With an improvement in socio-economic status and hygienic conditions in Hong Kong, people are now suffering less from infectious diseases compared to the last few decades.1 Despite this, effective prevention and control of infectious diseases are still of importance due to the risk of outbreaks that could occur at any time with the emergence of new infectious agents.1 Professor Yuen Kwok-Yung, was invited to share his insights on emerging infectious diseases and beyond at the Hong Kong Academy of Medicine 25th Anniversary Congress.
Emerging infectious disease (EID) is defined by the World Health Organization (WHO) as “one that has appeared and affected a population for the first time, or that has existed previously but is rapidly increasing, either in terms of the number of new cases within a population, or its spread to new geographical areas”.2 EID is a serious concern and poses major challenges to public health as it causes a high death toll, as well as having a vast social and economic impact.2 There are two main factors that can lead to the emergence of new diseases; changes in geographical range and adaptive emergence.3 Changes in geographical footprint of microorganisms can lead to a spread globally via humans or animals, such as from infected travelers or the trading of infected animals or animal products.3 Adaptive emergences are the genetic changes of the microorganism, enabling the invasion of a new ecosystem.3 Urbanization and the destruction of natural habitats can cause humans and animals to live in closer proximity, where zoonotic diseases (conditions from animals that can infect humans) can spread easier.2 These factors all enable infectious agents to evolve, and to reach, adapt and spread between hosts, and the significance of its impact can be difficult to predict.2
Asia has often been at the epicenter of discovery of new infectious diseases.2 According to the Department of Health, there are currently 50 notifiable infectious diseases in Hong Kong, with the total reported cases of infectious diseases amounting to 18,515 in 2017.1
Outbreak of influenza A (H5N1)
The first outbreak of H5N1 virus (Avian Influenza A) in humans happened in Hong Kong during 1997, and back then, the known subtypes of influenza A found in birds were also found to infect other animals including domestic animals, marine mammals, and humans.4 This H5N1 subtype was observed to be the first avian influenza virus directly infecting humans from poultry.2 The primary risk factor for human infection likely occurs through direct or indirect contact with infected poultry, including the handling and preparation of poultry for consumption or of contaminated products.2
The rate of complications was found to be higher with H5N1 than the other human influenza virus subtypes, H3N2 and H1N1, including gastrointestinal malfunctions, and liver and renal dysfunctions, and there was a 42% mortality rate in patients admitted to hospital.4 Rapid diagnosis of the influenza was deemed to be useful in clinical management to start antiviral therapy earlier.4 “After many years of preparation in clinical infectious diseases, microbiology and molecular biology, we were able to launch the rapid [reverse transcriptase polymerase chain reaction] RT-PCR test for managing the first human epidemic of infection by the avian influenza A H5N1 virus,” explained Prof. Yuen, and the H5-subtype-specific assay was useful for rapid detection of the virus directly in respiratory specimens.4
H5N1 reappeared in Hong Kong again in 2003 and spread to other parts of Asia, through to Europe and Africa.2,5 A meta-analysis suggested that there was a seropositive rate of 1.2% amongst the exposed population.5 There have been observations in seasonal variation and differences in the mean age of patients affected in different countries.5 In Egypt, the country with the highest incidence rate since 2009, infection tended to peak in late winter and early spring, with the affected median age being 6 years, whereas the most affected age group in Asia is 20-29 years old.5
Despite worldwide efforts to contain this epidemic in Southeast Asia, there were still cases of H5N1 reported in 2017.5,6 The total number of cases reported to the WHO to date is 860, with a total mortality of 454 people.6 Vaccinations, though effective, are impaired by low uptake rate in farms and the lack of cross-protection within and between different groups of organisms.7 Currently, a vaccine is available for the H5N1 strain but there is no vaccine to prevent H7N9 or other avian influenza strains in humans.2,7
Inside hospitals: Healthcare-associated infections
Healthcare facilities are places of outbreak amplification; between staff and patients and then transmission back into communities.8 One of the most prevalent adverse event that can threaten the safety of a patient is said to be healthcare-associated infections (HAIs),9 and the WHO states that hundreds of millions of patients are affected by inadequate infection and prevention control practices in every day healthcare delivery.8 It is estimated that there are over 2.5 million cases of HAIs occurring within the European Union and European Economic Area (EU/EEA) annually,10 but data from Asia is scarce and limited to the developed Asian Nations only, such as Korea and Japan.11 In a prevalence survey conducted by the Hospital Authority (HA) of Hong Kong in 2010, a total of 3.1% of the 20,355 patients surveyed had contracted a HAI.12
HAIs are associated with increased morbidity and mortality, yet many cases are preventable.10 Prof. Yuen spoke about a case in his management of healthcare-associated hepatitis C infection in the secondary care setting in Hong Kong.
