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Jan. 19, 2017

Inside the global campaign to get rid of By Erik Stokstad

ON A SUNDAY EVENING last July, relative urged her to travel the die from rabies worldwide Flora Gichonge was walking with 16 kilometers to the nearest each year, almost all infected her friends to church near the hospital to get immunized by dogs. Malaria, HIV, and village of Gesarya, . against rabies. Her husband, tuberculosis take much higher Suddenly, they were attacked by a businessman, had the $40 tolls. But the horrible suffering something hellish: A rabid dog, to buy three doses of the life- caused by rabies—some foaming at the mouth, charged saving vaccine from a pharmacy. patients have convulsions and out of the dense bushes lining A few days later, she was back become aggressive, just like the dirt road. “We tried to run at work, gathering and selling rabid dogs—and the fact that away, in fear,” the 25-year-old nuts. She knows she was lucky, many victims are children led recalls. But she tripped and fell. although now she’s afraid of the World Health Organization The dog lunged and bit her in strange dogs. (WHO) and other groups in 2015 the backside before her friends to announce a goal to eliminate drove it away by throwing stones. Many others are less fortunate. rabies deaths worldwide by After Gichonge limped home, a An estimated 59,000 people 2030. In theory, nobody should die from rabies. It’s one of the few viral Taking aim at a global scourge diseases where administering The World Health Organization and other groups have announced the goal a vaccine after exposure can of eliminating rabies as a public health problem. The key to fighting it: still save your life. Developing vaccinating dogs. countries try to provide enough doses to hospitals and clinics. Unfortunately, supplies often run out. People who can’t afford to buy the jabs from private pharmacies, or don’t get them in time, are doomed. Untreated rabies is the deadliest of all diseases, fatal almost without exception.

That’s why the global plan calls for cheaper and faster treatment for people. But its long-term bet (GRAPHIC) J. YOU/SCIENCE; (DATA) K. HAMPSON ET AL., PLOS NEGLECTED TROPICAL is on vaccinating domestic dogs, DISEASES 9 (16 APRIL 2015) ©PLOS ONE which pose the biggest threat to people in the developing world. “It’s the only way you’re going to eliminate the problem,” says A campaign pays off Louise Taylor, scientific director Some developing countries have succeeded in eliminating rabies. Others of the Global Alliance for Rabies have made great progress. As Sri Lanka ramped up dog vaccinations, for Control, an advocacy group based example, human deaths declined. The country has also spent heavily on in Manhattan, Kansas. To rid a postexposure vaccines, further cutting deaths. canine population of the virus, vets aim to immunize at least 70% of dogs for several years. After that, a lower coverage level suffices to keep outbreaks at bay.

This strategy has stopped rabies as a killer in developed nations. Elsewhere, the challenges are enormous, and nowhere bigger than in sub-Saharan Africa. Poor countries can hardly pay for millions of dogs to be vaccinated, J. YOU/SCIENCE; (DATA) PUBLIC HEALTH VETERINARY SERVICES, SRI LANKA MINISTRY OF and their governments often have HEALTH trouble organizing vaccination campaigns across vast rural they often face obstacles. The welfare charity near Arusha, areas—even if they have the veterinary teams that typically Tanzania. “The connection with political will. Big donors, for their run them don’t work together saving human lives is not there.” part, prefer to work on diseases with public health authorities and with a higher death toll or believe tend to prioritize cattle and other Now, in pilot projects underway in that reaching enough dogs is too valuable livestock, which usually Tanzania, Kenya, and a few other complicated. die of other diseases. “In Africa, African countries, scientists are what’s a dog? It’s worth nothing,” testing strategies for reaching and In fact, dog campaigns are says Jens Fissenebert, who vaccinating dogs more efficiently. relatively straightforward, but runs Mbwa Wa Africa, an animal They are also collecting data to pin down the toll of rabies, demonstrate the connection On its way out between dog vaccination and Countries in Latin America and the Caribbean have made steady progress human health in poorer countries, toward eliminating canine rabies. With help from the Pan American Health and quantify the economic benefits Organization, they jointly purchase and share vaccines, use standardized of national campaigns. surveillance, and coordinate vaccination along borders.

