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Control of Viral Diseases Derek Wong “Wong’s Virology” http://virology-online.com

Control of Viral Diseases Derek Wong “Wong’s Virology”

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Page 1: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control of Viral Diseases

Derek Wong

“Wong’s Virology” http://virology-online.com

Page 2: Control of Viral Diseases Derek Wong “Wong’s Virology”

Terms Containment – to contain the disease as to prevent it from

becoming a worse problem. Containment is usually the

only option available for the majority of infectious

diseases.

Elimination – to eliminate the disease even though the

infectious agent may remain e.g. rabies and polio had been

eliminated in many countries, and probably SARS in 2003.

Eradication – to eradicate the infectious agent altogether

worldwide e.g. smallpox

Page 3: Control of Viral Diseases Derek Wong “Wong’s Virology”

Epidemiology (Gr.Studies upon people)

Study of health and disease as it occurs in the community either in groups of person or the entire population. It deals with

Nature of the disease Distribution of the disease Causation of the disease Mode of transfer of the disease Prevention and control of the disease

Page 4: Control of Viral Diseases Derek Wong “Wong’s Virology”

Surveillance of Infectious Diseases

Page 5: Control of Viral Diseases Derek Wong “Wong’s Virology”

Strategies for Surveillance of Infectious Diseases

Notifiable diseases – make it a statutory duty for physicians to notify the disease.

Virus isolation or serologic evidence reported through diagnostic laboratories

Specific Epidemiological Studies e.g. hantavirus, hand foot and mouth disease surveillance

Page 6: Control of Viral Diseases Derek Wong “Wong’s Virology”

Notifiable viral diseases (Hong Kong)

Yellow fever Poliomyelitis Measles Mumps Rubella Rabies (Human and Animal) Viral Hepatitis Dengue fever Chicken Pox H5N1 influenza SARS

Page 7: Control of Viral Diseases Derek Wong “Wong’s Virology”

Requirements for surveillance based on clinical case

Occurrence of clinical illness

Sufficient severity to seek medical care

Availability of medical care

Capability of physicians to diagnose illness

Laboratory support of diagnosis

Reporting of disease to Health Department

Collection and analysis of data by Health Department

Page 8: Control of Viral Diseases Derek Wong “Wong’s Virology”

Laboratory based surveillance

Scientific source of information

Coherent and consistent information on trends of infection

Qualitative detail information

Page 9: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control Measures Available

Page 10: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control Measures Available

To control the spread of the disease in the population by

Agent - removing the source of the agent by targeting

its reservoir

Controlling its transmission

Patient – immunization, prophylaxis, antiviral therapy.

Page 11: Control of Viral Diseases Derek Wong “Wong’s Virology”

Removing the Source Every pathogen has a reservoir, which may be in humans, animals or

both. One may aim to remove the pathogen from the reservoir, or remove the reservoir completely.

Human Reservoir Isolating the patient Curing the patient completely Preventing infection in susceptible individuals by vaccination

Animal Reservoir Isolating/observing the animal e.g. rabid dog Eradicate the animals involved e.g. slaughter of rabid dog, vector control Vaccinating the animals e.g. vaccination of dogs and foxes. It is very

difficult to vaccinate wild animals.

Page 12: Control of Viral Diseases Derek Wong “Wong’s Virology”

Controlling its transmission

Prophylactic chemotherapy or vaccination among individuals exposed to or susceptible to infection.

Contact tracing Improvement in hygiene and living standards Modification of lifestyle and behavior Health education Screening of potential sources of infection e.g. blood,

foods, water Controlling vectors that may be involved in transmission

Page 13: Control of Viral Diseases Derek Wong “Wong’s Virology”

Man-Arthropod-Man Cycle

Page 14: Control of Viral Diseases Derek Wong “Wong’s Virology”

Animal-Arthropod-Man Cycle

Page 15: Control of Viral Diseases Derek Wong “Wong’s Virology”

Examples of Arthropod Vectors

Aedes AegytiAssorted Ticks

Phlebotmine SandflyCulex Mosquito

Page 16: Control of Viral Diseases Derek Wong “Wong’s Virology”

Vaccination

Page 17: Control of Viral Diseases Derek Wong “Wong’s Virology”

Types of Vaccination Strategies

There are two types of vaccination policies: Universal Vaccination – every person is vaccinated in the hope of

eliminating/eradicating the disease from the community

Selective Vaccination – only individuals in particular risk groups

are vaccinated.

