Control of Viral Diseases

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

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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

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Surveillance of Infectious Diseases
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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

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Notifiable viral diseases (Hong Kong)

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

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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

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Laboratory based surveillance

• Scientific source of information
• Coherent and consistent information on trends of
  infection
• Qualitative detail information

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Control Measures Available
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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.

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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.

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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

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Man-Arthropod-Man Cycle
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Animal-Arthropod-Man Cycle
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Examples of Arthropod Vectors
Aedes Aegyti
Assorted Ticks
Phlebotmine Sandfly
Culex Mosquito
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Vaccination
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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.

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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

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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?

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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.

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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

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Eradication of Small Pox
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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.

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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.

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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.

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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

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The SARS Crisis
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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.

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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.

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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
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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.

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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

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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.

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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.

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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.

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H5N1 Avian Influenza
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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.

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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
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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.

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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.

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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.

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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.