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Can rabies be eliminated from Asia by 2020?

Updated Tuesday, 25 August 2015
The World Health Organisation wants rabies eradicated from Asia in the next five years. They've got an uphill struggle, reports Mary-Rose Abraham.

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A pile of puppies cower under a parked car. The men grab one, but two escape down the street, forcing them to give chase. Five scrappy adult shorthairs – of an indiscriminate breed commonly known as an ‘Indian dog’ – appear from nowhere. Pointed ears pricked with curiosity, they howl as if sounding an alarm throughout the neighbourhood: the ‘catchers’ are here.

The catchers’ van travels the tree-lined, mostly residential streets to the next area. On the way, a couple of dogs seem to recognise the vehicle, either by sight or by smell. They bark and take chase. Each time the team catches a dog in one of its giant butterfly nets, the mutt twists and turns and howls, trying to escape. 

This ritual repeats several times through the day across 50 square kilometres of the south Indian city of Bangalore. The men, a team from the NGO Compassion Unlimited Plus Action (CUPA), are on a mission: to catch stray dogs, sterilise them and vaccinate them against rabies.

They catch ten dogs on this particular day. The dogs are taken to CUPA’s Animal Birth Control centre, where they will be sterilised and have their ears clipped so they can be identified as having undergone the surgery. They will be vaccinated, then returned to their home on the streets.

“What people need to understand,” says Vijay Kumar, manager of the CUPA centre, “is that the Animal Birth Control program is as much about human welfare as it is for dogs.”

This is part of an ongoing – and some say uphill – battle to eliminate rabies from India. Around 59,000 people die from rabies every year, according to a 2015 study published in PLOS Neglected Tropical Diseases. The overwhelming majority are in Asia and Africa: India alone accounts for 20,847 deaths, more than one-third of the world’s total, giving it the highest incidence of rabies globally.

Louis Pasteur conducting an experiment while investigating rabies Pasteur injects a rabbit with rabies as part of his work into the causes of rabies

Rabies is a vicious killer, a virus transmitted through saliva. Any warm-blooded mammal is susceptible. Dogs can become infected through a bite by a rabid wild animal or fellow canine; in turn, a bite from an infected dog is the most common method of human infection.  

The rabies virus attacks the nervous system and causes humans who are infected to hallucinate, become aggressive and even fear water. When someone is bitten, it’s crucial to wash the wound immediately and vaccinate them as soon as possible. But this rarely happens in India. Instead, many people end up being improperly treated – for example, not receiving a full course of vaccinations after exposure. Others turn to herbs, spices or local remedies that have no effect.

The World Health Organization (WHO) wants to eliminate rabies from the South-East Asia region by the year 2020. It is a goal that India is unlikely to meet, public health experts say. For one thing, the actual number of rabies deaths in the country may be far higher than we know because of unreported or untreated cases.

What’s needed is an effort no less committed than it took for India to eliminate polio in 2014. But with rabies, the country doesn’t even know the extent of the disease. There is no requirement for doctors to report human infections, and no information on how widespread it might be among animals. In 2014 India’s government said it would set up a national rabies control programme, but at the time of writing it has only launched a pilot project in the northern state of Haryana to advise on managing the problem nationwide.

Meanwhile, the government leaves it to the local city authorities to carry out programmes for vaccinating stray dogs on the street. Most deal with the problem by hiring NGOs like CUPA. That leaves rural areas, where rabies strikes hardest, all but ignored. 

“Rabies will always be in India,” says Dr S N Madhusudana, a professor at Bangalore’s National Institute of Mental Health and Neurosciences who has studied the disease for three decades. “It will never go away.” 

Four-year-old Bhuvan sits quietly in his mother’s lap at the clinic. Nearly all of the right side of his neck is an open wound, where a street dog grabbed hold of him and dragged him for four feet before his great-aunt Veena came out of the house screaming.

