MG - Great infectious diseases: Three further examples

• Most recent global pandemic of influenza began in March 2009 – spread in the form of 2 major waves of infection
• Influenza was first coined in Italy (1743)
• Viral disease of mammals (humans, pigs, horses, etc) and domesticated/wild birds
• Highly contagious respiratory disease, characterised by sudden onset of symptoms after an (very short) incubation period of 1-4 days. 
• Symptoms disappear after 7-10 days (mild cases), but mental and physical depression may persist
• Potential complications include;

  a.     Bronchitis

  b.     Sinusitis

  c.     Pneumonia (common cause of mortality in influenza)

• Mortality is rare (1% case fatality – concentrated in young and old age groups) BUT high case levels ensure a high absolute mortality. However, during specific pandemics – much higher case mortality rates 

A virus – undergoes major and minor genetic changes, and a prior exposure does not guarantee life-long immunity

B virus – fixed, a single exposure confers life-long immunity and epidemics rely on the build-up of sufficient numbers of susceptible

C virus – not associated with epidemic events 

• Begin with a pandemic across the world – immunity begin to rise
• New susceptible are born, resulting in an epidemic before immunity increases again
• Environmental factors changing – creates a shift
• Since 1700 there have been 14 definite/probable pandemics of influenza across the world. On average every 20-25 years over the past 300 years. But the important point to note is that these pandemics have been very irregular events. Range from 2 years to 55 years since last pandemic. Place of origin/first report was regularly Russia from early 1700s to end of 1800s – then often in China. 

• General characteristics of 18^th and 19^th century influenza pandemics in Europe
  1. The disease was usually recognised first in European Russia in the winter months preceding the main pandemic period
  2. The disease spread progressively with a well-defined wavefront
  3. The direction of spread was usually east to west
  4. 19^th century pandemics appeared to cross the European continent at the same rate as 18^th century pandemics – there was no acceleration in the spread process over time 

• 20 million died in a few months
• The most destructive in history

• This pandemic spread across the world in 3 distinct waves

• The first wave spread in June and July in 1918 – the mortality from this wave wasn’t particularly destructive/noticeable

• The next wave caused much of the destruction in November and December – this great mortality rate was achieved in only a few months
  The tertiary wave spread in February and March 1919

• In India, 12,500,000 or 4% of the total population are said to have been killed by influenza in the autumn of 1918. 

• Spreading out of Reykjavik 

• 20^th century influenza epidemics in Iceland

  1.     30 epidemics between 1900 and 1974

  2.     Influenza follows the same hierarchical-contagious diffusion process as measles: the hierarchical component is more important than the contagious component for both diseases

  3.     Statistically, the hierarchical-contagious model serves as a more accurate descriptor for the diffusion of influenza than measles

  4.     Contagious diffusion plays a  more important role in the spread of influenza than measles

  5.     On average, influenza epidemics pass through Iceland more rapidly than measles epidemics

  6.     As for measles, the velocity of influenza spread to (and within) Reykjavik has reduced relative to provincial Iceland during the 20^th century 

• Despite being different disease – seems to follow same diffusion pathways to measles

• Average of 5.2 months for influenza to reach around all of Iceland, measles took 7.6 months  

The Geography and Mortality of the 1918 Influenza Pandemic

• The influenza pandemic took more lives than the plague
• The disease first reached France abroad American troop ships in early April
• Spain did not censor news as it was neutral in the war so the epidemic there was widely publicized - this gave rise to the misleading term of 'Spanish flu'
• The fall virus was much more lethal - Most likely origin hypothesis is that the new stain emerged in early august by genetic mutation in Western France 
• The disease covered much of Europe in a matter of weeks
• Spread of the disease was quickened by the railroad networks that spanned the continents
• Coastal introductions in Africa and Latin America
• Incompleteness of reporting and lack of accurate diagnosis are problems that remain today
• Official regestration systems were distrupted by war in many European countries and many poor countries such as in Africa and Asia were very inaccurate in their reporting of the diseases.
• Europe suffered over 2 million deaths
• Influenza deaths in Russia were not recorded

