Tuberculosis, BCG, toddlers and doctors

Factual Questions
1

China bambinas (26 months old) were diagnosed today with having TB based on a skin test. Xrays didn’t show any sign of infection thankfully.

bambinas also had the BCG vaccination against TB a few months ago. CDC website says that the BCG can cause a false positive result. Also that BCG is not widely used in the US.

We live in China, which is a high risk area for TB. We have had multiple household helpers from the countryside in our home and exposed to the bambinas.

I wasn’t at the visit (on a biz trip), but the doctor did ask if a BCG vaccination had been done. Said doctor then prescribed a 9 month treatment program of Isoniazid. Said doctor did not proscribe any other confirmation tests such as sputum, smear, culture or QuantiFERON®-TB Gold Test.

As a layman, I’m thinking that if BCG often produces a false positive, then a confirmation test is in order. Then again, it also seems difficult to rule out a false positive 100%. It is a nasty disease, especially for kids, so maybe a 9 month course of antibiotics is the prudent thing to do even if a confirmation tests fails to conclusively show TB.

I don’t have a lot of trust in this pediatician, who is from New York, based a on previous experience. I’ll be contacting the pediatrician tomorrow.

Anyone with experience or advice?

2

Medical advice here is worth what you pay for it, unless you are a member, and then it’s worth less than what you paid to be a member.

BCG can give you a positive PPD skin test. The more proximate the skin test to the BCG the more likely it will be positive. This close to a BCG is a great example of BCG really clouding the issue. If you are a few years out from the BCG, it’s a different story–the further out, the more you should assume a positive PPD is exposure to TB and not the BCG. My guess is that it’s the BCG here, but hey…who am I?

TB is a nasty disease and your baby is from an area where it’s endemic. Moreover, it’s a communicable disease, so there is the chance of infecting others if the baby develops an active infection.

The tuberculosis bacillus can sort of hide in an indolent way for many years before it produces active disease. It’s unlikely, absent any other symptoms, that your baby has TB active enough to be found on any other ordinary test. This doesn’t mean the baby wasn’t exposed to TB.

I have read ( http://www.medscape.com/viewarticle/522380 for example), that BCG does not creat a false positive for the Quantiferon test. A specialist might help you decide if a Quantiferon is worth pursuing.

There is no urgency to decide if the bab(ies?) are not sick.

Get your advice from a pediatric Infectious Disease specialist. Ask for a referral. Any doctor comfortable with his own decisions is comfortable having them reviewed by a specialist.

3

Noticed the link made you sign in. Here’s an excerpt of the article:

“The QuantiFERON-TB Gold test is recommended for assessing the presence of either latent or active TB. Its sensitivity and specificity were reported to be high in a variety of studies, which are referenced in the guideline. Infection with M tuberculosis and pathogenic M bovis will give a positive test response; the only other mycobacteria that appear to produce positive results are M kansasii, M marinum, and M szulgai. Immunization/infection with bacillus Calmette-Guerin (BCG) should not produce a positive rest response. [This specificity is a potential advantage over skin testing, especially in patients who have a history of recent exposure to BCG. The Morbidity and Mortality Weekly Report (MMWR) indicates that this test can be used in place of skin testing and that a positive result should have the same clinical and public health implications as a positive TST. CDC cautions that the QuantiFERON test must be used in conjunction with clinical judgment when considering the need for chemoprophylaxis or treatment. CDC also notes that the TST gives a greater number of positive results than the QuantiFERON test; this could be due to higher sensitivity or lower specificity (or both) for skin tests. There are not a lot of data on the use of this test with either immunosuppressed patients or with children.”

I hope it’s OK to post this in this way. If I get kicked off or something, I’m near the end of free tenure anyway.

4

That sounds like as good a reason as any to pony up the $14. Welcome aboard.

5

A lot of my patients had the BCG when younger. Before considering treating them for TB, I generally get the quantiferon gold test. I would not want to commit anyone to INH for 9 months who has had the BCG vaccine and whose only finding now is a positive skin test.

