Journalist and Author
By coincidence, there’s a paper out today that’s a great follow-up to my last post. In the Archives of General Psychiatry, researchers from Emory University, University of Colorado and University College London propose that the excessive cleanliness of modern life doesn’t only contribute to the rise in allergic disease, but is responsible for increase in major depressive disorder as well.
In case you needed another reason not to buy antibacterial hand sanitizers and soap. [Read more…]
When I talk to people about drug-resistant organisms and how to protect yourself against them, hand-washing and hand hygiene — for individuals and especially for health-care workers — are at the top of my list. Inevitably, I’ll get asked next about hand sanitizers, the alcohol-based gels that now are just about everywhere: outside hospital rooms, in public bathrooms, near elevators in public buildings, and in cute little bottles in bins next to the cash register in almost any drug store.
Hand sanitizer is a good thing: If it’s used properly, it kills reliably. (Except for Clostridium difficile; you need proper hand-washing to keep that down, because alcohol can’t penetrate the hard wall of the spore that the bacterium forms.) That observation usually moves the conversation pretty quickly to the more-is-better impulse that seems so central to American culture. If it’s protective to use regular hand sanitizer, surely highly antibacterial, super-duper-extra-protective, Kills Everything Smaller Than Your Head ™ sanitizer would be better?
The answer to that, counter-intuitively, is no. When it comes to the rise of resistant organisms, topical-antiseptic hand sanitizers seem likely to be part of the problem. And very new research published over the Thanksgiving holiday suggests that they may be problematic in more dimensions than we know.
The chemicals that antibacterial products use for bacterial killing work on organisms in a manner similar to antibiotics’ effect, though they are less potent — and just as organisms have evolved resistance to antibiotic compounds, they have begun to develop resistance to antibacterial compounds too. Which would be a risk worth taking if the compounds provided necessary protection; but studies show that in regular household use, regular soap provides the same amount of protection against disease organisms that antibacterial soaps do. [Read more…]
There’s huge news today in the results of a major drug trial for HIV prevention, but the news comes balanced with significant cautions and caveats. For the first time, researchers have shown that if men who are not infected with HIV take routine doses of AIDS treatment drugs, they can markedly reduce their risk of becoming infected.
Writing in the New England Journal of Medicine, a multi-national team show that, when HIV-negative sexually active men take the once-daily pill Truvada (actually a combination of two AIDS drugs, FTC and DTF), they reduce their risk of becoming infected with HIV by an average of 44 percent. Among men who took the pill diligently — proven in the trial not only by counting their remaining pills but by analyzing their blood for drug residue — the protection rose to 73 percent.
The finding is powerful evidence that it is possible to protect people who are at high risk of infection — even in very resource-poor settings — from acquiring HIV. The 2,499 men in six countries who participated in the study were chosen because they were very high risk: they had sex with other men, as gay men or as self-identified transgender women; they had multiple sexual partners (on average, 18 in the 3 months before the study began); two-thirds regularly had anal sex without condoms; and two-fifths regularly traded sex for drugs, food, shelter or money. [Read more…]
Among the many skills admired by journalists (always finding the free food; never going out of the office; yes, those are said in jest), skidding in just under deadline may be the most valued. I am making a flourish of that skill here, sliding in a mention of an important observance this week just as the week ends.
(Sorry. There was a lot of news this week.)
So: In case you hadn’t yet noticed, this is (was) Get Smart About Antibiotics Week, 2010.
The Get Smart week is co-sponsored by the CDC and the FDA, and its goal is to alert people to the continuing overuse of antibiotics in human medicine. (A separate but just as important issue as overuse of antibiotics on the farm, which I’ve talked about a number of times here.)
If you’re concerned about this — and who shouldn’t be — the CDC’s sites have a plethora of information about this crucial issue. There are briefings, posters, brochures, radio and TV PSAs, a blog by federal researchers and others and — possibly the most directly useful to parents in the whole campaign — a form letter that doctors can download and fill out to give to working parents, explaining why a child with a sniffle or a sore ear can be admitted to daycare without an antibiotic prescription. [Read more…]
I came down hard — justifiably, I think — on health care workers a few days ago in discussing the extraordinary toll of hospital-acquired infections on vulnerable patients. So for equal time, here’s the story of some health care workers who take risks on their patients’ behalf instead of subjecting them to risk.
In its weekly bulletin today, the CDC describes the case of two first responders who contracted meningitis while checking on a 36-year-old man who had not been seen outside his house for several days. One was a police officer, the first one to enter the bedroom where the man was lying unconscious in a mess of feces and vomit; the second was a respiratory therapist who helped suction out the man’s airway and intubate him when he arrived at the emergency department.
Two days after the man was found and transported to an ER, the 30-year-old officer had a sore throat and felt nauseated. He went to his primary-care physician four days after that. While he was in the doctor’s office, he got a call from another member of his department: The hospital had diagnosed the patient with meningococcal meningitis, and the health department was tracing all his contacts.
I’m giving a speech at a conference this morning, so this has to be quick, but I can’t let it pass by, and neither should anyone else: It’s huge, sad news.
The Office of the Inspector General of the US Department of Health and Human Services released a report this morning showing that 13.1 percent of Medicare patients experienced a medical error during hospital stays that caused serious patient harm: prolonged hospital stay, permanent harm, life-sustaining intervention, or death.