• An acute intestinal disease with severe symptoms appearing within hours or days of infection
• Duration if illness is 12 hours – 1 week with death in 40-60% of untreated cases (death often within days of onset)
• Primary route of transmission: ingestion of faecal contaminated water
• Contaminated rivers and watercourses are the most common originating sites of infection

Critical factors in cholera outbreaks;    

o   Water velocity (strong negative association between water velocity an persistent cholera)

o   pH of water; cholera vibrios multiply faster (and remain viable for longer periods) in alkaline conditions

o   Cold: acts an inhibiting factor in bacterium survival – slows down spread (cholera epidemics tend to collapse in winter) 

• Fear of cholera – probably more than anything else – simulated the sanitary reform and public health movements in Europe and North America 

Six pandemics during the 19th century:

• 1817-23
• 1826-36
• 1840-55
• 1863-69
• 1881-85
• 1892-93

• Reasons for the outpourings may relate to steady improvements in transport and travel during the century 
• Pandemic 1 – first time that cholera spread out of Asia - towards Southern Europe - didn't reach the Americas
• Pandemic 2 - spread out from natural locus to middle east – north Africa – spread across the whole of Europe – first time in UK – spread across Atlantic to North America
• Pandemic 3 – increasing spatial extent – spread across Asia, North Africa, Europe, UK, transatlantic carriage – and south America for first time 

• Pandemic 4 – first truly global pandemic – whole of Asia, Africa, Europe, Americas inc. Caribbean 

• Pandemic 5 – more geographically limited – just to Europe

• Pandemic 6 – Europe, North America

1832 epidemic – cholera spread in a purely contagious fashion. Two entry points; Quebec in Canada (8^th June), second point was in New York (26^th June). Settlements fairly close to the origin was infected first. The urban system was embryonic while transportation was dominated by slow movements along coastal and inland waterways

1849 epidemic – cholera spread as a mixed contagious-hierarchical process. 2 entry points; coast of Louisiana – spread to New Orleans and the second entry point was New York in the following year. 

1866 epidemic – cholera spread purely as a hierarchical process – spread down the urban population hierarchy. Biggest spatial epidemic. One entry point in New York. A rational urban hierarchy had begun to develop and rapid overlap rail transport had begun to emerge

Hierarchical transmission – works way down urban rank – larger cities are infected early on 

Russia in the 19th century

• The dominant diffusion process was contagious
• There was no evidence of a hierarchical diffusion component
• Unlike the USA, there is no evidence that the contagious diffusion process gave way to hierarchical diffusion as the century progressed
• This may be attributable to the lack of development of the Russian urban hierarchy

General

Natural locus of disease activity in delta region of the Ganges and the Brahmaputra

Cholera diffusion in Russia, 1823 - 1923

• Cholera was a frequent visitor to the Russian Empire during the 19th and early 20th centuries.
• Cholera transmision is favored by crowded, unsanitary environments and warm weather, and depends on human mobility to infect new places [7-91. Nineteenth century Russia, with its poverty, crowded rural and urban housing, weak sanitary infrastructure, and extensive long distance trade and labor migration patterns, provided excellent conditions for cholera
• Except for the first pandemic, the pattern was for either rapid spread in the first year, or ‘seeding’ in a small area followed by a rapid expansion in the second year.
• The harsh Russian winter inhibited the pathogen’s survival in the environment, but infection was kept going in large cities, especially Moscow and St Petersburg, and in a few rural foci, usually in the south. 
• Russia was a vast, poor, overwhelmingly rural country with a weak administration in the countryside and an even weaker medical presence there.
• In 1848 some people in both Moscow and St Petersburg hid patients for fear that the authorities would take the sick to special ‘hospitals’ to kill them  

Two types of small pox

1.     Variola major – mortality rate 20-30% and recognized through much of history

2.     Variola minor – a much milder infection, mortality rate 1% and recognized from the late nineteenth century – 1920-30 epidemic

No animals that can become a reservoir of smallpox virus, only humans

Clinical course

1.     High fever headache and muscle ache

2.     Within 2-5 days the characteristic smallpox rash appeared, especially sense on the face, palms and soles

3.     Within days, the pimples of the rash turned to pustules which would dry up and crust 8-9 days after the initial eruptions

4.     Severe scarring of the face was a common sequel to the infection; other effects included blindness and, occasionally, male infertility

5.     Smallpox ended in one of two ways – death or lasting immunity

How did the virus spread?

