enb - ministry of health...enb quarterly | vol 45 (4) | 115scientific contributions epidemic...

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• Preventing Re-establishment of Malaria in Singapore • Control of Antimicrobial Resistance in Singapore Investigation into Norovirus Gastroenteritis in a School • Field Epidemiology Response Training • Singapore's Experience on International Health Regulations • Role of Defense in Epidemic Response Epidemic Intelligence and Response + PLUS Working with Wolbachia in Dengue Control See page 151 See pages 115-150 EPIDEMIOLOGICAL NEWS BULLETIN OCT 2019 Vol. 45 No. 4 SINGAPORE ENB Bumper Edition! Quarterly

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Page 1: ENB - Ministry of Health...ENB Quarterly | Vol 45 (4) | 115SCIENTIFIC CONTRIBUTIONS Epidemic Intelligence and Response Khine Nandar1, Pei Pei Chan1, Steven Peng-Lim Ooi1,2 1Communicable

ENB Quarterly | Vol 45 (4) | 113

• Preventing Re-establishment of Malaria in Singapore• Control of Antimicrobial Resistance in Singapore• Investigation into Norovirus Gastroenteritis in a School• Field Epidemiology Response Training• Singapore's Experience on International Health

Regulations • Role of Defense in Epidemic Response

Epidemic Intelligence and Response

+ PLUSWorking with Wolbachia in Dengue Control See page 151

See pages 115-150

EPIDEMIOLOGICAL NEWS BULLETIN OCT 2019Vol. 45 No. 4 SINGAPORE● ● ●

ENBBumper

Edition!

Quarterly

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114 | ENB Quarterly | Vol 45 (4)

ARTICLESScientific Contributions

115 Epidemic Intelligence and Response

120 Preventing Re-establishment of Malaria in Singapore

125 Control of Antimicrobial Resistance in Singapore

129 Investigation into Norovirus Gastroenteritis in a School

134 Field Epidemiology Response Training

139 Singapore's Experience on International Health Regulations

146 Role of Defense in Epidemic Response

NEWSDESKNotes from the Field

151 Working with Wolbachia in Dengue Control

Fast Facts

156 Norovirus Illness

Surveillance Summary

160 Infectious Diseases Update

CONTENTS

This year-end issue of ENB Quarterly marks our culmination of 45 volumes of continuous publication! Fittingly, in a bumper edition of seven articles, we focus on some pillars of the Ministry of Health (MOH)’s public health system.

Besides introducing the principles of epidemic intelligence and response, we have lined up scientific contributions which report on a malaria risk assessment, the control of antimicrobial resistance, and a gastroenteritis outbreak investigation. These articles highlight important applications of our One Health approach. Next, urban health security concerns form the framework for three more articles - on collaboration between the National Centre for Infectious Diseases (NCID) and the School of Public Health (SPH) in a national initiative to provide field epidemiology response training, on Singapore's experience with International Health Regulations, and on the role of defense in epidemic response.

In addition, our Notes from the Field brings readers to a facility producing mosquitoes with Wolbachia as a novel way for dengue control while Fast Facts focuses on norovirus illness.

This issue is special because it marks our ‘season finale.’ There will be a hiatus as the Ministry undertakes systematic review to sharpen thinking on how to effectively serve our wider public health community. I shall be seconded shortly from MOH to undertake dual appointment as senior consultant at NCID and associate professor at SPH. As one chapter closes, my grateful thanks go to the hard-working editorial team with whom I had the privilege of working together.

As we move into the traditional year-end holiday season, may I wish you all merry Christmas and a happy new year ahead.

Enjoy!

Editor’s note

Steven

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SCIENTIFIC CONTRIBUTIONS

Epidemic Intelligence and ResponseKhine Nandar1, Pei Pei Chan1, Steven Peng-Lim Ooi1,2

1Communicable Diseases Division, Ministry of Health, 2Saw Swee Hock School of Public Health, National University of Singapore

a national surveillance programme should be able to identify diseases of public health importance in the local population for prevention and control actions.6 Indicator-based surveillance to determine the national incidence of selected diseases depends on mandatory notifications by registered medical practitioners and clinical laboratories, as stipulated under the First Schedule of the Infectious Diseases Act (IDA). As of 2019, there are 44 diseases on the Schedule7 which is reviewed and adjusted periodically as the risk assessment changes. The current list of notifiable diseases can be found at Annex 4. All notifications are verified to fulfil surveillance case definitions before being classified as cases. For vector-borne, food-borne and environment-related diseases, MOH works closely with public health agencies such as National Environment Agency (NEA) and Singapore Food Agency (SFA) to investigate and implement control measures. For those that are spread through human-to-human transmission, MOH works closely with the healthcare community to effect control measures involving isolation, vaccination and chemoprophylaxis.

Syndromic surveillanceSyndromic surveillance provides data on disease conditions which cannot be obtained through passive reporting systems.8 MOH conducts sentinel surveillance through the collection of disease data from a network of carefully selected reporting sites known as sentinel sites. Polyclinics located throughout the country act as sentinels providing us with weekly returns on the number of patients who have been treated for acute respiratory infection, conjunctivitis and diarrhoeal illness. Outpatient attendances for these syndromes are obtained from their computerised system which collates data on the clinical diagnoses of all patients treated at polyclinics.

Virological surveillanceMOH in collaboration with the National Public Health Laboratory conducts virological surveillance which is the ongoing and systematic collection and analysis of viruses in order to monitor their characteristics.

INTRODUCTION

Traditional surveillance programmes are often referred as indicator-based surveillance and they provide structured data of selected communicable diseases of public health importance. On the other hand, event-based surveillance supplements intelligence information on unusual occurrence of diseases and conditions not usually captured by the traditional surveillance programmes.1, 2 In a rapidly evolving environment, the public health authority can no longer rely just on classical surveillance mechanisms to recognise emergence of new threats. Epidemic intelligence and response deals with the systematic gathering of information on suspect or confirmed communicable diseases to enable early detection of outbreaks and to implement timely interventions of public health measures.3 Singapore’s epidemic intelligence and response system comprises its national surveillance programmes, event-based surveillance, field epidemiologic investigations, and epidemic response capabilities.

NATIONAL SURVEILLANCE PROGRAMMES

National surveillance programmes are essential for the monitoring of communicable diseases and the timely prevention and control of outbreaks through early detection.4 Global travel and trade bring new threats of communicable diseases, while data management and diagnostic technologies can transform the way we monitor and respond to such threats.5 In addition to the legally required disease notifications, animal surveillance for zoonotic diseases, environmental surveillance for mosquito breeding and rodent infestation, as well as food safety surveillance for foodborne pathogens, all contribute towards our national surveillance programmes. In addition, we are seeing advances in monitoring by syndromes, viruses, serology and molecular methods.

Disease notificationsAccording to the World Health Organization (WHO),

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Examples of virological surveillance include:

• Influenza types isolated from respiratory specimens taken from hospitalised patients and those presenting with influenza-like symptoms at polyclinics and sentinel GP clinics;

• Enteroviruses isolated from throat swabs taken from HFMD patients seen at emergency departments or hospitalised in paediatric public hospitals and those presenting with HFMD symptoms at polyclinics and sentinel GP clinics;

• Dengue virus serotypes isolated from blood specimens taken from cases tested positive for dengue virus infection;

• Chikungunya virus detection from blood specimens tested negative for dengue in sentinel GP clinics; and

• Enteroviruses isolated from stools of cases presenting with acute flaccid paralysis as well as patients diagnosed with associated conditions (e.g. encephalitis, transverse myelitits).

Serological surveysFrom time to time, serological surveys are carried out to assess the herd immunity of our population against specific diseases, and to evaluate the effectiveness of the national childhood immunisation programme. For instance, National Seroprevalence Studies (NSS) in 2005 and 2012 showed that childhood immunisation efforts have been successful in increasing the population immunity against rubella.9 The coverage of the national childhood immunisation programme is monitored via a notification system maintained at the National Immunisation Registry.

Molecular epidemiologyWith new molecular methods, we are able to study the molecular epidemiology of pathogens.10 MOH increasingly applies molecular surveillance to complement the existing surveillance systems and to assist in epidemiological investigation. For instance, HIV molecular surveillance enables monitoring of recent infections among newly-diagnosed, treatment-naïve HIV-positive individuals, circulating HIV subtypes, and transmitted antiretroviral resistance.11 Molecular serotyping of Salmonella isolates provides the most common Salmonella serotypes causing local salmonellosis. Whole genome sequencing conducted as part of outbreak investigations12 supplements our field observations and facilitates detection of possible transmission pathways.

EVENT-BASED SURVEILLANCE

Event-based surveillance looks at anecdotal and unofficial information on unfolding events that could pose a public health risk. Two types of event-based monitoring are the reporting of significant events by medical practitioners and the use of internet-based external surveillance, both complementing our national surveillance programmes.

Reporting of significant eventsAd-hoc reports of suspect/confirmed disease clusters or outbreaks by astute physicians are valuable because they are the front-line sensors in detecting unusual occurrences in the number of patients with a particular illness. Such information enables MOH to detect outbreaks early, and even pick up conditions which are new and not legally notifiable. Three examples of significant events alerted by astute physicians are an outbreak in 2015 of Group B Streptococcus infections with epidemiological links to the consumption of raw fish13 , our first Zika virus disease outbreak in 201614 and a large community outbreak in 2016 of rotavirus15 affecting a neighbourhood.

Internet-based surveillanceInternet-based external surveillance is used by MOH to routinely monitor and track communicable disease threats overseas through a systematic framework of horizon scanning and risk assessment.16 Recognising the potential for outbreaks to be introduced across borders, information available on internet from mainstream media and social media17 are regularly processed into epidemic intelligence information for assessing the risks to local public health. This ongoing process enables public health preparedness and early detection of imported infection.

FIELD EPIDEMIOLOGIC INVESTIGATIONS

In addition to single and sporadic infections, disease clusters are common in settings such as nurseries, pre-schools, schools, army camps and long-term care (LTC) institutions. These settings often present conditions for disease to spread because their populations experience close proximity and difficulty in ensuring compliance with good personal hygiene practices and respiratory etiquette.18 The response to a disease cluster must include field epidemiologic investigations to ascertain an outbreak, actively find cases, identify the source of infection and mode of transmission, and prevent further disease transmission.

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Outbreak ascertainmentUpon notification of a disease cluster, we would need to verify the diagnosis to rule out misdiagnosis and laboratory error and ascertain whether an outbreak exists. This requires review of case notes and confirmation of the laboratory results. Laboratory specimens must be obtained from the initial cases reported to test for the pathogen. If the disease is life-threatening but the aetiology is still uncertain, it is necessary to recommend immediate precautionary measures based on knowledge about infections that are clinically similar.

Active case finding and contact tracingA proper case definition is required in order to identify all persons with the infection by place and time. Case definitions should be sufficiently sensitive, but also differentiate between probable and confirmed cases. For air and droplet-borne diseases, contacts (persons who have had contact with known cases during their infectious period) should be identified, located and, under some conditions, asked to stay at home or be placed under quarantine for the duration of the incubation period.

Descriptive and analytic studiesAll cases should be interviewed to provide information on their demographics, symptoms, travel history, movement history, contact history, and exposure to risk factors such as animals or lifestyles. This information will be useful in identifying the source of infection and mode of transmission. Once a possible source has been identified, alternate hypotheses on the chain of infection should be developed and analytic studies conducted to determine the chronology of events leading to spread of infection. Knowing the population-at-risk ensures that proper surveillance and control measures can be undertaken.

Prevention of further transmissionPrecautionary measures are applied to break the chain of infection and prevent further transmission. Such measures may include social distancing, closure of institutions, avoidance of specific foods, and culling of animals. Vigilance is necessary until there are no new cases after two incubation periods of the disease.

EPIDEMIC RESPONSE CAPABILITIES

An epidemic is defined as the occurrence in a community of cases of a disease clearly in excess of normal expectancy whereas an outbreak is the aggregation of disease in space and time that

can be attributable to a single source. Often, the need to protect public health and maintain public confidence dictate immediate control measures while an investigation is ongoing. Public health response measures include, among many actions, establishing a task force/outbreak response team, managing ill persons, sizing the extent and severity of illness, instituting epidemic control measures, and undertaking risk communications.19 To effectively coordinate responders, intelligence gathering, and health interventions, we need a dedicated physical space, documentation of meeting decisions, joint plans of action, and tools for communicating to stakeholders.20 In the event of a pandemic where an epidemic occurs worldwide, the response will be maximised into a national level and the whole-of-government approach will be implemented.21

The One Health approach We adopt the One Health approach in epidemic response and outbreak management. This is a collaborative, multi-sectoral, and transdisciplinary approach – working at the local and global levels – to achieve optimal health outcomes recognising the interconnection between people, animals, plants and their shared environment.22 Under One Health, multiple public health agencies work together to investigate and control disease outbreaks comprehensively.

For instance, Singaporeans like to eat out and are exposed to multiple risks ranging from contaminated food imports to insanitary practices at food establishments involving poor food and personal hygiene.23 The principal considerations for epidemic response are for: (i) MOH to protect public health by minimising disease transmission; and (ii) SFA to ensure food safety by prompt recall of implicated food products from the market. The latter has an integrated food safety system which includes accreditation of countries and overseas export plants, import inspection as well as the regulation of farms, food factories, and retail food establishments.

Risk communications MOH employs various risk communications platforms for information sharing with medical practitioners and other stakeholders. Depending on the urgency and type of information to be disseminated, they include the following:

MedAlert System - During outbreaks, the MedAlert System enables the rapid dissemination of information to all medical practitioners, via SMS, email and fax. Medical practitioners receive timely updates on the outbreak situation via this system.

SCIENTIFIC CONTRIBUTIONS

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REFERENCES

1. Paquet C, Coulombier D, Kaiser R et al. Epidemic intelligence: a new framework for strengthening disease surveillance in Europe. Euro Surveill 2006;11(12):pii=665.

2. Yan SJ, Chughtai AA, Macintyre CR. Utility and potential of rapid epidemic intelligence from internet-based Sources. Int J Infect Dis 2017;63:77-87.

3. World Health Organization. Emergencies preparedness, response: Epidemic intelligence – systematic event detection. Available at https://www.who.int/csr/alertresponse/epidemicintelligence/en/ (accessed on 28 Apr 2019)

4. World Health Organization. Health topics: Public health surveillance. Available at https://www.who.int/topics/public_health_surveillance/en/ (accessed on 3 Apr 2019)

5. Groseclose SL, Buckeridge DL. Public Health Surveillance Systems: Recent Advances in Their Use and Evaluation. Annu Rev Public Health 2017;38:57-79.

6. World Health Organziation. Setting priorities in communicable disease surveillance, 2006. Available at https://apps.who.int/iris/bitstream/handle/10665/69332/WHO_CDS_EPR_LYO_2006_3_eng.

