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Control of Viral Diseases

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Title: Control of Viral Diseases


1
Control of Viral Diseases
Derek Wong Wongs Virology http//virology-onlin
e.com
2
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

3
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

4
Surveillance of Infectious Diseases
5
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

6
Notifiable viral diseases (Hong Kong)
  • Yellow fever
  • Poliomyelitis
  • Measles
  • Mumps
  • Rubella
  • Rabies (Human and Animal)
  • Viral Hepatitis
  • Dengue fever
  • Chicken Pox
  • H5N1 influenza
  • SARS

7
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

8
Laboratory based surveillance
  • Scientific source of information
  • Coherent and consistent information on trends of
    infection
  • Qualitative detail information

9
Control Measures Available
10
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.

11
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.

12
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

13
Man-Arthropod-Man Cycle
14
Animal-Arthropod-Man Cycle
15
Examples of Arthropod Vectors
Aedes Aegyti
Assorted Ticks
Phlebotmine Sandfly
Culex Mosquito
16
Vaccination
17
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.

18
Characteristics of vaccines
  • The 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

19
Developing a vaccination policy
  • The following questions should be asked when a
    vaccination policy against a particular virus is
    being developed.
  • What proportion of the population should be
    immunized to achieve eradication.
  • What is the best age to immunize?
  • How is this affected by birth rates and other
    factors
  • How does immunization affect the age distribution
    of susceptible individuals, particularly those in
    age-classes most at risk of serious disease?
  • How significant are genetic, social, or spatial
    heterogeneities in susceptibility to infection?
  • How does this affect herd immunity?

20
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.

21
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

22
Eradication of Small Pox
23
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 lt1
    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.

24
Eradication of Smallpox - 2
  • The 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.

25
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.

26
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

27
The SARS Crisis
28
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 relatives 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.

29
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.

30
The SARS associated virus
A 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
31
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.

32
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33
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

34
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.

35
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.

36
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.

37
H5N1 Avian Influenza
38
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.

39
Human Cases Reported to the WHO as of April 2008
Country 2003 2003 2004 2004 2005 2005 2006 2006 2007 2007 2008 2008 Total Total
Country
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
40
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.

41
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.

42
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.

43
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.
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