Osteoarticular tuberculosis in children.

One hundred and four cases of osteoarticular tuberculosis were studied. There were 74 boys (71.2%) and 30 girls (28.8%). The mean age at the onset of symptoms was 7.3 years, ranging from 9 months to 18 years. Seventy four cases (71%) reported 3 months after onset of symptoms. The spine was the commonest site involved (43%) followed by hip (14.9%) and knee joints (10.3%). Evidence of active or inactive pulmonary tuberculosis was found in 16.2%. All cases were treated by three drug regimen of rifampicin, isoniazid and ethambutol; rifampicin was discontinued after 6 months, ethambutol after 12-14 months. In 12 cases (11.5%) isoniazid was continued for 18 months. Along with chemotherapy suitable braces, splints, tractions, exercises and other form of physical therapy produced satisfactory results. Seventy eight patients (75%) showed clinical and radiological improvement with one year of treatment. The follow up period ranged between 4 months to 24 months with an average of 17 months. Children because of capacity to grow, showed progressive deformity in knee in 3 cases (2.8%), hip in 98 cases (8.6%), shortening of limbs in 14 cases (13.4%) and kyphosis in 13 cases (12.5%).     

Treatment of childhood tuberculosis with a six month directly observed regimen of only two weeks of daily therapy

BACKGROUND: Recommended treatment of childhood tuberculosis is 6 months in duration with at least 3 drugs. We studied a regimen requiring as few as 58 doses, given entirely by directly observed therapy (DOT), under program conditions. METHODS: An observational trial was conducted to determine the effectiveness of a completely DOT 6-month regimen for pulmonary, pleural and lymph node tuberculosis in children with the use of 2 weeks of daily isoniazid, rifampin and pyrazinamide therapy; then 6 weeks of twice weekly isoniazid, rifampin and pyrazinamide therapy; followed by 16 weeks of twice weekly isoniazid and rifampin. All therapy was given by workers from the health department, and patients were followed by the Children's Tuberculosis Clinic in Houston, TX. Patients were evaluated for changes in symptoms, weight, clinical or radiographic findings and adherence to therapy. RESULTS: Of the 175 evaluable children (159 pulmonary/thoracic node, 4 pleural, 12 cervical lymph node), 81% of children completed treatment in 6 months. Of the 33 patients who received extended treatment, 3 did so because of physician choice, 17 had an inadequate response to initial therapy, 2 had significant adverse reactions to drugs and 16 had poor adherence to the DOT. Only 37% of patients had complete resolution of disease at the end of treatment, but all continued to improve after therapy was stopped. There was only 1 patient who relapsed after 4 years. CONCLUSION: This regimen had results comparable with those of 6-month regimens with longer durations of daily therapy. Determining treatment response in pediatric tuberculosis is difficult because of the slow resolution of chest radiograph abnormalities. DOT is an important aspect of treatment but does not solve all problems with treatment adherence.     

Intensive short course chemotherapy for treatment of Greek children with tuberculosis.

This prospective study with an 18-month posttreatment follow-up evaluated the efficacy of intensive short course chemotherapy in Greek children with pulmonary or extrapulmonary tuberculosis. Between November, 1988, and March 1991 a 2-month regimen of rifampin, 10 to 12 mg/kg/day, isoniazid, 10 to 12 mg/kg/day, and pyrazinamide, 30 to 35 mg/kg/day, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to 36 children with tuberculosis. Twenty-three boys and 13 girls ages 8 months to 12 years (mean, 5 1/2 years) were enrolled in the study. The diagnostic criteria for establishing tuberculosis were tuberculin skin test reactivity, radiographic findings compatible with tuberculosis, epidemiological data and clinical and laboratory findings. Four children had extrapulmonary and 32 had pulmonary tuberculosis; 9 of the latter were asymptomatic. Among the pulmonary cases there were 2 children with pleural effusion. Clinical response to therapy was apparent within 7 to 14 days; the pleural effusions resolved in 2 to 6 weeks and the pulmonary infiltrates cleared in 2 to 6 months. Hilar adenopathy regressed within 18 months or longer. No serious problems with drug tolerance or toxicity were noted during the treatment period. Temporary hyperuricemia and transient elevation in serum transaminases were observed in 11 patients but no drug modification was required. There were no posttreatment relapses. These findings suggest that intensive short course chemotherapy for the treatment of Greek children with pulmonary or extrapulmonary tuberculosis appears to be effective, safe, of good patient compliance and comparable to the longer treatment regimens.     

