Giuseppe
Emeritus
To see full texts of these abstracts, please follow the links:
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Contents:
(1.1) Antiviral Drugs for the Control of Pandemic Influenza Virus
(1.2) Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat
(1.3) Prevention and Control of Avian Influenza in Singapore
(1.4) Preparing for an Influenza Pandemic in Singapore
(1.5) Avian Influenza and Pandemic Influenza Preparedness in Hong Kong
(1.6) Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia [Supari]
(1.7) A Global Perspective on Avian Influenza
(1.8) Twentieth Century Influenza Pandemics in Singapore
(1.9) The Efficacy of Influenza Vaccination in Healthcare Workers in a Tropical Setting: A Prospective Investigator Blinded Observational Study
(1.10) A Cross-sectional Study of Primary-care Physicians in Singapore on Their Concerns and Preparedness for an Avian Influenza Outbreak
(1.11) Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
See original abstracts at the source site. EDITED.]
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(1.1) Antiviral Drugs for the Control of Pandemic Influenza Virus
Richard J Sugrue,1PhD, Boon-Huan Tan,2PhD, Dawn SY Yeo,1MSc, Richard Sutejo,1BSc (Hons) - 1 Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore - 2 Detection and Diagnostics Laboratory, Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore - Address for Correspondence: Dr Richard J Sugrue, Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University,
60 Nanyang Drive, Singapore 637551 - Email:rjsugrue@ntu.edu.sg
Abstract
In the advent of an influenza virus pandemic it is likely that the administration of antiviral drugs will be an important first line of defence against the virus.
The drugs currently in use are effective against seasonal influenza virus infection, and some cases have been used in the treatment of patients infected with the avian H5N1 influenza virus.
However, it is becoming clear that the emergence of drug-resistant viruses will potentially be a major problem in the future efforts to control influenza virus infection.
In addition, during a new pandemic, sufficient quantities of these agents will need to be distributed to many different parts of the world, possibly at short notice.
In this review we provide an overview of some of the drugs that are currently available for the treatment and prevention of influenza virus infection.
In addition, basic research on influenza virus is providing a much better understanding of the biology of the virus, which is offering the possibility of new anti-influenza virus drugs.
We therefore also review some new antiviral strategies that are being reported in the scientific literature, which may form the basis of the next generation of antiviral strategies during a future influenza virus pandemic.
Ann Acad Med Singapore 2008;37:518-24
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(1.2) Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat
Alan W Hampson,1,2BSc, MSc, Hon MD - 1 Interflu Pty Ltd - 2 Honorary Senior Research Fellow, School of Applied Sciences and Engineering, Monash University - Address for Correspondence: Dr Alan William Hampson, 6 Monica Street East Doncaster Victoria 3109, Australia. - Email: Interflu@bigpond.net.au
Abstract
Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic.
The bulk of current vaccines are inactivated split virus vaccines produced from egggrown virus and have only modest improvements compared with those first introduced over 60 years ago.
Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically na?ve recipients.
The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity.
There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic.
New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.
Ann Acad Med Singapore 2008;37:510-7
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(1.3) Prevention and Control of Avian Influenza in Singapore
Hon Keong Leong,1BVSc (Massey), MSc (Lond), Cheryl S Goh,1BVSc (Hons) (Melb), Siang Thai Chew,2DVM (UPM), MS (VPH) (Texas A&M), Chee Wee Lim,3BVMS (Glas), MMDV (Manchester), Yueh Nuo Lin,3BSc (Hons) (Monash), Siow Foong Chang,2BVMS (Glas), MSc (Lond), Him Hoo Yap,2BVSc (Hons) (Queensland), MPVM (UC Davis), Sin Bin Chua,2BVSc (Hons) (Queensland) - 1 Agri-Food and Veterinary Authority, 5 Maxwell Road, #04-00, Tower Block, MND Complex, Singapore 069110 - 2 Inspection Services & Epidemiology Division, Veterinary Public Health Centre, 10 Perahu Road, Singapore 718837 - 3 Animal & Plant Health Laboratories, 6 Perahu Road, Singapore 718827 - Address for Correspondence: Dr Leong Hon Keong, Inspection Services & Epidemiology Division, Veterinary Public Health Centre, 10 Perahu Road, Singapore - 718837. Email: leong_hon_keong@ava.gov.sg
Abstract
The highly pathogenic avian influenza (HPAI) H5N1 virus was first detected in 1996 in Guangdong, China.
Since 2003, H5N1 outbreaks have been reported in parts of Asia, Europe, the Middle East, and Africa.
It is currently entrenched among poultry in parts of Asia and poses a major challenge to animal and human health.
Singapore is free from HPAI. Given Singapore?s need to import food, the Agri-Food and Veterinary Authority (AVA) has adopted a pro-active risk management system to prevent the introduction of HPAI.
AVA?s approach maybe described as a multi-layered control strategy for the prevention and control of HPAI. The strategy includes control measures at source, border control measures, local control measures and emergency preparedness.
