Background

Streptococcus pneumoniae, also known as the pneumococcus, is a Gram-positive pathogen recognized as a major cause of pneumonia worldwide. It resides as a commensal in the nasopharynx of healthy carriers, but in susceptible individuals this bacterium can spread to other body locations and cause life-threatening disease. The main group risks are the elderly, immunocompromised people and infants. In fact, approximately 900,000 children die each year due to pneumococcal disease, of which >90% occur in developing countries. In addition, a high number of pneumococcal infection cases are diagnosed in developed countries and can be associated with high morbidity in children and are an important factor that influences quality of life and produces significant mortality in adults. There are licensed polysaccharide-based vaccines to prevent pneumococcal infections, but their efficacy is limited. Therefore, pneumococcal community-acquired pneumonia (CAP) remains as an important health problem and once it has occurred, early diagnosis with accurate diagnostic methods is essential in order to provide patients with prompt and appropriate therapy. The ability to identify pneumococci as a causative agent in lung infections is quite limited and blood cultures are often negative. Serological diagnosis of pneumococcal disease based on a single antigen is often challenging, due to the interference of natural antibodies elicited by previous colonization events and the antigenic variability. Therefore, to better discriminate between diseased and healthy people, a combination of antigens would be desirable.

The Project

The aim of PNEUMOFLUIDICS is to develop an innovative point-of-care diagnostic for the early detection of Streptococcus pneumoniae (pneumococcus) infections on a serological basis. Results of multiplex analyses will be transferred to a microfluidic protein array (MPA), i.e. a biosensor on which proteins are immobilized and on which a novel serodiagnostic method can be established with minimal serum samples.

The Science

Research aims to develop a sensitive and quantitative tests for the rapid and specific detection of pneumococcal infections. For the validation of a microfluidic protein array (MPA), the detection of IgM antibodies as well as specific IgG antibodies will be performed in larger patient cohorts using initially well-established multiplex platforms for pneumococcal antigens. Selected pneumococcal antigens can also be used for immunostrips that will be probed with independent sets of patient sera. These immunostrips are a diagnostic test can be an easy-to-use tool for diagnosis in healthcare systems, especially in low-resource areas. The pneumococcal-specific MPA will be further used for a broad range of applications such as monitoring epidemiological episodes or discovering new protein vaccine candidates. This strategy will help to distinguish between patients with different diseases. The multiplex platforms or MPA can be employed in epidemiological surveillance programs to monitor possible outbreaks of pneumococcal disease around the world.

The Team

The PNEUMOFLUIDICS partners are:

• Coordinator : Prof. Dr. Sven Hammerschmidt,  Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomcis of Microbes,Universität Greifswald, Germany. 
• Brio Apps AlphaSip S.L. (BAA), Calle María de Luna 11, Nave 13, Zaragoza 50018, Spain, represented by the CEO, Miguel Angel Roncalés Poza
• Prof. Dr. Manuel J. Rodríguez Ortega, Departamento de Bioquímica y Biología Molecular, Edificio "Severo Ochoa", planta baja Campus de Rabanales, Universidad de Córdoba, Spain (subpartner of Brio Apps Alphasip)
• Prof Dr. Shinta Purwanto, Universitas Sam Ratulangi (USR), Jalan Kampus Bahu Malalayang, Kota Manado 95115, North Sulawesi Utara, Indonesia
• Dodi Safari, PhD, Eijkman Institute for Molecular Biology, Jl. Diponegoro no 69, Jakarta, Indonesia 10430 (associated partner)
• Dr. Moh Moh Htun, MBBS, MMedSc, PhD (Pathology),  Director (Research), Biomedical Research Centre (BRC), Department of Medical Research, No. 5, Ziwaka Road, Dagon Township, Yangon 11191, Myanmar

Contact: Prof. Dr. Sven Hammerschmidt; Email: sven.hammerschmidt@uni-greifswald.de

Featured image from:  Hammerschmidt, S., S. Wolff, A. Hocke, S. Rosseau, E. Muller, and M. Rohde. 2005.

