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28 Apr 2017

Institut Pasteur in Guinea: One Health training to strengthen local expertise

Guinea remains marked by the Ebola virus outbreak, which highlighted the overall weakness of its health systems. It coud still be the scene of emerging zoonotic diseases with epidemic potential. A better understanding of the conditions for the emergence of those zoonosis and the good practices allowing their detection and prevention is therefore essential to reduce the risk of (re) appearance.

As part of the LAB-NET project coordinated by Expertise France and implemented by Institut Pasteur and Fondation Mérieux, a training course is being led by the Institut Pasteur in Guinea, to strengthen the expertise of Guinean laboratories in the detection and surveillance of pathogens circulating in the area. A theoretical and practical training on the “One Health” concept was organized from 15-25 March 2017 in the city of Dalaba, in collaboration with the Institut Supérieur des Sciences et de Médecine Vétérinaire (ISSMV) in Dalaba and the Friedrich Loeffler Institute (Germany).

© Institut Pasteur

Read more on The Research Journal of the Institut Pasteur (27 April 2017).

27 Apr 2017

First case of Japanese encephalitis in Africa

Researchers from the Institut Pasteur in Paris and the Institut Pasteur in Dakar (Senegal) have detected a co-infection by the Japanese encephalitis virus (JEV) and the Yellow fever virus (YFV) in a patient in Angola. This concerning news raises the issue of the risk of circulation of JEV in Africa, when it is known to be endemic to Asia and Western Pacific. The detection was the subject of a correspondence in The New England Journal of Medicine, on 13 April 2017.

In March 2016, a yellow fever outbreak affected Angola and the Democratic Republic of the Congo. The total number of confirmed cases reached 965 across the two countries, with thousands more cases suspected (WHO). Later on, researchers from the Institut Pasteur in Dakar and the Institut Pasteur in Paris, working in collaboration with colleagues at WHO obtained a sample from an Angolan patient (who had not traveled abroad) to process high-throughput RNA sequencing (RNA extraction in Dakar and construction of libraries and sequencing in Paris). Because the protocol uses « randomly primed cDNA synthesis, it provides a comprehensive and quantitative view of all RNA present in the sample and enables the characterisation of potential connecting viruses ». The scientists were surprised by the sequencing result: in addition to the expected YFV genome, they also found a JEV genome, not likely to be due to contamination.

Transmitted by different species of mosquitoes, YFV and JEV both belong to the family of Flaviviridae (a family also including Dengue and Zika viruses among others). They also circulate in disjunct geographic areas: while YFV is found  in tropical areas of Africa and South America, JEV was till now only found in Asia and Western Pacific. The detection of such a co-infection raises the issue of the risk of circulation of JEV in Africa. Even if this autochtonous infection by JEV could only be an isolated case, the presence of competent mosquitoes in Angola, as well as other animal hosts (swine or waterfowl) could still allow the virus to circulate more durably.

Geographical distribution of risk areas for YFV and JEV (© Institut Pasteur)

This work demonstrates the importance of seroepidemiological investigations to estimate the proportion of the Angolan population that has been exposed to JEV. Such studies would enable an assessment of the need for implementing disease control measures, specifically vaccination campaigns as an efficient vaccine is available. It also demonstrates the relevance of random high-throughput screening technique for pathogens surveillance. The Institut Pasteur and its International Network (IPIN) fully adhere to this technological effort.

Increased global population movements, notably between Asia and Africa, are a factor facilitating the spread of infectious diseases. Recently, there has been imported cases of Yellow fever or Rift Valley Fever in China.

The publication:

Autochthonous Japanese Encephalitis with Yellow Fever Coinfection in Africa, N Engl J Med 2017; 376:1483-1485, April 13, 2017, DOI: 10.1056/NEJMc1701600

Simon-Loriere E, Faye O, Prot M, Casademont I, Fall G, Fernandez-Garcia MD, Diagne MM, Kipela JM, Fall IS, Holmes EC, Sakuntabhai A, Sall AA.

Source:

Institut Pasteur, press release, 14 April 2017 (in French)

03 Apr 2017

Rabies, a neglected disease that is still rife in Cambodia

Rabies is an acute neurological syndrome caused by a lyssavirus in the Rhabdoviridae family. One hundred percent of declared cases are fatal. Rabies has the highest death rate of all known diseases in humans. It may, however, be prevented in 100% of cases by means of post-exposure prophylaxis (PEP), following a bite, for example. This consists of vaccination, where applicable associated with the administration of immunoglobulins.

Learn about the situation of rabies in Cambodia, and the work done by colleagues of the Institut Pasteur in Cambodia to control the disease and vaccinate the population, with Didier Fontenille, director of the institute.