Although the 2030 target seems improbable, if not impossible, proponents point to a few successful efforts—including the brief defeat of dog rabies in N’Djamena, the capital of dirt-poor Chad—to show that the disease can be beaten back even in Africa. (GRAPHIC) V. ALTOUNIAN/SCIENCE; (DATA) M. C. SCHNEIDER ET AL., CADERNOS DE SAUDE PUBLICA, RIO DE JANEIRO, 23 (9): 2049–2063, SET, 2007; PHILOSOPHICAL TRANSACTIONS “It’s not going to be fast, easy, OF THE ROYAL SOCIETY B 2013 368, 20120143 (24 JUNE 2013) or inexpensive,” says Charles Rupprecht, a rabies expert and consultant near Atlanta. “But it can rabies, and almost all had been at face of the planet, as smallpox was, be done.” least partially immunized. because so many mammal species harbor it. These reservoirs pose THE RABIES VIRUS IS A MARVEL Louis Pasteur developed the first a continuing, albeit minor risk for of biological ingenuity, cruelly rabies vaccine, made from the humans: In the United States, one manipulating its host’s behavior dried spinal cords of infected or two people still die each year to further its own reproduction. rabbits, and famously used it to after being bitten by rabies-infected After a dog becomes infected, save the life of a 9-year-old Parisian bats. In Eastern Europe, rabid foxes usually through a bite by another boy in 1885. Today’s versions are a concern. dog, the virus travels to the brain are produced from virus grown and renders the animal hyper- in cultures of human cells, then As with other neglected diseases, aggressive and excitable, with a chemically sterilized; they are more it is difficult to know the exact hoarse howl. The virus also spreads effective, far less painful, and human toll. Asia currently suffers to the salivary glands, which start have fewer side effects. Three to the highest number of deaths, producing saliva laden with billions five jabs over several weeks will an estimated 35,000. Africa has of viral copies. By interfering prevent the virus from reaching fewer, but the individual risk of with the pharyngeal nerves, the the brain if given quickly enough. dying of rabies is particularly high virus makes it hard for the dog to A dose of rabies antibodies is in sub-Saharan countries (see swallow, leading to more saliva and also recommended for people not map, p. 241) because of the many increased chances of transmission. previously inoculated. unvaccinated dogs—they’re widely used for guarding livestock and The disease is similarly gruesome Dog vaccines were first developed homes—and underfunded health in humans. In what’s known as in the 1920s. Still, it took decades systems. paralytic rabies, about one in five to eliminate rabid dogs as a public patients slips into a coma and dies health threat in Europe, Japan, “DANGER! DANGER! RABIES of respiratory and heart failure. and elsewhere. Now, Latin America KILLS” says the poster on the Furious rabies is even worse, with is on the verge of replicating the mud-brick building. A makeshift symptoms including fear of water— success (see timeline, below), clinic has been unloaded from a even to drink—spasms, terror, and following a concerted and battered Land Rover in Ligamba, aggression. Human-to-human coordinated campaign that reaches a small village in the Mara region transmission of rabies is believed 40 million to 50 million dogs each here, to offer free shots for dogs. In to be extremely rare, and has only year. the shade of a tree, Imam Mzimbiri been documented from a few organ wields a hypodermic needle. He or cornea transplants. Only 15 Rabies can never be wiped off the tells a middle-aged man to grasp people are known to have survived the neck of his large dog. The man Park from rabies. In 2002, the researchers are trying to quantify digs his sandals into the sand, U.S. National Science Foundation the benefits of dog vaccination. but the dog leaps away and nearly provided $1.5 million for a study Ahmed Lugalo, a veterinary breaks his rope leash. Mzimbiri, of carnivore disease ecology in the epidemiologist affiliated with a veterinarian with the Serengeti park. As part of the work, veterinary Sokoine University of Agriculture Health Initiative run by the Lincoln epidemiologist Sarah Cleaveland in Morogoro, Tanzania, follows Park Zoo in Chicago, Illinois, of the in the up on dog bites and rabies casually walks off and then circles United Kingdom and colleagues cases recorded in logbooks back behind the dog. He darts in started vaccinating dogs around from clinics and hospitals. He and jabs the needle into its thigh. the borders, hoping to keep rabies also has a network of dozens “This one was hard to handle,” he from spreading to other wildlife in of paraveterinary assistants in says. the Serengeti. surrounding villages who keep an ear out for reports of rabid dogs, conduct interviews, and, when possible, take brain samples of dogs suspected to have died of rabies. The effort, directed by veterinary epidemiologist Katie Hampson of the University of Glasgow and funded by the Wellcome Trust, provides data that allow researchers to create and test models of rabies transmission and the effects of vaccination.

