Following the recent outbreak of monkeypox, researchers from the Pasteur Network and ANRS | Emerging Infectious Diseases have published a complete portrait of the disease in the New England Journal of Medicine. This is an opportunity to review the signs of the disease, its origin, and also the projects undertaken by the Pasteur Network, such as AFRIPOX, supported by the Institut Pasteur and in collaboration with the Institut Pasteur de Bangui.

All information on this publication can be found in the dedicated article on the Institut Pasteur website.

For more information:
Article from the Institut Pasteur: Monkeypox: a detailed profile of the disease
Review article: Monkeypox
New England Journal of Medicine, 26 octobre 2022.
Antoine Gessain, M.D., Emmanuel Nakoune, Ph.D., and Yazdan Yazdanpanah, M.D.
DOI: 10.1056/NEJMra2208860

During an epidemic, it can happen that no diagnostic test is perfectly adapted to the pathogen. In order to contain the epidemic as quickly as possible, screening is done using several tests. The interpretation of the results of the different tests becomes more complex, which can make individual diagnosis difficult and lead to an underestimation of the disease’s prevalence. Using the plague outbreak that affected Madagascar in 2017 as a case study, researchers from the Institut Pasteur and the Institut Pasteur de Madagascar propose an analytical framework to characterize the performance of different tests and estimate the true prevalence of the outbreak. Published in the journal Plos Biology, these results will help improve the quality of diagnosis during future epidemics.

Between August and November 2017, 2,414 cases clinically suspected of carrying Yersinia pestis, the plague bacillus, were reported, with a large proportion of pulmonary plague. The samples were analyzed using three types of diagnostic tests: bacterial culture, rapid plague test, and molecular biology or qPCR. Significant discrepancies were observed between the different tests, making interpretation of the results complex. The greatest uncertainty related to the extent of the pneumonic plague outbreak, with positive cases ranging from 1% to 18%. The analytical framework used in this study estimated that 7-15% of suspected cases were carriers of Yersinia pestis for this outbreak.  

Estimating the performance of a diagnostic test

Two parameters, specificity and sensitivity, determine the performance of a test. Specificity is the probability of being found negative when uninfected while sensitivity is the probability of being found positive when infected. When there is a reference test with perfect sensitivity and specificity, it is easy to estimate the sensitivity and specificity of other tests by comparing them to the reference test. In the absence of a reference test, as was the case for this plague epidemic, the authors had to estimate the performance of each test and then the prevalence of the epidemic. To do this, they used the latent class method, which is based on the comparison of the results of different imperfect tests. This analysis revealed that molecular biology had the best performance; and that the rapid detection test had limited specificity during the 2017 plague outbreak. Its performance was better the following year, 2018, suggesting that the context of response to a large epidemic can impact diagnostic quality.

Combining results to reconstruct an epidemic

Once the performance of the different tests was known, the researchers determined how to improve case classification algorithms to minimize the risk of false positives and false negatives. They were also able to reconstruct, in a more refined way, the epidemiological trends of the epidemic in space and time. Better classification of cases is particularly important for the allocation of scarce resources, for example by accurately targeting contact tracing efforts where incidence is highest. This avoids deploying resources to false positives and maximizes the impact of mobile testing facilities.

While the development and availability of high quality diagnostics remains a priority, this analytical framework could be a valuable tool to reduce uncertainty for other infectious diseases that lack reference diagnostics. For example, it is already used by the Institut Pasteur de Madagascar to diagnose tuberculosis.

For more information:
Evaluating and optimizing the use of diagnostics during epidemics: Application to the 2017 plague outbreak in Madagascar
Plos Biology, August 15th, 2022.
Quirine ten Bosch†*, Voahangy Andrianaivoarimanana, Beza Ramasindrazana, Guillain Mikaty, Rado JL Rakotonanahary, Birgit Nikolay, Soloandry Rahajandraibe, Maxence Feher, Quentin Grassin, Juliette Paireau, Soanandrasana Rahelinirina, Rindra Randremanana, Feno Rakotoarimanana, Marie Melocco,Voahangy Rasolofo, Javier Pizarro-Cerda, Anne-Sophie Le Guern, Eric Bertherat, Maherisoa Ratsitorahina, André Spiegel, Laurence Baril, Minoarisoa Rajerison, Simon Cauchemez
† These authors contributed equally to this work.
* Corresponding author.

A study conducted as part of the Afriobiota project involving several members of the Pasteur Network, in collaboration with the University of Lausanne, unravels the link between the gut ecosystem and stunting that affects undernourished children. The results of this research that included nearly 1,000 children aged 2 to 5 years between 2016 and 2018 are published in the journal PNAS.

In children, undernutrition – the consumption and/or assimilation of insufficient food to cover the body’s needs – manifests itself mainly through stunted growth. According to the Food and Agriculture Organization of the United Nations, 22% of children under 5 years of age worldwide will be affected by stunting (estimate for the year 2020).

