„It took us seven years to arrive to this point” – interview with Dr. Grațiela Chiriac, Chief of the Pulmonology Laboratory in Bacău county

Grațiela Chiriac is the chief of the pulmonology laboratory in Bacău, one of the 8 laboratories equipped with high-end technology through the project “Improving the Health Status of the Romanian Population in Romania by Increasing Tuberculosis Control”. Dr Chiriac is laboratory doctor and member of the Laboratory Working Group of the National Tuberculosis Prevention, Surveillance and Control Program. We asked her what would be the advantages of the new equipment of the laboratory network.

How does rapid diagnosis help the patient?

The patient’s benefit is considerable, since they can receive the diagnostic early, together with conclusive information about the sensitivity of the infectious strain. Thus, the patient has the opportunity of a treatment initiated early and tailored according to the result of the drug sensitivity test. In these circumstances, the doctors take the right decisions regarding the treatment and the development of chemo-resistance is avoided, as it would make the cases difficult to treat. The liquid media diagnostic method implies inoculation in a liquid media tube, with a standardized technique, and placing it in the equipment which shall monitor the culture. The positive result, which basically confirms the disease, is obtained in 7 – 14 days, and the final result in 42 days. Comparing with the method on solid media, the benefit is obvious: the time to obtain the positive culture is of 7 – 14 days, versus 21 – 60 days; a complete result, culture and drug sensitivity test in 21 days, versus 50 days or even 4 months.

What does this new technology mean for the doctors working in the field?

For the clinicians, the purpose of the activity within the tuberculosis network is to initiate an adequate treatment, as soon as possible, and for the doctors in the laboratories to establish a correct diagnostic, as soon as possible. Correct diagnostic means the isolation of the strain which determines the disease, identifying it as belonging to the Tuberculosis Complex, testing and determining the sensitivity to drugs.

How many patients were diagnosed so far, with this new method, in the laboratory you run?

By the end of June 2015, we had processed through this method 151 culture samples and sensitivity tests. Bacău is among the counties with a tuberculosis incidence above the country average and with an increased number of re-treatments (ed.: relapses, defaults or failures to previous treatments). That is why is necessary to do cultures on liquid media, to ensure a rapid result. In 2008, we considered the idea of the semi-automated MGIT, at that moment being a routine method in Europe. It was a really special moment, although the method is quite time consuming (each tube was manually passed through the fluorescence reader). The automated method we use now, which indicates with sound and visual signals the positive state of one tube, is beyond comparison, even if it took 7 years to get to this point.

„Each patient comes with an emotional, social and cultural background” – interview with Dr. Ariadna Petronela Fildan, MDR coordinator in Constanța county

Starting with March 2015, 1,000 people with multidrug resistant tuberculosis shall receive complete, continuous and quality treatment. By the end of June, 139 MDR TB patients were enrolled countrywide and receive treatment within the project “Improving the Health Status of the Romanian Population in Romania by Increasing Tuberculosis Control”.

The doctors in the local tuberculosis dispensaries monitor the health status of the patients enrolled in the program, thus helping them not to give up the treatment. We asked Dr Ariadna Petronela Fildan, MDR coordinator in Constanţa county, which are the advantages of this integrated system of patients treatment. Medical sciences PhD and associated professor at the Faculty of Medicine of the Ovidius Univerity, Dr. Fildan has been a pulmonology doctor at the Constanţa Pulmonology Clinical Hospital starting with 2008.

In this project, what does patient-centred approach mean?

The core of the project is the patient, everything – from human to material resources –gravitating around him, aiming to heal the patient and contain the spread of the disease. Once the multidrug-resistant tuberculosis diagnostic confirmed, the fight with the disease begins, fight which is based on well established rules. First of all, the patient is informed by the attending doctor about the new diagnostic methods, the therapeutic options, the duration, advantages and possible complications of the therapy, concurrently underlying the fact that the disease can be defeated if the treatment if followed on a continuous basis, without interruption for the entire duration indicated by the doctor. One shall try to motivate the patient in order to enter the program, bringing as supreme argument the cure and the chance to a normal life. Each patient represents a specific case; they don’t come only with a diagnostic and a disease we must treat, but with an emotional, cultural and social background which we must consider when trying to motivate the patient. We try to answer to all the questions related to the disease and treatment, to provide them as much information as possible, in a clear way, tailored to the personal level of understating.

How important is the medical care accompanied by psychological care, how does this actually take place in hospitals? Which are the advantages and what is the difference between the new possibilities and what was done before?

