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.

Comparative growth pattern of multi drug resistance versus susceptible isolates of Mycobacterium tuberculosis in mice lungs.

Background & objectives: Rise in prevalence of multi-drug resistance (MDR) in tubercle bacilli is a serious cause of concern. As mutations with two house keeping genes rpoB and katG are associated with resistance to two important anti-tubercular drugs rifampicin and isoniazid respectively, there is a need to understand the growth kinetics of organisms with such mutated genes in experimental animals. This study was undertaken to study the growth kinetics of susceptible as well multi-drug resistance Mycobacterium tuberculosis isolates in mice. Methods: Two MDR (having mutations in rpoB and catG) and two drug susceptible isolates of M. tuberculosis along with H37Rv were grown in mice after aerogenic infection. Results: The MDR isolates grew slowly up to 3 wk though the growth was significantly different from sensitive strains. However, after 3 wk, the growth in sensitive as well MDR strains was similar, suggesting that even the mutations in the MDR strains did not have any impact on the growth kinetics. Interpretation & conclusions: The effect of mutations in other parts of these genes need to be studied. Retention of property of MDR strains to establish infection after aerogenic infection has epidemiological significance in terms of the transmission of MDR tuberculosis.

PCR and in-situ hybridization for diagnosis of leprosy.

OBJECTIVE: To assess the diagnostic value of Polymerase Chain Reaction (PCR) and in situ hybridization. METHODS: This prospective study was carried out in 22 patients RESULTS: The histopathological examination confirmed the clinical diagnosis in 27.2% cases only. In situ hybridization showed a positivity of 42.8% in early (I/BT) and 46.7% in BB/BL group. In situ hybridization thus enhanced the diagnosis by 18.1%. PCR targeting 36 kDa gene of M. leprae was performed on 15 cases. In these 15 cases, histopathology confirmed the diagnosis in 4 cases (26.6%) and PCR confirmed the diagnosis in 10 cases (66.6%), thus enhancing the diagnosis by 40%. CONCLUSION: 36 kDa PCR and in situ hybridization enhance the diagnosis of leprosy when compared to routine histopathology. They are important diagnostic tools for definitive diagnosis in early and doubtful cases of leprosy.

Diagnostic value of in situ Polymerase Chain Reaction in leprosy.

OBJECTIVE: This prospective study was carried out to assess the diagnostic value of in situ Polymerase Chain Reaction in leprosy, particularly in enhancing the histopathological diagnosis. METHOD: Clinical examination of 20 patients (< 16 yr) was done and skin smear for AFB was prepared. Biopsy of lesion site was taken for histopathological examination and in situ PCR testing. RESULTS: The histopathological examination confirmed the clinical diagnosis in 45% cases only; non-specific histopathology was reported in the remaining 55% cases. In situ PCR showed a positivity of 57.1% in early/localized form of leprosy (IIBT) and 61.5% in (BB/BL) group. When compared to histopathology examination, a significant enhancement of 15% in diagnosis was seen. With in situ PCR, the diagnosis could be confirmed in 4/11 (36.3%) cases with non-specific histopathological features, (which is common in early disease) in addition to confirmation of 8/9 (88.8%) histopathologically-confirmed tissue sections. Histopathology and in situ PCR, combined together, confirmed the diagnosis in 13/20 cases (65% of total cases). CONCLUSION: Thus, in situ PCR is an important diagnostic tool especially in early and doubtful cases of leprosy.

Patients presenting with defined areas of sensory loss--a preliminary study.

Thirty patients presenting with circumscribed areas of clearly demonstrable hypoesthesia were chosen from amongst those attending this Institute. Their history and clinical features were recorded, lepromin test was done for reading at four weeks, and peripheral part of the hypoesthetic area was biopsied for histopathology and immunostaining. The subjects were predominantly adult males with the symptomatic sites limited to the extremities. On routine histopathological examination of the symptomatic sites, the diagnosis of leprosy, using defined criteria, could be made in six cases (20%). Immunostaining of the remaining sections showing either no pathology or a nonspecific pathology revealed the presence of mycobacterial antigen in five of the 24 cases (20.83%). Overall, leprosy could be diagnosed in 11 of the 30 cases studied (36.66%). This study shows that leprosy may be an important cause of circumscribed areas of sensory deficit.

Assessment of viability by normal mouse foot-pad and bacillary ATP bioluminescence assay in multibacillary cases treated with an MDT regimen using conventional as well as newer drugs like minocycline and ofloxacin.

The therapeutic effect of a drug regimen of conventional drugs as well as newer drugs like ofloxacin and minocycline in smear-positive multibacillary (MB) leprosy cases was assessed by mouse foot-pad and ATP bioluminiscence methods. Biopsies were taken before starting treatment and after one year of treatment. They were processed for viability assessment by normal mouse foot-pad inoculation and bacillary ATP assay techniques. The test regimen was quite effective in its anti-bacterial effect as it was found to result in loss of bacillary viability in all the cases, as assessed by both methods.

The nature of bones and joints: a new perspective.

In human ontogeny recapitulating phylogeny, bones arrive late on the scene--long after neurogenesis, musculogenesis, organogenesis and so on are over--as islands of ossification in an ocean of collagen. This study confirms this developmental sequence by demonstrating, in cadavers, the rather independent nature of bone, to which nothing--muscle, tendon, ligament or articular cartilage--is attached. Bone is like the air in a tubeless tyre; it gives rigidity and shape to the tyre, and in return takes the shape of the tyre. The tibia, for example, is the bony tissue that is contained in tyre-like casing made of peritibial soft tissues whose inner limit is the periosteum, which continues proximally and distally as capsules of knee/ankle joint, and to which only are the articular cartilages of the knee and ankle attached, being clearly free from the bones. This study also exposes the truer nature of a joint wherein the articular cartilage assumes anatomic and physiologic significance hitherto unthought of.