Background 

A large majority of human diseases is due to zoonotic pathogens, and a significant proportion of those originate from domestic animals. Dog was the first domesticated animal, with the initial centre for domestication located in Asia, and it is currently the most widespread and abundant human commensal. Dogs play an important role of reservoirs for major public health infectious threats, such as rabies. However, apart from rabies, dog-human epidemiological relationships have received relatively little attention, with disease such as cystic echinococcosis being classified as a neglected zoonotic disease. Similarly, is still unclear what roles dogs may play in Asia in the epidemiology of leptospirosis, emerging rickettsiosis or Japanese encephalitis. A key knowledge gap is the paucity of information regarding the behavioral, ecological, and socio-economic determinants of dog-human interactions in SE Asia, in order to improve the management of dog populations for veterinary and public health benefits.

The Project 

SEA-dog-SEA project will study the social and ecological dimensions of dog zoonotic diseases in rural sites selected in Indonesia (Bali), with additional sites in Cambodia and Thailand supported by complementary surveys. The field surveys will combine: i) dog ecology, population dynamics and contact network (GPS tracking, camera traps); ii) dog shared microbiome and prevalence of selected dog-borne diseases (e.g. leptospirosis, internal helminths and rickettsia); iii) perceptions and practices of local populations regarding dog keeping and management (anthropology, social-network of owners…): iv) modelling of multi-layered networks and zoonotic risks associated with dogs. The comparisons between countries will highlight the main drivers of dog-associated zoonotic risks and allow for improved management of dog populations for better prevention of spill-over risks.

The Science

The project adopts an interdisciplinary approach to analyse the linkages between dogs’ spatial behaviour and population dynamics with the socio-cultural and environmental characteristics of the study sites. The movements and distribution of selected dogs will be assessed during radio-tracking sessions using GPS collars, combined with camera-trap monitoring of marked/unmarked dog populations. A questionnaire survey (translated in Balinese/Thai/Khmer), key-informants interviews and participatory mapping will be carried out in the participating villages in order to assess local perceptions and practices regarding dog keeping and management. The screening of zoonotic pathogens in selected dogs will use standardised laboratory diagnostic techniques (rabies antibodies, leptospirosis, rickettsiosis… depending on the sites), while NGSs will be used to analyse the microbiota of sympatric free-ranging dogs based on faecal samples collected. The analysis of contact networks between dogs, and associated social networks between dog-owners, will aim at identifying key individuals/”superspreaders” and key areas/resources to target the management of spill-over risks..

The Team

The SEA-dog-SEA paartners are:

• SEA-Dog-SEA project associates several European and SE Asian partners, most of them being members of GREASE network.

• Coordinator: CIRAD, UMR117-ASTRE, Montpellier, France and Kasetsart University, Thailand
• Co-Principal Investigator: One Health/EcoHealth Resource Center of the University Gadjah Mada, Yogyakarta, Indonesia.
• Co-Principal Investigator: Conservation Genetics Laboratory,Université de Liège, Liège, Belgique.
• Institutions of other associate project partners: Institut Pasteur Cambodia (Cambodia), Kasetsart University (Thailand), Udayana University (Indonesia)

Contact

Michel de Garine-Wichatitsky: degarine@cirad.fr

Featured image from unsplash.com

Background

Malaria and human immunodeficiency virus (HIV) are two highly dangerous global infectious diseases that cause major harm especially to societies in the Southeast Asia (SEA) region. Current diagnostic technologies are cumbersome, expensive and require sophisticated equipment that can only be maintained in specialized hospitals. This means unfortunately that diagnostics are not available where and when truly needed. Specifically, current diagnostic tests for Malaria are based on microscopy, antigen/antibody detection and nucleic acid-based assays. The gold standard for the detection of mutations in HIV is Sanger sequencing. At the same time, recent advancements in biosensor and rapid-test diagnostics have demonstrated their powerful potential in addressing exactly these complex diagnostic needs in resource-limited settings. Based on our joint diverse and broad strong expertise in Malaria, HIV infectious diseases, biosensors, and nucleic-acid based systems, we propose the development of paper-based and biosensor technologies for the simultaneous detection of Malaria or HIV drug resistance, leading to a simple and low-cost, yet highly reliable and sensitive diagnostic kit.

