control measures taken, an epidemic occurred. The often pauci-symptomatic clinical pictures resulted in a delay in identification. CESPA was able to carry out this epidemiological investigation within a highly constrained timeframe, showing all the interest of its integrated public health model.

Zika virus infections.

Since its discovery in 1947 in Uganda, the Zika virus (ZIKV) remained in the shadows emerging in 2007 in Micronesia, where hundreds of dengue-like syndromes were reported. Then, in 2013-2014, it was rife in French Polynesia, where the first neurological effects were observed. More recently, its arrival in Brazil was accompanied by an unusually high number of children with microcephaly born to mothers infected with ZIKV during the first trimester of pregnancy. In 2016, the World Health Organization declared ZIKV infection to be a public health emergency and now talks about a ZIKV pandemic. This review aims to summarize the current knowledge about ZIKV infection, successively addressing its transmission, epidemiology, clinical aspects, diagnosis, treatment, and prevention before discussing some perspectives.

Feedback on the management of the 2011 measles outbreak by French military general practitioners: an evaluation study.

OBJECTIVE: Preventive measures were implemented in the French armed forces to limit the measles outbreak that occurred in 2010 and 2011. This study aimed to obtain feedback concerning the management of this outbreak by the French military general practitioners. METHOD: A cross-sectional study was conducted among the general practitioners (GPs) in military units located in metropolitan France. The 60 military units that reported at least one measles case in 2011 were included. Data were collected using self-administered questionnaires. RESULTS: The acceptance of preventive measures against measles was good (measures "totally justified" for 77.8%) and most of the military GPs considered that the outbreak had no significant impact on their activities. The management of measles cases was perceived as not very problematic but difficulties were encountered in the identification of contacts around cases (48.1% of respondents) and in the identification of vaccine recipients among these contacts (more than 80% of respondents reporting difficulties in the collection of measles and vaccination histories). The organization of vaccination around cases was also perceived as difficult. CONCLUSIONS: Preventive measures around measles cases were well accepted by the military GPs, which could reflect their preparedness in the face of the outbreak. However, vaccination did not seem to be well understood or accepted by military patients, underlining the essential role of military GPs in patient information. Difficulties in the collection of vaccination and measles histories among contacts could be overcome by an early transcription of individual medical records in the military medical files of newly enlisted personnel. A more generalized use of oral fluid testing devices, which can be shipped at ambient temperature, would simplify diagnosis in the armed forces.

Emergence of Plasmodium ovale malaria among the French Armed Forces in the Republic of Ivory Coast: 20 years of clinical and biological experience.

BACKGROUND: French military surveillance identified an increase in Plasmodium ovale attacks among soldiers in Ivory Coast. This emergence and the low sensitivity of biological tests raise the question of a possible role of P. ovale variant species. METHODS: Epidemiological data about P. ovale attacks from 1993 to 2012 were studied; the species diagnosis was based on a thin blood smear and/or a quick diagnostic test. Clinical and biological features in soldiers hospitalized in 2 French military hospitals were also reviewed. Malaria polymerase chain reaction followed by genotyping was performed when available. RESULTS: French military physicians declared 328 P. ovale attacks over the 20-year study. A peak of incidence occurred in 2005. Among patients with positive blood smears, the quick diagnostic test was positive in 33 of 101 tests performed. The hospital study showed that symptoms and biological changes were not specific, which made diagnosis challenging: fever, anemia, and thrombocytopenia were not present in 20%, 71%, and 23% of the 45 confirmed cases, respectively. It was possible to perform molecular investigations on 19 clinical isolates: 18 were classic haplotypes with additional polymorphism and 1 was variant. CONCLUSIONS: This emergence of P. ovale malaria enabled a good description to be made in nonimmune patients. The lack of sensitivity of both clinical features and quick diagnostic tests suggests an underestimation. Reasons for this outbreak are especially intense exposure to the vectors and the insufficient efficacy of doxycycline against P. ovale. The polymorphism of classic haplotypes of P. ovale rather than variant forms could be involved.

