Mycobacterial infection in an inner city children's hospital.

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.     

MYCOBACTERIAL LYMPHADENITIS

It is probable, though not as yet definitely proven by culture, that the great proportion of cases of mycobacterial lymphadenitis are now due to organisms other than M. tuberculosis. The double Mantoux test will differentiate the two infections. Isolation of these patients with those suffering from tuberculosis is probably unwise as infection with atypical myco-bacteria confers little resistance to tuberculosis. Chemotherapy is not required and is of little value. Surgical excision of affected lymph nodes is the treatment of choice.     

Diagnosed tuberculosis during the follow-up of a cohort of human immunodeficiency virus-infected children in Abidjan, Côte d'Ivoire: ANRS 1278 study

INTRODUCTION: Most data on tuberculosis in human immunodeficiency virus (HIV)-infected children in Africa come from hospital-based and cross-sectional studies. OBJECTIVES: To estimate the incidence of tuberculosis in HIV-infected children participating in an observational cohort. METHODS: HIV-infected children in Abidjan, C?te d'Ivoire, are followed in a prospective cohort. At enrollment, all children had a physical examination, CD4 lymphocyte counts, chest radiograph and a tuberculin test. Quarterly follow-up visits are organized. All patients with suspected tuberculosis undergo specific investigations including gastric aspiration and culture. All isolates are tested for susceptibility. RESULTS: From October 2000 to December 2003, 129 girls and 153 boys were recruited. Of children without a current or previous diagnosis of tuberculosis, 6.5% (13 of 199) had a tuberculin test result of >5 mm, compared with 17.5% of children (10 of 57) with current or previous tuberculosis (P < 0.02). Forty-eight children (17%) had a history of treated tuberculosis, and 27 children were being treated for tuberculosis at enrollment or during the first month of follow-up. Eleven children were diagnosed with tuberculosis after the first month of follow-up, and the diagnosis of mycobacterial infection was confirmed in 7 cases. Of 5 tested isolates of Mycobacterium tuberculosis, 3 were resistant to at least 1 antitubercular drug.Cumulative incidence of tuberculosis was 2060/100,000 at 12 months, 3390/100,000 at 2 years and 5930/100,000 at 3 years. The 3-year risk was 12,400/100,000 in immunocompromised children (CD4 <15%) and 3300/100,000 in other children (P < 0.0001). CONCLUSION: The risk of tuberculosis among HIV-infected children in C?te d'Ivoire is strongly associated with the degree of immunodeficiency in HIV infection.     

Mycobacterial lymphadenitis in childhood

A total of 42 cases of childhood mycobacterial adenitis have been studied to define the optimal steps that lead to the correct diagnosis of this disease. Antigens from the atypical mycobacteria are not currently available, so the usefulness of tuberculin skin testing as a diagnostic tool was examined. Skin testing differentiates mycobacterial adenitis from infection caused by pyogenic bacteria. In addition, repetitive skin testing with tuberculin over a three- to six-month period is also useful in differentiating adenitis caused by atypical mycobacteria from that due to Mycobacterium tuberculosis. Children with atypical mycobacterial adenitis have a decreasing tuberculin response to repeated testing, while children with tuberculous adenitis have a stable response. Other factors that assist in the differentiation of adenitides include a history of recent exposure to tuberculosis and evidence of extralymphatic tuberculosis. Needle aspiration or partial excision in mycobacterial adenitis may lead to drainage and sinus tract information. A PPD skin test should be done prior to surgical manipulation of enlarged nodes. Children with reactive skin tests should undergo complete excision.     

Tuberculosis in children 10 years of age and younger: three decades of experience during the chemotherapeutic era

The 863 patients, aged 10 years and younger, treated at the Children's Chest Clinic of Bellevue Hospital during three decades (1953 through 1981) clearly indicated the success of antituberculosis therapy. There were no deaths from tuberculosis. Early treatment is associated with a reduction in the serious forms of disease, eg, meningitis, miliary disease, and bone infections, and with preventing death. Medication was well tolerated: only 1.1% of the patients had adverse reactions, all of which were reversible. Consistent compliance with medication of only 62% of patients is a challenge to the medical profession. Only 22.5% of mycobacterial cultures were positive. Long-term follow-up of patients was rewarding: seven pregnancies with healthy mothers and babies, and no reactivation of tuberculosis by later infections, even those such as measles or pneumonia. The severity of disease was related largely to patient's age (3 years and younger) and intimacy of contact, the highest rate being when the mother was the contact. The long-term experiences emphasizes the value of early identification, therapeutic compliance, and comprehensive contact, tracing in the future elimination of tuberculosis. Prophylactic therapy and close observation should be considered for contacts, especially those exposed to human immunodeficiency virus infections and addicted to drugs.     