Text published on The Research Journal of the Institut Pasteur (29 March 2017): here

Child photographed during World Rabies Day on September 28, 2013 in Cambodia. © Arnaud Tarantola - Institut Pasteur Cambodge

03 Apr 2017

How to improve BCG vaccine?

Scientists at the Institut Pasteur and collaborators from the international consortium “TBVAC 2020” have just developed a tuberculosis (TB) vaccine candidate. This TB vaccine candidate stemmed from the conventional BCG vaccine (Bacillus Calmette–Guérin vaccine, the only available vaccine against TB) experimentally shows enhanced efficacy. A heterologous proteins secretion system strongly increases the quality and the scale of the immune response against virulent strains of Mycobacterium tuberculosis, the bacterium causing TB. The researchers have published their results in Cell Reports (14 March 2017).

TB is a chronic bacterial infection caused by Mycobacterium tuberculosis. It is still one of the 10 deadliest diseases in the world with 1.8 million people dying from TB each year (WHO) mainly in India, Indonesia, China, Nigeria, Pakistan and South Africa. The BCG vaccine is made from an attenuated Mycobacterium bovis strain. While it is very efficient against the most severe forms of TB in children, it does not sufficiently protect adults, particularly from the most transmissible form: pulmonary TB. Thus, developing a vaccine that would allow a broader protection is a primary objective for TB control.

For several years, scientists at the Institut Pasteur have deciphered the characteristic mechanisms underlying the interaction between Mycobacterium tuberculosis and the host immune cells. During the infection, the bacterium is ingested by host immune cells into their vacuoles. Through the intervention of a specialized secretion system, ESX-1, the locked in bacterium damages the vacuole’s membrane to access the inside of the host cell. This breakout triggers a series of innate immune responses inside the cell to eliminate the bacterium. The BCG strain lacks the ESX-1 secretion system due to the deletion of a chromosome segment. Its protective action does not rely on the trigger of this powerful innate immune chain reaction.

The researchers from the unit “Integrated Mycobacterial Pathogenomics” led by Roland Brosch at the Institut Pasteur in Paris hypothesized that restoring these innate immune responses within a vaccine strain could enhance the immunogenic potential, and in this way improve the BCG vaccine. By expressing the secretion system ESX-1 from Mycobacterium marinum (a low-virulence marine bacterium) in the BCG strain, they created a recombinant BCG strain able to induce the same type of immune response as Mycobacterium tuberculosis. “The key mechanism is setting up a contact between bacterial components and the cytosol of the host cell when the BCG remains trapped by the vacuoles and have limited communication with the host cytosol” said Brosch. The induced innate and adaptive immune responses are both qualitatively and quantitatively improved and allow a better recognition of mycobacterial antigens (mouse vaccination models). The obtained recombinant strain keeps an attenuated virulence property, making it a good vaccine candidate. Mice vaccinated with the new strain were better protected against later infection by highly virulent Mycobacterium tuberculosis compared to mice vaccinated with parental BCG.

© 2017Gröschel et al.

Bosch and his colleagues have published the results in Cell Reports. They have opened up interesting horizons for the development of more efficient vaccine against the different pathologies caused by Mycobacterium tuberculosis, including pulmonary TB in adults. Experiences are in progress prior to a potential clinical development with trials in humans. The scientists have patented their “new BCG strain”.

The paper:

Recombinant BCG Expressing ESX-1 of Mycobacterium marinum Combines Low Virulence with Cytosolic Immune Signaling and Improved TB Protection, Cell Reports, Volume 18, Issue 11, p2752–2765, 14 March 2017. http://dx.doi.org/10.1016/j.celrep.2017.02.057

Matthias I. Gröschel (1,2), Fadel Sayes (1), Sung Jae Shin (3), Wafa Frigui (1), Alexandre Pawlik (1), Mickael Orgeur (1), Robin Canetti (1), Nadine Honore (1), Roxane Simeone (1), Tjip S. van der Werf (2), Wilbert Bitter (4, 5), Sang-Nae Cho (3), Laleh Majlessi (1) and Roland Brosch (1, 6)

(1) Unit for Integrated Mycobacterial Pathogenomics, Institut Pasteur, 75015 Paris, France

(2) Department of Pulmonary Diseases & Tuberculosis, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands

(3) Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 03722 Seoul, South Korea

(4) Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 HZ Amsterdam, the Netherlands

(5) Section Molecular Microbiology, Amsterdam Institute of Molecules, Medicine and Systems, Vrije Universiteit Amsterdam,1081 HZ Amsterdam, the Netherlands

(6)   Lead Contact

From Institut Pasteur press release (31 March 2017, in French).