[Epidemics of schistosomiasis in military staff assigned to endemic areas: standard diagnostic techniques and the development of real-time PCR techniques]. / Épidémies de bilharziose chez des militaires projetés en zone d'endémie, techniques de diagnostic classique et mise au point de techniques de réaction en chaîne de la polymérase (PCR) en temps réel.

The authors report the results of molecular biology techniques for the early diagnosis of cases (invasion phase) of schistosomiasis during two epidemics occurring during French military projects in the Central African Republic and Madagascar. The use of these techniques in real time for subjects not residing in the endemic area significantly improves the sensitivity of screening. The attack rates of these episodes, according to a case definition that took positive specific PCR results into account, were 59% and 26%. These results are a concrete illustration of the proverb that "yaws begin where the trail stops".

Malaria attacks due to P. vivax or P. ovale in two French military teaching hospitals (2000 to 2009).

CONTEXT: Non-falciparum malaria is less studied than Plasmodium falciparum malaria, both in endemic and non-endemic zones. PATIENTS AND METHOD: A retrospective study was made of the medical files of patients managed for attacks of malaria due to Plasmodium vivax or Plasmodium ovale, between 2000 and 2009, in two French military teaching hospitals. RESULTS: Seventy-five percent of attacks occurred after a stay in French Guiana, in the Comoros Archipelago, or in the Ivory Coast Republic. The most frequent symptoms two months after coming back were a flu-like syndrome with headaches, and occasional digestive symptoms, without any difference between the first attack and recurrence. One third of patients presented with anemia, 78% with thrombocytopenia, and 12% with liver dysfunction. DISCUSSION: This study was the most important made in France on imported non-falciparum malaria. Military patients and immigrants accounted for a majority of patients due to the specificity of military hospitals and local recruitment. Clinical and biological features were not specific and did not allow guiding the diagnosis. Diagnostic tools were less sensitive for P. ovale. CONCLUSION: Patient management could be optimized by more efficient diagnostic tools, specific guidelines for the diagnostic and therapeutic management, and a dedicated medical training for family practitioners as well as hospitals practice.

A large outbreak of scombroid fish poisoning associated with eating yellowfin tuna (Thunnus albacares) at a military mass catering in Dakar, Senegal.

On 26 November 2010, an outbreak of scombroid fish poisoning occurred in the French Armed Forces in Dakar, Senegal. This chemical intoxication, due to high histamine concentration in fish, is often mistaken for an allergic reaction. A case-control study was undertaken including the 71 cases and 78 randomly selected controls among lunch attendees. The usual symptoms for scombroid fish poisoning were observed in cases, i.e. flushing (85.9%), headache (83.1%), rapid/weak pulse (59.1%) and diarrhoea (47.9%). Symptoms occurred from within a few minutes to up to 3 h following the meal. Most patients quickly recovered with antihistamine and/or symptomatic treatment. Tuna was the only food item positively associated with illness (odds ratio 36.3, 95% confidence interval 6.3-210.0), with the risk of illness increasing with the quantity of fish consumed. No bacterial contamination was found in leftover food, but histamine concentration in tuna was found to be 4900 mg/kg, almost 50-fold higher than the concentration allowed by European regulations. This report is unique because of the large size of the case series - to our knowledge, the largest event of scombroid fish poisoning ever reported - and the chemical and bacteriological analyses results obtained on leftover food.

Increase in reported adverse events following seasonal influenza vaccination among the French armed forces, 2008-2009: possible role of stimulated reporting and background cases of influenza-like infection.