BCG is protective againt TB meningitis in infants in children. IIRC, it doesn’t significantly reduce the incidence of pulmonary TB in any age group.

WARNING: I do not currently treat a pediatric population, unless you consider a few 16 year old patients to be a pediatric population. Get straight answers from a qualified pediatrician who has experience with this type of situation.

6

Thank you for the advice. First step is to speak directly to the pediatrician today. After that I’m not sure…Uncertain if the QuantiFERON-TB Gold test is available here in Shanghai, there are concerns on false positives from young children, and proximity to the BCG vaccination. I need to get a TB test myself as well. Rest of the household had the skin test yesterday.

I’m not sure where to see a specialist, but can probaqbly track one down through the Chinese CDC or local hospital. We are currently getting treatment through a foreign clinic. I had 100% confidence in the previous pediatrician, but he repatriated back to the US. This new pediatrician sets of my alarm bells (we had a previously bad experience).

regardless of how, I want to get some sort of confirmation before doing 9 months of antibiotics.

Oldest daughter had her BCG 6.5 years ago and tested negative on the skin test.

The twins (26 months) both tested positive and started the Isoniazid yesterday.

7

the foreign center pediatric center is closed today but the pediatrician is on tomorrow.

We spoke with a Chinese pediatric TB specialist at the Shanghai disease control. She thinks we have two false diagnosis. First, that any child with BCG will show a positive result on the skin test. If the skin test reaction is +1 or +2 mm enlarged, that means that the immunization was successful and the test is reacting to the BCG.

I will go to the foreign clinic tomorrow to confirm the BCG record and the size of the skin test reaction. Also as the pediatrician regarding alternate tests to confirm TB.

Second, false diagnosis is that if my 6 year old tests negative, that strongly indicates that her BCG immunization was not effective and she needs a new BCG and is at risk.

I am also going to make an appointment to speak with the Clinic Director as it appears this pediatrician may be shall we say not as professionally competent as she needs to be.

8

My Father was exposed to TB when he was a child, (his Grandfather had it) As a health professional they periodically test him (tine test) for the disease & he tests positive… from my understanding, he then had to get a chest X-ray to get the all-clear.

9

I spoke with the Director of the foreign clinic by phone tonight. He is a GP although these days an administrator that runs the pretty sizeable operations (4 locations, 12 bed inpatient, birth facilities, etc) here in Shanghai. So points to him for both checking email on a Saturday, having a phone discussion with the pediatrician and then calling me.

He believed that the pediatrician did carefully consider the situation. Her diagnosis to start the treatment was based on positive reaction to the skin test (in the +1mm to +2mm range), and living in a high risk environment (TB rates in China are high, and we have had multiple household helpers in very close proximity from the countryside).

When I queried if further testing to confirm or rule out latent TB infection was warranted, the Director said that was outside of his personal expertise and couldn’t comment. Fair enough. However, layman that I am, I’m thinking that futher tests to confirm or rule out latent TB would be the logical next step. That said, there **may be ** valid reasons that such tests would not be conclusive.

The Director said that our original pediatrician, who looked after the twins from birth until he moved back to the US 2 months ago, was extremely well versed in infectious diseases and a consultant to their Shanghai operations. I trust our original pediatrician 100%. He was the delivery pediatrician who resuccitated and restarted the heart of our youngest twin. He volunteered his time to visit her together at the Chinese NICU, arranged for feeding therapy, and then twisted the arm of this same Director and others at the foreign clinic to bring her back after 18 days in the NICU until she was ready to come home 18 more days later. He’s also a wonderful guy. And on top of all that, had been an AIDS researcher for a number of years in the US. So, not only do I trust him completely, he is also quite competent in infectous diseases. What he recommends will be the way we will go.

Will also take my 6.5 year old daughter to the Infectious Disease TB specialist for testing in one month, and then a new BCG if warranted. For what it’s worth, she does not have a noticeable scare from her bcg vaccination.

