PANDEMIC

A pandemic (from Greek pan all +

demos people) is an epidemic of
infectious disease that spreads through
human population across a large
region (for example a continent), or
even worldwide.
 DEFINITION

 the emergence of a disease new to

the population.
 the agent infects humans, causing
serious illness.
 the agent spreads easily and
sustainably among humans.
A disease or condition is not a pandemic merely
because it is widespread or kills many people; it
must also be infectious. For example cancer is
responsible for many deaths but is not a pandemic
because the disease is not infectious or
contagious.
 WHO pandemic influenza phases
Interpandemic period:
 Phase 1: No new influenza virus subtypes have been detected in
humans.
 Phase 2: No new influenza virus subtypes have been detected in
humans, but an animal variant threatens human disease.
Pandemic alert period:
 Phase 3: Human infection(s) with anew subtypes but no human-to-
human spread.
 Phase 4: Small cluster(s) with limited localized human-to-human
transmission.
 Phase 5: Large cluster(s) but human-to-human spread still localized.
Pandemic period:
 Phase 6: Increased and sustained transmission in general
population.
 Pandemics and notable epidemics through
history
 Peloponnesian War, 430 B.C. Typhoid fever killed a quarter of the
Athenian troops and a quarter of the population over four years.
This disease fatally weakened the dominance of Athens, but the
sheer virulence of the disease prevented its wider spread; i.e. it
killed off its hosts at a rate faster than they could spread it.
 Antonine Plague, 165-180. Possibly smallpox brought to the Italian
peninsula by soldiers returning from the Near East, killed a quarter
of those infected and up to 5 million in all. At the height of the
second outbreak (251-266) 5,000 people a day are said to be dying
in Rome.
 Plague of Justinian, from 541-750, was the first recorded outbreak
of the bubonic plague. It started in Egypt and reached
Constantinople the following spring, killing 10,000 a day at its height
and perhaps 40% of the city’s inhabitants. The plague went on to
eliminate a quarter to a half of the human population that it struck
throughout the known world. It caused Europe’s population to drop
by around 50% between 550 and 700.
 Black Death, started 1300’s. Eight hundred years after the last
outbreak, the bubonic plague returned to Europe. From Asia, the
disease reached Mediterranean and western Europe in 1348, and
killed 20 to 30 million Europeans in six years, a third of the total
population and up to a half in the worst-affected urban areas.
 Cholera;
~ The First Pandemic 1816-1826. Began in Bengal, then spread
across India by 1820.
~ The Second Pandemic 1829-1851. Europe, London in 1832,
Ontario, Canada and New York in the same year, and the Pacific
Coast of North America in 1834.
~ The Third Pandemic 1852-1860. Russia, over a million deaths.
~ The Fourth Pandemic 1863-1875. Europe and Africa.
~ 1866, outbreak in North America.
~ 1892, contaminated water supply in Hamburg, Germany, 8,606
deaths.
~ The Seventh Pandemic 1899-1923. Europe and Russia.
~ The Eight Pandemic. Began in Indonesia in 1961, called El Tor
after the strain, reached Bangladesh in 1963, India in 1964, and
the USSR in 1966.
• Influenza;
~ The “first” pandemic of 1510 traveled from Africa and spread
across Europe.
~ the “Asiatic Flu”, 1889-1890. First reported in May of 1889 in
Bukhara, Russia. By October, reached Tomsk and Caucasus. Hit North
America in December 1889, South America in February-April 1890,
India in February-March 1890, and Australia in March-April 1890.
Purportedly caused by the H2N8 type of flu virus and had a very high
attack rate and mortality rate.
~ The “Spanish Flu”, 1918-1919. Identified in March of 1918 in US
troops in Camp Funston, Kansas. By October 1918, had become a
worldwide pandemic in all continent. In six months, 25 million were
dead, 17 million in India, 500,000 in US and 200,000 in UK. The virus
was that of H1N1.
~ The “Asian Flu”, 1957-58. An H2N2 caused about 70,000 deaths
in the US.
~ The “Hong Kong Flu”, 1968-69. H3N2 caused about 34,000
deaths in the US. Influenza A (H3N2) viruses still circulate today.
 Typhus; also called “camp fever”, “gaol fever” or “ship fever” for its
habits of flaring up in times of strife and in cramped quarters in jails
and ships.