OBJECTIVES: In September 2009, an increase in seasonal influenza vaccine adverse events (VAE), compared with reports for previous years, was detected among the French armed forces in the setting of an extended immunization campaign. This work presents the results of this investigation. STUDY DESIGN: VAE were surveyed among all French military personnel from 2008 to 2009 by Epidemiological Departments of the French Military Health Service. For each case, a notification form was completed, providing patient and clinical information. METHODS: Case definitions were derived from the French drug vigilance guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAE to the number of vaccine doses injected. RESULTS: Forty-seven seasonal influenza VAE were reported in continental France: 18 in 2008 and 29 in 2009. The annual reporting rate was higher in 2009 (31.6 vs 16.6 VAE per 100,000 injections, respectively). The highest monthly incidence was observed in September 2009 (60.8 events per 100,000 injections). Two other peaks were observed in February 2008 and March 2009. The incidence in September 2009 was not significantly different from the incidences in February 2008 and March 2009. It was observed that incidence peaks occurred during influenza epidemic periods. One serious neurological VAE was observed. CONCLUSIONS: The increase in seasonal influenza VAE in late 2009 mainly involved non-serious events, and could reflect stimulated reporting in the context of the A(H1N1)pdm09 pandemic. VAE reporting rates were highest during influenza epidemic periods, which could be explained by VAE being wrongly attributed to the vaccine when symptoms could reflect coincident background cases of viral infection.

Resurgence of measles in the French military forces in 2010.

Since the start of 2010 there has been a flare-up of measles in France, following on the resurgence observed in 2008. The aim of this study was to present results of the epidemiological surveillance of measles in the French armed forces and to describe the increase in incidence. Measles was surveyed from 1992 to 2010. Criteria for report were those used for French national compulsory notification. The data, concerning active military personnel, were provided by the physicians in the armed forces using anonymous data collection forms. Between 1992 and July 2010, 689 cases of measles were notified. Since 2002, the mean incidence rate was 1 case per 100,000. A significant increase has been observed for 2010 (13.9 cases per 100,000 in 2010 versus 1.8 in 2009). The 28 cases reported in 2010 involved five clusters and three isolated cases. The mean age of affected subjects was 27 years. Only 30% of cases had been vaccinated. The epidemic resurgence of measles observed in 2010 in the French armed forces follows the same pattern as that observed nationally and at European level, and can be seen as the likely consequence of inadequate vaccination cover.

[A(H1N1) influenza surveillance in the French armed forces: adapting the surveillance systems to the pandemic setting]. / Surveillance épidémiologique de la grippe A(H1N1) 2009 dans les armées françaises: adaptation des systèmes de surveillance au contexte pandémique.

OBJECTIVES: An outbreak of A(H1N1) virus influenza, detected in Mexico during April 2009, spread around the world in nine weeks. French armed forces had to adapt their epidemiological surveillance systems to this pandemic. Our aim was to present surveillance results. DESIGN: There are two influenza surveillance systems in French armed forces: one permanent throughout the year and one seasonal, the Military influenza surveillance system (SMOG). The pandemic threat led to an early reactivation of SMOG, before the initiation of a daily surveillance system specifically dedicated to A(H1N1) influenza. RESULTS: In metropolitan France, the increase of respiratory infections was observed as of September 2009, with a maximum of 401 cases for 100,000 at the beginning of December according to SMOG. The estimated rate of consultations related to A(H1N1) influenza ranged between 46 and 65 cases for 100,000. For military units operating outside of metropolitan France, a peak of incidence was observed in August (400 cases for 100,000). CONCLUSION: The trends observed by influenza military surveillance networks were compatible with French ones. Concerning French forces in operations, the increase of incidence observed in August was the consequence of the influenza outbreak in the Southern hemisphere. Estimations of consultations rate related to A(H1N1) influenza, ranged between 127 and 194 cases for 100,000 at the beginning of December, lower than the national rate (1321 cases for 100,000), a consequence of the age pyramid in the military population.

Porcine reproductive and respiratory syndrome (PRRS) virus-specific interferon-gamma(+) T-cell responses after PRRS virus infection or vaccination with an inactivated PRRS vaccine.