Ann Acad Med Singapore 2008;37:504-9
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(1.4) Preparing for an Influenza Pandemic in Singapore
Jeffery Cutter,1MMed (PH), MSc, FAMS - 1 Ministry of Health, Singapore - Address for Correspondence: Dr Jeffery Cutter, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854. - Email: Jeffery_cutter@moh.gov.sg
Abstract
The national strategy against pandemic influenza essentially consists of 3 prongs:
(i) effective surveillance,
(ii) mitigation of the pandemic?s impact, and
(iii) render the population immune through vaccination.
When the pandemic hits Singapore, the response plan aims to achieve the following 3 outcomes:
(i) maintenance of essential services to limit social and economic disruption,
(ii) reduction of morbidity and mortality through antiviral treatment, and
(iii) slow and limit the spread of influenza to reduce the surge on healthcare services.
The biggest challenge will come from managing the surge of demand on healthcare services. A high level of preparedness will help healthcare services better cope with the surge.
Ann Acad Med Singapore 2008;37:497-503
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(1.5) Avian Influenza and Pandemic Influenza Preparedness in Hong Kong
Ping Yan Lam - 1FHKAM (Community Medicine), FFPH (UK), FRACMA - Address for Correspondence: Dr Lam Ping Yan, 21/F, Wu Chung House, 213 Queen?s Road East, Wan Chai, Hong Kong. Email: pylam@dh.gov.hk
Introduction
In 1997, Hong Kong became reputed by identifying the first instance of human infection with avian influenza H5N1.
A total of 18 cases occurred that year resulted in 6 deaths.1-6 The outbreak was completely terminated after the culling of over 1.5 million chickens.
In 2003, two H5N1 human cases were again detected, and subsequent epidemiological investigations showed they had acquired the infection outside Hong Kong.7
Since 2004, while the virus appears from time to time in the wild bird population, Hong Kong has remained free from H5N1 outbreaks in humans and live poultry.8
Meanwhile, since 2003, outbreaks of avian influenza H5N1 among poultry and humans have been reported in an increasing number of countries.
In view of the epizootic and epidemiological situation, the World Health Organization (WHO) concluded that among all highly pathogenic avian influenza viruses, H5N1 is probably the most threatening for human health and is a likely candidate for causing the next pandemic.9
Pandemic Planning Framework
Since 2005, the Hong Kong Special Administrative Region Government (HKSARG) has developed an updated pandemic preparedness plan with specific reference to avian influenza.
The plan is underpinned by several strategic principles, namely reducing the risk of human infection, detecting pandemic influenza in a timely manner, and enhancing emergency preparedness and response.10
The plan sets out a three-tier response system (Alert Response Level, Serious Response Level and Emergency Response Level), which provides the command, control and coordination framework for emergency response.11,12
These levels are based on different risk-graded epidemiological scenarios relevant to Hong Kong (Table 1), and each of them prescribes a corresponding set of public health actions. Reference is made with regard to strategies 1 The Government of the Hong Kong SAR
Abstract
Avian influenza A H5N1 continues to be a major threat to global public health as it is a likely candidate for the next influenza pandemic.
To protect public health and avert potential disruption to the economy, the Hong Kong Special Administrative Region Government has committed substantial effort in preparedness for avian and pandemic influenza. Public health infrastructures for emerging infectious diseases have been developed to enhance command, control and coordination of emergency response. Strategies against avian and pandemic influenza are formulated to reduce opportunities for human infection, detect pandemic influenza timely, and enhance emergency preparedness and response capacity. Key components of the pandemic response include strengthening disease surveillance systems, updating legislation on infectious disease prevention and control, enhancing traveller health measures, building surge capacity, maintaining adequate pharmaceutical stockpiles, and ensuring business continuity during crisis.
Challenges from avian and pandemic influenza are not to be underestimated. Implementing quarantine and social distancing measures to contain or mitigate the spread of pandemic influenza is problematic in a highly urbanised city like Hong Kong as they involved complex operational and ethical issues. Sustaining effective risk communication campaigns during interpandemic times is another challenge. Being a member of the global village, Hong Kong is committed to contributing its share of efforts and collaborating with health authorities internationally in combating our common public health enemy.
Ann Acad Med Singapore 2008;37:489-96
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(1.6) Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia
Endang R Sedyaningsih,1,2DrPH, Siti Isfandari,1,2MA, Triono Soendoro,2PhD, Siti Fadilah Supari,3DR
Abstract
Introduction:
As the country hardest hit by avian influenza, both in poultry and in human, Indonesia?s decision to withhold samples of avian influenza virus A (H5N1) has fired up a global controversy. The objective of this paper is to describe the position taken by Indonesia in the events leading to the decision and in those conducted to resolve the situation.
Methods:
The sources for this paper are the Indonesian human influenza A(H5N1) case reports and study results, summaries, minutes and reports of national and international meetings of virus sharing, and other related Indonesian and WHO documents.
Results:
The International Health Regulations 2005 have been applied in different ways based on different interpretations. While one party insists on the importance of free, non-conditional, virus sharing for risk assessment and risk response, Indonesia ? as supported by most of the developing countries ? stresses on the more basic principles such as sovereignty of a country over its biological materials, transparency of the global system, and equity between developed and developing nations.
