Download WHO`s list of global health threats Epidemic

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WHO’s list of global health threats
ƒ Epidemic-prone diseases
• H1N1
• Re-emerging cholera, yellow fever and tuberculosis
• Emerging diseases such as Ebola, Marburg haemorrhagic fever and Nipah virus
ƒ Food/waterborne diseases (new variant CJD/BSE, E. coli H0157H7, Crytosporidium,
Salmonella, Listeriosis)
ƒ Accidental or deliberate contamination
• Toxic chemical accidents
• Nuclear accidents
• Deliberate releases of biological/chemical contaminants
ƒ Environmental
• Heat waves/monsoons/hurricanes
• Environmental exposures to toxic chemicals
• Hospital acquired infections (C. difficile, MRSA, etc.)
Filtered through the lens of the DALY
ƒ Disease burden is not distributed evenly across the world
ƒ There are significant differences by age and gender
ƒ The DALY (disability adjusted life year): a time-based measure combining years of life lost
due to premature mortality and years of life lost due to time lived in states of less than full
health.
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Understanding environmental health issues is challenging because there is no
“best” way to categorize topics
ƒ Environmentally related diseases may be categorized (in the media) by hazard (water, air,
food); by individual risk factors (POPs, UV-B); or according to the nature of the hazard
(microbial, chemical, occupational)
ƒ Of the 102 major diseases reported in WHO Reports, 85 are at least partly caused by
exposures to environmental risk factors.
ƒ WHO’s HDR 2004* suggested environmental causes contributed to 23% of the mortality
associated with disease and 24% of the number of years of healthy life lost (disease
burden or DALY)
ƒ Although this is a significant contribution to the overall disease burden, it is a conservative
estimate because there is as yet no conclusive evidence for a link between environment
and the disease
ƒ As an example: the disease burden associated with changed/damaged ecosystems, which
remains unquantifiable, even though the associated health effects are readily apparent, e.g.
HIV (WHO 2005), H1N1 (?)
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How might we categorize “disease”?
How do we report disease?
ƒ The prevalence of a disease is the number of diseased individuals at any one time
ƒ The incidence is the number of new cases of a disease that occur over time.
ƒ Prevalence, incidence, or both, are usually given as a rate, meaning the number of cases in
a fixed number of people, e.g., cases per 100,000 (prevalence), new cases per week
(incidence)
ƒ Excessive incidence of a disease above what is normally expected is an epidemic
• common source epidemics arise from a contaminated source, such as water or food (e.g.
botulism, hepatitis)
• host-to-host infections are transmitted from one infected individual to another (e.g.
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H1N1, TB, HIV)
ƒ When an epidemic extends beyond the confines of a continent and becomes more
widespread, it is a pandemic
Categorizing disease: Communicable (cd or infectious) vs non-communicable
(ncd)
•CDs are generally defined as diseases transmittable from person to person and caused by
pathologic agents or vectors (e.g. H1N1, tuberculosis, measles)
ƒ1,400 human infectious agents (60-75% are zoonotic-can be passed from animals to
people)
•CDs generally follow predictable patterns (i.e. epidemics/pandemics), spreading across
vulnerable populations
ƒAll (most) populations are generally vulnerable to “primary pathogens”
ƒPopulations whose health is already compromised may be vulnerable to “secondary” or
“opportunistic pathogens” that normally do not cause disease in healthy populations
•NCDs (mental disorders, cancer, diabetes) are not usually thought of as being caused by a
pathologic agent
ƒ However some health care advocates are beginning to argue that unhealthy behaviours
(smoking, alcohol consumption, physical inactivity, or other lifestyle choices, i.e.
‘determinants’) act similarly to pathologic vectors
ƒ They label such determinants social ‘vectors’ and argue that like pathogens, they
spread disease across vulnerable populations as people copy behaviours promoted as
desirable (e.g. access to fast food, smoking, alcohol consumption) or where low
socioeconomic status/education level restricts healthy lifestyle choices.
ƒ Like pathologic vectors, unhealthy behaviours can be passed on through families,
communities, and populations (how might this be related to the ‘epidemic’ spread of
obesity and diabetes in NA starting in ~ the 1990s?)
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acute vs chronic
• Acute conditions are sudden in onset, often severe, but generally relatively short in
duration, e.g. an asthma attack or a cold or flu
• Chronic conditions are usually a slowly-developing syndrome but may have long latent
periods where disease is not evident e.g. COPD, AIDS, diabetes, osteoporosis, cancer
• Note:
ƒ There is no generalizable connection between infectious and acute diseases nor chronic
and non-communicable
ƒ Heart attacks or strokes are acute episodes with no known infectious agents, (although
there is evidence that periodontal bacteria may increase the risk for heart attack)
ƒ HIV, Hep B or C, and Helicobacter pylori are infectious agents but they lead to chronic
rather than acute syndromes: AIDS, liver failure/cancer, gastric ulcers/cancer
respectively
ƒ Acute episodes may occur in the midst of chronic conditions (e.g. asthma, herpes)
ƒ Initial, apparently acute episodes may go ‘dormant’ but lead to a chronic situations, e.g.