** Effects of Colonization. Encounters between European explorers

and populations in the rest of the world often introduced local
epidemics of extraordinary virulence. Disease killed the entire native
(Guanches) population of the Canary Island in the 16th century. Half
the native population of Hispaniola in 1518 was killed by smallpox.
Smallpox also ravaged Mexico in the 1520’s, killing 150,000 in
Tenochtitlan alone, including the emperor. Measles killed a further
two million Mexican natives in the 1600’s. Some believe that the
death of 90-95 percent of native American population of the New
World was caused by the Old World disease.

 Dengue; spread of Dengue disease in South Asia by mosquito.

There are also a number of unknown diseases that were
extremely serious but have now vanished, so the
etiology of these diseases cannot be established. The
cause of English Sweat in 16th-century England, which
struck people down in an instant and was more greatly
feared even than the bubonic plague, is still unknown.
 Concern about possible future pandemics

 Ebola virus and other quickly lethal diseases

Lassa fever, Rift Valley fever, Marburg virus, Ebola virus and Bolivian
hemorrhagic fever are highly contagious and deadly diseases with the
theoretical potential to become pandemics. Their ability to spread
efficiently enough to cause a pandemic is limited, however, as
transmission of these viruses requires close contact with the infected
vector. Furthermore, the short time between a vector becoming
infectious and the onset of symptoms allows medical professionals to
quickly quarantine vectors and prevent them from carrying the
pathogen elsewhere. Genetic mutations could occur which could
elevate their potential for causing widespread harm, thus close
observation by contagious disease specialists is merited.
 Antibiotic resistance
Antibiotic-resistant microorganisms, sometimes referred to as
"superbugs", may contribute to the re-emergence of diseases which
are currently well-controlled. For example, cases of tuberculosis that
are resistant to traditionally effective treatments remain a cause of
great concern to health professionals. The World Health
Organization (WHO) reports that approximately 50 million people
worldwide are infected with multiple-drug resistant tuberculosis
(MDR TB), with 79 percent of those cases resistant to three or more
antibiotics. In 2005, 124 cases of MDR TB were reported in the
United States. Extensively drug-resistant tuberculosis (XDR TB) was
identified in Africa in 2006, and subsequently discovered to exist in
17 countries including the United States.

In the past 20 years, common bacteria including Staphylococcus

aureus, Serratia marcescens and Enterococcus, have developed
resistance to various antibiotics such as vancomycin, as well as
whole classes of antibiotics, such as the aminoglycosides and
cephalosporins. Antibiotic-resistant organisms have become an
important cause of health care-associated (nosocomial) infections
(HAI). In addition, infections caused by community-acquired strains
of methicillin-resistant Staphylococcus aureus (MRSA) in otherwise
healthy individuals, have become more frequent in recent years.
 HIV infection
HIV — the virus that causes AIDS — is of pandemic proportions
with infection rates as high as 25% in southern and eastern Africa.
Effective education about safer sexual practices and bloodborne
infection precautions training have helped to slow down infection
rates in several African countries sponsoring national education
programs. Infection rates are rising again in Asia and the Americas.

 SARS
In 2003, there were concerns that SARS, a new, highly contagious
form of atypical pneumonia caused by a coronavirus dubbed SARS-
CoV, might become pandemic. Rapid action by national and
international health authorities such as the World Health
Organization helped slow transmission and eventually broke the
chain of transmission, ending the localized epidemics before they
could become a pandemic. The disease has not been eradicated,
however, and could re-emerge unexpectedly, warranting monitoring
and case reporting of suspicious cases of atypical pneumonia.
 Influenza
Wild aquatic birds are the natural hosts for a range of influenza A
viruses. Occasionally viruses are transmitted from these species to
other species and may then cause outbreaks in domestic poultry or
(rarely) give rise to a human pandemic.

