Characterizing Risk at the Poultry-Pig Interface to Strengthen Surveillance for Novel Influenza Viruses in Lao PDR

This project is funded by the Global Emerging Infections Surveillance program of the US Department of Defense.

Influenza A viruses (IAV) circulate widely in animal and human populations, with important public health, animal health, and socio-economic consequences. The emergence of new IAV strains, which is facilitated by virus transmission between animal and human species, poses a considerable pandemic risk. With limited resources for animal influenza surveillance, there is a need to develop risk-based strategies that target subpopulations where the risk of novel IAV emergence is high. Designing cost-effective and practical surveillance strategies for early detection, prevention, and mitigation of novel IAVs requires understanding of risk “hotspots” in relation to livestock systems.

Aims and objectives

This study aims to characterise the risk of emergence and transmission of IAV in relation to swine and poultry production systems in the Lower Mekong sub-region, with a focus on areas of Laos bordering China. This will help inform the design of targeted, risk-based surveillance strategies for novel influenza virus detection in animals. The specific objectives are:

Objective 1: Conduct interviews, focus groups, and a cross-sectional survey among key actors, producers and traders in the pig value chain in northern Laos, to characterise pig production systems, trading networks, and their interface with poultry.

Objective 2: Initiate slaughterhouse sampling of pigs to determine influenza A viral prevalence and serological prevalence and assess the diversity of circulating virus stains.

Objective 3: Conduct epidemiological, contact network and model simulation analyses to assess the risk of influenza virus introduction and transmission within and between pig production systems.

Partners

The project is a collaboration between:

• London School of Hygiene & Tropical Medicine
• National Animal Health Laboratory, Vientiane, Laos
• NAMRU-2
• Vysnova Partners

People

At the London School of Hygiene & Tropical Medicine, the project involves:

• James Rudge
• Arata Hidano
• Hannah Holt
• Anna Durrance-Bagale

Understanding the risks of zoonotic disease from swine production systems in Cambodia (PigFluCam+)  

A study, funded by the US Defense Threat Reduction Agency, as of 2019.

Influenza pandemics present a profound global health and socio-economic threat, and are initiated by animal viruses adapting to sustained transmission in humans. However, little is known about the ecology and evolution of influenza viruses in pigs, particularly in low- and middle-income countries in Southeast Asia.

This four-year project aims to characterize zoonotic and pandemic risk from pig-rearing systems in Cambodia, with a focus on influenza. Such evidence can help inform where surveillance and control measures should be targeted. 

Objectives:

1. Identify spatio-temporal patterns in the epidemiology and diversity of swine influenza in relation to pig production systems;
2. Identify how rates of zoonotic influenza transmission vary across demographic and occupational groups;
3. Develop mathematical models of the influenza dynamics of influenza at the human-swine interface;
4. Promote and enhance capacity for One Health research, surveillance, and collaboration among the human health and veterinary communities in Cambodia.

Partners

The project is a collaboration between

• London School of Hygiene & Tropical Medicine
• Duke-NUS, Singapore
• University of Health Sciences, Cambodia
• National Animal Health and Production Research Institute, Cambodia
• NAMRU-2
• Livestock Development for Community Livelihood (formerly Celagrid), Cambodia

People

At the London School of Hygiene & Tropical Medicine, the project involves:

• Arata Hidano
• Hannah Holt
• William Leung
• James Rudge (PI)

Establishment of biopharmaceutical and animal vaccine production capacity in Thailand and neighbouring SE Asian countries

Led from University of Kent, this project aims to:

• produce life-saving Biopharmaceuticals in Thailand for the first time at a cost that allows wide access to patient
• produce a suite of veterinary vaccines against the major porcine disease that will be made available to farms in Thailand, resulting in a sustained reduction in livestock losses
• establish state of the art technical capacity for recombinant protein production by Thai groups, which can be expanded and consolidated for future growth
• give neighbouring Southeast Asian countries full access to the programme’s technology and expertise in order to effectively plan similar ventures

