Patient History

Hearing of a hospital cook in a Somalian coastal village in the mid 1970s be cured of variola minor virus may seem insignificant and a largely uneventful medical story, however the recovery of Ali Maow Maalin allowed the World Health Organisation to mark the first time in human history that a major deadly disease was eradicated through human effort. This virus, smallpox is rarely considered or talked about in modern conversation and thankfully doesn’t need to be given much thought seeing as the only places where traces of the virus remain are in research facilities in Atlanta Georgia and Koltsovo Russia. However there was a time, not too long ago when smallpox decimated European, Asian, American and African populations through unforgiving final days of vomiting, high fever, body lesions and despair as survival chances were always slim no matter the form of the virus. Those lucky enough to survive could be left blind, infertile and riddled with permanent scarring. So how did this disease send its shockwave through populations, how did it kill its host so effectively and how did global health organisations come together to defeat the disease that claimed the lives of 300 million people in the 20th century alone.

Transmission

The earliest recorded evidence of smallpox arises from Egyptian mummies around 1500BC although the disease had likely been an inconvenience for millennia before these mummies had been embalmed. Since then no Eurasian civilisation could exist without having the disease ravage its cities and populations, claiming the lives of aristocrats, artists and warriors although most frequently the lives of children living is destitution in cramped and unsanitary conditions. So, what was the mechanism of the disease that killed a third of japans population in a two-year period during the 8th century. Well if you were one of these unfortunate nameless victims to contract the disease you had most likely inhaled droplets of airborne variola from face to face contact with infected individuals around yourself. Once inside, your mucous membranes in the throat would be targeted and from there the virus would soon establish itself in the lymph nodes and begin to multiply. For you however, during this solidifying period, life for you would continue as normal for up to fourteen days after contraction. Then after two weeks an internal hell would break loose; high fever, vomiting, general malaise and headaches would set in. On the sixteenth day after contraction the infamous scabbing across your skin would begin. Internally the picture wouldn’t be any prettier. The virus would be dominating the immune system defence systems. Much of the virus’s lethality would arise through its ability to blitz through the body as White blood (dendritic cells) become carries of the virus to other areas of the body. Furthermore the immune system would be unable to use interferons (infection fighting proteins) to signal the body to mobilise against infection since variola would deactivated these, the complement system would shut off, capillaries would die off, lungs would fill with fluid, toxic build up would lead to organ damage, a highly destructive immune member, Neutrophil would be activated, doing more harm to the body than the infection and pus filled lesions containing billions of variola viruses would appear over the organs and skin. Back on the outside, the following two weeks would consist of the development of the ill-famed rash from red spotted macules to pus filled pustules and eventually to the formation of scabs. Those who survived would experience the scabbing and the pockmarks that would remain after the disease had left its host, while those who perished would usually succumb to the infection between the sixteenth to the twenty-second day. 

Structure 

After that disturbing journey through the tactical movement of the disease, what is the science behind the structure of this killer? Smallpox is a large brick shaped virus with a single linear double stranded DNA genome with a hairpin loop at each end, the genus belonging to the Orthopoxvirus, with other notable cousins including, horse pox, mpox and importantly cow pox. The disease comes in two strains, Variola minor or Variola major (the more common and severe form of the disease) with around a 1% and 30% mortality rate respectively. Zooming in closer you see that when categorising the disease by clinical presentation you arrive at four strains of smallpox that usually appear as a result of the major strain. Starting in the deep end there is ordinary smallpox which contributed to around 90% of recorded cases among the unvaccinated and killed a third of the infected. Ordinary smallpox produced a discrete rash in which pustules stood out on the skin separately and the majority of said rash presided on the face and other extremities rather than the torso. Conversely, modified smallpox was more common in the vaccinated but thankfully was almost never fatal. In this form the prodromal illness occurred but less severe than the ordinary type. There was typically no fever during the development and skin lesions, despite developing faster were fewer in numbers, were superficial and didn’t consistently have the same character of more common smallpox variations. Malignant historically accounted for 5-10% of cases most commonly in children. Typically attended with a severe prodromal period and an intense fever, this presentation almost always killed its host between the 8th and 12th day with a 90% above mortality rate. This form is often believed to arise as a result of inadequate cell-mediated immunity, a specific response system using T-cells to fight pathogens. Finally there is the hemorrhagic form, if this title rings some alarm bells it should as this form had a mortality rate just shy of 100%. This inevitability is because of the extensive bleeding into the skin, intestinal tract and major internal organs. Even vaccination provided no hope as the hemorrhagic forms showed no signs of responding to immunity.