Although field studies have found porcine reproductive and respiratory syndrome (PRRSV) inactivated vaccines to be beneficial in reducing losses linked to PRRSV infection, immune mechanisms induced by these vaccines need better understanding. In the study reported here, we examined the interferon-gamma(+) (IFNgamma(+)) PRRS-specific T cell responses induced after infection and vaccination with an inactivated PRRS vaccine. Autologous monocyte-derived dendritic cells loaded with the PRRSV P120 strain were used to re-stimulate ex vivo T cells that had been primed in vivo by either the virus or the vaccine, or both. Virus-specific IFNgamma(+) T cells were quantified by using a porcine IFNgamma- ELISpot assay. A specific but low live virus-induced response was observed between days 35 and 70 for most of the pigs tested, while a significant inactivated vaccine-induced PRRSV-specific IFNgamma(+) T-cell response was measured soon after vaccination. Moreover, we observed that vaccination of pre-challenged pigs clearly favoured the PRRSV-specific cell-mediated immunity primed by the live virus. To characterize further the nature of the PRRSV-specific T cells, the different T-cell subsets involved in PRRSV immunity were analyzed by flow cytometry. We showed that the inactivated vaccine was able to prime both CD4(+)CD8(int+) and CD8(high) virus-specific T cells and that CD4(+)CD8(int+) were preferentially recalled by the live virus.

Quantitative analysis of the antigen-specific IFNgamma+ T cell-mediated immune response in conventional outbred pigs: kinetics and duration of the DNA-induced IFNgamma+ CD8+ T cell response.

It is now well established that antigen-specific CD8(+) T cells play a major role in vaccine-induced immunity against intracellular pathogens and tumor cells. The detection of these immune cells in outbred animals has been hampered mainly by the need to generate individual autologous antigen-presenting cells (APCs) due to the high degree of polymorphism of the major histocompatibility complex (MHC) Class I loci. We used individually derived immature porcine dendritic cells infected with a pox-based recombinant viral vector to ex vivo stimulate PBMCs from vaccinated conventional pigs. The frequencies of antigen-specific T cells was determined by the number of IFNgamma-secreting cells in a quantitative enzyme-linked immune spot (ELISPOT) assay. Using this approach we were able to rank different pseudorabies virus (PRV) vaccines strategies for their ability to prime viral-specific IFNgamma(+) T cells. Plasmid DNA has recently emerged as a promising tool with multiple applications in the field of infectious diseases, allergy and cancer. We showed for the first time in this study that DNA immunization induced a long-lived antigen-specific IFNgamma(+) T cells response in conventional pigs. Additional studies allowed us to show that these virus-specific IFNgamma(+) responding cells detected in this ELISPOT assay were MHC-restricted and comprised in the CD8alpha(bright) pig T cell subset. These new data confirm the usefulness of DNA vaccines to control diseases requiring cellular immunity in pigs.

Characterization of an unusual Mycobacterium: a possible missing link between Mycobacterium marinum and Mycobacterium ulcerans.

In an attempt to characterize an unusual mycobacterial isolate from a 44-year-old patient living in France, we applied phenotypic characterizations and various previously described molecular methods for the taxonomic classification of mycobacteria. The results of the investigations were compared to those obtained in a previous study with a set of temporally and geographically diverse Mycobacterium ulcerans (n = 29) and Mycobacterium marinum (n = 29) isolates (K. Chemlal, G. Huys, P.-A. Fonteyne, V. Vincent, A. G. Lopez, L. Rigouts, J. Swings, W. M. Meyers, and F. Portaels, J. Clin. Microbiol. 39:3272-3278, 2001). The isolate, designated ITM 00-1026 (IPP 2000-372), is closely related to M. marinum according to its phenotypic properties, lipid pattern, and partial 16S rRNA sequence. Moreover, fingerprinting by amplified fragment length polymorphism (AFLP) analysis unequivocally classified this strain as a member of the species M. marinum, although it lacked two species-specific AFLP marker bands. However, PCR and restriction fragment length polymorphism analysis based on M. ulcerans-specific insertion sequence IS2404 showed the presence of this element in a low copy number in isolate ITM 00-1026. In conclusion, the designation of this isolate as a transitional species further supports the recent claim by Stinear et al. (T. Stinear, G. Jenkin, P. D. Johnson, and J. K. Davies, J. Bacteriol. 182:6322-6330, 2000) that M. ulcerans represents a relatively recent phylogenetic derivative of M. marinum resulting from the systematic acquisition of foreign DNA fragments.

Accurate molecular mass determination of mycolic acids by MALDI-TOF mass spectrometry.

