Are There Other Reliable Analysis Tests To Confirm The Presence Of "active" Bacteria In Biopsied Cells From Uterus Apart From TB PCR?
Question: Dear Dr. Raichle,
Thank you so much for your detailed response to our query regarding genital TB. We read that the TB PCR assay of the biopsy material has many false positive results. Are there other reliable analysis tests done to confirm the presence of "active" bacteria in the biopsied cells from the uterus apart from TB PCR?
Basically, we would like to know whether the genital TB diagnosis will be confirmatory/reliable based on these tests. We would like to make this evaluation to rule out the possibility of genital TB in my wife, but at the same time we would not want her to take anti-TB drugs based on false positive TB-PCR assays.
We will appreciate your response.
Regards
Thank you so much for your detailed response to our query regarding genital TB. We read that the TB PCR assay of the biopsy material has many false positive results. Are there other reliable analysis tests done to confirm the presence of "active" bacteria in the biopsied cells from the uterus apart from TB PCR?
Basically, we would like to know whether the genital TB diagnosis will be confirmatory/reliable based on these tests. We would like to make this evaluation to rule out the possibility of genital TB in my wife, but at the same time we would not want her to take anti-TB drugs based on false positive TB-PCR assays.
We will appreciate your response.
Regards
Brief Answer:
Please clarify one thing first..
Detailed Answer:
Did your wife ever have the PPD, or skin test for TB? Has it ever been positive in the past if / when she has had it done?
With regard to your question, please give me some time to research the answer to this question. I will get back to you within the day with a great answer!
Thank you for being patient.
Dr. Raichle.
Please clarify one thing first..
Detailed Answer:
Did your wife ever have the PPD, or skin test for TB? Has it ever been positive in the past if / when she has had it done?
With regard to your question, please give me some time to research the answer to this question. I will get back to you within the day with a great answer!
Thank you for being patient.
Dr. Raichle.
Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar
Dear Dr. Raichle,
She was positive on PPD (doc had said borderline), when we did it in 2007 for our green card processing. However, her chest x-ray was negative. She did not take any medications for the latent infection at them time. Now, it has been 6 years since the positive PPD and away from India. She also has had BCG vaccination in her childhood.
Please let us know if you need any other information.
Thanks.
She was positive on PPD (doc had said borderline), when we did it in 2007 for our green card processing. However, her chest x-ray was negative. She did not take any medications for the latent infection at them time. Now, it has been 6 years since the positive PPD and away from India. She also has had BCG vaccination in her childhood.
Please let us know if you need any other information.
Thanks.
Brief Answer:
Complicated question, sorry about delay!
Detailed Answer:
First of all, let me address the borderline positive PPD. This could certainly be related to the prior BCG vaccine administration. Here is a quote from the CDC regarding this exact scenaria:
"BCG vaccination may cause a false-positive reaction to the [skin test], which may complicate decisions about prescribing treatment. The presence or size of a [skin] reaction in persons who have been vaccinated with BCG does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a TST reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by [latent infection or the prior BCG vaccination."
So, I will interpret this to mean that in all likelihood, the borderline positive value was related to the prior vaccine, but it does not rule out latent infection. My guess is that given she had the vaccine, that the chance of TB causing her infertility is extremely unlikely. Also, the PPD will possibly always be falsely positive and certainly confuse things further!
