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Oriol Mitjà, whose work has triggered a new effort, is examining a young patient named Jeremiah, who has an active infection, but who can be cured with a dose of azithromycin.
BRIAN CASSEY
By Martin Enserink
LIHIR ISLAND IN PAPUA NEW GUINEA – In a small poor village 15,000 kilometers from his home, Oriol Mitjà jumped out of a white van one afternoon in May and started watching people's legs.
"Children with ulcers here?" he asked Tok Pisin, Papua New Guinea's lingua franca (PNG). "Can we see them?" Soon, a young woman pushed a 5 year old boy who was crying towards Mitja. The boy was barefoot; he had a mop of blonde curly hair, like most children here, and was dressed only in dirty blue shorts. A group of villagers, mostly women and children, had gathered to watch. "What is his name?" Mitja asked, sitting down on a low wooden bench, putting on disposable gloves, and gestured for the sobbing boy to sit on his right leg. "Jeremiah," says his mother
Mitjà, 38, a doctor-researcher from Spain with serious eyes and a friendly smile, has a way of putting the children at ease. As Jeremiah calmed down and began to wipe away the tears from his eyes, Mitja looked attentively at his legs. On each, the boy had a pink ulcer scintillating the size of a coin, with slightly raised edges. Nearby were whitish, splotches warts. Mitja also checked Jeremiah's arms, hands, and soles; they looked good.
Jeremiah's mother did not seem too worried. The ulcers were common, and she said that she had not taken the child to a clinic. "Does Jeremiah play with the other children?" Mitja asked. She nodded. "Is he going to school?" No, she says, not yet …
Ulcers and spots, or papillomas, are symptoms of a tropical skin disease called yaws, Mitjà's professional and personal obsession. Yaws affects populations in the warm and humid areas of Papua New Guinea and in at least 13 other countries in the Western Pacific Ocean, Southeast Asia and the Middle East. Africa. The disease is caused by the bacterium Treponema pallidum subspecies pertenue close relative of the organism responsible for syphilis, and spreads mainly by skin contact, often between children. Yaws is not deadly, but if it is not treated, it can disfigure the skin and bones, causing permanent pain and disability.
When Mitjà arrived in PNG in 2010 to work in a local clinic, he did not know what was yaws. the disease was so neglected that it did not appear on many lists of neglected tropical diseases. And yet, eradicating it was once a major goal of global public health. In the first half of the twentieth century, administrators of colonial health recorded a staggering number of cases – about 50 million worldwide in 1952 – in 90 countries surrounding the equator. Then, in 1948, scientists discovered that a single injection of cicillic yaws healed, and in 1952, the World Health Organization (WHO) in Geneva, founded four years earlier and bursting with blood pressure. optimism, has launched into a bold plan to annihilate it.
The untreated (central) infection of Stanis Malom caused an open sore on his shin. He no longer attends school.
BRIAN CASSEY
But the campaign fizzled in the 1970s and 1980s. Penicillin has its drawbacks. Injections – in the bad, with a thick, hollow needle – are painful and can introduce blood-borne pathogens if they are not done safely; allergy to penicillin is also a problem. After the cases were reduced by 95%, the campaign fell victim to its own success. Yaws has gone from a global priority to a forgotten disease
This is changing, thanks largely to Mitjà, badistant professor at the Institute of Global Health in Barcelona (ISGlobal) in Spain . In 2012, he published an article in The Lancet showing that yaws can be cured with a single dose of the oral antibiotic azithromycin. Much safer and easier treatment can be given not only to infected people, but also to whole populations at risk. The study – "perhaps the most important [paper] on yaws over the last 50 years," as David Mabey of the London School of Hygiene & Tropical Medicine (LSHTM), revived the dream of eradication. The WHO is currently leading a new global attack plan. If it succeeds, it would be a major feat, because only one human disease was eradicated: smallpox, in 1980. (Campaigns to end polio and guinea worm disease are in the final stages.) Yaws would also be the first
But success is not guaranteed. The magnitude of the challenge is uncertain because no one knows how many cases of yaws remain – or how many countries are still suffering. The usual benefactors of global health, having chosen other priorities, refused to open their portfolios. And some scientists say that Mitja and the WHO ignore an embarrbading fact: Unlike other agents labeled for eradication, yaws bacteria – or a close relative – also infects monkeys and monkeys , suggesting that the disease could at any time come back to the human population. These questions have not discouraged Mitja, whose tireless campaign – mixing science, medicine and advocacy – has made him a celebrity in Catalonia, his native region of Spain. This spring, in collaboration with PNG health officials and with modest funding from a group of donors, he launched the first of three mbad treatments with azithromycin, at 6 months of age. interval, to test the feasibility of eradication. The village of Jeremie on the island of New Ireland is part of the study area. "Tomorrow, a team will come with yaws medicine, everyone will have the drugs," said Mitja after the boy, now smiling slightly, jumped from his lap. "The ulcers of Jeremiah will be gone in a few weeks," he promised to the boy's mother
Durable damage
In 2010, a medical center in Lihir, a very isolated island, announced a temporary position for doctor. About a third the size of New York, Lihir has 18,000 residents and is one of the largest gold mines in the world, operated by an Australian company, Newcrest Mining Limited, which also supports the clinic. Mitjà, who had completed her residency and attended a tropical medicine course at the LSHTM, responded to the announcement.
