Tuberculosis continues to be a nationwide problem in spite of the efforts by the government to subdue this disease like giving free BCG vaccines and Anti-TB meds. The Philippine Pediatric Society in cooperation with the Philippine Academy of Pediatric Pulmonologists provided us with the Childhood TB guidelines way back in 2008 and the society is currently waiting for the latest edition which will come out this year. In the interim, PPS held its 4th Scientific Meeting for the year last August to review and clarify some of the issues regarding Tuberculosis.
The video conference was held last August 25, 2016 from the PPS Auditorium and simulcast at the Asian Hospital and the PPS Central Visayas Chapter, specifically, Cebu. The Invocation was led by the PPS treasurer Dr. Florentina Ty. The welcome remarks was given by the Director of the Council on Continuing Professional Development, Dr. Francis Xavier Dimalanta, and the speaker was introduced by the Philippine Academy of Pediatric Pulmonologists president, Dr. Mary Therese Leopando. The speaker, Dr. Agnes Rico-Mendoza, gave the following learning outcomes for the session: When to expect? How to screen? How to make a diagnosis? When to request for new diagnostic tests? Review treatment and prevention of childhood tuberculosis.
In children, tuberculosis should be suspected in the presence of the following: Cough or severe pneumonia that is not improving; weight loss or failure to gain weight or severe malnutrition; prolonged fever; cervical lymphadenopathy of >1.5 cm; persistent symptoms (>2 weeks) without improvement following: 1) broad-spectrum antibiotics for pneumonia, 2) anti-malarial treatment for fever or 3) nutritional rehabilitation for malnutrition. Risk Factors for TB Infection include: contact with source case (proximity and duration), source case characteristics (smear positivity and cavities on CXR), increased exposure (high endemic communities and children of families living with HIV). While Risk Factors for TB Disease are: Immunosuppression (malnutrition, post-measles, HIV), age <5 years, and no BCG vaccine. Dr. Mendoza also reiterated the WHO symptom-based screening which stated that for symptomatic children who are in close contact with a case of sputum smear-positive TB, evaluation for TB disease is recommended. If the exposed child is >5 years old and is asymptomatic, no treatment is given. However, if the exposed, asymptomatic child is under 5 years of age, preventive therapy is already warranted. Careful attention should be given to the atypical clinical presentations of TB like acute severe pneumonia unresponsive to antibiotics; in asymmetrical, persistent wheezing not responsive to bronchodilators which may indicate an enlarged tuberculous hilar lymph nodes; and in HIV-infected children. The WHO recommends that all children with suspected TB should be tested for HIV because of the marked clinical overlap between the two and the impact that HIV infection has on PTB treatment. Contact screening is also recommended to aid in active case-finding and preventive therapy for at-risk contacts without TB. It should be remembered that children usually develop TB within 2 years after exposure, about 90% of which, happen in the first year. That is why, if no source case is identified, always look for someone in the household who is experiencing chronic cough. There is a 30-40% risk of acquiring TB from a sputum smear(+) household exposure. On the other hand, the likelihood of getting TB based on intensity of exposure and geographic proximity to smear(-) source is at 17%. It was also emphasized that close contact with source case with sputum(+) PTB has more value than the tuberculin skin test.
