Nontuberculous Mycobacterial Infections In Children Research Articles

A Japanese retrospective study of non-tuberculous mycobacterial infection in children, adolescents, and young adult patients with hematologic-oncologic diseases.

Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. Post-transplant patients were infected with NTM at 24 sites, including the lungs (n = 12), skin and soft tissues (n = 6), bloodstream (n = 4), and others (n = 2). Nine of twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; n = 5), inborn errors of immunity (IEI; n = 6), and others (n = 4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, three typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GVHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GVHD, who may require active screening for NTM.

Non-tuberculous mycobacterial infection in children

Abstract Non-tuberculous mycobacteria (sometimes known as atypical mycobacteria) are environmental mycobacteria found throughout the world in soil, dust, water, foodstuffs and other animals. They are defined simply in contrast to those mycobacteria which cause tuberculosis or leprosy, but a small number of species are considered to be human pathogens in their own right and the incidence of human infections has increased in recent decades. Characterised by their relative resistance to many classes of antibiotics, sometimes including those used to treat tuberculosis, non-tuberculous mycobacteria can cause a wide range of diseases in children, including lymphadenitis, skin and soft tissue infections, respiratory infections and disseminated infections. Diagnosis relies on a high index of clinical suspicion, collection of appropriate samples for culture on specialised media, and is now augmented by evolving molecular techniques. Treatment often involves surgical debridement and complex multi-drug regimens taken over many months, particularly in those children with underlying respiratory or immunological illnesses. Controlled clinical trials to identify optimal combinations of anti-mycobacterial drugs for use by such patients are desperately needed to treat these emerging infections.

Nontuberculous mycobacterial infections in children in the Czech Republic in the period 2003-2018.

Comparision of the incidence of cervical lymphadenitis caused by nontuberculous mycobacteria in two equal time periods before and after the ending of widespread calmetization (tuberculosis vaccination). Backgroung. From 2011 to 2018, 89 children were registered in the Tuberculosis Register with cervical lymphadenitis caused by nontuberculous mycobacteria, as confirmed by cultivation. In the majority of cases, the infection was caused by a mycobacterium belonging to the Mycobacterium avium complex. Only 7 cases of cervical lymphadenitis of the same etiology were registered during the same time interval between 2003 and 2010. The authors consider the ending of widespread calmetization (tuberculosis vaccination) in 2010 to be the main cause of the growing incidence. A comparison of data for the period 2003-2018 about cases of the illness caused by atypical mycobacteria as reported in the Tuberculosis Register. The average incidence per year in the first interval was 0.04/100 000 children and in the second interval 0.53/100 000 children. During the second time interval, there was an increase from 0.14/100 000 children in 2011 to 1.40/100 000 children in 2018. While the incidence during the first time interval did not show any time trend (P=0.885), the year 2010 marks a significant turning point, with growth during the second interval being highly statistically significant (P<0.001).

Nontuberculous mycobacterial pulmonary disease in a 16-year-old female patient with bronchiectasis

Nontuberculous mycobacterial (NTM) pulmonary disease generally occurs in old people with underlying lung disease. However, unlike adults, NTM infections in children with normal immunity are rare, and they occasionally manifest as lymphadenitis. We herein present a rare case of NTM pulmonary disease in a girl who is the youngest patient reported in Korea. A 16-year-old female was brought to the hospital because of dyspnea on exertion, fever, and productive cough. The patient had bronchiectasis. She under went Fontan operation for right isomerism, double outlet right ventricle, pulmonary stenosis, and had been taking prophylactic an tibiotics for asplenia. NTM were found in the sputum and bronchoalveolar lavage fluid by acid fast bacillus (AFB) staining and cul ture, which were identified as Mycobacterium avium. The treatment started with azithromycin, ethambutol and rifampicin. After 6 months of treatment, respiratory symptoms improved and the sputum AFB culture became negative. She is currently on medica tion with above-mentioned drugs for 10 months without any adverse effects. This case suggests that NTM pulmonary disease should be suspected and properly treated especially in children and adolescents with underlying lung disease. (Allergy Asthma Respir Dis 2020;8:231-236)

Nontuberculous mycobacterial disease in childhood – update on diagnostic approaches and treatment

Recent studies suggest that the incidence of nontuberculous mycobacterial infections in children may be increasing. Nontuberculous mycobacterial lymphadenitis, skin and soft tissue infection, and pulmonary disease each present unique challenges in relation to diagnosis and treatment. In this update, we critically review the recent literature on the epidemiology, clinical features, diagnostic approaches and treatment of nontuberculous mycobacterial disease in children. In addition, we outline key areas warranting further research.