“That’s when the dog grabbed onto my face,” says Veena, her own right cheek imprinted with the faint outline of canine teeth. She later lost consciousness as she and Bhuvan were being driven to their local, rural hospital. A doctor there gave them each a dose of a therapeutic anti-rabies vaccine that will help stimulate their immune systems. It will take up to two weeks for their bodies to produce antibodies, but they also need to attack the virus immediately. That requires another, stronger form of medication only available 150 km further away at an anti-rabies clinic in the nearest city, Bangalore.

Veena and Bhuvan travelled immediately, arriving at midnight at Kempegowda Institute of Medical Sciences. Despite appearances, their wounds aren’t severe. “These dog bites are milder,” says Dr D H Ashwath Narayana, the head of the hospital’s Department of Community Medicine, surveying the torn flesh on Bhuvan’s neck. “I’ve seen far more severe bites.”

That morning, Narayana spends hours calling suppliers for two doses of the crucial treatment: rabies immunoglobulin, a concentrated solution of rabies antibodies. Two vials arrive just after noon.

Bhuvan is placed on a clinic bed, where an attendant holds him down as he writhes and tries to move away. A medical student begins a series of injections directly into the raw wounds on his neck. The immunoglobulin must penetrate the exact place where the dog bit into the flesh in order to neutralise the virus. As the boy screams in pain for his parents to help, his mother leaves the room, unable to bear her child’s cries. Next, a moaning Veena is injected seven times in the cheek and upper lip.

The disease develops when the rabies virus enters a person’s nervous system, but after the bite there is a window of opportunity to prevent that from happening. The rabies immunoglobulin binds to the rabies virus lodged in Veena and Bhuvan’s wounds, preventing it from entering their nerve endings. Meanwhile, the initial anti-rabies vaccine they were given at the local hospital continues its work, prompting their bodies to produce their own antibodies. Four more doses over a month help in that regard. With a full course of treatment, they have a chance that rabies will not develop. “The deeper the wound, the more danger that the virus goes into the nerves,” Narayana says. “In rabies, it is better to overtreat than undertreat.”

According to WHO, rabies immunoglobulin is undergoing a critical shortage worldwide. It is also prohibitively expensive for many victims in a country where 60 per cent of the population lives on under US$2 a day: Veena and Bhuvan paid close to 450 Indian rupees, about US$7, for each vial. In India, only three companies produce it, with relatively high manufacturing costs.

Rabies immunoglobulin is collected from the plasma of either humans or horses injected with the rabies vaccine. At a fraction of the cost of the human-derived type, horse immunoglobulin is the only kind available to most low-income countries. Yet complying with India’s strict animal welfare laws can be expensive, according to Dr Anand Kumar, deputy managing director of Indian Immunologicals Ltd. The pharmaceutical firm is India's largest producer of both human and animal rabies vaccines but stopped producing rabies immunoglobulin about a year ago. “We followed the guidelines strictly,” he says about the company’s stock of horses. “Complying with animal ethics was very expensive, so manufacturing costs became too high.”

What immunoglobulin is available tends to concentrate in cities, leaving rural dog bite victims to either forego treatment or travel great distances to urban clinics. Bhuvan and Veena are among the lucky ones.

Two years away from retirement, Dr Madhusudana is still haunted by the death of a 21-year-old student who was once in his care. Like Bhuvan and Veena she lived in a rural village, hours from Bangalore, in the southern state of Karnataka. She had been washing dishes behind her home in May 2013 when she was bitten twice by a street dog. The girl was injected with the rabies vaccine, but her treatment ended there. She never received any immunoglobulin.

Without proper treatment, it can take anywhere from a few days to more than a year for rabies to develop. But when symptoms appear, the disease is invariably fatal. Two months after she was bitten, the student developed a fever for which her local doctor gave her sedatives. She lapsed into a coma and was brought to Bangalore, where she was finally diagnosed with rabies and died 17 days later.

Rabies manifests in two ways: dumb rabies (also known as paralytic rabies) and furious rabies.

The two forms differ in the path the virus takes to reach the brain. In dumb rabies, the virus travels via motor nerves, damaging them in the process and leading to a slow progression from muscle paralysis to coma. This type accounts for 30 per cent of rabies cases with at least 12 people worldwide known to have survived it.

