Features and Outcome of Hepatobiliary Tuberculosis among Filipino Children: Report of a Six-year Experience

Background@#The features and outcome of hepatobiliary tuberculosis (HBTB) have not been extensively reported in children.@*Objective@#To describe the clinical, biochemical, radiologic, microbiologic and histologic features and outcome of children diagnosed with HBTB. @*Methods@#Data of HBTB patients aged 0-18 years were collected by review of medical records and as they were admitted. Cases were classified as bacteriologically-confirmed (positive AFB smear, TB culture or PCR of bile/liver tissue) or clinically-diagnosed (clinical, histologic and/or radiologic evidence). @*Results@#A total of 36 patients were included (mean age: 13yrs; 64% males): three bacteriologically-confirmed and 33 clinically-diagnosed. Most common signs/symptoms were weight loss (69%), fever (67%), hepatomegaly (61%) and jaundice (53%). Of the total, 68% had hypoalbuminemia, 50% increased transaminases and 47% prolonged prothrombin time. Fifteen (42%) patients were AFB positive on various microbiologic specimens. Most common imaging finding was hepatic calcification (64%). Of 11 patients with liver biopsy, seven (64%) had chronic/ granulomatous inflammation. All 36 were managed medically. Eight were lost to follow up, six died, and 22 (61%) are alive, nine with complete resolution of liver disease. @*Conclusion@#Hepatobiliary tuberculosis presents with non-specific clinical and biochemical findings. Several investigations are necessary to confirm the diagnosis. Overall response to anti-TB treatment is satisfactory with possible resolution of liver disease.

A retrospective study on sensitivity, specificity, negative predictive value, positive predictive value of TB PCR versus TB Culture in diagnosing tuberculosis in Filipino children aged 3 months to 18 years at a tertiary care center

Objectives@#This study aimed to establish the accuracy of TB PCR versus TB culture and rifampicin resistance detection by PCR versus conventional susceptibility testing of body fluids in diagnosing tuberculosis in pediatric patients 3 months to 18 years with suspected tuberculous disease at a tertiary care center. @*Methods@#This is a retrospective analytical study of patients seen between January 1, 2012 to May 31, 2017, with clinical and radiographic features suggestive of tuberculosis, who had diagnostic testing of body fluids for TB PCR and TB culture. @*Results@#Among 159 patients suspected of TB, 46 (28%) tested positive by PCR, of which one was rifampicin-resistant. The sensitivity, specificity, positive predictive value and negative predictive values of TB PCR, using TB culture as the gold standard were 90%, 91.6%, 78.3%, and 96.5% respectively. The sensitivity, specificity, positive predictive value, and negative predictive values of TB PCR for detecting rifampicin resistance, using TB culture and sensitivity as the gold standard, were 33%, 100%, 100%, and 95%, respectively. Overall, the accuracy of TB PCR in detecting TB disease is 91.2% and the accuracy of TB PCR in detecting rifampicin resistance is 95%. @*Conclusion@#Findings in our study suggest that TB PCR play an important role in TB disease diagnosis, but clinical and radiological assessment continue to be essential in the diagnosis of childhood tuberculosis. The accuracy of TB PCR in detecting TB disease in children is 91.2% and the accuracy of TB PCR in detecting Rifampicin resistance is 95%.

Lurking in the dark: Latent Tuberculosis infection.

