Overcoming resistance

Nwe Nwe Oo (28), of Yangon, and her family regularly went without food when she was forced to...
Nwe Nwe Oo (28), of Yangon, and her family regularly went without food when she was forced to give up work after contracting HIV and tuberculosis. Photo: Bruce Munro.
Dr Htin Lin Aung (right) discusses research data with staff at a Tb clinic in northern Yangon,...
Dr Htin Lin Aung (right) discusses research data with staff at a Tb clinic in northern Yangon, Myanmar. Photo: supplied.
In the end, a Tb-infected person dies, drowning in the remains of their own lungs. Photo: Getty.
In the end, a Tb-infected person dies, drowning in the remains of their own lungs. Photo: Getty.
Dr Htin Lin Aung (centre) with microbiology and immunology department professor Greg Cook (left)...
Dr Htin Lin Aung (centre) with microbiology and immunology department professor Greg Cook (left) and University of Otago Centre for International Health co-director Prof Philip Hill at the time of the $450,000 Health Research Council funding...
Ko Zaw (29), a member of Myanmar’s Rakhine ethnic minority, was no longer welcomed by extended...
Ko Zaw (29), a member of Myanmar’s Rakhine ethnic minority, was no longer welcomed by extended family and fell behind in his career after contracting HIV and tuberculosis. Photo: Bruce Munro.

Tuberculosis is exacting a heavy toll in Myanmar, but a world-first collaboration between the University of Otago and the Myanmar Ministry of Health, spearheaded by microbiologist Dr Htin Lin Aung, aims to rob tuberculosis of its power, writes Bruce Munro.

When tuberculosis forced Nwe Nwe Oo to give up sex work, the family did it hard.

Harder than when her father died. Tragedy that that was, at least the family had been able to make up the lost income through the then-22-year-old’s prostitution.

She was the eldest child. Naturally, she had done what she could to fulfil her filial duty, providing for her 50-year-old mother and siblings ranging in age down to a 2-year-old brother.

But four years later, experiencing symptoms that included fever, loss of appetite and insomnia, Miss Oo was exhausted. She simply could not keep working. What she did not yet know was that her efforts to support her family had been robbing her of the ability to continue doing that.

Tests at the hospital in her township in Yangon, Myanmar’s most populous city, came back negative. But Miss Oo knew she was too ill to work.

They were dark days, she recalls.

"Some days, we ate. Some days, we didn’t," Miss Oo says through a translator.

Eventually, a friend took her to a Population Services International (PSI) drop-in centre for gay men and female sex workers, where she was tested again. The results were positive for both HIV and tuberculosis (Tb). Due to a lack of information and resources to practice safe sex — although, it could be argued the real problem was the absence of effective social security when disaster struck — she had unknowingly contracted the deadly disease which attacked her body’s healthy immune system, giving Tb the opportunity to also get a foothold.

Ten thousand kilometres away, in a secure laboratory on the University of Otago campus, Dr Htin Lin Aung (34) is testing a DNA sample taken from a known Tb patient by his team in Myanmar.

Dr Aung and his assistants are doing something novel, potentially revolutionary, with the Tb bacteria in that sample. They are sequencing its entire genome to determine what, if any, drugs it is already resistant to. It is one important step in Dr Aung’s ambitious plan to rob Tb of its power to devastate lives and communities worldwide, and particularly in his home country.

For a person with a weak immune system, Tb is a nasty threat. The bacteria can multiply rapidly, invading different organs of the body. In the lungs, for example, "it eats them from the inside out", states the Global Health Education’s Tb Facts website.Tb first weakens the infected person. As it progresses, pulmonary Tb causes the chest to "fill up with blood and the liquidy remains of the lungs".

"Cough that up, even in microscopic ... droplets, near other people, and they have a very good chance of getting Tb too."

In the end, the Tb-infected person dies, drowned in the remains of their own lungs.

In 2015, there were an estimated 10.4 million new cases of Tb worldwide. About 1.8 million people died of the disease.

Myanmar is one of a score of countries where Tb takes a heavy toll. Each year, in this poor Southeast Asia country, about 200,000 people contract Tb and 28,000 die of it.

It can be tackled with a cocktail of drugs.

For most sufferers, treatment takes about six months and can inflict severe side-effects.

When Miss Oo was diagnosed, the PSI charity put her on two treatment regimens; antiretroviral drugs to slow down the HIV and another multidrug mash-up for the Tb.

During the first two months on the Tb drugs, she felt dizzy, her heart raced and she was often hungry.

Comparatively, however, she can count herself one of the fortunate ones. A growing number of people are discovering their Tb is resistant to one or more of the treatment drugs.

For those who have drug-resistant Tb, the treatment period quadruples to 24 months; two years of taking a concoction of powerful drugs, with all the attendant side-effects. It is enough to make people stop treatment before the course is completed; particularly in a developing nation such as Myanmar where if people, like Miss Oo, don’t work, they don’t eat. They cannot afford to be ill for long, even if it kills them.

But that only compounds the growing problem of drug-resistant Tb. Not seeing out the 24-month treatment increases the chance of Tb bacteria not being killed off and instead developing resistance to one or more of the drugs. If the person then coughs on others, they could contract the now drug-resistant disease.

There is a test to determine whether someone has a drug-resistant form of Tb. But the test only looks at one small portion of the bacteria’s DNA, checking whether it is resistant to one of the drugs. If so, a different drug or two is substituted in the cocktail and the longer treatment is recommended. What the test cannot say, is whether the Tb is resistant to some of the other drugs that are being administered. If it is, the two years might be endured in vain; the only result being the possibility that the drug-hardened bacteria becomes even more difficult to eradicate.This is where Dr Htin comes in.