 H5N1
In February 2004, avian influenza virus was detected in birds in
Vietnam, increasing fears of the emergence of new variant strains. It
is feared that if the avian influenza virus combines with a human
influenza virus (in a bird or a human), the new subtype created
could be both highly contagious and highly lethal in humans. Such a
subtype could cause a global influenza pandemic, similar to the
Spanish Flu, or the lower mortality pandemics such as the Asian Flu
and the Hong Kong Flu.
From October 2004 to February 2005, some 3,700 test kits of the 1957
Asian Flu virus were accidentally spread around the world from a lab in
the US.
In May 2005, scientists urgently call nations to prepare for a global
influenza pandemic that could strike as much as 20% of the world's
population.
In October 2005, cases of the avian flu (the deadly strain H5N1) were
identified in Turkey. EU Health Commissioner Markos Kyprianou said:
"We have received now confirmation that the virus found in Turkey is
an avian flu H5N1 virus. There is a direct relationship with viruses
found in Russia, Mongolia and China." Cases of bird flu were also
identified shortly thereafter in Romania, and then Greece. Possible
cases of the virus have also been found in Croatia, Bulgaria and in the
United Kingdom.
By November 2007 numerous confirmed cases of the H5N1 strain had
been identified across Europe. However, by the end of October only 59
people had died as a result of H5N1 which was atypical of previous
influenza pandemics.
Despite sensational media reporting, avian flu cannot yet be
categorized as a "pandemic" because the virus cannot yet cause
sustained and efficient human-to-human transmission. Cases so far
are recognized to have been transmitted from bird to human, but as of
December 2006 there have been very few (if any) cases of proven
human-to-human transmission. Regular influenza viruses establish
infection by attaching to receptors in the throat and lungs, but the avian
influenza virus can only attach to receptors located deep in the lungs of
humans, requiring close, prolonged contact with infected patients and
thus limiting person-to-person transmission. The current WHO phase of
pandemic alert is level 3, described as "no or very limited human-to-
human transmission." according to the WHO website.
WHO: "Prepare Now for Influenza Pandemic”

A recent report from the World Health Organization

(WHO) warns that the world is closer to an influenza
pandemic than at any time since 1968. It calls for
urgent international action to prepare for "an
unpredictable but potentially catastrophic event."

Avian Influenza: Assessing the Pandemic Threat was released in

pre-publication form in January to elicit comments from the scientific
and public health community. The report summarizes a 14-month saga
of outbreaks of H5N1 in birds and humans, and analyzes
developments in the virus and its ecology that strongly suggest a new
flu pandemic could break out in the near future.
Starting in late 2003, a series of major outbreaks of lethal avian
influenza have caused severe economic losses in a number of Asian
countries. Of greater concern, the virus has also infected humans, with
what appears to be a high mortality rate. As of early March 2005, 69
human cases of H5N1 had been officially confirmed, with 46 deaths.

According to the report, the H5N1 virus appears to have established

itself as endemic in parts of Asia, with "a permanent ecological niche in
poultry." Human cases continue to emerge, and "the virus may be
evolving in ways that increasing favor the start of a pandemic," the
report says.

Studies show that H5N1 has become both more pathogenic in poultry
and hardier than in the past, with an ability to survive several days
longer. It has also expanded its host range to include cat species and
other mammals: last October, the virus sickened 147 captive tigers in
Thailand that had been fed infected chicken carcasses.
Also alarming is the recent detection of highly pathogenic H5N1 in
dead migratory birds. "Wild waterfowl are the natural reservoir of all
influenza A viruses and have historically carried low-pathogenic
viruses," the report notes. This suggests "the role of migratory
waterfowl in the evolution and maintenance of highly pathogenic H5N1
may be changing."

