Bacterial Infections immunocompromised persons.50–52 In adults, certain human leucocyte
antigen (HLA) alleles and polymorphisms in genes encoding for natural resistance-associated macrophage protein (NRAMP1), vitamin D receptor and IL-1 receptors have been associated with susceptibility to TB,53–56
but findings have not been consistent in different populations and few candidate gene studies included children.51,52
Disease Spectrum Tuberculosis
The most common clinical manifestation of childhood TB is intrathoracic TB (60–80 %). Cervical lymphadenitis (67 %) is the most frequent extrapulmonary manifestation, followed by TB meningitis (13 %), pleural (6 %), miliary/disseminated (5 %) and skeletal TB (4 %).57 Intrathoracic disease manifestations are diverse.58
A primary
parenchymal (Ghon) focus develops at the site of infection, but this is usually transient and rarely visualised. However, in infants and severely immunocompromised individuals, poor containment and unrestrained organism proliferation may cause progressive parenchymal damage, with ultimate breakdown of the Ghon focus.34,58 Hilar and/or paratracheal adenopathy is the most common intrathoracic manifestation and is usually regarded as the hallmark of primary TB in children.58
Complications arising from lymph node
The most frequent symptoms of pulmonary TB include chronic unremitting cough, weight loss and anorexia. TB meningitis most often develops when a caseating meningeal or sub-cortical focus – the Rich focus – discharges its contents into the subarachnoid space.
involvement include lobar or segmental hyperinflation due to a check-valve effect, or collapse resulting from complete airway obstruction, while distal aspiration of caseous material may result in an expansile pneumonic process with/without cavitation. Typical adult-type disease with partially immune-mediated parenchymal destruction and formation of apical lung cavity emerges around adolescence.34,58
Non-tuberculous Mycobacteria Disease NTM disease represents a variety of clinical syndromes affecting both immunocompromised and immunocompetent children. The disease spectrum includes chronic pulmonary disease, superficial lymphadenitis, skin and soft tissue disease, osteoarticular involvement and disseminated disease.8,20,21
Localised lymph node
disease, especially involving the anterior cervical chain, but also the submandibulary, submaxillary and preauricular nodes, is the most common presentation of NTM disease in children.8,21
It is unilateral in
95 % of cases and can result in fistulae of the overlying skin. NTM species associated with localised lymphadenopathy varies in different geographic regions, but some frequently encountered species include M. avium/intracellulare complex (MAC), M. scrofulaceum, M. haemophilum, M. malmoense and M. kansasii.8
NTMs most
associated with pulmonary disease include MAC followed by M. kansasii (see Table 1).8
The most frequent symptoms of pulmonary
disease include chronic coughing, malaise, fever, weight loss and anorexia.20–22
Unique species-specific diseases include Buruli
Other disease manifestations include soft tissue and/or osteoarticular involvement, such as disease caused by M. fortuitum, which is usually associated with penetrating injuries or surgical interventions.20–22
ulcer, a chronic, necrotic skin disease caused by M. ulcerans, which is the third most common mycobacterial disease after TB and leprosy and found in Africa, Southeast Asia and Australia. M. marinum may cause classic ‘fish tank granulomas’ or respiratory disease related to contact with fish aquariums or contaminated swimming pools.8
106 Leprosy
The clinical classification of leprosy is shown in Table 2. TL tends to develop earlier in life than LL.14–16,43–45
TL is characterised by the
presence of high immunological resistance and low bacilli load, LL by low resistance and high bacilli load and borderline forms (BT, BB or BL) with variable resistance and bacilli loads. Paucibacillary types with minimal risk of transmission include TL and BT (with no acid fast rods on the smear).
TL patients usually present with one or a few well-defined hypo-pigmented or erythematous skin patches, with central loss of sensation and/or palpably enlarged peripheral nerve.14–16
LL patients
The nerve involvement pattern at diagnosis were single nerve involvement in 61, two in 57, three in 21 and more than three in 47 children.16
Diagnosis of Infection and Disease Tuberculosis
Diagnosis of MTB infection is based on T-cell reaction against MTB antigens as well as contact history. The traditionally used TST lacks sensitivity, especially in very young and immunocompromised children, while specificity is reduced by the presence of BCG vaccination and NTM exposure.22,27,32
usually present with ill-defined skin involvement and intact sensation. In a recent retrospective study of 306 children with leprosy, 35.3 % had a single skin patch, 48.4 % one to five and 13 % multiple (greater than five) patches.16
Blood tests based on the stimulation of lymphocytes with ‘MTB-specific’ antigens ESAT-6 and CFP-10 are referred to as IFN-γ release assays (IGRAs). IGRAs have increased specificity compared with TST, but may be false positive with specific NTM infections such as M. bovis or M. marinum and share the TST’s inability to distinguish between MTB infection and active disease.58,59
A major constraint of childhood TB management is the difficulty of establishing an accurate diagnosis of active disease. The main issue being the poor yield of microscopic and bacteriological tests, due to the paucibacillary nature of childhood TB and difficult specimen collection.22,27,32,33,58–61
Young children (<7–8 years) cannot
expectorate sputum and gastric aspirates are cumbersome due to the requirement of nasogastric tube placement.61
Moreover, gastric
aspirates can be contaminated by waterborne mycobacterial species, which reduces the specificity of microscopic diagnosis and requires at least MTB complex identification.8
Using a combination of induced
sputum and gastric aspirates is currently the most feasible alternative,61,62
but culture yields remain low (30–40 %),57 disease extent is considerable.61,64 unless Culture confirmation should always
be attempted in other samples such as cerebrospinal fluid, joint fluid and tissue biopsy by suspected extrapulmonary disease. In the absence of a reliable gold standard for diagnosis, different algorithms and scoring systems based on TB exposure, clinical signs and symptoms, TST and radiographic abnormalities have been developed, but none have been adequately validated.64
Recent attempts to
improve the TB diagnostic arsenal with more sensitive bacteriological tests that would be feasible in resource-limited settings include the microscopic observation drug susceptibility (MODS) assay, phage-based tests, solid culture calorimetric systems and molecular methods such as line probe assays and Xpert® MTB/rifampin (RIF) (Cepheid, Sunnyvale), but is unlikely that they perform better than liquid culture.32,57,65
Fine needle aspiration biopsy (FNAB) is
a safe alternative for sampling superficial peripheral masses, such as cervical lymph nodes and excellent diagnostic yields have
EUROPEAN INFECTIOUS DISEASE
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92