‘Furious’ rabies – so called because of victims’ hyperactivity and agitation ­– is far more common. Its symptoms appear sooner than those of dumb rabies, as the virus travels from the nerve endings, along the spinal cord and to the brain. Beginning with fever, headache and a tingling feeling at the wound site, victims can become aggressive, start hallucinating and develop a marked fear of water, even shrinking from the sight of a glass filled with it. This is because rabies causes painful muscle spasms in the throat and larynx, and water can trigger the spasms. Death results from blocked airways, seizures or widespread paralysis. “Within three or four days, the victim is dead,” says Madhusudana. “It’s a pathetic, horrible death.” 

Theoretically, no human should die from rabies in the 21st century. Rabies is one of the oldest diseases known to man – the earliest records of it stretch back to Ancient Egypt around 2300 BCE – and since the late 19th century we’ve had painful but effective treatments.

French scientist Louis Pasteur formulated the first vaccine in 1885 by injecting the rabies virus into rabbits, killing them, then drying the nerve tissues to weaken the virus. When he injected this into a nine-year-old boy bitten by a rabid dog, the child did not develop the disease.

It is another, infamously painful, vaccine developed in 1911 that was synonymous with rabies treatment for years. David Semple, a British Army officer and immunologist who founded a branch of the Pasteur Institute in northern India, injected the rabies vaccine into the brain of a live sheep and goat. The animals were killed and their dried and churned brain tissue injected 14 times into the lower abdomen of people exposed to rabies – once for each of the lymph nodes associated with antibody production. Despite severe side-effects such as paralysis, the Semple treatment was used for most of the 20th century. It wasn’t until 1992 that the WHO advised against it, and even then India continued to use it until 2004.

Today’s rabies vaccines are grown in a lab, using cell cultures (in a process that’s very different to producing immunoglobulin in humans or horses). The virus is inactivated, purified, then administered by injection into the skin or deeper into muscles of the arm. Side-effects are far fewer, but this production is more expensive. The higher cost probably explains why the crude Semple vaccine was used for so long.  

Worldwide, scientists are still researching new methods of treatment. But Madhusudana believes the focus, at least in India, should be elsewhere. We know enough about the virus to fight it, he says. What we aren’t doing is effectively using that knowledge to stop it: India is a country where many health professionals, let alone citizens, don’t know how to treat a dog bite properly.

“Research on rabies should not be the priority,” says Madhusudana. “All money should go to education and vaccination. All we need is to educate, educate, educate.”

At the Rani Sarala Devi School in Bangalore – the school Madhusudana attended as a child – doctors are busy conducting a free vaccination clinic for children from families with low incomes.

“Our children are from the slum area,” says teacher R G Sudha, as more than 400 kids aged 5 to 13 line up dutifully to receive their shots. “They play with cats and dogs, and they don’t know [about rabies]. So many children have been bitten.”

Three doctors and two medical students are injecting each child in his or her arm. Some of the children are brave, gritting their teeth; some begin crying in line before receiving their shots. Each injection produces a raised swelling on the skin, with the pocked texture of an orange peel. The children will need two more injections over the next three weeks before they produce enough antibodies for full immunity.

If any of these children are then bitten by a dog with rabies, they will not need the painful immunoglobulin shots into their wounds because they will have already developed rabies antibodies. It’s a small consoling measure of certainty when dealing with a disease with an uncertain future in India.

Rabies is a zoonotic disease, meaning it developed in animals and jumped to humans. A variety of animals cause human infections, depending mostly on region. In the USA, raccoons, bats and skunks are the most commonly reported rabid wildlife. In places like India – with its estimated 30 million stray dogs – dogs account for more than 95 per cent of human transmissions in areas where they live in close contact with people.

Young children are particularly vulnerable. About one in 143 Indians are bitten by a dog at some point in their lives, according to the 2015 PLOS study (693 per 100,000 of the population), and the Global Alliance for Rabies Control says around half of the world’s rabies victims are children.