7. Ministry of Health. Legislation: Infectious Diseases Act. Available at https://www.moh.gov.sg/policies-and-legislation/infectious-disease-act (accessed on 3 Apr 2019)

8. World Health Organization. Immunization, Vaccines and Biologicals: Sentinel surveillance. Available at https://www.who.int/immunization/monitoring_surveillance/burden/vpd/surveillance_type/sentinel/en/ (accessed on 28 Apr 2019)

9. Ang LW, Tiong WW, Chua YX et al. Epidemiology of rubella among women of reproductive age in Singapore. Epidemiol News Bull 2013;39:57-63.

10. European Centre for Disease Prevention and Control. Surveillance of communicable diseases in Europe – a concept to integrate molecular typing data into EU-level surveillance. Stockholm: ECDC; 2013.

Weekly Infectious Diseases Bulletin – MOH’s Weekly Infectious Diseases Bulletin publishes detailed information on the weekly incidences of infectious diseases including graphs demonstrating trends and comparisons with the preceding year. The bulletin is available online at https://www.moh.gov.sg/resources-statistics under the filter type “Infectious Disease Statistics.”

In addition, we are exploring new technologies in health informatics to enhance existing systems for dissemination of important public health information. Effective risk communications empower the population, and uphold their trust which is placed in the public health authority.24 However, advancements in information technology also alter the pace and breath of information people acquire, and can pose serious challenges to the public health authority to stay effective.25 Information provided to the public must be simple, reliable and timely. Various communication media channels such as televisions, newspaper and social media exist. Effective communication is important because it maintains public confidence, avoids undue anxiety, and helps individuals and the community to understand the situation.

CONCLUSION

We have outlined Singapore’s epidemic intelligence and response system which comprises its national surveillance programmes, event-based surveillance, field epidemiologic investigations, and epidemic response capabilities. Early disease detection relies on astute physicians and close collaboration between the animal health, wildlife and human health sector. Under the One Health protocol, multiple public health agencies work together in epidemic response. Risk communications are disseminated regularly and in a timely manner so that medical practitioners, stakeholders and the public can make informed decisions and participate in prevention and control.

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11. Ministry of Health, Singapore. Communicable Diseases Surveillance in Singapore 2017. Available at https://www.moh.gov.sg/resources-statistics/reports/communicable-diseases-surveillance-in-singapore-2017 (accessed on 5 May 2019)

12. Foo K, Nandar K, Low C et al. Concurrent Outbreaks of Respiratory Pathogens in Three Long-Term Care Facilities. Epidemiol News Bull 2018;44:71-7.

13. Tan S, Lin Y, Foo K, Koh HF, To  C, Zhang Y, et al. Group B Streptococcus serotype III sequence type 283 bacteremia associated with consumption of raw fish, Singapore. Emerg Infect Dis 2016;22:1970–3. 

14. Singapore Zika Study Group. Outbreak of Zika virus infection in Singapore: an epidemiological, entomological, virological, and clinical analysis. Lancet Infect Dis 2017;17:813-821.

15. Lee JJ, Thu M, Ho M et al. A community outbreak of Rotavirus in a Singapore neighbourhood. Epidemiol News Bull 2016;42:123-7.

16. Nandar K1, Han HK1, Ang LW et al. Horizon scanning and risk assessment in public health. Epidemiol News Bull 2011;37:63-7.

17. Zhang EX, Yang Y, Shang RD et al. Leveraging social networking sites for disease surveillance and public sensing: the case of the 2013 avian influenza A(H7N9) outbreak in China. Western Pacific Surveillance and Response Journal 2015;6:66-72.

18. A Guide on Infectious Diseases of Public Health Importance in Singapore (7th edition). Printed in 2011 ISBN: 978-981-08-8155-9

19. Control of Communicable Diseases Manual 20th Edition. American Public Health Association. ISBN: 978-0-87553-018-5

20. Managing epidemic: key facts about major deadly diseases. ISBN: 978- 92-4- 156553-0. https://www,who.int/emergencies/diseases/managing-epidemics-interactive.pdf Last accessed 24 May 2019.

21. Ministry of Health Singapore. MOH pandemic readiness and response plan for influenza and other acute respiratory diseases (revised April 2014). Available at (accessed on 18 Jun 2019)

22. One Health. https//www.cdc.gov/onehealth/index.htm. Last accessed 17 May 2019.

23. WHO (2008) Foodborne disease outbreaks guidelines, available at www.who.int/foodsafety/publications/ foodborne_disease/outbreak_guidelines.pdf. Last accessed 10 Oct 2018

24. World Health Organization. An Introduction to Risk Communication 2014. Available at https://www.who.int/risk-communication/introduction-to-risk-communication.pdf?ua=1 (accessed on 5 May 2019)

25. World Health Organization. 21st century challenges and opportunities for risk communications. Available at https://www.who.int/risk-communication/21st-century-challenges-opportunities-for-risk-comms.pdf?ua=1 (accessed on 5 May 2019)

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INTRODUCTION

People often consider malaria a rural disease and Singapore’s urbanization with robust disease surveillance would be barriers for its re-establishment in our tropical city-state. Since the island was declared malaria free by WHO in 1982, there has been no sustained local transmission despite periodic imported cases.1-3 Sanitation, construction of a comprehensive drainage system, anti-larval oiling programme, strong epidemiological and vector surveillance remain strong disease control measures. Potential threats loom, such as emergence of malaria resistance to artemisinin and artemisinin-like drugs in the Greater Mekong Subregion (GMS).4

Singapore’s reliance on foreign workers from neighboring countries which are malaria endemic predisposes to the importation of disease.5,6. The above concerns, coupled with high travel volume between Singapore and malarious destinations, have prompted us to review the risks of malaria re-establishing itself in Singapore. In this assessment, we report on recent epidemiological trends of malaria in Singapore, measures in place to prevent the introduction of cases, and potential threats for the re-establishment of local malaria problems.

EPIDEMIOLOGICAL SURVEILLANCE

Epidemiological data is obtained almost real-time under the Infectious Diseases Act which stipulates that medical practitioners and laboratories are to notify within 24 hours from time of diagnosis all malaria cases to the Ministry of Health (MOH)’s Communicable Diseases Division.7 Imported cases indicate that the infection was diagnosed locally but acquired in a malarious area outside of Singapore. For locally acquired infections, introduced cases indicate that the infection was contracted directly secondary to a known

imported case, while indigenous cases indicate that the infection was either contracted directly secondary to a known introduced case, or contracted without evidence of importation (travel history) nor direct links to an important case. During the ten year period from 2008-17, annual incidence has declined steadily from early highs of 2.1-2.6 per 100,000 population to current levels of around 0.4 per 100,000 population. There were 39 laboratory confirmed malaria cases reported in 2017, compared to 104 in 2008 and 166 in 2009. The observed high in 2009 could be attributed to a spike in malaria involving 29 foreigners who had worked/lived in Mandai-Sungei Kadut, Sembawang and Jurong Island.

Epidemiological investigations into 1,240 malaria case notifications over the decade showed that 1,203 (97.0%) were imported cases. Most imported infections were from India (58.5%) and Southeast Asia (28.3%), and foreign workers accounted for the largest proportion of imported cases at 534 (44.4%). The predominant strain of imported malaria parasite remained throughout as Plasmodium (P.) vivax (73.9%), probably because of its unique liver dormancy phase constituting a reservoir of infection.

PREVENTION AND CONTROL MEASURES

Vector surveillance and control, active case finding, and screening of at-risk populations constitute key measures in disease control. The National Environment Agency (NEA) is responsible for environmental control of vector breeding sites with use of surface drains and subsoil pipes as well as anti-larval oiling. Our forested catchment areas with clear water and streams are favorable for the propagation of Anopheles maculatus, while coastal areas containing brackish waters are favourable for the propagation of Anopheles sundaicus. NEA intensifies oiling when water salinity reaches a suitable level for the latter species.

SCIENTIFIC CONTRIBUTIONS

Preventing Re-establishment of Malaria in SingaporeJoshua Tan1, Zeenathnisa Aribou2, Nur Afidah Mohamed Suhaimi3, Wanhan See3, Cherie See3, Charlene Tow3, Steven Peng-Lim Ooi3,4

1Lee Kong Chian School of Medicine, Nanyang Technological University, 2Preventive Medicine Residency Programme, National University Health System, 3Communicable Diseases Division, Ministry of Health, 4Saw Swee Hock School of Public Health, National University of Singapore

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Use of larvicides, thermal fogging and residual spraying with adulticides, regular light trapping and human baiting of mosquitoes are deployed under epidemic vector control conditions as a strong response system to break any cycle of transmission .8

One major endeavour for the elimination of malaria from our offshore islands was undertaken by the Singapore Armed Forces (SAF) in 2007 at Pulau Tekong. This malaria control programme comprised four rings of prevention: (1) a restriction period on all visitors to the island who visited malaria endemic areas over the past eight weeks; (2) education of service personnel on malaria symptoms and testing for malaria in all cases of fever; (3) reduction of mosquito breeding habitats with intense insecticide regimen; and (4) personal protection of SAF staff using bed-nets and pre-treatment of uniforms with permethrin.9

Whenever a local cluster of malaria is suspected in Singapore, MOH undertakes risk-based blood screening for persons living or working in the designated malaria receptive areas. In addition, all foreign workers applying for a work permit are required to undergo compulsory medical examination which includes a blood film to screen for malaria parasites prior to approval by the Ministry of Manpower,. These measures are in line with recommended strategies to maintain malaria elimination by identifying possible reservoirs of infection and performing appropriate screening tests.

POTENTIAL MALARIA THREATS

Three potential threats for the re-establishment of problems in local malaria are outlined below.

Persistent malaria receptivitySingapore has multiple malaria-receptive areas where the ecosystem is conducive for the anopheline vector. An influx of infected individuals who may or may not be symptomatic would make us vulnerable to outbreaks. In 2017, 17.4 million visitors arrived in Singapore with over 1.5 million from South Asia and 6.2 million from Southeast Asia (SEA).10 Although African visitors make up a much smaller proportion (6,792 visitors in June 2019), a threat from imported cases of P. falciparum which is the predominant malaria parasite strain in Sub-Saharan Africa, remains significant.

Since 1997, foreign workers undergo mandatory screening for malaria as part of their pre-employment medical examination.11 However, P. vivax often presents with lower parasite density compared to

P. falciparum and it develops dormant hypnozoites in the liver of the human host which causes relapses months after the primary attack.12,13 Even though microscopy can detect up to 50 parasites per microliter of blood, asymptomatic, submicroscopic malaria infections can be missed by conventional diagnostics which can contribute to transmission.14-16

Additionally, some foreign worker dormitories and workplaces are often located within malaria receptive areas, hence increasing the risk of malaria re-introduction and local transmission (Fig. 1).17

Complacency without chemoprophylaxisWhen travelling to malaria endemic regions, chemoprophylaxis does not prevent malaria infection but works on eliminating the parasite either within the red blood cells (erythrocytic stage) or within hepatocytes (exoerythrocytic stage) thus preventing the clinical disease and the subsequent transmission. Chemotherapeutic regiments include, doxycycline, mefloquine and atovaquone (malarone). Depending on the type of regimen used, the duration, the start and end of the therapy and side effects, may vary.18 Though studies have shown that chemoprophylaxis regimen is effective against malaria, it also has significant problems which prevent travellers from commencing and adhering to the treatment.19,20

Estimates show 16% of all imported cases in the last decade could have been avoided if there was compliance to malaria chemoprophylaxis.21 In a retrospective review of 214 patients with smear positive malaria treated at Singapore General Hospital between year 2000 and 2010, only 2 of 71 residents took malaria chemoprophylaxis but were non-compliant.22 Further studies are needed to determine the barriers to malaria chemoprophylaxis amongst the local population as identifying the main reasons for non-compliance to malaria chemoprophylaxis in our local population is important in developing recommendations for more targeted interventions.23

Drug–resistant malaria Drug resistance to artemisinin-based therapies is a potential concern from the GMS countries. Resistance to artemisinin is now firmly established in parts of Myanmar, Cambodia, Thailand and Vietnam and reportedly increasing in Laos.24,25 Rates of treatment failure with artemisinin combination therapies (ACT) regimens like artesunate-mefloquine in Thailand and dihydroartemisinin-piperaquine in Cambodia have also been on the rise.26 This emergence of drug-resistant malaria is multi-factorial, with a key driver being the widespread circulation of counterfeit

SCIENTIFIC CONTRIBUTIONS

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and sub-standard anti-malarial drugs, with up to 40% of ACT in SEA being counterfeit.27-29

The National Public Health Laboratory (NPHL) can detect mutations associated with drug resistance by molecular methods, including the K13 marker analysis recommended by the WHO. K13 is a molecular marker of the slow clearance phenotype that has been identified to detect mutant alleles associated with resistance to artemisinin-based therapies that are used to treat P. falciparum.30 In 2008-17, 10 out of 192 P. falciparum cases in 2008-17 showed mutations associated with artemisinin resistance through testing with K13. These cases recovered without clinical complications nor significant treatment failure.31 Nonetheless, geographical proximity to GMS, increased travel by Singaporean residents to these regions, and low uptake of chemoprophylaxis make it crucial that we maintain vigilance for resistance markers.

CONCLUSION

There is a robust multi-layered malaria control program in place in Singapore with no significantoutbreak in the last decade. However, there is no room for complacency. Greece, which was malaria free for over 30 years, had a large outbreak in 2012 and antimalarial mass drug administration had to be implemented before it was brought under control.32 The reality is that there are multiple risk factors for the re-establishment of malaria problems in Singapore: foreign workers

harboring P. vivax; residents not complying with chemoprophylaxis when travelling to malariarious areas; and the emergence of anti-malarial resistance in our neighboring countries. Enhanced screening for malaria, enhanced disease and vector surveillance, environmental control, and vigilance for drug-resistant malaria should be continued.33,34

REFERENCES

1. Lee YC, Tang CS, Ang LW et al. (2009). Epidemiological characteristics of imported and locally-acquired malaria in Singapore. Ann Acad Med Singapore; 38(10): 840-9

2. Chiam PT, Oh HM, Ooi EE. (2003). Localized outbreak of falciparum malaria in Singapore. Singapore Medical Journal. 2003 Jul; 44(7): 357-8.

3. Kang ML, Hsu L, Kurup A. (2007). A large cluster of imported Plasmodium falciparum malaria among the Nigerian expatriate students. American Journal of Tropical Medicine and Hygiene; 77(4): 790-2.

SCIENTIFIC CONTRIBUTIONS

Figure 1. Malaria-receptive areas (coloured red) and foreign worker dormitory locations (blue)

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4. World Health Organization (2018). World malaria report. p.56-7.

5. Ministry of Manpower Singapore. Foreign workforce numbers. 2019. Available at: https://www.mom.gov.sg/documents-and-publications/foreign-workforce-numbers [Accessed 7 Aug. 2019]

6. Anvikar AR, Shah N, Dhariwal AC et al. (2016). Epidemiology of Plasmodium vivax malaria in India. American Journal of Tropical Medicine and Hygiene, 95(6 Suppl), 108–120. doi:10.4269/ajtmh.16-0163

7. Ministry of Health, Singapore. Infectious Diseases Act. 1977. Available at: https://www.moh.gov.sg/docs/librariesprovider5/default-document-library/list-of-infectious-diseases-legally-notifiable-under-the-ida.pdf [Accessed 7 Aug 2019]

8. National Environment Agency. Mosquito control. Mosquito control in construction sites. Available at: https://www.nea.gov.sg/our-services/pest-control/mosquito-control/mosquito-control-in-construction-sites

9. Lee V, Tan M, Seet B et al. (2010). Elimination of malaria risk through integrated combination strategies in a tropical military training island. American Journal of Tropical Medicine and Hygiene, 82(6): 1024-9

10. Tablebuilder.singstat.gov.sg. (2019). Selection of variables/time period | SingStat Table Builder. [online] Available at: https://www.tablebuilder.singstat.gov.sg/publicfacing/createDataTable.action?refId=1991 [Accessed 19 Aug. 2019].