Role of gastric lavage and broncho-alveolar lavage in the bacteriological diagnosis of childhood pulmonary tuberculosis

OBJECTIVE: To compare the mycobacteriological yield from gastric lavage (GL) and bronchoalveolar lavage (BAL), in children with pulmonary tuberculosis. METHODS: 58 consecutive children with chest radiograph suggestive of tuberculosis and positive Mantoux test or a positive history of family contact with a case of tuberculosis were prospectively subjected to gastric lavage on three consecutive mornings and broncho-alveolar lavage on the last day. The samples were subjected to bacteriological isolation. RESULTS: Samples from 10 (17.2%) children grew Mycobaterium tuberculosis from gastric lavage and 12 children had their BAL positive for this bacteria(p>0.05). Overall mycobacterial isolation was possible in 20 patients (34.4%) as two children had grown Mycobacterim tuberculosis in GL as well as BAL. Addition of BAL to the diagnostic work up increased the mycobacteriological yield from 17.2% with gastric lavage alone to 34.4% when BAL was also performed (p=0.013). CONCLUSION: There is no difference in mycobacterial isolation rates from gastric lavage and BAL when studied in isolation. However, when both GL and BAL are used; these procedures complement each other to double the diagnostic yield.     

TB in developing countries: diagnosis and treatment

Childhood tuberculosis poses great challenges to the public health manager as well as the pediatrician. While mycobacterial detection and isolation remain the gold standard but has a poor sensitivity for several reasons. The diagnosis of the disease is often based on indirect methods like PPD positivity, radiological features and history of contact. Serology and PCR based diagnostic methods have failed to help a clinician working at the peripheral level. The review shares and discusses the place of the various tests in the diagnosis of tuberculosis. WHO has been propagating the use of intermittent supervised treatment for all cases including children. We discuss the concerns of the pediatricians and share our experience on this therapy.     

Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disorder of phagocytic oxidative bursts leading to recurrent pyogenic infections. Affected individuals are most prone to infections caused by staphylococci, Salmonella, Candida, and Aspergillus, but previously we observed a high incidence of Mycobacterium tuberculosis infection in Chinese children with CGD. OBJECTIVE: To determine the spectrum of infections in patients with X-linked CGD, with an emphasis on mycobacterial infections, and to review all CYBB gene mutations identified in our center. RESULTS: From 1988 to 2005, 17 Chinese male children were diagnosed to have X-linked CGD. Fifteen mutations were identified, including 3 splice site defects (IVS1-1G>C, 266G>A, IVS3-1G>A), 5 missense mutations (591T>C, 627T>A, 949T>A, 1039T>A, 1512G>C), 3 nonsense mutations (882C>T, 1451C>A, 1569G>T), 1 insertion (756_757insA), and 3 deletions (660_662delTTC, 727delT, 1341delT). Eight of these were novel mutations. Recurrent pneumonia, lymphadenitis, and bacterial skin abscess were the commonest types of infection. Seven patients had tuberculosis (TB). Seven patients had prolonged scarring or abscess formation at the Calmette-Guérin bacillus (BCG) injection site, and 1 had disseminated BCG infection. Three patients had pulmonary aspergillosis. Four patients underwent hemopoietic stem cell transplantation, but 2 died of complications. CONCLUSIONS: Patients with CGD are susceptible to TB and BCG complications. Our observation suggests that oxidative burst is probably important in host defense against mycobacterial infections. Because interferon-gamma is the key cytokine involved in mycobacterial immunity, there may be a stronger indication for its use in CGD patients living in areas endemic for TB.     

Childhood tuberculosis in Victoria, 1970-86

With the declining incidence of tuberculosis, childhood tuberculosis has become an uncommon disease in Australia. This study examines tends in childhood tuberculosis in the state of Victoria, Australia, over the period 1970-86. There was a decline in the incidence of pulmonary disease from 2.76 cases per 100,000 population in the period 1970-76 to 1.97 in the period 1980-86 (P less than 0.005). Non-pulmonary tuberculosis continued at a constant rate throughout the 17 year period. During the period of the study, 381 cases of pulmonary tuberculosis and 79 cases of non-pulmonary tuberculosis (most of which affected lymph nodes) were encountered in a total of 460 cases. Of these, 84 (18%) cases occurred in Indo-Chinese refugees.     