The Project

The MalHivPOCTs project aims to develop rapid point-of-care diagnostic devices that will detect Malaria (Plasmodium genus and two species of Plamodium) and HIV drug resistance to antiretroviral using isothermal amplification methods, paper-based microfluidics and visual readout.

This project will involve parallel developments of the different components of the paper-based device from 4 partners (Germany, Indonesia, Philippines and Thailand) and hence take advantage of their respective expertise in a collaborative effort.

The Science

The MalHivPOCTs will be based on developing strategies to lyse the pathogens in the blood sample, extract DNA/RNA, amplify specific target sequences, and finally detect the product in a set of paper-based analytical devices (PADs). The device will be made from a patterned piece of chromatography paper with wax ink functioning as hydrophobic barriers and hydrophilic channel. It will integrate all sample assay steps from lysis to detection. Electrospun nanofibers will be studied to enhance DNA/RNA extraction. The recombinase polymerase amplification (RPA) is used to amplify DNA/RNA and single or simultaneous detection using colloidal gold or liposomes will result in visual detection.

The Team:

The MalHivPOCTs partners are:

• • Dr. Patsamon Rijiravanich: National Center for Genetic Engineering and Biotechnology (BIOTEC), Pathum Thani, Thailand, (Project Coordinator)
  • King Mongkut’s University of Technology Thonburi (KMUTT), Bangkok, Thailand
  • Prof. Dr. dr. Fitri Engga Luki: Universitas Brawijaya (UB), Brawijaya, Indonesia,
  • Angelo dela Tonga: University of the Philippines Manila, Manila (UPM), Manila, Philippines
  • Prof. Dr. Antje Bauemner: University of Regensburg (UREG), Regensburg, Germany
  • Universitas Islam Indonesia (UII), Yogyakarta, Indonesia,

Contact:

Patsamon Rijiravanich: patsamon.rij@biotec.or.th

Featured image from unsplash.com

Background

Hepatitis B is one of the major causes of acute and chronic viral hepatitis, an infection that affects the liver. According to World Health Organization (WHO), an estimated 257 million people were living with hepatitis B virus (HBV) infection in 2015 and Hepatitis B resulted in 887 000 deaths, mostly from complications (including cirrhosis and hepatocellular carcinoma). The virus is transmitted through contact with the blood or other body fluids of an infected person. It constitutes a public health threat and is an important occupational hazard for health workers. In addition, only 9% of HBV-infected people are diagnosed always according to WHO. One reason is the limited access to affordable hepatitis tests and especially ones that can be performed by non-laboratory staff. Hence the development of diagnostic tools of infection by HBV is crucial on a public health point of view. 

The Project

The project aims to develop new diagnostic tests of Hepatitis B virus that should be inexpensive, easy to use and highly sensitive. To this end, paper-based label-free electrochemical immunosensor will be designed to integrate silver nanoparticles as redox probes for signal enhancement of the assay. Special attention will be carried out on the ease of synthesis and use.