If you project the study population — 780 patients over one month in October 2008 — out to the US population, that’s the equivalent of 134,000 people suffering serious medical harm in a year.
One and half percent of the patients died as a result of those errors: the equivalent of 15,000 patients in a year.
And an additional 13.5 percent experienced a medical error that caused them temporary harm.
And those adverse events, permanent or temporary, caused — just in the study month — an additional $324 million in health care spending.
And — if your jaw hasn’t dropped to the floor by now, this will do it — FORTY-FOUR PERCENT of those harms and errors were preventable. (Sorry to shout.)
Just. Outrageous.
And the government agrees, saying in the report’s Executive Summary that these errors are occurring at an “alarming rate.” (p. iv)
Those of you who are on the hospital and infection control sides of the aisle will know how long — and sometimes seemingly fruitless — the struggle against medical error has been. (Medical error includes hospital infections, which include MRSA, the subject of my recent book and therefore my part-time obsession.) It seems sometimes that we have done nothing since the publication of To Err is Human, the seminal 2000 Institute of Medicine report that exposed the rate of medical error in the US to be at least 98,000 events a year, but rack up fresh estimates of horror.
The report came out of the new initiative by the HHS Center for Medicare and Medicaid Services to deny reimbursement for care following adverse events, as a carrot-and-stick approach to attempting to force errors down. It is dry and sober and precise in its methodology, and not long, less than 80 pages. It is worth reading in its entirety.
(H/t to my AHCJ colleague Charles Ornstein of ProPublica, who flagged the report’s release on Twitter.)
Image by Flickr user Romana Klee under CC
This is just amazing.
Ninety-two years and a few months ago, a US Army private died at what is now called Fort Riley, Kansas. It was July 1918, and the 21-year-old recruit had been sick for two days with a fever and a headache, an aching chest and a hard, hacking cough that didn’t bring anything up. He was admitted to the base infirmary, where they found his temperature was a scorching 105.4 degrees and his entire right lung was not functioning properly. He was diagnosed with pneumonia.
It was 10 years before Alexander Fleming would find the mold that produced penicillin, the first antibiotic, on a contaminated culture plate in his laboratory, and 25 years before World War II service-members would benefit from the compound. The medical staff at Fort Riley had almost nothing to offer the private except a primitive immunotherapy: serum refined from the blood of earlier victims of streptococcal pneumonia. It did nothing for him. He died on July 20, nine days after being admitted.
Because he was a member of the armed forces, the base hospital followed a directive that dated back to U.S. Surgeon General William Hammond in 1862: They performed an autopsy on his body, and recorded and preserved the results. Their diagnosis had been right: His lung tissue was positive for S. pneumoniae. But the damage done to his body by the infection and his immune system’s response to it was dramatic: The middle and lower lobes of his right lung, and both kidneys and his spleen, were inflamed and necrotic and speckled with hemorrhages.
In accordance with Hammond’s Civil War order, the medical staff wrote up the autopsy findings and preserved snips of the soldier’s tissues in blocks of paraffin, and sent them all to a repository that Hammond had ordered created: the Army Medical Museum, later called the Armed Forces Institute of Pathology, in the northwest corner of Washington, D.C. And there they sat, among many thousands of other records and samples, until a member of the institute’s staff delved into its archives 80 years after the soldier’s death.
Yesterday and today are early-publication days for the December issue of Emerging Infectious Diseases, the free peer-reviewed journal published by the Centers for Disease Control and Prevention. (Are you reading it? Why not? Your tax dollars pay for it. Go, now.) Among many interesting stories — more on those in later posts — there are two important, complex and saddening papers updating the relentless spread of the “Indian supergene,” New Delhi metallo-beta-lactamase or NDM-1.
(Pause for commentary: I hope we’ve put to rest by now the canard that naming this gene after New Delhi indicates some secret agenda to inflict stigma on the subcontinent’s burgeoning medical-tourism industry. It is a long-standing convention that the acquired metallo-beta-lactamases are named for their point of origin: Holland, Singapore, Germany, et al. You don’t see Vienna complaining, do you? ‘Nuf said.)
A brief recap, for those who spent August focused on something more interesting that bacterial resistance: NDM-1 is a gene that produces an enzyme that confers resistance on gram-negative bacteria to almost all the drugs used to treat them. The American Type Culture Collection, which sells isolates for research, recently published the table of resistance results, and it’s phenomenal: All Rs, all the way down. It was first identified in 2008 in a native of India, resident in Sweden, who had been hospitalized while on a visit back home; then found in the UK in 2009; and then found in the US in June this year. It renders bacteria that are common causes of hospital-acquired infections — Klebsiella, Acinetobacter, E. coli — resistant to all but one or two drugs. It’s extremely bad news. (My NDM-1 posts are here.)
It’s been clear since 2009 that NDM-1 is spreading around the world with great speed. The newest papers in EID confirm that and fill in the details — and wow, some of them are so sad.