On a recent afternoon, Lugalo and a paravet drive to the outskirts of Mugumu to interview Ghati Muhingira about a serious dog bite. Her children play nearby, as scrawny chickens peck in the dirt yard. A breeze rustles corn fields. This past August, Muhingira’s Mostly, the animals cooperate. Cleaveland quickly became equally oldest daughter, Asha, was bitten Over several hours, the team concerned about rabies’s impact on her leg by a dog as she walked vaccinates 145 dogs. Traveling on people. “As soon as you start to school. Gazing vacantly into to all the villages within 10 studying rabies in wildlife, you’re the distance, Muhingira says that kilometers of Serengeti National confronted by the human tragedy,” after she saw the deep wound, she Park, Mzimbiri and his team notch she says. Fortunately, the dog called a motorbike taxi and rushed up 45,000 dogs a year. They also campaign helped bring down 7-year-old Asha to the hospital. vaccinate the occasional cat; human cases and alleviated other The staff only gave her a tetanus although cats are uncommon pets hardships. Villagers bitten by a injection, because the dog’s owner in Africa and not a reservoir of the rabid dog can spend 25% of their said it had been protected against virus, they can transmit rabies to annual income on inoculations, rabies. people. which cost an average of $60 for a full five shots. (Most people get In early October, Asha told her The work has helped make this three.) And rabid dogs can infect mother that her healed leg was part of Tanzania an exemplar cattle, driving annual livestock aching. Two days later, when she of progress in the fight against losses across Africa that cost some became feverish and had trouble rabies. The campaign started out $280 million a year. swallowing, her mother took her of concern for endangered African to the hospital. It was rabies. The wild dogs (Lycaon pictus), which In Mugumu, a dusty town on the owner of the dog had lied about had died out in Serengeti National northwestern side of the park, its vaccination. A few hours before she died, Asha, delirious, thought although feasible, may be she saw her school teacher and Starting in 2010, government a logistical challenge, and called out: “I’m healed. I want to go workers began to vaccinate surprisingly expensive. An audit by home.” 150,000 dogs across Tanzania’s Rupprecht and colleagues found southeast, covering about 18% that costs ranged from $7.30 to Later in the day, Lugalo says that of the country, and on the island $11.27 per dog, much more than such stories take an emotional of Pemba in the north. Health the $1 to $1.50 they had expected. toll—he recently became a father and veterinary workers used text Higher startup costs, such as himself. During the interview, message questionnaires to report vehicles and other equipment, however, he’s all business. He asks dog bites and use of human contributed, but the bulk of the how much Muhingira spent on the vaccine, which led to better, bill was due to per diem payments hospital visit. Then he asks about faster, and cheaper surveillance, that Tanzania charged WHO for the the dog. It had bitten another child, researchers reported in PLOS services of government vets. Muhingira says. Lugalo advises Medicine last April. By the third her to get her own dog immunized, year, 65% of dogs in the target The government is now drawing up and the team leaves to interview villages had been vaccinated, on a strategy to expand the scheme the mother of the other victim. average. The coverage was lower in to the entire country. Tanzania will Not taking any chances, she remote villages. have to do the job without support had already gotten her daughter from the Gates Foundation, vaccinated. The dog owner, who however, which funded only pilot lived next door, boarded up his projects, hoping that governments house after the police started an and other donors would then investigation. “He has run away, take over. The test of Tanzania’s like his mad dog,” says Lugalo’s resolve will come in September, co-worker Matthias Magoto, when the next vaccination round shaking his head. is due to start.