Eradication 

Despite this morbid and frankly depressing description of the evil of smallpox that swept through settlements globally for the best part of recorded history there was light at the end of the tunnel even for those who lived long before the creation of the modern vaccine. Before the widespread availability of modern vaccination as we know it, records reveal that as far back as the 10th century, Chinese dynasties were using inoculation against smallpox well before the arrival of inoculation into Europe. One process commonly seen in Africa and India involved exposing a healthy patient to small amounts of material from a smallpox patient by creating an incision on the skin and rub the powdered material in. Nasal insufflation was a method more typical of Chinese medical practice where powdered smallpox scabs were inhaled through the nose of healthy people using a pipe. The mortality rates form inoculation were still a threat however nothing in comparison to the 30% death rate of an actual smallpox infection. Variolation was the first edition of the vaccine although the precision and effectiveness was limited in comparison to the vaccine development by Edward Jenner in the late 1700’s. The Gloucestershire country doctor observed milkmaids who had contracted cowpox did not later catch smallpox. Jenner then tested this in reality and used an 8 year old boy for this test. The boy was given cow pox through an insertion of a sore on an ill milkmaid’s hand into his skin. After the expected uneasiness and general sickness from cowpox, the body was then inoculated with smallpox, no disease followed.

Jenner repeated his experiment 23 times and in 1798 wrote a book on how to prevent people from catching smallpox by exposure to cow pox. He coined his method vaccination after the Latin word for cow, Vacca. Jenner was met with opposition from a variety of groups and doctors who were unwilling to lose their earnings through inoculations. Despite this, in 1852 the British government made the vaccine compulsory but globally the problem was far from over.

A century later as the progress behind education and availability of the vaccine slowly continued, the first hemisphere-wide effort for eradication was made in 1950 by the pan American health organisation. All countries in the Americas except for Argentina, Brazil, Columbia, and Ecuador were free from smallpox. 8 years later USSR health minister Viktor Zhdanov called on the World Health Assembly to undertake a global initiative to eradicate smallpox. The proposal was accepted, likely without much backlash since 2 million lives were still being claimed annually. Progress was regrettably disappointing. In 1967 the WHO intensified the fight, a large portion of this was due to the disease surveillance method to control the spread through isolation. When outbreaks occurred, isolation of the surrounding area would be instituted and all those living close by were vaccinated. This ring vaccination relied on close surveillance of cases in community as well as efficient containment after a breakout. Naturally the reporting of cases to the authorities was insufficient. However by 1975 through the widespread provision of vaccines and education, the disease had been cornered into the Horn of Africa. A widely under appreciated factor in the eradication work mentioning was due to smallpox only being carried by humans, if say mosquitos or livestock had been carriers the long-term effects on societies would be devastating. Despite the difficulty in reaching communities through civil wars, famines and lack of infrastructure. A final vaccination push involving the usual containment and surveillance programmes in the region meant that Ali Maalin was discovered to be ill with a minor strain after being in a car with sick children. Maalin had been offered the vaccination before his contraction but said that he was put off being vaccinated as it looked like the shot hurt. Maalin did listen to experts and followed procedure by self isolating while 50,000 people living near Maalin and the hospital staff Maalin worked with being vaccinated over a two-week period. 3 years later after the campaign could definitively state that Ali Maow Maalin was the last patient, the World Health organisation marked the end of the torment of smallpox for the first time in human history.