Bacteria, not cancer, terrorists and disasters claimed the lives of a huge number of people. Yersiniapestisalone (plague wand) resulted in the death of 150 million people. Taking antibiotics is the main method of combating bacterial infections. But what if the drugs stop working?

This is not a rhetorical question and not an introductory one for modeling a hypothesis, but a real situation in the foreseeable future against the background of increased bacterial resistance. The World Health Organization (WHO) and national services have a common plan of action, but no state has a detailed algorithm for preventing a bacterial pandemic.

We will talk about the causes of the impending catastrophe, as well as about attempts to find a way out of the medical impasse with the help of related disciplines – genomics, mathematics and virology.

Against life

Knowledge is power !: Superinfection, antibiotics and apocalypse models
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Even in antiquity, doctors used to treat purulent wounds with moldy bread. Of the hundreds of potions that existed in ancient Egypt, stale bread was one of the few effective remedies – an antibiotic from mold did relieve inflammation.

Having no idea about the growth and development of microorganisms, the Egyptians acted blindly. In the Middle Ages, doctors completely forgot about successful practice and treated someone in what a great deal, especially fond of bloodletting.

Only at the end of the XIX century. several researchers independently began to study molds from the genus Penicillium , paving the way for the appearance of penicillin. It soon became clear that the substances obtained from the fungus are active against many pathogenic microorganisms.

The British bacteriologist Alexander Fleming announced the discovery of penicillin on September 30, 1928. In 1938, scientists isolated pure penicillin in Oxford, and already in 1941 the drug was used to treat bacterial infections. In 1945, Fleming received the Nobel Prize for his services in the field of medicine.

The action of the first antibiotics (literally from the Greek “anti” – against, “bios” – life) is based on the suppression of the synthesis of molecules involved in the construction of the outer cell membrane of the bacterium.

The video shows how bacteria (on the left side of the screen) literally explode when penicillin is added – antibiotic-thinned cell walls cannot contain intracellular pressure. Fortunately, the structure of the membrane of human and animal cells is different from the bacterial one.

Efficiency trap

Knowledge is power !: Superinfection, antibiotics and apocalypse models
The daily dose of antibiotics per 1 thousand people, distributed across countries with different income levels. 

The potential danger of antibiotic resistance, that is, bacterial resistance to antibiotics, was pointed out by Alexander Fleming himself, but for decades the therapy has been uncontrolled. The “heady efficacy” became the fault – new drugs treated bronchitis, otitis media, conjunctivitis, skin infections, pharyngitis, diarrhea and plague.

Today, antibacterial drugs defeat gastritis, sexually transmitted diseases and even some tumors . Accordingto WHO experts, in developed countries, antibiotics have added approximately 20 years to the average life expectancy of a person. It is not surprising that in America alone today they produceabout 17 thousand tons of antibiotics.

Humanity seemed to have set itself the goal of defeating all the microbes on Earth, but the battle in this world war is not in our favor. Antibiotics have been around for less than a century, and bacteria have been living on the planet for 3 billion years, and create new generations every 20 minutes.

In 2014, the project “Review of Antimicrobial Resistance”, created under the patronage of British Prime Minister David Cameron, published estimates of global losses from antibiotic resistance after 30 years: 10 million deaths annually is more than cancer.

US Center for Disease Dynamics report showsdisturbing results in the development of resistance to last-line drugs prescribed in the absence of a reaction to other drugs. As people increasingly take antibiotics uncontrollably, treatment in medical facilities is losing their effectiveness.

The reports from hospitals in all regions of the world, especially in developing countries, which indicate the occurrence of incurable or almost incurable infections, are very worrying. Simple diseases that were easily treated with affordable drugs in the past become fatal.

According to the WHO, antibacterial resistance in the XXI century. is one of the most serious threats to human health, food security and the global development of civilization.

Infectious foci

Knowledge is power !: Superinfection, antibiotics and apocalypse models
Distribution of methicillin-resistant Staphylococcus aureus (Methicillin-resistant Staphylococcus aureus, MRSA), the causative agent of complex diseases, such as sepsis and pneumonia, resistant to most antibiotics (in percent). 

Sustainability is a natural response of evolution, an attempt to find a way out of the impasse inherent in natural conditions not only for microorganisms. Weeds “learn” to survive under the attack of pesticides, insects are looking for a way to eat plants with a built-in gene of protein toxins, and a person fights pathogens with his mind – this powerful process is associated with the adaptation of all living things to each other.

The problem is that the length of the generation of bacteria is several days or hours, and a person lives for decades. We adapt too slowly. Even taking control over the course of evolution with the help of science, we did not take into account the human factor in the distribution of antibiotics, therefore:

  • the maximum possible dose is taken in a long course;
  • the drug is not used for its intended purpose (for the treatment of viral infections);
  • massive use of the same drugs is carried out without making a reserve.

More than 50% of antibiotics in many countries are used improperly. Among the “culprits” are both ordinary people who violate all conceivable instructions, and hospital staff, contrary to sanitary rules, contributing to the spread of infections between patients with open wounds and a weakened immune system.

Back in the XIX century. in hospitals, they chopped onions finely, killing some bacteria in polluted air. Today gloves, dressing gowns and masks, although mandatory protection, should be given a conditional “zero” level of security corresponding to the class of a medical institution in Central Africa.

A modern hospital can be equipped with HEPA filters (High Efficiency Particulate Arrestance) for air purification, unidirectional air distribution systems, ultraviolet disinfection lamps, and photocatalytic filters with natural oxidizing agents.

The hygienic requirements for the design, equipment and operation of hospitals, maternity hospitals and other medical hospitals in Russia are rather modest , but are still violated sometimes: the staff does not have time or forgets to sanitize the premises, although it is enough to use an ultraviolet lamp and bleach.