11. Sadarangani S, Lim P, Vasoo S. (2017). Infectious diseases and migrant worker health in Singapore: a receiving country’s perspective. Journal of Travel Medicine, 24(4).

12. Sattabongkot J, Suansomjit C., Nguitragool W et al. (2018). Prevalence of asymptomatic Plasmodium infections with sub-microscopic parasite densities in the northwestern border of Thailand: a potential threat to malaria elimination. Malaria Journal, 17(1).

13. Mueller I, Galinski M., Baird J et al.(2009). Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. The Lancet Infectious Diseases, 9(9): 555-66.

14. Bousema T, Okell L, Felger I et al. (2014). Asymptomatic malaria infections: detectability, transmissibility and public health relevance. Nature Reviews Microbiology, 12(12): 833-40.

15. Okell L, Bousema T, Griffin J et al.(2012). Factors determining the occurrence of submicroscopic malaria infections and their relevance for control. Nature Communications, 3(1).

16. Ndao M, Bandyayera E., Kokoskin E et al. (2004). Comparison of blood smear, antigen detection, and nested-PCR methods for screening refugees from regions where malaria is endemic after a malaria outbreak in Quebec, Canada.  Journal of Clinical Microbiology, 42(6): 2694-700.

17. Govtech (2016). Malaria receptive areas-data.gov.sg. Available at: https://data.gov.sg/dataset/malaria-receptive-areas [Accessed 7 Aug. 2019]

18. Schwartz E. (2012). Prophylaxis of Malaria. Mediterranean Journal of Hematology and Infectious Diseases, 4(1), p.2012045.

19. Walz E, Volkman H, Adedimeji A et al. (2019). Barriers to malaria prevention in US-based travellers visiting friends and relatives abroad: a qualitative study of West African immigrant travellers. Journal of Travel Medicine, 26(2).

20. Weber R, Schlagenhauf P, Amsler L. et al.(2003). Knowledge, Attitudes and practices of business travelers regarding malaria risk and prevention. Journal of Travel Medicine, 10(5): 312.

21. Ministry of Health (2017). Communicable Diseases Surveillance, Singapore 2017.

22. Chung SJ. (2014). Malaria in a tertiary hospital in Singapore – Clinical presentation, treatment and outcome: An eleven year retrospective review. Travel Medicine and Infectious Disease. 12(6), 738–44.

23. Lee VJ, Wilder-Smith A. (2006). Travel characteristics and health practices among travellers at the travellers' health and vaccination clinic in Singapore. Ann Acad Med Singapore. 35(10): 667-73

24. Spread of Artemisinin Resistance in Plasmodium falciparum malaria. (2014). New England Journal of Medicine, 371(8): 786.

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25. Cui L, Yan G, Sattabongkot J et al. (2012). Challenges and prospects for malaria elimination in the Greater Mekong Subregion. Acta Tropica, 121(3): 240-5.

26. World Health Organization (2018). Artemisinin resistance and artemisinin-based combination therapy efficacy.

27. Karunamoorthi K. (2014). The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence. Malaria Journal, 13(1).

28. Lon C, Tsuyuoka R, Phanouvong S et al. (2006). Counterfeit and substandard antimalarial drugs in Cambodia. Transactions of the Royal Society of Tropical Medicine and Hygiene, 100(11): 1019-24.

29. Dondorp A, Newton P, Mayxay M et al. (2004). Fake antimalarials in Southeast Asia are a major impediment to malaria control: multinational cross-sectional survey on the prevalence of fake antimalarials. Tropical Medicine and International Health, 9(12): 1241-6.

30. WWARN K13 Genotype-Phenotype Study Group. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments—a WWARN individual patient data meta-analysis. (2019). BMC Medicine, 17(1).

31. Zhang E. (2019). Assessment of the risk posed to Singapore by the emergence of artemisinin-resistant malaria. International Journal of Infectious Diseases. 79 (s1), 27–27.

32. Andriopoulos P, Economopoulou A, Spanakos G et al. (2013). A local outbreak of autochthonous Plasmodium vivax malaria in Laconia, Greece—a re-emerging infection in the southern borders of Europe?.International Journal of Infectious Diseases, 17(2): e125-8.

33. Sturrock H, Roberts K, Wegbreit J et al. (2015). Tackling imported malaria: an elimination endgame. American Journal of Tropical Medicine and Hygiene, 93(1): 139-44.

34. Moonen B, Cohen J, Snow R et al. (2010). Operational strategies to achieve and maintain malaria elimination. Lancet, 376(9752): 1592-603.

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INTRODUCTION

Antimicrobial resistance (AMR) develops naturally in microorganisms such as bacteria, viruses, fungi and parasites and occurs most commonly upon exposure to antimicrobial substances.1 Posing a perilous threat to global health, drug-resistant diseases presently contribute to at least 700,000 deaths every year.2 It is estimated that by 2050, this will escalate to 10 million deaths annually and cost upwards of USD 100 trillion to global economic output if no immediate action is taken. AMR threatens effective prevention and treatment of an increasing range of infections, and currently treatable infections may become fatal when numerous antimicrobials become obsolete. It also elevates the risk of various medical procedures such as organ transplantation, chemotherapies and other major surgeries due to the lack of effective prophylactic antimicrobial agents.3

The problem of AMR is not unique to humans. Animals, food products and the environment do carry AMR organisms or AMR genes which can be transmitted to humans.4 The interconnection between people, animals, plants, and their shared environment imply that strategies addressing the AMR issue cannot be confined to a single sector. To tackle AMR holistically, a coordinated and cohesive One Health approach will need to be adopted.

BACKGROUND

In the bid to address the AMR problem within public hospitals, the National Antimicrobial Taskforce (NAT) was established in 2009.5 Surveillance and monitoring of major drug-resistant pathogens and antimicrobial prescription in hospitals were made compulsory two years later, based on recommendations from NAT. Public hospitals were also given financial support in order to implement antimicrobial stewardship programmes (ASP) and develop clinical decision support systems.

These served to curb antibiotic misuse and support guideline-based antibiotic prescriptions. With the aim of maintaining AMR surveillance and risk assessments within public hospitals while extending engagement to private hospitals and doctors in the community, NAT was reconstituted as the National Antimicrobial Resistance Control Committee (NARCC) in 2014. NARCC is further supported by two advisory panels, the National Antimicrobial Resistance Expert Panel (NAREP) and National Antimicrobial Stewardship Expert Panel (NASEP) which comprise microbiologists, and infectious diseases (ID) physicians and pharmacists respectively.

Recognising the need for a One Health approach in tackling AMR, the One Health Antimicrobial Resistance Work Group (OH AMRWG) was assembled by the One Health Coordinating Committee in Singapore in early 2017.5 The work group was then represented by members from the former Agri-food & Veterinary Authority (AVA), Ministry of Health (MOH), National Environment Agency (NEA) and PUB, the National Water Agency. Through the collation of existing responses and coordination of efforts across the animal, human, food, and environment sectors, the National Strategic Action Plan (NASP) on AMR was conceived by the work group in November 2017.5,6 The NSAP set in place a framework to:

• Unify and formalise existing response across animal, human, food, and environment sectors

• Address existing gaps and prioritise future interventions

• Complement existing strategies against infectious diseases

The Antimicrobial Resistance Coordinating Office (AMRCO) was subsequently established as a coordinating body to facilitate the implementation, monitoring of the NSAP and the coordination of AMR efforts across the sectors.

SCIENTIFIC CONTRIBUTIONS

Control of Antimicrobial Resistance in SingaporeXin Mei Ong, Astrid Khoo, Yueh Nuo Lin, Tau Hong Lee

Antimicrobial Resistance Coordinating Office, National Centre for Infectious Diseases

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ONE HEALTH ANTIMICROBIAL RESISTANCE WORK GROUP (OH AMRWG)

The OH AMRWG is currently represented by members from National Parks Board (NParks)/Animal & Veterinary Service (AVS), Health Promotion Board (HPB), Ministry of Health (MOH), National Environment Agency (NEA), PUB, the National Water Agency and Singapore Food Agency (SFA). It reports directly to the One Health Coordinating Committee (OHCC) which provides the strategic direction in setting priorities on One Health issues. The work group established three technical sub-groups to implement cross-sectoral initiatives in the education, surveillance and research domains. The main functions of the OH AMRWG are to:

• Develop and review the NSAP;

• Oversee the implementation, monitoring and evaluation of the NSAP;

• Maintain information-sharing among all relevant sectors and stakeholders;

• Establish policies relating to AMR issues;

• Review proposed NSAP activities and initiatives;

• Engage other relevant sectors as necessary.

NATIONAL STRATEGIC ACTION PLAN ON ANTIMICROBIAL RESISTANCE (NSAP)

The World Health Assembly endorsed the Global Action Plan on Antimicrobial Resistance in May 2015 with the aim of maintaining successful treatments and prevention of infectious diseases through the use of effective and safe medicines which are quality-assured, utilized responsibly and available to everyone who require them.7

In alignment with this plan and benchmarks set by the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE), Singapore’s National Strategic Action Plan on antimicrobial resistance aims to curtail the emergence and restrict the transmission of drug-resistant organisms through five main strategies5 as follows.

EducationIt is vital for all relevant parties and the community to have accurate knowledge and perception with regard to the effects of AMR on health and society. In order to achieve significant changes in behaviour particularly

within practices affecting AMR, different messaging strategies ought to be adopted when targeting professions and the public. Some of the key focus areas in this domain include:

• Raising public awareness and understanding of AMR and the importance of appropriate antibiotics utilisation; and

• Reinforcing education initiatives for professionals working in human and animal health.

Surveillance and risk assessmentTo facilitate rapid and efficient responses in tackling AMR, regular surveillance and monitoring of AMR along with risk assessments will need to be conducted. Information on resistance rates in particular organisms, epidemiological data of drug-resistant infections, antimicrobial utilisation levels and health outcomes will reveal resistance patterns over time. Accompanied with risk evaluations, these data can provide insights into the socioeconomic burden attributed to AMR and guide assessments of subsequent programmes. Key priority areas in this core strategy consists of:

• Consolidating surveillance efforts across human, animals, food and environment sectors;

• Publishing and reporting relevant surveillance data at the national, regional and international levels;

• Expanding surveillance to include private hospitals; and

• Broadening AMR surveillance to all animal production sectors

ResearchAppreciating the underlying mechanisms and risk factors leading to the initial occurrence and subsequent transmission of drug-resistant organisms is necessary to design corresponding interventions. Globally, there are gaps in existing research pertaining to the development of novel vaccines and drugs for bacterial infections and better diagnostic assays that facilitates proper antimicrobial utilization. Several prioritised areas identified are:

• Mapping of AMR research conducted locally and providing more avenues for collaboration;

• Incorporating AMR research into existing research programmes;

• Identifying and providing funding for more areas related to One Health AMR research.

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Prevention and control of infectionVaccination has been recognised as a crucial yet cost-saving method against AMR as it can protect both humans and animals from infectious diseases. Additionally, suitable prevention and control measures can reduce risks for infections and thus lower the need to prescribe antimicrobials. Some of the priority areas for further action include:

• Strengthening infection prevention and control measures in hospitals;

• Raising the uptake of vaccination in community and animals;

• Enhancing animal health management practices.

Optimisation of antimicrobial useOne of the key drivers for AMR has been identified as the improper use of antimicrobials in both humans and animals. With the intention to encourage informed and evidence-based prescribing decisions among physicians, antimicrobial stewardship programmes were initiated in public hospitals. Having rapid and effective diagnostic tests will also be able to reduce antimicrobial utilization when dealing with infections of an unfamiliar source or nature. Priority areas in this core strategy encompasses:

• Enhancing antimicrobial stewardship and utilisation within hospitals and community;

• Strengthening the system to ensure prudent antimicrobials usage in the veterinary sector and reduce improper use of antimicrobials for food-producing animals.

IMPLEMENTATION OF NSAP

Antimicrobial Resistance Coordinating Office (AMRCO) The AMRCO was set up in September 2018 by MOH under the auspices of the National Centre for Infectious Diseases. Through collaborations with One Health agencies and various other stakeholders, AMRCO seeks to oversee and coordinate efforts in implementing, monitoring and evaluating the proposed activities and plans under the NSAP.8 The key functions of AMRCO consist of:

• Strengthening and coordination of AMR education efforts across different sectors;

• Collation and analysis of surveillance data as well as assessment of control strategies;

• Coordination of research relating to AMR; and

• Secretarial support for several national committees (OH AMRWG, NARCC, NAREP, NASEP)

Key achievementsSince the launch of the NSAP in November 2017, significant progress has been made. A national coordinating centre has been established to support the national agenda for AMR. A One Health AMR work plan detailing particular activities and programmes to be accomplished over the span of five years had also been developed. Under the education sector, public education campaigns such as the “Use Antibiotics Right” by HPB propagated messages to the public that “Antibiotics do not work on the flu virus”.9 Outreach events organised by the NUS Saw Swee Hock School of Public Health at local regional libraries since 2016 were expanded to include a pet component and engaged children in fun hands-on activities to learn about antibiotic resistance while educating adults on how they can play their part to reduce AMR.10 Through unification of efforts across different ministries and agencies, the first joint report on AMR surveillance and antimicrobial utilisation was generated.11 This is a significant step in achieving better integration with regards to local surveillance in antimicrobial resistance and utilisation. Healthcare professionals within the different healthcare facilities can now refer to the national infection control guidelines for healthcare facilities formulated by the National Infection Prevention and Control Committee (NIPC).12 Following the establishment of ASP in public acute care hospitals, NASEP has recently engaged with the local community hospitals to initiate similar programmes.

Regional and international collaborationsThe movement of people, animals and goods globally due to trade or travel exacerbates the transmission of drug-resistant organisms and corresponding resistance genes. It is therefore essential for Singapore to collaborate with international partners to tackle AMR in an effective manner. The Association of Southeast Asian Nations (ASEAN), of which Singapore is a member, jointly developed the ASEAN Strategic Plan for AMR using a One Health approach, which was launched at the 14th ASEAN Health Minister Meeting in 2019. This framework outlines certain goals and targets relevant to AMR control that ASEAN Member States should achieve in areas of human health, animal health, agriculture and environment. Singapore also voluntarily participated in the WHO Joint External Evaluation (JEE) in 2018, and was recognised to have notable capacity in preventing, detecting and responding to public health threats, including AMR.13

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CHALLENGES AND THE ROAD AHEAD

With Singapore being a global trade and tourist hub, international movement and trade contributes significantly to dynamic trends and patterns of resistance. Hence, sustained collaboration and engagement at both regional and international platforms are critical. As there is generally low public awareness of AMR, a more directed approach will need to be adopted for education strategies. There is also incomplete data on antimicrobial utilization in specific areas such as among the general practitioners, veterinary clinics and aquaculture. Appropriate approaches to streamline data collection from different systems are currently being explored. To further the commitment towards reducing infections and optimising antimicrobial use, support for resources and efforts must be combined with defined targets to ensure longer-term sustainability.

