Bacterial Infections been reported.60 More invasive approaches include transbronchial biopsies and bronchoalveolar lavage.
Non-tuberculous Mycobacteria Disease NTM infection can be demonstrated by species specific skin testing where available, for example PPD-A (M. avium), PPD-S (M. scrofulaceum) and PPD-K (M. kansasii), although the accuracy and clinical relevance of these tests have not been validated. In most cases, PPD-TB is added to exclude MTB infection, although some degree of cross-reactivity is common. A recent comparative study found a significant difference in median TST induration to PPD-TB of 0 mm (interquartile range [IQR] 0–9 mm) in asymptomatic children with isolated NTM as compared to 12 mm (IQR 0–20 mm) in children with MTB isolates.22
However,
the European experience in children with cervical lymphadenitis suggests that a positive TST (≥10 mm) in the absence of documented TB exposure is highly suggestive of NTM disease, while variability in response size may be explained by differing species immunogenicity or individual genetic variability.12,13,20,21,66
IGRAs offer improved specificity
to distinguish NTM disease from TB, especially in children from TB non-endemic areas.66
A FNAB would be the best specimen to collect in
children with a peripheral lymph node mass, while a combination of induced sputum, gastric aspirates or bronchoalveolar lavage specimens may be indicated in children with pulmonary disease.22 Culture isolation with consistent species identification from more than one specimen represents the diagnostic gold standard. All mycobacteria are relatively slow growers and some require special growth media in addition to prolonged incubation times.8
M. haemophilum, a slow
growing non-pigmented NTM, is unique among mycobacteria in its requirement of hemin and ferric ammonium citrate supplementation for growth. The use of molecular techniques and better bacteriological methods for the growth of fastidious mycobacteria species has improved the yields and the rapidity with which clinically relevant NTM species can be identified.8
Leprosy
The diagnosis of leprosy is mainly clinical. No laboratory tests are sensitive or specific enough to replace clinical diagnosis, including serological assays, phenolic glycolipid 1 (PGL-1) tests, tests for cell-mediated immunity, the lymphocyte transformation test (LTT) and lepromine test.67
Recently, a nucleic acid sequence based amplification (NASBA) test successfully detected M. leprae in all untreated multibacillary cases, but often failed detection in paucibacillary patients.68
Treatment Options Table 3 contains a brief summary of the most common treatment options for TB, NTM disease and leprosy.
Tuberculosis
TB treatment has multiple aims, first to cure the individual patients, but also to limit ongoing transmission and the risk of acquiring drug resistance.69
Preventive therapy, with six-month isoniazid (INH) monotherapy, or three-month combination of INH and rifampicin (RMP), is provided to vulnerable contacts with prolonged or close
110
Future Challenges Table 4 contains a brief summary of the perceived most important future challenges for the management of mycobacterial infections and disease in children, which for practical reasons are subdivided according to the structure used in this review paper. n
EUROPEAN INFECTIOUS DISEASE
Laboratory diagnosis of leprosy is made by histology and examination of appropriate Ziehl-Neelsen (ZN) stained slit skin smears (SSS) for acid fast bacteria (AFB). Bacilli are usually found in LL, BL and BB variants, but may be scanty or absent with BT and TL. Nasal secretion smears assist to assess the infectiousness of a patient, being positive in untreated LL and BL cases, but absent in BB, BT and TL. The smears are classified according to a bacterial index (BI) and a morphological index (MI).67
exposure to the index case or MTB infection (see Table 3). Standard treatment of drug sensitive TB consists of two phases. A two-month intensive phase using four drugs INH, RMP, ethambutol (EMB) and pyrazinamide (PZA) kills the vast majority of actively metabolising bacilli. The four-month continuation phase using two drugs (INH and RMP) eradicates persistent intermittently metabolising bacilli. Children with paucibacillary and fully drug sensitive disease can be effectively treated with only three drugs during the intensive phase, excluding EMB. Recent data demonstrated that children require higher mg/kg doses of the first-line drugs compared to adults,69
which prompted the World
Health Organization (WHO) to issue new dosage recommendations for children.70
Extended treatment courses of between six and 12 months are recommended for severe manifestations such as TB meningitis, miliary/disseminated or osteoarticular TB, although limited evidence supports this recommendation.69,70
for HIV-infected and HIV-uninfected children,70
WHO recommendations are similar although prolonging
the total duration of treatment to nine months should be considered in all immunocompromised children, due to increased risk of TB relapse.69 The treatment of drug-resistant TB (multidrug- and extensively drug-resistant) is complicated and has recently been reviewed.71
Non-tuberculous Mycobacteria Disease Treatment options (see Table 3) are highly variable and species specific and should always be guided by laboratory assessment of drug susceptibility.
Surgical excision of NTM cervicofacial lymphadenitis is the treatment of choice in children, if at all feasible and considered safe.72,73
In an
intention-to-treat randomised controlled trial in the Netherlands, surgical excision was more effective than antibiotic treatment (cure rates 96 and 66 % respectively),72
and excessive scarring should be considered.72,73
although the risks of facial paralysis The combination of
a macrolide (clarithromycin or azithromycin) with RMP and/or EMB for three to six months demonstrated considerable efficacy in the treatment of NTM disease.72–74
However, treatment efficacy is highly
dependent on NTM species and may also be influenced by age, size and site of lesion, time since onset and drug susceptibility profile.73
The American Thoracic Society (ATS) recommends combination therapy for MAC disease, using a macrolide, RMP or rifabutin and EMB for cavitory, severe nodular or disseminated disease, with consideration of three-times weekly amikacin or streptomycin in the initial phase of therapy and treatment continuation until resolution of symptoms or recovery of cell-mediated immune function.74
For
the treatment of M. Kansasii pulmonary disease, a regimen of INH, RMP and INH is recommended.74
Leprosy
Two treatment regimens are recommended, one for paucibacillary and the other for multibacillary patients (see Table 3).75
The
paucibacillary leprosy treatment regimen for children includes unsupervised six-monthly dosages of RMP and dapsone, while the multibacillary regimen includes the addition of supervised once monthly clofazimine (lampren®).
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