结核菌素皮试和全血γ干扰素测定试验的儿童结核感染诊断应用研究

目的 评价结核菌素（PPD）皮试和全血γ干扰素（IFN-γ）测定试验诊断儿童结核病的准确性。方法 选择2006年7月至2010年4月首都医科大学附属北京儿童医院住院临床诊断结核和呼吸系统疾病的患儿为研究对象。根据患儿所暴露的结核感染危险因素分为5组：A组：无结核病密切接触史的非结核病的呼吸系统疾病患儿;B组：有活动性结核病患者密切接触史的非结核病的呼吸系统疾病患儿;C组：无结核病密切接触史的临床诊断结核病患儿;D组：有活动性结核病患者密切接触史的临床诊断结核病患儿;E组：病原学或病理学确诊的活动性结核病患儿。患儿于入院当日行PPD皮试,入院后1~7 d采集外周静脉血行全血IFN-γ测定。以敏感度、特异度、阴性预测值、阳性预测值和似然比评价PPD皮试和全血IFN-γ测定对结核病的诊断价值。结果 125例患儿进入分析。A组40例,B组11例,C组29例,D组27例,E组18例。①PPD皮试取硬结≥10 mm为阳性判断标准时,诊断结核病的敏感度为77.0%,特异度为70.6%;取硬结≥15 mm为阳性判断标准时,诊断结核病的敏感度为50.0%、特异度为80.2%;全血IFN-γ测定的敏感度为85.1%、特异度为94.1%。②PPD皮试取硬结≥10 mm为阳性判断标准诊断结核病时,<3岁患儿PPD皮试的敏感度和特异度均显著低于≥3岁患儿,城区和郊区患儿的敏感度和特异度接近;全血IFN-γ测定诊断结核病的敏感度和特异度在不同年龄、居住地间差异无统计学意义。③全血IFN-γ测定阳性率与结核感染暴露因素的相关性优于PPD皮试（取硬结≥10或15 mm为阳性判断标准时）。结论 潜伏结核感染筛查时以硬结≥15 mm作为PPD皮试阳性判断标准,可提高诊断的特异度;临床疑似结核病的诊断以硬结≥10 mm作为PPD皮试阳性判断标准,可提高诊断的敏感度。全血IFN-γ测定诊断结核病的敏感度和特异度均较好。     

Childhood tuberculosis in Victoria, 1970–86

Abstract With the declining incidence of tuberculosis, childhood tuberculosis has become an uncommon disease in Australia. This study examines tends in childhood tuberculosis in the state of Victoria, Australia, over the period 1970–86. There was a decline in the incidence of pulmonary disease from 2.76 cases per 100 000 population in the period 1970–76 to 1.97 in the period 1980–86 ( P < 0.005). Non-pulmonary tuberculosis continued at a constant rate throughout the 17 year period. During the period of the study, 381 cases of pulmonary tuberculosis and 79 cases of non-pulmonary tuberculosis (most of which affected lymph nodes) were encountered in a total of 460 cases. Of these, 84 (18%) cases occurred in Indo-Chinese refugees.     

Paediatric home care in the UK.

Paediatric home care services in the UK were ascertained in 1991 and 1992. Respondents from 209 (97%) UK health districts and boards identified 62 general and 124 specialist paediatric home care services by January 1993, 15% having opened in the previous year. Of all UK children, 30% lived in a district with a general home care service. Five health regions had only specialist services. Districts differed widely in the availability of home care for different disorders. The home care services were small, general services employing a mean (SD) of 2.5 (1.6) whole time equivalent (WTE) nurses, and specialist services 1.3 (0.8) WTE nurses. Few services were available 24 hours a day. Funding arrangements were diverse and some services had difficulties in obtaining consumables and equipment for home use. Despite rapid growth there remains considerable scope for the development of paediatric home care throughout the UK.     