This project brings together:

• Thai groups at the forefront of the country’s new programme to produce recombinant proteins
• UK groups that have developed state of the art E. coli- and CHO cell-based expressed systems as well as down-stream processing and analytic tools
• Bangkok-based UK specialists in SE Asian healthcare, economic policies and dissemination tools

The work is funded by the Global Challenges Research Fund and will contribute towards several UN Sustainable Development Goals:

• Zero hunger
• No poverty
• Good health and well-being
• Industry, innovation and infrastructure

Partners

The project is a collaboration between:

• University of Kent
• London School of Hygiene & Tropical Medicine
• UCL
• BIOTEC
• Imperial College London
• National Biopharmaceutical Facility

People

At the London School of Hygiene & Tropical Medicine, the project involves:

• Richard Coker
• Fatim Lakha

Outputs

• Project brief (Thai)
• Project brief (English)

Health systems and antimicrobial resistance, Cambodia 

Visit the Health systems and antimicrobial resistance, Cambodia project website for more information.

Protecting Indonesia from the threat of antibiotic resistance (PINTAR)

PINTAR is a three-year research study, begun in 2018, to improve the use of antibiotics and ultimately reduce the global spread of antimicrobial resistance (AMR). Researchers analyse the way private drug sellers in Indonesia dispense antibiotics and how they interact with their clients. Based on this analysis, the team will design a comprehensive intervention to reduce the number of antibiotics that PDS sell inappropriately.

People

• Johanna Hanefeld
• Mishal Khan
• Marco Liverani
• Virginia Wiseman (PI)
• Shunmay Yeung

Completed Projects

Combating drug resistance through better governance of informal antibiotic sellers in Cambodia (HSRI CAM) 

What are the barriers to, and interventions for, improving governance of the informal healthcare sector? 

This case study investigates antibiotic dispensing in Cambodia by informal providers, to understand:

• the health system gaps they fill
• the features that allow them to become trusted health providers
• their knowledge of antibiotic
• policymakers' views on controlling inappropriate access to antibiotics

Despite being very commonly used for minor illnesses in LMIC, there is little research on informal health care providers and their role as sellers of antibiotics. This is the first project to investigate invisible medicine sellers (who provide health services without having a marked and specifically designated outlet for this purpose) in Cambodia. 

We conducted community focus group discussions in two peri-urban districts in Phnom Penh to identify all visible and invisible healthcare providers, and then interviewed all identified providers as well as policy actors at the community and national level.

People

• Mishal Khan

• Sonia Rego

Partners

• University of Health Sciences, Cambodia
• Vonthanak Saphonn
• Sovanthida Suy
• Sothavireak Bory

Papers

Prescription only access to antibiotics could exacerbate health inequalities in LMICs

Invisible medicine sellers and their use of antibiotics: a qualitative study in Cambodia

Is enhancing the professionalism of healthcare providers critical to tackling antimicrobial resistance in low- and middle-income countries?

Policy-relevant Evaluation of Health Care Provider Training in China

The Eli Lilly Multi-drug Resistant Tuberculosis Partnership (MDR-TB) funded the Chinese Centre for Disease Control and Prevention (China CDC) and China Medical Association to develop and implement a standardised healthcare provider training programme on TB/MDR-TB. The pilot project trained healthcare providers in 11 provinces.  

Mishal Khan and Shishi Wu designed and implemented an evaluation of the pilot programme in two phases, with the first phase focusing on identifying what indicators of training programme success are most valuable to Chinese policymakers.

End date 31 July 2019.

The AsiaFluCap Project

This project analysed how resources can be deployed effectively and efficiently in countries in Asia in the event of a pandemic. Funded by the European Commission, the goal was to provide a framework to evaluate health system operational capacity and systematically determine gaps in four settings (Vietnam, Indonesia, Thailand, Taiwan), in order support containment and mitigation of pandemic influenza. With additional support from the Rockefeller Foundation, the study was expanded to cover Lao PDR and Cambodia. 