I will also go see the current pediatrician (although we had a previous bad experience with her) tomorrow to see what she says. I’ll get my own TB test done as well.

also a correction to my earlier posts, the BCG immunizations given to the twins were done around birth. Twin A before she left the hospital (so 1-2 days after birth or 26 months ago). Twin B was immunized sometime around 1 month of age, so 25 months ago). Eldest China Bambina was immunized 6.5 years ago.

I’ll also point out that when it comes to the top level Chinese doctors, in my experience they are quite competent and extremely experienced. They see a lot of patients and get a lot of hands on experience, especially with say TB versus your average US doctor. BCG vaccinations of newborns I believe are universal in China, and certainly in the big cities. Therefore, they are very experienced in BCG, what a skin test with BCG innoculated kids looks like, etc. Certainly more so than a Manhattan pediatrician.

Anyhoo, I appreciate the feedback (with the caveat of very real standard disclaimers) from both Chief Pendant and Qadgop. I take this very real risk of TB seriously, but also don’t want to subject my kids to 9 months of antibiotics if it is not warranted.

10

Welcome to the wacky world of medical decision-making. It’s difficult enough to make a decision when the only consideration is personal outcome. When cost/benefit/effectiveness is layered on top of that it’s really hard, and when personal v. common good is weighed it gets even harder. Throw in public policy and you’ve got yourself enough fodder to have no clue what to do.

Whatever advice you seek, you want to weigh the source of the advisor’s opinion. If, for example, the advice comes from a pediatrician very experienced in TB in China, that carries a lot of weight. It would not surprise me, however, if Chinese public health policy 1) does not include a quantiferon test in the decision-making tree and 2) errs on the side of using INH (isoniazid). Where resources are limited, public health policy generally weights common good over personal benefit. Also, in a developing country such as China, recommendations are often based on simplified guidelines because the decision tree needs to be kept as simple as possible in order that the broadest possible range of implementers can follow it. You don’t get to have a specialist dissect every permutation.

If it were my babies, and cost was not an issue, here are the questions I’d ask when I finally got to the person whose expertise I trusted:

  1. We are under 3 years post-BCG. Isn’t this well within the range that can produce a small amount of induration on the Tuberculin Skin Test?
  2. There is only 1-2 mm of induration. Why isn’t this considered a non-reactive result?
  3. Do you do Quantiferons here, and is that part of the decision-making tree for TSTs that are ambiguous? Will a follow-up QFT be useless because the TST might create a false positive QFT? (CDC does not recommend it as a TST confirmation for this reason Guidelines for Using the QuantiFERON ) If a QFT is negative, is there any reason for INH?
  4. What’s the experience with babies getting TSTs within 3 years of their BCGs? Why is it even done? Are there any data to show how frequently the PPD is reactive, what the degree of reactivity is, and how frequently an untreated weakly reactive PPD progresses to active disease in this situation?
  5. We are going to stay in China (x) more years. When the course of INH is done, the babies will still be exposed to TB on an ongoing basis until we leave. If their TST is still positive, do we give them another 9 months of chemoprophylaxis at that point? Why? Why not?

And FWIW, ask nicely and be polite. Nothing will cut off an answer faster than the impression the questioner has already decided the answer and is simply challenging the expert. Instead, couch questions as if you were at the feet of the Master sucking up pearls. A little ego massage will go a long way in helping you figure out if the expert really knows the reasons why (s)he holds an opinion.

11

Wow, thanks for the questions and advice. Yes, cost is absolutely not an issue in this case.

You’re right as well that we’re balancing a 20 year experienced Manhattan pediatrician, who decides it’s TB and immediately starts the antibiotics. Versus the Chinese infectous disease expert, that has probably been working with minimum 50-100 TB cases per week for the past 20 years, who basically said “is your doctor smoking crack?!? That’s such a rookie mistake.”