REFERENCES

1. World Health Organization. Antimicrobial resistance 2018. Available from: https://www.who.int/en/news-room/fact-sheets/detail/antimicrobial-resistance

2. Interagency Coordination Group (IACG) On Antimicrobial Resistance. No Time to Wait: Securing the future from drug-resistant infections. April 2019. Available from: https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_final_report_EN.pdf?ua=1

3. O’neill J. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Rev Antimicrob Resist. 2014;20:1-16.

4. Secretariats of World Health Organization, World Intellectual Property Organization, World Trade Organization. Antimicrobial resistance - a global epidemic. Available from: https://www.wto.org/english/news_e/news16_e/heal_29aug16_e.pdf

5. Agri-Food & Veterinary Authority of Singapore, Ministry of Health, National Environment Agency, and National Water Agency. National Strategic Action Plan on Antimicrobial Resistance, Singapore. 1 Nov 2017. Available from: https://www.moh.gov.sg/docs/librariesprovider5/resources-statistics/reports/sg-national-strategic-action-plan-on-amr.pdf

6. Launch of National Strategic Action Plan on Antimicrobial Resistance [press release]. 1 November 2017.

7. World Health Organisation. Global action plan on antimicrobial resistance. 2015. Available from: https://apps.who.int/iris/bitstream/handle/10665/193736/9789241509763_eng.pdf?sequence=1

8. National Centre for Infectious Diseases. Antimicrobial Resistance Coordinating Office. 2019. Available from: https://www.ncid.sg/About-NCID/OurDepartments/Antimicrobial-Resistance-Coordinating-Office/Pages/default.aspx

9. Health Promotion Board. Use Antibiotics Right. Available from: https://www.healthhub.sg/programmes/146/use-antibiotics-right.

10. Singapore SLING. World Antibiotic Awareness Week 2018, #WAAW2018. 26 November 2018. Available from: https://blog.nus.edu.sg/singaporesling/2018/11/26/world-antibiotic-awareness-week-2018-waaw2018/.

11. Ministry of Health, Agri-Food & Veterinary Authority of Singapore, National Environmental Agency, PUB Singapore’s National Water Agency. Joint Report on Antimicrobial Utilisation and Resistance in Singapore. 2018.

12. National Centre for Infectious Diseases. Infection Control Guidelines for Healthcare Facilities. 15 Jul 2019. Available from: https://www.ncid.sg/Health-Professionals/Pages/Infection-Control-Guidelines-for-Healthcare-Facilities.aspx.

13. World Health Organisation. Joint external evaluation of IHR core capacities of Singapore: mission report: 16-20 April 2018. 2018.

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INTRODUCTION

Norovirus is a leading cause of sporadic cases and outbreak of acute gastroenteritis across all age groups, and has been associated with 18% of acute gastroenteritis globally.1 Norovirus outbreaks commonly occur in healthcare settings, as well as in areas of human congregation, such as hotels, schools and military camps.2-6 Noroviruses are a group of genetically diverse viruses that belong to the family Caliciviridae and can be classified into six different genogroups, of which viruses from genogroup 1 (GI), GII and GIV are responsible for disease in humans.7 Of the genogroups, GII and GIV are most frequently implicated in outbreaks of acute gastroenteritis.Transmission of norovirus typically occurs via the faecal-oral route, but can also occur via ingestion after contact with contaminated environmental surfaces and through ingestion of inhaled aerosolized particles from vomitus.3,4

On 4 January 2019, the Ministry of Health (MOH) was notified of an outbreak of diarrhoeal illness among students and staff at a school in Singapore. This school has a total of 484 attendees (370 students and 114 staff) and is housed on a campus with four floors. Students from this school belong to one of five levels (Year 1 to 5). While students from Year 1 to 3 attend lessons on the campus, Year 4 and 5 students have majority of their curriculum sited off-campus. Classrooms are situated on all four floors, while staff rooms are situated on the second to fourth floors only. Communal facilities such as the canteen and basketball court are found on the first floor, and the school hall is found on the second floor. Our investigations into this outbreak are reported herein.

METHODS

Under the One Health framework, MOH, National Environmental Agency (NEA), Singapore Food Agency (SFA), formerly known as Agri-Veterinary Authority (AVA) and Public Utilities Board (PUB) conducted joint field investigations at the implicated school premises on 4 and 10 January 2019. As the lead agency in epidemiological surveillance and disease control, MOH’s aim was to determine the extent of the outbreak, source of infection and mode of transmission, as well as to assess the risk of ongoing transmission or propagation of the outbreak and implement infection control measures accordingly.

Thinking that the outbreak could have been of a food-borne nature, the school decided to temporarily cease canteen operations and perform a clean-up of the school premises on 4 January 2019. As such, no ready-to-eat (RTE) food samples were available for testing during the 4 January 2019 field investigation. Instead, one food sample (ice cubes) and four environmental swabs (from knives and chopping boards) were collected and sent for laboratory tests at SFA. The school premises were also investigated for any lapses in hygiene and environmental sanitation. All canteen food handlers were interviewed on their hygiene practices, food preparation practices and the presence of any illness prior to the outbreak. All canteen food handlers were also referred to a designated hospital for stool screening of food-borne pathogens, rotavirus and norovirus.

Between 4 and 10 January 2019, the school provided a list of the cases, including the classes they attended, symptoms, date and time of symptoms onset, medical treatment sought, hospitalisation (if any), and

SCIENTIFIC CONTRIBUTIONS

Investigation into Norovirus Gastroenteritis in a SchoolLeonora Liu1, Yi Kai Ng2, Nigel Chong2, Steven Peng-Lim Ooi,3, 4

1Preventive Medicine Residency Programme, National University Health System, 2National Public Health Laboratory, 3Communicable Diseases Division, Ministry of Health, 4Saw Swee Hock School of Public Health, National University of Singapore

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Figure 1. Onset of diarrhoeal illness among students and staff at a school, 2-10 January 2019

a history of food or beverages consumed from the school canteen. Stool samples were collected from willing cases for laboratory testing at the National Public Health Laboratory (NPHL).

In order to collect RTE food samples from the school’s canteen and to gain better clarity on the source of the outbreak, a second field investigation was conducted on 10 January 2019. Five RTE food samples were collected from the re-opened canteen. Staff and cleaners were also interviewed to collect further information on possible sources of the infection and modes of transmission. Eight environmental swabs were also collected from high touch points where exposure could have occurred. All samples collected were sent for laboratory tests at SFA and NPHL.

Stool samples from cases were tested using FilmArray® Gastrointestinal Panel (BioFire Diagnotics, Salt Lake City, Utah) according to manufacturer’s instruction. Viral RNA from norovirus positive samples was extracted using QIAamp® viral RNA mini kit (Qiagen, Germany) according to manufacturer’s instructions. Norovirus typing was performed using qualitative real time PCR8 and genotyping was performed using a conventional RT-PCR assay targeting the partial capsid ORF2 of the norovirus RNA.9 Amplicons of approximately 300bp were purified using ExoSAP-IT (Affymetrix) and sequenced. The nucleotide sequences were genotyped using norovirus typing tool.10 Representative sequences from the school outbreak and reference sequences were further analysed using Maximum likelihood method and a phylogenetic tree was constructed using MEGA611 to confirm the genotype of the norovirus strains.

RESULTS

A case was defined as a previously well student or staff from the school who developed vomiting and/or diarrhoea (with or without fever, abdominal pain, nausea or headache) between 2 and 10 January 2019. A total of 87 cases (73 students and 14 staff) were identified in this outbreak. This translated into an attack rate of 19.7% (73/370) among students and 12.3% (14/114) among staff. The overall attack rate was 18.0% (87/484). Of the 87 cases, 55 (63.2%) were male and 32 (36.8%) were female. Affected students were in Year 1, 2 and 3. Affected staff included administrative staff and teachers who taught classes in Year 1-5. The epidemic curve of the outbreak is shown in Figure 1.

In order of descending frequency, reported symptoms among the cases were vomiting (82.6%), fever (67.8%), abdominal pain (59.8%), watery diarrhoea

(57.5%), nausea (49.4%) and headache (44.8%). Four cases were hospitalised and all were discharged in stable condition. Other cases either sought outpatient medical treatment, self-medicated, or self-recovered without medication or physician consultation. Among the cases, some had consumed food or drinks purchased from the school canteen on 2 and 3 January 2019. However, no common stall, food or beverage item was implicated. There were also cases who did not consume any food or beverage from the school’s canteen on 2 and 3 January 2019.

Five stool samples were collected from cases, of which all tested positive for Norovirus GII.3. The phylogenetic analysis of norovirus samples from the cases is shown in Figure 2. All food handlers reported no illness in the period prior to the outbreak, and were all tested negative for food-borne pathogens, rotavirus and norovirus. Food samples collected during the 4 and 10 January 2019 field investigations were found to be satisfactory, except one food sample (RTE egg sandwich) which had incidental findings of unsatisfactory levels of faecal coliform (Table 1). One environmental swab (swabs from bidet handle at level 2 male toilet), where the suspected index case had washed his soiled garments, was positive for Norovirus GII.3. All other environmental swabs collected during the 4 and 10 January 2019 field investigations were found to be satisfactory (Table 2).

Our investigations revealed that the index case was a Year 1 student whose symptoms (fever, vomiting, watery diarrhoea and abdominal pain) developed on the morning of 2 January 2019, prior to the start of school.

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He proceeded to attend school and participated in an outdoor game as part of his first day of school activities.

The outdoor activity entailed station games in a round-robin fashion and was attended by all Year 1 students, all Year 1 teachers, and some Year 2 and 3 prefects. Halfway through the game, the index case soiled his pants. The index case was pulled out of the activity, and changed/ washed his soiled pants, in the level 2 male toilet using the bidet. The soiled garments were double-bagged and the index case re-joined his classmates in the classroom. In addition, some students had attended school in the days after 2 January 2019, despite being unwell. There was anecdotal reporting of another student vomiting in the school hall during morning assembly, although the exact date of this occurrence was unclear.

Although the school had cleaned up all areas contaminated with stool and vomitus from 2 to4 January 2019 and performed a school-wide clean up on 4 January 2019, cleaners were unfamiliar with recommended cleaning guidelines for disinfecting areas contaminated with stool/vomitus. They had been using products containing quaternary ammonium compounds as a cleaning and disinfecting agent instead of the recommended diluted sodium hypochlorite (chlorine bleach) solution. No other lapses in hygiene and environmental sanitation were noted.

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Figure 2. Maximum likelihood tree showing norovirus samples collected at a school as Group II.3

Table 1. Laboratory test results of food samples taken on 4 and 10 January 2019

Food sample Result (pathogen)

Sample taken on 4 January 2019

In House Ice Cubes (Stall D) Satisfactory

Sample taken on 10 January 2019

RTE Brown rice (Stall B) Satisfactory

RTE Fried mid-wing chicken (Stall B)

Satisfactory

RTE Hardboiled egg (Stall B) Satisfactory

RTE Egg sandwich (Stall D) Unsatisfactory (F. coliform 75MP-N/g)

RTE Roasted chicken, sliced (Stall C)

Satisfactory

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Environmental swabs taken Result (pathogen)Swabs taken on 4 January 2019Swabs from knife for vegetables (Stall C) Satisfactory

Swabs from chopping board for vegetables (Stall C) Satisfactory

Swabs from knife for raw chicken (Stall C) Satisfactory

Swabs from chopping board for raw chicken (Stall C) Satisfactory

Swabs taken on 10 January 2019Swabs from wash hand basin, male toilet Satisfactory

Swabs from wash hand basin, female toilet Satisfactory

Swabs from water cooler at canteen Satisfactory

Swabs from wash hand basin at canteen Satisfactory

Swabs from wash hand basin at canteen’s handicap toilet Satisfactory

Swabs from suspected index case’s class seating area in school hall Satisfactory

Swabs from bidet handle at level 2 male toilet Positive (Norovirus GII.3)

Swabs from table top at suspected index case’s classroom table top Satisfactory

Table 2. Laboratory test results of environmental swabs taken on 4 and 10 January 2019

DISCUSSION

Our findings pointed towards an outbreak of Norovirus GII.3 gastroenteritis that was propagative in nature and not food-borne. With regards to the unsatisfactory food sample, NEA, as the licensing authority for the school canteen, followed-up on actions for the school canteen.

This outbreak of Norovirus GII.3 gastroenteritis showed a peak that was attributable to the multiple environmental touch points that occurred during the widely-participated round-robin-style outdoor activity on 2 January 2019. The propagation is explained by the attendance of symptomatic secondary cases on subsequent days of school, despite the school instructing students who were unwell to seek medical consultation and to stay at home during the entire duration of their physician-issued Medical Certificate (MC). One such secondary case was noted to have vomited in the school hall during morning assembly.

In the United States’ (US) experience, GII.4 is the predominant genotype implicated in sporadic cases and outbreak of acute gastroenteritis.12 Non-GII.4 norovirus genotypes are still associated with a significant number of acute gastroenteritis cases. Norovirus GII.3, in particular, is prevalent in up to 17% of acute gastroenteritis cases internationally.12-14 According to the US Centers for Disease Control and Prevention’s (CDC) guidelines for norovirus outbreak

management and disease prevention,15 contaminated surfaces should be cleaned to remove organic loads such as faecal material before the surface is disinfected with either sodium hypochlorite (chlorine bleach) solution at a concentration of 1,000–5,000 ppm or other commercial product registered with Environmental Protection Agency (EPA) as effective against norovirus. Products containing phenolic compounds (including quaternary ammonium compounds) have been shown to be less effective against human norovirus.16

This outbreak has highlighted the importance of ensuring students’ absence from school when medically unfit, as well as the importance of adherence to cleaning guidelines for areas contaminated with stool/vomitus. Unfamiliarity with recommended cleaning guidelines for disinfecting areas contaminated with stool/vomitus with diluted bleach solution had resulted in using products containing quaternary ammonium compounds as a cleaning and disinfecting agent instead. Upon MOH’s advice, the school had cleaned and disinfected all contaminated areas with the appropriate diluted bleach solution from 4 January 2019 onwards and this eventually broke the chain of transmission.

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REFERENCES

1. Sharia MA, Aron JH, Anne ER, Linda V, Prasanna P, Umesh DP, Marion K, Benjamin AL. (2014). Global prevalence of norovirus in cases of gastroenteritis: a systemic review and meta-analysis. Lancet Infectious Diseases, 14(8): 725-730.

2. Vipond IB, Caul EO, Hirst D, Carmen B, Curry A, Lopman BA, Pead P, Pickett MA, Lambden PR, Clarke IN. (2004). National epidemic of Lordsdale Norovirus in the UK. Journal of Clinical Virology, 30(3): 243-7.

