Tuberculous meningitis in children: Clinical management & outcome

Although the occurrence of tuberculous meningitis (TBM) in children is relatively rare, but it is associated with higher rates of mortality and severe morbidity. The peak incidence of TBM occurs in younger children who are less than five years of age, and most children present with late-stage disease. Confirmation of diagnosis is often difficult, and other infectious causes such as bacterial, viral and fungal causes must be ruled out. Bacteriological confirmation of diagnosis is ideal but is often difficult because of its paucibacillary nature as well as decreased sensitivity and specificity of diagnostic tests. Early diagnosis and management of the disease, though difficult, is essential to avoid death or neurologic disability. Hence, a high degree of suspicion and a combined battery of tests including clinical, bacteriological and neuroimaging help in diagnosis of TBM. Children diagnosed with TBM should be managed with antituberculosis therapy (ATT) and steroids. There are studies reporting low concentrations of ATT, especially of rifampicin and ethambutol in cerebrospinal fluid (CSF), and very young children are at higher risk of low ATT drug concentrations. Further studies are needed to identify appropriate regimens with adequate dosing of ATT for the management of paediatric TBM to improve treatment outcomes. This review describes the clinical presentation, investigations, management and outcome of TBM in children and also discusses various studies conducted among children with TBM.

Tuberculosis of the temporomandibular region

Objective:@#To describe a unique case of extrapulmonary tuberculosis (TB) of the temporomandibular area focusing on its insidious and destructive course over a 2-year period with insights into the diagnostic and therapeutic pitfalls encountered throughout its clinical development. @*Methods:@#Study Design: Case Report. Setting: Tertiary Government Hospital. Patient: One. @*Results@#A 33-year old man initially presented with right pre-auricular swelling and trismus that were unresponsive to antibiotic therapy. On subsequent follow-ups, initial symptoms were accompanied by a non-healing right pre-auricular wound, right ear discharge, trismus, and right facial paralysis (House-Brackmann III). Cranial and temporal bone computed tomography scans revealed osteolytic destruction of the right temporomandibular region extending to the auditory canal and of the right mastoid bone extending to the right mandibular condyle and parotid. Infected malignancy of the parotid, mandible and temporal bone were considered, but definitive diagnosis from an incision biopsy revealed caseating granulomatous inflammation consistent with tuberculosis. He was started on anti-tuberculosis medications with significant resolution of pre-auricular swelling, non-healing pre-auricular wound, facial paralysis and ear discharge but minimal improvement in mouth opening.@*Conclusion@#Tuberculosis of temporomandibular region is rare and is associated with nonspecific manifestations. Delay in diagnosing and initiating appropriate treatment can lead to morbidity and serious complications involving destruction of the temporal bone, middle ear, mandible and parotid gland over its progression. A high index of suspicion by the physician and awareness of the patient’s health seeking behaviors could have aided in the early diagnosis and treatment of this extrapulmonary TB.

Vitamin D levels in Indian children with intrathoracic tuberculosis.

Background & objectives: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. Methods: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. Results: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (≥ 20 ng/ml). lLevels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient (p<0.05). Interpretation & conclusions: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did.

Hígado y terapia antituberculosa / Hepatotoxicity of antituberculosis therapy

La toxicidad hepática en pacientes tratados con drogas antituberculosas es relativamente infrecuente, probablemente debido a este hecho no contamos con una buena definición de toxicidad hepática. Existen algunas condiciones de los enfermos en que la hepatotoxicidad es más frecuente, tales como pacientes envejecidos, bebedores de alcohol, desnutrición, uso de ciertas drogas e hipoalbuminemia. Las drogas antituberculosas más frecuentemente involucradas en hepatotoxicidad son la pirazinamida, la isoniacida y la rifampicina. En este artículo analizamos el problema clínico de la hepatotoxicidad de la terapia antituberculosa y proponemos el manejo de diferentes situaciones. Discutimos cuando se debe suspender la administración de una droga, cómo se debe evaluar el daño hepático y qué drogas alternativas pueden usarse durante el tratamiento de la tuberculosis.

Liver toxicity in patients being treated with antituberculosis drugs is relatively uncommon, although transient elevation of liver enzymes is very common. Probably because of this there is not a good definition for liver toxicity. There are conditions in which hepatotoxicity is more frequent, such as elderly patients, alcohol consumption, malnutrition, use of certain drugs, and hypoalbuminemia. Pirazinamide, isoniazid and rifampicin are the antituberculosis drugs more commonly involved in liver toxicity. In this article we analyze the clinical problem of hepatotoxicity of antituberculosis therapy and propose the management of different situations. We discuss when a drug administration should be discontinued, how liver damage should be assesed and which alternative drugs should be used during the antituberculosis treatment.

Adverse Effects of Antituberculosis Drugs and the Solutions

The principle of antituberculosis therapy is to apply a combination regimen of at least two bactericidal drugs to which the bacteria are susceptible for sufficient duration, thus improving the efficacy of the therapy and preventing the development of resistant strains. If a certain side effect develops during the therapeutic trial, the next step includes identifying the causative drug, estimating the type and magnitude of the side effect, and finally deciding whether the regimen should be discontinued. In a clinical setting, however, these decisions cannot be made easily. Many antituberculosis drugs causes similar side effects, and even if the causative drug is identified, the decision to discontinue the drug must be based on its relative importance in the current antituberculosis regimen. Effective application of antituberculosis medication requires the physician to fully understand what adverse effects each drug is associated with, which side effect necessitates withdrawal of the drug, and how to rechallenge the drug with side effects when it is absolutely required in the regimen.