Both policies are in use for rubella. The US started off with universal vaccination.

The UK and HK started off with selective vaccination of primary

school girls but decided to switch to universal vaccination because

the uptake rate was not good enough.

Page 18: Control of Viral Diseases Derek Wong “Wong’s Virology”

Characteristics of vaccinesThe characteristics of the vaccine used is a major determinant on the outcome of the vaccination strategy. Factors to consider include

Response rate Type of protection Duration of protection Local immunity Side effects Route of administration Stability Cost

Page 19: Control of Viral Diseases Derek Wong “Wong’s Virology”

Developing a vaccination policy

The following questions should be asked when a vaccination policy against a particular virus is being developed.

1. What proportion of the population should be immunized to achieve eradication.

2. What is the best age to immunize?

3. How is this affected by birth rates and other factors

4. How does immunization affect the age distribution of susceptible individuals, particularly those in age-classes most at risk of serious disease?

5. How significant are genetic, social, or spatial heterogeneities in susceptibility to infection?

6. How does this affect herd immunity?

Page 20: Control of Viral Diseases Derek Wong “Wong’s Virology”

Coverage Required for eradication Basic concept is that of the basic rate of the infection R0. For most viral infections, R0 is the average number of secondary cases produced by a

primary case in a wholly susceptible population. Clearly, an infection cannot maintain itself or spread if R0 is less than 1.

R0 can be estimated from as B/(A-D);B = life expectancy, A = average age at which infection is acquired, D = the characteristic duration of maternal antibodies.

The larger the value of R0, the harder it is to eradicate the infection from the community in question.

A rough estimate of the level of immunization coverage required can be estimated in the following manner: eradication will be achieved if the proportion immunized exceeds a critical value pinc = 1-1/R0.

Thus the larger the R0, the higher the coverage is required to eliminate the infection. Thus the global eradication of measles, with its R0 of 10 to 20 or more, is almost sure to

be more difficult to eradicate than smallpox, with its estimated R0 of 2 to 4.

Page 21: Control of Viral Diseases Derek Wong “Wong’s Virology”

Critical Coverage

Av Age of Epidemic Critical

infection Period Ro Coverage

Measles 4-5 2 15-17 92-95

Pertussis 4-5 3-4 15-17 92-95

Mumps 6-7 3 10-12 90-92

Rubella 9-10 3-5 7-8 85-87

Diptheria 11-14 4-6 5-6 80-85

Polio 12-15 3-5 5-6 80-85

Page 22: Control of Viral Diseases Derek Wong “Wong’s Virology”

Eradication of Small Pox

Page 23: Control of Viral Diseases Derek Wong “Wong’s Virology”

Eradication of Smallpox - 1 Smallpox was transmitted by respiratory route from lesions in the respiratory tract of

patients in the early stage of the disease

During the 12 day incubation period, the virus was distributed initially to the internal

organs and then to the skin.

Variola major caused severe infections with 20-50% mortality, variola minor with <1%

mortality

Management of outbreaks depended on the isolation of infected individuals and the

vaccination of close contacts.

Smallpox was eradicated from most countries in Europe and the US by 1940s. By the

1960s, smallpox remained a serious problem in the Indian subcontinent, Indonesia and

much of Africa.

The WHO listed smallpox as the top on the list for eradication in 1967.

Page 24: Control of Viral Diseases Derek Wong “Wong’s Virology”

Eradication of Smallpox - 2The initial strategy was separated into 3 phases;

Attack phase - This applied to areas where the incidence of smallpox exceeded 5 cases per 100,000 and where vaccination coverage was less than 80%. Attention was given to mass vaccination and improvement in case surveillance and reporting. This phase lasted from 1967-1973. A large amount of financial resoureces were provided for setting up surveillance centres and reference centres. Priority was given to Brazil, sub-saharan African, S.Asia and Africa.

Consolidation Phase - In areas where the incidence was less than 5 cases per 100,000 and vaccination coverage exceeded 80%, the objective was the elimination of smallpox. Vaccination uptake was to be maintained and surveillance improved. Facilities should be made available for isolation.

