Ending antimicobial resistance is the lynchpin to #endTB as well as health security

Shobha Shukla *

While reaffirming their commitment to end TB by 2030, the draft Political Declaration in the fight against tuberculosis by governments at the first UN High-Level Meeting on TB (#UNHLM to #endTB) acknowledges that "TB, including its drug-resistant forms, is a critical challenge and the leading infectious disease cause of death, the most common form of antimicrobial resistance (AMR) globally."

Dr Tedros Adhanom Ghebreyesus, WHO's Director General, calls AMR a global health emergency that will seriously jeopardize progress in modern medicine. It is creating superbugs that are making it impossible to treat many previously curable diseases, including TB. While the call for accelerating research and development for new treatments is rightly getting more attention, we are also losing on the efficacy of existing drugs with more and more disease causing microorganisms becoming resistant to them.

AMR already contributes to an estimated 700,000 deaths a year globally, and the the figure could rise to 10 million deaths a year and $100 trillion in lost global productivity by 2050 if nothing is done to stop its spread.

What is AMR?

Dr Manica Balasegaram, of Global Antibiotic Research and Develpment Partnership (GARDP) explains that AMR happens when micro-organisms - like bacteria, virus, fungi, other parasites - undergo genetic changes making them resistant to the medicines that they responded to earlier. This is an evolutionary change but the process can be accelerated due to overuse and misuse of drugs in human, animal and agricultural use, as well as due to lack of infection control.

Key actions to stem AMR

In an interview given to CNS (Citizen News Service), Dr Soumya Swaminathan, Deputy Director General for Programmes at the World Health Organization (WHO) and a globally recognised researcher on TB and HIV, underlined the importance of infection control in all healthcare settings so that all healthcare personnel follow standard guidelines for the use of antibiotics.

"Stop irrational veterinary and agricultural use of antibiotics as crop promoters or for prevention of disease and use them only for treatment where needed. Also, antibiotics listed under reserved category in WHO's classification of antibiotics should be reserved for humans and not used for animals. It is also important to have systems in place for production and disposal facilities of antibiotics so that they do not contaminate water and soil and do not spread the resistant mutations to bacteria which are in the environment", she said.

What is India doing to stem AMR?

Dr Kamini Walia, a Senior Scientist at the Indian Council of Medical Research (ICMR) who is currently leading the setting up of Antimicrobial Surveillance Network in India, pointed out that ICMR started its antimicrobial resistance initiative in 2012 as no nationwide data on AMR was available in the country. Its AMR surveillance network focused on six pathogenic groups that were causing a large number of drug resistant infections in the hospitals and in the communities.

ICMR has 20 hospitals in its network and uses data gathered from these hospitals to guide treatment interventions. ICMR has also brought out hospital infection control policy as well as treatment guidelines which is based on ICMR data. She said that, “Our data shows that antibiotic pressure is driving a lot of drug resistance that one sees in India’s hospitals. So to reduce antimicrobial resistance, overuse of antibiotics needs to be controlled, along with reducing hospital infections, because it is the large denominator of hospital acquired infections which are giving actually rise to drug resistant infections”.

Drug resistance/ AMR in TB

The growing threat of AMR to anti-TB medicines (more commonly referred to as drug resistance) is undermining efforts to eliminate the disease by 2030. Explained Dr Soumya Swaminathan that drug resistance in TB is of two kinds. One is primary drug resistance, which one gets due to direct transmission from a drug resistant TB patient. The other is acquired drug resistance (secondary drug resistance) which occurs when a patient of drug-sensitive TB is either on treatment with the wrong combination of drugs or does not take the right doses timely.

"TB bacteria are capable of developing mutation just like other bacteria if they are exposed to the drugs in the wrong dosage and/or for insufficient time. So it is very important to use them in the correct dosage (with the right companion drugs) for the correct time duration in which they need to be given", she said.

Addressing AMR in TB

Dr Mario Raviglione, former Director of WHO's Global TB Programme, blames mono-therapy to be the main reason for TB becoming resistant to drugs. He cautions that TB bacteria should never be treated by a single drug, but by a combination of 3-4 highly effective drugs. Hence it is essential to know the resistance profile of the bacteria before starting treatment. Another mistake is adding just one extra drug to a regimen that is already failing, as there is a very high likelihood of the TB becoming resistant to that new drug also, cautions Dr Raviglione.

Acquired drug resistance is now being addressed through the recent WHO guidelines which require that every presumptive TB patient must get upfront molecular diagnostic test for drug resistance done, so that the he/she can be given the right combination of drugs. Soumya insists that not only should patients have the right diagnosis and appropriate treatment but they should also be supported by way of counselling, peer support, nutritional support to be able to complete their treatment.

Dr Mario Raviglione airs similar sentiments: “To prevent drug resistant TB we need to do good basic practice in TB care and control; provide the best possible treatment to a TB patient using the recommended drug regimen based upon the results of drug susceptibility test done upfront, and follow the patient closely through the long journey of treatment.”

Cautious use of new TB drugs: Bedaquiline and Delamanid

After 40 years, the TB world has hailed the arrival of 2 new drugs Bedaquiline and Delamanid. They hold a great potential to improve cure in TB patients, especially in those with drug resistant TB. South Africa has already introduced Bedaquiline upfront for all drug-resistant TB patients. But one needs to tread with caution to prevent their irrational use.

WHO has come out with specific guidelines for judicious use of these drugs. Dr Soumya Swaminathan cautions that, “While on one hand we need to safeguard these drugs to make sure that they are effective at least for the next couple of decades, at the same time they should not be so restrictive that people who need them are not getting them”.

Bedaquiline use in India

No wonder, India is treading carefully for the rational use of Bedaquiline. For Dr KS Sachdeva, Head of India’s national TB programme and Deputy Director General, Ministry of Health and Family Welfare, Government of India: it is very important to know at what point in a patient’s journey towards TB cure, should Bedaquiline be introduced.

He shared with CNS (Citizen News Service www.citizen-news.org) that Bedaquiline was approved for use in India’s national TB control programme three years ago on a pilot basis. Subsequently after completing the training of the healthcare providers Bedaquiline based treatment regimen has been scaled up nationally and is being offered to patients under conditional access through the public sector to ensure that there is no misuse of the drug.

“We have an entry criteria for its use and also to rule out certain pre-conditions before the patient becomes eligible to get that drug. Within India’s TB programme, only those drug-resistant TB patients who are intolerant to the conventional drugs, or who have an additional drug resistance to an injectable or the oral drug quinolone, are being offered this drug. Currently 1800 patients are on Bedaquiline based treatment and it is being scaled up in a holistic and systematic manner through a duly approved national algorithm. Patients have to be made comfortable in its use and be very vigilant with the side effects”, he said.

World leaders commit to ambitious targets at #UNGA

World leaders meeting at the 73rd UN General Assembly have committed to ensure that 40 million people with TB receive the care they need by 2022. While powerful new drugs, and simpler treatment regimens, especially for drug-resistant TB, will go a long way in making the fight against TB easier, let us not forget to put proper safeguards in place to ensure that TB bacteria does not become resistant to them in future.