The WHO recommends pre-exposure vaccinations for everyone in rabies-endemic countries. India's own Academy of Paediatrics also recommends children are vaccinated, but relatively few are ever immunised. People may not realise the extent of the danger – and the benefit of vaccination – or else cannot afford it. A three-dose anti-rabies vaccine course costs about 100 rupees (US$1.57), which is most of a day’s living allowance for many.

Madhusudana’s lab diagnoses at least one case of human infection every week. He has little hope that infections will stop given that India’s population is exposed to 17.4 million dog bites a year.

To truly eliminate rabies from India, animal health is key. “Elimination of human rabies is dependent on the elimination of dog rabies,” says the WHO in its strategic framework for eliminating the disease. Yet the extent of rabies infection in the country’s animals remains a mystery.

India has only one laboratory for diagnosing rabies in animals, located in Bangalore at the Veterinary College of the Karnataka Veterinary, Animal and Fisheries Science University. It tests the brains of not only dogs but also cats, cattle, buffalo, goats and jackals. A forest official dropped off the decapitated head of a wolf recently.

Dr Shrikrishna Isloor runs the lab on the ground floor of the Veterinary College. Only he and three others have access to the core testing site, where animal tissues containing the live virus are handled. All four are vaccinated against rabies.

They are able to determine whether a specimen is infected with rabies within two hours of receiving a brain sample. It allows them to give crucial information to health professionals about whether treatment is needed. Did the animal have rabies in the first place? But many animals that attack are never caught, while countless others are never tested. The stray dog that attacked Bhuvan and Veena was quickly clubbed to death by neighbours and removed from the neighbourhood without any samples being taken, which meant the doctors had to assume the worst.

Isloor wants to see more testing centres set up across India, and he has started talking with scientists in other states. According to him, India won’t be able to control the disease without monitoring rabies rates in animals as well as humans. “Rabies doesn’t differentiate between humans and dogs. It should be a holistic effort,” he says. “To make [elimination of rabies by] 2020 happen, we have to work on a war footing.” Medical and veterinary communities must fight the battle on a united front.

In India, culling dogs is not allowed on humanitarian grounds. A 2001 Indian law details how dogs should be humanely caught, housed, sterilised and released back onto the street. Experts say culling isn’t very effective anyway, considering at least half of the patients with rabies were bitten by pet dogs.

So the authorities turn to vaccinating not just the human population, but the dogs as well. If 70 per cent of the dog population were vaccinated, that would be enough to contain the spread of the virus. According to the 2015 PLOS study, by 2010 India had vaccinated just 15 per cent of its dogs. And vaccinations are not enough. The dogs must also be sterilised to make sure new animals – potential reservoirs for the virus – aren’t introduced into the community. At the time of writing, India has no national or state-wide plans in effect to make this happen.

Instead, says Dr Abdul Rahman, a Bangalore-based veterinarian who heads the 55-nation Commonwealth Veterinary Association, India is limping along with a “knee-jerk program of ad hoc projects”. Sterilisation efforts have “not made a dent in controlling rabies”, he says, although he does note that a few cities have been successful, including Jaipur, Chennai and Tirupati. In Bangalore, the city municipal body confirms that there have been no reported rabies cases in dogs for the past four years.

But, says Rahman, unless the Animal Birth Control program is undertaken on a serious note, as has been done in polio control, it won’t change rabies control. He says that he doesn’t blame the stray dogs for all the problems, however, and reiterates that 54 per cent of rabies is due to irresponsible pet ownership.

So the dog catchers of Bangalore keep at it. They roll out once again, this time aiming to catch dogs they’ve already sterilised and vaccinated once in order to give them the booster shot they need one year later. Once a dog is caught, the vaccine is quickly injected and a worker dabs bright blue paint onto the dog’s forehead, which helps them avoid re-injecting the same dogs.

The team from CUPA arrives in a poor neighbourhood, densely crowded with livestock and littered with dead rats and stagnant puddles. Barefoot children chase behind them, giggling ecstatically at the sight of grown men chasing dogs.

This article originally appeared on Mosaic, under a CC-BY licence

 

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