3. Cheesbrough JS, Green J, Gallimore CI, Wright PA, Brown DW. (2000). Widespread environmental contamination with Norwalk-like viruses (NLV) detected in a prolonged hotel outbreak of gastroenteritis. Epidemiology and infection, 125(1): 93-8.

4. Marks PJ, Vipond IB, Carlisle D, Deakin D, Fey RE, Caul EO. (2000). Evidence for airborne transmission of Norwalk-like virus (NLV) in a hotel restaurant. Epidemiology and infection, 124(3): 481-7.

5. Marks PJ, Vipond IB, Regan FM, Wedgwood K, Fey RE, Caul EO. (2003). A school outbreak of Norwalk-like virus: evidence for airborne transmission. Epidemiology and infection, 131(1): 727-36.

6. Yap J, Qadir A, Liu I, Loh J, Tan BH, Lee VJ. (2012). Outbreak of acute norovirus gastroenteritis in a military facility in Singapore: a public health perspective. Singapore Medical Journal, 53(4): 249-254.

7. Green K. (2013). Caliciviridae: the noroviruses, p 583-609. In KnipeDM, Howley PM (ed), Fields virology, 6th ed, vol 1. Lippincott Williams & Wilkins, Philadelphia, PA.

8. Trujillo AA, McCaustland KA, Zheng DP, Hadley LA, Vaughn G, Adams SM, Ando T, Glass RI, Monroe SS. (2006). Use of TaqMan real-time reverse transcription-PCR for rapid detection, quantifiation, and typing of norovirus. Journal of Clinical Microbiology, 44(4): 1405-12.

9. Kojima S, Kageyama T, Fukushi S, Hoshino FB, Shinohara M, Uchida K, Natori K, Takeda N, Katayama K. (2002). Genogroup-specific PCR primers for detection of Norwalk-like viruses. Journal of Virological Methods, 100(2002): 107-114.

10. Kroneman A, Vennema H, Deforche K, Avoort H, Peñaranda S, Oberste M.S, Vinjé J, Koopmans M. (2011). An automated genotyping tool for enteroviruses and noroviruses.

11. Journal of Clinical Virology, 51(2011): 121-125. Retrieved from www.rivm.nl/mpf/norovirus/typingtool.

12. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. (2013). MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Molecular biology and evolution, 30(12): 2725–2729.

13. Cannon JL, Barclay L, Collins NR, Wikswo ME, Castro CJ, Magaña LC, Gregoricus N, Marine RL, Chhabra P, Vinjé J. (2017). Genetic and epidemiologic trends of norovirus outbreaks in the United States from 2013 to 2016 demonstrated emergence of novel GII.4 recombinant viruses. Journal of Clinical Microbiology, 55(7): 2208-2221.

14. Zhou HL, Zhen SS, Wang JX, Zhang CJ, Qiu C, Wang SM, Jiang X, Wang XY. (2017). Burden of acute gastroenteritis caused by norovirus in China: a systematic review. The Journal of Infection, 75(3): 216-224.

15. Kumthip K., Khamrin P, Maneekarn N. (2018). Molecular epidemiology and genotype distributions of noroviruses and sapoviruses in Thailand 2000-2016: a review. Journal of Medical Virology, 90(4): 617-624.

16. Centers for Disease Control and Prevention. (2011) Updated norovirus outbreak management and disease prevention guidelines. MMWR Recommendations and Reports, 60(RR-3): 1-18.

17. Doultree JC, Druce JD, Birch CJ, Bowden DS, Marshall JA. (1999). Inactivation of feline calicivirus, a Norwalk virus surrogate. The Journal of Hospital Infection, 41(1): 51-7.

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Field Epidemiology Response Training Steven Peng-Lim Ooi1,2, Ken Wah Teo3

1Communicable Diseases Division, Ministry of Health, 2Saw Swee Hock School of Public Health, National University of Singapore, 3Preventive Medicine Residency Programme, National University Health System

INTRODUCTION

Field epidemiology response training constitutes an important line of public health defence for the world against emerging infectious diseases.1 Originally designed by the United States (US) Centers for Disease Control and Preventoin (CDC)’s Epidemic Intelligence Service (EIS) based on a core curriculum of practical competencies, there are 69 such programmes today across five continents.2,3 The Singapore field epidemiology training programme (S-FETP) which was modelled after the US EIS joined the Training Programs in Epidemiology and Public Health Interventions Network [known as TEPHINET] in 2010 and is a founding member of the ASEAN+3 field epidemiology training network.4

Our tropical city state’s status as a densely populated urban trade and travel hub creates the transmission potential for many outbreaks. The Ministry of Health (MOH) currently trains a pool of non-physicians through S-FETP to meet its need for competent public health officers who can carry out field investigations and safeguard public health. To address the wider epidemiology needs of other agencies (eg, Singapore Food Agency (SFA), National Environment Agency (NEA), AVS , hospitals), a national training platform is required for sustainable workforce development. This paper outlines the collaboration between the National Centre for Infectious Diseases (NCID) and School of Public Health (SPH) with MOH on a new S-FETP framework to allow for stepwise training of more medical and public health officers to meet national needs.

DEVELOPMENT APPROACH

Beginning with what worksWe performed a systematic review to study the characteristics of FETPs and included reference programmes in US, United Kingdom (UK), and Europe, as well as less established front-line ones from the

Americas and Africa.5-9 All FETPs devoted over 80% of their training time on fieldwork. Variations in admission and course criteria were observed to tailor to local needs and resources.

Seeking expert adviceIn 2017-18, as chair of the ASEAN+3 training network steering committee, Singapore cross-consulted with other member countries on novel training methods and other enhancements to engage millennials.10,11 We also sought feedback at a joint external evaluation of our IHR core capacities and S-FETP’s efficacy was affirmed with the maximum score of 5/5.12 The experts strongly recommended that our programme be expanded to involve public health agencies outside MOH, with re-design of human resources towards more high-level functioning as innovations in technology are introduced. They noted that the S-FETP experience was valuable and should be shared with the wider global health workforce.

Meeting the needs of stakeholdersWe conducted focus group discussions with public health staff who were interested in field epidemiology training, S-FETP fellows and residents, and management personnel from MOH and other local agencies. We then followed up with key informants and resource persons to refine our provisional framework and curriculum. The following common stakeholder needs were identified:

• Develop a tiered approach to meet training at various levels

• Focus on practical learning on-the-job with buddy/mentorship

• Tailor curriculum to our tropical city state context

• Minimize administrative burden by streamlining processes

• Build capacity for integrated response to health security issues

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NATIONAL FIELD EPIDEMIOLOGY TRAINING PLATFORM

Taking the above into account, we have introduced a three-tiered pyramid model for Singapore’s sustainable field epidemiology workforce development (Figure 1). S-FETP will be opened to medical and public health officers as a tripartite collaboration between NCID, SPH and MOH from 2020, tapping on each other’s strengths.

Foundational Tier is provided to frontline staff, including rapid response teams, according to the needs of each specific agency in the form of a primer in field epidemiology practice (workshops of up to a week duration). Training consists of classroom interactions interspersed with on-the-job learning. The officer acquires basic awareness and understanding of core competencies, with skills to perform field epidemiology objectives under supervision.

Intermediate Tier is offered to interested medical and public health officers (in the form of 6-12 months course) with cross-training and selected field exposure/projects in surveillance, epidemiology and response. Academic components will be at SPH in the form of Masters level modules (for a total of eight credits) amounting to a Graduate Certificate by SPH upon the candidate’s successful completion.

This proficiency level accords the officer essential knowledge and skills in field epidemiology so as to be able to work independently with minimal supervision.

Senior Tier is reserved for epidemic intelligence service trainees who continue for a total of two years for relevant experiences in applied epidemiology and global health practice. They will be tested as subject matter experts for situational field leadership roles, and have options to obtain a Diploma or Masters in applied epidemiology and public health. This level of proficiency requires an in-depth knowledge of field epidemiology, and sufficient application of knowledge and skills to guide and mentor others.

We aim to customise the core curriculum, which is based on the US CDC’s FETP standard curriculum, to agencies’ needs in the domains and instructional goals that constitute competencies for each officer’s continuing professional development (Table 1). Agency-specific emphasis such as food hygiene, environmental sanitation, or One Health goals can be set out clearly so as to provide a checklist for trainees to track progress in an itemized manner. Operating out of NCID and the agencies for fieldwork, and SPH for academics, the revised S-FETP is designed to meet the needs of public health practitioners at all levels of field epidemiology practice.

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Figure 1. Three Tiers for Field Epidemiology Workforce Development

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Domains Instructional goalsLevel of Training

Specialist Intermediate Foundational

Basic Field Epidemiology

Describe epidemiologic roles and functions within the Agency

Advanced Proficient Proficient

Identify and address communicable diseases of national priority

Advanced Proficient Proficient

Review public health literature to develop recommendations

Advanced Proficient Proficient

Conduct descriptive epidemiological studies

Advanced Proficient Developing

Design and conduct analytic studies Advanced Proficient Developing

Create tables, graphs, charts and maps for data analysis

Advanced Advanced Proficient

Analyse and interpret data from descriptive and analytic studies

Advanced Advanced Proficient

Follow ethical guidelines during a field investigation

Proficient Developing Developing

Investigate an outbreak and develop an intervention strategy

Advanced Proficient Developing

Participate in teams and provide situational leadership during investigations

Advanced Proficient Proficient

Communicable Diseases

Understand and prioritize diseases of public health importance

Advanced Advanced Proficient

Apply the principles and practices of disease prevention and control

Proficient Proficient Developing

Prepare for and respond to public health emergencies

Advanced Advanced Proficient

Table 1. Example of Customised Domains and Instructional Goals*

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*to be tailored to needs of each requesting Agency

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CHALLENGES MOVING FORWARD

We have built on strong foundations set by the original MOH programme, creating a holistic national approach which caters to all levels of workforce. The new S-FETP adopts a three-tiered framework where not all staff have to complete two years of training. This flexibility allows trainees at the foundational and

intermediate levels to perform competently at their jobs while maintaining an advanced level of training for those willing and able to become subject matter experts.

Major challenges remain. Firstly, we need to maintain relevance to the changing needs of different public health agencies, so that S-FETP can be an essential step

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Table 1 (continued). Example of Customised Domains and Instructional Goals*

Domains Instructional goalsLevel of Training

Specialist Intermediate Foundational

Public Health Surveillance

Describe the roles and responsibilities in surveillance practice

Advanced Proficient Proficient

Plan and implement a surveillance system

Proficient Developing Developing

Analyse and interpret data obtained from surveillance

Advanced Advanced Proficient

Operate different types of surveillance in the system

Advanced Advanced Proficient

Identify an appropriate public health response based on surveillance data

Advanced Advanced Proficient

Evaluate a surveillance system Advanced Developing Developing

Understand the roles and functions of laboratory based surveillance

Proficient Proficient Proficient

Risk Communi-cations

Create field reports Advanced Advanced Proficient

Communicate risks and response to various stakeholders

Advanced Proficient Developing

Write scientifically for an epidemiologic bulletin

Proficient Developing Developing

Policy Assist

Formulate recommendations for policy development in the Agency

Proficient Developing Developing

Use health outcome measures to prioritize prevention strategies

Proficient Proficient Developing

*to be tailored to needs of each requesting Agency

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2. Centres for Disease Control and Prevention, United States. Field epidemiology training program standard core curriculum, 2006;3.

3. Subramaniam R, Herrera D, Kelly P. An evaluation of the global network of field epidemiology and laboratory training programmes: a resource for improving public health capacity and increasing the number of public health professionals worldwide. Hum Resour Health, 2013;11

4. Ooi PL, Seetoh T, Cutter J. The Singapore field epidemiology service: insights into outbreak management. J Prev Med Public Health, 2012;45;277-82.

5. Public Health England, United Kingdom. Field epidemiology training programme prospectus, 2015.

6. Aftab JMM, Bohlin A, Jung H, et al. Manual for ECDC fellowship programme – EPIET and EUPHEM paths, cohort 2017. Stockholm: European CDC, 2016.

7. Traicoff DA, Suarez-Rangel G, Espinosa-Wilkins Y, et al. Strong and flexible: developing a three-tiered curriculum for the regional Central America field epidemiology training program. Pedagogy in Health Promotion, 2015;1:74-82.

8. Bhatnagar T, Gupte MD, Hutin YJ, et al. Seven years of the field epidemiology training programme at Chennai, Tamil Nadu, India: an internal evaluation. Hum Resour Health, 2012;10:36.

9. Andre AM, Lopez A, Perkins S, et al. Frontline field epidemiology training programs as a strategy to improve disease surveillance and response. Emerging Infectious Diseases, 2017;23:S166-73.

10. FETN Coordinating Office, Bangkok. Summary report of the 8th steering committee meeting of ASEAN plus three field epidemiology training network, 2017.

11. Patcharin T, Ooi PL. Regional experience in use of novel field epidemiology training methods. Epidemiol News Bull, 2018;44:50-4.

12. WHO, Geneva. Joint external evaluation of IHR core capacities of Singapore, 2018.

for building public health careers and competencies. We will need to work with these agencies to customise the training (including protected time), refine the reward and recognition system (to incentivise staff) and align with Skillsfuture mechanisms (for continuing professional development).

Secondly, we need to build up our very limited pool of experienced field epidemiology faculty who can provide proper curriculum delivery and mentorship across each training cohort, and improve on the academic modules in urban field epidemiology, health security and outbreak management. Relevant components should also be taught in the preventive medicine residency programme and in undergraduate medicine. We will draw on core faculty from NCID/SPH to be supported by experienced persons at MOH, SFA, NEA and AVS .

Thirdly, we need to cultivate our global health network ties to enable sharing of practical experiences on public health emergencies of international concern. S-FETP already has well established ties with WHO, GOARN, TEPHINET and counterparts in the ASEAN+3 network, and we need to continue building on our strong links. Regular exchange with international partners also help to secure relevant global health experiences for our advanced trainees.

CONCLUSION

We envisage a time frame of 3-5 years for NCID and SPH to develop this national field epidemiology training platform for sustainable workforce development. Successful outcome will deliver a cadre of highly competent medical and public health professionals who, having cross-trained in field epidemiology with other hospitals and agencies, can provide domain expertise in public health with skills and knowledge for outbreak management and pandemic response.

REFERENCES

1. White ME, McDonnell SM, Werker DH, et al. Partnerships in international applied epidemiology training and service, 1975-2001. Am J Epidemiol, 2001;154:993-9.

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Singapore's Experience on International Health RegulationsWanhan See1, Steven Peng-Lim Ooi1,2, Khine Nandar1, Jeffery Cutter1

1Public Health Group, Ministry of Health, 2Saw Swee Hock School of Public Health, National University of Singapore

INTRODUCTION

The International Health Regulations (IHR) (2005) is an international legal instrument that binds 196 countries, including 194 States Parties of the World Health Organization (WHO).1 The objective of IHR (2005) is to prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade.2, 3

In order to prevent and manage public health events, countries should possess functioning systems at a national level. WHO had outlined the essential core capacities in IHR (2005) and States Parties were required to fulfil it not later than five years after the date of entry into force, as of June 2007. These capacities include surveillance, reporting, notification, verification, response and collaboration activities, and activities concerning designated airports, ports and ground crossing in the aspect of preventing the international spread of public health threats. Singapore, being a member of WHO Western Pacific Region (WPR), is obliged to fulfil the IHR requirements.

