The Plague Cycle

by Charles Kenny

  Thankfully, Ashley didn’t contract chickenpox and was fine. But as the number of people who are immuno-suppressed climbs thanks to transplants, treatments against cancer, and diseases including HIV, the risk of the unvaccinated to others will increase. A (dated) estimate suggests there are at least 10 million immuno-compromised people in the United States alone.22

  The parents who choose not to vaccinate their children are not uncaring monsters. They are acting in what they see as the best interests of their loved ones. Vilifying them won’t help. But there’s a place for legally obliging vaccination, and there should be no tolerance for doctors who risk public health by pandering to conspiracy theorists.

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  The international effort to eradicate polio has also suffered at the hands of vaccine deniers. In 2003, the governor of Kano state in Nigeria warned that polio vaccines would sterilize recipients—that they were part of a US conspiracy to depopulate the developing world.23 Polio rates in the country increased fivefold between 2002 and 2006. The Nigerian strain spread to re-infect countries that were previously polio-free. More recently, the opposition to vaccination spread to Pakistan. It began in 2007 with the assassination of the head of polio eradication in the north of the country, who died a victim of the theory that the vaccination campaign was designed to sterilize Muslim girls.

  Violence dramatically picked up in 2012, after Taliban leaders called for a jihad against all immunization workers. More than sixty polio vaccinators and security personnel in the country were killed between December 2012 and April 2014.24 Salma Farooqi was one victim. On the 22nd of March 2014, she spent the day walking through Khyber Pakhtunkhwa province, vaccinating children against the crippling disease. On the night of the 23rd she was back home, asleep with her husband and children in their house in Peshawar. Militants stormed the house, beat her husband, and tied up the children. Salma was dragged from her bed, tortured, and shot, and her body dumped in a field a few miles from her house.25

  As a result of the violence and intimidation, polio infections doubled between 2009 and 2011 in Pakistan, and a polio virus strain originating from the country was discovered in sewage samples collected as far away as Cairo. From only three countries seeing infections a few years previously, polio cases were reported in ten countries in 2014, including Syria, Iraq, and Egypt.26

  One factor behind that 2012 surge in violence against vaccinators was the Global War on Terror. In 2011, CIA agents closing in on the location of Osama Bin Laden hatched a scheme to trace the terrorist’s DNA. They hired a Pakistani doctor, Shakil Afridi, to orchestrate a hepatitis B vaccination drive in Abbottabad and collect the needles. DNA from the blood in the needles could be compared with a sample from the Al Qaeda leader’s sister, who’d died in Boston in 2010. The vaccination team was admitted to the Bin Laden compound, but the operation nonetheless failed—for reasons that remain classified.

  The CIA-backed vaccination drive didn’t even have the fringe benefit of protecting locals against hepatitis: the second shot of the vaccine, required for immunity, was never given. But when the story of the operation leaked, it stoked suspicions in Pakistan that all vaccination campaigns were part of a Western plot. The Taliban took aim at polio vaccination workers in both Afghanistan and Pakistan, and ever more parents refused to have their children immunized. In 2014, the White House announced that it was no longer CIA policy to make operational use of vaccination programs, but the damage had been done.

  Even among the great majority worldwide who believe vaccines are safe, many fail to act. Most vaccinations are given as an automatic part of pediatrician visits. But when they aren’t, vaccination rates drop dramatically. In 2012, if the influenza vaccine rate had hit 70 percent rather than the actual level of 45 percent, thirty thousand fewer people would have been hospitalized in the US with flu. Some may have had the excuse that it was too difficult or expensive to get the shot, perhaps others were ignorant of the benefits, but for too many (including me, I’m ashamed to say) the only explanation is they were too selfish or lazy to avail themselves of protection—despite the benefits that provides for others.