Evidently, the psychological support is very important; a trained person can find the methods adequate to each patient to motivate them not to give up the treatment. In fact, the most important aspects in the success of a treatment are, first and foremost, the compliance and ensuring continuity. Psychological counselling at the initiation of the treatment but also during the entire course, when complications – some quite difficult to deal with and to control – might appear, is a major contributor to the therapeutic success. Unfortunately, not all the hospitals have trained staff and in this situation is our hospital in Constanţa as well. To bridge the gap, the discussions with the patient take place with the participation of the attending doctor, the chief of department or the chief of dispensary (according to the case, if the patient is hospitalized or in ambulatory), the medical director and the program coordinator. The advantages we have at this moment are considerable, starting with the fact that we can have an MDR TB diagnostic in a few hours, compared to a few months, through access to the newest molecular diagnostic methods, continuing with access to modern therapy, ensuring continuity, the treatment regimens being those established by the MDR commission, according to the international guidelines.

Social support: what is the role of the social vouchers?

The role of these vouchers is a motivational one. It has been observed that providing monthly “bonuses” – if the patient came to the doctor and was given the treatment in the presence of the doctor or nurse – increases the treatment compliance rate. As it is very well known, many of the patients face serious material difficulties and thus any help is welcome.

What feedback do you have from your patients, regarding this approach?

The patients are satisfied because they have the continuous treatment ensured, have an additional chance, by being included in this program, and understand the importance of the correct administration, without interruption, of the medication, because this is the only way they can be cured.

How many patients are enrolled in this program in Constanța?

Currently there are five patients enrolled for complete regimens and eleven patients enrolled for social support in order to increase their compliance to treatment. We hope as many as possible will be accepted.

What is the situation in the county regarding tuberculosis?

In Constanţa County, the tuberculosis incidence decreased constantly in the past 10 years, from the 3^rd place at national level to the 12^th place. Last year 634 cases of tuberculosis, new cases and relapses were notified, representing an incidence of 87.6 versus 89.9 per 100,000 inhabitants, in 2013. 38 cases were notified in children. What we noticed for the first half of this year is the high number of severe cases registered in our hospital, extended, milliary forms, meningo-encephalitis. Until now we had 13 deaths due to tuberculosis, which probably can be explained by the long latent period between the occurrence of the symptoms and the visit to the doctor.

“It has to pass!” you end up saying – the story of Marian Istrate, patient at “Marius Nasta” Institute

Marian Istrate is 41 years old, lives in Bucharest and in April 2015 was hospitalized at the “Marius Nasta” Pulmonology Institute in Bucharest, with the diagnostic of multidrug resistant tuberculosis. He left at home his wife and their 19 years old daughter who just had the bachelor degree exam, worried that there are chances he would have given them the Koch bacillus. In an interview conducted in his room from “Marius Nasta” Institute, Istrate told us how he ended up being diagnosed with tuberculosis and what his hopes for the future are.

“I don’t know, I have several problems, and the most important is Crohn’s disease, which I have been fighting for 10 years now. (ed.: Chron’s is a chronic inflammatory disease, localized in the digestive tract wall). Because of this disease I had a stroke, trombophlebitis, there were several things linked to each other. Then some biologic treatments for the Chron’s disease appeared and the doctors proposed to follow them.

Thus, as I ended up doing all sorts of investigations in hospitals, in 2007 they discovered I had pleurisy. Then, in 2013, they noticed a spot on the right superior lobe of the lungs and the doctors told me I had TB. I followed 1^st line treatment, except that the spot didn’t become larger, but it didn’t shrink also. And I thought to myself: if I cut my finger, then it swallows, it gets infected or it heals. But in my case the spot remained there, even after the treatment.

I took the TB treatment for 6 months, plus the biologic treatment for my disease and it went ok. I used to go to Fundeni, but I wasn’t hospitalized, I was going twice a month and get a dose every two weeks. And at the end of last year they changed my treatment with an intravenous one. I had only two doses and during New Years Eve, in December 2014, I had fever, chills. It passed after 2-3 days or so and, after about half a month, I thought I should go to the hospital to see what’s going on.

I had an X-ray and they told me I had a tumour. And I had to have a bronchoscopy done afterwards and it didn’t turn out to be TB, cancer, or any tumour, but some sort of pneumonia. I was put for 20 days on Cefort iv treatment, and in the sputum sample didn’t appear anything. In March, they put me on 1^st line treatment, but the spot remained. By end of April, a lady doctor calls me, telling they did the drug sensitivity test and that it turned out multidrug resistant tuberculosis. “Wouldn’t I better go and buy a coffin?” I said to myself.