Extrapulmonary tuberculosis such as TB adenitis, Pleural TB, TB meningitis, Miliary TB, Abdominal TB, Spinal TB, TB of the bones and joints, and pericardial TB were also discussed. The value of the tuberculin skin test(TST) was also reiterated. TST is used as an adjunct in the diagnosis of TB infection. The target population for TST include: contacts of person with active TB, foreign born, history of travel or household visitors from a TB-prevalent country (Mexico, Philippines, Vietnam, India, China), high-risk adult contacts (homeless, incarcerated, HIV, IV drug users), and chronic illness (DM, renal failure, malnutrition, immunodeficiencies). In high risk children (exposed, <5 years old, HIV) the cut-off is >5mm . Positive result for all other children with or without BCG is a measurement of >10mm. A negative skin test, though, does not rule out PTB. Newer modalities of latent TB testing were discussed. In Vitro interferon-γ Release Assays (IGRAs) is marketed as Quantiferon TB-gold(QFT-G) and enzyme-linked immunospot assay (ELISPOT). QFT-G has >70% sensitivity and >90% specificity for diagnosing latent TB while ELISPOT has a sensitivity and specificity of >90% and >93%, respectively. IGRAs compared with TST, are more specific, as they are not shared with any BCG vaccine or selected non-TB strains hence, avoids overdiagnosis of TB. Gene Expert, another alternative diagnostic, utilizes real-time PCR technology to both diagnose TB and detect rifampicin resistance with a case detection rate of 76% and specificity of 98.8% (Nicol, et.al., 2011). Other notable diagnostics mentioned were Gas Sensor Assay, In-house Nucleic Acid Amplification (NAA) Assays, Serum Adenosine Deaminase (ADA), and the Polymerase Chain Reaction (PCR). The PCR which has >90% sensitivity and specificity may be used to determine TB in the following: 1) difficult samples with negative microscopic exam, negative culture, or scarce sample; 2) differentiate M. tuberculosis from atypical mycobacteria from samples; and 3) identify genetic variations that could lead to anti-mycobacterial agent resistance. Hence, PCR may have a special role in the diagnosis of extrapulmonary and pulmonary TB especially in children where sputum smears are usually unrevealing. Although the discussed innovative diagnostics looks promising, availability and cost may be an issue for some of the patients.
Careful history (TB contact and symptoms suggestive of TB), clinical examination (including growth assessment), tuberculin skin test, bacteriological confirmation whenever possible, investigations relevant for suspected PTB or EPTB, and HIV testing remains relevant in the diagnosis of tuberculosis. Dr. Mendoza emphasized, however, that neither TST nor culture is required for making a decision to treat for TB in cases where both diagnostics are not available.
The WHO revised dosages for the anti-TB meds for children up to 25 kilograms, which, the Pediatricians are reminded to use in the treatment course, are as follows: Rifampicin(R) 15 (10-20) mkday (max: 600mg/day), Isoniazid(H) 10 (10-15) mkday (max: 300mg/day), Pyrazinamide(Z) 35 (30-40) mkday, and Ethambutol(E)) 20 (15-25) mkday. Children above 25 kg may use the adult dosages and preparation. The revisions were done to minimize the risk of drug-induced hepatotoxicity. Other revisions in the recommendation include: 1) Four drugs (HRZE) in intensive phase for all new cases in HIV endemic setting 2) No intermittent(twice-weekly or thrice-weekly doses) regimens in HIV-endemic setting 3) Streptomycin no longer recommended as first-line therapy and 4) 12- month regimens for TB meningitis and osteo-articular TB (HRZE for 2 months, HR for 10 months). For MDR-TB, Fluoroquinolone is the treatment of choice.
Many pediatricians are still wary of giving Ethambutol in the intensive phase treatment because of its many side effects. However, Dr. Mendoza reminded everybody that the risk of toxicity in children is negligible when used in recommended dosages and at a limited duration of time, which is 2 months.
Response to anti-TB treatment is usually noted by the end of the intensive phase as indicated by resolution of symptoms and weight gain. Failure to do so may indicate: poor adherence, incorrect diagnosis, drug resistance, incorrect dosages, and co-morbidities like HIV. Hence, it is recommended that HIV status should be determined in all children treated for TB. Approaches to childhood TB prevention include: Improved case-finding and management, BCG immunization for severe disseminated TB, and contact screening and management. These approaches, however, should not only be the responsibility of the pediatrician but requires team effort from the family, the physician, the LGUs, and the DOH.
Thank you to Dr. Soidemer Claire C. Grecia for contributing this article.