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  Alongside under-use of proven sanitation and vaccination techniques, overuse of some of our weapons against infection is also a risk. A comparatively minor concern with overuse is that disinfecting wipes and HEPA filters may be driving our infection-fighting cells to distraction. If not exposed to enough microbes early in life, the immune system may start fighting against the wrong thing—developing allergies as a reaction against pollen, for example. It can sound counterintuitive—or at the very least, like bad parenting—but setting babies down on the rug and giving them a bit of exposure to bacteria carried on cockroaches, mice, and cat dander may make them less likely to develop asthma later on.27 Conversely, exposing children to triclosan—the active ingredient in antibacterial soap—may increase the likelihood they’ll be diagnosed with allergies or hay fever.28 There’s some evidence that early exposure to antibiotics leads to obesity as well.29 That isn’t to say we were better off in the age of mass infection. Allergies are a good deal better than a case of cholera. But exposure to at least some minor infection risks may be better than no exposure at all.

  The more serious examples of overuse involve taking our sharpest weapons against infection and blunting them through profligate deployment, increasing the risk of a return to higher rates of disease. And that’s linked to the evolution of both microbes and the vector animals that carry them, most significantly mosquitoes. Overuse puts a time limit on the efficiency of a range of different infection-fighting tools, something we’ve been battling for more than a half century.

  In 1958, President Eisenhower used his State of the Union address to declare war on an infectious disease: “We now have it within our power to eradicate from the face of the earth that age-old scourge of mankind: malaria. We are embarking with other nations in an all-out five-year campaign to blot out this curse forever,” he announced.30

  The miracle that would allow America to achieve this goal was a pesticide: dichloro-diphenyl-trichloroethane. DDT spraying was intended to kill mosquitoes, while the drug chloroquine (an artificial relative of quinine from the fever tree) was used to suppress the malaria parasites in infected people. The combined approach had worked to almost completely wipe out the problem of US soldiers succumbing to malaria as they fought across the Pacific in the Second World War.

  Sadly, DDT wasn’t only used to spray houses during the global malaria campaign—it was widely used on crops to increase yields by killing bugs that ate plants. That helped speed the evolution of DDT-resistant mosquitoes. (It also meant that the chemical entered the environmental food chain: in the US that decimated populations of animals including the peregrine falcon.) Not for the last time, as we’ll see, a potentially powerful weapon for human health was blunted by inappropriate use in agriculture. And owing in part to incomplete treatments and poor quality drugs, the malaria parasite evolved as well, developing resistance to the anti-malarial drug chloroquine.31 In some parts of the world, malaria rebounded to kill more than ever.32 Soon after, the US, the major backer for global eradication efforts, pulled funding.

  Around one-half of the world’s countries have eliminated malaria, most in the period after the Second World War. Of the ninety-nine still blighted by the disease, thirty-two are pursuing an elimination strategy, including China, Mexico, Argentina, and South Africa.33

  There is still hope that humanity can eradicate the disease.34 That points to the importance of newer techniques to reduce mosquito populations, including genetic manipulation of the insects.

  And the eradication effort will have to respond to growing resistance not just to chloroquine but also to an alternative treatment, artemisinin, spreading from the Mekong Delta where it first emerged. The planet has seen dramatic progress against malaria in the last decade, but that means there are more and more young people unexposed. If they stop sleeping under bed nets, or if spraying is reduced
or becomes less effective, the disease could roar back as it has before.35

  It isn’t just malaria that is showing stubborn resistance to drugs: in Europe and America HIV that is resistant to at least one antiretroviral drug infects between 10 and 17 percent of patients, even if they haven’t used antiretrovirals previously.36 Multidrug-resistant tuberculosis is also spreading—the result of people failing to complete their treatment because of irregular supply or lack of medical supervision.37 Curing one patient of extensively drug-resistant tuberculosis costs as much as treating two hundred patients with nonresistant tuberculosis.38 But perhaps the biggest concern with resistance involves general-use antibiotics, where a return to a pre-antibiotic world would be catastrophic for modern medicine.