51 Network infectivity analysis of NTM infection in children with cystic fibrosis (CF) in the North East of England

Objective Non-tuberculous mycobacterial (NTM) infection is an emerging clinical problem in children and adults with CF. Transmission between patients has been observed but not consistently demonstrated. Using network analysis we investigated whether children in our CF clinic were more likely to isolate NTM following attendance on the same day as another patient with NTM. This was before clinic segregation by NTM status was implemented. Methods Retrospective data on 139 children with CF at our centre were collected. 10 isolated Mycobacterium abscessus . Attendance at clinics were recorded for a period of 33 months, between January 2011 and October 2013. ‘Dangerous contacts' (i.e. contacts of uninfected children with infected ones) were identified. Analysis determined whether children who subsequently cultured NTM had a statistically significant risk of a ‘dangerous contact'. During the study period standard CF segregation and clinic hygiene practices were in place. Results Network analysis showed that subsequently NTM positive individuals experienced higher numbers of ‘dangerous contacts' pre-first isolation compared to those who never tested NTM positive (7.9 vs. 5.3 contacts; one-tailed Wilcoxon test W=430.5, p=0.035). VNTR typing identified two clusters of related clones involving five patients. Other isolates appeared unrelated. Conclusion Our analysis suggests cross-infection of NTM may have occurred between children in our service. In the absence of molecular epidemiological data, we cannot assume this represents a definite demonstration of transmission. A nationwide NTM molecular aetiological study is ongoing and will provide data to investigate this further.

52 Clinical characteristics and diagnosis of NTM infection in children with cystic fibrosis (CF) in the North East of England

Objective Non-tuberculous mycobacterial (NTM) infection is an emerging clinical problem in people with CF but the threshold for treatment is uncertain. American Thoracic Society (ATS) criteria exist for the diagnosis of NTM infection but are not CF specific and their usefulness in children is uncertain. We audited whether NTM affected patients in our service met these criteria relative to decisions regarding treatment. Methods Clinical, radiographic and microbiological data were collected on all NTM affected patients. The ATS diagnostic criteria are a. presence of pulmonary symptoms; b. nodular or cavitary opacities on CXR OR multifocal bronchiectasis plus nodules on HRCT; and c. positive cultures from 2 or more sputum samples. Results Ten children (7 male, median age 13.5 years, 6 × DF508/ DF508) isolated Mycobacterium abscessus between 1 and 18 times (median 5.5). Median % predicted FEV1 pre-NTM isolation was 82.5% and post was 82.0% (p=NS). Median weight-for-age Z score pre-isolation was 0.18 and post-isolation was –0.25 (Kruskal–Wallis p = 0.056). Four of ten patients fulfilled clinical, radiographic and microbiological criteria at isolation of NTM. Five patients were treated for NTM infection; of these three met the ATS criteria at the time of commencing treatment. Conclusion Acquiring NTM was not associated in a decline in lung function in children in our service. ATS criteria were of limited clinical utility in our clinic but the recent publication of consensus guidelines will help to improve this situation.

A hospital-acquired outbreak of catheter-related nontuberculous mycobacterial infection in children on peritoneal dialysis.

Catheter-related nontuberculous mycobacterial infection in children with chronic renal failure on peritoneal dialysis (PD) is rare. However, there have been five such infections in infants among PD patients at our center. Although the patients were treated with antibiotics to which the organisms showed in vitro sensitivity, they were clinically drug resistant. Hence, all PD catheters needed to be removed. Thereafter, following hemodialysis treatment for approximately 1month, the PD catheters were replaced, with no recurrence of infection. On investigation of the infection route, it was found that these bacteria had colonized around a shower head in one of the bathrooms. These findings suggest that, in cases where hot water systems at hospitals are considered at a high risk, frequent sterilization is needed, especially around the shower heads. It is also necessary to reconsider current standard practices in the management of catheter exit sites, especially if the national incidence of infection increases.