Rifampicin and isoniazid prophylactic chemotherapy for tuberculosis

Prophylaxis of tuberculosis in children with four month (n = 53) and three month regimens (n = 213) of rifampicin and isoniazid from 1987 to 1996 were tolerated without any toxicity. The reduction in the proportion of paediatric tuberculosis, which was seen after the introduction of chemoprophylaxis with longer regimens in 1981,was maintained with the shorter duration regimens. Altered immigration patterns and a fall in the proportion of infectious tuberculosis, as defined by sputum culture positivity, have been excluded as factors in the reduced paediatric proportion of tuberculosis. The data show such regimens have little toxicity and provide indirect evidence that three months chemoprophylaxis may be as effective as longer regimens.     

Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection.

A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1-infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available.     

Perinatal tuberculosis: four cases and use of broncho-alveolar lavage

Despite the high prevalence of tuberculosis in adults and children, congenital and perinatal forms of tuberculosis are rare. Four patients with perinatal tuberculosis are described. Diagnosis was made by demonstration of acid-fast bacilli (AFB) on broncho-alveolar lavage (BAL) specimens (two cases), gastric aspirate smear (one case) and lymph node fine-needle aspirate (one case). All of the above specimens were subsequently positive on culture. Two infants died of progressive pulmonary failure, and one of the mothers died, despite the institution of anti-tuberculous therapy. BAL specimen examination for AFB is useful in the diagnosis of perinatal tuberculosis, especially in infants with smear-negative gastric aspirate.     

Hepatotoxicity of rifampicin and isoniazid in children treated for tuberculosis

In order to determine the hepatotoxicity of rifampicin in children treated for tuberculosis, a survey was performed of 18 children receiving this medicine in combination with isoniazid. Fifteen of the 18 children (83%) showed a rise in ASAT values and 11 (61%) in ALAT values exceeding 39 U/L. Seven children with maximal ASAT values between 40 and 100 U/L were treated without any changes in the regimen and the transaminases normalized later in the treatment. Six out of the eight children with ASAT values over 100 U/L were allowed a three-week pause in their therapy, one was given the same dose of rifampicin, and in one the treatment was discontinued entirely. The therapy was discontinued in an additional three children because of a second high rise in the transaminase values. Liver injury can occur at any time during treatment, and thus makes continuous follow-up tests necessary.     

Category based treatment of tuberculosis in children

BACKGROUND: Childhood tuberculosis is treated with multiple regimens for different clinical manifestations. World Health Organization has suggested a category-based treatment of tuberculosis that focuses on adult type of illness. To include children as DOTS beneficiaries, there is a need to assess the feasibility of classification and treatment of various types of childhood tuberculosis in different categories. METHODS: The study was conducted in the Pediatric Tuberculosis (TB) Clinic of a tertiary care hospital in North India. All children registered in the TB clinic were classified in four categories, similar to the categorization in World Health Organization's guidelines for treatment of tuberculosis in adults. All children with freshly diagnosed serious form of tuberculosis were included in category I. Category II included patients who had treatment failure, had interrupted treatment, relapse cases and those who were suspected to have drug resistant tuberculosis. Patients with primary pulmonary complex (PPC), single lymph node tuberculosis, minimal pleural effusion and isolated skin tuberculosis were included in category III. Category IV included patients who did not improve or deteriorated despite administration of 5 drugs (as per Category II) for at least 2 months. Results: A total of 459 patients were started on antituberculosis drugs and were available for analysis. Pulmonary tuberculosis was the commonest followed by lymph node tuberculosis. Identification of AFB was possible only in 52 (11 percent) of the patients and was more commonly seen in lymph node tuberculosis. The mean age of the children was 93 months and sex distribution was almost equal. 323 patients were in category I, 12 in category II, 120 in category III and 4 in category IV. 365 (80 percent) children completed the treatment. Of these, 302 (82.7 percent) were cured with the primary regimen assigned to them in the beginning, 54 (14.8 percent) required extension of treatment for 3 months and 9 (2.5 percent) patients required change in the treatment regimen. Side effect in form of hepatotoxicity was observed in 12 (2.6 percent) patients and was significantly more in patients who were getting category IV treatment. Conclusion: It is feasible to classify and manage various types of tuberculosis in children in different categories similar to WHO guidelines for adult tuberculosis.     

