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The return of TB

Annunziata Faustini is a doctor in the epidemiological unit of the Lazio Regional Public Health Agency in Italy, and was chief of surveillance of infectious diseases from 1996 until 2002.

by Annunziata Faustini

Generations of doctors, politicians, and public health officials have struggled to defeat tuberculosis. But, after years of success, TB is making a comeback. The increase in TB in the developed world since 1992 was initially attributed to HIV. However, over time, other factors behind the growing number of cases, such as immigration and a particular type of drug-resistant TB, have emerged.

The World Health Organization has developed a strategy to fight TB’s return, including a standardized therapy that specifies appropriate drugs, doses, and timing of therapy. Unfortunately, multi-drug resistant tuberculosis (MDR-TB), which is any TB resistant to the traditional treatments of isoniazid and rifampicin, represents a serious challenge: because standard treatment is less effective in curing it, its transmission continues.

Moreover, any inadequately treated TB becomes multi-drug resistant, so that treatment failure can be either cause or consequence of MDR-TB. This underscores the need for a determined regimen to treat TB today, as well as a more complex strategy to control the disease, one which cures as many cases as possible, prevents acquired drug resistance and decreases the transmission of infection. The WHO recommends what it calls a "Directly Observed Therapy Strategy" (DOTS) and has set diagnostic thresholds of at least 70% of infectious cases, and curative thresholds of 85%.

We conducted a systematic review of published reports to identify the factors that cause unsuccessful TB treatment in Europe. Twenty-six papers were included in the review, covering 13 countries (the former USSR, the Czech Republic, Poland, and Romania in Eastern Europe, and Denmark, France, Germany, Italy, the Netherlands, Northern Ireland, Spain, Sweden, and Switzerland in Western Europe) in the period from 1988-2001.

On average, the studies found that 74.4% of the curative outcomes were "successful," falling short of the WHO’s 85% target. Patients were treated "unsuccessfully" 12.3% of the time, and 6.8% of treated patients died.

MDR-TB was inversely associated with successful treatments. We found that populations with at least 10% MDR-TB showed a notable reduction in successful outcomes. Surprisingly, no relationship was found between TB treatment outcomes and immigrant status in these studies, perhaps because all immigrants were combined, regardless of country of origin.

These results suggest the following clinical and public health implications:

  • since successful TB treatment outcomes are below the 85% threshold, an enhancement of national TB control programs is needed in most European countries;
  • MDR is the most important obstacle to controlling TB in Europe;
  • analyzing immigrants by specific country of origin, timing of immigration, and previous treatment can help define the risk of MDR-TB associated with immigrants;
  • treatment characteristics need to be reported more consistently in order to identify and correct the factors related to inadequate treatment of TB in Europe.

Although some characteristics of TB therapy, such as interruption of treatment, are well known predictors of multi-drug resistance, other aspects of treatment that reflect the health-care system, such as the drugs used and the length of therapy, must be studied to help improve control programmes. For example, one of the studies that we reviewed found that no standard therapy in the initial or secondary phase of treatment was associated with an unsuccessful outcome or death. Moreover, some aspects of patient management emerged as risk factors for not completing therapy, which suggests difficulties in access to health services for TB patients.

Structural barriers do not represent the only problems of access to treatment in the health care system. Foreign-born patients may interrupt treatment due to lack of confidence in diagnosis and care, or they may ignore the more minor symptoms of the illness. Patients who feel better after the initial treatment may also fail to complete therapy.

Social factors other than birthplace should be studied to evaluate what causes primary multi-drug resistance. Treatment interruption has been associated with asylum seekers and refugees in Switzerland. Interruption was also associated with homelessness, intravenous drug use, and alcohol dependence in Hamburg. In Spain, homelessness was a risk factor for interruption and HIV positivity, and intravenous drug use was a risk factor for unsuccessful treatment.

I also believe that there is a relationship between the need for therapy and the political choices that countries make. The DOTS strategy is not implemented in all European countries, owing in part to disagreement about whether treatment is a duty or a right. Public health workers argue that therapy should be imposed upon patients who are at risk of failing to complete it – a policy that others claim would violate individual liberty.

Unless we act to step up the fight against TB, many health-care systems may find themselves facing a less abstract problem: securing the economic resources and organizational capacity to ensure treatment for the growing number of patients who want and need it.

