Evaluation of PCR using TRC(4) and IS6110 primers in detection of tuberculous meningitis.

We have evaluated a new set of primers (TRC(4)) in comparison with the IS6110 primers commonly used in PCR to detect tuberculous meningitis among children. The levels of concordance between the results of IS6110 PCR and TRC(4) PCR with cerebrospinal fluid specimens from patients with clinically confirmed tuberculous meningitis were 80 and 86%, respectively. Results with the two primer sets were concordant for 55 positive and 22 negative specimens (n = 98). We conclude that the sensitivity of PCR can be increased by using both IS6110 and TRC(4) primers.

Excessive free radical generation in the blood of children suffering from asthma.

The aim of the present study is to evaluate the biochemical parameters in blood relevant to oxygen free radicals and antioxidant defenses in children with asthma. A total of 210 asthmatic children, aged 5-18 years, were studied at two different times, once during a severe episode of wheeze (during episode category) and the other after recovery (resting condition). A total of 180 healthy children participated in the study as age and sex matched healthy controls. Superoxide and hydroxyl radical assays were used as a measure of free radical formation. Antioxidant enzymes and free radical scavengers in blood were also assayed. Lipid peroxidation products were assayed in plasma and erythrocytes to evaluate the imbalance (if any) between oxidant (radical) formation and their inactivation. Serum IgE concentrations and peak expiratory flow rate (PEFR) were used as measures of allergic reactions and residual lung capacity, respectively. Excessive production of superoxide and hydroxyl radicals were noted in the blood cells in asthmatics and were correlated to the severity of disease measured as PEFR. Superoxide dismutase and free radical scavengers in blood were significantly lower in asthma, even during resting condition. The present observations endorse the correlation between disease severity and oxygen radical production in asthma subjects. Oxygen metabolites may play a direct or indirect role in the modulation of airway inflammation. Excessive superoxide and hydroxyl radical production may be used as a marker for susceptibility to asthma and for monitoring therapeutic measures.

Tuberculin and BCG tests.

The tuberculin test is widely used for the diagnosis of tuberculosis in children as it is the only one that provides evidence of infection with M. tuberculosis. Of the tuberculins that are available, the most widely used are PPDS and PPDRT 23, in various strengths. A positive test indicates prior infection with the tubercle bacillus but not necessarily active disease. A positive test may also result from BCG vaccination though the response is usually less than 10 mm and tends to wane with time. In areas with a high prevalence of atypical mycobacteria in the environment, positive reactions may also be due to cross-reactivity. BCG has been recommended by some workers as a diagnostic test but suffers from the disadvantages of low specificity.

Survival of childhood acute lymphoblastic leukemia: experience in Chennai.

The object of this study was to evaluate the treatment outcome in children with acute lymphoblastic leukemia (ALL) in Chennai. The problems inherent in a developing country which affect outcome are analyzed. The importance of prognostic factors especially immunotyping is assessed. The period of study was from June 1991 to December 1995. A total of 135 children were studied. Pre B CALLA positive (CD10, CD19, HLA, DR) was the dominant immunotype in 75 children (69 per cent). T-cell ALL was seen in 15 (14 per cent), biphenotype in three (2 per cent), and B in one (0.9 per cent). Seventy children (53 per cent) were treated with a high risk protocol, 25 (17 per cent) received an intermediate risk, and 40 patients (30 per cent) received a standard risk protocol. Analyzing the outcome in 135 children, 34 (27 per cent) had event free survival (EFS) at the time of analysis; of these 41 per cent had EFS after 2 years of therapy, 31 per cent after 3 years and 18.7 per cent after 4 years (i.e. 1 year after stopping 3 years of therapy). Fifty-seven children (41 per cent) dropped out; 25 (18 per cent) died due to sepsis. Treatment obstacles included delay in diagnosis, poor health education and facilities, poor supportive care, and socio-economic problems.

Sino-bronchial syndrome in children with asthma.

Thirty children in the age group of 2 to 12 years were brought with a history of recurrent non-seasonal moderate to severe wheezy episodes associated with symptoms of nasal congestion, sneezing and occasional headache. All of them had maxillary or pan sinusitis with 26 having associated right, left or bilateral lower lobe pneumonitis or bronchiectasis. Serum immunoglobulins were normal in 22 and was not done in eight. There was positive (2 to 4+ above negative control) skin test response to dust and dust mite in 15 of the 22 children tested. Throat swabs/sputum or nasal secretions grew B-hemolytic streptococcus or streptococcus pneumoniae in twenty-seven. All the children were put on bactericidal drugs for 6 to 8 weeks and bronchodilators were used when needed. At the end of 6 to 8 weeks follow-up X-ray of sinuses and chest showed significant clearing of the lesions which coincided with marked clinical improvement. Sinus X-ray should be considered in bronchial asthma resistant to medical management since untreated bacterial sinusitis can be an underlying cause of chronic poorly controlled asthma.

Patterns of resistant Salmonella typhi infection in infants.

Culture-proven cases of enteric fever (182) were studied during the period May 1991 to April 1992; 39 per cent of the children were below 3 years. There was male preponderance. Infants presented within first few days of onset of fever with severe systemic manifestation, such as repeated convulsion, puffiness of face and oedema, massive hepatomegaly, and bleeds due to thrombocytopenia. Only 49-52 per cent of the cultures were sensitive to ampicillin, chloroamphenicol, and cotrimoxazole. The infants were treated with cephalosporin such as cefotaxime or quinolones as ciprofloxacin, since 100 per cent of the cultures were sensitive to this drug. Three infants had meningitis, two interstitial nephritis, and six had marrow hypoplasia. Two children who had been treated prior to admission with ampicillin or chloroamphenicol died within 48 h of admission, one of a liver abcess and peritonitis, and the other due to meningitis. Markedly prolonged hypothermia was seen during recovery in few cases. Forty-six per cent of infants had complications as against 2 per cent in older children. Drug Resistant Salmonella typhi infection seems to have a rapidly progressive severe course with multiple organ involvement such as meningitis, liver abcess, nephritis, and marrow hypoplasia. Initiation of appropriate antibiotics depending on local sensitivity pattern is needed early in the disease to avoid mortality and morbidity.

