This is the first article in a four part series looking at how infectious diseases have influenced our culture and evolution, and how we, in turn, have influenced them.

In 2013, the World Health Organisation declared antibiotic resistance was a threat to global health security. It can seem hard to believe that in the 21st century infectious diseases remain such a profound existential risk. But this declaration highlights the ever-lingering threat of infectious diseases and our dependence on antibiotics to stave off their impact on human and animal health and industry.

It also reminds us to appreciate antibiotics as one of many advances in infectious diseases and public health during the past century, and reflect on some of the greatest, still persistent, infectious disease challenges facing us today.

Here we explore our past and present struggles with four of the most significant infectious diseases human beings have faced, some of the progress we’ve made in prevention and treatment, and possible future directions.

Reprinted with permission from Macmillan Publishers Ltd: Nature. Paulson T. Epidemiology: a mortal foe. Nature 2013;502(7470):S2-3, copyright 2013

Tuberculosis

Tuberculosis (or TB) has been responsible for the death of more people than any other infectious disease in history; over a billion deaths in the past 200 years. Its origin is unclear, but it infects a number of other species, including cattle.

Today, about a third of the world’s population is thought to be infected with TB, in its dormant form. This means the bacteria is present but it’s controlled by the immune system, the infected person has no symptoms, and it can’t be spread to others. The bacteria will reactivate in a small proportion of people and they may develop symptoms including fever, sweats, weightloss, fatigue, cough, and haemoptysis (coughing up blood).

TB occurs in every country, including Australia, but mostly occurs in people born in countries where TB is more common, due to the reactivation of dormant TB infection. Patients with weakened immune systems due to chemotherapy, HIV or other medical illnesses are at higher risk of TB.

In 2015, there were 10.4 million new cases of TB, and 1.8 million TB-related deaths around the world, with the vast majority of cases in developing countries. The infection and death rate have been declining internationally since the early 1900s.

Long before the availablility of treatment options, improvements in sanitation, housing, and vaccination led to a reduction in the rates of TB in some countries. But antibiotics made it a curable disease; without them, up to 70% of people with active infection die from TB.

But treatment is complicated, and typically involves taking four medications for two months, then two medications for a further four months. These medications are not without side effects, and can be poorly tolerated. Unfortunately, when medications are not taken or prescribed properly, the TB bacteria can become resistant to these treatments.

In recent years, drug-resistant TB has been documented all over the world, but is much more common in people previously treated for TB, and in Russia, China and India.

Treatment of resistant TB is much more complicated, takes longer, is more prone to failure, and often uses more toxic drugs. New rapid tests can diagnose TB, and whether or not the bacteria will be resistant to our first-line drugs.

A vaccine for TB has been available for around a century, but is most effective in preventing severe TB infection in children. The vaccine’s efficacy is much less clear in adults.

Despite advances in treatment, tuberculosis continues to occur disproportionately in the developing world. Although progress is being made, ongoing and increased political and financial support is essential to ensure coordinated diagnosis, surveillance and care strategies, and universal access to these. Similarly, continued investment is needed for the development of new tools to detect and treat TB.

Smallpox

Smallpox was caused by the variola virus, which plagued humanity for millennia and had a lasting impact on human history. As late as the 1960s, smallpox was still endemic in Asia and Africa, with an estimated two million deaths occurring annually.

Smallpox was spread easily between people by sneezing or shared contact, leading swiftly to the characteristic disfiguring pustular lesions on the skin. The disease was severe, with about 30% of affected people dying, while the rest were left with complications associated with infection. These included a multitude of scars, blindness, infections and arthritis.

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Those who survived, however, were generally protected from reinfection. Building on observations that milkmaids were protected from smallpox, Edward Jenner, an 18th century British physician, developed and popularised a technique called “vaccination” whereby he deliberately inoculated a patient with cowpox, a closely related virus the milkmaids were exposed to. This led to protection from smallpox.

While a popular origin story, alternative approaches to protection, such as inhaling dried smallpox lesions, had likely been practised in China and India for many years previously, and had already been introduced into the United Kingdom. However, inoculation with smallpox came with a risk of severe infection in a significant number of recipients, and Jenner’s safer approach was adopted for larger scale immunisation programs.

In 1980, smallpox became the first, and so far only, human infectious disease to be declared eradicated by the World Health Organisation. This came about via a coordinated international response, led by an Australian microbiologist, Frank Fenner. This involved mass-vaccination, along with public health surveillance and preventative measures, which aimed to educate communities, and identify and contain individual cases.

The last case of smallpox was reported in Somalia in 1977, with the unfortunate death of medical photographer Janet Parker in 1978 serving as a final warning of this deadly condition.