This paper aims to describe the development of IHR and core capacities, as well as Singapore’s commitment in the IHR journey.

HEALTH SECURITY DEVELOPMENTS

European cholera epidemics in 1830-47 had brought about international concerns and sparked off the call for communicable disease diplomacy and multilateral cooperation in public health.3 The first International Sanitary Conference was held in France in July 1851, with the objective of harmonizing and reducing costly maritime quarantine requirements among European

nations. Cholera and plague were the first two diseases to be addressed in international conferences.4

After the first world war, two independent international health organizations co-existed in Europe – the Office International d’Hygiene Publique and the Health Organization of the League of Nations. Across the Atlantic, the equivalent health organization was known as the Pan American Sanitary Organization. In April 1945, at a United Nation (UN) conference, China and Brazil proposed that an international health organization should be established. This notion brought about the birth of the WHO.

The constitution of WHO was adopted and signed by 51 members of the UN and ten other nations at the International Health Conference in New York City on 22 Jul 1946. This constitution came into force on 7 April 1948 and WHO was officially commissioned on 1 Sep 1948. During the world health assembly in 1951, state parties of WHO adopted the International Sanitary Regulations. This was replaced in 1969 by the IHR5 which had as its primary objective the control of six diseases, namely plague, cholera, yellow fever, smallpox, typhus and relapsing fever.3,6

The inadequacies of IHR (1969) became apparent in the 1990s with major epidemics such as cholera in South America in 1991, plague in Surat, India in 1994, and Ebola in Kikwit, Democratic Republic of Congo in 1995.7 The scope of IHR (1969) was also found to be inflexible in responding to pandemic diseases such as influenza and to non-infectious health threats.8 Other limitations of IHR (1969) were: (a) notification of diseases being solely dependent on official reports by governments; (b) lack of formal internationally coordinated mechanisms to contain international spread of disease; (c) absence of definite measures to detect and assess risks; (d) lack of strategies to improve surveillance capabilities of States Parties;

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and (e) inability of WHO to ensure compliance by state parties.

In 1995, a resolution was made to call for a drastic revision to IHR (1969). The momentum for the revision was accelerated by the SARS pandemic in 2003.9 Following many deliberations, the revised IHR (2005) was adopted by the world health assembly on 23 May 2005 and came into effect on 15 Jun 2007.

REGULATORY ENHANCEMENTS

There are seven enhancements to IHR (2005) that transformed the previous passive regulations to a pro-active set of rules, with more defined procedures and responsibilities between WHO and the state parties. The new regulations placed emphasis on the collaborative actions between state parties and WHO in the identification and assessment of events, and the corresponding responses to public health emergencies.10

Broader scope of public health threatsIHR (2005) has expanded coverage to a wider range of public health threats including natural disasters, as well as chemical and nuclear events.11 Instead of specifying the types of diseases subjected to the regulations, IHR (2005) defines public health threats as “illness or medical condition, irrespective of origin or source that presents or could present significant harm to humans”.2

Obligations on States Parties to notify WHO of events that may constitute Public Health Emergency of International Concerns (PHEIC)State parties are obligated to notify WHO of events which may constitute a PHEIC within 24 hours of an assessment, based on a decision instrument stipulated under Annex Two of the IHR (2005) (Figure 1).2 A PHEIC is defined as “an extraordinary event which is determined to constitute a public health risk to other States through the international spread of diseases and potentially requires a coordinated international response”.10 State parties are required to furnish additional information of the public health event such as situation update, laboratory results and response measures to WHO when available.

Authorization of WHO to consider unofficial reports of public health events and to obtain verification from States PartiesWHO is authorized to consider reports from unofficial sources related to a public health event other than official notification, and to seek verification of the event with the country where the event is alleged occurring.2

This allows WHO to: (a) assess the seriousness of the event; (b) recommend appropriate actions; (c) facilitate or help coordinate technical assistance when needed; and (d) inform other state parties of the public health risk involved.3

Establishment of IHR national focal points and WHO IHR contact pointWith an expectation of timely notification, state parties are required to establish an IHR national focal point which serves as the point of contact for communications with WHO. Likewise, WHO has appointed IHR contact points in each region to receive information and communicate with the national focal points.3

State Party obligations to develop minimum core public health capacitiesStates parties are required to develop, strengthen and maintain core public health capacities for the purpose of surveillance and respond to public health events.3

Powers of Director-General to determine a public health event a PHEIC, and to issue corresponding temporarily recommendationThere is provision of powers to the WHO Director-General (DG) to determine if a public health event constitutes a PHEIC.2 The DG shall consult the implicated country if the health authority is in agreement with the assessment. Once consensus is reached, DG will seek the views of the Emergency Committee, which will also advise on the temporary recommendations to respond to the event.

Protection of human rights of person and travellers In the name of preventing spread of diseases across borders through travel, state parties may apply additional health measures to suspect or infected travellers including least intrusive and invasive medical examination.10 However, no medical examination, treatment or health measures should be carried out on the travellers without their informed consent.

MONITORING IHR CORE CAPACITIES DEVELOPMENT

To assist States Parties to conduct self-assessment on the development of core capacities outlined in IHR (2005), a monitoring framework was developed by WHO12.

In the monitoring framework,13 core capacities were outlined to detect and respond to human health events at the Points of Entry (PoE) (Table 1).

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Notwithstanding the status of achieving IHR requirements, States Parties are required to report to WHO annually on the core capacities development in a form of questionnaire (IHR Monitoring Questionnaire, MQ).13 When this was first administered in 2010, state parties made their own assessments whether their national capacities have met the requirements under the IHR (2005).14 In 2018, WHO introduced a new reporting tool known as the IHR State Party Self-Assessment Annual Reporting Tool (IHR SPS ART). This provided for the use of a five progress level table to assess indicators, and a scoring system at indicator and capacity level.

Following recommendations from a second IHR review committee, WHO has developed the new IHR monitoring and evaluation framework which combined qualitative and quantitative review processes.15 State parties are now recommended to conduct the monitoring and evaluation process through a four-year cycle anchored in the national health system review cycle. The new framework comprises four interrelated components:

Annual reporting of IHR SPS ART • Joint external evaluation (JEE) – State parties are

encouraged to conduct at least one JEE every four years.

• After-action review – State parties should conduct reviews on real public health events to draw lessons and identify gaps for improvement.

• Simulation exercise – In the event where there is no suitable public health event to review, States Parties can consider conducting simulation exercise to test the functions of IHR core capacities.

At the end of the first deadline for States Parties to fulfil the core capacities of IHR, in June 2012, only 42 of 193 States Parties reported that they had met the core capacities requirements.16 A total of 121 States Parties had requested and granted with a two-year extension.12 At the end of the second deadline in June 2014, a total of 65 States Parties reported that they had

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Core Capacities

IHR MQ New IHR SPAR Remarks

1 National legislation, policy and financing

Legislation and financing No change

2 Coordination and NFP communications

IHR Coordination and NFP communications

No change

3 Surveillance Zoonotic events and the human-animal interface

Core capacity 6 in IHR SPAR

4 Response Food safety New Core capacity 8 in IHR SPAR

5 Preparedness Laboratory New Core capacity 8 in IHR SPAR

6 Risk communication Surveillance Core capacity 10 in IHR SPS ART

7 Human resource capacity Human resource No change

8 Laboratory National Health Emergency framework

Core capacity 5 in IHR SPAR

9 Points of Entry (PoE) Health service provision (New) Core capacity 11 in IHR SPAR

10 Zoonotic events Risk communication Core capacity 3 in IHR SPAR

11 Food safety Points of entry Core capacity 4 in IHR SPAR

12 Chemical events Chemical events No change

13 Radiation emergencies Radiation emergencies No change

Table 1. Core capacities in IHR QM and IHR SPAR

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met the minimum requirement, and 84 had requested for an additional two-year extension.17

Results of IHR Monitoring QuestionnaireIn 2017, 167 of the 196 States Parties (85%) had responded to IHR MQ.18 The global scores for IHR MQ 2017 is summarised in Table 2. Globally, the core capacities that had the lowest scores were Human Resource (61%), Points of entry (62%), Chemical (56%) and Radionuclear (57%), while the remaining nine core capacities had scored over 70% in 2017. Compared to 2010, when the first questionnaire was administered,19 the global scores of all indicators had showed an improvement with the greatest leap in Legislation, Surveillance, Preparedness and Human Resource. In terms of regional performance, the West Pacific Region (WPR) scored the highest in seven core capacities in 2017 (Figure 1).

Within the WPR region, there was an overall improvement of the scores in the past seven years, although the scores for 2017 were on average lower than 2016 (Figure 2). The improvement could be a result of regional engagement by WHO and its partners, as well as the implementation of Asia Pacific Strategy for Emerging Diseases (APSED) framework that assisted States Parties to enhance its capacities.

Joint External EvaluationThe JEE comprises two components, a self-assessment of capacities by the States Parties, and an on-site visit by a team of external evaluators.20 The objective of JEE is to identify the most urgent gaps in the country’s health system, and to prioritize the areas and plans for strengthening. The first evaluation will establish

the baseline measurement of the capacities, and subsequent evaluations will highlight the progress that were made, if any. The JEE tool covers 19 capacities under four main areas - a) prevent, b) detect, c) respond, and d) other IHR-related hazard and PoE.

Since WHO adopted the JEE tool in February 2016, a total of 96 evaluations had been conducted in six WHO regions as of May 2019.21 Most of the countries that had completed the assessment with country reports published on WHO’s website were from AFR, Eastern Mediterranean Region and South-East Asia Region.22 Within the WPR, nine out of 27 States Parties were reported to have completed JEE.

SINGAPORE’S EXPERIENCE

Core capacitiesSince IHR (2005) entered into force in 2007, Singapore has conscientiously ensured that our policies and public health responses are in line with WHO’s IHR requirements, and to achieve the stipulated core capacities.

The Ministry of Health (MOH), National Environment Agency (NEA), Singapore Food Agency, and National Parks Animal and Veterinary Service work together in an integrated (One Health) manner to oversee the surveillance, verification, response and notification of infectious diseases in human and animal, as well as border health control to prevent international spread of diseases. Also, MOH and NEA work closely with the Singapore Civil Defence Force on matters related to chemical

Core capacities 2017 (%) 2016 (%) 2015 (%) 2010 (%)Legislation 75 81 83 58Coordination 78 84 84 70Surveillance 83 87 88 65Response 79 85 86 71Preparedness 70 75 75 51Risk communication 74 81 82 64Human resources 61 61 65 41Laboratory 82 82 84 67Points of entry 62 65 62 54Zoonosis 83 89 87 72Food safety 78 80 78 67Chemical 56 60 58 42Radionuclear 57 65 60 46

Table 2. Comparing the global scores of IHR core capacities for past three years (2015-2017) versus 2010

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and nuclear threats. In addition, MOH together with NEA, Civil Aviation Authority of Singapore, Maritime & Port Authority of Singapore and Immigration and Checkpoint Authority, have put in place a set of border health measures to prevent the incursion of public health threats, and to mitigate its spread under the legal power of the Infectious Diseases Act.23 For example, in response to the ongoing threat of Middle East respiratory syndrome coronavirus (MERS-CoV), temperature screening is conducted at the international airport on passengers disembarking from flights from the Middle East. Symptomatic travellers suspected for

MERS-CoV by the healthcare providers at the point of entry would be transferred to a designated hospital for isolation and testing.

IHR monitoring and evaluationSince the IHR MQ was rolled out in 2010, we have responded to the questionnaire annually. In Oct 2011, Singapore officially informed WHO that the country had established the requisite national core capacities set out in the IHR (2005). In Apr 2018, the country was evaluated by a team of external evaluators for these core capacities in detecting and responding to

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Figure 1. Scores of IHR core capacities by regions for 2017

Figure 2. Score of IHR core capacities in Western Pacific Region between 2010 and 2017

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potential public health emergencies. This joint external evaluation exercise gave us a high overall score for public health preparedness, and the WHO evaluation team assessed that Singapore demonstrated good capacity and notable progress in the implementation of the IHR.

CONCLUSION

Global health security is important because, with today’s ease of travel, emerging infectious diseases can be readily introduced into Singapore. Extensive outbreaks can result in high mortality and morbidity, and also enormous economic loss to the country. To date, there are no completely effective screening tools to detect a traveller with imported disease at the points of entry. Having a robust public health system with detailed preparedness plans will help to detect outbreaks earlier, and mitigate its spread locally and internationally. references

REFERENCES

1. World Health Organization. International Health Regulations (2005). Third Edition. Available at http://apps.who.int/iris/bitstream/10665/246107/1/9789241580496-eng.pdf?ua=1

2. World Health Organization. Frequently asked questions about the International Health Regulations (2005). Available at: http://www.who.int/ihr/about/faq/en/

3. World Health Organization. Origin and development of health cooperation. Available at: http://www.who.int/global_health_histories/background/en/

4. WHO Official Records, No. 176, 1969, resolution WHA22.46 and Annex I.

5. Stowman K. International sanitary regulations. Public Health Rep. 1952 Oct;67(10):972-6.

6. Calain P. Exploring the international arena of global public health surveillance. Health Policy Plan. 2007 Jan;22(1):2-12.

7. Baker MG, Forsyth AM. The new International Health Regulations: a revolutionary change in global health security. N Z Med J. 2007;120(1267).

8. Andrus JK, Aguilera X, Oliva O, Aldighieri S. Global health security and the International Health Regulations. BMC Public Health. 2010 Dec 3;10 Suppl 1:S2. doi: 10.1186/1471-2458-10-S1-S2.