Nontuberculous mycobacterial infections in children with inborn errors of the immune system

Severe mycobacterial disease is mostly confined to patients who are immunocompromized either by acquired or inherited causes. One such genetic disorder is Mendelian Susceptibility to Mycobacterial Disease (MSMD), a hot topic within the field of primary immunodeficiency. This single gene disorder is characterized by isolated infection with mycobacteria or Salmonella due to a defect in the type-1 cytokine response. In the last two decades, ten genes have been labeled as causing MSMD when they harbor germline mutations, namely IL12B, IL12RB1, IFNGR1, IFNGR2, STAT1, IKBKG, CYBB, TYK2, IRF8 and ISG15. The mutations lead to either insufficient production of IFN-γ, or to an insufficient response to the cytokine. Current treatment options include recombinant IFN-γ and hematologic stem cell transplantation (HSCT). In the future, gene therapy, antisense-mediated exon skipping and chemical intervention in glycosylation problems may become successful alternatives. Furthermore, it is likely that many new candidate genes and pathways crucial for mycobacterial immunity will be identified.

Management of lymphadenitis due to non-tuberculous mycobacterial infection in children

Non-tuberculous mycobacterial (NTM) infection is an important cause of cervico-facial lymph node enlargement in young children. The optimal treatment is thought to be early complete excision without chemotherapy. We compared management of patients referred to our centre to this "gold standard" and determined clinical outcomes by type of primary surgical intervention (complete excision vs. incomplete excision). Retrospective study of management and clinical outcomes of all children (<12 years) with NTM lymphadenitis referred to a single UK centre between May 1998 and May 2008. We identified 43 children. Median time from onset of swelling to operation was 6 weeks. Management was: no operation (n = 1, 2 %), complete excision (n = 20, 47 %), incision and drainage (n = 17, 40 %) and fine needle aspirate (n = 5, 12 %). Children not treated by primary complete excision were more likely to have: re-operation (91 vs. 30 %; χ(2) = 16.48; p < 0.0001); persistent lymphadenitis (77 vs. 30 %; χ(2) = 9.45; p = 0.002); sinus formation (26 vs. 5 %; χ2 = 3.74; p = 0.05). Failure to undertake primary complete excision leads to further morbidity. A high index of suspicion is required for timely appropriate management to avoid unnecessary morbidity and further intervention.

Nontuberculous mycobacteria.

Nontuberculous mycobacteria.

Differential avian and human tuberculin skin testing in non-tuberculous mycobacterial infection.

To determine the sensitivity of differential avian and human delayed-type hypersensitivity skin testing in the diagnosis of non-tuberculous mycobacterial lymphadenitis. Retrospective review of all patients with culture proved non-tuberculous mycobacterial lymph node infections who also had differential avian and human skin testing performed over a 10 year period from 1986 to 1996. One hundred and twenty four patients had non-tuberculous mycobacteria isolated from lymph nodes over this period, 59 of whom had differential skin testing performed. The sensitivity of a response of >/= 10 mm to the avian precipitin was 58 of 59. No patient had both a negative human and avian Mantoux. The sensitivity of the human Mantoux alone for diagnosing non-tuberculous mycobacterial infection was 81% for a response of >/= 5 mm and 66% for >/= 10 mm. Ten patients had a 0 human response. Fifty five of the 59 patients had an avian response at least 2 mm greater than the human response. The avian Mantoux is a very sensitive method of diagnosing non-tuberculous mycobacterial infection in children. The human Mantoux is not sensitive enough to be used alone as a surrogate to diagnose non-tuberculous mycobacterial infection.

Non-Tuberculous Mycobacterial Infection in Children with Cancer

Non-Tuberculous Mycobacterial Infection in Children with Cancer

Circulating cryoglobulins in nephropathic cystinosis

occurred without specific drug therapy. Progressive disease is often difficult to treat because of the frequently encountered pattern of drug resistance of the nontuberculous mycobacterial organisms. As the nontuberculous mycobacterial organisms are usually of low virulence, children with serious infections should be suspected of having underlying disease or immunodeficiency disorders. Herrod et al ~ reported pulmonary disease in two children caused by nontuberculous mycobacterial organisms. One boy with acquired hypogammaglobulinemia experienced progressive pulmonary involvement with Mycobacterium intracellulare avium infection for several years prior to his death. A boy with Mycobacterium fortuitum pulmonary infection responded to prolonged antituberculous therapy. In adults, most pulmonary infections caused by Mycobacterium intracellulare avium were found to be chronic, with persistently positive sputum cultures and no response to antituberculous therapy. The results of surgical resection were also disappointing because of recurrences. Although the majority had underlying disease, approximately one third of the infections occurred in young adults free of co-existing disease? The most frequent manifestation of nontuberculous mycobacterial infection in children is local infection of the superficial lymph glands. 1'4 Surgical excision is the preferred treatment if anatomically feasible, although antituberculous drugs, especially rifampin, have been efficacious as an alternative to surgery in some patients?. ~ Most