Paediatric home care in the UK

Paediatric home care services in the UK were ascertained in 1991 and 1992. Respondents from 209 (97%) UK health districts and boards identified 62 general and 124 specialist paediatric home care services by January 1993, 15% having opened in the previous year. Of all UK children, 30% lived in a district with a general home care service. Five health regions had only specialist services. Districts differed widely in the availability of home care for different disorders. The home care services were small, general services employing a mean (SD) of 2.5 (1.6) whole time equivalent (WTE) nurses, and specialist services 1.3 (0.8) WTE nurses. Few services were available 24 hours a day. Funding arrangements were diverse and some services had difficulties in obtaining consumables and equipment for home use. Despite rapid growth there remains considerable scope for the development of paediatric home care throughout the UK.     

Evaluation of infection control advice for patients at risk of chemotherapy-induced neutropenia in 2 pediatric oncology centers: Cape Town, South Africa, and Newcastle-Upon-Tyne, UK

Childhood cancers are treated with myelotoxic chemotherapy. Resultant neutropenia can lead to life-threatening infections. There is no consistent guidance on infection control precautions for neutropenic patients who are not yet febrile or infected. Although it is not possible to eradicate infection risk, it is conceivable that the risk could be reduced by effective infection prevention. This study compared infection control measures advised to pediatric and adolescent oncology patients receiving chemotherapy in 2 centers (Cape Town, South Africa, and Newcastle, UK). Prospective, observational, cross-sectional surveys of staff and patients/parents were undertaken using standardized, study-specific questionnaires. Seventy-eight staff and 56 patients/parents participated. Precautions advised in Newcastle were significantly different to Cape Town (all P < .05), except both agreed inpatient isolation was unnecessary. Over 40% of patients/parents felt isolation was important (P < .01). In Cape Town, staff and patients had similar views. In Newcastle, patients/parents had stricter opinions on particular precautions than staff, for example, attending school, playing outside and avoiding busy places (P < .01). Patient/parent responses were similar between centers. Over 90% of staff felt advising patients/parents about hand washing was important. Currently infection prevention advice is inconsistent. Further research is needed to elucidate effective guidance for infection prevention in pediatric neutropenic patients.     

Sub acute and chronic meningitis in children—An immunological study of cerebrospinal fluid

Cerebrospinal fluid (CSF) from 274 cases of subacute to ohronic meningitis in age groups from 3 months to 12 years were analysed for the presence of antibody response to mycobacterial and cysticercal antigens by enzyme linked immunosorbent assay (ELI8A). Simultaneously other correlative parameters such as CSF cell cytology by cytospin studies, mycobacterial antigens of Lipoarabinomannan (LAM) type (a polysaccharide antigen) by reverse passive haemagglutination assay (RPHA) CSF C-reactive protein (CRP) by latex agglutination and microbial cultures for mycobacterium tuberculosis and fungi were carried out Antimycobacterial antibody was present in 35.4% of the cases. In 57.66% of the oases there was no demonstrable immune response to either mycobacterial or cysticercal antigens. However, it was interesting to note that 5.47% of the cases revealed the presence of anticysticercal antibody in the CSF. The mycobacterial antigen (LAM poiysaccharide antigen) was found in 72.6% of the cases. There was no evidence of carcinomatous or cryptococcal meningitis. This study stresses the role of multimodal diagnostic tests on CSF for investigating cases of chronic and subacute meningitis irrespective of leading dues such as tuberculosis.     

Diagnostic usefulness of mycobacterial skin test antigens in childhood lymphadenitis

Nontuberculous mycobacterial (NTM) infections are a frequent cause of chronic lymphadenitis in children. Previous studies of NTM antigen skin testing were inconclusive as a result of problems with study design and antigen formulation. The present study was undertaken with the Centers for Disease Control to determine whether newly formulated NTM skin test antigens applied in a double blind manner with a standard purified protein derivative could accurately distinguish NTM infections from those caused by Mycobacterium tuberculosis. Among the 11 children enrolled at our institution the NTM antigens correctly identified the 5 children with culture-proved NTM infections, as well as 2 other children with clinical or histopathologic data consistent with NTM lymphadenitis (P = 0.003, Fisher test). None of the 11 children cross-reacted with the Centers for Disease Control-supplied purified protein derivative. The NTM antigens appear to be useful in the diagnostic evaluation of lymphadenitis and perhaps in the evaluation of children with positive purified protein derivative skin tests.     