My WiSci blogging colleague, Brian Switek, AKA Laelaps, has written a book, Written in Stone: Evolution, the Fossil Record, and Our Place in Nature (Bellevue Literary Press), that’s out this week. It’s his first book, and it’s very good. (To sample some of the swelling chorus of praise, visit Speakeasy Science or The Intersection or Skulls in the Stars or Not Exactly Rocket Science or Observations of a Nerd. Everyone loves it.)
Laelaps and I seem to be connected on multiple axes: We both have new books (here’s mine), we both are science bloggers here at the new Wired network, and we were both also bloggers at Scienceblogs until earlier this year. (Also, we were both on a panel at ScienceWriters 2010 this past weekend.) So because everyone else is already kvelling about the excellence of the book, I asked Brian instead to talk about why he wrote it, and about how he sees blogging intersecting with science writing.
Superbug: Written in Stone came about after your proposal to teach a class of fifth graders about whale evolution was turned down as being too controversial. If common misperceptions about evolution were better understood — or if some of today’s spectacular discoveries were better reported — would creationism be put to rest?
Laelaps: There is no single reason why the best of evolutionary science is not being communicated to the public; evolution remains a persistent public controversy for a variety of reasons ranging from how science is communicated to the background of those receiving the messages. But our fragmented media landscape makes it very difficult to develop an understanding of evolution. Many news stories are one-shot pieces about new discoveries that provide little context as to how the new findings fit in with what has been found before. That was part of my motivation behind composing Written in Stone; I wanted to tie together the disparate threads of recent discoveries and place them in a historical context.
So, following on polio, a little more about diseases crossing borders.
As a kid, I went to a girls’ convent school outside London. (Blazer, boater, motto, crest. Elocution and deportment. Embroidery classes.) There were about three Americans that I remember, and a few South Asians living in the UK, and some girls whose parents were British but living abroad. One of the regular features of the return to term was an interrogation by the headmistress: Had anyone had any illness in their family over the holidays? One New Year, not knowing any better, I put up my hand. Why, yes, I said innocently; my brothers had had measles.
Fingers drummed. Jaws locked. I was whisked to the headmistress’s study. My mother was summoned. She protested that I had been vaccinated. The headmistress was unmoved. I was barred from school for the presumed incubation period. My mother was not pleased. (“You should have lied,” she hissed once we got home.)
I talked on Monday about the risks to the worldwide polio eradication campaign of vaccine-derived polio (VDPV), the mutated form of the vaccine virus. New bulletins from the World Health Organization and the Centers for Disease Control and Prevention remind us that original wild polio can bounce back in perilous ways as well.
The WHO said Thursday that Congo, which saw its last case of wild-type polio in 2000, is in the midst of an outbreak that so far has racked up 120 cases of paralysis and 58 deaths, with half the cases occurring just in the last 10 days. (That’s the Republic of Congo, AKA Congo-Brazzaville. As distinguished from the Democratic Republic of the Congo, AKA the former Zaire, with which it shares a border. Clear?) In polio circles, every case of paralysis is taken to represent from 150 to 200 cases in which people experience no symptoms but are still carrying and transmitting the virus — so this outbreak is very large, and still growing.
Discouraging news from India, in the long campaign of polio eradication that has seen so many ups and downs (my last post on polio here): A girl who was vaccinated against polio in one of the enormous national campaigns held every few months there has become paralyzed. But not for the reason that is usual in India, that the vaccine did not take and she became infected with wild-type polio. Instead, her paralysis was caused by the vaccine virus itself, mutating back to infectiousness and causing what’s known as vaccine-derived polio or VDPV.
As reported in the Telegraph of Calcutta and the Deccan Chronicle, the 9-year-old’s case raised alarms because she lives in the state of Tamil Nadu, which has been polio-free for 4 years. Then she was discovered to be infected with polio virus type 2, which was eliminated in India 10 years ago but still is being vaccinated against, in case it returns. (There are three types.) She is one of three children in India to develop VDPV this year; 15 chldren there did last year. Ironically, only a few days before her case was announced, another newspaper, the Deccan Herald, cautioned that the possibility of VDPV was a “ticking time bomb” that could derail polio eradication if not closely watched.
VDPV is one of the ever-present complexities of polio eradication. It poses a significant risk to the campaign’s end-game that really hasn’t been publicly discussed.
[Read more…]
There’s some new news out — along with a fair amount of public reaction — regarding “pig MRSA” or, to use the technical term, MRSA ST398, the “third epidemic” strain that emerged in pigs in the Netherlands in 2004 and has since appeared, in animals, retail meat, and humans, across the European Union, in Canada, and in the United States. (My last post on it is here, and a long archive of my posts on it starts here.)
I wish I could say the attention to ST398 was being paid in the United States, where there is almost certainly more MRSA in livestock than has been recorded, given that the only published surveillance, from 2009, covered only Iowa and Illinois. Unfortunately, there is still no indication that federal agencies have any intention to test for the presence of the organism in animals or in meat. In fact, the major surveillance mechanism for drug-resistant organisms in meat animals, retail meat and meat-eaters in the US, the National Antimicrobial Resistance Monitoring System or NARMS, doesn’t test for MRSA at all; it handles only enteric or gut-borne bacteria such as Salmonella and Campylobacter. (NARMS IS shared among three agencies: the CDC handles drug-resistant foodborne bacteria in humans, the FDA looks for the same bacteria in food, and the USDA looks for those bacteria being carried by livestock.)