IT’S PAINSTAKING WORK like A FEW OTHER CAMPAIGNS have this that helps clarify the true emboldened rabies fighters in burden of rabies. Cleaveland has sub-Saharan Africa. A team led developed a now widely used by Jakob Zinsstag, a veterinary method to estimate the death epidemiologist at the Swiss toll, using the numbers of bites Tropical and Public Health by dogs thought to be rabid, as Institute in Basel, eliminated well as records of postexposure canine-transmitted rabies for 2 vaccine use. The best estimate years in N’Djamena, although one for the current toll in Africa, rabid dog was detected in 2014, 21,000 deaths, comes from a apparently an invader from the 2015 paper by Hampson and The effort halved the number of countryside. KwaZulu-Natal has colleagues; it’s 100 times higher reported dog bites overall, and seen success at a bigger scale. than official figures. rabies appears to be almost In 2007, rabies cases in dogs gone from about a third of the 28 and humans were at their highest The initial numbers from the districts in the program. For 2 years recorded levels; they have declined Serengeti were enough to turn the dog population on Pemba was dramatically thanks to vaccination Cleaveland into an advocate free of the virus. Unfortunately, efforts supported by another Gates for better control of rabies and, this past August, an infected dog Foundation–funded program. ultimately, its elimination. She brought in from the mainland Kenya is the latest country to get helped WHO win what became caused a small outbreak. “It was on board, with growing political $12 million from the Bill & Melinda really disappointing,” Hampson support. It released a national Gates Foundation for pilot projects says. strategy for rabies elimination in in Tanzania, South Africa’s 2014 and has started two pilot KwaZulu Natal province, and the The main lesson of the pilot: projects. Philippines. Eliminating rabies in Tanzania, Even national success won’t be enough in the long run, says Thumbi Mwangi, a veterinary epidemiologist at Washington State University (WSU) in Pullman and an adviser to Kenya’s Zoonotic Disease Unit. “The day we have fully eliminated rabies in Kenya, we will start to get incursions” from neighboring countries, he says. Ultimately, Africa will need to develop the kind of regional cooperation that has worked well in Latin America.

For Africa as a whole, rabies elimination would cost between $800 million to $1.55 billion, says François-Xavier Meslin, a former director of neglected tropical yet it would save many lives by diseases at WHO in Geneva, providing human postexposure Switzerland. The price could “Ultimately, rabies vaccines to developing countries, come down, however. In 2012, advocates say; governments could the World Organisation for Animal elimination in then use some of their health Health started a “virtual” dog Africa requires regional budget for dog vaccines instead. vaccine bank, which lowers prices Some experts worry, however, that by allowing buyers to purchase cooperation. A the availability of more human collectively. Another potential rabies-free Kenya vaccine could actually lower the saver emerged just 2 months ago. is only protected pressure to eliminate rabies in dogs Until now, the dog vaccine has and thus perpetuate the problem. always had to be kept below 8°C— from incursions from impossible in far-flung villages neighboring countries Slow-moving governments and without electricity. In November hesitant donors have left some 2016, scientists reported that the when they too, control advocates frustrated. “I just have vaccine works just as well if it has for rabies” this anger bubbling up about why been kept for 3 months at 30°C or we think it is OK to let this go on,” for 6 months at 25°C, potentially -Thumbi Mwangi, veterinary epidemiologist at Washington State University Cleaveland says. But Hampson is enabling remote communities hopeful that the stories collected to keep vaccines on hand and in the field—including those of immunize their dogs by themselves. Asha’s death and Flora’s survival— “It could be transformative,” says up millions of dollars for dog will ultimately make a difference. WSU’s Felix Lankester, director of vaccinations. GAVI, the Vaccine Africa’s rabies researchers, she the Serengeti Health Initiative, who Alliance, will consider rabies says, “see things that policymakers led the study. when it reviews its $1.6 billion will never see. They are able to give investment strategy in 2018. GAVI a voice that otherwise won’t be There may even be a way to free does not pay for animal vaccines, heard.”

Original article at Go.vetmed.wsu.edu/RabiesScience Read more rabies vaccination news at go.vetmed.wsu.edu/rabies/vaccination-news Join our fight for their lives at www.RabiesFreeAfrica.org Follow the Paul G. Allen School for Global Animal Health on Twitter: www.twitter.com/wsuglobalhealth Follow the WSU College of Veterinary Medicine on Twitter: www.twitter.com/wsuvetmed