Tuberculin reaction in children treated with isoniazid

This study involved 370 children infected by Mycobacterium tuberculosis. Follow-up tests, three to nine years after a course of isoniazid treatment, showed that the tuberculin reactions remained strongly positive, although some fluctuation in size was observed. The persistence of tuberculin hypersensitivity in these patients was considered an asset, as delayed-type hypersensitivity and cell-mediated immunity are related closely, according to recent studies on antituberculosis immunology. With the risk of endogenous disease removed by isoniazid treatment, the patients gained a bonus of cell-mediated immunity to protect them from future exogenous reinfection.     

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa.

BACKGROUND: Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children. AIMS: To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children. SUBJECTS AND METHODS: 149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrollment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis. RESULTS: Sputum induction was successfully performed in 142 of 149 children. M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosis was cultured in 10 of 100 HIV infected children compared to six of 42 HIV uninfected children (p = 0.46). CONCLUSION: Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.     

Pyridoxal‐5‐phosphate plasma concentrations in children receiving tuberculosis chemotherapy including isoniazid

Aim: Little is known about pyridoxine nutriture of children treated with isoniazid (INH) regimens. This study documents plasma pyridoxal 5′‐phosphate (PLP) concentrations in children, HIV‐infected and HIV‐uninfected, receiving INH regimens. Methods: Children from the Western Cape of South Africa hospitalized for tuberculosis (TB) management were studied. Plasma PLP concentrations were determined on enrolment, 1‐month after commencing TB treatment, and again after 4‐month’s treatment. The children received a supplement meeting pyridoxine requirements. Results: Nineteen HIV‐infected and 33 HIV‐uninfected children received INH (dosage range 4–20 mg/kg) daily. Mean PLP plasma concentrations on enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV‐infected and HIV‐uninfected children, respectively (p = 0.11) and after 4‐month’s treatment 6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p < 0.001). On enrolment 9 (50%) HIV‐infected and 5 (15%) HIV‐uninfected children (p = 0.016) had suboptimal PLP concentrations (<6 ng/mL); after 4‐month’s treatment 8 (42%) and 2 (6%) (p = 0.004). Conclusion: Plasma PLP concentrations in children treated for TB were low on enrolment in HIV‐infected and HIV‐uninfected children; after 4‐month’s treatment low values were still common in HIV‐infected children. Additional pyridoxine supplementation of malnourished children treated for tuberculosis is advisable, particularly those HIV‐infected.     

Intermittent isoniazid and thiacetazone in childhood tuberculosis with reference to clinical intolerance

Summary One hundred and forty-eight children with tuberculosis of the various organs (lungs, pleura, lymphnodes, intestine, peritoneum) were given thiacetazone and isoniazid daily for the first month and then twice a week to study the intolerance to these drugs as manifested by signs and symptoms for a period ranging from 1 month to 24 months. Twenty-five children (16.9%) had some adverse reactions like nausea, vomiting, anorexia, diarrhoea, pruritis, rashes and urticaria, during the first month of therapy except one child who developed a bluish discoloration of the nails after about 9 months of therapy. None of these manifestations was severe enough to warrant withdrawal of the drugs. From the Department of Child Health, R.N.T. Medical College, Udaipur.     

CONTROL OF STREPTOMYCIN AND ISONIAZID IN MALNOURISHED CHILDREN TREATED FOR TUBERCULOSIS

Abstract Akbani, Y., Bolme, P., Lindblad, B. S. and Rahimtoola, R. J. (The Paediatric Clinics ofJinnah Postgraduate Medical Centre, Karachi, Pakistan and St. Goran's Children's Hospital, Stockholm, Sweden). Drug control of streptomycin and isoniazid in malnourished children treated for tuberculosis. Acta Paediatr Scand, 66:237, 1977.—In 12 malnourished children, who were treated for tuberculosis, plasma levels of streptomycin and isoniazid were followed. Streptomycin was administered i.m. in a dose of 25–50 mg/kg/24 hours. High initial plasma levels were reached (mean: 44.3 μg/ml at 30 min). Streptomycin levels were followed for 5 hours and the mean plasma level at that time was 17.0 μg/ml. From the present data a plasma half life of streptomycin of 3.5 hours has been estimated. It is advised that streptomycin should not be given in doses above 25 mg/kg/24 hours to avoid potential toxic plasma levels especially if plasma levels cannot be measured. It is also concluded from our study that renal function is not affected in malnourished children to an extent where streptomycin clearance is greatly affected. Isoniazid was given orally, 10 mg/kg/24 hours. From 30 min to 6 hours after administration, mean plasma levels of isoniazid above 0.5 μg/ml were observed. In all children measurable plasma levels were obtained. It is concluded that also children with malnutrition can absorb isoniazid after oral administration. From our data it is suggested that the majority of the children in our study were rapid inactivators of isoniazid.     