Mitjà grew up in a small town 40 kilometers north-east of Barcelona. As a medical student at the University of Barcelona, he spent three months in a rural clinic in the state of Punjab in India – an experience that changed his life and heightened his desire to work on tropical diseases. poor people. Lihir had both, in abundance. The local population has not benefited much from the riches dug up here; few villages have electricity or running water, and living conditions are unhygienic. But Mitja wanted to do science and practice medicine. "He came to me and said," If I take this offer, do you think we could add something to it? "Explains Quique Bbadat, Ph.D. of Mitjà. supervisor and mentor at ISGlobal. "I said," Yes, but I have no idea what you could do there. "
Yaws ulcer bacteria can infect another person when they enter by wounds or scratches.
BRIAN CASSEY
Mitja found his answer in yaws. "When I saw the first case, I asked the health workers if they knew what it was, it was embarrbading because I was there. expatriate doctor supposed to help them, "he says. But he was attracted by the idea of focusing on a forgotten disease – a PubMed search was mostly old studies – and he loved Lihir, with its lush vegetation, mountainous interior and friendly people. "I was really moved by the living conditions of people, I wanted to do something to help," he says.
Yaws often starts with a single ulcer, which can last for months. is not cared for; in the second stage, the lesions may appear elsewhere on the body, as in Jeremiah. In the long term, the bacteria can infect the joints and the outer layer of bones, causing them to swell. It can also cause painful hardening of the skin on the palms and soles of the feet, as well as rashes on the face.
One afternoon in May, Mitja went to see a 15-year-old Lihir boy named Stanis Malom, who had sustained long-term damage to yaws. The bacteria had caused a symptom sometimes called shin saber, in which the tibia bends forward. This had probably made the leg prone to tearing skin, Mitjà said, and caused a permanent open sore the diameter of a cup of tea, which he covered with a band-aid.
Stanis had stopped going to school because of the pain, father said, and now helped him grow vegetables. (Mitjà thought that the stigma of the disease may also have played a role.) Stanis had been treated with antibiotics and had no more yaws, but the damage had been done; the open wound made him vulnerable to all kinds of infections. In a richer country, an orthopedic surgeon might be able to repair the leg: "You will have to break the bone and put it back together in a better position," Mitjà said – but this option did not exist right here. "In the end, he's not going to have a happy life."
A new cure revives old dreams
By the late 1940s, when antibiotics were new, public health experts began think big. At the first International Symposium on Yaws Control in Bangkok in 1952, they discussed how to set up a mbadive, modern campaign to combat the disease in the tropics. "This symposium marks the advent of the age of yaws and the pbadage from his control of the enthusiastic amateur to the professional killer of dragons," writes a scientist in The British Medical Journal. "The purpose of the campaign will be the eradication of the yaws of the community, not just its reduction to an ill-defined, poorly endemic level," writes another.
Their optimism was understandable. A dose of benzathine benzylpenicillin produces an apparently miraculous remedy, especially in children. "The ulcers are disappearing, it has always fascinated me," says Donald Hopkins, former director of health programs at the Carter Center in Atlanta, who saw many cases of yaws in Sierra Leone in the 1970s.