Instead, as so often seems to happen with antibiotic resistance, the country paying attention is in Scandinavia — in this case, Denmark. The annual report from Denmark’s surveillance scheme, DANMAP (Danish Integrated Antimicrobial Resistance Monitoring and Research Programme) is out. Denmark does surveil for MRSA, and here’s what they found: 13% of pigs, at slaughter, were positive for MRSA ST398.
[Read more…]
The annual meeting of the Infectious Diseases Society of America is taking place this week in Vancouver. This afternoon, one of the researchers presenting there released a startling bit of news: the spread in Ohio (and likely elsewhere in the United States) of a MRSA strain that is common in the rest of the world but so unusual in the US that it was last seen here in the 1990s and has never caused infections here.
The strain is ST239, sometimes called the Brazilian clone, and it’s serious stuff: It causes major epidemics and is responsible for something like 90 percent of all the MRSA infections in hospitals in Asia. Its hallmark is that it very multi-drug resistant — including to just about all the oral antibiotics that are used against MRSA.
Brief recap — disease geeks, go on ahead and we’ll catch up: MRSA stands for methicillin-resistant Staphylococcus aureus, the most common drug-resistant infection in the world (and, shameless self-promotion alert, the subject of my recent book). All MRSA strains, at a minimum, are indifferent to the beta-lactam antibiotics, a group of drugs that share a four-cornered arrangement of atoms at the center of their base molecule. That structure allows the beta-lactam drugs to disrupt staph’s cell membrane, killing the bacterium. When staph evolved a work-around for that attack, it became resistant not just to methicillin, which hasn’t been sold for years, but to all the other beta-lactams as well — of which there are dozens; they are the fundamental, basic antibiotics used in medicine every day. Over the years, MRSA has also gained the ability to defuse the attack of additional drugs and drug families, by exchanging with other bacteria bits of DNA containing additional resistance genes. At the same time, the pace of new-drug approvals has slowed dramatically.
OK, back to today’s news.
At IDSA this afternoon, Dr. Shu-Hua Wang, an assistant professor of medicine at Ohio State University, revealed the results of an analysis of MRSA strains that showed up in a surveillance network that links Ohio State and seven rural hospitals nearby. Between January 2007 and January 2010, 7 percent of the 1126 MRSA strains they found in sick patients turned out to be ST239 — the first ST239 infections ever recorded in the US.
The infections were serious: half of the patients had bloodstream infections and one-fourth had pneumonia. And they were unusually difficult to treat: The bacterial samples were indifferent not only to the beta-lactams, but to a wide array of additional drugs: clindamycin, tetracycline, trimethoprim/sulfamethoxazole (TMP/SMX, usually called Bactrim or Septra), moxifloxacin, and gentamicin. They were susceptible only to vancomycin, the MRSA drug of last resort for decades, and one newer drug, linezolid (Zyvox).
That is a dismaying list. Here’s why: In the search for drugs that still work against MRSA, medicine has increasingly turned to older drugs — ones that until recently were never been used against the bug, because there were newer, better drugs available. Tetracycline and TMP/SMX are two of the great remaining hopes for treating MRSA infections without rolling out the really big-gun drugs that should be reserved for life-threatening emergencies. If the resistance factors carried by ST239 knock out the older generics, MRSA infections will become yet harder to treat. As appears to have happened in Ohio:
“Twenty-two percent of the patients experienced relapse and failure of their drug regimens,” Wang said in a briefing for the media. “Another 22 percent died within 30 days.”
The 77 patients infected with ST239 tended to be male and older, and they were apparently already ill: 74 percent had been hospitalized before, 44 percent had had surgery, 29 percent had been in a nursing home, 17 percent had been on dialysis. Where the ST239 first came from and how it spread isn’t clear, Wang said, except that the surveillance network results show the earliest cases to have been treated at Ohio State. It may have spread to the rural hospitals from there.
The most worrisome implication of today’s news may not be the appearance of ST239 itself — it is so common in the rest of the world that its return to the US may just have been a matter of time — but rather the possibility that public health may not be able to keep track of it. In everyday medicine, isolates are tested enough to identify the organism and to determine its susceptibility to antibiotics; those results deliver enough information to determine a patient’s best treatment. Multi-locus sequence typing, the test that identified ST239 in the Ohio patients, is expensive and complex and delivers more information than a clinician really needs; it’s most used in academic research labs. So it is entirely possible that patients could become infected with this strain without the strain being detected, unless the physician treating them happened to put together the puzzle pieces of the unusual resistance pattern.
This possibility seems to have been on Wang’s mind in Vancouver. To track the spread of ST239, “Increased molecular surveillance is needed,” she said. But she offered some workarounds — less expensive, more commonly used assays — whose results could be used to cast a net of detection for the spread of this new strain.
MRSA image from the Public Health Image Library, CDC; poster previously sold by Threadless, original design by Olly Moss
Here at Casa Superbug, we’re in the midst of moving 1,200 miles, so I’m a little slower reading email than I really ought to be. That’s scant excuse, unfortunately, for not noticing one of the biggest global-health stories in years. Mitigating circumstance: Almost everyone else missed it too.
The news is the effective eradication of rinderpest, a viral disease of cattle. Rinderpest does not infect humans, and even in animals it barely occurs in the Americas (or Australia or New Zealand), though until recently it was common and devastating in Africa, South Asia and the Middle East. So unless you are a large-animal veterinarian or a cattle farmer, the disease might never have been on your radar.
So why care that it is on the verge of being removed from the world? Because this marks the first time that a disease of animals has ever been eradicated — and only the second time that any disease has been eradicated at all. The first was smallpox. That was 30 years ago.
Since then, seven other human diseases have been targeted for eradication: Guinea worm (dranunculiasis), elephantiasis (lymphatic filariasis), measles, mumps, rubella, cysticercosis, and above all polio. None of those eradication programs have yet reached their target. Polio has probably come closest, at the cost of billions of dollars and undoubted millions of hours of volunteer effort — yet each time the goal seems within reach, the disease roars back again.
It has been so long since the eradication of smallpox that — I suspect — we have lost any appreciation for the effort it takes to wipe a disease from the planet. Eradication is hard, hard work. It requires that certain conditions exist, to start with: a robust lab and surveillance infrastructure, an easily-delivered vaccine, an absence of any secondary reservoir that can give the organism a refuge. (Whuch explains why tetanus, living in soil, could never be eradicated.) It takes money, time, extraordinary numbers of people and enormous amounts of political will.
More than anything, perhaps, it requires an up-front acknowledgment of what a difficult task it is going to be. We look back on smallpox, from three decades’ distance, as a historic inevitability — but the smallpox campaign wasn’t the first try at eradicating a disease, only the first successful one. There had been four campaigns before — for malaria and yaws, among others — that failed. Writing almost 20 years after the last case, Dr. DA Henderson, one of the architects of smallpox eradication (and author of the recently published Smallpox: The Death of a Disease) reflected:
…eradication was achieved by only the narrowest of margins. Its progress in many parts of the world and at different times wavered between success and disaster, often only to be decided by quixotic circumstance or extraordinary performances by field staff. Nor was support for the programme generous,whatever the favourable cost-benefit ratios may have been. A number of endemic countries were themselves persuaded only with difficulty to participate in the programme; the industrialized countries were reluctant contributors: and UNICEF… decided that it wanted nothing to do with another eradication programme and stated that it would make no contributions. … Cash donations to WHO during the first 7 years of the smallpox programme, 1967-73, amounted to exactly US $79,500.That is not per year, but the total for that entire period. (Henderson, Bulletin of the World Health Organization, 1996
At a certain point, success begins to breed success; the smallpox campaign succeeded in part because people saw that it was working. But the very last days of the campaign were exhausting. I talked to a number of the smallpox warriors for my first book and heard them describe how, time after time. they thought they were done, only to reach another village and find yet another child with the evil telltale rash. Polio now is caught in the same asymptote: The goal has been so close, for so long, and yet the gap to zero has never quite been closed. With much less fanfare, the rinderpest campaign succeeded.
It is a little shaming to admit that I never noticed how dire a disease rinderpest was, or how robust the campaign against it — which began in 1994 — turned out to be. The United Nation’s Food and Agriculture Organization said last week:
At its height in the 1920s, the rinderpest footprint extended from Scandinavia to the Cape of Good Hope and from the Atlantic shore of Africa to the Philippine archipelago, with one outbreak reported in Brazil and another in Australia.
In the early 1980s, the disease was still ravaging livestock herds around the world, with devastating epidemics hitting South Asia, the Middle East and Africa. Losses in Nigeria in the 1980s totalled $2 billion. A 1994 outbreak in northern Pakistan wiped out more than 50 000 cattle and buffalo before being brought under control with help from FAO.
Rinderpest was a lesson in the porousness of borders: It spread around the world, over thousands of years, wherever cattle were herded or traded. (It was in Egypt thousands of years ago, but was probably introduced to sub-Saharan Africa in the late 1800s by cattle bred in India but brought by Italian colonialists.) And it was an illustration of the profound social effects of epidemics: The devastation it caused in Africa, killing 90 percent of the cattle that were the basis of tribal economies, may have paved the way for the takeover and exploitation of traditional African societies by European monarchies.
So hearing the news of the eradication of rinderpest is especially heartening, not just for the animals and livelihoods that will be saved, but also for what it says about the possibility of organizing other eradication efforts for the future. In making the announcement of eradication, the FAO called it “a powerful example of what can be achieved when the international community and individual country’s veterinary services and farming communities cooperate.” That kind of cooperation will be so necessary for future eradication campaigns — not to mention changing antibiotic prescribing patterns to decrease resistance — and it is reassuring to see that, in this case, the collaboration worked so well.
Image courtesy Flickr user publicenergy under CC
…And does paying it keep them poor?
That’s the provocative question that underlies a report released Thursday by the World Health Organization: Working to overcome the global impact of neglected tropical diseases.
What’s a “neglected tropical disease,” or NTD for short? In the WHO’s definition, there are 17; they are bacterial, viral and parasitic, and include dengue, rabies, trachoma, leprosy, Chagas, sleeping sickness, leishmaniasis, river blindness and Guinea worm. They not only have different causes, they affect different organs of the body and even occur in different climate zones. But in a hard-hitting speech delivered Thursday in Geneva, WHO director Dr. Margaret Chan underlined what links them all: They are diseases of the devastatingly poor, those who exist on $2 or less per day, and thus until now have largely been ignored. Chan said:
What brings these diseases together is our collective failure as an international community to do a better job of reducing poverty and addressing the diseases that are bred by poverty.
The neglected tropical diseases form a group because of one shared feature: all occur almost exclusively among very poor people living in tropical parts of the world. All thrive in impoverished settings, where housing is often substandard, safe water and sanitation are scarce, environments are filthy, and insects and other vectors are abundant.
Together, these diseases blind, maim, disfigure, disable, and otherwise impair the lives of an estimated 1.2 billion people. Less visibly, they damage internal organs, cause anaemia, retard the growth of children, impair cognitive development, and compromise pregnancy outcomes.
The significant damage to health is frequently compounded by the misery of stigma and social exclusion, especially for women and girls. In many societies, this is a fate worse than death.
Out of all the scary diseases, none seem to make people horripillate quite as much as the viral hemorrhagic fevers: Ebola, Lassa, Marburg and the rest. That might be due to their still-murky origins, crossing over from the edges of the world of animals into the infringing habitats of men. It might be their uncomfortable classification in biosafety level 4, reserved for life-threatening infections that spread by fine exhaled aerosols and for which there is no vaccine and no treatment. (Four is the highest level. There is no 5.) Probably it is due in part to the enduring impact of the 15-year-old book The Hot Zone by Richard Preston, which in its early pages conducts a master class in describing truly revolting symptoms:
He is holding an airsickness bag over his mouth. He coughs a deep cough and regurgitates something into the bag. The bag swells up. Perhaps he glances around, and then you see that his lips are smeared with something slippery and red, mixed with black specks, as if he has been chewing coffee grounds. His eyes are the color of rubies, and his face is an expressionless mass of bruises. The red spots, which a few days before had started out as starlike speckles, have expanded and merged into huge, spontaneous purple shadows: his whole head is turning black-and-blue.
The cultural response to the viral hemorrhagic fevers has always struck me as interesting. They’re terrifying, and yet we love to hear about them, in a Scary Stories to Tell in the Dark kind of way. When I’ve asked people why the fascination (because I, myself, am much more frightened of parasites, thanks to Carl Zimmer. And brain amoebas), they usually say back to me that it feels like a don’t-leave-the-campfire fright, a safe fright — because, you know, Ebola is over there somewhere. It’s not like it’s coming here.
The problem with that is that VHFs do come here. Actively infectious VHF has been diagnosed in the United States at least six times — most recently in January, in Philadelphia.
Since July, the Food and Drug Administration has been moving — quietly and cautiously, but moving — to raise the stakes in its long and so-far unsuccessful battle to rein in overuse of antibiotics in agriculture. For those new to the topic, this is the use of antibiotics not in treatment-sized doses, to cure disease in farm animals, but in smaller doses to prevent disease or simply to make the animals gain weight faster so they can raised more efficiently and sold off more quickly than they would have otherwise.
There are decades of research by now, demonstrating that this contributes to the development of antibiotic-resistant organisms on farms that then move off harms and threaten human health. It’s not really a scientific question any longer; it’s a question of economics and politics.
(For a long discussion of what the FDA is proposing — and how much force it will, or won’t, have — see this post — at SUPERBUG’s earlier location, because we haven’t yet moved over all the archives.)
Yesterday, FDA Commissioner Dr. Margaret Hamburg gave a speech at the National Press Club at which she raised this issue and made some intriguing remarks. The overall point of the speech (see this AP article) was to promise increased investment and modernization — but she raised both the problem of antibiotic resistance generally and, in answer to a question, the problem of antibiotic use in farming.
First, here’s what she said generally about resistance (my transcription from CSPAN’s video above, starting at about 7:00):
There is increasing alarm about the problem of antibiotic resistance, and we worry with good cause. Today, antibiotic resistance mechanisms have been reported for virtually all known antibacterial drugs currently available for clinical use, which affects everything from global infectious diseases to ear infections in school children to staph infections in locker rooms. People actually talk today about a potential return to the, quote, pre-antibiotic era, unquote, where we no longer have effective tools to treat serious infectious disease. Clearly we must encourage more judicious use of these important drugs through improved infection control, rational prescribing and better patient compliance.
But even if we improve these practices, resistant bacteria will continue to develop no matter what. We need new and better drugs and we need them now. Yet the research and development pipeline is distressingly low. The number of newly approved antibiotics, not just new formulations of previously existing drugs, has fallen steadily since the 1980s, and the range of new antibiotics in distribution is limited in terms of the types of classes of new antibiotics available and the diseases they can treat.
And here’s what she said about farm use, in response to a question (starting at about 31:00):
There historically has been a very considerable use of antibiotics as part of animal husbandry and also agriculture. I think that for many years individuals and organizations in public health and medicine have raised those very concerns, about what is the impact of the use of antibiotics in animal populations on human health and the availability of effective antibiotics to treat disease. We are in the midst of very serious scrutiny of these issues and we have made recommendations in support of judicious use of antibiotics. Nobody wants to deny antibiotics to animals that need medical treatment. But the use in certain preventive contexts, where it is not clearly medically indicated, is of growing concern,. And it is an area that, working with our partners in government, both the CDC and the USDA and others, that we are taking a very serious look at. (Emphasis mine.)
People who are interested in infections that are transmitted in hospitals (umm, ghouls like me) have a special sick relish for Clostridium difficile, or in its short form, C. diff. C. diff lives in the intestines, part of a complex population of many bacteria — you did know there are more bacteria in your body than there are cells that belong to you, right? — but it roars out of control if those other bacteria are wiped out by a course of antibiotics, especially clindamycin. Removing the other bacteria clears out space for C. diff to reproduce in much greater numbers; the toxins it produces irritate the lining of the intestine, producing colitis, and triggering fever, cramps and diarrhea, and in the worst cases, sepsis. miscarriage and death.
C. diff colitis is one of the most common and serious hospital-acquired infections because — if you’re reading this over breakfast, you might want to stop eating now — severe diarrhea in a hospital patient who is confined to a bed and using a bedpan tends to get everywhere. Really, everywhere: bed linens and bedrails, floors and walls, stethoscopes, telephones, computer keyboards, and the hands of the healthcare personnel who operate those devices and then touch another patient.
C. diff persists so spectacularly because in the outside air, it forms a hard-shelled spore that protects its genetic material from assault — including from the alcohol in the hand gel that most healthcare workers use to clean their hands in between patients, and from the stomach acid of patients who swallow it. (See, I told you to stop eating.) Because of that, and because it’s such a devastating infection, hospitals toil incredibly hard at sanitizing to get rid of it.
C. diff colitis is a stubborn and ugly infection. Earlier this summer, an Illinois man named Ed Corboy Jr. described his mother Joan’s experience with it to the Infectious Diseases Society of America:
I watched helplessly as [she] grew weaker, more dehydrated, and nearly died. She was started on intravenous fluids and standard antibiotics while in the hospital two different times that December. Her blood pressure dipped dangerously low on many occasions. She had lost almost 55 pounds in the previous five months, and she was so profoundly exhausted, tired, and wasting away that it became apparent in early January she might die from this. She could hardly get to a bedside commode without two people helping her. Prior to this she was able to walk to her bathroom with her walker on her own for years.
Starting about 10 years ago, C. diff got dramatically more problematic: more virulent, more resistant to treatment, and more commonly occurring in people who would not have been expected to have it — often, healthy young people who had not been in hospitals, who seemed to be developing the illness in the outside world. Two CDC researchers said in 2008:
In the United States, the number of hospital discharges where (C. diff associated diarrhea, CDAD) was listed as any diagnosis doubled between 2000 and 2003, with a disproportionate increase for persons aged > 64 years. By 2003, regional reports of CDAD outbreaks from hospitals throughout the US and in Quebec, Canada emerged, describing severe disease associated with greater numbers of complications, including colectomies, treatment failures, and deaths. In 2004, the attributable mortality rate of nosocomial CDAD in Quebec hospitals was 6.9%, compared to 1.5% among Canadian hospitals in 1997. In the US, death certificate data suggest mortality rates due to CDAD increased from 5.7 per million population in 1999 to 23.7 per million in 2004. (Gould, Critical Care, 2008)
The reason for the surge has been understood to be the emergence of a new, hypervirulent strain of C. diff that produces up to 20 times more toxin than earlier ones. (C. diff nomenclature will make your brain hurt, but the strain is generally known as NAP1/027/BI, toxinotype III.) But increased virulence doesn’t explain the increased incidence, and the transmission patterns of the new strain have been murky.
An emerging line of inquiry suggests that the transmission patterns become much more clear if you look in a different place for the bacterium’s origin: not in hospitals, but in food.
C. diff has been identified in live pigs, cows and chickens. The bacterium has been found in retail meat in the United States and in Canada (in three separate studies), and in salad greens in Scotland. And in a paper published this month, the main authors from those Canada studies establish that minimum recommended cooking temperatures for ground beef don’t kill C. diff spores.
(You’re really not eating now, right?)
So, OK: But are the C. diff strains found in animals the same ones that are causing human disease? The answer turns out to be Yes. Several researchers have found overlaps, in 2007, 2009 and earlier this year, in a study with the perfect title: “Innocent bystander or serious threat?”.
And in what looks certain to be a provocative presentation, a team of researchers from Houston is going to present a paper at the annual meeting of the Infectious Diseases Society of America in a few weeks, titled: “Potential Foodborne Transmission of Clostridium Difficile Infection In a Hospital Setting.” (Uh-oh.)
The case for C. diff as a foodborne illness still isn’t made. In an excellent paper published last month, L. Hannah Gould and Brandi Limbago of the CDC go over the findings so far, and detail what evidence and further research are still needed.
It is reasonable to assume that the general public is and has been often exposed to low numbers of potentially infectious C. difficile spores. There is currently limited epidemiologic evidence to support or refute the hypothesis that C. difficile is transmitted by the foodborne route; the presence of C. difficile on retail foods suggests but does not prove that some proportion of infections is acquired this way. The food supply may thus serve as a source of new strains causing human infections; alternatively, food could be another constant and normally innocuous exposure. (Gould, Emerging Infectious Diseases, 2010)
What’s really interesting, though, is that microbiologists aren’t the only ones noticing this accumulation of evidence. C. diff as a possible foodborne pathogen caught the attention of foodborne-illness attorney Bill Marler early last year. If Marler — the most aggressive and, I suspect, successful foodborne-injury lawyer on the planet, dating back to the 1993 Jack-in-the-Box outbreak — is starting to notice the evidence tying C. diff outbreaks to food, there might be a lot more attention paid to this connection fairly soon.
Image of C. diff by Janice Carr, courtesy of Public Health Image Library, CDC.
A few days ago, health authorities in southern France announced that they’d found two cases of the mosquito-borne disease chikungunya in the Var, in Provence. Chikungunya is a nasty disease; it causes high fevers and severe joint pain, and its name comes from words in a Mozambiquan dialect that describe victims being “bent over” in spasms. Chikungunya perks along steadily in the tropics — Africa, Asia, India — and every year, a few travelers arrive back in the temperate zones suffering from infections they picked up on holiday (e.g., into Europe from the Maldives and from Thailand, both in 2009).
There was something unusual about the cases in the Var, though. Neither of the victims, 12-year-old girls who are friends and live in the town of Frejus, had been outside France. They were the first locally acquired cases of chikungunya that France has ever recorded. And they happened to follow, by two weeks, the discovery of France’s first locally acquired cases of dengue, which is, after malaria, the most serious mosquito-borne disease in the world.
So, on the one hand: Few cases, everyone treated, nobody died.
On the other hand: An early warning signal worth listening to.
Unlike some other vector-borne diseases, chikungunya and dengue are carried only by humans; there are no intermediate hosts, no birds or deer or horses to keep the organism circulating in the environment. A human gets bitten by a mosquito; the mosquito bites someone else; the infection passes on. That tight cycle of transmission requires only a few things: that the human be recently infected, so that the viral load in the blood is relatively high; that the mosquito be one of the few species that transmit the disease; and that the mosquito population be robust — and, ideally, not killed off by winter temperatures.
Put them all together, and you get the Democratic Republic of the Congo in 2004, Reunion Island in 2006 and Singapore in 2008 — all significant epidemics, all tropical locations. But you also get Ravenna, in northeast Italy, where there was an outbreak of more than 200 cases of chikungunya in summer 2007. Ravenna is hardly tropical. Neither is Frejus. But both of their outbreaks started with a recently arrived traveler: a visitor from India in Ravenna, and in Frejus apparently a 7-year-old girl who was in Asia with her family. And both areas share something that gravely worries global-health planners: an apparently increasing population of the key mosquito species, which have ranged further north as average temperatures rise.
In Europe, chikungunya (and dengue) are being spread by Aedes albopictus, the Asian tiger mosquito. It used to be only a tropical species, but it was first spotted in Europe in 1979, in Albania, and it arrived in Italy in 1990. It’s not a long-distance flyer, just a smart adapter: It’s moved around the world, including to the United States (more on that in a minute), via shipments of used tires and sales of those “lucky bamboo” stalks you can find in any gift shop. It has landed in places as far north as Germany and the Netherlands, and has established itself in Albania, Croatia, France, Greece, Monaco, Montenegro, Slovenia and Spain, with the densest populations in Italy.
Where will it go, facilitating disease spread as it moves? The European CDC took an in-depth look at the possibility a year ago. In a report plugging in a variety of climate change models, they concluded there isn’t really, any good news. On the left, in red, is their most conservative short-term estimate of the mosquito’s likely range (for 2010; the maps were generated in 2008 and the report published in 2009); on the right, the most pessimistic estimate, for 2030. Either way, that’s a lot of potential disease transmission.
So what about the United States? By 2006, 37 travelers had arrived in 17 states and Washington DC while infected with or recovering from chikungunya; five of them were viremic enough to be potentially infectious. And in 2008, 14 church workers came back to the US with active dengue— but by luck, returned to the cold-climate states of Minnesota and Iowa, where mosquitoes don’t live very long. They persist for much more of the year in Key West: Between September 2009 and April this year, 28 people, some of them snowbirds from northern states, were infected with dengue in the first local, sustained US outbreak since 1945.
When the European CDC was calculating the potential current range of the mosquitoes that carry dengue and chikungunya, one of the measures they used was mean annual temperature: At a mean of 11 C (52 F), Ae. albopictus are more likely to survive the winter and so hang on from year to year. When you map the United States by mean annual temperature, this is what it looks like; anywhere in yellow is warm enough, long enough, to keep the mosquitoes going.
So, to recap: First Italy, and then France, experienced infected travelers returning to areas where newly established mosquito populations were large and long-lived enough to sustain the importation of disease. In the US, we know we have the travelers; we can see we have the mosquitoes; and given the Key West dengue outbreak, we know transmission of disease by the same mosquito vector has already happened.
In an early sign of what might come next, the Iowa Electronic Health Markets— a prediction engine for disease outbreaks — has just opened a market on the likelihood of dengue occurring in the US.
It might be time to buy a little more DEET.
Maps from Technical report: Development of Aedes albopictus risk maps, ECDC, 2009. Image courtesy of Flickr user Matteo Dudek. Inspiration from ProMED Mail.