Nosocomial transmission of hepatitis C in Hong Kong
According to the WHO, the number of deaths from viral hepatitis is on the rise.13 It is estimated that over 70 million people are infected and living with hepatitis C virus (HCV) around the world.13 HCV is a blood-borne pathogen which is a public health concern as it is associated with healthcare-associated transmission either via contaminated blood and/or unsafe injections.14 It can be found in various biological fluids but the transmission is mainly via percutaneous exposure to blood with high viral load.14,15 In a healthcare setting, the main places of transmission are in the transplantation wards, hemodialysis units or via the use of contaminated needles and syringes.14
In 2017, a post-liver transplant patient in Hong Kong was found to have contracted HCV and an investigation was conducted due to the initially unidentifiable origin of the pathogen as the donor and used blood products were all HCV negative.15 During the index patient’s period of stay in the liver transplant center, four known HCV carriers were also in the same ward and it was discovered that the phlebotomy trolley and reusable tube holders were shared between the patients, leading to a risk of cross infection.15 It could not be determined whether the tube holders were disinfected between use, and when samples were collected from all surfaces of the phlebotomy trolley and all of the apparatus, HCV RNA genotype 6a (matching the then deceased patient’s genotype) was detected on the inner surface of the tube holder.15 After in-vitro studies were conducted by Prof. Yuen’s team, it was suggested that the rubber sleeve of the sleeved needle was contaminated after insertion into the same tube holder that was used on a HCV-positive patient prior.15 It is thought that once the tourniquet was released after drawing blood from the index patient, blood from the vein flowing back to the heart due to negative pressure could have caused the reflux of HCV-contaminated blood from the space between the rubber sleeve and needle and into the index patient’s vein.15 “By DNA sequencing, the virus inside the tube holder, in the patient and the source were almost identical,” explained Prof. Yuen. This suggested clonality, but the study is limited as there was only one case of this happening and it was not possible to determine the exact mechanism of transmission.15
Prof. Yuen further explained that healthcare workers were not told to follow the manufacturer’s advice to disinfect the tube holders between use by emersion in household bleach for five minutes. Nevertheless, following the investigation, the HA stopped the use of all reusable collection tube holders and have since switched to using single-use disposable tube holders.
Outside of infectious diseases – the increase of antimicrobial drug resistance
“One of our top global public health challenges is the worsening antimicrobial resistance, which many doctors and administrators do not admit [to],” said Prof. Yuen. Antimicrobial resistance (AMR) is an increasingly serious threat to public health, with reduced treatment effectiveness and an increased cost of health care, risk of spreading to others, and mortality.16 It was estimated that 700,000 deaths may be caused annually by AMR worldwide.17 The WHO therefore states that “all countries need national action plans on AMR.”16
The Centre for Health Protection (CHP) in Hong Kong recognizes that AMR is posing a significant threat to the public health in Hong Kong, with an increase of five-fold of community-associated methicillin-resistant Staphylococcus aureus (MRSA) between 2007-2016.17 Prof. Yuen presented data showing Hong Kong blood culture isolates of MRSA are four times that of cultures from the United Kingdom which he described as “really alarming”. The CHP is also committed for Hong Kong to adopt global directions in AMR containment measures.17
Emerging AMR – Carbapenemase-producing Enterobacteriaceae
Carbapenemase-producing Enterobacteriaceae (CPE) are emerging multidrug-resistant gram-negative organisms, and the prevention of transmission in healthcare settings are important as it is associated with a 37% mortality rate upon infection of the bloodstream.18 From a study in Hong Kong conducted over 4 years, 66,672 fecal specimens where screened, of which the overall gastrointestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) was found to be 1.6%.18 The prevalence of both CPE and CRE increased between 2012-2015 by 15- and 30-fold respectively, and in 2015, over 20% of patients with CRE isolates had carbapenemase-producing strains.18
Some sources of infection could be determined, such as hospitalization outside of Hong Kong (especially in mainland China where CPE was prevalent); carbapenemase-producing microorganisms reportedly found in food products and animals, and nosocomial acquisition.18 It was also found that the use of broad-spectrum antibiotics including cephalosporins and carbapenems was associated with CPE acquisition and could prolong its colonization, of which could be between 6 months to three years in the gastrointestinal tissues.18
The use of proton pump inhibitors (PPIs), especially in combination with broad-spectrum antibiotics, were also found to be a risk factor for both colonization of CPE and C.difficile.18 Although it is unclear how CPE colonizes the gastrointestinal tract, it is believed that the suppression of hydrochloric acid in gastric secretions by PPIs allowed the passage of CPE from oral intake or tube feeding to the lower intestines of these patients.18 It is therefore suggested that rigorous hand hygiene practice in hospitalized patients before meals and medications is important, especially in those on concomitant antibiotics and PPIs, in order to minimize risk of oral ingestion of CPE.18 It was observed that the use of both of these classes of drugs together delayed the clearance of CPE, and this finding supports the necessity to limit the use of these drugs concurrently to facilitate clearance.18
Prof. Yuen expressed, “as doctors, we have the responsibility to provide health advice for personal protection to patients who are prescribed antibiotics or PPIs.” Prof. Yuen explained that the HA used printed health advice warning labels when dispensing antibiotics since 2016, but it was not until November 2018 that Queen Mary Hospital started to use additional warning labels when dispensing PPIs too, which has the following advice: “Avoid raw or uncooked food. Wash hands frequently.”
From the cases discussed, infectious diseases can be acquired through several channels, from the community or a healthcare setting. With emerging infectious disease and constant evolution of existing infectious agents, there will always be a need to enhance the extent of prevention and control as far as possible. Despite the discovery of over 60 novel viruses at the University of Hong Kong, Prof. Yuen stated, “just finding new viruses is not our objective; we must find ways to control them.”
Antimicrobial drug resistance is also an ever-increasing problem,16 but measures can be, and should be, taken to reduce further emergence of new resistant organisms.