At the same time, domestic ducks, which generally fall ill when infected
with H5N1, have been found recently to be secreting large amounts of
lethal virus without showing any symptoms of disease. This suggests
that healthy ducks "play a role in maintaining transmission by silently
seeding outbreaks in other poultry." It may also explain why some
recent human cases cannot be linked to contact with diseased poultry.
During 2004, a number of large bird flu outbreaks on commercial
poultry farms were successfully contained through culling and
vaccination.

A greater concern now, says the report, is with outbreaks in rural areas
of Asia, where most families keep free-ranging ducks and chickens.
Outbreaks on these small family farms "may escape detection, are
difficult to control, and increase the likelihood of human exposures,
which may occur when children play in areas shared by poultry or when
families slaughter or prepare birds for consumption."
H5N1's potential to ignite a pandemic depends, however, on its
acquiring the ability to pass easily between humans. There are two
ways this could occur. H5N1 could infect someone who also is infected
with a human form of influenza A, and the two viruses could exchange
genes (re-assortment). Or, the virus could adapt in an evolutionary
fashion during subsequent human infections, acquiring the ability to
transmit itself efficiently from one person to another (adaptive
mutation). The deadly 1918 Spanish flu pandemic is believed to have
been caused by a virus that mutated in this way.

The report notes that opportunities for either of these events to occur
continue to increase and appear more likely.

The WHO report also notes that a virus that gradually acquires an
improved ability to pass between humans would be harder to detect
through surveillance than a fully transmissible pandemic virus that
emerged from a re-assortment event. "The resulting explosion of cases
would be difficult for any surveillance system to miss."
 Past pandemics may hold some important lessons about how to
prepare for and cope with any new pandemic. The report highlights
several conclusions:

 Pandemics are as unpredictable as the viruses that cause them.

Different pandemics have shown very different levels of mortality,
severity of illness, and patterns of spread.
 All pandemics produce a rapid initial surge of cases, which then
increase exponentially. This means "a sudden sharp increase in the
need for medical care will always occur."
 The overall impact of a pandemic depends on its ability to cause
severe illness in nontraditional age groups, particularly young
adults. Milder pandemics have tended to target the elderly and the
very young, those most affected by ordinary influenza.
 Pandemics tend to unfold in waves. Age groups and areas not
affected initially are likely to be more vulnerable during a second
wave, which is often more severe.
 Good surveillance is key to early detection of the onset of a
pandemic. It makes it possible to alert heath services, isolate and
characterize the virus, and make it available to vaccine makers.
 Surveillance capacity in Asia is particularly important, as this is
where most pandemics have originated.
 Quarantine and travel restrictions have proved ineffective in
stopping the international spread of pandemics. But within countries,
banning public gatherings and closing schools are potentially
effective measures.
 Stopping the pandemic's spread is extremely difficult, but slowing it
can help health services cope by having fewer people ill at one time.
 In the past, vaccines have arrived too late and in too little quantities
to have an impact. Nevertheless, the report emphasizes the
importance of advance work to prepare the way for vaccine
production once a pandemic virus emerges.
 Countries with a domestic manufacturing capacity will be the first to
receive vaccines.
 The "best-case scenario" is a pandemic that has its main impact on
the very old, the very young and the chronically ill, as these can be
more easily targeted with vaccines. Still, health systems must
anticipate a high demand for medical care.
The report notes that vaccine development and production will by
necessity be primarily the responsibility of wealthier countries.
However, many experts believe an effective vaccine against a
pandemic version of H5N1 will have to be developed using "reverse
genetics," a process that would result in a "genetically modified
organism," raising bio-safety issues that could delay production in
Europe.