The Science

Hepatitis B virus has a lipid envelope containing hepatitis B surface antigen (HBsAg) and this antigen is found in the blood during the incubation period and in case of acute and chronic infection. Therefore, HBsAg is considered as a major index of hepatitis B viruses (HBV) infection. Due to the highly specific binding of antigens and antibodies, immunoassays are particularly adapted to detect HBsAg. Label-free electrochemical immunosensors has attracted interest since a long time to give up the classical sandwich-type structure. Indeed this structure requires to perform several biorecognition steps to introduce a label, like in ELISA tests. On another hand, nanomaterial has also intensively been investigated for signal enhancement and improvement of the limit of detection of immunosensors due to their intrinsic advantages such as electrical properties and large surface area. Lastly, the development of microfluidic devices has been stimulated in the field of sensors with the goal to produce low-cost point-of-care diagnostics and on-site detection. Recent developments suggest that bioassays on paper-based substrates may be an interesting alternative for solid support due to the numerous advantages of paper (abundance, inexpensive, sustainable) and variety of inkjet printing techniques available for its functionalization. 

The Team

The PHIShINg partners are: 

Dr. Philippe Banet: University of Cergy Portoise (UCG) , France

Dr. Jaroon Jakmune: Chiang May University (CMU), Thailand

Dr. Akhmad Sabarudin: Brawijaya University (UB), Indonesia

Contact: 

Philippe Banet : philippe.banet@u-cergy.fr

Featured image from unsplash.com

Background:

Animal farming is a worldwide industry, with millions of people involved in the production of animal products every day. Protecting farmed animals from disease and infection is therefore vitally important not only for livestock and consumer wellbeing, but also for those working within the farming industry.

The Project:

The FarmResist project will use a “One Health” approach, to investigate the occupational risk for pig and poultry farmers of of catching animal-associated ESBL-E and colistin-resistant enterobacteria. It is hoped that this research will lead to the development of preventive measures for avoiding the transmission of zoonotic bacteria from animal to farmers, as well as reducing the spread of antibioresistance in the environment.

The Science:

The researchers will study both small family farms and medium-big industrial farms. At each farm, faecal samples of farmers, animals (included pets and rodents) will be collected. The prevalence, genotyping and microbiota diversity will be studied by using both culture-dependent methods, molecular biology and next generation sequencing.

The association between farm parameters and antimicrobial resistance will be analysed in order to propose preventive measures to avoid the transmission of zoonotic bacteria from animal to farmers and to reduce the spread of antibioresistance in the environment.  The influence of faecal carriage of ESBL-E or colistin resistant bacteria on the faecal microbiota of farmers will then also be studied.

The Team:

The FarmResist partners are:

• Visanu Thamlikitkul, Siriraj Hospital, Mahidol University.

• Pariwat Poolperm, Kasetsart University, Bangkok, Dpt of Farm Resources and Production Medecine.

• Suwit Chotinun, Chiang Mai University, poultry clinic.
• Morand Serge, Kasetsart University, Bangkok, Faculty Veterinary Technology

• Jean-Marc Rolain, URMITE- IHU Méditerranée Infection, Valorization and Transfer, Marseille, France

• Morand Serge, CNRS- Cirad, France
• Markus Hilty, IFIK, Bern University, Switzerland
• Oppliger Anne, IST, Lausanne University, Switzerland

Contact:

Anne Oppliger: Anne.Oppliger@hospvd.ch

Background:

Dengue and Zika are viruses spread through mosquito bites which can cause serious illness and even death. They are highly prevalent both in Southeast Asia, with an estimated 390 million dengue infections worldwide every year.[1] The number of outbreaks for both viruses is increasing every year, and recent cases of Zika outbreaks in French Polynesia and Brazil in 2013 and 2014 made news around the world.  As of 2016, the WHO has declared ZIKV infection is a Public Health Emergency of International Concern.

There is currently no specific treatment for either the Dengue or Zika viruses. A Zika vaccine is yet to be discovered, while despite two decades of dengue vaccine development, only one vaccine has been licensed in a few countries, which not cover all 4 types of the virus, and cannot be used by all ages – leaving those under the age of 9 or over 45 at risk.

The Project:

The DeZi project aims to address this issue by proposing new concepts for vaccine development. It hopes to addresses the bottleneck of flavivirus vaccine development starting from the hypothesis that development of these vaccines should be based on an integrative approach by studying cross-reactivity among flaviviruses.