Conclusions:
This event demonstrates the unresolved imbalance between the affluent high-tech countries and the poor agriculture-based countries. Regional, global and in-country meetings must continue to be conducted to find solutions acceptable to all.
Ann Acad Med Singapore 2008;37:482-8
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(1.7) A Global Perspective on Avian Influenza
Adrian Ong,1MBBS, Dip ABIM (Inf Dis), MPH, Mary Kindhauser,1MA, Ian Smith,1MB,ChB, MPH, Margaret Chan2
Abstract
Global public health security is both a collective aspiration and a mutual responsibility that demands cooperative action at all levels.
The expansion of the current H5N1 avian influenza enzootic and its incursion into human health presents a real and significant threat of an influenza pandemic.
The world has for the first time an unprecedented opportunity for pandemic preparation.
Current global efforts to tackle the H5N1 pandemic threat are centred around the framework of the International Health Regulations (2005) that requires countries to openly share disease intelligence including clinical samples, viruses and epidemiological information.
Present international initiatives also seek to establish more equitable allocation and sharing mechanisms for developing countries, of therapeutic resources, public health interventions and other broadbased support in the event of a pandemic.
To be sustainable, country preparatory efforts need to be integrated within wider national emergency preparedness frameworks and emphasise the strengthening of basic capacities in disease surveillance, outbreak response and health systems that can respond to a range of public health emergencies.
Such capacity building represents permanent investments in health that will have enduring benefits beyond a pandemic. Preparations must also go beyond the health sector; greater promotion of intersectoral cooperation and an adoption of a whole-of-society approach to preparation is recommended.
Broad collaboration is vital in addressing the complex challenge posed by influenza to our collective security.
Ann Acad Med Singapore 2008;37:477-81
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(1.8) Twentieth Century Influenza Pandemics in Singapore
Vernon J Lee,1,2MBBS, MPH, MBA, Chia Siong Wong,1MBBS, MMed, Paul A Tambyah,3,4MD, FAMS, Jeffery Cutter,5MMed, MSc, FAMS, Mark I Chen,1MBBS, MMed, MSc, Kee Tai Goh,6MMed, MD, FAMS - 1 Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore - 2 Health Services and Outcomes Research, National Healthcare Group, Singapore - 3 Yong Yoo Lin School of Medicine, National University of Singapore, Singapore - 4 Department of Medicine, National University Hospital, Singapore - 5 Communicable Diseases Division, Ministry of Health, Singapore - 6 Ministry of Health, Singapore - Address for Correspondence: Dr Vernon J Lee, Block 802, Communicable Disease Centre, Moulmein Road, Singapore 308433. - Email: vernonljm@hotmail.com
Abstract
Introduction:
Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted.
Materials and Methods:
We reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore.
Results:
The 1918 epidemic in Singapore occurred in 2 waves ? June to July, and October to November ? resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics.
Conclusions:
Tropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.
Ann Acad Med Singapore 2008;37:470-6
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(1.9) The Efficacy of Influenza Vaccination in Healthcare Workers in a Tropical Setting: A Prospective Investigator Blinded Observational Study
Si Wei Kheok,1 Chia Yin Chong,2MBBS, M Med (Paeds), FRCPCH, Grace McCarthy,1,3MD, Wai Yee Lim,2RN, Khean Teik Goh,4MBBS, M Med (Fam Med), Lubna Razak,4MPH, Nancy WS Tee,2MBBS, FRCPA, Paul Ananth Tambyah,1,4MBBS, FAMS - 1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore - 2 Kandang Kerbau Women?s and Children?s Hospital, Singapore - 3 Duke University Health System, Durham NC, USA - 4 National University Hospital, Singapore - Address for Correspondence: A/Prof Paul Ananth Tambyah, Division of Infectious Diseases, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, Singapore 119074. - Email: mdcpat@nus.edu.sg
Abstract
Introduction:
Influenza vaccine has been shown to be highly effective in temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs) are advised to receive regular influenza vaccination to protect themselves and their patients. However, there are limited data on the efficacy of influenza vaccine in HCWs in the tropics.
Materials and Methods:
In this observational, investigator blinded cohort study, bi-monthly questionnaires recording influenzalike illness (ILI) episodes and medical leave were administered to 541 HCWs at the Singapore
National University Hospital and KK Women?s and Children?s Hospital from 2004 to 2005. ILI was defined according to a standard symptom score.
Results:
Baseline characteristics were comparable in both the vaccinated and non-vaccinated groups. Overall, the relative risk of selfreported ILI in vaccinated HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P = 0.107]; medical leave taken was lower in the vaccinated group [mean 0.26 ? 0.6 days per visit, compared with 0.30 ? 0.5 days in the non-vaccinated group (P = 0.40)]. Because of the reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort and determined that the group which received a matched vaccine had a relative risk of ILI of 0.49 (95% CI, 0.37-0.66; P <0.001), achieving a vaccine efficacy of 51%. Mean medical leave decreased significantly in HCWs who
received the matched vaccine, compared with those who did not receive vaccination (0.13 ? 0.3 vs 0.30 ? 0.5; P <0.001) and with HCWs vaccinated with mismatched strains (0.13 ? 0.3 vs 0.39 ? 0.9; P = 0.01).