And, as I check my email, I have a quite detailed ppt from our original pediatrician, who also said to call as soon as we can and we will discuss through on the phone. I’ll update later after my wife is up and we do the call.

12

Bah! Where were you when I just came to the states! grumble I had to go through treatment even though I had notarized documentation I had a vaccine as a child.

13

When did you come to the states? The quantiferon gold test hasn’t been around all that long.

14

well, Chief Pendant, I didn’t ask all of your questions but today did talk with our original pediatrician Dr. O who is now in the US. I also went in and got my skin test and spoke with this new pediatrician Dr. N (who is Taiwanese but US educated and practiced in NY for 20 years).

  1. Dr. O said this could realistically be a false positive reading owing to BCG. BCG affect has a very scattered distribution, so difficult to quantify. Dr. O has treated thousand (s) of patients, mainly from Mexico where it is also common to use BCG, so he’s familiar with the effect on the skin test.

  2. Dr. N said that Serena was 11-12 mm and Audrey 12-13 mm induration, and raised, so her professional judgement that this was a real reaction. According to the CDC guidelines, over 10 in a high risk environment (which we are) means to do the antibiotics. Dr. N is following guidelines that say 5 mm if exposed to a known TB case, 10 mm if in a high risk environment, and 15 mm for anyone.

  3. Dr. O said that Quantiferons when he checked 3 months ago, were still not reliable to differentiate a BCG false positive from real exposure. He expects that in a few more years, it probably will be. For now, there is no reliable test to conclusively differentiate between a BCG effect and PTBI. He’s the experienced one, I didn’t ask Dr. N.

  4. Dr. O said that the normal reaction is so scattered, that one can’t really answer with any authority this questions.

  5. I didn’t ask this question. Dr. N said that after 1 year BCG shouldn’t affect the skin test as it wears off. But if want to retest should wait 1 year for time passage to be meaningful as this will be a significant time change since innoculation. This logic seemed wierd to me.

Okay, I felt better after speaking with Dr. N - she’s erring on the side of caution and prefers immediate treatment. I have a real problem with her bedside manner as she didn’t explain things well to my wife but went immediately into defcon 5 and you’ve got to start the antibiotics this minute. Dr. N also said she follows CDC and international standards, and has no idea about what the Chinese standards are and frankly doesn’t want to. I find this to be off putting, and not the best bedside manner for someone like my wife who is Chinese.

Dr. O gave 4 alternatives:

  1. Do nothing - not recommended
  2. Retest - sometime within 1- 3 months. Dr. O recommends 2 months
  3. Use a different test - not recommended as no current test is known to effectively differentiate between BCG and the LTBI
  4. Treat with Isoniazid - Dr. O said in his experience, he does not find it required to test for side effects. There can be nausea but in the low daily doses it is usually not an issue.

If retest, ensure the testing procedure is correct
· Ensure the initial injection is done correctly
· No scratching
· Interpret the results correctly
Oldest daughter Jacqueline, who received a BCG at birth about 6.5 years ago: absence of reaction and lack of a scar really don’t say anything about the BCG effectiveness. Dr. Jenkins does not recommend re-immunizing as

  1. Could boost the antibody levels for several years and result in future false positives
  2. BCG is a live virus and could cause a strong reaction.

I just looked for the first time. At 96 hours, you can barely see a tiny induration for Serena. Audrey still has a small red spot maybe 5mm in diameter, maybe a tiny bump.

Given the x-rays were negative, Dr. O was okay with retesting in 2 months. I did explain we were leaning toward retesting if the household have x-rays that show no active TB and Dr. O was okay with that. I got the skin test today and my wife will do so soon. Will talk over with my wife tonight.

15

Arghhh, I glossed over this and didn’t ask anyone today. I need to find out more.

16

Don’t overthink the whole thing too far. It will drive you nuts.