Varicella zoster (Varicella produces chickenpox on initial infection but remains latent and
can produce a chronic disease called "shingles“ many years later)
ƒ An initially acute condition, e.g. a first asthma attack, may lead to a chronic syndrome if
untreated
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While humans have always been subject to infectious diseases, the world became
complacent in the 1950s/60s
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ƒ The prevalence of antibiotics and vaccines lead the U.S. Surgeon General to declare that
“the war against infectious disease has been won” (1967)
ƒ Within a decade (1976), Legionaire’s and Lyme disease became the first modern ERIDs in
the developed world
• a pulmonary infection caused by Legionella pneumophila
• its emergence as a human pathogen might not have occurred were it not for the
environmental niche provided by air-conditioning systems
ƒ An unknown number of Americans developed Guillain-Barré syndrome (chronic fatigue) in
1976-77 in conjunction with contaminated “swine flu” vaccine
ƒ Hundreds died in the first documented outbreak of Ebola (in 1976 in Zaire – now the
Democratic Republic of the Congo)
Emerging/re-emerging infectious diseases (ERIDs)
• EIDs are new diseases, RIDs are increases in infections from a known disease formerly
causing so few infections as to not be considered a public health issue
• ERIDs remind us that all organisms respond to evolutionary pressures and that pathogenic
organisms like all organisms are in dynamic relationships with their environment (i.e.
genetics and co-evolution)
• ERIDs are anthropogenic and usually associated with human population growth, behavioral
patterns and/or technologies
• Mechanisms (?)
ƒ agricultural practices (H1N1, NV-CJD, SARS, Salmonella)
ƒ densely populated urban centers with weak public health infrastructure (E. coli 0157:H7,
diphtheria)
ƒ changing land use (Ebola, Lyme disease)
ƒ climate change (Hanta virus, malaria)
ƒ globalization, emigration and travel (West Nile, SARS, H1N1)
ƒ technology, (MRSA, C. difficile, Legionaire’s)
ƒ war or other factors destroying social cohension (HIV)
• ERIDS tend to come from zoonotic reservoirs (75% of ERID pathogens have been animalhuman transmissions)
• ERIDs are expected to remain a challenge for the foreseeable future.
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ERIDs (red = EID, blue = RID)
Deliberately emerging infections
ƒ Bio-warfare is probably not new
ƒ Frequently cited examples of bioterrorism
• Mongol army is alleged to have catapulted plague-ridden corpses over the walls in the
1346 siege of Caffa (now the Crimean port of Feodosia in Ukraine) – concomitantly
bringing the first Black Death plague to Europe
• The dispatch of smallpox-impregnated blankets to First Nations people by British officers
in the Seven Years War (1754–1763)
ƒ In 1984, an Oregon (U.S.) religious cult spiked restaurant salad bars with Salmonellae in an
attempt to sway a local election
ƒ But if anyone remembers deliberate attacks, it is likely the 2001 US anthrax, in which
anthrax-spore-filled letters were delivered by mail to prominent figures, including two US
senators. 5 individuals died, 18 people became ill. (Bruce Ivins, a long-time employee at
the US Government's biodefence research laboratory in Fort Detrick, Maryland, may have
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been responsible, but committed suicide in July 08 before being arrested)
ƒ There are six category A bio-warfare agents (anthrax, smallpox, plague, tularaemia, viral
haemorrhagic fevers and clostridial botulinum toxin)
ƒ The U.S. is believed to have a national bio-warefare defence plan which includes
development of countermeasures (i.e. diagnostics, therapeutics and vaccines) against biowarfare agents
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disease emergence is a complex interaction among infectious agents, hosts and
the
environment
Example #1: HIV
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ƒ Genetic analyses suggest HIV probably ‘jumped’ to humans in the 1930s, possibly as a
consequence of the consumption of primate ‘bush meat’ (chimpanzees and mangabeys)1
ƒ But HIV/AIDS may never have ‘emerged’ had it not been for disruptions in the socioeconomic infrastructure of post-colonial sub-Saharan Africa.