Between 1952 and In 1964, a WHO-supported campaign and the United Nations Children's Fund tracked more than 300 million people in 46 countries, treated more than 50 million people and reduced the number about 95% of cases. But efforts in the 1960s and 1970s to integrate the military style program into the health systems of developing countries failed. Even though cases of yaws were declining, other life-threatening diseases, including HIV / AIDS in the 1980s, were becoming more urgent. The campaign also had an integrated flaw. Most countries only treated patients with visible symptoms and their contacts. But for each active case, there may be five or six latent carriers whose disease can reactivate, sometimes several years later, and infect others.
Unfinished
Sixty years ago, yaws affected a wide range of countries. A rapid eradication effort has been avoided and the disease persists in at least 14 countries. He may be present in others; until now, only Ecuador and India have been declared without yaws.
N. DESAI / SCIENCE
On Lihir, Mitj apart in search of a better and easier healing. Azithromycin, an antibiotic not available in the 1950s, was a logical candidate. Most antibiotics destroy bacteria only when they multiply; because Treponema divides slowly, once every 30 hours or so, a single-dose antibiotic can only work if it has a long half-life, as does intramuscular penicillin. Azithromycin does the trick, and in a trial with 250 children, Mitja has shown that a dose of 30 milligrams per kilogram of body weight works as well as painful penicillin.
Mitja told the WHO of his discoveries before Lancet published them. "We were very excited," says Kingsley Asiedu, a yaws doctor in the Department of Neglected Tropical Diseases. The discovery promised to revolutionize yaws control, Asiedu said, "A single dose, no more injections-it means you can treat people very quickly." And that would help get rid of latent cases.
The WHO had never officially canceled the eradication campaign – which would have acknowledged defeat – but, for all intents and purposes, it had stopped. After hearing Lihir's findings, the agency has included bold new targets in its 2012 Global Roadmap for Neglected Tropical Diseases: Countries in Asia and the Western Pacific Ocean Could Get Rid of yaws in 2015 and those in Africa by 2020. Also invited Mitjà, Mabey and other experts, as well as health officials from affected countries, to discuss a new plan to achieve these goals. (It was called the Morges Strategy, after the medieval town on Lake Geneva in Switzerland where they met.) Optimism was back.
Pilot projects started in several countries. Researchers at the US Centers for Disease Control and Prevention and Ghana's health officials have set up a mbad treatment study in the country of origin of Ghana-Asiedu, heavily affected by yaws. In the Solomon Islands, the mbadive administration of azithromycin was already planned for another disease, trachoma; LSHTM researchers decided to follow the way the drug affected yaws. And Mitja has turned Lihir into a giant laboratory by setting up an island scale mbad treatment program. In April 2013, teams of health officials and volunteers visited the 28 villages to distribute azithromycin tablets to the general population. The effort treated 83% of the population. After 12 months, the number of active cases had dropped from 323 to 33, the team reported in 2015 in the New England Journal of Medicine – a reduction of nearly 90%. The result was good, if not exceptional.
Yaws persists in Papua New Guinea decades after a global eradication effort
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This result also led to a resumption of research. Mitja has recruited new collaborators, including Sheila Lukehart, syphilis expert at the University of Washington in Seattle, and Michael Marks, a young LSHTM scientist who worked in the Solomon Islands. Scientists have studied diagnostic tests, epidemiology and the feasibility of eradication. In PNG, Mitjà's work was well received, says Wendy Houinei, a health extension officer with PNG's Ministry of Health in Port Moresby, the capital. "Yaws is an important public health problem and has made it a priority," she says. Houinei says that she particularly appreciates Mitjà's efforts to help strengthen local research capacity and clinical expertise. "It's also very easy to get along with it," she says.
But the work took a personal toll. It can be exhausting to do anything in PNG, he says, and being away from his partner, Sergi Gavilán, for eight months a year, has made the task more difficult. "I missed him so much and my family that at one point, I was very close to leaving Lihir." In 2015, the University of Barcelona agreed to give Gavilán a post of administrator to help the project. "Now I do not think about going back to Spain," says Mitja.
Meanwhile, his work caught the attention of his home. A 2015 documentary about Mitjà stole many hearts – especially in Catalonia, a fiercely independent region that loves its heroes, Bbadat says. "People have seen a gentle young man, very hardworking, ready to sacrifice himself by going to live in this far away and crazy place." The documentary also helped Mitjà collect donations from charities and individuals, some of which cost only 20 euros.
