Nipah spurs calls to use candidate medicine
May 28, 2018
New Delhi: The nipah virus outbreak in Kerala has prompted India's health research agency to propose reduction of the delays posed by the standard regulatory requirements for clinical trials and rapid deployment of candidate therapeutic molecules against rare and fatal infections on "compassionate grounds".
The Indian Council of Medical Research had, on a request from the Kerala government, sought from research groups in Australia a candidate molecule against the nipah virus that had been tested on animal models and given to 20 people exposed to the virus outside India.
Council director-general Balaram Bhargava had made the request within a day of the nipah infection being confirmed in Kozhikode on May 19. But health officials and epidemiologists say that India may not need the molecule for now, given the localised nature of the outbreak and the absence of new cases over the past three days.
Health authorities had until Saturday confirmed the nipah infection in 15 people, 13 of whom have died. Twenty-six others, who have developed symptoms or came into close contact with the nipah patients, are now under observation in two hospitals.
The molecule Bhargava had requested is a human monoclonal antibody called m102.4. It was developed jointly by the Australian Animal Health Laboratory in Victoria and the Uniformed Services University of the Health Sciences in the US in an effort led by US microbiologist Christopher Broder. It has been stockpiled by the Queensland health department.
Kerala's additional chief secretary in charge of health, Rajeev Sadanandan, said the state was expecting a shipment of 50 vials of the antibody.
"We're not taking any chances - we're taking all precautions possible," he said.
He said the antibody would be given, if required, to confirmed patients of the nipah infection.
In a paper in the journal PLOS One in 2009, Broder and his Australian colleagues had reported successfully testing the m102.4 in ferrets that had been given high-dose intra-nasal sprays of the nipah virus. All the ferrets that had received m102.4 within 10 hours of exposure to the virus survived.
"We're not sure whether we'll really have to use this monoclonal antibody. The outbreak appears to be a localised occurrence and under control," said Raman Gangakhedkar, a senior scientist and head of the ICMR's communicable diseases division.
But the council is examining strategies to enable India to rapidly deploy such candidate therapies, which are in research mode, during future outbreaks - and not just for nipah. Virologists say that fruit bats, the reservoirs of nipah, are widespread across the Indian subcontinent.
If the m102.4 antibody becomes widely available, it would be possible to offer it as post-exposure therapy also to healthcare workers or family members who have come into close contact with nipah-infected patients. A nurse who had cared for a nipah patient has died in Kerala.
"This antibody has already been administered to 19 people in Australia and one person in the US and found to be safe," Gangakhedkar said.
"We had sought it for use on compassionate grounds but we need to have in place protocols for the rapid deployment of candidate therapies during such outbreaks."
The standard regulatory requirements for clinical trials - mandatory before commercial deployment of drugs or vaccines - demand multiple sets of clinical trials in increasing numbers of volunteers to establish safety and efficacy.
"But the epidemiology and the sporadic nature of nipah outbreaks make large-scale clinical trials difficult," Benjamin Satterfield, a senior microbiologist at the University of Texas Medical Branch in the US and his colleagues had written in the journal Vaccine two years ago.
They had, however, underscored the importance of preparedness. More than 250 million people in Bangladesh and Bengal are at risk of acquiring a nipah infection, and over 2 billion people worldwide live in places where the carrier fruit bats are found.
Gangakhedkar believes that the only way to assess the efficacy of medical interventions during small but deadly epidemics is to deploy candidate molecules each time an outbreak occurs and analyse the results using scientific protocols.
Health officials say it should be possible to provide candidate therapies to patients, healthcare workers and others exposed to a lethal infection on compassionate grounds even in the absence of formal clinical trials.
They say that medical ethics guidelines do allow doctors, in the case of select infections, to provide candidate therapeutic molecules to humans who face likely death if these have been successfully tested on reliable animal models.
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