This study focuses on the role of gut microbial communities (microbiota) in undernutrition. This research was coordinated by Prof. Philippe Sansonetti and conducted within the Pasteur Network. It was conducted over a period of six years by the Institut Pasteur in collaboration with the Institut Pasteur de Madagascar and the Institut Pasteur de Bangui as part of the Afriobiota project supported by the Total Foundation.

The work, carried out in Madagascar and the Central African Republic on 1,000 children aged 2 to 5 years, showed that more than 80% of stunted children have an abnormal bacterial overgrowth in the small intestine (SIBO). More specifically, these are bacteria initially present in the mouth that proliferate in the small intestine. Using experimental models (cell cultures and mice), researchers have shown that this phenomenon slows down the assimilation of lipids. This malabsorption of fats could partly explain the growth retardation suffered by children.

For more information:
Stunted children display ectopic small intestinal colonization by oral bacteria, which cause lipid malabsorption in experimental models
PNAS, October 05th, 2022.
Pascale Vonaesch*, João R. Araújo, Jean-Chrysostome Gody, Jean-Robert Mbecko, Hugues Sanke, Lova Andrianonimiadana, Tanteliniaina Naharimanananirina, Synthia Nazita Ningatoloum, Sonia Sandrine Vondo, Privat Bolmbaye Gondje, Andre Rodriguez-Pozo, Maheninasy Rakotondrainipiana, Kaleb Jephté Estimé Kandou, Alison Nestoret, Nathalie Kapel, Serge Ghislain Djorie, B. Brett Finlay, Laura Wegener Parfrey, Jean-Marc Collard, Rindra Vatosoa Randremanana, Philippe J. Sansonetti* and The Afribiota Investigators
* Corresponding authors.
Flash Research of the University of Lausanne

Monkeypox virus (MPXV) is a neglected tropical pathogen whose recent emergence has accelerated its study. In this context, Pasteur Network researchers have developed rapid MPXV diagnostic tests that can be viewed by the naked eye in less than 30 minutes, and are as consistent as the current PCR-based nucleic acid test used for MPXV diagnostics. This new diagnostic tool will contribute to the control and prevention of MPXV epidemics.

In May 2022, outbreaks of monkeypox virus (MPXV) were reported simultaneously in Europe, North America and South America, outside the virus-endemic regions of Africa. Pasteur Network researchers collaborated to develop and validate tests for the rapid detection of MPXV. These newly designed tests can produce reliable fluorescence or lateral flow results on a strip in 20 to 30 minutes. Led by the teams of Emmanuel Nakouné (Institut Pasteur de Bangui) and Nicolas Berthet and Gary Wong (Institut Pasteur de Shanghai), the study presenting the results of these rapid diagnostic tests was published in the journal Viruses.

The tests are based on isothermal amplification of a targeted region of the virus genome, and are based on recombinase with or without CRISPR/Cas12. The tests gave consistent results with the reference molecular test, PCR in real time, for the 19 clinical samples used to validate the assay. In addition, the tests were specific and did not cross-react with other pox viruses, such as vaccinia.

MPXV, a neglected tropical pathogen, is closely related to smallpox, a disease that has been eradicated in humans since the 1980s. Although MPXV epidemics are regularly reported in Africa among the poorest communities, it remains understudied, even after the first MPXV epidemic was reported outside the endemic areain the USA during 2003. Rapid, sensitive and specific detection of MPXV is essential to inform health authorities of suspected cases as soon as possible, in order to monitor epidemic developments. These results therefore provide a point-of-care platform for the early diagnosis of potential MPXV cases, and will contribute to the prevention and control of current and future MPXV epidemics.

For more information:
Article from the Institut Pasteur de Bangui (in French)
Development and Characterization of Recombinase-Based Iso-thermal Amplification Assays (RPA/RAA) for the Rapid Detection of Monkeypox virus
Viruses, September 2022.
Lingjing Mao, Jiaxu Ying, Benjamin Selekon, Ella Gonofio, Xiaoxia Wang, Emmanuel Nakoune, Gary Wong*, Nicolas Berthet*
* Corresponding authors.

The first conference of French-speaking science journalists was held in Dakar from October 10th to 16th, 2022. It was attended by nearly 60 journalists from more than 20 countries[1]. The Pasteur Network partnered with the event with the aim of sharing the scientific knowledge of its members, all of which are experts in global health. The idea was to bring scientists and journalists together to ensure that only factually verified scientific information reaches the public. Several scientists from the Institut Pasteur de Dakar spoke at the event, demonstrating this commitment to delivering quality scientific information.

The conference was organized by the French-speaking Africa Science Journalists’ Network (RJSAF) with the French Association of Science Journalists (AJSPI), the Quebec Association of Science Communication (ACS) and the Swiss Association of Science Journalism (SASJ). It was held at the Center for Studies in Information Science and Technology (CESTI) at Cheikh Anta Diop University (UCAD).

The main theme of the conference was journalism and the climate crisis. Several of the topics proposed by the organizers were related to health, an area of expertise for Pasteur Network members like the Institut Pasteur de Dakar.