A subset of the tuberculous population has latent tuberculosis infection (LTBI). It is a condition wherein the affected individual is infected with Mycobacterium tuberculosis, but does not have any signs or symptoms of tuberculosis nor is he infectious to others. Risk of progression to active tuberculous infection is influenced by co-morbidities like HIV, diabetes, malignancy requiring chemotherapy, infants and children in close contact with susceptible individuals, and healthcare workers. Early diagnosis of LTBI is paramount. In addition to tuberculin test, Interferon gamma release assay (IGRA) is the new diagnostic modality that can be used for this purpose. Quantiferon-TB Gold In-Tube (QFTGIT) and T-SPOT TB are the two currently available IGRAs, of which the latter is slightly more preferred. More recently, TB PCR (Polymerase Chain Reaction) has aided accurate and early diagnosis of all forms of TB. While treating LTBI, it is observed that Isoniazid (INH) has stood the test of time and still prevails as the treatment of choice for active infection and for LTBI. Of course, adverse effects of INH and need for regular laboratory monitoring persist. Recently, moxifloxacin has been used as a substitute for INH. Newer drugs like rifapentine, nitromidazopyran, metronidazole and nitrofurans have all been tried with variable success and several clinical limitations, depending on comorbid conditions. India’s burden of extensive prevalence of TB is compounded by paucity of data on the same. The World Health Organization has estimated a mortality of 36 million by 2020 due to TB. This projection should encourage aggressive research into this entity.

An in-house multiplex PCR test for the detection of Mycobacterium tuberculosis, its validation & comparison with a single target TB-PCR kit.

Background & objectives: The conventional techniques used in TB diagnosis like AFB (acid fast bacilli) smear microscopy lack sensitivity and the gold standard, culture test takes time. A test based on multiplex polymerase chain reaction (PCR) targeting the 38 kDa gene and IS6110 insertion sequence, specific to Mycobacterium tuberculosis was developed to further increase the sensitivity of a TB-PCR kit targeting only 38 kDa gene developed earlier in the same laboratory. The multiplex test was validated using sputum samples from pulmonary TB (PTB) cases. The sensitivity and specificity were compared with AFB smear examination and Lowenstein-Jensen (LJ) culture test. Methods: Multiplex PCR amplifying 340 and 245 bp sequence of 38 kDa gene and IS6110, respectively was standardized and analytical sensitivity was verified. Sputum samples (n=120) obtained from PTB cases were subjected to AFB smear examination, LJ culture and a multiplex as well as single target PCR test. Additionally, 72 non-TB respiratory samples were included in the study as negative controls. Results: Analytical sensitivity of multiplex PCR was found to be 100 fg for 38 kDa gene and 1 fg for IS6110. Multiplex PCR, using both the targets, showed highest sensitivity of 81.7 per cent, followed by 69.2 per cent for L-J culture test and 53.3 per cent for AFB smear when clinical diagnosis was considered as a gold standard. The sensitivity of detection of M. tuberculosis in AFB smear positive and negative samples by multiplex PCR was 93.7 and 67.9 per cent, respectively. Sensitivity of 77.1 per cent observed for the detection of M. tuberculosis with single target PCR increased to 89.2 per cent with multiplex PCR in culture positive samples. Four samples showed positive PCR results only with primers for 38 kDa gene. Interpretation & conclusions: Multiplex PCR increased the sensitivity of single target PCR and will be useful in diagnosing paucibacillary smear negative samples. Further, it can also be used to detect samples with M. tuberculosis strains lacking IS6110.

Usefulness of Automated PCR Test for the Detection of Mycobacterium Tuberculosis in Fresh Biopsy Tissues / 결핵및호흡기질환

BACKGROUND: Although there have been several studies regarding the clinical value of an automated TB-PCR study using sputum, bronchial washing, and other body fluid samples for the detection of pulmonary tuberculosis, there are only a few reports on the use of fresh tissue samples. MATERIALS AND METHODS: The acid-fast bacilli stain(AFB), tuberculosis culture, automated TB-PCR study, and histopathology examination were performed in 42 fresh tissue samples. RESULTS: Among the 42 cases, 18 cases were diagnosed with tuberculosis based on the clinical findings. Sixteen of the 18 cases were TB-PCR positive and of these 16 cases, only 2 cases were positive in the AFB stain or culture study. However, all 18 cases showed the histopathology findings of chronic granulomatous inflammation that was compatible with tuberculosis. Based on the clinical findings, the sensitivity, specificity, positive predictability, and negative predictability of the automated TB-PCR study were 88.9%, 100%, 100%, and 92.3% respectively. CONCLUSION: An automated TB-PCR assay is an important diagnostic tool for diagnosing tuberculosis in fresh tissue samples.