ƒ Rebel insurgency, economic and general urban migration, poverty and weakened family
structures promoted promiscuity/prostitution facilitating HIV transmission2
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Example #2: the relationship between re-emergent TB and AIDS
ƒ By the middle of the last century, effective drugs for TB lead to the dismantling of most
public health TB surveillance/control systems
ƒ Then immune deficiencies of people with AIDS allowed latent Mycobacterium tuberculosis
infections to progress to the active state of the disease during which it could be transmitted
to others (opportunistic or secondary infection)
ƒ Inadequate anti-tuberculosis therapy then lead to the emergence of drug-resistant and
multidrug-resistant strains of the bacteria
ƒ TB in general is associated with crowding and inadequate hygiene. The continuing
expansion of global populations living in poverty is going to make TB difficult to control.
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Example #3: Malaria
ƒ Malaria is caused by a parasitic protozoa (Plasmodium sp.) that is transmitted between
humans by mosquitoes
ƒ Similarly to TB, wide-spread use of DDT and apparently effective malaria control by way of
mosquito control lead to the abandonment of other malarial control programs and the
disease was neglected for several decades
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ƒ When DDT was banned (mosquitoes had developed resistance to it in any event), malaria
re-emerged
ƒ Re-emergence was followed relatively quickly by Plasmodium resistance to the only two
antimalarial drugs available at the time (chloroquine and mefloquine)
ƒ In contrast to bacterial antibiotic resistance, the mechanism(s) by which Plasmodium
developed drug resistance are not clearly understood
ƒ There are more cases of malaria today than 30 years ago
ƒ Malaria now kills over 1M people a year (some estimates are as high as 2M, but definitive
identification of the disease is difficult)
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Projected Risk of Malaria Transmission in the year 2020 based on a global
temperature increase of 1ºC and no human efforts to contain the spread of
malaria
Example #4: Hanta virus or HPS (Hanta virus pulmonary syndrome)
ƒ Hanta and other viruses in the group (the haemorrhagic fever virus group) have all coevolved with specific rodent species
ƒ The first epidemic of HPS, detected in the southwestern region of the US in 1993, resulted
from a population boom of the deer mouse Peromyscus maniculatis, caused by climaterelated proliferation of rodent food sources (increased rainfall, increased plant growth and
seed availability)
ƒ Eventually the mouse populations outgrew their food supply, driving millions of mice into
homes in search of food. There people were exposed to rodent droppings containing the
virus
ƒ As of the first three months of 2006, the US has had 465 cases of HPS with a 35%
mortality.
ƒ In Canada HPS is so-far restricted to the west (BC, AB, MA, SK) where there have been 35
cases and 14 deaths. (Slightly higher mortality in Canada – 40% - is attributed to
unfamiliarity with the disease and hence delayed treatment.)
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Example #5: New-variant Creutzfeldt–Jakob disease (nvCJD)
ƒCJD belongs to a family of human and animal diseases known as the transmissible
spongiform encephalopathies. TSEs are transmitted by a non-living, virus like protein, know
as a prion. There are three distinct types of Creutzfeldt-Jacob
•Sporatic CJD occurs spontaneously with no known risk factors. It represents about 85% of
CJD cases (Canada and US)
•Hereditary CJD is related to a mutation in the PRNP gene (15% of cases).
•nvCJD is different from these ‘regular’ forms of the disease. Molecular analyses of the
prions from BSE-infected cattle and human nvCJD confirm the link between BSE (mad cow
disease) and nvCJD and identify infected beef as the source
•With the exception of UK associated cases, no instances of nvCJD have been diagnosed in
Canada or the US
ƒBSE is believed to have emerged due to now outlawed practicse of using animal carcasses
as cattle food (in particular sheep carcasses infected with a prion caused disease called
scrapie)
ƒAlthough the amount of infected tissue ingested is a critical determinant for the transmission
of nvCJD, mutation at codon 129 of the PRNP gene plays a role in susceptibility to nvCJD
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ƒUncertainties about the extent of an nvCJD outbreak remain as the incubation period is
unknown
•If the average incubation period of nvCJD is ~10 years, the earliest human infections
would have begun in the late 1980s, when exposure to BSE was maximal. In this case, the
outbreak of nvCJD should remain small and confined primarily to the EU
•If the time frame is longer and larger numbers of infected people are incubating the
disease, the potential for human-to-human (iatrogenic) spread may be of concern. This
seems unlikely.
•Iatrogenic means spread by medical/surgical procedures, e.g. endoscopies, vascular
catheterizations, operations, blood and organ donations.
ƒThe only other known orally transmissible spongiform encephalopathies are Kuru, a
degenerative brain disease associated with ritual cannibalism (restricted to specific aboriginal
groups in New Guinea and declining) and two rare genetic diseases
ƒThere are significant uncertainties about the relationship between CJD (nvCJD included) and
Alzheimer’s Neither disease can be confirmed until autopsy
•There are reports of patients clinically diagnosed with Alzheimer's proven to have CJD at
autopsy.