Maintenance Phase - once smallpox had been eliminated, it was essential it was not reintroduced. This phase was entered in 1978. In 1980, the world was declared to be free of smallpox.

Page 25: Control of Viral Diseases Derek Wong “Wong’s Virology”

Eradication of Smallpox - 3 It soon became clear that smallpox could not be eradicated with mass vaccination alone.

In some countries, it was not possible to achieve a smallpox vaccination uptake rate of 80%.

Therefore more attention was paid to case tracing and isolation procedures. Experience in West Africa and Indonesia had shown that smallpox can be eliminated without mass vaccination, provided that a high rate of case detection was achieved.

The Indian subcontinent was a special problem because of its large size and population. It provided a reservoir for variola major infection. Extra attention was paid to search out unnotified cases that proved to be highly effective. The last cases of variola major occurred in the Indian subcontinent in 1975.

The last case of variola minor occurred in Somalia in 1977. The last cases of smallpox occurred in a Birmingham laboratory in 1979.

It was estimated that the smallpox eradication campaign costed US $312 million. If smallpox had not been eradicated, routine efforts to control smallpox would have costed US $1000 million.

Page 26: Control of Viral Diseases Derek Wong “Wong’s Virology”

Features that made Smallpox an eradicable disease

1. A severe disease with morbidity and mortality 2. Considerable savings to developed non-endemic countries 3. Eradication from developed countries demonstrated its feasibility 4. No cultural or social barriers to case tracing and control 5. Long incubation period 6. Infectious only after incubation period 7. Low communicability 8. No carrier state 9. Subclinical infections not a source of infection 10. Easily diagnosed 11. No animal reservoir 12. Infection confers long-term immunity 13. one stable serotype 14. Effective vaccine available

Page 27: Control of Viral Diseases Derek Wong “Wong’s Virology”

The SARS Crisis

Page 28: Control of Viral Diseases Derek Wong “Wong’s Virology”

Key Events Early Feb 2003 – Guandong province reported 305 cases and 5 deaths

caused by atypical pneumonia of unknown cause. 19th Feb – WHO influenza network activated emergency pandemic

plans after receiving a report from Hong Kong confirming a case of Influenza H5N1 infection.

21st Feb – Prof Liu Jian Lung came to Hong Kong to attend a relative’s wedding. He stayed at Rm 911 of the Metropole Hotel. Six people were infected and they carried the infection to the rest of Hong Kong, Vietnam and Canada.

Early March - Carlo Urbani identified SARS as a unique clinical entity in patients who had been infected by Johnny Chen in a Vietnam hospital. WHO was put on alert. Urbani himself later became infected and died.

Page 29: Control of Viral Diseases Derek Wong “Wong’s Virology”

Discovery of the Virus 18th-20th March – Paramyxovirus RNA and particles reported by

CUHK and other laboratories in Germany and Canada. 21st March – HKU reported isolating an unknown virus from 2

patients with SARS in FRhK4 cells, and demonstrated a rising antibody response against this virus by IF in patients with SARS. Furthermoe, EM revealed virus-like particles in lung autopsies.

22nd March – CDC isolated a virus that caused a CPE in Vero E6 cells from a patient from Thailand and showed coronavirus-like particles on electron microscopy. Serum from SARS patients were sent by the GVU to the CDC for confirmation. GVU visualized coronavirus particles in faeces of a mouse that had been inoculated (this was proved later not to be SARS-CoV)

23rd March – CDC identified the new agent as a coronavirus and gave sequences of initial primers to collaborating laboratories.

Page 30: Control of Viral Diseases Derek Wong “Wong’s Virology”

The SARS associated virusA Coronavirus

Enveloped single-stranded RNA virus

Virions 80-100 nm in diameter.

Pleomorphic morphology. Characterised by surface spikes giving a crown-like appearance. (Not seen in SARS agent)

There are two known serogroups of coronaviruses: OC43 and 229E, but the SARS agent do not belong to either.