This is a good lesson for me in not clarifying the situation, as well. You had made this comment in an earlier post: “…We spoke with a Chinese specialist… If the skin test reaction is +1 or +2 mm enlarged, that means that the immunization was successful and the test is reacting to the BCG…”

I inferred from this that the babies themselves had a 1-2mm reaction. I see above that they had >10mm of induration. That’s why someone jumped all over the INH recommendation. We don’t see true positives like that from BCG on average, but this close to the BCG you might, and therein lies the dilemma.

In reply to your earlier comment that “Dr. O said that Quantiferons when he checked 3 months ago, were still not reliable to differentiate a BCG false positive from real exposure…” I must say that gives me pause. Cellestis says that the ESAT6 and CFP10 proteins which are assayed for in the QFT are not found in any BCG strains. http://www.cellestis.com/IRM/content/gold/QFT-Gold_US_Clinicianguide.pdf I am way out of the TB loop (although I did have the pleasure of a childhood BCG having been born overseas…) but I’m nervous about Doctors who have a quick reply that doesn’t have solid substantiation. From a practical standpoint, it may be water over the dam. There is a small chance the PPD could make the QFT positive, so if it’s positive now, a new cycle of “might be” will start.

Read over the citation above. It might seem like gobbledygook at first but by the second or third pass it should start to make sense. Pay attention to Table 1 and the paragraph under Table 3. Don’t hesitate to print it out and just ask the doc whether or not it’s accurate. I am aware that manufacturers are automatically suspect in today’s climate, but generally speaking these sorts of guides are reasonable resources. You’ve already gotten the CDC’s take. Be aware that broad public health recommendations are frequently based on the total cost-effectiveness of implementing them. If cost is no personal issue for you, within reason, then the question you need to ask is not “What is the recommendation?” but “What is the recommendation if cost-effectiveness is not a consideration?”

I would personally lean toward doing a QFT b/c I personally would be comfortable not treating my babies in this circumstance if a QFT was definitively negative. As advice, though, this comment is worth absolutely nothing–from your standpoint I could be a nutcase on the Internet whose real job is doing bikini waxes. (Would that it were so…)

The good news is, the babies are going to do fine no matter which course you take. Millions of others have.

Cheers.

17

Hey, many thanks for the link. I’ll check with Dr. O as he likes to be up on the latest, and see if this is something that is available in shanghai. Although as I read it through a few times it does say one thing not tested for is someone under 17 years of age. Regardless, I am checking with Dr. O on this.

Others may take the advice on a message board too literally, but I appreciate the hints and being able to use this place as a sounding (and venting) board. Advice and especially medical advice needs to be vetted by the treating doctor (s).

Heck I wouldn’t get a bikini wax based on message board babble, but it might consider learning more :stuck_out_tongue:

thanks again for the pointers and hope you register

18

short update. I’ve got to find someone that both my wife and I trust at the Chinese center for disease control or infectious diseases bureau. Then get their diagnosis.

the pediatrician that I trust who repatriated back to the US warned against do nothing and believe all is well. He’s okay with monitoring and retesting on a regular basis. He also said that there is no test for kids that can rule out false positive, and not even the maker makes that claim. Maybe in a few more years. So, I’ve got to keep on this and figure out how to monitor and follow up.

Audrey still has a slightly red dime sized spot on her arm where the test was done 9 days ago. No induration. Not sure if that’s meaningful or not in differentiating a false positive from a real positive.

I can’t see anything where Serena was tested (eg, no redness). My own TB test was completely without reaction.

19

IANAD/N, but I do work in the medical field with direct patient contact/care involved. I also work with patients with suppressed immune systems. I get a TB test once per year, and each time, I’ve shown a lot of redness, and that spot has stayed visibly darker than the rest of my (very pale Caucasian) skin for up to 2-3 weeks. The only person that’s ever shown any alarm at that was a younger nurse at my first TB test, who called in her supervisor to see. The supervisor was unimpressed and though I didn’t get the full meaning of the explanation, the redness and very-barely-raised spot was not significant and (I think) more of a raised spot would have been necessary.

I do know that coworkers who show a positive test reaction need to get a chest x-ray to show that they are not infected.