Post‐varicella thrombocytopenic purpura

Aims: The aim of the study was to characterize the clinical course of post‐varicella idiopathic thrombocytopenic purpura (ITP) and to asses the risk of acquiring ITP after varicella infection. Methods: A retrospective study of all children diagnosed with ITP in a tertiary medical centre during 1998–2008. Findings were compared with the Intercontinental Childhood ITP Study Group database. The risk of acquiring ITP after a varicella infection was assessed. Results: Ten children were diagnosed with post‐varicella ITP. The incidence of post‐varicella ITP was 1.9% amongst children diagnosed with ITP and 1.1% amongst children hospitalized for varicella. ITP was diagnosed, on average, 8.5 days after the onset of the varicella rash. The female‐to‐male ratio was 1:1.5. The average minimal platelet count was 9.5 × 10⁹ platelets/L. Post‐varicella ITP had an acute course in 80% of cases and a chronic course in the remaining 20%. Bleeding episodes occurred in three patients. During the follow‐up period, 11 patients with previously diagnosed ITP developed varicella. The infection had no apparent affect on the platelet count of the children with acute ITP, but caused a relapse in 71% of the patients with chronic ITP. Conclusions: Post‐varicella ITP has similar clinical features and course to non‐varicella associated ITP. The calculated risk of ITP as a complication of varicella infections is approximately 1:25 000.     

The diagnosis of tuberculosis

Childhood tuberculosis accounts for a significant proportion of the global tuberculosis disease burden. However, tuberculosis in children is difficult to diagnose, because disease tends to be paucibacillary and sputum samples are often not easy to obtain. The diagnosis of tuberculosis in children is traditionally based on chest radiography, tuberculin skin testing, and mycobacterial staining/culture from appropriate samples. Newer diagnostic strategies have included improved bacteriologic and molecular methods, as well as new methods for sample collection from children. Recently, immune-based diagnostics, such as the interferon-gamma release assays, have been introduced for clinical use. These tests do not offer substantial improvements in sensitivity over tuberculin skin testing for the diagnosis of active disease but may be useful in excluding false-positive tuberculin skin tests. Further research is needed to develop better diagnostic tests for tuberculosis in children.     

Immunologische Diagnostik der Tuberkulose — Interferon-γ-Tests

In Germany, about 270 children are currently diagnosed with tuberculosis (TB) each year. Although its incidence continues to decline, TB will remain an important differential diagnosis in the presence of pulmonary infections in childhood, partly because of population movements. In contrast, the incidence of infections with non-tuberculous mycobacteria (NTM) appears to be rising, especially among young children. The most common manifestation of NTM infections is cervical lymphadenopathy, in most cases due to Mycobacterium avium. For adequate therapeutic consequences, it is important to differentiate between the different mycobacterial infections. When clinical examination leads to the suspicion of TB infection the first step in diagnosis is the tuberculin skin test (TST). However, due to cross-reactions not only with NTM infections but also with BCG vaccination, the specificity of the tuberculin skin test is not adequate. New immunological tests, known as interferon-γ assays, have demonstrated a high specificity in differentiating between TB- and NTM infections. Those assays measure the interferon-γ secreted by T-lymphocytes as the immunological response to in vitro stimulation with antigens specific for M. tuberculosis. Two interferon-γ assays, QuantiFERON-TB^® Gold In-Tube and T SPOT?.TB, are commercially available in Germany. These tests have proved helpful in supplementing conventional diagnostic tests for mycobacterial infections, especially in problematic cases.     

Aspiration cytology for diagnosis of tuberculosis--perspectives in India

Tuberculosis (TB) a common cause of mortality can readily be diagnosed by fine needle aspiration. The technique is a simple, cost effective, out patient procedure with a high diagnostic accuracy both in adults and children. The diagnostic morphologic findings comprise of epithelioid cell granulomas and giant cells with or without necrosis. Often an acute inflammatory exudate is obtained. Stain for acid fast bacilli immensely augments diagnosis especially in cases where necrosis or an inflammatory exudate is obtained. Culture studies on aspirated material are time consuming though diagnosis is enhanced. PCR can be applied to detect mycobacterial DNA and has been applied on aspirated material and found to be more sensitive in the detection of tuberculosis. In children TB of lymph nodes is readily identified and so also from other sites such as bone and soft tissues. In children FNAC also plays a role in detection of BCG adenitis, infection with atypical mycobacteria and co-existing infections such as HIV and AIDS.