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  Antibiotic resistance has been around almost as long as the drugs themselves. Alexander Fleming himself understood the dangers of antibiotics misuse—in his acceptance speech for the Nobel Prize in Medicine in 1945 he warned that “it is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them.”39

  And it did not take long for resistant microbes to start killing people. In 1972, an outbreak of typhoid fever exploded in Mexico, infecting more than ten thousand people. The condition leaves victims feeling weak, with stomach pains and headaches, and fevers reaching 104 degrees. Untreated, as many as 20 percent of sufferers can die.40 The Salmonella typhi bacterium can be killed with antibiotics. Doctors in Mexico prescribed chloramphenicol—a powerful antimicrobial that usually drops mortality rates well below 1 percent. But the treatment didn’t work. The bacteria simply wouldn’t die. Worse, a range of other antibiotics also proved ineffective, including streptomycin, sulfonamide, and tetracycline. Antibiotic-resistant Salmonella typhi were found in the early 1970s in countries as far apart as Singapore, India, and the United Kingdom.

  E. S. Anderson of the United Kingdom’s Enteric Reference Laboratory, who tracked the spread of the resistant bacteria, explained what was behind it:

  The cause of the rise of chloramphenicol resistance in the typhoid bacillus is unfortunately only too evident. It is the result of the widespread, protracted and indiscriminate use of chloramphenicol and other antibiotics in man and animals.41

  Every time an antibiotic is prescribed, there is a risk that resistance to that antibiotic will develop: some bacteria may survive the treatment because of a greater genetic tolerance. If they go on to infect again, once again the bacteria that are naturally more resistant to antibiotics will be more likely to thrive. The more antibiotics are used, the more opportunity there is for resistance to develop. And the risk is magnified if patients don’t finish their course of antibiotics or use low doses or substandard drugs—because more bacteria will survive.

  That makes profligate prescription a deadly problem. Half of all the antibiotics that are prescribed to people in the US aren’t needed or aren’t optimally effective. For example, only 10 percent of acute bronchitis cases in the US are caused by bacteria, but doctors prescribe antibiotics to treat the condition 70 percent of the time.42 You can even buy antibiotics online without a prescription—a recent study found 136 sellers would ship them to the US, for example, which means many people buy them direct for illnesses for which they’ll be of no help.43 And the US is hardly the worst case.44 The average person in China consumes ten times the volume of antibiotics each year as a person in America. Worldwide, around half of all antibiotics for human use are purchased from private vendors without a prescription.45

  The resistance problem is exacerbated by the antibiotic dosing that is occurring with animals—indeed, most antibiotics don’t go to treat people but are used on farms. In the 1940s, researchers accidentally discovered that giving livestock feed laced with antibiotics could make them grow faster. Subsequently, farmers began routinely administering small doses of antibiotics to their hogs, cattle, and chicken. In the US today, four-fifths of antibiotics produced each year are used in agriculture, largely to enhance growth. By making this dosing routine—especially on factory farms—we’ve taken a historically significant source of new human infections, supersized it, and given the infections a perfect environment to develop immunity to our most powerful tools to fight them. The result is unsurprising.

  In 1976, microbiologist Dr. Stuart B. Levy traveled forty miles to the west of Boston and set up a farm with 300 chickens. The birds were separated into two groups—one set of 150 birds was given normal feed while the other was fed grain laced with the antibiotic oxytetracycline. The research team collected bird droppings from each group and tested them in the lab. Within two days of the experiment’s start the birds fed the antibiotic were excreting out E. coli bacteria that were resistant to stronger doses of tetracycline. And after three months on the feed, the chickens were excreting E. coli that wasn’t just resistant to the antibiotic that they’d been fed but a range of others: sulfonamide, ampicillin, streptomycin, and carbenicillin.