On 29 April I was hospitalized. It is suspected that I took it (ed. the bacillus) from somewhere in a hospital. At least 2 month I’ll stay here at “Nasta”. To my surprise, I coped with the treatment, although I was afraid I couldn’t do it. As a patient here, one begins to get used with the idea of the disease, of tuberculosis, of severe diagnostic. I still have bad nausea, sometimes I even feel sick to drink water. It has to pass, you end up saying to yourself.”

Marian Istrate is only one of the thousands of patients with multidrug-resistant tuberculosis in Romania, to whom the lack of high performance methods of rapid and correct diagnosis of the disease made loose precious time. Two years – the time when Marian was incorrectly treated for sensitive tuberculosis – represent a period when multidrug resistant tuberculosis would have been cured, with the proper and timely initiated medication.

Access to rapid diagnostic, thanks to the high-end equipment procured through the project “Improving the Health Status of the Romanian Population in Romania by Increasing Tuberculosis Control” allows receiving the diagnostic in very short time (from few hours up to few days) and beginning the correct treatment, offering the patients like Marian Istrate the chance to be cured and have a normal life.

*Marian Istrate is a fictional name; we decided to change it at the patient’s request.

“Through the methods we’ve had so far, we got results after two or two and a half months”

We asked Dr. Daniela Homorodean how the national laboratory network looks now, what are the challenges of the specialists’ activity and what will the new equipment bring. This is what she said for us:

“For the current situation in Romania, doing a microscopic exam for tuberculosis control is not enough. For a better surveillance of the endemic we need, for each patient, microscopic exam, as well as culture and drug sensitivity test. In the sputum we examine routinely for the pulmonary tuberculosis there must be 10,000 bacilli per millilitre of product, for us to be able to see one bacillus at the microscopic exam.

When bacilli appear, which we see coloured through special colorations at the microscopic exam, the lesions of the lung are quite advanced. Then, using other methods, we increase the chances to highlight the bacilli in early stages of the diseases, when the lesions are not so advanced. Thus, the chances of curing with less scars and lesions on the lung increase, because tuberculosis is a treatable infectious disease which can be cured. But, if the lesions are too extended, then it is cured through fibrosation, a scar-like tissue is formed. It is a fibrous tissue which doesn’t allow the lung to normally expand and relax. The bigger the lesions, the more extended is the fibrosis.

There are about 100 laboratories that diagnose and have as scope of work the bacteriologic diagnosis of tuberculosis, spread in all the counties. In each county there is a lab doing tuberculosis diagnosis. Starting with 2003, we began to run visits in the laboratory network and we selected some enthusiasts among the colleagues working in TB labs, good professionals, willing to participate in the control and guidance visits in the laboratories in the country. Immediately after we had the opportunity to accredit the laboratories according to the EU quality standards. Initially, 38 laboratories out of 50 proposed got accreditation, because only those met the criteria. Through the methods we’ve had so far, we got results after two or two and a half months, when we found out whether the germs eliminated by the patients were sensitive to the antimicrobials or resistant.

In eight regional laboratories and two national ones – Bucharest and Cluj – we have now the possibility to run genetic testing, in 24 or 48 ours, for the presence of the microbe in the sputum and the resistance of that microbe to the most powerful drugs – Isoniazid and Rifampicine. The resistance to these two drugs defines the multidrug-resistant TB. If the microbe is resistant to these two drugs, other substances, more powerful and more expensive, some of them with toxic effects, should be added to the treatment. It is best if, from the beginning, the patients accept the treatment so that the microbes not gain resistance, follow exactly the treatment without missing one single doze and not give up some of the drugs, because they think that three or four are too many. It is a big mistake, because from a treatable and curable disease, the person can develop a form difficult to treat and maybe impossible to cure. Then, such a non-compliant patient could make other people ill, and they will have since the beginning drug resistant tuberculosis. To find out about these cases as soon as possible, the genetic tests received through the Norwegian funds are essential. These are equipments which function with specific reagents and need special fit-up design. The reagents are procured also from Norwegian funds.

Through these projects, 9 cars shall be procured for the transport of products from the periphery to the diagnostic centres, so that by collecting the products we shall have rapid and quality diagnosis. It is not at all cost-efficient to keep a laboratory that only tests 3 sputa per day.

In 1999 we had other funding from the World Bank and five laboratories received the same equipment for doing culture on liquid media. Through that project, the laboratories had reagents for one year. Then, due to lack of funding, some of the laboratories stopped their activity, some others continued, but at a very low level, for serious forms.