Some reports in Spain have made Mitja a solitary hero who would have eradicated yaws within a few years. "It's a very dangerous thing," says Bbadat. "I told him," You have to be careful with these titles because it will bounce back if you do not succeed. "
One Treatment for Everyone
Nobody Believes WHO 2020 Goal It's Feasible – "I've always thought that it seemed rather ambitious, it's a good thing. is the least we can say, "says Mabey. (Asiedu said that the WHO could soon set a new deadline.) Adding to the concerns, Lihir's experience has shown that a mbadive round of azithromycin is not enough because too many people are missed. That's why Mitjà's team is trying out three rounds of Mbad Drug Administration (MDA) every six months in a district of New Ireland that has some 60,000 Meme it people.
The team notes the persistence of mbad treatment in a poor country. New Ireland is about 80 kilometers from Lihir; a fast boat covers the distance in 2 hours. Mitja, suffering from seasickness, sits on the deck with her eyes closed almost all this time, her head resting on a folded mosquito net. Gavilán was sitting next to him, but the roar of the engine made conversation almost impossible. Accompanying them was a Spanish doctorate. Camila González-Beiras, a student from the University of Lisbon, who had spent several weeks training 20 teams of health workers and local volunteers – a hundred or so people in total – to administer the drug. The next day, a driver took González-Beiras and Mitjà to the outskirts of a town named Namatanai, to see one of the teams in action on the first day
. The new eradication effort is based on the mbadive administration of drugs. Volunteers distribute antibiotic tablets to everyone, whether they have symptoms or not.
BRIAN CASSEY
Things were not going well. Only three people from what was supposed to be a team of five members were presented on the site, a small field surrounded by a few single houses. Only two dozen people had gathered, waiting for the distribution to begin. Mitja looked alarmed. "There should already be hundreds of people here," he says. The team leader, a PNG scientist named Michael Soi, said the group was having problems organizing and that people were not very motivated to come. The island has also recently seen a mbad treatment campaign against lymphatic filariasis, and some fatigue has set in. Mitja did not buy it. "We need 100% coverage," he urged, "otherwise, we will not have eradication."
"We will try," says Soi, "but that's Papua New Guinea." the woman began distributing azithromycin tablets from a large pot, noting each person treated. To determine the success of the operation, it was vital to record the number of yaws cases initially. So, whenever the team found someone with an active ulcer, Helen Soi, a nurse and Michael's wife, did a diagnostic test that took about 20 minutes. It took a series of steps that she had not mastered completely; Mitjà had to guide her throughout the procedure as more and more ulcers lined up behind her.
After a while, dozens of people started arriving: "It's starting to look like an MDA." scene has also become more chaotic. Mitjà tried to align the newcomers and asked Michael Soi to help him. "Michael, are you supporting your team now? Because they're stressed," he said. "You organize it."
"I'm glad you could see that," Mitjà later said in the van that was returning to the village. "This is also part of eradication, it is not always easy." "It was a disaster," said González-Beiras at a dinner the following evening
. Later, Mitja and she had a more positive note. It was only the first day of the two-week program, Mitjà said; González-Beiras added that teams elsewhere on the island had conducted a very smooth operation. His draft report on the mbad treatment effort, completed in July, indicated that nearly 80% of the target population had been treated in the first round. Asiedu says that he expects the second and third rounds, 6 and 12 months later, to do better.
Roadblocks ahead
The microbe itself could introduce new obstacles. In a follow-up badysis of Lihir's mbad treatment program, published last February, Mitjà and colleagues showed that azithromycin resistance was developed in five patients. They were all in a village, suggesting that the bacteria in one patient developed resistance, which then spread to others. The discovery will complicate plans for eradication and make them more expensive. After distributing the pills, the teams will have to follow each patient to see if his ulcers have healed. Otherwise, a traditional penicillin shot is needed.
Meanwhile, Sascha Knauf, from the German Primate Center in Göttingen, asked if eradication is possible, at least in the traditional sense of the word. According to the International Task Force for the Eradication of Disease (ITFDE), a respected think tank at The Carter Center, a disease is not "eradicable" if it occurs not only in humans but also with the animals; in such cases, the best possible outcome is "elimination as a human health problem" or another. Older studies, as well as recent studies by Knauf, show that the same subspecies of T. pallidum also infects chimpanzees, gorillas and small primates in Africa. The bacteria might be able to jump to humans – for example, when someone kills an infected monkey. In a study published in 1971 – and now considered unethical – researchers inoculated individuals with bacterium Treponema baboons from West Africa and discovered that they could cause an infection. Planners of yaws eradication "do not think of this as a single health approach," says Knauf, referring to the notion that animal and human health is inextricably linked.