With ministerial support across the sites, the results from this work inform revisions of strategic and operational pandemic influenza plans, provide a critical resource for the war room in the event of a pandemic and inform decisions about future resource allocation. 

Papers

Krumkamp R, Mounier-Jack S, Ahmad A, Reintjes R, Coker R. Evaluating health systems’ preparedness for emerging infectious diseases: A novel conceptual and analytic framework. Health Policy 98(2010) 91 - 97 

Krumkamp R, Kretzschmar M, Rudge J W, Ahmad A, Hanvoravongchai P, Westenhoefer J, Stein M, Putthasri W, Coker R. Health service resource needs for pandemic influenza in developing countries: a linked transmission dynamics, interventions and resource demand model. Epidemiol. Infect., 2010, 1-9

de Sa J, Mounier-Jack S, Darapheak C, Ly Khunbun N, Phetsouvanh R, Chanthakoummane N, Touch S, Phommasack R, Coker R. Responding to Pandemic Influenza in Cambodia and Lao PDR: Challenges in Moving from Strategy to Operation. Southeast Asian J Trop Med, 48(2010)

Hanvoravongchai P, Adisasmito W, Chau P N, Conseil A, de Sa J, Krumkamp R, Monier-Jack S, Phommasack B, Putthasri W, Shih CS, Touch S, Coker R. Pandemic influenza preparedness and health systems challenges in Asia: results from rapid analyses in 6 Asian countries. BMC Public Health, 2010 10:322

Adisasmito W, Hunter BM, Krumkamp R, Latief K, Rudge JW, Hanvoravongchai P, Coker RJ. Pandemic Influenza and Health System Resource Gaps in Bali: An Analysis Through a Resource Transmission Dynamics Model. Asia Pac J Public Health. 2011 Nov 14

Yu-Chen Hsu, Yi-Ta Yang, Shih-Yan Yang, Shu-Mei Chou, Jen-Hsiang Chuang. Analysis on District Medical Resources and Preparedness Gap on the Health Outcomes of the 2009 H1N1 Influenza Pandemic in Taiwan. Taiwan Epidemiology Bulletin. 2011 Nov 22/Vol.27/No.22

James W. Rudge, Piya Hanvoravongchai, Ralf Krumkamp, Irwin Chavez, Wiku Adisasmito, Pham Ngoc Chau, Bounlay Phommasak, Weerasak Putthasri, Chin-Shui Shih, Mart Stein, Aura Timen, Sok Touch, Ralf Reintjes, Richard Coker. Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories. PlosONE, 2012 7(2): e31800

Stein ML, Rudge JW, Coker R, van der Weijden C, Krumkamp R, Hanvoravongchai P, Chavez I, Putthasri W, Phommasack B, Adisasmito W, Touch S, Sat le M, Hsu YC, Kretzschmar M, Timen A. Development of a resource modelling tool to support decision makers in pandemic influenza preparedness: The AsiaFluCap Simulator. BMC Public Health. 2012 Oct 12;12:870

Hanvoravongchai P, Chavez I, Rudge JW, Touch S, Putthasri W, Chau PN, Phommasack B, Singhasivanon P, Coker R; iaFluCap Project Consortium. An analysis of health system resources in relation to pandemic response capacity in the Greater Mekong Subregion. Int J Health Geogr. 2012 Dec 14;11:53. doi: 10.1186/1476-072X-11-53.

Developing evidence-based investment options in support of pandemic preparedness policy in Cambodia (CamFlu)

Led by Tom Drake and funded by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ), this research investigated gaps in pandemic response capacity and cost-effective ways to fill them, in order to inform national ministries and international donors about where investments would yield maximum benefits for Cambodia’s health system. 

