Sexagenarian Shekhar Verma* lives in Faridabad, Haryana which is part of National Capital Region. A general store owner, he has developed resistance to many crucial antibiotics while being treated for tuberculosis for the last couple of years. The doctor at the National Institute of Tuberculosis & Respiratory Diseases told Verma that the only antibiotic that has high success for patients like him is Bedaquiline. But he cannot get Bedaquiline under the Revised National Tuberculosis Control Programme, government’s tuberculosis control programme.
To get the drug under the RNTCP, Verma will need to show that he lives in Delhi, one of five cities in which the government is providing the drug. He does not have proof of address in Delhi. He approached a private hospital for Bedaquiline but since the medicine is not available in retail shops, no doctor will prescribe the drug.
Verma's work at his store sustained his family of four for many years. Owing to his unstable health, he stopped going to the store, which is wife now manages. The elder of his two sons works in a security firm.
Akruti Kumar’s* father too has developed extreme drug resistant tuberculosis, often abbreviated as XDR-TB, with a first line of antiobiotic treatment failing him and now relying on second-line treatment. The RNTCP cannot treat him with Bedaquiline since he is a resident of NOIDA and not Delhi.
Location, location, location
Bedaquiline was rolled out under the conditional access programme of the RNTCP in which six hospitals in five Indian cities were chosen to provide the drug under World Health Organisation guidelines. Patients needed to belong to either Delhi, Mumbai, Chennai, Ahmedabad or Guwahati. The government has received doses for 300 patients in donation from the United States Agency for International Development which administers civilan aid from the US to other countries. Three hundred more treatment doses will be donated next year.
Sunil Khaparde, head of Central TB Division of the health ministry said that geographical criterion is important to follow up with patients. “Bedaquiline is administered for six months and follow-up of patients continue for six more months," he said. "Thus, we have to be careful about patients’ proximity to the hospitals.”
“It is a new antibiotic and we need to use it judiciously,"said Delhi State TB officer Ashwani Khanna. "We do not want antibiotic resistance to develop against this medicine.”
Khanna added that superior laboratory facilities are needed to determine which patients can be given the medicine. “Very few hospitals can meet all the requirements – trained doctors and staff, laboratory with all facilities and other facilities in case of an adverse effect.”
He said that the government was being extra cautious with Bedaquiline since it had not undergone a third phase of clinical trials, which are normally large scale trials on human subjects. The USFDA had exempted Bedaquiline from third phase clinical trials on the grounds on exceptional results from the first two rounds of trials and to make the drug available to the public as soon as possible.
Moving too cautiously?
The activist speaking on condition of anonymity said that providing access to treatment is not as difficult as it is made out to be. Patients can even be monitored long-distance with new technological tools. "The main thing to be monitored while administering Bedaquiline is patient’s heart because it disturbs function of heart," he said. "Any patient who is close to ECG testing machine for electrocardiogram, can be given the medicine and monitored from long distance.”
Rational use of antibiotics does not necessitate restricting use. “A robust programme can ensure that there is no misuse of antibiotics and still all needy patients get it," said an activist on condition of anonymity. "To stop misuse, it should not be sold in open market or in private treatments. But it cannot be restricted in a government programme.”
The rigid regime has meant that only about 30 patients have been started on Bedaquiline in RNTCP in the past three months. There is fear that the available doses will go waste if the government does not ramp up its utilisation.
“Delhi has 10 patients and there is a similar number is in Mumbai," said an official who did not want to be identified. "The other cities have 4 or 5 patients each. We can treat 300 patients and the doses expire in October next year.”
India’s progress is “pathetic” and “glacially slow” in providing such crucial medicine to its ailing population, said Dr Zarir F Udwadia, consultant physician and tuberculosis specialist at Hinduja Hospital in Mumbai. Udwadia is currently treating 25 patients with Bedaquiline citing compassionate use.
“This is almost half of all patients being treated in India,” he remarked. On the grounds of compassionate use, a drug manufacturer gives a medicine free-of-cost to patients if their doctor has convincing evidence that the patients will die without the medicine. Janssen Pharmaceuticals, an arm of Johnson and Johnson, is the drug-maker giving out Bedaquiline. The company has also provided the doses that USAID has donated to the Indian government.
Getting the drug on grounds of compassionate use, however, is not easy. The doctor need to fill in numerous forms based in each of the patient's test results and few practitioners are willing to spend the time. Even when the medicine is arranged through compassionate use, the cost of diagnostics borne by the patient can run into tens of thousands or rupees.
India has 71,000 multi-drug resistant tuberculosis patients. According to a World Health Organisation report, nearly 10% of all multi-drug resistant TB patients have extensively drug resistant TB or XDR-TB, for whom both the first and second lines of antibiotic treatment have failed. Thus, India is estimated to have more than 7,000 XDR-TB patients.
Bedaquiline is administered to pre-XDR-TB patients. These are patients with resistance to isoniazid and rifampicin used to treat MDR-TB and either a fluoroquinolone or a second-line injectable agent, but not both.
The rates of prevalence of XDR-TB are not uniform everywhere, doctors say. “In Delhi nearly 22% of all MDR cases are XDR and pre-XDR. In Mumbai, it is nearly 60%,” said Khanna. Taking this into account, there would be a much higher number of patients needing Bedaquiline.
“It is good that government launched the much needed drug but they are moving too slow," said Chapal Mehra, a TB activist in New Delhi. "We do not know on what basis was the figure of 300 and 600 was arrived at. The government has to estimate both in the public and private sectors who need the medicine and work towards achieving that target.”
Mehra said that the government should work with the private sector to start patients on Bedaquiline.
“There are multiple-barriers to the medicine right now," he pointed out. "Why should a patient from Jharkhand be not eligible for it? Patients from private sector also do not have access to it (through the RNTCP). The programme is structured to privilege a few.”
Learning from South Africa
“India is one of the high burden countries for DR-TB," said Jennifer J Furin, lecturer on Global Health and Social Medicine at Harvard Medical School. "A lot more patients have to be given Bedaquiline soon. The government should use the drug carefully because we cannot waste it to resistance, but the progress is too slow.”
India is lagging behind South Africa, which, through its robust TB programme, has put a large number of patients on Bedaquiline.
“South Africa launched the drug in July 2015," said Furin. "Within three months they had 200 patients on Bedaquiline. As we speak, the country is giving the medicine to 3,000 patients, which is a huge progress.”
India, on the other hand, will not be able to give Bedaquiline to more than 600 patients for the next two years. And this will only create bigger hurdles to fighting TB. Furin said the understanding is that the donors will see India’s progress with regard to the first 300 treatment doses. If this is not satisfactory, then the further donation will face impediments.