Neglected and emerging diseases in Africa 

Dr. Xavier Berthet, the Institut Pasteur de Dakar’s, Scientific Director, spoke alongside Dr. Digas Ngolo Tete from DNDi during an expert panel discussion on “Neglected and emerging diseases in Africa” on Monday October 10th, the opening day of the conference. Their presentation was an opportunity to take a closer look at these diseases, caused mostly by parasites (sleeping sickness and schistosomiasis) or bacteria (trachoma and Buruli ulcer), that can be very debilitating for those affected. Dr. Xavier Berthet explained how problems affecting populations can be tackled via the initiatives implemented at the Institut Pasteur de Dakar, like the manufacture of biological products at its future vaccine facility, currently under construction in Diamniadio, and infectious disease surveillance.

Zoonoses: situation and challenges in the age of climate change 

A panel of virology experts from the Institut Pasteur de Dakar addressed the question “Zoonoses: situation and challenges in the age of climate change” on Wednesday October 12th. Dr. Jean-Michel Héraud pointed out that 75% of the diseases that have emerged recently are of zoonotic origin. Out of the total estimated number of viruses on the planet, known as the “virome,” few are as yet known to infect humans. Factors contributing to emergence, like demographics, uncontrolled urbanization, human-induced environmental changes and climate change, were explained to the journalists in attendance. Dr. Oumar Faye, winner of the 2019 Pasteur Network Talent Award, reiterated the role of WHO Collaborating Centers in identifying viruses. He shared his experiences of the Ebola outbreak and more recently the Zika outbreak in Brazil, which helped him to anticipate and prepare for future outbreaks, for example with a mobile laboratory facilitating access to samples and speeding up virus identification. The scientists emphasized the value of One Health approaches, methods to identify viral reservoirs and the use of genomic surveillance to rapidly detect new threats to human and animal health and better anticipate their emergence.

The conference continued for a further four days, covering other scientific fields such as agricultural models in a +1.5°C climate scenario, with events including workshops for journalists. A visit to a virology laboratory at the Institut Pasteur de Dakar and to the Diamniadio manufacturing site brought the week to a close.

Full program:

[1] Countries represented: Benin, Burkina Faso, Burundi, Cameroon, Canada, Central African Republic, Côte d’Ivoire, Democratic Republic of the Congo, Egypt, France, Guinea, Haiti, Madagascar, Mali, Morocco, Niger, Rwanda, Senegal, Switzerland, Togo, Tunisia

Genomic sequencing enables live tracking of the spread of a virus. A Science paper, released on September 15th, 2022, analyzing more than 100,000 genomes, recalls the benefits of local sequencing while studying the spread dynamics of SARS-CoV-2 and its variants of interest on the African continent. More than 300 authors combined their research including 10 members of the Pasteur Network who shared locally sampled SARS-CoV-2 sequences. The results show that most of the introductions of the virus in Africa were from abroad. They also highlight the critical need to invest in diagnostics and genomic surveillance in Africa to best prepare for and respond to future emergencies and epidemics.

This study reveals a mapping of the transmission dynamics of COVID-19 on the African continent. Increased local sequencing capacity has resulted in improved turnaround times and more regular routine surveillance. Pasteur Network members have shared, via the GISAID initiative, the SARS-CoV-2 sequences in the framework of the REPAIR and AFROSCREEN projects.

The spread of the different COVID-19 variants in the continent was heterogeneous, especially for the Alpha, Beta, Delta and Omicron variants which have followed and still follow distinct patterns of dispersion. The Alpha variant that occurred on the continent emanated mainly from Europe before spreading to 43 countries. Most of the Delta variant introductions (about 72%) came from India, while introductions between African countries of the same variant represented only 7% of cases. As for the Omicron variant, its emergence came from Europe, as well as North America and Asia.

The 200 signatory institutions[1] of this study constitute the largest consortium of African scientists and public health institutions united to respond to COVID-19 using local data. The establishment of the Africa Pathogen Genomics initiatives by the Africa CDC and the continental network by the Africa CDC and WHO AFRO are testament to the intent to expand access to sequencing across the continent. Following the example of this study, sustained monitoring remains essential to maintain quality surveillance of both the circulation of COVID-19 and other emerging or re-emerging infectious diseases that may affect Africa.

For more information:
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
Science, September 15th, 2022.
Houriiyah Tegally, Tulio de Oliveira*, Eduan Wilkinson†* and al.
These authors contributed equally to this work.
* Corresponding author.
DOI: 10.1126/science.abq5358
Press release:

[1] This study was conducted by the Centre for Epidemic Response and Innovation (CERI) at Stellenbosch University, and the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP) at the University of KwaZulu-Natal, in coordination with Africa CDC, WHO AFRO, and more than 200 partner institutions, including 10 Pasteur Network members: the CERMES Niger, the Institut Pasteur, the Institut Pasteur d’Algérie, the Institut Pasteur de Bangui, the Institut Pasteur de Côte d’Ivoire, the Institut Pasteur de Dakar, the Institut Pasteur de Guinée, the Institut Pasteur de Madagascar, the Institut Pasteur de Tunis, the Pasteur Center in Cameroon.