Conclusions:
A well-matched influenza vaccine is effective in preventing ILI and reducing sickness absence in healthcare workers in tropical settings. Efforts need to be made to increase influenza vaccination rates and to improve the currently available vaccines.
Ann Acad Med Singapore 2008;37:465-9
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(1.10) A Cross-sectional Study of Primary-care Physicians in Singapore on Their Concerns and Preparedness for an Avian Influenza Outbreak
Teck Yee Wong,1MBBS, M Med (Fam Med), Gerald CH Koh,1MBBS, M Med (Fam Med), FCFP, Seng Kwing Cheong,1MBBS, M Med (Fam Med), FCFP, Meena Sundram,2MBBS, M Med (Fam Med), Kelvin Koh,3MBBS, M Med (Fam Med), MCFP, Sin Eng Chia,1MBBS, MSc (OM), MD, David Koh,1MBBS, PhD, FAMS - 1 Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore - 2 National Healthcare Group Polyclinics, Singapore - 3 SingHealth Polyclinics, Singapore - Address for Correspondence: Dr Wong Teck Yee, Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. Email: cofwty@nus.edu.sg
Abstract
Introduction:
During an avian influenza (AI) pandemic, primary-care physicians (PCPs) are expected to play key roles in the prevention and control of the disease. Different groups of PCPs could have different concerns and preparedness level. We assessed the concerns, perceived impact and preparedness for an outbreak among PCPs in Singapore.
Materials and Methods:
A cross-sectional survey of PCPs working in private practice (n = 200) and public clinics (n = 205) from March to June 2006 with an anonymous self-administered questionnaire on concerns (12- items), perceived impact (10 items) and preparedness (10 items) for an outbreak.
Results:
Two hundred and eighty-five PCPs responded ? 149 (response rate: 72.7%) public and 136 (response rate: 67.3%) private. The majority were concerned about risk to their health from their occupation (95.0%) and falling ill with AI (89.7%). Most (82.5%) accepted the risk and only 33 (11.8%) would consider stopping work. For perceived impact, most felt that people would avoid them (69.6%) and their families (54.1%). The majority (81.3%) expected an increased workload and feeling more stressed at work (86.9%). For preparedness, 78.7% felt personally prepared for an outbreak. Public PCPs were more likely to be involved in infection-control activities and felt that their workplaces were prepared.
Conclusions:
Most PCPs felt personally prepared for an outbreak but were concerned about their exposure to AI and falling ill. Other concerns included social ostracism for themselves and their families. Public PCPs appeared to have a higher level of preparation. Addressing concerns and improving level of preparedness are crucial to strengthen the primary-care response for any AI outbreak.
Ann Acad Med Singapore 2008;37:458-64
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(1.11) Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
Sardikin Giriputro,1MD, Rismali Agus,1MD, Sri Sulastri,1MD, Dewi Murniati,1MD, Fitryani Darwis,1MSc PH, IB Sila Wiweka,1MD, Adria Rusli,1MD, Sondang Sirait,1MD, Susi Marhaningtyas,1MD, Tuti Hendrawardati,1MD, Rinaldi,1MD, Tony Soetanto,1MD, Elly Deliana,1MD, Iman Firmansyah,1MD
Abstract
Introduction:
Since the first human cases of H5N1 avian influenza virus infection were detected in Indonesia in 2005, the Sulianti Saroso Infectious Diseases Hospital in Jakarta has managed 27 confirmed cases from September 2005 to December 2007.
Materials and Methods:
We reviewed the clinical and epidemiological data of these patients.
Results:
Clinical and radiological features were not specific. Most patients were young and had indirect contact with infected poultry. The majority of cases presented to the Infectious Diseases hospital late when the patients already had features of the systemic inflammatory response syndrome (SIRS). The mortality was high at 77%.
Conclusion:
There is clearly an urgent need for better field diagnostics and therapeutics for the management of this emerging pathogen.
Ann Acad Med Singapore 2008;37:454-7
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1st batch) http://www.flutrackers.com/forum/showpost.php?p=168821&postcount=1
2nd batch) http://www.flutrackers.com/forum/showpost.php?p=168822&postcount=2
3rd batch) http://www.flutrackers.com/forum/showpost.php?p=168823&postcount=3
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Contents:
(1.1) Antiviral Drugs for the Control of Pandemic Influenza Virus
(1.2) Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat
(1.3) Prevention and Control of Avian Influenza in Singapore
(1.4) Preparing for an Influenza Pandemic in Singapore
(1.5) Avian Influenza and Pandemic Influenza Preparedness in Hong Kong
(1.6) Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia [Supari]
(1.7) A Global Perspective on Avian Influenza
(1.8) Twentieth Century Influenza Pandemics in Singapore
(1.9) The Efficacy of Influenza Vaccination in Healthcare Workers in a Tropical Setting: A Prospective Investigator Blinded Observational Study
(1.10) A Cross-sectional Study of Primary-care Physicians in Singapore on Their Concerns and Preparedness for an Avian Influenza Outbreak
(1.11) Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
See original abstracts at the source site. EDITED.]