Cutaneous hypersensitivity reactions due to thiacetazone in the treatment of tuberculosis in Zambian children infected with HIV-I.

Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV. In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented. This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I). Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment. Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88). These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV. These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen. Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome. All 12 of these children with the Stevens-Johnson syndrome were infected with HIV. The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction). No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis. The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.     

卡介苗性淋巴结结核临床治疗体会

目的 研究卡介苗性淋巴结结核的临床特点、诊治方法及预后.方法 回顾性分析158例卡介苗性淋巴结结核患儿临床资料,男123例,女35例;年龄30d至1岁,其中＜6个月者136例(86.1％);卡介苗接种在左侧上臂,淋巴结结核发生在左侧腋下或(并)左侧锁骨上149例,卡介苗接种在右侧上臂,淋巴结结核发生在右侧腋下或右侧锁骨上9例.全组均采用手术治疗;术后给予抗结核药物治疗6个月,即同时服用异烟肼和利福平3个月,后改为单服用异烟肼3个月.本组回访病例按照服抗结核药物情况分三组,对照组:47例,未服用抗结核药物;服药Ⅰ组:38例,同时服用异烟肼和利福平3个月后停药;服药Ⅱ组53例:同时服用异烟肼和利福平3个月改为单服异烟肼3个月后停药.结果 本组回访138例,服药Ⅰ组治愈36(94.7％)例,服药Ⅱ组治愈52(98.1％)例,对照组治愈46(97.9％)例,服药Ⅰ组、服药Ⅱ组及对照组治愈率与服抗结核药物之间差异无统计学意义(P＞0.05).结论 卡介苗性淋巴结结核主要依据临床特点、病理检查确定诊断,手术是治疗卡介苗性淋巴结结核的最佳方法,其预后与抗结核药物应用可能无关,主要取决于是否完整切除病灶.     

Adherence to isoniazid preventive chemotherapy: a prospective community based study.

BACKGROUND: Current international guidelines recommend 6-9 months of isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis in children exposed to a susceptible strain of M tuberculosis. However, this is dependent on good adherence and retrospective studies have indicated that adherence to unsupervised INH preventive chemotherapy is poor. AIM: To prospectively document adherence to six months of unsupervised INH monotherapy and outcome in children with household exposure to an adult pulmonary tuberculosis index case. METHODS: From February 2003 to January 2005 in two suburbs of Cape Town, South Africa, all children <5 years old in household contact with an adult pulmonary tuberculosis index case were screened for tuberculosis and given unsupervised INH preventive chemotherapy once active tuberculosis was excluded. Adherence and outcome were monitored. RESULTS: In total, 217 index cases from 185 households were identified; 274 children <5 years old experienced household exposure, of whom 229 (84%) were fully evaluated. Thirty eight children were treated for tuberculosis and 180 received preventive chemotherapy. Of the children who received preventive chemotherapy, 36/180 (20%) completed > or =5 months of unsupervised INH monotherapy. During the subsequent surveillance period six children developed tuberculosis: two received no preventive chemotherapy, and four had very poor adherence. CONCLUSION: Adherence to six months of unsupervised INH preventive chemotherapy was poor. Strategies to improve adherence, such as using shorter duration multidrug regimens and/or supervision of preventive treatment require further evaluation, particularly in children who are at high risk to progress to disease following exposure.     