Millions of people are catching new infections in hospitals or taking antibiotics to treat the flu and colds. In addition, the use of antibacterial drugs in livestock and agriculture is growing.

Knowledge is power !: Superinfection, antibiotics and apocalypse models
The global consumption of antibiotics in livestock (in milligrams per 10 km²). 

In 2018, Roskontrol discovered antibiotics and antimicrobial agents in all tested chicken samples.

In the United States, approximately 80% of antibiotics are used by Fildena store: It is not surprising that antibiotics are associated with a high frequency of resistant bacteria in the intestinal flora of chickens, pigs and other food animals.

Antibiotics enter the bloodstream through a hospital dropper, in tablet form, along with a piece of steak, even from a fresh loaf of rye bread, since antibiotics are used to combat some plant diseases, and medicines consumed by animals enter the soil and plants with feces urine.

The threat affects everyone – globalization has made the world vulnerable to pandemics. People die from super infections that are resistant to all available antibiotics.

According to a report by the US Centers for Disease Control and Prevention, millions of people in America come into contact with antibiotic-resistant bacteria every year , and at least 23,000 die from infections.

On a global scale, the figure is amazing – 700 thousand victimsannually .

Mathematical models of epidemics

Knowledge is power !: Superinfection, antibiotics and apocalypse models
For 1990—2016. 146 models were created for the analysis of infections caused by the most common types of pathogens: HIV, flu, malaria, MRSA, tuberculosis (the size of the pie chart is proportional to the number of studies). 

Mathematicians and Data Science experts use special predictive models to develop new algorithms to deal with highly lethal rapidly spreading infectious diseases.

A few years ago, a student team of physicists at Leicester University (England) proposed one of these models to calculate the scale of the zombie epidemic.

Apparently, it will be difficult to survive in the apocalypse: 100 days after the outbreak of the epidemic, zombies that turn into undead daily with a 90% probability of at least one person will not be able to catch only 300 people around the world.

The basis of this study was the real epidemiological model of SIR, since 1927 used to describe the spread of diseases among the population. S → I → R , where S (t) is susceptible , the number of susceptible healthy (not yet ill) at time t , I (t) is infected , the number of patients at time t , R (t) is recovered , the number of immune to a disease (e.g., ill) at time t.

Also, the parameter N is sometimes used – number of people , the total number of people covered by the model: S (t) + I (t) + R (t) .

Knowledge is power !: Superinfection, antibiotics and apocalypse models
A sharp outbreak quickly depletes the susceptible pool. The days are indicated on the X axis, and the percentage of the population on the Y axis , where 1.0 = 100%. 

The model divides the population into infected, infected, and dead / recovered. SIR also takes into account the frequency of spread and extinction when individuals in a population come in contact with each other.

Knowledge is power !: Superinfection, antibiotics and apocalypse models
SEIR model with an 8-day incubation period. 

Researchers modified SIR many times . For example, a modelSEIR received the incubation parameter of infected but not yet infectious patients (Exposed population). SEIR is good at simulating outbreaks of tuberculosis caused by the bacterium Mycobacterium tuberculosis .

Knowledge is power !: Superinfection, antibiotics and apocalypse models
In this model, 17% of the population is constantly infected. 

SIS shows that the survivors do not acquire immunity, but return to the susceptible group. Because people remain susceptible after infection, the disease reaches a steady state in the population.

Fortunately, the distribution schedule for most resistant bacteria cannot be directly compared to the zombie epidemic model. In simulation models, most often do not take into account human behavior, its interaction with the environment and bacterial biology.

To create realistic antibiotic-resistant bacteria distribution schedules, millions of different scenarios must be taken into account – the process is remotely similar to modern meteorology and in terms of complexity will give odds to many well-known mathematical problems.

Knowledge is power !: Superinfection, antibiotics and apocalypse models
Simulation of the spread of resistant bacteria across Orange County, California: squares – no specific control measures; black lines – inconsistent control measures when threshold values ​​are reached; gray lines – coordinated control at threshold values. 

The illustration above is an example of a good model that calculates the likelihood of infection spreading to 28 hospitals and 74 nursing homes in a typical urban district. In the model, all infected people move around the healthcare ecosystem: they interact with doctors, nurses, beds, chairs and doors hundreds of millions of times.

The model shows that without enhanced control measures, including regular testing of patients for infection immunity, and quarantine for all carriers, the infection will circulate in the ecosystem on an ongoing basis – in almost every hospital for a decade.

When collecting data for models in the epidemiology of resistance, it will not be superfluous to consider antivirals. The vaccination movement arose shortly after the creation of the first smallpox vaccine by the British physician Edward Jenner . In 1885, 62 years after the explorer’s death, about 100 thousand. Protesters held a march, carrying banners antivaktsinatorskie, children’s coffins and effigies Jenner.

Nearly one and a half centuries have passed, and things are still there – recent outbreaksmeasles from New York to Moscow are associated with an exacerbation of the anti-vaccination campaign. Measles is an extremely contagious viral disease, but many vaccines are created against bacterial infections.

Knowledge is power !: Superinfection, antibiotics and apocalypse models
Map of infection in a biological simulator . 

Even game developers have joined in the fight against human stupidity. In the simulator Plague Inc. the player must infect the virus and destroy the earth’s population in a pandemic. In 2019, anti-vaccinators were added to the game. The result was a visual model: the anti-vaccination movement accelerates the spread of epidemics around the world.

Mathematics does not answer the question of how to resist an infection escaping from quarantine. Under the conditions of an epidemiological threat, the development of new methods of counteracting bacteria becomes a step of “last hope” – in the next part we will talk about attempts to find a way out of the bacteriological impasse.