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(1.1) Antiviral Drugs for the Control of Pandemic Influenza Virus
Richard J Sugrue,1PhD, Boon-Huan Tan,2PhD, Dawn SY Yeo,1MSc, Richard Sutejo,1BSc (Hons) - 1 Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, Singapore - 2 Detection and Diagnostics Laboratory, Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore - Address for Correspondence: Dr Richard J Sugrue, Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University,
60 Nanyang Drive, Singapore 637551 - Email:rjsugrue@ntu.edu.sg
Abstract
In the advent of an influenza virus pandemic it is likely that the administration of antiviral drugs will be an important first line of defence against the virus.
The drugs currently in use are effective against seasonal influenza virus infection, and some cases have been used in the treatment of patients infected with the avian H5N1 influenza virus.
However, it is becoming clear that the emergence of drug-resistant viruses will potentially be a major problem in the future efforts to control influenza virus infection.
In addition, during a new pandemic, sufficient quantities of these agents will need to be distributed to many different parts of the world, possibly at short notice.
In this review we provide an overview of some of the drugs that are currently available for the treatment and prevention of influenza virus infection.
In addition, basic research on influenza virus is providing a much better understanding of the biology of the virus, which is offering the possibility of new anti-influenza virus drugs.
We therefore also review some new antiviral strategies that are being reported in the scientific literature, which may form the basis of the next generation of antiviral strategies during a future influenza virus pandemic.
Ann Acad Med Singapore 2008;37:518-24
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(1.2) Vaccines for Pandemic Influenza. The History of our Current Vaccines, their Limitations and the Requirements to Deal with a Pandemic Threat
Alan W Hampson,1,2BSc, MSc, Hon MD - 1 Interflu Pty Ltd - 2 Honorary Senior Research Fellow, School of Applied Sciences and Engineering, Monash University - Address for Correspondence: Dr Alan William Hampson, 6 Monica Street East Doncaster Victoria 3109, Australia. - Email: Interflu@bigpond.net.au
Abstract
Fears of a potential pandemic due to A(H5N1) viruses have focussed new attention on our current vaccines, their shortcomings, and concerns regarding global vaccine supply in a pandemic.
The bulk of current vaccines are inactivated split virus vaccines produced from egggrown virus and have only modest improvements compared with those first introduced over 60 years ago.
Splitting, which was introduced some years ago to reduce reactogenicity, also reduces the immunogenicity of vaccines in immunologically na?ve recipients.
The A(H5N1) viruses have been found poorly immunogenic and present other challenges for vaccine producers which further exacerbate an already limited global production capacity.
There have been some recent improvements in vaccine production methods and improvements to immunogenicity by the development of new adjuvants, however, these still fall short of providing timely supplies of vaccine for all in the face of a pandemic.
New approaches to influenza vaccines which might fulfil the demands of a pandemic situation are under evaluation, however, these remain some distance from clinical reality and face significant regulatory hurdles.
Ann Acad Med Singapore 2008;37:510-7
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(1.3) Prevention and Control of Avian Influenza in Singapore
Hon Keong Leong,1BVSc (Massey), MSc (Lond), Cheryl S Goh,1BVSc (Hons) (Melb), Siang Thai Chew,2DVM (UPM), MS (VPH) (Texas A&M), Chee Wee Lim,3BVMS (Glas), MMDV (Manchester), Yueh Nuo Lin,3BSc (Hons) (Monash), Siow Foong Chang,2BVMS (Glas), MSc (Lond), Him Hoo Yap,2BVSc (Hons) (Queensland), MPVM (UC Davis), Sin Bin Chua,2BVSc (Hons) (Queensland) - 1 Agri-Food and Veterinary Authority, 5 Maxwell Road, #04-00, Tower Block, MND Complex, Singapore 069110 - 2 Inspection Services & Epidemiology Division, Veterinary Public Health Centre, 10 Perahu Road, Singapore 718837 - 3 Animal & Plant Health Laboratories, 6 Perahu Road, Singapore 718827 - Address for Correspondence: Dr Leong Hon Keong, Inspection Services & Epidemiology Division, Veterinary Public Health Centre, 10 Perahu Road, Singapore - 718837. Email: leong_hon_keong@ava.gov.sg
Abstract
The highly pathogenic avian influenza (HPAI) H5N1 virus was first detected in 1996 in Guangdong, China.
Since 2003, H5N1 outbreaks have been reported in parts of Asia, Europe, the Middle East, and Africa.
It is currently entrenched among poultry in parts of Asia and poses a major challenge to animal and human health.
Singapore is free from HPAI. Given Singapore?s need to import food, the Agri-Food and Veterinary Authority (AVA) has adopted a pro-active risk management system to prevent the introduction of HPAI.