Short course chemotherapy for childhood tuberculosis

A prospective study, with an attempted 24-month-post-treatment follow-up, of children with tuberculosis (TB) treated with short course chemotherapy (SCC) for 6 months was carried out because published experience of SCC in childhood TB was limited. All children in Port Moresby diagnosed as having TB between November, 1984, and November, 1986, entered the trial. Of the 639 children 165 (26%) were younger than 2 years old. Of these, 227 (35%) had extrapulmonary TB (peripheral lymph node, 110; central nervous system, 43; abdominal, 27; miliary, 16; bone and joint, 11; pleural, 11; polyserositis, 9). Clinical response to SCC was rapid. Adverse drug reactions occurred in 15 (2%), mainly to streptomycin. Twelve (2%) died, 38 (6%) transferred out and 145 (28% of the 518 who did not die, transfer or live too far from a treatment centre) defaulted. Three hundred seventy-three (58%) completed a 2-month course of daily rifampin, isoniazid, pyrazinamide and streptomycin followed by a 4-month course of twice weekly rifampin and isoniazid. A further 71 (11%) had their treatment modified because of their distance from a treatment center. Only 70 (19%) of the 373 children available for post-treatment follow-up attended the every-3-month follow-up visits for 24 months, although 223 (60%) attended one or more of the follow-up visits. Seven of the 373 children relapsed, mostly within 3 months. Five of these children had been irregular with their treatment. SCC for childhood TB is safe and effective for pulmonary and extrapulmonary disease.     

Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa

BACKGROUND—Bacteriological confirmation of pulmonary tuberculosis is difficult in infants and young children. In adults and older children, sputum induction has been successfully used; this technique has not been tested in younger children.
AIMS—To investigate whether sputum induction can be successfully performed in infants and young children and to determine the utility of induced sputum compared to gastric lavage (GL) for the diagnosis of pulmonary tuberculosis in HIV infected and uninfected children.
SUBJECTS AND METHODS—149 children (median age 9 months) admitted to hospital with acute pneumonia who were known to be HIV infected, suspected to have HIV infection, or required intensive care unit support. Sputum induction was performed on enrolment. Early morning GL was performed after a minimum four hour fast. Induced sputum and stomach contents were stained for acid fast bacilli and cultured for Mycobacterium tuberculosis.
RESULTS—Sputum induction was successfully performed in 142 of 149 children. M tuberculosis, cultured in 16 children, grew from induced sputum in 15. GL, performed in 142 children, was positive in nine; in eight of these M tuberculosis also grew from induced sputum. The difference between yields from induced sputum compared to GL was 4.3% (p = 0.08). M tuberculosis was cultured in 10 of 100HIV infected children compared to six of 42 HIV uninfected children (p = 0.46).
CONCLUSION—Sputum induction can be safely and effectively performed in infants and young children. Induced sputum provides a satisfactory and more convenient specimen for bacteriological confirmation of pulmonary tuberculosis in HIV infected and uninfected children.