Smallpox may be gone as a disease, but the variola virus controversially remains, kept secure in laboratories in Russia and the US. Concern has emerged about the prospect of smallpox as a weapon of bioterrorism. The impact of such an event could be devastating, given people are no longer routinely immunised against smallpox.

HIV/AIDS

In the early 1980s, a small number of gay men in the United States started presenting with unusual infections, previously only seen in people with severe immune deficiencies. Over the subsequent years, the human immunodeficiency virus (HIV) was discovered, and its global burden was recognised.

The virus, which had most likely originated in primates in Africa, had probably been infecting humans for close to a century, and had spread across the globe. Untreated HIV causes a slow destruction of the infected person’s immune system, leading to a plethora of opportunistic infections and cancers, known as the acquired immunodeficiency syndrome (AIDS).

Without treatment, almost all people with HIV progress to AIDS, and die. At its peak in the 1990s, around 1,000 Australians a year died from HIV/AIDS.

HIV/AIDS mobilised western communities to act like never before. In Australia, a grassroots campaign led by communities most deeply affected resulted in a number of public health interventions and legislative changes. This included safe sex campaigns, needle exchange programs, and mandatory condom use and STI testing for commercial sex workers.

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These changes led to reductions in rates of new HIV cases, while global investment in research and public health led to the development of “antiretroviral” drugs, which stopped the virus from replicating, helped control HIV infection, and markedly reduced the risk of progression to AIDS.

To date, about 40 million people have died from AIDS, and an estimated 36.7 million are living with HIV. Nevertheless, most people affected by HIV in western countries live a long and healthy life.

Although an effective vaccine for HIV is not available, progress is being made in diagnosis, reducing transmission and improving the health of those affected.

Treating those with HIV to a point where the virus isn’t detectable in their blood reduces the possibility of onward transmission by 90-95%. And it leads to numerous individual health benefits for the infected individual. In contrast, uninfected people at high risk of contracting the virus can take antiviral medications known as pre-exposure prophylaxis that prevent infection. These have shown to be highly effective if taken properly.

There are hopes these treatments will end the epidemic by 2030.

Influenza

It’s easy to forget about the danger of influenza. In most cases, this virus is responsible for a respiratory illness of varying severity that generally doesn’t require treatment. However, influenza has been responsible for more deaths in the last century than HIV/AIDS.

Usually, seasonal influenza outbreaks occur annually and affect around four million people, with about 250,000 deaths worldwide. Typically older patients, with pre-existing illnesses such as heart failure or chronic lung disease, and pregnant women are at the greatest risk of death.

Many people have a degree of immunity, due to vaccination or previous infection. It’s worth noting that although safe, the influenza vaccine is imperfect; it’s developed using strains of influenza virus circulating in winter, in the opposite hemisphere, and is about 50% effective at preventing infection. But vaccination is still an important strategy to protect those at risk of most severe infection. It reduces hospital admission and symptomatic infection.

Occasionally, an influenza virus not usually seen in humans is transmitted from its reservoir in aquatic birds, poultry or pigs, to humans. As a consequence, those exposed have no natural immunity, and are not protected by the vaccine at all. If this virus evolves to readily infect and spread between humans, it can have devastating consequences.

In the last century, this has happened several times, with numerous fatalities. The Spanish influenza pandemic of 1918 led to the deaths of more than 40 million people; more than double the number of fatalities in the First World War in the preceding four years. It progressively spread around the globe, with the modernisation of transport and trade systems, and mass-movement of military troops.

In more recent times, smaller outbreaks have occurred, with bird flu and swine flu. There is an ever-lingering threat of a repeat influenza pandemic, due to the industrial scale farming of chickens and pigs, that are also susceptible to infection and the close proximity of humans to these animals.

Due to the rapid and fluid movement of people around the globe for business and leisure, a new pandemic virus could easily be transported around the world. In recent years, countries have stockpiled influenza medications and vaccines in preparation for a possible influenza pandemic.

These are only four of the infectious diseases that have shaped the last century. In reality, there are a number that could have been included in this list of threats including polio, malaria, cholera and syphilis.

Each of these diseases is very different, and as such, our responses to them have been very different too. In part this is because quite different organisms cause these infections, but it’s also because the social context in which diseases happen is critical.

If we are to save the world from the threat of infectious diseases, we need to learn the lessons of past outbreaks, including the value of international collaboration, perseverance and commitment to humanity.

The Conversation , CC BY-ND

Read the other instalments in the series:

How infectious diseases have driven human evolution

How we change the organisms that infect us

How infectious diseases have shaped our culture, habits and language