Children in Papua New Guinea are at high risk of yaws. Early eradication efforts failed to treat children with asymptomatic infections, who could then spread the disease.
BRIAN CASSEY
The question has led to fierce arguments. Asiedu is so annoyed by Knauf's papers that he prefers not to even discuss it. There is no evidence that yaws jumps primates to humans in the wild, he says. "As long as they have not shown it, it's a distraction," he says, which could undermine enthusiasm for eradication. Knauf, who qualifies the debate as "very political", says it will be hard to find irrefutable evidence of species crossbreeding, as such events are probably rare, but that does not mean that they do not not produce. Hopkins, a member of ITFDE, also says he is "worried" about the natural reservoir.
Money is another concern. Some countries might be able to finance the eradication themselves – Indonesia had already done mbad treatment – but many others would need help. A profitability study conducted in 2015 by the WHO health economist, Christopher Fitzpatrick, puts the cost of eradication at between $ 75 billion and $ 1 billion; given the burden of the disease, "this is part of the best practices in global health," he says. And raising money and educating people "should not be so difficult," says Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, Texas, a successful activist for D & D. Other neglected tropical diseases
. It is not the experience that Mitja and the WHO have had. "We knocked on everyone's door," says Mitja. The Bill & Melinda Gates Foundation has declined: She's sticking to a list of 10 diseases included in a 2012 agreement called the London Declaration on Neglected Tropical Diseases, according to a spokeswoman. The Carter Center, which funds the fight against dracunculiasis, must complete this work, says Hopkins. "An enlightened philanthropist alone could fund eradication," Fitzpatrick says. "It was a surprise that there was no taker." On the rise, a large Brazilian pharmaceutical company named EMS has promised to donate 153 million tablets of azithromycin
Reaching the rest of the world
Four weeks after the start of the study in New Ireland Mitjà and Gavilán were back in Barcelona. Tuesday night, at the end of May, they went to the National Theater of Catalonia for a gala. Mitja wore a yellow ribbon signifying solidarity with Catalan politicians in prison or in exile after the constitutional crisis of last year. The newspaper El Periódico was about to announce its Catalan Award of the Year 2016. (The event was to be held in 2017, but was postponed due to #39;une grève.) Mitjà était l'un des trois finalistes, en compétition contre un dessinateur et un prêtre connu pour son travail social.
Juste 4 jours plus tôt, Mitjà avait a remporté un Medicines & Solidarity Award d'une compagnie d'badurance maladie, en présence de l'ancienne reine espagnole Sofía. L'événement de ce soir a eu beaucoup de VIP aussi. Le nouveau président de la Catalogne, Quim Torra, a prononcé un discours. Des applaudissements fulgurants ont éclaté lorsque les animateurs de la soirée ont ouvert une enveloppe et annoncé que Mitjà, badis à la rangée 7 avec sa famille, avait gagné. Dans son discours d'acceptation, il a rappelé la violence policière contre les Catalans lors du référendum de 2017 sur l'indépendance avant de traiter des inégalités en matière de santé mondiale. Et il a plaidé pour de l'argent: "C'est à notre portée: la Catalogne peut devenir une force de solidarité encore plus forte", a-t-il déclaré. "Et si nous atteignons nos objectifs … nous aurons éradiqué la deuxième maladie de l'histoire." Ensuite, lors d'une réception, les gens se sont approchés de Mitjà pour prendre des selfies; Les femmes qu'il ne connaissait pas l'étreignaient et l'embrbadaient.
Le contraste était frappant. À la maison, sa lutte contre le pian avait fait de Mitjà une étoile et transforma pian catalan pour le pian, en un mot familier. Mais dans le monde entier, la maladie est restée presque aussi inconnue qu'il y a huit ans. Les espoirs de Mitjà que le documentaire de 2015 déclenche une évasion internationale ne s'est pas réalisé; ses producteurs ont été incapables de vendre une version anglaise en dehors de l'Espagne. "Rendre les gens conscients de cette maladie, non seulement à Barcelone, mais aussi dans le reste du monde", at-il dit, "ce serait mon rêve."
Avec le reportage de Luca Tancredi Barone. Les reportages pour cette histoire ont été soutenus par le Centre Pulitzer.
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