We have to make sure that all the laboratories provide comparable diagnosis. The patients are quite mobile during the months or years of illness and go from one hospital to another. Or maybe they travel, get sick and get another set of tests. The results are compared with the previous bacteriological tests and they should be comparable, so that the monitoring can be correct and real and we can use the same scale and system of expressing results. I really like to believe that we had good results in the laboratories. It’s not a pleasure to work daily with sputum – not the best sight – but if you can deal with it and consider it a necessity, then you understand the relief of establishing a positive diagnosis and telling the patient that they have tuberculosis, not cancer. It is indeed, a relief.”

Simona, 37, Bucharest. “Everything starts with you”

Simona (37) is an economist in Bucharest and she was told she has MDR-TB almost two months ago. She has been in hospital ever since.

“I got TB from my brother-in-law, who is also hospitalized here.

It started with pneumonia – I started coughing, so I went to the doctor and he told me I had an untreated pneumonia. I underwent treatment with antibiotics; then the doctor did an X-ray and told me it looked better. I told him I had come for my pneumonia but also because I had a case of TB in the family. He said that if I had had TB, the antibiotic he had given me would not have had any effect.

The next time I came for an X-ray, the doctor told me he had the impression there was something else there, that it was no longer pneumonia. One week later, I got a call from the clinic and I was told to come urgently. The DST had come out with tuberculosis.

I have never been ill, neither have I taken drugs, underwent treatment or been admitted to any hospital. I had a good immune system, I eat healthy, I do not smoke and I do not drink coffee or alcohol. In 37 years, I have never been in hospital. If I felt ill, I would let the system fight on its own, and I would not take drugs.

Sunday before I left for the hospital, I cried a lot. Everything was new for me: from an active and healthy person, suddenly I had to be hospitalized.

At first, it was difficult in the hospital; I would wake up in a state of panic in the morning, when I had to take the medication. I felt fear and rejection inside. It is not easy because there are days when I simply cannot walk and I can barely articulate words. There are days and days…

I have to be strong and take it easy. You need to encourage yourself and learn to do things on your own. Everything starts with you.”

Ioana, 45, Medias. “I am not as strong as before, yet I drag myself along”

“I am not as strong as before, yet I drag myself along”

Ioana (45) comes from Mediaș and she suffers from extensive resistant tuberculosis. In March, she was hospitalized along with her daughter (14) also a MDR suspect. Should the suspicion be confirmed, her daughter will become one of the patients included in the project “Improving the Health Status of the Romanian Population through the Increase of the TB Control Capacity”.

“Last year I spent 9 months here. I am unfit to work, but I am glad I can cook, clean and help my daughter. We can barely make ends meet from my pension and her survivor’s benefit. We limit ourselves to what we have. We live in a studio where we have what we need. We are poor, but we can afford to pay for the heating and to buy food.

When I was 19 years old, I suffered from drug-sensitive tuberculosis. I have had two relapses since then and, in the third, the doctors diagnosed me with MDR. When I was little, I had once a sore throat so severe that I could no longer speak, and when I enrolled at the university, they did some X-rays. ‘No file, no university – the hospital’, they told me. After me and my husband divorced, I had a relapse, my immune system was weakened, and I keep telling myself it was nerve-related.

My eldest boy’s father, who also has TB, died in 1995 of TB and we still do not know what kind of TB it was. One of my husband’s brothers also died of TB. His mother and sister had no idea what drugs he was taking. When the doctor learned that I had MDR-TB, he told me that I got it from my husband.

He hardly followed his treatment.

I had a 12 hours a day job and I neglected my diet. I worked as a clothes manufacturer. I finished post-secondary school, I was in the Technical Quality Control for a while and then I was somewhat of a shift manager. I have not worked since 2007. Until 2008, I was on first-line therapy. It was in 2008 that the doctors in Mediaş considered testing me to see whether I was resistant to drugs. The tests showed I was resistant to two drugs and they kept me there for another 4 months. When my child got sick, I did not leave him in Mediaş, instead I took him to Sibiu and later to Bucharest.

His condition is improving.

I am feeling so-so now. I am not as strong as before, yet I drag myself along. My daughter is in the 8^th grade and she wants to go to the military high school so she had to do some tests. There was something wrong with her lungs. The doctors still do not know what it is, but they suspect she got it from us.

We were not alarmed because she was feeling well and ate well. She is a good student and she wants to study mathematics and computer science, however she can no longer enrol at the military high school. We have been in hospital for almost a month now, but we are to go home soon.

When I was ill and I could not manage on my own, my mother and my daughter would help me, and we would help each other. We are used to living on our own, just the two of us.