Varied manifestations of viral myocarditis.

Nine children in the age group of new born to 10 years were seen during the period October 1989 to January 1993 with varying manifestations of Myocarditis. This ranged from cardiogenic shock due to fulminant cardiac failure, recurrent wheezy episodes (mistakenly treated as bronchial asthma) bronchiolitis and rhythm disturbances. Clinical picture was collaborated by radiological evidence of cardiomegaly, ECG changes of low voltage QRS complexes with ST depression, T wave inversion or signs of left ventricular dilatation. SGOT, SGPT, CPK, LDH were elevated significantly in 7 cases. Echocardiographic changes ranged from left ventricular dilatation to global hypokinesia and mild mitral incompetence. Viral studies suggested infection with Coxsackie B1 in 4 cases, B4 in 2, B5 in 2 and Dengue 3 in 1 case. All the children recovered well with routine anti failure measures and treatment of arrhythmias and 2 children needed steroid therapy. At the end of follow up of 6 months to 1 year there has been complete reversal of ECHO changes to normal. Viral Myocarditis can manifest in varied ways in children and if treated adequately may lead to complete recovery.

Immunological spectrum of childhood tuberculosis.

Fifty-three children with tuberculous meningitis (TBM) were studied in parallel with 37 children with primary pulmonary complex (PPC), 32 tuberculin skin positive controls, and 38 skin negative controls for immunological evaluation. Proportions of peripheral blood total T and T helper lymphocytes (TH) were significantly reduced in TBM (T55, TH32) as compared to PPC (T70, TH40) and Controls (T74, TH43), but response to mitogens phytohaemagglutinin (PHA) and poke weed mitogen (Pwm) were comparable in all the groups. Response of peripheral blood lymphocytes to tubercular protein (PPD) was significantly greater in the tuberculin skin positive group, but comparable between the TBM and PPC groups. There was no significant difference in the proportion of B lymphocytes, antibody levels to PPD and monocyte capacity to release hydrogen peroxide in the four groups. These findings suggest that there is no definite immunological spectrum in childhood tuberculosis.

Maternal fetal immunological relationship particularly mycobacterial immunity.

Thirty-nine paired maternal and cord blood from normal full term deliveries were tested for lymphocyte function by proliferative response to mitogens-Phytohemagglutinin-P (PHA) and Poke week mitogens (PWM). Monocyte function was assessed by the ability of the monocytes to release hydrogen peroxide (H2O2) in response to standard stimulus (PMA). Mycobacterial immunity was assessed by lymphocyte proliferative response to purified proteins derivative (PPD) and IgM and IgG antibody response to H37Rv and 5 atypical mycobacteria. Lymphocyte functions were significantly lower in cord blood (PHA 20.6, PWM 21.2) as compared with maternal blood (PHA 65.8, PWM 37.8). The capacity of fetal monocytes to release H2O2 was comparable to maternal monocytes. The mean proliferative response of fetal lymphocytes to tubercular protein (PPD) was 0.67 as compared (P less than 0.01) to maternal lymphocytes (3.79). Nearly 86% of the cord blood did not show any response to PPD. None of the cord blood showed IgM antibody response to H37Rv nor to any of the range of 5 atypical mycobacteria though maternal IgM and IgG response was present. There was only passive transfer of IgG antibody from mother to fetus. Hence, though this is a highly endemic area for atypical mycobacteria and M. tuberculosis, there was apparently no transplacental transfer of antigen in normal sensitized mothers.

Post-streptococcal acute glomerulonephritis: a clinical, bacteriological and serological study.

Eight hundred and sixty four children were admitted with Acute post-streptococcal glomerulonephritis (APSGN) at the Institute for Child Health, Madras, during the period January 1981 to January 1983. Majority of the cases followed infected scabies or impetigo. 135 children were investigated and followed up for a period of 1-2 years. The disease had an excellent prognosis in these children. None of those examined 2 years after discharge had proteinuria or hypertension. Group A beta hemolytic streptococcus (BHS) was isolated in 13.4% of patients and 11.25% of skin infection controls. Eight different T types were identified in patients and 6 T types in pyoderma cases. All patients and 87% of skin infection controls had elevated anti-D Nase B titres, while ASO titres were not significantly raised.

Cell mediated immunity in childhood malaria.

Children with malarial infection, due to P. Vivax and P. falciparum, were tested for cell mediated immunity (CMI) by lymphocyte proliferative response to mitogens PHA (phytohaemagglutinin) and PWM (poke weed mitogen) and antigen PPD (purified protein derivative). This was done during the period of parasitemia and after treatment, and compared to 19 normal matched controls. There was no significant difference between the patients and the control group with regard to PHA (patients 57.4 +/- 50.5; controls 61.3 +/- 54.9); PWM (patients 27.4 +/- 19.9, controls 29.9 +/- 24.5); PPD (patients 2.2 +/- 1.2, controls 1.9 +/- 1.4). There was also no significant difference in the lymphocyte responses during the period of parasitemia and after treatment. Hence, there does not seem to be any depression of CMI as shown by lymphocyte proliferative responses during childhood malaria.