To do this, the project team will firstly transfer technology of DNA vaccine production from France to Thailand. Once in place, they will aim to demonstrate that their vaccine protects against dengue virus.

The Science:

The researchers believe that a more efficient dengue vaccine should contain either T-cell epitopes or both B-and T-cell epitopes. The best animal model for prediction of vaccine efficacy should demonstrate its protection against the effect of ADE, not only primary infection.

This would prevent imbalanced immunity among the four serotypes upon tetravalent live attenuated dengue vaccine. In addition, these T cells epitopes will allow us to create a single component vaccine composed of multiple Dengue & Zika epitopes (4DZVx), which will cover concurrently the four DENV serotypes and ZIKV at the same time.

The team hypothesise that balanced immunity against all four DENV serotypes and ZIKV with a protective T cell response can prevent the risk of ADE. The 4DZVx will include the T cell component of the anti-DENV and -ZIKV response. Ideally, the T-cell response will protect against the adverse effect of ADE due to pre-existing antibodies induced following primary infections as occurring in endemic countries.

The Team:

The DeZi partners are:

• Bionet Asia, Bangkok, Thailand, http://www.bionet-asia.com
• St. Luke’s College of Medicine, Manila, Philippines, http://stlukesmedcollege.edu.ph/
• Institut Pasteur Cambodia, Phnom Pehn, Cambodia, http://www.pasteur-kh.org
• Institut Pasteur, Paris, France, https://www.pasteur.fr/fr
• InCellArt, Nantes, France, http://www.incellart.com

Contact:

Anavaj Sakuntabhai: anavaj@pasteur.fr 

[1] https://www.webmd.com/a-to-z-guides/dengue-fever-reference#1

Background

Antibiotics are life-saving medicines, but increasing antibiotic resistant bacteria are making common infections increasingly difficult to treat, and antibiotic resistance is now recognised as one of the greatest threats to global health. The main cause of this increasing resistance is the unnecessary use of antibiotics, which forces bacteria to adapt in the so-called “selective pressure”.

During normal childbirth without complications, antibiotics should not be used; however, reports and small studies from Asian countries show alarmingly high levels of antibiotic use in these cases. Similarly, there is a worrying trend of over-prescribing and poor use of antibiotics for treating children under five years of age.  Focusing particularly on Lao PDR, little is known about the situation of potential overuse and misuse of antibiotics during childbirth and for treating children.

The Project

The CAREChild project aims to understand and improve antibiotic use in relation to pregnancy, childbirth and children in Lao PDR with the long-term aim of containing antibiotic resistance.

The team will explore and assess perceptions, knowledge, attitudes and reported practice as well as actual practice among health care providers and in the community, to estimate antibiotic prescribing to estimate the situation of antibiotic resistance, focusing particularly on ESBLs in Escherichia coli in infections and carriage in faecal samples.

The Science

The study is an intervention study with a formative phase leading to the development of the intervention, which will be implemented and evaluated through time series analysis. The content of the innovative intervention will be based on qualitative and quantitative findings from the formative phase and contain two components: a participatory and process-based educational intervention aimed towards health care providers, and an mHealth component aimed at pregnant women, and mothers of children under five years of age.

The main outcome measure will be the proportion of uncomplicated vaginal deliveries during which antibiotics are used, and to show changes over time during the intervention using time series analysis over a 24-month period. Additional outcomes will be knowledge and attitudes to antibiotic use and resistance, as well as antibiotic resistance levels.

Data will be collected using structured interviews regarding knowledge and practice of antibiotic use and resistance. In addition, individual interviews and focus group discussions will be held with relevant stakeholders to further understand perceptions about antibiotic use and resistance and how the situation can be improved.

The study is expected to generate important knowledge regarding antibiotic use and resistance development in Lao PDR, but with potential implications to other South East Asian countries and beyond. Furthermore, our project aims to strengthen collaborative ties between Laos-Sweden-Vietnam and to create a long-term collaboration between the partner countries that will serve the purpose of exchange of knowledge and expertise between those countries.