•Carleton Gajdusek, awarded a Nobel Prize for his work with prion diseases, estimates that
1% of people in Alzheimer clinics actually have CJD
•Stanley Prusiner, who won the Nobel Prize for his discovery of prions, speculates that
Alzheimer's may turn out to be a prion disease as well.
•However since neither disease is currently treatable and both are invariably fatal, we’ll just
have to stay tuned!
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How do prions work?
ƒ Prions enter brain cells converting normal brain cell protein (PrPC) to the prion form of the
protein (PrPSC)
ƒ When normal (PrPC) molecules transform into PrPSC molecules, the protein changes shape
ƒ A + feedback sets up, with more and more normal molecules transformed into PrPSC
molecules.
ƒ As the shape of the protein changes, it causes brain cell misfire so various brain functions
work poorly or don't work at all
CJD mortality in Canada
Example #6: Drug resistance, et al.
Staphylococcus aureus
ƒ Resistance to sulpha drugs in the 1940s
ƒ Penicillin in the 1950s
ƒ Methicillin in the 1980s (MRSA or ‘hospital acquired infection’)
• Methicillin-resistant staphylococci are now being isolated from livestock that have been
fed with growth-promoting antibiotics1
ƒ Vancomycin in 2002 (the antibiotic used againt MRSA – leading to VRSA)
• This last resistance came when Enterococcus faecalis, which had became fully resistant
to vancomycin by 1988 (VRE), transferred its vanA resistance genes to the Staph
bacterium during co-infection in three very ill patients in different U.S. hospital ICUs over
a period of 2 years.
• VRE has been unequivocally linked to the use of avoparcin (a vancomycin related
chemical) as a growth promoter in animal food in the EU2
• The EU banned use of avoparcin in 1997, but it is still permitted in animal feeds in the
U.S. and Canada
ƒ MRSA has just been reported in pigs in Ontario3
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M-serotype Group A Streptococcus (GAS)
ƒ In addition to transferring antibiotic resistance genes, bacteriophages or plasmids can also
insert novel genetic sequences into bacteria that increase their virulence
ƒ Group A Streptococcus bacteria are commonly found on our skins, nasal passages and
normally cause no disease
ƒ However the so-called M-serotype GAS are highly virulent causing necrotizing fasciitis, toxic
shock and streptococcal pneumonia
ƒ M-serotype GAS differ from the rest of the Group A Strep in having a unique genetic region
also characterized by bacteriophage markers
E. coli 0157:H7
ƒ Cholera is caused by the bacteria Vibro cholera and spread by exposure to contaminated
water/food
ƒ It causes acute diarrhea leading to dehydration and elecrolyte loss in a period of hours
(mortality is estimated at ≈30%).
ƒ The choleral bacteria can persist in copepods (small marine invertebrates)
ƒ DNA analysis suggests that the gene related to cholera morbidity/mortality (Cl- regulation
and electrolyte imbalance) “jumped” from V. cholera to E. coli (probably via a retrovirus) in
the warm, sewage contaminated waters off S. America relatively recently.
Clostridium difficile (C. diff)
ƒ Now the most common cause of “hospital” acquired infections (contrasted with community
acquired or MRSA/VRSA)
ƒ C. difficile never responded to most antibiotics and though it has subsequently developed
antibiotic resistance to one that was effective (fluoroquinolone), AR is not the issue per se
ƒ Most people have C. difficile in their intestines along with a bunch of other bacteria that are
mostly “good”
• Treatment with broad-spectrum antibiotics suppresses normal colon flora, allowing C. diff
populations to grow exponentially significantly releasing the 2 cytotoxins that lead to C.
diff associated illness: colitis, sepsis and sometimes death
• In the past two years, a new variant with an 18 bp deletion in gene tcdC has emerged the source of the Quebec C. diff outbreak
•Correlated with increased toxin production (18-fold for toxin A, 23-fold for toxin B)
•Associated with increased disease severity and death
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Thursday: flu as an ERID?
ƒ Flu occurs every year – so-called “seasonal” flu
• It generally affects 15-30% of the population
• There are deaths (usually the older, younger or immuno-compromised)
ƒ Hippocrates seems to have been the first observer to record an influenza pandemic in the
year 412 B.C.
ƒ Since 1580, there have been thirty-one recorded flu pandemics, but pandemics remain rare
• Spread rapidly affecting 30-50% of a population
• Deaths are more or less indiscriminate
• Spanish flu of 1918-19 (killed 21M, 40% of people in world were ill)
• 1957 Asian flu and 1968 Hong Kong flu (together these pandemics killed ~1.5M people)
Both of these flu strains were re-assorted avian viruses.
• The 1976 “swine flu” (US president Gerald Ford's decision for an american inoculation
program against swine flu is still controversial)
• H1N1 (~ 6250 deaths to 13 Nov)
• This time last year, the concern was H5N1!
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