Hepatic toxicity of antituberculous drugs in children.

Three cases of children who developed hepatic toxicity of different degree while on antituberculous treatment with isoniazid and rifampicin are reported. The clinical picture is presented and the pathogenesis of the hepatic damage is discussed. The pathological findings in the liver are those of a drug induced hepatitis. The combined treatment of tuberculosis in children with isoniazid and rifampicin is potentially dangerous and should be reserved for cases in which resistance to other drugs has been demonstrated.     

Exposition d’une cohorte de nouveau-nés à une tuberculose bacillifère dans un service de néonatalogie

IntroductionA nursery nurse that was working in the neonatology service had been diagnosed with tuberculosis. As a consequence, the newborn infants were in danger of a possible contamination during a 4-month period.MethodologyOne hundred and thirty kids that had been in touch with the nurse were given attention. Prophylactic treatment for three months with isoniazid and rifampicin has been proposed to all families. Each of them was screened with a tuberculin sensitivity test and was given chest radiography initially and after three months.ResultsNone of the children was initially suspected for tuberculosis. Among the chest radiographies, 97.6% were normal and all the intradermal tuberculin were either negative or in the norm following a vaccination by the Bacillus Calmette-Guerin. In most cases, the treatment tolerance was high.ConclusionA 4-year-long surveillance ensured that no infant was infected. This procedure has established that the risk of transmission by a nurse is low, should it be for newborn babies, as long as guidelines are strictly adhered to.     

Sero diagnosis of tuberculosis in children using two ELISA kits

The diagnosis of childhood tuberculosis is based on circumstantial evidence in the absence of a gold standard in the majority of cases. Sero-diagnosis offers scope for an early diagnosis in a variety of clinical conditions and is simple to perform. A number of mycobacterial antigens have been used for antibody detection assays and several are available as kits in the market. This study was done to evaluate the value of antibody detection kits (ELISA) against the A60 antigen and 38 kDa antigen of Mycobacterium tuberculosis in the diagnosis of childhood tuberculosis at the outpatient department of the Institute of Social Paediatrics, Government Stanley Hospital in collaboration with Tuberculosis Research Centre, Chennai. Thirty five children with pulmonary tuberculosis, 7 with TB lymphadenitis and 22 healthy controls were studied. In addition to routine investigations including gastric lavage for AFB culture, serum antibodies against the A60 and 38 kDa antigens were assayed using commercially available ELISA kits. With A60, IgM serum levels were positive in 74% of pulmonary TB cases, 57% of TB lymphadenitis cases and 50% of controls. A60 IgG was positive in 17% of pulmonary TB, 86% of TB lymphadenitis and 14% of controls. The 38 kDa IgG antibody was positive in 37% of pulmonary and 86% of TB lymphadenitis cases and 27% of controls. Among 10 culture confirmed cases, A60 IgM was positive in 8, A60 IgG in 3 and 38 kDa IgG in 5 patients. The sensitivity of the tests ranged between 29% and 71% and specificity between 50% and 86%. Although the numbers are small, the results suggest that serodiagnosis using the currently available antigens of M. tuberculosis is unlikely to be a confirmatory test for tuberculosis in children.     

A randomized trial of fully intermittent vs. daily followed by intermittent short course chemotherapy for childhood tuberculosis

Fully intermittent short course chemotherapy regimens have been used successfully in adults but not in children. We report the results on 76 children with tuberculosis, excluding central nervous system tuberculosis and primary pulmonary complex. Isoniazid, rifampin and pyrazinamide were used for treatment. They were randomly allocated to Regimen A (52 doses) and Regimen B (94 doses). Overall efficacy of both schedules was greater than 95% in 27 children with lymphatic, 43 with pulmonary and 6 with disseminated tuberculosis. Compliance in 10 children after 2 to 4 months of therapy was poor because rapid improvement was mistaken by parents for cure. Two children died, probably of underlying lung disease. Follow-up for up to 2 years did not reveal any case of relapse or recurrence of the disease. Therapy for 6 months involving administration of only 52 or 94 doses of drugs was found to be economical, effective and safe for treating children with tuberculosis.     