     

Antituberculosis chemoprophylaxis in a public hospital - study of 100 children

OBJECTIVE: To evaluate recommendations for antituberculosis chemoprophylaxis in children according to the guidelines of the National Tuberculosis Control Program, and in special situations, as very young children, BCG vaccinated children with positive tuberculin skin test and recent or current exposure to infected cases. METHODS: A retrospective cross-section study has been made of 100 children who underwent chemoprophylaxis at a public hospital in Rio de Janeiro. Variables analyzed were sex, age, BCG vaccination, nutritional status, tuberculin skin test, recent tuberculosis converters, infection source for tuberculosis, adherence to prevention, monotherapy failure and isoniazid side effects. RESULTS: The case history was made up of 57 males and 43 females, 62% were younger than five years of age, there was reference to previous BCG vaccination in 92%, malnutrition in 28% and recent tuberculosis converters in 9% of the cases. Parents represented 60% of infection source known, there was adherence to prevention in 73%, monotherapy failure in 1% and isoniazid side effects in 1% of the cases. CONCLUSIONS: It has been concluded that 15% followed the Health Department guidelines thoroughly, which included the 9 cases of recent tuberculosis converters; 85% of the recommended chemoprophylaxis were due to the coverage of high-risk groups to develop the disease.     

Control of streptomycin and isoniazid in malnourished children treated for tuberculosis.

In 12 malnourished children, who were treated for tuberculosis, plasma levels of streptomycin and isoniazid were followed. Streptomycin was administered i.m. in a dose of 25-50 mg/kg/24 hours. High initial plasma levels were reached (mean: 44.3 mug/ml at 30 min). Streptomycin levels were followed for 5 hours and the mean plasma level at that time was 17.0 mug/ml. From the present data a plasma half life of streptomycin of 3.5 hours has been estimated. It is advised that streptomycin should not be given in doses above 25 mg/kg/24 hours to avoid potential toxic plasma levels especially if plasma levels cannot be measured. It is also concluded from our study that renal function is not affected in malnourished children to an extent where streptomycin clearance is greatly affected. Isoniazid was given orally, 10 mg/kg/24 hours. From 30 min to 6 hours after administration, mean plasma levels of isoniazid above 0.5 mug/ml were observed. In all children measurable plasma levels were obtained. It is concluded that also children with malnutrition can absorb isoniazid after oral administration. From our data it is suggested that the majority of the children in our study were rapid inactivators of isoniazid.     

Unintended consequences: mandatory tuberculin skin testing and severe isoniazid hepatotoxicity

After mandatory school-enrollment tuberculin skin testing, a 4-year-old girl who was at low risk for Mycobacterium tuberculosis infection had severe isoniazid hepatotoxicity that was managed with a liver transplant. Although severe isoniazid hepatotoxicity is very uncommon in children, this case emphasizes the need to limit skin testing to persons who have a risk factor for infection and to educate parents on how to monitor for adverse effects during treatment.     

Computed tomography with normal chest radiograph in tuberculous infection

Children with primary tuberculosis infection without disease must be identified and treated preventively to avoid an increase in the incidence of tuberculosis in children. However, the recognition of infected cases without disease is often difficult. In particular, minimal active disease may be present in many cases but unrecognised on chest radiography. Computed tomography was therefore performed in 15 children with tuberculous infection and a normal chest radiograph to measure the size of their mediastinal lymph nodes. Ten control children without tuberculosis were also evaluated. When compared with controls it was found that nine of 15 (60%) infected children had enlarged lymph nodes. Adenopathies were more frequent in infected children less than 4 years old than in those over 8 years old. The demonstration of unrecognised active disease in many infected children raises the question of the adequate treatment for these children. It is proposed that a two drug regimen would be more appropriate than isoniazid alone in these cases.     

Computed tomography with normal chest radiograph in tuberculous infection.

Children with primary tuberculosis infection without disease must be identified and treated preventively to avoid an increase in the incidence of tuberculosis in children. However, the recognition of infected cases without disease is often difficult. In particular, minimal active disease may be present in many cases but unrecognised on chest radiography. Computed tomography was therefore performed in 15 children with tuberculous infection and a normal chest radiograph to measure the size of their mediastinal lymph nodes. Ten control children without tuberculosis were also evaluated. When compared with controls it was found that nine of 15 (60%) infected children had enlarged lymph nodes. Adenopathies were more frequent in infected children less than 4 years old than in those over 8 years old. The demonstration of unrecognised active disease in many infected children raises the question of the adequate treatment for these children. It is proposed that a two drug regimen would be more appropriate than isoniazid alone in these cases.     