AVA?s approach maybe described as a multi-layered control strategy for the prevention and control of HPAI. The strategy includes control measures at source, border control measures, local control measures and emergency preparedness.
Ann Acad Med Singapore 2008;37:504-9
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(1.4) Preparing for an Influenza Pandemic in Singapore
Jeffery Cutter,1MMed (PH), MSc, FAMS - 1 Ministry of Health, Singapore - Address for Correspondence: Dr Jeffery Cutter, Ministry of Health, College of Medicine Building, 16 College Road, Singapore 169854. - Email: Jeffery_cutter@moh.gov.sg
Abstract
The national strategy against pandemic influenza essentially consists of 3 prongs:
(i) effective surveillance,
(ii) mitigation of the pandemic?s impact, and
(iii) render the population immune through vaccination.
When the pandemic hits Singapore, the response plan aims to achieve the following 3 outcomes:
(i) maintenance of essential services to limit social and economic disruption,
(ii) reduction of morbidity and mortality through antiviral treatment, and
(iii) slow and limit the spread of influenza to reduce the surge on healthcare services.
The biggest challenge will come from managing the surge of demand on healthcare services. A high level of preparedness will help healthcare services better cope with the surge.
Ann Acad Med Singapore 2008;37:497-503
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(1.5) Avian Influenza and Pandemic Influenza Preparedness in Hong Kong
Ping Yan Lam - 1FHKAM (Community Medicine), FFPH (UK), FRACMA - Address for Correspondence: Dr Lam Ping Yan, 21/F, Wu Chung House, 213 Queen?s Road East, Wan Chai, Hong Kong. Email: pylam@dh.gov.hk
Introduction
In 1997, Hong Kong became reputed by identifying the first instance of human infection with avian influenza H5N1.
A total of 18 cases occurred that year resulted in 6 deaths.1-6 The outbreak was completely terminated after the culling of over 1.5 million chickens.
In 2003, two H5N1 human cases were again detected, and subsequent epidemiological investigations showed they had acquired the infection outside Hong Kong.7
Since 2004, while the virus appears from time to time in the wild bird population, Hong Kong has remained free from H5N1 outbreaks in humans and live poultry.8
Meanwhile, since 2003, outbreaks of avian influenza H5N1 among poultry and humans have been reported in an increasing number of countries.
In view of the epizootic and epidemiological situation, the World Health Organization (WHO) concluded that among all highly pathogenic avian influenza viruses, H5N1 is probably the most threatening for human health and is a likely candidate for causing the next pandemic.9
Pandemic Planning Framework
Since 2005, the Hong Kong Special Administrative Region Government (HKSARG) has developed an updated pandemic preparedness plan with specific reference to avian influenza.
The plan is underpinned by several strategic principles, namely reducing the risk of human infection, detecting pandemic influenza in a timely manner, and enhancing emergency preparedness and response.10
The plan sets out a three-tier response system (Alert Response Level, Serious Response Level and Emergency Response Level), which provides the command, control and coordination framework for emergency response.11,12
These levels are based on different risk-graded epidemiological scenarios relevant to Hong Kong (Table 1), and each of them prescribes a corresponding set of public health actions. Reference is made with regard to strategies 1 The Government of the Hong Kong SAR
Abstract
Avian influenza A H5N1 continues to be a major threat to global public health as it is a likely candidate for the next influenza pandemic.
To protect public health and avert potential disruption to the economy, the Hong Kong Special Administrative Region Government has committed substantial effort in preparedness for avian and pandemic influenza. Public health infrastructures for emerging infectious diseases have been developed to enhance command, control and coordination of emergency response. Strategies against avian and pandemic influenza are formulated to reduce opportunities for human infection, detect pandemic influenza timely, and enhance emergency preparedness and response capacity. Key components of the pandemic response include strengthening disease surveillance systems, updating legislation on infectious disease prevention and control, enhancing traveller health measures, building surge capacity, maintaining adequate pharmaceutical stockpiles, and ensuring business continuity during crisis.
Challenges from avian and pandemic influenza are not to be underestimated. Implementing quarantine and social distancing measures to contain or mitigate the spread of pandemic influenza is problematic in a highly urbanised city like Hong Kong as they involved complex operational and ethical issues. Sustaining effective risk communication campaigns during interpandemic times is another challenge. Being a member of the global village, Hong Kong is committed to contributing its share of efforts and collaborating with health authorities internationally in combating our common public health enemy.
Ann Acad Med Singapore 2008;37:489-96
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(1.6) Towards Mutual Trust, Transparency and Equity in Virus Sharing Mechanism: The Avian Influenza Case of Indonesia
Endang R Sedyaningsih,1,2DrPH, Siti Isfandari,1,2MA, Triono Soendoro,2PhD, Siti Fadilah Supari,3DR
Abstract
Introduction:
As the country hardest hit by avian influenza, both in poultry and in human, Indonesia?s decision to withhold samples of avian influenza virus A (H5N1) has fired up a global controversy. The objective of this paper is to describe the position taken by Indonesia in the events leading to the decision and in those conducted to resolve the situation.