The report says it is "impossible to predict with any accuracy” the

number of deaths that would result from a new pandemic. "Best case
scenarios," modeled on the relatively mild 1968 pandemic, predict
excess deaths ranging from 2 million to 7.4 million. However, "other
estimates that factor in a more virulent virus, similar to that responsible
for the deadly 1918 pandemic, estimate much higher numbers of
deaths."
Ten things you need to know about pandemic influenza

1. Pandemic influenza is different from avian influenza.

2. Influenza pandemics are recurring events.
3. The world may be on the brink of another pandemic.
4. All countries will be affected.
5. Widespread illness will occur.
6. Medical supplies will be inadequate.
7. Large numbers of deaths will occur.
8. Economic and social disruption will be great.
9. Every country must be prepared.
10. WHO will alert the world when the pandemic threat
increases.
5N1 avian influenza – first steps towards development
of a human vaccine

On 6 August, government scientists at the US National Institute of

Allergy and Infectious Diseases announced results from initial clinical
trials of a vaccine being developed to protect humans against infection
with H5N1 avian influenza. Preliminary data indicate that the
experimental vaccine evoked an immune response in a small group of
healthy adults.

Although more trials are needed, the new findings reconfirm the
feasibility of developing an H5N1-specific vaccine.

H5N1 is presently considered the most likely virus to ignite the next
pandemic. The increasing spread and evolution of H5N1 viruses in
Asia have brought the world closer to another pandemic than at any
time since 1968, when the last of the previous century’s three
pandemics began.
Vaccines are the principal medical intervention for protecting
individuals against pandemic influenza. If available rapidly and in
sufficient quantities, they can reduce the morbidity and mortality that
have traditionally made pandemics such socially disruptive as well as
deadly events.

However, many problems need to be resolved before vaccines can

assume such a role in mitigating the effects of the next pandemic. The
most important need is to find vaccine formulations that make the best
use of limited antigen supplies.

Antigen is the component of the vaccine that elicits an immune

response. The US trial provides important insight into possible vaccine
formulations. It used doses that are higher than the amount of virus
antigen contained in influenza vaccines produced yearly for normal
seasonal epidemics.
Strategies for stretching limited antigen supplies – by adding an
adjuvant to the vaccine formulation or injecting the vaccine into the skin
rather than into muscle – have been proposed. Adjuvants are
chemicals that can be added to the vaccine formulation to boost the
immune response, theoretically allowing the use of smaller doses of
antigen to achieve an immune response. Such antigen-sparing
strategies using adjuvants are currently being tested by several
manufacturers, and preliminary results are expected within the next
three months.

At present, 90% of production capacity for all influenza vaccines is

concentrated in Europe and North America in countries that account for
only 10% of the world’s population. Current global manufacturing
capacity (estimated at 300 million doses of regular trivalent influenza
vaccine per year) is inadequate to meet the expected global needs
during a pandemic and cannot be rapidly augmented.
Influenza pandemics are unique infectious disease events that can
spread to every country in the world within months, resulting in a high
and universal demand for preventive and treatment measures.
Pandemics thus throw into sharp relief inequities in global access to
vaccines and other medical interventions during an emergency. Based
on past experience, countries with local manufacturing capacity are
likely to meet domestic demand for vaccines and other critical
resources fully before freeing supplies for the export market.
Because the present total global manufacturing capacity for influenza
vaccine is limited, any decision to manufacture a pandemic vaccine in
large quantities prior to the start of a pandemic would, of necessity,
compromise the capacity to produce vaccines for seasonal influenza.
Seasonal epidemics of influenza predictably cause an estimated
250,000 to 500,000 deaths each year. In the current situation, the
capacity to respond to seasonal influenza must be balanced against
preparations for pandemic influenza. However, once a pandemic has
been declared, all manufacturers would stop production of seasonal
vaccines and produce only the pandemic vaccine.
WHO has produced advice on a broad range of preparedness
measures that can be undertaken by countries, taking into
consideration that adequate supplies of vaccine will not be available at
the start of a pandemic in any country.