The natural history of peanut allergy in young children and its association with serum peanut-specific IgE

OBJECTIVES: To observe the nature and frequency of adverse reactions caused by accidental peanut exposure in young children with clinical peanut hypersensitivity and to determine the value of serum peanut-specific IgE levels during follow-up. STUDY DESIGN: Eighty-three children with clinical peanut hypersensitivity diagnosed before their fourth birthdays were contacted yearly to track adverse peanut reactions. Serum peanut-specific IgE levels were determined in 51 of 83 subjects. RESULTS: Fifty-eight percent (31/53) of subjects followed up for 5 years experienced adverse reactions from accidental peanut exposure. Regardless of the nature of their initial reaction, the majority with subsequent reactions (52%, 31/60) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51, 22%) had lower serum peanut-specific IgE levels than the group with respiratory and/or gastrointestinal symptoms (40/51, 78%) (median: 1.25 kU(A)/L vs 11. 65 kU(A)/L, P =.004, Wilcoxon rank sums test). Despite this, there was no threshold level below which only skin symptoms appeared to occur. Four selected subjects had negative double-blind placebo-controlled food challenge responses to peanuts during follow-up. CONCLUSIONS: The majority of children with clinical peanut hypersensitivity followed up for 5 years will have adverse reactions from accidental peanut exposure. Symptoms experienced during subsequent adverse peanut reactions may not be consistent with symptoms reported during initial reactions. Therefore proper education regarding peanut avoidance and treatment of adverse reactions is necessary in all cases of clinical peanut hypersensitivity. Young children who are allergic to peanuts can lose clinical hypersensitivity.     

Evaluation of young children in household contact with adult multidrug-resistant pulmonary tuberculosis cases.

BACKGROUND: The prevention and management of multidrug-resistant (MDR) tuberculosis has received much attention, but little attention has been given to children with MDR tuberculosis or children in contact with adults with MDR tuberculosis. The aim of this study was to determine the prevalence of tuberculous infection and disease in childhood contacts of adults with MDR pulmonary tuberculosis. METHOD: All children <5 years of age in household contact with 75 recently diagnosed adults with MDR pulmonary tuberculosis were evaluated. Evaluation included clinical examination, tuberculin skin test, chest radiography and culture for Mycobacterium tuberculosis from gastric aspirates. RESULTS: One hundred twenty-eight children, median age 27 months, were evaluated. Fifty children had recent contact with other adult tuberculosis cases. Sixty-six children previously had chemoprophylaxis or treatment of whom 36 defaulted treatment or received insufficient chemoprophylaxis. One child had HIV infection. Forty-seven children were classified as noninfected, 66 were considered infected only (Mantoux test, > or = 15 mm) and 15 had disease. Three children, who had not previously received antituberculosis drugs, had positive cultures for M. tuberculosis; all were multidrug-resistant. CONCLUSION: This study documents the transmission of multidrug-resistant M. tuberculosis to childhood contacts, the development of disease in these contacts and the importance of knowing the index case's M. tuberculosis susceptibility pattern in choosing a proper treatment regimen for the childhood contact.     

Impact of human immunodeficiency virus 1 infection on clinical presentation,treatment outcome and survival in a cohort of Ethiopian children with tuberculosis

BACKGROUND: Childhood tuberculosis (TB) is difficult to diagnose reliably because signs and symptoms are nonspecific and sputum for direct microscopy is difficult to obtain, especially in very young children. This diagnostic dilemma is thought to have increased with the HIV pandemic. Few studies on treatment outcome of dually infected children in high endemic countries have been reported. This study examines the impact of HIV infection on clinical presentation, diagnostic criteria and treatment outcome of TB in Ethiopian children. METHODS: A prospective cohort study of children with TB diagnosed in Addis Ababa from December 1995 to January 1997 in which HIV-positive children were compared with HIV-negative children with regard to medical history, signs and symptoms, nutritional status, chest radiography, tuberculin skin test, response to TB treatment and final outcome. Mycobacterium tuberculosis was cultured in children with pulmonary manifestations. RESULTS: HIV-positive children were younger, were underweight and had a 6-fold higher mortality than HIV-negative children. The tuberculin skin test was less sensitive and chest radiography was less specific in HIV-infected patients. Adherence to treatment was high (96%), and the cure rate was 58% for HIV-positive and 89% for HIV-negative TB patients. CONCLUSION: HIV-positive children are at risk of diagnostic error as well as delayed diagnosis of TB. TB manifestations are more severe and progression to death is more rapid than in HIV-negative children. Weight for age may be used to identify children at high risk of a fatal outcome.     

Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndrome

Toxic epidermal necrolysis and Stevens-Johnson syndrome are described as variants of the same disease with distinct severity and constitute the most frequent cutaneous reactions in children, causing considerable morbidity. Several reports support the use of intravenous immunoglobulin therapy in these entities. We report the cases of two patients, one with toxic epidermal necrolysis and the other with Stevens-Johnson syndrome, in whom immunoglobulin treatment was successfully used. We also reviewed the outcomes of 13 patients with toxic epidermal necrolysis and Stevens-Johnson syndrome in the previous 10 years in the Hospital Infantil de Mexico, in whom conventional treatment was used.     

芳香族类抗癫痫药诱发Stevens-Johnson综合征与HLA-B*1502基因的相关性研究

HLA-B*1502基因与芳香族类抗癫痫药（AEDs）诱发的Stevens-Johnson综合征（Stevens-Johnson syndrome,SJS）在华中地区汉族研究对象的相关性研究。方法　2007-2009年武汉市儿童医院神经内科住院就诊的因服用AEDs而导致药物副反应（cADRs）的16例癫痫患儿为cADRs组,其中5例表现为SJS,高敏综合征（HSS）2例和斑丘疹（MPE）9例。同时,按1 ∶ 2的比例收集32例服AEDs无副反应的患儿为AED-耐受组,其年龄、性别及所服用药物与cADRs组匹配;选取38名正常儿童为正常对照组。采用等位基因特异性多重PCR分型技术（ARMS-PCR）检测HLA-B*1502的基因型。结果　5例由芳香族类AEDs所诱导的SJS皆为HLA-B*1502基因阳性,而在AED-耐受组中2例、正常对照组中3例HLA-B*1502基因阳性。HLA-B*1502基因频率在cADRs组（33.3%）明显高于AED-耐受组（6.25%,P <0.05;OR=7.5,95%CI 1.25～44.89）和正常对照组（7.89%,P < 0.05;OR = 5.30,95%CI 1.09～25.84）。若以SJS或表皮性红斑（TEN）为研究对象则检测到HLA-B*1502基因与SJS或TEN有更强的相关性（P < 0.0001;OR = 247.99,95% CI 5.87～3831.70）。若以AED-耐受组为对照组,HLA-B*1502基因预测芳香族类AEDs诱发SJS的敏感性为100%（95%CI 81.5%～100%）,特异性为71.4%（95%CI 30%～95%）。HLA-B*1502基因与MPE及HSS无相关性。结论　HLA-B*1502基因与芳香族类AEDs诱导的SJS在华中地区汉族研究对象呈强相关,HLA-B*1502基因可作为由卡马西平为代表的芳香族类AEDs诱发SJS的易感基因,筛查该基因有助于指导癫痫患儿临床个体化药物治疗。     

Old and new drugs for the treatment of tuberculosis in children

During the first 2 days of the 2-month intensive phase of tuberculosis treatment, isoniazid kills 90% of viable bacilli; this renders the patient non-infectious and reduces the risk of drug resistance. Already, during this phase, pyrazinamide contributes to sterilisation or the prevention of relapse, and ethambutol or streptomycin prevent drug resistance developing. During the 4-month continuation phase, rifampicin kills the last remaining bacilli while isoniazid assists in preventing drug resistance. For paucibacillary childhood tuberculosis, a three-drug intensive phase is sufficient. The lesions of childhood tuberculosis often respond slowly, but this does not imply that treatment should be prolonged. Young children are exposed to lower serum concentrations of antituberculosis agents than are adults receiving equivalent doses and should receive doses at the higher end of recommended ranges. For the first time in three decades, new antituberculosis agents have entered clinical trials, but it may be several years before their evaluation is complete.     

Primary drug-resistant tuberculosis in children. Correlation of drug-susceptibility patterns of matched patient and source case strains of Mycobacterium tuberculosis

The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts. We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child. Strains resistant to one or more antituberculous drugs were emphasized in our study. For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections. All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin. There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs. In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns. Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid. The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy. In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.