Copyright: Project Syndicate, 2006.

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Greg Moylan: More on TB

Greg: I was talking to a repiratory physician the other day and asked him about the BCG vaccine. He basically confirmed what I had found out, ie that there was certain controversy over its effectiveness, but it had been seen to be beneficial in disseminated TB, ie TB affecting the other organs, but not the common pulmonary infection.

He said it is not used in Australia these days. Regarding the rise in TB he said there was a general rise but mostly amongst immigrant population where drug resistancy was the biggest problem.

He also said that the drug resistancy was not so much a problem amongst the existing population here and in fact that TB was still very drug sensitive amongst that population.  He agreed that poor drug regimes, and living conditions in the third world was leading to the rise in drug resistancy overseas. This more or less supports what is said in the Post here.

He did say that patients no longer have to take those dreadful PAS tablets and the main form of treatment was by antibiotics, streptomycin being the main one. That was also the antibiotic of choice way back in the 1960s when I was nursing so it must be pretty effective, so long as the DR strains do not take hold.


TB and BCG

Greg: Your question prompted me to do a bit of research of the web as I really do not know much about the effectiveness today of BCG and I left the nursing profession back in 1963.

From the sites I googled it seems there is conflicting evidence as to the effectiveness of the vaccine. But what I did find was that WHO declared a TB emergency in 1993, and there is a WHO program to reduce deaths by 14 million between 2006 and 2015 so it is obviously a big problem.

In 2004 (from Wikipedia) there were 14.6 million people living with active TB with 2 M deaths. Most were in developing countries but it is on the increase in developed countries due in part to the compromised immune systems of HIV sufferers.

BCG is said to have a "modest effect" in preventing extrapulmonary TB, but is not effective against the more aggressive pulmonary TB. However the vaccine is now being found to have a better result with children than was at first thought, particularly tuberculosis meningitis. As you may know TB is not just a disease of the lungs.

Yes, most kids got the BCG in the 1950s and 60s as a routine vaccination. All the kids in our family, including myself, showed positive mantoux tests. We believe this was probably as a result of drinking unpasteurised milk from cows we kept at a time when TB was rife in cattle on the north coast of NSW. But we were deemed to have a natural immunity rather than the infection so there was never any follow up and we did not get the BCG if we had the reaction. I am surprised you had to have follow up for so long but there are different readings of the positive mantoux tests, so you may have been different. It is all so long ago! As I recall, if you had a positive mantoux you had to go for a chest X Ray.

The problem however of drug resistant bacteria is very serious as we all know and this will be the biggest worry with TB. It was never an easy disease to treat. I remember patients having to take 8 of those very large PAS tablets a day, and it was also treated with a combination of two antibiotics. I remember this well as I had to inject an aboriginal woman from one of the islands and she did not like it one bit and she nearly strangled me for my trouble. Another patient on crutches saved my life!

The crazy use of antibiotics in the livestock industries would have played a major role in the emergence of DRB.. I do not have their book to check but I recall Singer and Mason saying that in the 1980s 50% of all antibiotic use in the US was as additives in animal foodstuffs, as growth promotants and as prophylactics in intensive industries where the confinement conditions made disease outbreaks more likely.

I know that E coli resistant bacteria were found on frozen chickens in a Victorian supermarket some years ago, so the problem is not confined to the US. Antibiotics were widely used in the poultry industry, but I do not know if that is now the case. I would surprised if it were permitted these days, but who knows. I must check that out when I have more time.

One thing that did come out of my check was that HIV abrogated any protection by BCG with extrapulmonary TB. That does not auger well for those countries with high incidence of HIV/Aids such as in many African, and Asian countries. Pulmonary TB is highly contagious.

Sorry. I am not really up to speed on all this but the literature is quite enlightening if you google it up. But one thing that was interesting is that BCG has been found to be effective in the treatment of some forms of cancer, particularly bladder cancer. So you live and learn.

Thanks Jenny

Jenny thank youfor taking the time to do that research and for providing me with a very detailed reply. I appreciate it very much. I'm currently living in Cambodia where active TB is rife and of course the subject is of some personal interest to me as I was one of very few people at the time I had the Mantoux test who returned a positive and it was always a mystery to my family as to how I had been exposed.