Mycolic acids, major and specific long-chain fatty (C70-C90) acid components of the mycobacterial cell envelope, were analyzed for the first time using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry operating in a reflectron mode. The various types of purified mycolates from representative mycobacterial species were analyzed using 2,5-DHB as matrix, because less than 10 pmol of mycolates was sufficient to obtain well-resolved mass spectra composed exclusively of pseudomolecular [M + Na]+ ions consistent with the structures deduced from the chemical analytical techniques applied to these molecules. Examination of the MALDI mass spectra demonstrated that the chain lengths of the various mycolates correlated with the growth rate of mycobacterial strains. Although slow growers, such as Mycobacterium tuberculosis and Mycobacterium ulcerans, produced a series of odd carbon numbers (C74-C82) of alpha-mycolic acids, rapid growers synthesized both odd and even carbon numbers. In addition, the main chain of oxygenated mycolic acids from slow growers were four to six carbon atoms longer than the corresponding alpha-mycolic acids, whereas rapid growers elaborated oxygenated homologues possessing the same chain lengths as their alpha-mycolic acids. Furthermore, a comparative analysis of the crude fatty acid mixtures from a wild-type strain of M. tuberculosis and its isogenic mutant effected in the synthesis of oxygenated mycolates by MALDI mass spectrometry revealed structural differences between the alpha-mycolates from the two strains. Thus, this technique appeared to be a rapid and highly sensitive technique for the analysis of mycolic acids, not only by providing accurate molecular masses and new structural information, but also by both reducing sample consumption and saving time.

Functional and phenotypic characterization of distinct porcine dendritic cells derived from peripheral blood monocytes.

Dendritic cells (DCs) are bone marrow-derived antigen-presenting cells that have an exquisite capacity to interact with T cells and modulate their responses. Little is known about porcine DCs despite the fact that they represent an important target in strategies that are aimed at modulating resistance to infection in pigs and may be of major importance in transplantation biology. We generated immature monocyte-derived porcine dendritic cells (MoDCs) directly from adherent peripheral blood cells treated with porcine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The cells were observed via electron microscopy and their phenotype was characterized using monoclonal antibodies. The functionality of the porcine MoDCs was demonstrated showing that the cells were capable of different specialized functions relevant to antigen capture and were potent stimulators in a primary allo-mixed leucocyte reaction. Treatment of the MoDCs with porcine cell line-derived necrotic factors resulted in the phenotypic and functional maturation of MoDCs. We confirmed also that monocyte-derived DCs were differentially regulated by cytokines, showing that transforming growth factor-beta1 (TGF-beta1) is able to redirect monocytic precursors into the differentiation pathway of Langerhans' cells presenting typical Birbeck granules. Interestingly, and in contrast to the human and murine model, we showed that the monocyte-derived porcine Langerhans'-type cells (MoLCs) were much more potent activators of allogeneic T cells than MoDCs obtained without TGF-beta1.

Overexpression of the human HAP1 protein sensitizes cells to the lethal effect of bioreductive drugs.

Abasic sites (AP sites) are generated in DNA either directly by DNA-damaging agents or by DNA glycosylases acting during base excision repair. These sites are repaired in human cells by the HAP1 protein, which, besides its AP-endonuclease activity, also possesses a redox function. To investigate the ability of HAP1 protein to modulate cell resistance to DNA-damaging agents, CHO cells were transfected with HAP1 cDNA, resulting in stable expression of the protein in the cell nuclei. The sensitivity of the transfected cells to the toxic effect of various agents, e.g. methylmethane sulfonate, bleomycin and H2O2, was not modified. However, the transfected cells became more sensitive to killing by mitomycin C, porfiromycin, daunorubicin and aziridinyl benzoquinone, drugs that are activated by reduction. To test whether the redox function of HAP1 protein was involved in this increased cytotoxicity, we have constructed a mutated HAP1 protein endowed with normal AP-endonuclease activity but deleted for redox function. When this mutated protein was expressed in the cells, elevated AP-endonuclease activity was measured, but sensitization to the lethal effects of compounds requiring bioreduction was no longer observed. These results suggest that HAP1 protein, besides its involvement in DNA repair, is able to activate bioreduction of alkylating drugs used in cancer chemotherapy.