  Levy’s team also examined the feces of the family working the farm. The E. coli that had worked its way through their intestines was also resistant to multiple antibiotics, far more than that of farmers on neighboring properties who weren’t using antibiotic-laced feed. Farmworkers had been exposed by breathing in aerosolized chicken feces. Most E. coli are harmless to humans, but some strains cause diarrhea, urinary tract infections, respiratory illnesses, and pneumonia, among other conditions. The study demonstrated that low-dosage antibiotic use on farms increased the risk of antibiotic-resistant infections spreading to humans.

  Four decades after Dr. Levy’s experiment, the microbiologist testified to the US House Committee on Energy and Commerce. He reported that, despite considerable additional research on the problem, “we are not gaining ground in the struggle against antibiotic resistance and all of us—you, me, and your constituents—are at ever greater risk of contracting a resistant bacterial infection and even one that is untreatable.”46

  That is because, for all Stuart Levy’s work and warnings, we’re still using the same drugs to dose animals as we use to protect people against septic cuts, or heal from surgery, or recover from a stomach bug. Nearly two-thirds of the drugs used in animal feed in the US—20 million pounds of antibiotics a year—are medically important for use in people.47 And China may consume as much as two hundred thousand metric tons of antibiotics each year, ten times US consumption.48

  US government tests of meat sold in supermarkets suggest that 50 percent of chicken samples contain campylobacter bacteria that is resistant to the antibiotic tetracyclin; moreover, of the salmonella found in chicken samples, half of it is multidrug-resistant.49 Campylobacter causes a week-long case of diarrhea often accompanied by vomiting, while salmonella infection is also associated with diarrhea, along with fever and abdominal cramps.50

  And in November 2015, Chinese scientists found, in both pigs and humans, mutant bacteria, including E. coli, that was resistant to all available antibiotics.51 If and when total resistance spreads in a more harmful microbe, doctors and patients will be faced with an infection for which they can do very little.

  With 1 billion plus pigs farmed worldwide, many fed a diet of low-dose antibiotics to aid growth, others fed with a cannibal diet of pig offal, we’ve created a global porcine petri dish for developing new superbugs. Bacon may be a crispy and delicious part of breakfast, but it can also be a crispy and delicious infectious disease–breeding nemesis if we don’t rein in inappropriate antibiotic use.

  Resistant microbes that cause infections of the urinary tract and bloodstream, pneumonia, septic wounds, meningitis, and diarrhea are expanding planet-wide.52 Infection’s most famous mass killer, bubonic plague, has evolved an antibiotic-resistant strain.53 And the Centers for Disease Control suggests that fifteen infections are urgent or serious threats in that they’re resistant to multiple antibiotics, including drug-resistant tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA, which causes skin abscesses filled
with bacteria that can burrow toward bones and lungs).

  We lack accurate data on the scale of deaths related to antibiotic resistance. An investigation by journalists Ryan McNeill, Deborah Nelson, and Yasmeen Abutaleb found widespread underreporting of antibiotic-resistant conditions on death certificates even in the US. For example, Emma Grace Breaux was reported to have died of pneumonia at age three, but unmentioned on the certificate was that her heart and lungs had been severely weakened by a case of MRSA she contracted at the hospital where she was born. Joshua Nahum was preparing to go home after a month in the hospital after a skydiving accident, but contracted drug-resistant bacteria that caused sufficient brain swelling to kill him. The death certificate blandly listed “delayed complications” from his injuries. Few states require notification of drug-resistant outbreaks in hospitals, and the hospitals themselves have little incentive to report what is in part the result of insufficient attention to sanitation by their staff.54

  But the best estimates are that MRSA kills eighteen thousand people a year in the United States alone.55 The toll in Europe and the US from antimicrobial resistance as a whole is around fifty thousand a year.56 Worldwide, resistant bacteria already kill as many as seven hundred thousand people a year—seven times the mortality burden of cholera and six times that of measles.57 And resistance is a problem that has the risk of exploding.

  There are many ways the post-antibiotic era would be a catastrophe—not least, it could bring surgery back toward the nineteenth century. In 2013, Tom Frieden, at that point US Centers for Disease Control director, warned: