WHEN he travels, David Scollard has learned that it鈥檚 best not to tell fellow passengers what he does for a living. 鈥淭he first response is to lean away from me in the seat,鈥� says Scollard, a pathologist at the National Hansen鈥檚 Disease Programs in Baton Rouge, Louisiana, the world鈥檚 biggest leprosy lab. 鈥淎nd then they look at me with that shocked look: 鈥業 thought that was gone.'鈥�
Those mildly alarmed travellers are not alone in wishing away a disease that has plagued humanity for at least 2600 years, bringing with it centuries of fear and stigma. After all, Scollard鈥檚 story is mirrored countless times whenever scientists or clinicians inform their astounded listeners that leprosy is still alive and, unfortunately, well.
A few years ago, there was widespread hope that leprosy would indeed soon become a thing of the past. Back in 1991 the World 午夜福利1000集合 Organization resolved to eliminate leprosy 鈥� officially known as Hansen鈥檚 disease 鈥� and set the end of 2005 as a target. But with the deadline looming, leprosy remains a stubborn foe, and the elimination programme is hampered by infighting, questionable statistics and a steadily diminishing pool of expertise. Several countries look certain to miss the deadline, and though the WHO is publicly sticking to its guns, in private it is admitting that its leprosy strategy needs rethinking. So where has it all gone wrong?
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Back in 1991, leprosy looked eminently defeatable. With new drug treatments on offer, the member states of the World 午夜福利1000集合 Assembly 鈥� the forum through which states govern the WHO 鈥� agreed to set 2000 as the deadline for 鈥渆liminating the disease as a public health problem鈥�, which was defined as reducing the global prevalence to less than one registered case per 10,000 people. In 2001, the WHO announced that it had hit that target. And while it acknowledged that leprosy was still a major problem in parts of Asia, Africa and South America, it declared that it would replicate its success elsewhere in the remaining hotspots by the end of 2005.
鈥淵ou don鈥檛 have to go to the developing world to see the devastating effects of leprosy first-hand鈥�
For such a feared disease, leprosy is surprisingly hard to catch, and rarely fatal. Yet it is extremely debilitating. Left undetected, it can wreak havoc at its preferred invasion sites: skin cells and specialised nerve cells known as Schwann cells at the cooler peripheries of the body. Gradual destruction of nerves, particularly in the ankles and arms, can leave patients with little or no sensation in their hands and feet, meaning they can inadvertently do themselves serious injury.
You don鈥檛 have to go to the developing world to see the effects first-hand. At a clinic in New York City鈥檚 Bellevue Hospital, physical therapist Louis Iannuzzi assesses patients with relatively advanced leprosy to help them avoid the repetitive injuries that can lead to severe inflammation, ulcers and gangrene. 鈥淚 have a patient who works with cars and doesn鈥檛 wait for the engine to cool down,鈥� Iannuzzi says. Without any pain sensation to warn him, he has repeatedly burned his hands and arms. Another patient dropped a can of soup and broke his toe without realising it.
The good news is that leprosy is relatively easy to diagnose and cure. It is caused by the microbe Mycobacterium leprae, which produces telltale symptoms of enlarged nerves and light-coloured patches of numb skin on a patient鈥檚 face or extremities. The WHO classifies the disease into two forms according to severity: paucibacillary leprosy, a mild version categorised by up to five skin patches, and the more infectious and tenacious multibacillary form, in which there are more than five patches. In reality, the disease is a spectrum ranging from localised skin infections to the most severe 鈥渓epromatous鈥� form, characterised by billions of widely disseminated bacteria. All forms of the disease, however, can be treated with a course of antibiotics and anti-inflammatories lasting anywhere from six months to five years.
The elimination programme has had its fair share of successes along the way. Among these were the first big push to determine the true extent of the disease, and a major drug distribution effort that provided free treatment for millions of patients. According to the WHO, the past 20 years has seen more than 14 million patients diagnosed and treated and a worldwide drop in patient numbers from an estimated 12 million to about 460,000.
The WHO maintains that everything is going well. In the 1 April issue of its Weekly Epidemiological Record it cited the steep drop in cases as 鈥渃lear evidence that the elimination strategy is sound and effective鈥�. The same report notes that only nine countries have yet to reach the 1 in 10,000 target, although the accompanying raw data suggest that another nine countries should be added to that list (see Graphic). And while the WHO cautions that not all the laggards will hit the target by the end of 2005, it says they 鈥渨ill certainly reach the goal in the next few years鈥�.
Widespread confusion
Not everyone sees the situation in quite such positive light, however. Critics say that the elimination programme is deeply flawed, not least because it is not really an elimination programme at all. 鈥淲hat the WHO proposed for leprosy actually means control,鈥� says Sunil Deepak, president of the International Federation of Anti-Leprosy Associations (ILEP), an association of 15 NGOs. 鈥淭hey decided to go about controlling the disease, but they gave it the title of elimination.鈥� As a result, there is widespread confusion about what the programme is achieving. Deepak says he has heard health ministers proudly proclaiming their countries leprosy-free despite evidence to the contrary.
By far the biggest bone of contention is the definition of elimination. Critics say the 1 in 10,000 figure is arbitrary and meaningless. 鈥淭hey assumed that at that level leprosy would die out naturally, but there was no evidence or models to back it up,鈥� says Diana Lockwood, a leprologist at the London School of Hygiene and Tropical Medicine. So even if a country has reached the target, that doesn鈥檛 mean it no longer has a leprosy problem.
Lockwood and other critics also fear that by choosing this way of measuring progress, WHO has opened the door to inaccuracy and fraud. They point out that prevalence figures are easily manipulated 鈥� for example, by revising the definition of a registered patient or shortening the treatment regimen.
There is good reason to believe that such tactics have contributed to the falling caseload. Between 1991 and 1998, the WHO鈥檚 recommended treatment duration fell three times, from three years to one. Some cases are now treated in just six months. And with each reduction comes a fall in the number of registered patients. 鈥淓very time you reduce by half the duration of treatment, you reduce by half the number of people on the register,鈥� Deepak says.
The trick works in other ways too, says Lockwood. Say a country鈥檚 official figures record only those patients who are in treatment in December. If health workers concentrate on finding new cases in January and February and put them on the six-month regimen, by December they are off the books. It鈥檚 as if they never happened.
Despite the WHO鈥檚 attempts to standardise the way that registered patients are counted, each country has its own system, and that makes fiddling the figures easier. In many countries, government officials are sold on the idea of elimination and don鈥檛 want to hear bad news, Deepak and other critics say, especially if the country has already met the elimination goal. Tanzania, for example, announced in 1996 that it had reached the elimination target, only to backtrack in 2002 when it emerged that cases were simply not being reported. Some anecdotal reports even tell of medical officials keeping two books 鈥� one destined for submission to the government and another containing the true number of cases.
Scollard and others say the problem of under-reporting is exacerbated by the intense stigma that still surrounds the disease. 鈥淭he first question that patients ask is, 鈥榳hy did I get this?鈥�, never 鈥榟ow?'鈥� he says. 鈥淎nywhere that people hear this diagnosis, they are usually very surprised, and very fearful.鈥� Indeed, when health officials in New Delhi, India, tried to visit their patients at addresses they had provided, they were unable to find nearly a third of them. 鈥淭hey had given false names,鈥� Scollard says, making it impossible to monitor them and complete the drug regimen. To make matters worse, Scollard claims that the WHO labels these vanishing patients as 鈥渘on-existent鈥�, artificially reducing the figures. 鈥淚t鈥檚 a flagrant misreading of the data,鈥� he insists.
If a study published last month is anything to go by, official under-reporting of cases is a serious problem. A house-to-house survey in Agra, India, conducted between July 2001 and July 2003 revealed an estimated incidence of 16.4 cases per 10,000 residents, in sharp contrast to the official 2002 figure of 0.5 per 10,000 (International Journal of Leprosy, vol 73, p 115). For these reasons, Lockwood and others advocate changing the way leprosy cases are counted. They say the WHO should abandon prevalence and instead measure the detection rate for new cases, which gives a far better reflection of the disease鈥檚 true abundance.
The WHO, though, defends its strategy, saying that prevalence is a good enough indicator for what it wants to achieve. 鈥淓limination is not eradication,鈥� stresses Denis Daumerie, who recently ended his tenure as head of the programme. 鈥淚t鈥檚 just a milestone on the way toward possible eradication.鈥�
That may be so, but the programme鈥檚 problems do not begin and end with statistics. There is troubling evidence that the much-lauded drug regimens are not as effective as once thought. The official WHO line is that relapse rates are extremely low. 鈥淭he rate is less than 1 per 1000 per year,鈥� Daumerie says. 鈥淵ou have a 99.9 per cent chance to be cured if you take the treatments.鈥�
Recent studies suggest much higher relapse rates, however. In December, an editorial in the International Journal of Leprosy (vol 72, p 493) cited relapse rates as high as 16 per cent among a group of 106 multibacillary patients in the Philippines who were treated for two years and followed for more than 12 years afterwards. Similar studies measured relapse rates as high as 20 per cent in Mali and 7 per cent in India. 鈥淭here are people who had very high numbers of bacilli for whom it appears that the standard treatment was not sufficient,鈥� says James Krahenbuhl, head of research at the National Hansen鈥檚 Disease Programs.
Meanwhile, work in the lab hasn鈥檛 fared much better. 鈥淵ou鈥檝e got to be masochistic to do research in leprosy,鈥� says Krahenbuhl. He has seen the corps of basic scientists dwindle and the grants for many labs decline amid a slew of unanswered questions about M. leprae. How do you keep it alive? How do you kill it? What is its main route of transmission?
The microbe鈥檚 closest relative is the tuberculosis bacterium, M. tuberculosis. Compared with the TB bug, however, the genome of M. leprae bears evidence of remarkable degradation, having only half the active genes of its cousin.
This dramatic gene loss, along with its preference for cool temperatures, may explain why M. leprae is so difficult to culture. Microbiologists are only able to grow it on the footpads of lab mice, or on the skin of nine-banded armadillos, the only wild animal that can catch leprosy. Even then, it grows at a breathtakingly sluggish pace, requiring up to two weeks for a single cell division.
No surprise, then, that we know so little about the bug. Even its route of transmission remains a mystery. The most likely route is through nasal secretions, and in fact M. leprae has been detected in a surprisingly high percentage of healthy people in endemic countries. Physical contact has been ruled out as a means of transmission, but the same cannot be said for contaminated soil or water.
Vaccine research, too, is at a virtual standstill. A TB vaccine has shown some success against leprosy, but work on a leprosy-specific version is a low priority. 鈥淲e are not placing any of our resources in this topic, believing that early specific diagnosis and treatment will virtually eliminate the disease,鈥� says Patrick Brennan, a leprosy expert at Colorado State University in Fort Collins.
But critics say the notion that leprosy could be eliminated in the absence of a vaccine is unparalleled in any other disease 鈥� and foolhardy. 鈥淲e look at this elimination programme as testing a hypothesis: can you eliminate a disease by treatment alone? The answer is no, you can鈥檛,鈥� says Krahenbuhl.
Amid all this doom and gloom, however, there are some positive signs. Several experts are cautiously welcoming what they see as a new openness within the WHO. Lockwood says recent meetings suggest that some officials are prepared to move away from arbitrary targets and focus instead on delivering therapies and care. Daumerie confirms that the WHO鈥檚 focus will move away from prevalence. 鈥淣ow that we are reaching the low levels that we were predicting to reach, we will switch the indicators to new case detection,鈥� he says.
鈥淎nyone who gets a diagnosis of leprosy is going to be very surprised and very fearful鈥�
And based on that benchmark, there are signs of success. After holding steady for years, new cases declined by about 33 per cent between 2001 and 2003, from 763,000 to 515,000 a year, although critics point out that it is not clear whether the decline is due to fewer cases or to fewer people looking.
However, there has not yet been any official announcement on a change of course, and nor is one likely until officials report on the end of the elimination programme to the World 午夜福利1000集合 Assembly in May 2006. Daumerie maintains that 鈥渢he programme is still aiming at reaching the target by the end of 2005鈥�, though he concedes that Brazil is the biggest remaining challenge and that they must overcome tricky logistical hurdles in war-torn Mozambique and Angola, and in poverty-stricken Madagascar.
Lockwood believes it would be enormously helpful if the assembly would acknowledge that leprosy has not, in fact, been eliminated, thereby ending the confusion and raising morale and motivation. She would also like an admission that leprosy is not going to disappear any time soon. 鈥淚n conventional terms, we won鈥檛 be able to eliminate leprosy,鈥� she says. 鈥淚 think it鈥檒l probably persist for at least another 100 years.鈥� Sounds like David Scollard is going to have to keep quiet on plane rides for a little while yet.