Antituberculous therapy in children

The advent of effective chemotherapeutic agents for the treatment of tuberculosis necessitates parallel emphasis in designing various short-course chemotherapy regimens in treating tuberculosis in children. Direct extrapolation from studies in adults is not appropriate because of differing pharmacokinetics and adverse drug reactions of antituberculous drugs in children. The pharmacological basis of antituberculous drugs and guidelines for using various drug regimens in relation to the varied clinical profile of tuberculosis in children have been discussed. It has been observed that the commonest type of tuberculosis in children is the pulmonary primary complex (71·4%), followed, by, progressive, primary disease (71·4%). Pleural effusion, bronchopneumonia and miliary tuberculosis are much less frequent. The 3 drug regimen does not seem to offer any advantage over the two drug regimen in the treatment of the primary pulmonary complex, as assessed by radiological clearance. Compliance is poorer in long-term and intermittent therapy as compared to short-course, continuous therapy. An erratum to this article is available at .     

Drug-resistant tuberculosis in Turkish children

The purpose of this study was to determine the prevalence of anti-tuberculosis drug resistance in children followed at Hacettepe University Ihsan Do?ramaci Children's Hospital. Sixty cases with tuberculosis for whom susceptibility testing was available were searched retrospectively. Teh overall drug resistance was 26.7 percent. Resistance to streptomycin (sm) was the most frequent (18.3%), followed by isoniazid (6.7%), rifampicin (6.5%), and ethambutol (4.2%). Strain resistant to more than one drug was present in two cases (3.3%). In summary, excluding SM, both single and multidrug resistance were relatively low in our pediatric patients.     

Mycobacterium tuberculosis infection in pediatric liver transplant recipients

OBJECTIVES: To study the incidence, clinical presentation, management, complications and outcome of tuberculosis in pediatric liver transplant recipients. METHODS: A retrospective review of the medical records of children who underwent liver transplantation between 1991 and 1998. RESULTS: Mycobacterium tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were common presentations; one-half had normal chest radiographs. The median time to confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests contributing to diagnosis included: Ziehl-Neelsen (ZN) stain (2 patients), M. tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and histopathology (4 patients). Family health screening was productive for 4 patients. Duration of treatment varied from 9 to 18 months. Isoniazid-induced hepatitis was observed in 2 patients but resolved with dose reduction. Two patients died while receiving treatment, one of Klebsiella spp. septicemia and the other of pulmonary hemorrhage. CONCLUSIONS: Tuberculosis after liver transplantation has a significant morbidity and mortality. Pretransplantation a personal and family history of tuberculosis must be sought, and screening of patients and their families should be considered. Standard regimens incorporating isoniazid and rifampin are effective, but regular monitoring of liver function is essential to detect drug-induced hepatotoxicity.     

Combinations of arabinosyl cytosine and 6-thioguanine for treatment of adults with acute leukemia

The combination of arabinosyl cytosine and 6-thioguanine has been effective for the treatment of acute leukemia. Three schedules of this combination were studied to determine which was most effective, especially in patients who had prior exposure to either or both of these drugs. Sequential and simultaneous 5-day courses of the combination were ineffective. A regimen consisting of a 5-day course of arabinosyl cytosine followed by a 5-day course of 6-thioguanine and another 5-day course of arabinosyl cytosine produced responses in 36% of 25 patients. Seven of the nine patients who responded were refractory to prior therapy with arabinosyl cytosine and 5 were refractory to prior therapy with 6-mercaptopurine. However, the median duration of response was only six weeks. Four patients developed central nervous system complications and three of these patients died while in complete remission. Major toxicity from all three regimens was myelosuppression. This regimen was about as effective as most other regimens used as secondary therapy in patients with acute myelogenous leukemia, but its toxicity was too great for routine usage.