·      Spread from Egypt to India, area around Calcutta in late Christian times

·      Into Europe with the expansion of the Russian empire 5/6^th century AD

·      15^th century – expansion of slave trade lead to small pox spreading to southern Africa from the uk

·      Spanish carried small pox over to the Americas, mainly Caribbean, in 1507 but this died away. Was then reintroduced in 1518

·      10^th jan 1517 1/3 population of Hispaniola. This then spread to cuba

·      Smallpox killed the Inca ruler and many royals. Making it easier for the Spanish to then take over

One of the very first infectious diseases to be maintain on ships from the uk to Australia

1789 – first evidence of smallpox in the native population of Australia

Small pox outbreaks were associated with importation, it is not endemic

Endemic threshold for smallpox is higher than measles, as by the end of the 19^th century measles was endemic but not small pox

7% of infected vessels passed the maritime quarantine measures of Australia

Long incubation period so could get on boat and off while still in the incubation period

1881-82 smallpox epidemic in Sydney

·      Worst epidemic to strike Australia between 1850 and 1900

·      Laid the foundations for the establishment of a board of health; an infectious diseases act; a medical school at the university; new guidelines for quarantine and disease control

·      First case appeared in Sydney on 25 may 1881 and assumed that the virus was imported from abroad

·      Epidemic lasted 271 days in the city, 163 reported case and 41 deaths

·      Six major diseases clusters, most in the poorest areas of the world

·      Many cases were associated with intra household diffusion (35% of all cases)

·      Inter-household diffusion – over 16% cases

·      Sydney was ill-prepared for the outbreak

·      No public health infrastructure

·      No infectious disease hospitals

·      Quarantine laws limited to maritime control

·      Several approaches to control were undertaken:

1.     Quarantine

2.     Cleansing

3.     Vaccination

Smallpox and its Eradication

• Unmistakable descriptions of smallpox did not appear until the 4th century AD in China, the 7th century in India and the Mediterranean, and the 10th century in south-western Asia. 
• Scientific literature mentions 3 egyption mummies whose skin was covered with lesions that looked like those of a smallpox rash.
• Smallpox may have occurred among the inhabitants of Egypt more than 3000 years ago, which is well over a thousand years earlier than any reliable references to the disease elsewhere in the ancient world. 
• Apart from Rome, there were few centres of population in Europe large enough to have supported endemic smallpox
• It is reasonable to argue that smallpox was endemic in the densely populated Nile and Ganges river valleys at the beginning of the Christian era. From there it spread west to south-western Asia and made periodic incursions into Europe
• By the end of the 19th century variola major was endemic in most countries of the world and in every inhabited continent except Australia; and a new mild variety of smallpox, variola minor, was endemic in.South Ariica and the USA.
• Patients with variola major usually excreted more virus and were thus more infectious than patients with variola minor, and variola major was more likely to overcome the effects of slight residual immunity due to vaccination. 

• One of the factors which led to the decision by the Twelfth World Health Assembly, in 1959, to adopt global eradication of smallpox as a major goal of the World Health Organization was the fact that by this time eradication had been achieved in all the countries of Europe and of Central and North America
• For political reasons, Switzerland had sealed its borders throughout the the war and as effective public health measures were reinstated, variola major became imported smallpox
• Smallpox was officially declared eradicated in 1980 and is the first disease to have been fought on a global scale.
• These strategies were used to combat the disease: Vaccination campaigns, surveillance and prevention measures aimed to contain epidemic hotspots and to better inform affected populations. 
• WHO created posters to publicize the disease or to support programme activities aiming to eradicate smallpox.