9. World Health Organization. Alert, response, and capacity building under the International Health Regulations (IHR). Ten things you need to do to implement the IHR. Available at: http://www.who.int/ihr/about/10things/en/

10. World Health Organization, The World Health Report. The world health report 2007 - A safer future: global public health security in the 21st century. Available at http://www.who.int/whr/2007/en/

11. World Health Organization, International Health Regulations (2005). IHR core capacities monitoring framework: Checklist and indicators for monitoring progress in the development of IHR core capacities in States Parties. 2013. Available at http://apps.who.int/iris/bitstream/10665/84933/1/WHO_HSE_GCR_2013.2_eng.pdf

12. World Health Organization. Monitoring of IHR core capacities development and maintenance after June 2012. Information for States Parties to the IHR. January 2013. Available on Event Information Site (secured website)

13. World Health Organization. Information to States Parties regarding determine of fulfilment of IHR core capacities requirement for 2012 and potential extensions. January 2012. Available at: http://apps.who.int/iris/bitstream/10665/70820/1/WHO_HSE_GCR_2012.1_eng.pdf

14. World Health Organization. Development, monitoring and evaluation of functional core capacities for implementing the International Health Regulations (2005) – Concept note. Available at: http://www.who.int/ihr/publications/concept_note_201407.pdf?ua=1

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15. World Health Organization. Implementation of the International Health Regulations (2005). Report of the Review Committee on Second Extensions for Establishing National Public Health Capacities and on IHR Implementation. 16 January 2015. Available at: http://www.wpro.who.int/about/regional_committee/63/documents/RC63_09_Item_14_IHR_FINAL_19_July.pdf?ua=1

16. World Health Organization. Implementation of the International Health Regulations (2005). Report of the Review Committee on the role of the International Health Regulations (2005) in the Ebola outbreak and response. 13 May 2016. Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_21-en.pdf?ua=1

17. World Health Organization, Global Health Observatory (GHO) data. International Health Regulations (2005) Monitoring Framework. Available at: http://www.who.int/gho/ihr/en/

18. World Health Organization. International Health Regulations (2005). Summary of 2011 States Parties report and IHR core capacities implementation. Available at: http://www.who.int/ihr/publications/WHO_HSE_GCR_2012.10_eng.pdf

19. World Health Organization. IHR (2005) Monitoring and Evaluation framework. Joint External Evaluation tool. Available at: http://apps.who.int/iris/bitstream/10665/204368/1/9789241510172_eng.pdf

20. JEE Alliance. Joint External Evaluation (JEE). Available at: https://www.jeealliance.org/global-health-security-and-ihr-implementation/joint-external-evaluation-jee/

21. World Health Organization. Strengthening health security by implementing the International Health Regulations (2005). Joint External Evaluation (JEE) mission reports. Available at: https://www.who.int/ihr/procedures/mission-reports/en/

22. Infectious Diseases Act. Last amendment on 28 September 2016.Available at: http://statutes.agc.gov.sg/aol/search/display/view.w3p;ident=c7e2964d-2f23-4a22-beac-e0299e28fe5f;page=0;query=DocId%3A5e69eb8c-5499-4f83-b096-9747cd9f1fa8%20Depth%3A0%20Status%3Ainforce;rec=0

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INTRODUCTION

Pandemics pose a major threat to global health security. In 2019, the World Economic Forum ranked the spread of infectious diseases as one of the top 10 risks in terms of potential impact. Over 12,000 disease outbreaks had been recorded between 1980 and 2013 at a global level.1 In the two first decades of the 21st century, the world had witnessed several major infectious disease outbreaks that crossed national borders and caused considerable human and economic damages. Three outbreaks that greatly compromised global health security were the 2003 Severe acute respiratory syndrome (SARS) pandemic, the 2009 H1N1 influenza pandemic, and the 2014 Ebola virus disease (EVD) epidemic in West Africa.2

In 2018, the World Health Organization (WHO) added ‘Disease X’ to its list of priority diseases.1 Disease X stands for a deadly disease that is currently unknown but that may eventually emerge in the future. The addition of Disease X to the list of priority diseases highlighted that the WHO was considering the likely possibility of a worst-case scenario of a pandemic caused by an unknown viral pathogen. Such a worst-case scenario occurred during the First World War (WWI) with the 1918 influenza pandemic - a pandemic that resulted from a novel virus which infected more than a third of the world’s population and cost more than 50 million lives.3 The 1918 influenza pandemic caused more casualties than the WWI itself.4 To prepare for future influenza pandemic, the deadly virus was recreated almost 90 years later by civilian and military researchers in the United States (US).5

MILITARIES IN GLOBAL HEALTH SECURITY

Naturally occurring infectious disease outbreaks have historically posed a threat to soldiers upon deployment on foreign grounds.6 However, the role of militaries in global health security has changed

in the 21st century, since national and foreign military forces have become more prominently deployed during public health emergencies. Their tasks range from containing outbreaks to maintaining public order and thereby ensuring trade, travel, and tourism, activities on which countries depend on economically.7

The deployment of militaries in a public health emergency had reached an unprecedented level during the 2014 EVD epidemic in West Africa, a mission which was sanctioned at the highest level of international security by the United Nations Security Council with resolution 2177.8 With more than 2,500 troops deployed, the US military contributed the largest number of military personnel among all foreign militaries involved in the international response to the EVD epidemic in Guinea, Liberia, and Sierra Leone.9 For the People’s Liberation Army (PLA), China’s military, it marked the first-ever deployment to respond to a public health crisis abroad. The PLA’s medical personnel notably provided direct treatment to local patients despite not having previous experience with the disease.10

Using existing military resources in the treatment of patients is just one of the several military capabilities that can bolster health security. Other capabilities include diagnostics, research, microbial forensics, logistics, security, assistance in the enforcement of quarantine measures, and disease surveillance.

Military capabilities in disease surveillanceSurveillance is the most crucial weapon in public health armamentarium. Surveillance systems provide critical medical intelligence and serve as early warnings to decision-makers, who need to anticipate the emergence of diseases, implement measures to monitor the situation, and evaluate disease outbreak responses.9

Military capabilities in public health surveillance with a global reach is uncommon as only a few superpower countries possess military bases on foreign territory. One of which is the US military, which maintains a

Role of Defense in Epidemic ResponseFrancesco Gaetano Fazzi

Lee Kuan Yew School of Public Policy, National University of Singapore

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global laboratory-based surveillance network with four military laboratories in Peru, Egypt, Kenya, and Thailand. The laboratories monitor influenza and respiratory diseases in host populations and among its military personnel and their families, and are part of the Department of Defense-Global Emerging Infections Surveillance and Response System (DoD-GEIS). DoD-GEIS comprises 500 additional laboratories in 75 partner countries and is a component of the larger WHO’s Global Influenza Surveillance Network.11 In 2009, DOD-GEIS responded to 76 outbreaks in 56 countries, mainly outbreaks of influenza, dengue, cholera, and hepatitis.12

The benefits of military surveillance programs in health security, for instance in the support of the implementation of the WHO’s International Health Regulations (IHR),13 are plentiful. Investments of foreign militaries in medical infrastructure (i.e. laboratories and equipment) in host countries as capacity-building efforts do not only help partner countries in becoming more resilient, but also strengthen the relationships between the host and the donor country.14

In the Global South, military forces are valuable state actors that can contribute to infectious disease surveillance as they can reach remote populations that are not served by civilian public health programmes. In these remote regions, militaries can provide health services to civilians and obtain surveillance data. These services provided to locals contribute to the implementation of WHO’s IHR. Establishing military surveillance capabilities in these remote areas generates a win-win situation as it mitigates the local population’s infectious diseases risk while providing an early warning to epidemics with potential of global significance.15

ASIA AS POSSIBLE DISEASE X HOTSPOT

DemographicsHistorically, hotspots of disease emergence were found in Central America, Tropical Africa, as well as East, South, and Southeast Asia (SEA).16 Asia is a region particularly susceptible to epidemics and pandemics. More people live in Asia than anywhere else on the planet,17 making it the most densely populated region in the world. Simultaneously, most of the population in Asia lives in low- to middle-income countries. Disparities in the quality of health systems between countries in Asia are reflected for instance in SEA, where life expectancy ranged from 56 years in Myanmar to 81 years in Singapore according to the WHO.18 East, South, and

SEA on their own host three of the five world’s largest countries by population size. SEA alone is home to 600 million people. The region lives right at the heart of emerging zoonotic, vector-borne diseases and multidrug-resistant bacteria that are of global significance, which burdened countries with the lowest incomes the most.18,19

Changes to human’s cultureBased on steady population growth, the susceptibility to epidemics in this region is expected to rise. The combination of a growing population, rapid urbanization, changes in agriculture practices, land use and food production, and intensified contact between humans and animal reservoirs creates an increasing likelihood for pathogens to transmit within human populations,19 and may give rise to a new disease in SEA. Furthermore, the rise of low-cost airlines has significantly amplified the frequency of domestic and international travel in the region,20 which increase the risk of spread of infectious diseases.

Weakness in surveillance In SEA, populations living in rural or remote areas are among the most disadvantage in health care coverage and therefore suffer most from the ‘triple burdens of diseases’ – persistent and emerging infectious diseases, non-communicable diseases, and injuries.21 At the same time, SEA suffers from poor surveillance systems due to the weak government policies and legal frameworks for surveillance and control of diseases emerging from natural reservoirs, low capabilities for diagnosis, and a lack of emphasis on animal surveillance.19 Hence, to improve health security, the surveillance of populations and livestock living in remote areas would be essential for several reasons.

Firstly, continued human expansion into wildlife habitats in SEA gives rise to emerging diseases as farmers’ livestock share a habitat with natural reservoirs of diseases and are exposed to an increase risk of cross-species transmission.19,22 Secondly, most emerging infectious diseases in the region are transmitted by their natural hosts or by vectors to human, either directly or over an intermediary hosts such as livestock.19

Thirdly, the region is home to a variety of natural hosts of infectious diseases. A recent study on wildlife reservoirs of flaviviruses demonstrated that SEA has the highest number of natural reservoirs for Zika virus and yellow fever virus globally.23

While SEA has experienced a major outbreaks of Zika virus in 2016,24 human cases of yellow fever have never been recorded in Asia to date,22 but yet may emerge.

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To make matters worse, SEA hosts more than 330 bat species, which accounts for one fourth of the world’s bat diversity.25 Bats are the reservoirs of many viral diseases that caused severe epidemics and pandemics in the past two decades, including Ebola virus, SARS coronavirus, Nipah virus, and the Middle East Respiratory Coronavirus.26 Scientific discoveries of novel viruses such as the Měnglà virus, which shares genetic characteristics with Ebola virus and Marburg virus, in a bat species in China27 is another reminder that the described reservoirs possess the potential to generate the next Disease X in Asia.

THE IMPORTANCE OF MILITARY SURVEILLANCE CAPABILITIES FOR SOUTHEAST ASIA

Through investment into surveillance capabilities in remote areas, militaries can tackle viral infectious diseases at the roots of the problem.28 Militaries in the Global North would be well advised to deploy their resources in surveillance and diagnostics in remote areas close to the natural reservoirs of viral diseases with militaries of countries in the Global South, particularly SEA, to obtain medical intelligence and to detect unusual disease occurrences as early as possible.

Wild animal species which are hosts for known and unknown viral diseases often reside in remote habitats in SEA. This circumstance makes it difficult to obtain large numbers of samples for detection and research of viruses,22 which is essential to establish surveillance programs that aim to identify new hosts of viral diseases.

POTENTIAL CHALLENGES

Complications from deploying military capabilities for public health purposes might arise due to a perceived lack of neutrality,29 regardless whether deployed military forces are national or foreign, an issue that arose during the 2014 EVD epidemic. As local authorities did not properly inform the population about the deployment of foreign militaries, false rumours about the reasons for their involvement were spread. In Guinea, health workers of the African Union were ambushed by the local community, which believed that the health workers were, in fact, spreading the disease rather than containing it. The health workers were rescued and evacuated by the military.30

Finally, the use of military capabilities remains contested, even among militaries. Although health security has been recognized as one of the most

important non-traditional security issues in current times,31 critics maintain that mobilizing military capabilities to bolster health security is diverging too strongly from militaries’ core business, detracts critical resources from military operations relating to war, and therefore weakens their national security.30

CONCLUSION

Militaries are the last line of defence during disease outbreaks with pandemic potential, which was demonstrated during the 2014 EVD epidemic. With their existing capabilities in disease surveillance, militaries have the potential to play a more proactive role in mitigating the risk of potential Disease X outbreaks, particularly in SEA, where the next pandemic is not a matter of if, but when.

Although militaries possess capabilities that can bolster global health security, they should not be considered a panacea to prevent and respond to public health crises. Military capabilities in disease surveillance can complement civilian capabilities, for instance in remote regions, but cannot replace the latter in the long run. Therefore, it is remains imperative for governments in the Global South to buttress their civilian public health capabilities, particularly capabilities for disease surveillance and outbreak response as these two capabilities cannot function independently from each other.

To improve health security and effectively avert disastrous outcomes, military capabilities should be incorporated into public health systems at a permanent basis, hence improving military-civilian cooperation for public health crises. Simultaneously, civilian capabilities should be reinforced to meet the standards set by the WHO’s IHR in the long run, thereby allowing militaries to concentrate on their core business, if geopolitical circumstances require them to do so. Given the recent emergence of militaries as non-traditional public health actors, it is furthermore recommendable to establish and publicly communicate international standards for militaries during public health crisis deployments that ensure their neutrality and dictate a clearly defined purpose of military operations.

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REFERENCES

1. World Economic Forum. The Global Risks Report 2019, 14th Edition. Available at: http://www3.weforum.org/docs/WEF_Global_Risks_Report_2019.pdf

2. Amul GG & Pang T. Regional Health Security: An Overview of Strengthening ASEAN’s Capacities for the International Health Regulations. Global Health Governance 2018; 7: 30-54. Available at: http://blogs.shu.edu/ghg/files/2018/12/Fall-2018-Issue.pdf

3. Centers for Disease Control and Prevention. 1918 Pandemic (H1N1 virus). 20 March 2019. Available at: https://www.cdc.gov/flu/pandemic-resources/1918-pandemic-h1n1.html

4. Copping J. WW1 dead and shell shock figures 'significantly underestimated. The Telegraph. 16 January 2014. Available at: https://www.telegraph.co.uk/history/world-war-one/10577200/WW1-dead-and-shell-shock-figures-significantly-underestimated.html

5. Centers for Disease Control and Prevention. Researchers Reconstruct 1918 Pandemic Influenza Virus; Effort Designed to Advance Preparedness. 5 October 2005. Available at: https://www.cdc.gov/media/pressrel/r051005.htm

6. Ho ZJM, Hwang YFJ & Lee, JMV. Emerging and re-emerging infectious diseases: challenges and opportunities for militaries. Military Medical Research 2014;1:1-10.

7. Heymann D. The Evolving Infectious Disease Threat: Implications for national and global security. Journal of Human Development 2003;4: 191-207.

8. United Nations Security Council. Resolution 2177 (2014). 18 September 2014. Available at: http://unscr.com/en/resolutions/doc/2177

9. Nevin RL & Anderson JN. The timeliness of the US military response to the 2014 Ebola disaster: a critical review. Medicine, Conflict and Survival 2016;32:40-69

10. Chen ZL, Chang GH, Zhang WY et al. Mobile laboratory in Sierra Leone during outbreak of Ebola: practices and implications. Science China Life Sciences 2015;58: 918-921

11. Sueker JJ, Blazes DL, Johns MC et al. Influenza and respiratory disease surveillance: the US military’s global laboratory-based network. Influenza and other Respiratory Viruses 2010;4; 155-161

12. Johns MC, Burke RL, Vest KG et al. A growing global network’s role in outbreak response: AFHSC-GEIS 2008-2009. BMC Public Health 2011;11: S3.

13. Thomson N, Littlejohn M, Strathdee SA et al. Harnessing synergies at the interface of public health and the security sector. The Lancet 2019;393: 207-09.

14. Michaud J, Moss K, Licina D et al. Militaries and global health: peace, conflict, and disaster response. The Lancet 2019; 393: 276-86.