Raised in Yangon by parents who knew the value of a good education, Dr Aung came to New Zealand in 2001 for his undergraduate studies in biomedical sciences. In 2005, he graduated from the University of Otago with a bachelor of science, first-class honours degree, majoring in genetics. He then worked as a research assistant at Otago and Massey universities, before beginning doctoral studies at Otago.

Dr Aung is now a postdoctoral fellow in Otago’s department of microbiology and immunology.

"When I first came to New Zealand, I wanted to contribute back to my country. But I didn’t know how," Dr Aung says.

"The more I studied the health situation in Myanmar, the more I realised that Tb is a massive burden.

"Studying here at Otago has given me the chance to discover what I really want to do with my life. I am really honoured to be part of this."

"This" is the first joint Myanmar-New Zealand health research project. After initial steps taken by Anna Sui, wife of the now-Second Vice-President of Myanmar, Henry Van Thio, Dr Htin has played a lead role in establishing this unique collaboration between the University of Otago and the Myanmar Ministry of Health and Sport’s National Tuberculosis Programme.

The research is engaging with one of the biggest battles in the war on Tb. Because an infected person can die within a few weeks, rapidly diagnosing drug-resistant Tb is crucial. But that "point of care" testing to identify exactly which drugs will be effective with each patient is virtually non-existent in the very countries that have the highest rates of Tb. Developing such a test and making it affordable and widely available could be the much needed sucker punch that opens Tb to a full-on assault.

While traditional drug-resistance testing targets just one DNA marker, Dr Aung and his team are using the latest technology to develop processes to quickly and accurately sequence the whole genome (all the DNA material) of Tb bacteria from each patient’s sputum sample.

"We are sequencing the whole genome because drug resistance in Tb bacteria is driven by mutation," Dr Aung explains.

"If we are able to work out these mutations as soon as possible, we will be able to work out what resistance is already present."

When it comes to Tb, Myanmar is what health workers call a "high burden, low resource" country. New Zealand is the opposite.

"So, at the moment, it is more feasible to do this sort of diagnosis in a country such as New Zealand," Dr Aung says.

"We cannot do it in Myanmar, because we cannot take all the expensive machinery there. But we can bring the samples here [to Otago], do the analysis and tell the clinicians in Myanmar exactly which drugs the patient is resistant to. The clinician can then make a customised cocktail of drugs to treat that individual.

"We want to demonstrate that we can do this ... that this intervention, this new technology, would improve the diagnosis and so improve the treatment outcome. 

"It will have a significant impact on Tb control."

This personalised approach is just starting to be used in "high resource" countries. But the Otago-Myanmar research is believed to be the first in a low resource, high burden country.

"It is not easy. So, until now no-one has been tough enough to give it a go."

Because drug-resistant treatment takes two years, it will be early 2018 before the success rates of the "customised" and "standard" care can be compared.

If the results stack up as Dr Aung expects, he hopes a compelling case can then be made for the Myanmar Government or other international organisations to purchase diagnostic equipment. That would enable diagnosis for targeted treatment within 24 hours.

The research has three years’ Health Research Council (HRC) funding worth $450,000.

"I had my training here ... Now, the university and the New Zealand Government, through the HRC, support me to do this research in my home country,’’ Dr Aung says.

"It highlights that the New Zealand Government and the University of Otago are being good global citizens.

"And of course, it makes me feel good, because I have always wanted to contribute something back to my country."

That contribution was recognised late last year. Dr Aung was included among a select group of 40 people honoured by the New Zealand Government for significantly contributing to the country’s deepening relationship with the Southeast Asia region.

Providing a breakthrough that improves treatment of drug-resistant Tb in developing countries is not the sum total of Dr Aung’s vision. Not by a long shot.

Dr Aung’s mentor in the microbiology department, Prof Greg Cook, is working on developing new Tb drugs, which they hope will allow a much shorter treatment period.

"Even if you have the perfect diagnostic, new drugs are required for effective treatment," Dr Aung says.

"We want to develop drugs that are effective against all sorts of Tb and which, instead of 24 months, the patient would only need to take for up to two weeks.

"We hope to have the drug ready within the next few years. It is ambitious, but you have to have ambition, right?"

Ko Zaw would heartily agree. The 29-year-old gay man is a member of the Rakhine ethnic minority. His parents died when he was 16. Since then he has lived in Yangon. But his training as a gold smith and his business acumen have often taken him back to his home region in the west of Myanmar. It was during a a trip in that border region, near India, that he noticed he had developed a persistent cough. He sought drugs from a street-corner pharmacist. Unfettered access to antibiotics is one of the drivers of drug resistance.

The cough became a fever and he started losing weight. The second time Mr Zaw was tested, he got a positive Tb result and was put on treatment.

The news was not well-received by his uncle’s family, with whom he had been staying. They asked him to leave. Feeling too ill to work, without money for food or a bed, Mr Zaw was relieved to be taken in at a Buddhist monastery. When he felt better, he stopped taking the drug treatment and went back to work. It was not long before he was feverish again and had to quit work.

It was then that Mr Zaw found a PSI website detailing the NGO’s free disease testing.

The results came back positive for HIV and Tb. Mr Zaw says through a translator that he wishes many things were different for himself. He hopes they will be for the next generation.

"I would be a marketing manager, a professional, by now," he says.

"I lost my job and so I’ve had to start at the bottom again. I don’t want that for other young people."

- Bruce Munro travelled to Myanmar with assistance from the Asia New Zealand Foundation.

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