Genome 29000 bases, appears to be a completely new coronavirus

Page 31: Control of Viral Diseases Derek Wong “Wong’s Virology”

Virological Aspects Incubation period:- mean 6.37 (95% CI 5.29-7.75) Risk of transmission is greatest around day 10 of illness. No evidence that patients can transmit infection 10 days after fever has

resolved. Children are rarely affected by SARS The implications of the Metropole Hotel are not yet fully understood. Risk of in-flight transmission – 5 international flights had been

associated with the transmission of SARS. No evidence of in-flight transmission after the 27 March advisory.

Page 32: Control of Viral Diseases Derek Wong “Wong’s Virology”

Positive Rate of Listed Cases(Sample Distribution)dated 30th Oct 2003

0

10

20

30

40

50

60

70

80

90

100

110

Day Di ff erence

% Positive Rate

Total Number of Sera

NPA

Faeces

Posi t i ve Rate 4. 35 2. 03 4. 03 18. 27 41. 67 74. 34 93. 41 95. 68 93. 75

Total Number of Sera 69 413 686 883 1003 1155 1337 1476 1572

NPA 34. 6 45. 2 58. 4 59. 7 41. 9 39. 1 12. 5 20 10

Faeces 12. 5 28. 3 46. 9 70. 3 68. 2 54. 2 38. 5 48. 3 11. 6

<=0 1- 3 4- 6 7- 9 10- 12 13- 15 16- 18 19- 21 22- 24

Page 33: Control of Viral Diseases Derek Wong “Wong’s Virology”

Epidemiological Aspects Incubation around 6 days. Spread by droplets – no evidence it is an airborne disease. Uncertain

whether faecal-oral spread can occur. Health care workers were at special risk, especially those involved in

procedures that may generate aerosols. In some cases, transmission to health care workers occurred despite that the staff was wearing full protection.

Risk of transmission is greatest at around day 10 of illness No evidence that patients can transmit infection 10 days after fever has

resolved. Children are rarely affected by SARS

Page 34: Control of Viral Diseases Derek Wong “Wong’s Virology”

Super Spreading Events Some infected individuals have spread the infection to large numbers

of people. They were originally called superspreaders but WHO now prefer to call them superspreading events.

In Hong Kong, 3 superspreading events occurred: Metropole Hotel – the mechanism is not completely understood. Prince of Wales Hospital – the use of a nebulizer by the patient was

responsible. Amoy Garden – this was a unique event. The index patient was a 33-yr

old man with chronic renal disease treated at PWH. He visited Amoy Garden frequently and had diarrhoea over a 3-day period. Dry U-traps in bathroom floors allowed contaminated sewage droplets to enter households.

Page 35: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control Measure Taken PPE provided for hospital staff, patients and visitors to hospitals. In

the later stages, hospitals were closed to visitors and all patients had to wear masks.

Home quarantine for contact cases. DH supervised cleaning and disinfection of the workplaces and homes

of those infected. Residents of Amoy Garden Block E were first quarantines before

transfer to a camp. Public education campaigns for workplace ad personal hygiene Schools were closed.

Page 36: Control of Viral Diseases Derek Wong “Wong’s Virology”

Future Control Measures Better drugs should be available Anti-viral prophylaxis Vaccines More sensitive diagnostic tests would enable the early

detection of cases. Better surveillance system Better contingency procedures Better education and facilities.

Page 37: Control of Viral Diseases Derek Wong “Wong’s Virology”

H5N1 Avian Influenza

Page 38: Control of Viral Diseases Derek Wong “Wong’s Virology”

H5N1 Avian Influenza First human infection by a highly pathogenic H5N1 avian influenza was

reported in Hong Kong in 1997. 18 persons were infected with 6 deaths. The outbreak was eventually controlled after culling all the chickens.

The virus resurfaced in Feb 2003 to cause 2 infections (one fatal) in a Hong Kong family who had recently traveled to China. It began to cause outbreaks in the rest of Asia that year that were unnoticed.

In 2004, Vietnam and Thailand started reporting human infections, followed by Cambodia, Indonesia and China in 2005. The strains exhibited divergence in these localities.

It is now thought that highly pathogenic H5N1 is now firmly endemic Asia and has also spread to Russia and Southern Europe.

It is thought that the virus is carried by migratory birds.