15. Chretien JP, Blazes DL, Coldren RL et al. The importance of militaries from developing countries in global infectious disease surveillance. Bulletin of the World Health Organization 2007; 85: 174-80

16. Jones KE, Patel NG, Levy MA et al. Global trends in emerging infectious diseases. Nature 2008; 451: 990-93

17. Casabón C. More people live inside this circle than outside it - and other demographic data you should know. World Economic Forum. 18 July 2017. Available at: https://www.weforum.org/agenda/2017/07/more-people-live-inside-this-egg-than-outside-of-it-and-other-overpopulation-data/

18. Acuin J, Firestone R, Htay TT, et al. Southeast Asia: an emerging focus for global health. The Lancet 2011; 377 534-35.

19. Coker RJ, Hunter BM, Rudge JW et al. Emerging infectious diseases in southeast Asia: regional challenges to control. The Lancet 2011; 377: 599-609

20. Damuri YR & Anas T, Strategic Directions for ASEAN Airlines in a Globalizing World, The Emergence of Low Cost Carriers in South East Asia. REPSF Project No. 04/008. October 2005, Available at: http://aadcp2.org/file/04-008-FinalLCCs.pdf

21. Minh HV, Pocock NS, Chaiyakunapruk N et al. Progress toward universal health coverage in ASEAN. Global Health Action 2014;7: 25856.

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22. Morand S, Jittapalapong S, Suputtamongkol Y et al. Infectious diseases and their outbreaks in Asia-Pacific: biodiversity and its regulation loss matter. PLOS One 2014; 9:e90032

23. Pandit PS, Doyle MM, Smart KM et al. Predicting wildlife reservoirs and global vulnerability to zoonotic Flaviviruses. Nature Communications 2018; 9:5425

24. Duong, V, Dussart P & Buchy P. Zika virus in Asia. International Journal of Infectious Diseases 2017;54:121-128

25. Deka MA & Morshed N. Mapping Disease Transmission Risk of Nipah Virus in South and Southeast Asia. Tropical Medicine and Infectious Disease 2018;3:57

26. Han H, Wen H, Zhou C et al. Bats as reservoirs of severe emerging infectious diseases. Virus Research 2015; 205:1-6

27. Yang X, Tan CW, Anderson DE et al. Characterization of a filovirus (Měnglà virus) from Rousettus bats in China. Nature Microbiology 2019; 4: 390-95

28. Lee WT & Tan MY. Military Operations in the SAF: A New Paradigm. SAF Medical Corps Monograph 2017;11: 12-17

29. Watterson C & Kamradt-Scott A. Fighting Flu: Securitization and the Military Role in Combating Influenza. Armed Forces & Society 2016; 42: 145-168

30. Sandy J, Schnabel A, Sovula H et al. The Security Sector’s Role in Responding to Health Crises: Lessons from the 2014–2015 Ebola Epidemic and Recommendations for the Mano River Union and Its Member States. Geneva Centre for the Democratic Control of Armed Forces (DCAF). 2017. Available at: https://www.dcaf.ch/sites/default/files/publications/documents/The%20Security%20Sector%27s%20Role%20in%20Responding%20to%20Health%20Crises.pdf

31. Heymann DL, Chen L, Takemi K et al. Global health security: the wider lessons from the west African Ebola virus disease epidemic. The Lancet 2015; 385: 1884-1901

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NOTES FROM THE FIELD

Working with Working with WolbachiaWolbachia in in

Dengue ControlDengue ControlInterview with Charlene Tow |Senior Public Health Officer

Communicable Disease Division, Ministry of Health

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NOTES FROM THE FIELD

Charlene, could you please give us some background?

Charlene: Sure, the Wolbachia facility is open for members of the public to learn about Wolbachia-carrying Aedes aegypti mosquitoes. These mosquitoes can suppress the population count of wild Aedes aegypti mosquitoes in the community and are being released into test-sites located at Braddell Heights, Nee Soon East and Tampines West. As part of the team investigating vector-borne diseases such as dengue, chikungunya and Zika, we felt it was important to understand this new technology.

What did you see inside the Wolbachia facility?

Charlene: Our first stop was the nursery room where mosquitoes are grown right from the from egg stage. Our guide, a senior technician explained how the Wolbachia-carrying egg on stripes of paper are first soaked in water and then transferred to a yellow tray for the larvae to grow (Figure 1). Each tray consists of approximately 4000 larvae as too many of them in a tray would reduce optimum growth. The time taken to grow from eggs to pupae takes less than a week. The light and temperature in this room are strictly monitored as the larvae need 12 hours of light per day and a temperature of 28oC to grow optimally.

How interesting. What else did you see at the facility?

Charlene: Our guide showed us how they separated the male and female mosquitoes at the pupae stage.

This is a very important step as only male Wolbachia mosquitoes will be released into the environment. Using only two glass panels of which the space in between can be adjusted manually, pupae of a certain size are trapped in between when pouring water containing the pupae through (Figure 2). Separation is possible as male pupae are smaller than female pupae and thus when pouring them through the glass, the females will get stuck in the glass panel while the male pupae will flow through. Adjusting the glass panel, our guide poured water through to allow the female pupae to flow out into a separate tray.

What happens next with the pupae?

Charlene: After separating, the pupae are taken into the adults rearing room where the pupae would eventually emerge into the adult mosquitoes (Figure 3). Each cage has approximately few thousand mosquitoes. They are given a sugar stick for their food. Commercial animal blood are also given to the female adult mosquitoes by attaching the blood pack to an electric heater so that it mimics the heat of an animal/adult. The female adult mosquitoes require blood meals before they will hatch their eggs. We were also brought into the Flight Room where the Wolbachia mosquitoes take their first flight out. The flight room was essentially a series of big cages where humans were allowed to stand inside (Figure 4). The male mosquitoes were placed inside blue containers and given to us to be released.

Ms Charlene Tow and some disease detectives paid a study visit to the National Environment Agency’s Wolbachia facility at Neythal Road this year. The following interview gives an account of what she learned.

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NOTES FROM THE FIELD

Figure 1. (A) double doors at entrance; (B) nursery room; (C) stacks of yellow trays with larvae; (D) Wolbachia egg strips; (E) larvae counter; (E) food for larvae

A) B) C)

D) E) F)

Figure 2. (A) pupae separator; (B) two trays showing males on left tray and females on right tray

A) B)

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NOTES FROM THE FIELD

Figure 3. (A) adult rearing room; (B) cage with about 6,000 adult mosquitoes; (C) electric heater and blood pack for the adult cage

A) B)

C)

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NOTES FROM THE FIELD

Figure 4. (A) walk-through in the cage; (B) containers to release mosquitoes

Figure 5. Quality control PCR to detect Wolbachia in adult mosquitoes

It was a unique experience to be standing inside the cages with the adult mosquitoes flying all around us!

What were your takeaways from the visit?

Charlene: The Wolbachia facility gave us some idea of how intensive the process of producing Wolbachia-carrying Aedes mosquitoes can be, especially at the quantity required to release at the selected trial sites. For effective suppression effects, male mosquitoes need to be released twice a week and approximately three mosquitoes per resident, especially since mosquitoes only have a lifespan of 50% mortality by Day 4. Further improvements using technology were also in progress to increase the throughput of this process. Quality control is essential. For every batch, the researchers tested for the presence of Wolbachia inside the male mosquitoes (Figure 5).

How do you think Wolbachia can benefit Singapore?

Charlene: Since the early 1960s, Aedes aegypti has changed to become highly adapted to living in our urban landscape. Even with intensive checks, enforcement by NEA officers, and multi-stakeholders coming together to reduce possible breeding habitats, dengue had never been eradicated in our community. As the mosquitoes evolve, we must also move in our methods to fight the vector. Wolbachia suppression strategy presents a very novel approach which, when complemented with other measures, should reduce the incidence of dengue!

A) B)

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FAST FACTS

Norovirus Illness

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FAST FACTS

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FAST FACTS

How You Get Norovirus From People or Surfaces

Norovirus spreads when a person gets poop or vomit from an infected person

in their mouth.

PROVIDING CARE

CHANGING DIAPERS

SHAKING HANDS

TOUCHING CONTAMINATEDSURFACES

TOUCHING YOUR MOUTH

YOU BECOME ILL WITH NOROVIRUS

For more information, visit www.cdc.gov/norovirus CS287713-A

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Stop Norovirus!Norovirus causes diarrhea and vomiting. It spreads easily from an infected person to others, especially in long-term care facilities. Elderly residents are more likely to become very sick or die from norovirus.

Protect yourself and elderly residents from norovirus.

WASH YOUR HANDS

Wash your hands often with soap and water for at least 20 seconds each time and avoid touching your mouth.

CLEAN SURFACES

Use a bleach-based cleaner or other approved product* to disinfect surfaces and objects that are frequently touched.

WASH LAUNDRY

Remove and wash soiled clothes and linens immediately, then tumble dry.

USE GOWN AND GLOVES

Use gown and gloves when touching or caring for patients to reduce exposure to vomit or fecal matter.

STAY HOME WHEN SICK

If you’re sick, stay home and don’t take care of or visit people in long-term care facilities for at least 2 days after your symptoms stop.

For more information, visit www.cdc.gov/norovirus

*Use a chlorine bleach solution with a concentration of 1000-5000 ppm (5-25 tablespoons of household bleach [5.25%] per gallon of water) or other disinfectant registered as effective against norovirus by the Environmental Protection Agency(EPA) at http://www.epa.gov/oppad001/list_g_norovirus.pdf

CS287713-C

FAST FACTS

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SURVEILLANCE SUMMARY

Infectious Diseases Update

E Week 39 Cumulative first 39 Weeks2019* 2018 Median 2019 2018 Median

2014 -2018 2014 -2018FOOD/WATER-BORNE DISEASESAcute Hepatitis A 2 1 0 50 56 56Acute Hepatitis E 1 0 1 28 45 49Campylobacteriosis 6 11 10 361 308 347Cholera 0 0 0 2 2 1Paratyphoid 0 1 1 9 13 18Poliomyelitis 0 0 0 0 0 0Salmonellosis 43 28 36 1553 1197 1472Typhoid 1 1 1 60 31 37VECTOR-BORNE DISEASESChikungunya Fever 1 0 1 45 6 24Dengue Fever 260 40 135 12293 2081 7570Dengue Haemorrhagic Fever 3 0 0 76 21 19Japanese Encephalitis^ 0 0 NA 0 0 NALeptospirosis^ 1 0 NA 16 32 NAMalaria 0 2 0 21 24 16Murine Typhus^ 0 0 NA 4 9 NANipah virus infection 0 0 0 0 0 0Plague 0 0 0 0 0 0Yellow Fever 0 0 0 0 0 0Zika Virus Infection 0 0 NA 11 1 NAAIR/DROPLET-BORNE DISEASES Avian Influenza 0 0 NA 0 0 NADiphtheria 0 0 0 0 0 0Ebola Virus Disease 0 0 NA 0 0 NAHaemophilus influenzae type b 0 0 0 3 3 3Legionellosis 1 2 1 17 16 15Measles 2 0 1 147 29 58Melioidosis 0 0 1 34 19 34Meningococcal Disease 0 0 0 6 6 6Mumps 8 7 12 315 380 380Pertussis 1 2 1 58 85 52Pneumococcal Disease (invasive) 1 2 2 107 101 106Rubella 0 1 0 0 10 11Severe acute respiratory syndrome 0 0 0 0 0 0Tetanus^ 0 0 0 0 1 0OTHER DISEASESAcute hepatitis B 1 1 1 30 36 35Acute hepatitis C 0 2 1 15 12 12Botulism^ 0 0 NA 0 1 NAMERS-CoV Suspect cases tested 0 2 NA 127 128 NA Other patients tested 0 2 NA 84 69 NAPOLYCLINIC ATTENDANCES - AVERAGE DAILY NUMBERAcute upper respiratory infections 2564 2767 2686 NAAcute conjunctivitis 88 79 84 NAAcute Diarrhoea 578 571 483 NAChickenpox 11 15 NA NAHand, Foot And Mouth Disease 19 17 NA NAHIV/STI/TB NOTIFICATIONS 2019 Aug Cumulative 2019HIV/AIDS 23 203Legally Notifiable STIs 309 3391Tuberculosis 132 993* Preliminary figures, subject to revision when more information is available.

As of E Week 39 (22-28 Sep 2019)

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SURVEILLANCE SUMMARY

INFLUENZA SURVEILLANCE

The average daily number of patients seeking treatment in the polyclinics for Acute Respiratory Infection (ARI) increased above 70th percentile in July 2019. It decreased below 70th percentile in Aug and Sept 2019. The proportion of patients with influenza-like illness (ILI) among the polyclinic attendances for ARI is 1.3%. The overall positivity rate for influenza among ILI samples (n=237) in the community was 19.8% in the past 4 weeks. Of the specimens typed for influenza in Sept 2019, these were positive for influenza A (H3N2) (22.2%), influenza A (H1N1) pdm09 (47.2%), and influenza B (30.6%). 0% of the influenza A specimens were untypable due to low titre.

Monthly Influenza Surveillance

Polyclinic Attendances for Acute Respiratory Infection, 2018-2019

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SURVEILLANCE SUMMARY

SURVEILLANCE OF SELECTED DISEASES

Dengue Fever/Dengue Haemorrhagic Fever

Chikungunya

Paratyphoid/Typhoid

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SURVEILLANCE SUMMARY

Mumps

Pneuomococcal Disease (Invasive)

Measles

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ENB Quarterly is published in Jan, Apr, Jul and Oct every year by the Ministry of Health, Singapore. Readership includes physicians, epidemiologists, microbiologists, laboratorians, researchers, scientists, and public health practitioners. Correspondence address: The Editor (ENB Quarterly), Public Health Group, Ministry of Health, 16 College Road, College of Medicine Building, Singapore 169854. A downloadable electronic format is provided free of charge at our website: https://www.moh.gov.sg/content/moh_web/home/Publications/epide-miological_news_bulletin.html Contribution by authors of articles to ENB Quarterly is a public health service and does not preclude subsequent publication in a scientific peer-reviewed journal. Opinions expressed by authors do not neces-sarily reflect the position of the Ministry. The material in ENB Quarterly may be reproduced with proper citation of source as follows: [Author]. [Article title]. Epidemiol News Bull [Year]; [Vol]:[inclusive page numbers]

Summary statistical data provided in ENB Quarterly are provisional, based on reports to the Ministry of Health. For more current updates, please refer to our MOH Weekly Infectious Diseases Bulletin: https://www.moh.gov.sg/content/moh_web/home/statistics/infectiousDiseas-esStatistics/weekly_infectiousdiseasesbulletin.html

Do you have any ideas or suggestions? Your views are important to us.

Please contact us [email protected]

EDITORIAL BOARDSteven Ooi, Chair

Jeffery CutterLalitha Kurupatham

Stefan Ma

SUB-EDITORSChan Pei Pei

Khine NandarNur-Afidah Md Suhaimi

See Wanhan

ADVISORY PANELDerrick Heng, Group Director

Vernon Lee, Communicable DiseasesLyn James, Epidemiology & Disease ControlExternal Advisors Charlene Fernandez

Chew Ming FaiDale FisherHsu Li Yang

Irving BoudvilleLeong Hon Keong

Lim Poh LianNancy Tee

Raymond Lin