The Team:

The CAREChild partners are:

• Karolinska Institutet
• Ministry of Health, Department of Food and Drugs, Vientiane Laos
• University of Health Sciences, Vientiane Laos
• National Institute of Public Health, Vientiane Laos
• Health Department of Vientiane Capital, Vientiane Laos
• Hanoi Medical University, Hanoi, Vietnam
• Hanoi University of Pharmacy, Hanoi, Vietnam

Contact:

Cecilia Stålsby Lundborg: Cecilia.Stalsby.Lundborg@ki.se

The Project:

Vaccination is one of the most effective strategies for the prevention and control of infectious diseases. However, not all vaccine are currently available in Thailand, particularly those for endemic diseases. This is in part due to low incidence and a lack of public information, but cost also plays an important factor, as most commercially available vaccines are imported, and too expensive for the general public to afford.

 The ThaiVacc project aims to address this issue through the research and development of vaccines for leptospirosis and dengue fever. By working with an international team of researchers in Thailand, Switzerland and France,  the project will not only help in strengthening the potential in vaccine research and development in Thailand, but will allow for knowledge and technology transfer between project partners in Europe and Southeast Asia.

The Science:

The project will be focused on the following activities:

• Investigating the use of adjuvant systems in order to enhance the immunogenic properties of new multiple subunit vaccines for leptospirosis and suitable tetravalent DNA vaccine for dengue fever to allow higher immunogenicity and enhanced protection.
• Developing new oral vaccination approaches against leptospirosis and dengue, which combine M-cell targeting strategies and specific mucosal adjuvants.
• Organizing a workshop on mucosal vaccination in Chulalongkorn University, with the collaboration of Swiss and French partners.

The Team:

The ThaiVacc partners are:

• Chula Vaccine Research Center (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, http://www.chulavrc.org
• University of Lausanne (UNIL), Lausanne, Switzerland, http://www.unil.ch/index.html
• University of Geneva (UNIGE), Geneva, Switzerland, https://www.unige.ch/
• Université Jean Monnet Saint-Etienne (UJM), Saint-Etienne, France, https://www.univ-st-etienne.fr/fr/index.html

Contact:

Assoc. Prof. Dr. Kanitha Patarakul, MD, PhD: Kanitha.Pa@chula.ac.th

The Project:

Patients suffering from serious infections which cannot be cured with standard treatments are prescribed so called ‘last-resort’ antibiotics, such as carbapenem and colistin. They are used only when all other drug options have failed, and can be vital for saving lives.

However, with growing concern over antibiotic resistance, studies are needed to ensure infections can be safely controlled in the future.

The PlasmID-SEA project will use state-of-the-art smartphone-based microscopy to study plasmids that cause carbapenem and colistin resistance, and will use this information for infection control, epidemiological studies and diagnostics.

The Science:

This project will study plasmids which cause resistance against carbapenem and colistin antibiotics in Southeast Asia. To do this, the researchers will use a modern technique, based on optical DNA mapping, to analyse single plasmids through smartphone-based microscopy. The assay will then be transferred to a smartphone-based instrument, thus guaranteeing its long-term sustainable use in the region.

The Team:

The PlasmID-SEA partners are:

• Chalmers University of Technology, Gothenburg, Sweden https://www.chalmers.se/en (Project coordinator)
• Siriraj Hospital, Mahidol University, Bangkok, Thailand; http://www2.si.mahidol.ac.th/en/departments/
• University of Health Sciences, Vientiane, Laos; http://www.uhs.edu.la/
• Vietnam National Children’s Hospital, Hanoi, Vietnam (external partner); http://benhviennhitrunguong.org.vn/

Karolinska University Hospital, Stockholm, Sweden https://www.karolinska.se/en

Contact:

Fredrik Westerlund: fredrikw@chalmers.se