Specific outputs included:

• distribution pattern of health service resources throughout Cambodia
• scenarios of cost effective options to improve pandemic response capacity
• evaluation of public health impact of scaling up health service resources to respond to pandemic influenza
• evidence-based options to scale-up health service resources to respond to pandemic influenza in Cambodia

Surge in demand for health services: evaluating health system impact and capacity to respond in countries with limited resources 

This project, funded by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ), produced new information in regard to Indonesia’s health system surge capacity, in order to:

• equip disease modelers and health system planners with potential resource mobilization needs
• inform analyses using a resource-linked mathematical model for simulating pandemic influenza scenarios 
• generate more robust estimates of where, and in which resource types, gaps are most severe
• enable policy makers to make evidence-based decisions on resource reallocation across geographical and administrative boundaries
• improve the national preparedness plans for pandemics and national disasters by estimating the surge capacity of health facilities 

Molecular Epidemiology of Influenza in Bali, Indonesia (Bali MEI) 

Led by James Rudge and funded by Hoffmann La Roche, this study conducted five years of active surveillance and characterisation of influenza viruses in Bali. The project:

• utilised a network of 21 health facilities across all nine districts of Bali to collect nasopharyngeal swabs from patients presenting with influenza-like illness
• screened the swabs for Influenza A and B, 
• subtypted influenza A-positive samples and tested them for genetic markers of resistance to oseltamivir
• administered case-history questionnaires to measure socio-demographic and other risk factors 
• sequencing samples and conducted phylogenetic analysis

End date October 2014.

AVEX Registry

The Avian/Pandemic Flu Registry is an international, on-line observational research effort that uniquely collects information regarding symptoms, diagnosis, treatments, and outcomes of patients affected by human avian influenza. The Registry makes it possible for experts to evaluate data and to understand the epidemiology and health consequences of the spread of the disease, and to assess the effectiveness of various interventions.

Led by Marco Liverani and funded by the Avian/Pandemic Flu Registry, the London School of Hygiene and Tropical Medicine worked with collaborators in Indonesia (Universitas Indonesia), Cambodia (Ministry of Health) and Lao PDR (NEIDCO) to gather data on cases for inclusion in the Registry.

Control and Prevention of Tuberculosis (CAP-TB)  

This project involved a three-pronged, interdisciplinary, mixed-methods programme of research to analyse the operation and effectiveness of Tuberculosis/Multidrug Resistant Tuberculosis (MDRTB) programmes in Myanmar and Yunnan province, China.

1. Macro-economic analysis. An evaluation of the most efficient allocation of funding to ensure TB control, control of MDRTB prevalent cases, prevention of new cases of MDRTB, and control of HIV-associated TB. A focus on public health outcomes (changes in incidence of TB, changes in incidence of MDRTB, mortality, HIV-associated TB, DALYs; and costs based on aggregate allocations to prevention, detection, treatment elements)
2. Case control study: Analysis of the risk factors associated with MDRTB in previously treated patients and those never treated
3. Gender analysis of incentives/disincentives at patient, provider and health system level. A mixed methods analysis of gender impacts on disease susceptibility and diagnosis, health (and related) outcomes, and incentives

Partners

• National University Singapore (NUS)
• University of Public Health, Myanmar
• FHI

People

• Richard Coker
• Samantha Watson
• Mishal Khan

End date 31 December 2016.

Determination of the association between livestock systems and influenza prevalence and diversity in swine, Cambodia (PigFluCam) 

This research on influenza ecology at the human-animal interface in Cambodia set out to:

• enhance influenza surveillance and characterisation among swine in Cambodia
• characterise the prevalence and genetic diversity of influenza viruses in pigs across various modes and stages of pig production in Cambodia, in relation to pig densities, movements, and interspecies interactions
• develop mathematical models of influenza transmission in Cambodia’s pig sector, to explore the potential impact of changing livestock practices on zoonotic and pandemic risk

People

• James Rudge
• Richard Coker

End date 29 July 2016.