I don't know why I was followed up on for so long. As I was living in Victoria maybe that was just the rules applied by its Health Department or maybe they had me as a subject for some long term survey. I do remember they were quite diligent. Even when I moved house without notifying them of my new address (I never bothered to do that) I'd find at the appropriate time a nicely worded letter inviting me to go to one of a list of hospitals at their expense, including travel costs, for an X-Ray. Since I was always glad to oblige I never found out what would have happened had I not done so.

I do wonder as to whether the use of antibiotics in the livestock industry plays a major role in the emergence of DRTB in Third World countries, dangerous and repellent though that practice is. In places like Cambodia the problem is the unregulated distribution of antibiotics to people. They buy them at pharmacies for the slightest illness and where they do have a bacteriial infection they will often stop taking the antibiotics when they feel better, without completing the course. Then again in countries like Cambodia  I expect that the health infrastructure required to ensure that active TB is identified and effectively treated and followed up on would be grossly inadequate. However I doubt that many cattle, let alone chooks, would ever get treated here with antibiotics for anything.

Thank you again for your research and your thoughtful reply.

TB in Asia

A question for you, Jenny. How effective is immunisation with the BCG vaccine? I recall that vaccination with it was a key part of the effective eradication of TB in Australia in the 1950s through to the 70s. However I have since seen a comment by a doctor in Cambodia, who runs several large children’s' hospitals, that it is not effective. I also note that vaccination doesn't seem to feature prominently in the strategies for TB eradication in Asian countries.

Michael, I am surprised at your comments about an alarming rise in TB in Vietnam, Indonesia and Thailand, especially in respect of Vietnam. It is my understanding that Vietnam has a very solid public health system and that TB cases, if not falling, remain fairly stable, and that there is high public awareness as well as an effective program of detection and DOTS treatment, although it’s sad that it remains a serious problem.

According to the World Lung Foundation, Thailand is experiencing an overall downward trend in TB, although its program of detection and treatment is not as good as that of Vietnam. (The Vietnamese do public health really well as shown during the SARS crisis.)

The WLF report for Indonesia indicates that because of unreliable previous data figures on TB prevalence are unreliable and that more reliable data taken in 2004 are still being analysed. Certainly the figures they give for the notification rate show an upward trend although this could be a result of improved detection rather than an increase in TB incidence.

I'd be surprised if there were an alarming increase in TB in any of those countries as active TB is partly related to poor nutrition and poor general health, and hence an inability to stave off the disease (or so my doctors told me during the 25 years of compulsory follow-ups I had after I returned a positive Mantau test as a ten year-old) and nutrition levels and general living standards have been rising in each of them over the last several years. Still, with the rise of drug-resistant TB I guess that, even if the overall new infection rate declines, prevalence can rise if those who have the disease cannot be cured.

on the rise in Asia

I've just returned from a 6 week tour of Thailand, Indonesia and Vietnam. TB is definitely on an alarming rise in these countries particularly Thailand and there is little education or acknowledgement about the disease.

Fiona: Good to see you again, Michael. Had been wondering where you were.

TB in indigenous communities

Alarm bells have been ringing now for many years over the re-emergence of TB in the developed world but this disease has remained a major issue amongst indigenous communities and no doubt in third world countries generally. Whilst nursing in the NT in the 1960s I worked mostly with aboriginal patients, andTB was the most common infectious disease amongst them, though leprosy was still prevalent also.

The most recent studies in SA show that rates of infection are still very high  in aboriginal communities (particularly rural) in that State, when compared with those in the general community. Those findings no doubt reflect the situation overall.

Contol of infectious diseases in hospitals requires 'barrier nursing"  to prevent cross infection, but this was never possible with the aboriginal communities with whom I worked. Passing cigarettes and pipes from mouth to mouth around the campfire was common practice, despite all efforts to educate those who had the illness that this was placing others at risk.

Therapy was imposed on infected persons with patients admitted to infectious wards for long term stay. However they were not gaols, and patients went fishing with relatives and communed together that way under the trees outside the wards, with very small children amonst them.

The conditions in communities with high acohol and drug abuse, and where there is general social breakdown will make uninterrupted treatment even more difficult today. This will lead to further drug resistance. Just another problem for a people already battling rampant levels of diabetes and other major diseases.

Infectious diseases are just that. Infectious. We will ignore this issue at our own peril.






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