In this series on superbugs—meaning bacteria that are becoming increasingly resistant to antibiotics—we’ve looked at germs on a national level. But you probably already know that bugs don’t respect borders: Drug resistance is definitely a global problem. And there are two particularly troubling examples when it comes to global drug resistance to bacteria: tuberculosis (TB) and malaria. We’ll take a look at each here:
TUBERCULOSIS
The Size of the Problem: In 2011 alone there were roughly 8.7 million new cases and 1.4 million deaths caused by TB. According to the World Health Organization’s (WHO) Global TB Report 2012, about 40 percent of the world’s TB cases can be found in India and China; and 24 percent occur in Africa.
How Infection Happens: Tuberculosis is caused by the Mycobacterium tuberculosis bacterium and is transmitted via air droplets: An infected person puts contaminated droplets into the air by speaking, coughing, or sneezing. Not everyone who breathes in tuberculosis becomes sick, though. People with latent TB have it living in their bodies but they don’t get sick and they can’t infect others. Others do become sick with TB disease because their bodies cannot stop the bacteria from growing—and they spread the disease.
What an Infection Looks Like: Signs of TB include persistent cough, chest pains, fever, weight loss, and coughing up blood or sputum (a fancy term for mucus). TB not only typically attacks the lungs, it can infect the brain, spine, or kidneys. Without proper treatment, TB can be fatal.
How It’s Treated: Tuberculosis treatment takes six to nine months and involves different phases. In the first two-month phase, TB that can be weakened by drugs is treated with some combination of ethambutol, isoniazid, pyrazinamide, and rifampin (which are antibiotics, not the names of moons from “Star Wars”). The drug regimen just for the first phase of TB treatment is complicated, to say the least: The CDC, American Thoracic Society, and the Infectious Diseases Society of America recommend one of the following:
• a dose a day for two weeks, followed by two doses weekly for six weeks; or
• three doses a week for eight weeks; or
• five doses a week for eight weeks, depending on the drug combination
This first round is followed by another four to seven months of another, equally difficult-to-follow drug regimen with some combination of three antibiotics.
Now I have to ask: How often have you goofed on taking your medicine? Who remembers to take a vitamin every single day? Tuberculosis treatment is tricky, and it is extremely important to follow the regimen, because, when you don’t, that’s when drug resistance can develop.
TB Superbugs: There are varying degrees of resistance in tuberculosis bacteria, and each comes with its own acronym: MDR-TB, or “multidrug resistant tuberculosis,” is resistant to at least isoniazid and rifampicin, which, according to the WHO, are the two most powerful drugs against TB. According to the WHO’s 2012 Global TB Report, about 3.7 percent of new TB cases and 20 percent of previously treated TB cases are estimated to be MDR-TB.
XDR-TB, which is short for “extensively drug-resistant TB,” refers to any TB bacterium that can’t be conquered by isoniazid, rifampin, any fluoroquinoline, and at least one injectable second-line drug (drugs are often separated into first, second, and sometimes third, lines depending on how well they work and their side effects). XDR-TB has been reported by 84 countries; the WHO estimates that nine percent of people with MDR-TB have XDR-TB, too.
It’s worth stopping for a reminder here: Drug-resistant strains can be transmitted from person-to-person. You may have never had TB before and be really diligent about taking antibiotics as prescribed, but given the “right” conditions, you could end up with XDR-TB.
From here things get even scarier: In May 2007, the European Centers for Disease Control reported two cases, dating from 2003, of tuberculosis infection in Italy that were resistant to every TB drug. Reports called the disease XXDR-TB (meaning extremely drug-resistant tuberculosis).
And if that weren’t bad enough, in December 2011 doctors in Mumbai, India, reported cases of totally drug-resistant tuberculosis (TDR-TB). Experts from the WHO, however, decided that no reliable definition of TDR-TB could be agreed upon, so before deeming a strain totally drug-resistant, more data needs to be collected and more research conducted.
Whatever you call this superbug, it raises an obvious and terrifying question: If TB does become resistant to the whole arsenal of anti-tuberculosis drugs, then what? Unfortunately, tuberculosis is not the only global infectious disease with growing drug resistance…
MALARIA
The Size of the Problem: Malaria, a disease endemic in 104 countries in 2012, according to the WHO, is also becoming a lot harder to treat. In 2011, 33 billion people were at risk for malaria. In 2010 alone, there were 219 million cases and 660,000 deaths caused by malaria. As with TB, the burden of malaria is concentrated in a few countries: the Democratic Republic of Congo, India, and Nigeria account for 40 percent of estimated cases.
How Infection Happens: Malaria is caused by a parasite found in the female Anopheles mosquito. There are four different parasite species that typically cause malaria in humans, all hailing from the Plasmodium genus: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. A fifth species, Plasmodium knowlesi, typically infects macaques, but was recently recognized as a cause of malaria transmitted from animal-to-animal.
What an Infection Looks Like: When malaria parasites enter the human bloodstream, they reproduce in liver cells and red blood cells, and then destroy red blood cells, which isn’t great since we need those to transfer oxygen. Uncomplicated malaria causes a flu-like illness, with fever and chills, but patients may also have nausea, vomiting, mild jaundice, and an enlarged liver. Severe malaria, however, can cause anemia, neurologic abnormalities, kidney failure, and severe difficulty breathing. Though malaria is a treatable and preventable disease, it obviously can be fatal.
How It’s Treated: Treatment for malaria may vary depending on where the malaria was contracted, because malaria species have different susceptibilities to different drugs. If you’re traveling to a malaria-endemic area, you may be prescribed drugs like atovaquone-proguanil (Malarone), mefloquine (Lariam), or doxycycline to protect against getting malaria in the first place.
Malaria Superbugs: Unfortunately—and predictably—several antimalarial drugs have already been removed from the market due to resistance. Three parasite species have developed resistance: P. falciparum, P. vivax, and P. malariae.
That leaves far fewer options for treatment, and so for now artemisinin-based therapies are the best option for combating the parasites. Artemisinin is found in the leaves of the wormwood plant and has been used in Chinese therapies for thousands of years. In the 1990s, the pharmaceutical company Novartis bought a patent and began producing artemisinin as an anti-malarial drug.
There isn’t much in line after artemisinin, so the WHO discourages use of artemisinin on its own and instead recommends that the drug be used as part of a combination therapy to reduce the chances that a patient will develop antibiotic resistance. But resistance already is developing: P. falciparum malaria parasites resistant to artemisinin have been in Thailand, Cambodia, Vietnam, and Myanmar, reports the WHO.
There is some good news, though: In May 2013 it was announced that genetically-engineered artemisinin has been approved, which would create more affordable antimalarial drugs. This synthetic version of artemisinin has a big advantage over plant-derived artemisinin, which is available only in certain seasons and is vulnerable to weather changes, reported Rachel Mundy on SciDev.net.
If there’s one thing that superbugs have taught us, it’s that we should never underestimate these microbes. They’ve been around and have survived for much longer than we have. So for now, humans’ best defense remains using antibiotics intelligently, because these drugs are losing effectiveness all too quickly.