Page 39: Control of Viral Diseases Derek Wong “Wong’s Virology”

Human Cases Reported to the WHO as of April 2008

Country2003 2004 2005 2006 2007 2008 Total

cases

deaths

cases

deaths

cases

deaths

cases

deaths

cases

deaths

cases

deaths

cases

deaths

Azerbaijan 0 0 0 0 0 0 8 5 0 0 0 0 8 5

Cambodia 0 0 0 0 4 4 2 2 1 1 0 0 7 7

China 1 1 0 0 8 5 13 8 5 3 3 3 30 20

Djibouti 0 0 0 0 0 0 1 0 0 0 0 0 1 0

Egypt 0 0 0 0 0 0 18 10 25 9 4 1 47 20

Indonesia  0 0 0 0 20 13 55 45 42 37 15 12 132 107

Iraq 0 0 0 0 0 0 3 2 0 0 0 0 3 2

Laos 0 0 0 0 0 0 0 0 2 2 0 0 2 2

Myanmar 0 0 0 0 0 0 0 0 1 0 0 0 1 0

Nigeria 0 0 0 0 0 0 0 0 1 1 0 0 1 1

Pakistan 0 0 0 0 0 0 0 0 3 1 0 0 3 1

Thailand 0 0 17 12 5 2 3 3 0 0 0 0 25 17

Turkey 0 0 0 0 0 0 12 4 0 0 0 0 12 4

Total 4 4 46 32 98 43 115 79 88 59 27 21 378 238

Page 40: Control of Viral Diseases Derek Wong “Wong’s Virology”

Risks of a pandemic The present H5N1 strains do not have the ability to transmit efficiently

between humans. To date, there had been no certain cases of human to human transmission.

It is thought an avian influenza may acquire this capability through either 1. Reassortment with human influenza viruses (1957 and 1968), or 2. gradual mutations ?1918.

Reassortments in 1957 (H1N1-H2N2), and 1968 (H2N2-H3N2) are thought to have occurred through an intermediary host such as the pig.

Direct infection of humans by H5N1 opens the possibility that reassortment can occur without an intermediary host.

Therefore many experts believe that a pandemic was stopped in 1997 by the culling of chickens.

The bottom line is that nobody knows when and if a pandemic will arise out of the current H5N1 outbreaks.

Page 41: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control Measures - 1 It would not be possible to control infection in migratory birds. Therefore

measures should be taken at reducing the risk of infection in poultry where there is much more contact with humans.

Measures should be taken to reduce the contact between poultry and migratory birds through increased biosecurity

Vaccination of poultry is controversial but is now practiced in Hong Kong Surveillance and laboratory diagnosis of infection in poultry should be

strenghened. Where infection is detected, prompt culling of the herd is essential.

Control of infection in poultry is complicated by the fact that ducks can excrete the virus silently.

Steps such as a central slaughtering facility would reduce the risk of contact with humans.

Page 42: Control of Viral Diseases Derek Wong “Wong’s Virology”

Control Measures - 2 Prototype H5 vaccines are now available but it is uncertain whether they

will be protective against a future pandemic capable strain. It is possible that the present H3N2/H1N1 may have some degree of

cross protectivity against H5N1 Tamiflu is currently the most effective drug against influenza and

countries are urged to stockpile it as a part of pandemic planning. It is essential that facilities for the surveillance and laboratory diagnosis

of avian influenza are upgraded. Where human cases occurred, prompt identification, isolation and

treatment of contacts is essential.

Page 43: Control of Viral Diseases Derek Wong “Wong’s Virology”

Pandemic Planning In August 2005, WHO sent all countries a document outlining recommended

strategic actions for responding to the avian influenza pandemic threat. Recommended actions aim to strengthen national preparedness, reduce opportunities for a pandemic virus to emerge, improve the early warning system, delay initial international spread, and accelerate vaccine development.

Despite an advance warning that has lasted almost two years, the world is ill-prepared to defend itself during a pandemic. WHO has urged all countries to develop preparedness plans, but only around 40 have done so.

WHO has further urged countries with adequate resources to stockpile antiviral drugs nationally for use at the start of a pandemic. Around 30 countries are purchasing large quantities of these drugs, but the manufacturer has no capacity to fill these orders immediately.

On present trends, most developing countries will have no access to vaccines and antiviral drugs throughout the duration of a pandemic.