Methods:
The sources for this paper are the Indonesian human influenza A(H5N1) case reports and study results, summaries, minutes and reports of national and international meetings of virus sharing, and other related Indonesian and WHO documents.
Results:
The International Health Regulations 2005 have been applied in different ways based on different interpretations. While one party insists on the importance of free, non-conditional, virus sharing for risk assessment and risk response, Indonesia ? as supported by most of the developing countries ? stresses on the more basic principles such as sovereignty of a country over its biological materials, transparency of the global system, and equity between developed and developing nations.
Conclusions:
This event demonstrates the unresolved imbalance between the affluent high-tech countries and the poor agriculture-based countries. Regional, global and in-country meetings must continue to be conducted to find solutions acceptable to all.
Ann Acad Med Singapore 2008;37:482-8
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(1.7) A Global Perspective on Avian Influenza
Adrian Ong,1MBBS, Dip ABIM (Inf Dis), MPH, Mary Kindhauser,1MA, Ian Smith,1MB,ChB, MPH, Margaret Chan2
Abstract
Global public health security is both a collective aspiration and a mutual responsibility that demands cooperative action at all levels.
The expansion of the current H5N1 avian influenza enzootic and its incursion into human health presents a real and significant threat of an influenza pandemic.
The world has for the first time an unprecedented opportunity for pandemic preparation.
Current global efforts to tackle the H5N1 pandemic threat are centred around the framework of the International Health Regulations (2005) that requires countries to openly share disease intelligence including clinical samples, viruses and epidemiological information.
Present international initiatives also seek to establish more equitable allocation and sharing mechanisms for developing countries, of therapeutic resources, public health interventions and other broadbased support in the event of a pandemic.
To be sustainable, country preparatory efforts need to be integrated within wider national emergency preparedness frameworks and emphasise the strengthening of basic capacities in disease surveillance, outbreak response and health systems that can respond to a range of public health emergencies.
Such capacity building represents permanent investments in health that will have enduring benefits beyond a pandemic. Preparations must also go beyond the health sector; greater promotion of intersectoral cooperation and an adoption of a whole-of-society approach to preparation is recommended.
Broad collaboration is vital in addressing the complex challenge posed by influenza to our collective security.
Ann Acad Med Singapore 2008;37:477-81
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(1.8) Twentieth Century Influenza Pandemics in Singapore
Vernon J Lee,1,2MBBS, MPH, MBA, Chia Siong Wong,1MBBS, MMed, Paul A Tambyah,3,4MD, FAMS, Jeffery Cutter,5MMed, MSc, FAMS, Mark I Chen,1MBBS, MMed, MSc, Kee Tai Goh,6MMed, MD, FAMS - 1 Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore - 2 Health Services and Outcomes Research, National Healthcare Group, Singapore - 3 Yong Yoo Lin School of Medicine, National University of Singapore, Singapore - 4 Department of Medicine, National University Hospital, Singapore - 5 Communicable Diseases Division, Ministry of Health, Singapore - 6 Ministry of Health, Singapore - Address for Correspondence: Dr Vernon J Lee, Block 802, Communicable Disease Centre, Moulmein Road, Singapore 308433. - Email: vernonljm@hotmail.com
Abstract
Introduction:
Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted.
Materials and Methods:
We reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore.
Results:
The 1918 epidemic in Singapore occurred in 2 waves ? June to July, and October to November ? resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics.
Conclusions:
Tropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.
Ann Acad Med Singapore 2008;37:470-6
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(1.9) The Efficacy of Influenza Vaccination in Healthcare Workers in a Tropical Setting: A Prospective Investigator Blinded Observational Study
Si Wei Kheok,1 Chia Yin Chong,2MBBS, M Med (Paeds), FRCPCH, Grace McCarthy,1,3MD, Wai Yee Lim,2RN, Khean Teik Goh,4MBBS, M Med (Fam Med), Lubna Razak,4MPH, Nancy WS Tee,2MBBS, FRCPA, Paul Ananth Tambyah,1,4MBBS, FAMS - 1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore - 2 Kandang Kerbau Women?s and Children?s Hospital, Singapore - 3 Duke University Health System, Durham NC, USA - 4 National University Hospital, Singapore - Address for Correspondence: A/Prof Paul Ananth Tambyah, Division of Infectious Diseases, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, Singapore 119074. - Email: mdcpat@nus.edu.sg
Abstract
Introduction:
Influenza vaccine has been shown to be highly effective in temperate regions with well-defined seasonal influenza. Healthcare workers (HCWs) are advised to receive regular influenza vaccination to protect themselves and their patients. However, there are limited data on the efficacy of influenza vaccine in HCWs in the tropics.
Materials and Methods:
In this observational, investigator blinded cohort study, bi-monthly questionnaires recording influenzalike illness (ILI) episodes and medical leave were administered to 541 HCWs at the Singapore
National University Hospital and KK Women?s and Children?s Hospital from 2004 to 2005. ILI was defined according to a standard symptom score.
Results:
Baseline characteristics were comparable in both the vaccinated and non-vaccinated groups. Overall, the relative risk of selfreported ILI in vaccinated HCWs was 1.13 [95% confidence interval (CI), 0.98-1.13; P = 0.107]; medical leave taken was lower in the vaccinated group [mean 0.26 ? 0.6 days per visit, compared with 0.30 ? 0.5 days in the non-vaccinated group (P = 0.40)]. Because of the reported Northern Hemisphere 2003/04 vaccine mismatch, we stratified the cohort and determined that the group which received a matched vaccine had a relative risk of ILI of 0.49 (95% CI, 0.37-0.66; P <0.001), achieving a vaccine efficacy of 51%. Mean medical leave decreased significantly in HCWs who
received the matched vaccine, compared with those who did not receive vaccination (0.13 ? 0.3 vs 0.30 ? 0.5; P <0.001) and with HCWs vaccinated with mismatched strains (0.13 ? 0.3 vs 0.39 ? 0.9; P = 0.01).
Conclusions:
A well-matched influenza vaccine is effective in preventing ILI and reducing sickness absence in healthcare workers in tropical settings. Efforts need to be made to increase influenza vaccination rates and to improve the currently available vaccines.
Ann Acad Med Singapore 2008;37:465-9
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(1.10) A Cross-sectional Study of Primary-care Physicians in Singapore on Their Concerns and Preparedness for an Avian Influenza Outbreak
Teck Yee Wong,1MBBS, M Med (Fam Med), Gerald CH Koh,1MBBS, M Med (Fam Med), FCFP, Seng Kwing Cheong,1MBBS, M Med (Fam Med), FCFP, Meena Sundram,2MBBS, M Med (Fam Med), Kelvin Koh,3MBBS, M Med (Fam Med), MCFP, Sin Eng Chia,1MBBS, MSc (OM), MD, David Koh,1MBBS, PhD, FAMS - 1 Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore - 2 National Healthcare Group Polyclinics, Singapore - 3 SingHealth Polyclinics, Singapore - Address for Correspondence: Dr Wong Teck Yee, Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597. Email: cofwty@nus.edu.sg
Abstract
Introduction:
During an avian influenza (AI) pandemic, primary-care physicians (PCPs) are expected to play key roles in the prevention and control of the disease. Different groups of PCPs could have different concerns and preparedness level. We assessed the concerns, perceived impact and preparedness for an outbreak among PCPs in Singapore.
Materials and Methods:
A cross-sectional survey of PCPs working in private practice (n = 200) and public clinics (n = 205) from March to June 2006 with an anonymous self-administered questionnaire on concerns (12- items), perceived impact (10 items) and preparedness (10 items) for an outbreak.
Results:
Two hundred and eighty-five PCPs responded ? 149 (response rate: 72.7%) public and 136 (response rate: 67.3%) private. The majority were concerned about risk to their health from their occupation (95.0%) and falling ill with AI (89.7%). Most (82.5%) accepted the risk and only 33 (11.8%) would consider stopping work. For perceived impact, most felt that people would avoid them (69.6%) and their families (54.1%). The majority (81.3%) expected an increased workload and feeling more stressed at work (86.9%). For preparedness, 78.7% felt personally prepared for an outbreak. Public PCPs were more likely to be involved in infection-control activities and felt that their workplaces were prepared.
Conclusions:
Most PCPs felt personally prepared for an outbreak but were concerned about their exposure to AI and falling ill. Other concerns included social ostracism for themselves and their families. Public PCPs appeared to have a higher level of preparation. Addressing concerns and improving level of preparedness are crucial to strengthen the primary-care response for any AI outbreak.
Ann Acad Med Singapore 2008;37:458-64
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(1.11) Clinical and Epidemiological Features of Patients With Confirmed Avian Influenza Presenting to Sulianti Saroso Infectious Diseases Hospital, Indonesia, 2005-2007
Sardikin Giriputro,1MD, Rismali Agus,1MD, Sri Sulastri,1MD, Dewi Murniati,1MD, Fitryani Darwis,1MSc PH, IB Sila Wiweka,1MD, Adria Rusli,1MD, Sondang Sirait,1MD, Susi Marhaningtyas,1MD, Tuti Hendrawardati,1MD, Rinaldi,1MD, Tony Soetanto,1MD, Elly Deliana,1MD, Iman Firmansyah,1MD
Abstract
Introduction:
Since the first human cases of H5N1 avian influenza virus infection were detected in Indonesia in 2005, the Sulianti Saroso Infectious Diseases Hospital in Jakarta has managed 27 confirmed cases from September 2005 to December 2007.
Materials and Methods:
We reviewed the clinical and epidemiological data of these patients.
Results:
Clinical and radiological features were not specific. Most patients were young and had indirect contact with infected poultry. The majority of cases presented to the Infectious Diseases hospital late when the patients already had features of the systemic inflammatory response syndrome (SIRS). The mortality was high at 77%.
Conclusion:
There is clearly an urgent need for better field diagnostics and therapeutics for the management of this emerging pathogen.
Ann Acad Med Singapore 2008;37:454-7
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