One study of 85 women with Genital TB in New Dehli India revealed methods of diagnosis to be:
1. Histopathological evidence of TB granuloma in 16 (18.8%)
2. Endometrial biopsy in 12.9%
3. Laparoscopy biopsy in 5.9% women
4. Demonstration of acid fast bacilli (AFB) on microscopy 2.3%
5. Positive AFB culture in 2.3%
6. Positive polymerase chain reaction (PCR) in 55 64.7%
7. Laparoscopic findings of genital TB in 47.1%
With regard to the utility of the PCR based test, it is hard to find the sensitivity, specificity and false-positive data. Here is one comment from a reputable source:
“Polymerase chain reaction (PCR) assays, which amplify mycobacterial 16S ribosomal RNA, show promise of rapid detection of mycobacteria. However, the utility of [peritoneal fluid] PCR assays in detecting TB peritonitis has not been well established. One review of 11 cases of abdominal tuberculosis revealed a positive PCR for M. Tuberculosis of the [peritoneal fluid] in all cases, suggesting a role for PCR analysis…”
So here is what I take from all of this in terms of ruling out TB, diagnosing her infertility issue, and deciding whether she needs treatment for latent disease:
1. If she has not had it already, she needs a laparoscopy to look into the pelvis, assess the tubes, and perform a culture and PCR of any fluid within the pelvis
2. At the same time, she needs a hysteroscopy (camera in the uterus through the cervix) at which time she should have a D&C with the specimen sent for culture and PCR for TB.
3. If these are all negative, then I think that she does not / never had genital TB and the PPD was a false-positive.
I believe that this would be the best way to detect “active” disease AND to assess whether there is any pelvic disease that would affect fertility. Given that she was vaccinated, the chance of genital TB being the cause seems extremely unlikely.
I hope that this helps – please feel free to ask followup questions!
Dr. Raichle
Complicated question, sorry about delay!
Detailed Answer:
First of all, let me address the borderline positive PPD. This could certainly be related to the prior BCG vaccine administration. Here is a quote from the CDC regarding this exact scenaria:
"BCG vaccination may cause a false-positive reaction to the [skin test], which may complicate decisions about prescribing treatment. The presence or size of a [skin] reaction in persons who have been vaccinated with BCG does not predict whether BCG will provide any protection against TB disease. Furthermore, the size of a TST reaction in a BCG-vaccinated person is not a factor in determining whether the reaction is caused by [latent infection or the prior BCG vaccination."
So, I will interpret this to mean that in all likelihood, the borderline positive value was related to the prior vaccine, but it does not rule out latent infection. My guess is that given she had the vaccine, that the chance of TB causing her infertility is extremely unlikely. Also, the PPD will possibly always be falsely positive and certainly confuse things further!
One study of 85 women with Genital TB in New Dehli India revealed methods of diagnosis to be:
1. Histopathological evidence of TB granuloma in 16 (18.8%)
2. Endometrial biopsy in 12.9%
3. Laparoscopy biopsy in 5.9% women
4. Demonstration of acid fast bacilli (AFB) on microscopy 2.3%
5. Positive AFB culture in 2.3%
6. Positive polymerase chain reaction (PCR) in 55 64.7%
7. Laparoscopic findings of genital TB in 47.1%
With regard to the utility of the PCR based test, it is hard to find the sensitivity, specificity and false-positive data. Here is one comment from a reputable source:
“Polymerase chain reaction (PCR) assays, which amplify mycobacterial 16S ribosomal RNA, show promise of rapid detection of mycobacteria. However, the utility of [peritoneal fluid] PCR assays in detecting TB peritonitis has not been well established. One review of 11 cases of abdominal tuberculosis revealed a positive PCR for M. Tuberculosis of the [peritoneal fluid] in all cases, suggesting a role for PCR analysis…”
So here is what I take from all of this in terms of ruling out TB, diagnosing her infertility issue, and deciding whether she needs treatment for latent disease:
1. If she has not had it already, she needs a laparoscopy to look into the pelvis, assess the tubes, and perform a culture and PCR of any fluid within the pelvis
2. At the same time, she needs a hysteroscopy (camera in the uterus through the cervix) at which time she should have a D&C with the specimen sent for culture and PCR for TB.
3. If these are all negative, then I think that she does not / never had genital TB and the PPD was a false-positive.
I believe that this would be the best way to detect “active” disease AND to assess whether there is any pelvic disease that would affect fertility. Given that she was vaccinated, the chance of genital TB being the cause seems extremely unlikely.
I hope that this helps – please feel free to ask followup questions!
Dr. Raichle
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Above answer was peer-reviewed by :
Dr. Chakravarthy Mazumdar