Bacterial Infections Table 4: Continued Mycobacterium tuberculosis
Disease Spectrum Defining MTB disease spectrum in immunocompromised and competent children: there is need for better
Non-tuberculous Mycobacteria Defining NTM disease spectrum in
immunocompromised and competent children: there is need for better
classification of disease spectrum (such as classification of NTM disease spectrum in disseminated forms and IRIS) in HIV-infected immunocompromised children and children children for optimal management
with chronic pulmonary diseases for optimal management
Diagnosis
Validation of well-defined symptom-based Lack of reference standard for the diagnosis in children in endemic TB settings: accurate diagnosis is essential for timely treatment. This will reduce morbidity and mortality associated with
diagnosis of childhood NTM: a uniform diagnostic standard for NTM infection is urgently needed
Difficulty in the interpretation of TST:
Diagnostic delay: the slow progression of leprosy leads to late diagnosis, which may in turn lead to uncontrolled transmission in the household to vulnerable high-risk groups, including infants, young children and
childhood TB. A well-defined and validated there is variability in TST result in children HIV-infected persons symptom-based screening may also have with NTM due to cross-reactivity with considerable value to improve access of other mycobacterial antigens preventive therapy
New tool to improve the collection of adequate samples in children:
Translation of immune-based tests for NTM diagnosis:
Need for new diagnostic tools: most of the available tools for the diagnosis of leprosy are neither sensitive nor specific enough. New diagnostic tools (see text under
• IGRAs may be useful for differentiating diagnosis) have been or are being
• Collecting an adequate sputum sample between NTM and TB in low TB incidence developed to address this issue, although presents a serious challenge, particularly areas, especially when the TST is in young children <7–8 years, who
strongly positive
cannot expectorate qualitative sputum • Translation of present immune-based • Gastric washing is cumbersome and requires two to three specimens which necessitates hospitalisation
antibody and antigen (e.g. MPB-64
• Hypertonic saline-induced sputum seems to provide the same yield as three gastric washing specimens. Hypertonic saline induction still needs to be validated outside the hospital setting and may have a risk of nosocomial transmission of TB
• The string test as a non-invasive collection method in children needs to be validated in different settings. There is a risk of contamination with NTM ingested via contaminated water sources Imune-based tests: • IGRAs – although IGRAs are regarded as more specific and potentially more sensitive than TST, paediatric studies have been small and inconsistent
• Identification, improvement and validation of present immune-based antibody and antigen (e.g. MPB-64 antigen)-based diagnostic methods are needed
Organism-based tests: • Efforts must be made to improve the establishment of a definitive tissue and/or culture diagnosis of TB with effective and cheap new tools
Treatment
• Improving and validating organism-based diagnostics such as calorimetric culture-systems (e.g. TK-Medium), Phage-based tests (e.g. FASTplaque-TB) and MODS PCR-based tests are ongoing Improving access to and facilitating
Translation of new tool for the immunological diagnosis of TB (CFP-10 and
antigen)-based diagnostic methods for ESAT-6 proteins and M. leprae specific TB to NTM
antigens genomic for clinical use in leprosy management
Addressing stigmatisation issues: as happened with HIV, social, cultural and logistical issues relating to stigmatisation which lead to diagnostic and treatment delay must be adequately addressed to break the chain of silence
their clinical relevance, especially in children, is still unknown
Mycobacterium leprae
child-friendly drug formulations: the Global there is a lack of standardised treatment Global Drug Facility has approved child-friendly TB drug formulations for deserving countries
regimen and duration of treatment in Improving adherence to both preventive evaluate drug therapy and disease 108
Standardised treatment regimen for NTM: Optimising the dose and duration of treatment and monitoring of possible adverse effects in pauci- and multibacillary
paediatric populations. Larger studies with diseased children long follow-up periods are needed to
Facilitating child-friendly drug formulations for children with leprosy: as with TB,
EUROPEAN INFECTIOUS DISEASE
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