Title of Case(s):

A paradoxical case of missed resistance

Background:

Paradoxical reaction (PR) to antituberculous therapy is well described in HIV infected children (immune reconstitution inflammatory syndrome). However, it is not uncommon in immunocompetent children, particularly when young. PR can be clinically challenging to differentiate from other causes of deterioration such as drug resistance, and in some cases they co-exist.

Case Presentation Summary:

A previously healthy, HIV uninfected 3-year-old girl presented to clinic in Cape Town, South Africa with chronic cough and TB contact (her mother – sputum GeneXpert MTB/RIF Ultra (GXPU) positive, rifampicin sensitive, no cultures done).

The child had never received BCG. On examination, bilateral crackles and expiratory wheeze heard, no respiratory distress. Tuberculin skin test positive (18mm) and chest radiograph highly suggestive pulmonary TB:

Empiric drug sensitive antituberculous therapy was started.

Initial improvement of symptoms at two weeks, however by one month there was clinical and radiological deterioration despite good treatment adherence. Clinical examination revealed decreased breath sounds in right upper and middle zones, no respiratory distressed. Repeat chest radiograph showed further enlarged lymph nodes, new bronchus intermedius attenuation and features suggestive lobar collapse.

Culture results showed INH-monoresistance. Child admitted for bronchoscopy revealing 100% occlusion of bronchus intermedius. CT chest confirmed compression by clusters of confluent necrotic lymph nodes and resultant lobar collapse. Prednisone 2mg/kg/day added and antituberculous treatment changed to appropriate drug resistant regimen. Sputum cultures and drug sensitivity testing requested for the mother.

Two weeks later there was significant clinical and radiological improvement. Shortly thereafter the mother’s sputum culture showed INH-monoresistance.

Key Learning Points:

Deterioration on TB treatment can present a clinical challenge differentiating causes such as poor adherence, PR or drug resistance. They can also occur simultaneously.

GXPU reports rifampicin resistance only, thus INH monoresistance can be missed. Routine drug culture and sensitivity is imperative in adult contacts of children in high burden settings.

Backgrounds:

In adults, there is a high risk of recurrent TB after successful treatment, however limited data is available in children. The aim of this study was to determine burden and risk factors of TB recurrence in children.

Methods

Retrospective descriptive study of TB recurrence in children aged 0-13 years presenting with presumptive pulmonary TB in Cape Town, South Africa from March 2012 to November 2017. Recurrent TB is defined as >1 episode TB treatment (both confirmed or clinically diagnosed disease).

Results:

Data of 608 children were reviewed for TB recurrence, the median age was 16.7 months (interquartile range, IQR: 9.5-33.3), 324 male (53.3%) and 72 living with HIV (LHIV, 11.8%).

A total of 52/608 (8.4%) of all children had reported previous treatment for TB. Of these, 28 were treated again as TB cases, and 2 were excluded due to misdiagnosis of TB at previous episode. Recurrent TB was thus seen in 26/281 (9.3%) of current TB cases.

8/26 (30.8%) of children had the same TB contact as the previous episode. Current TB episode was confirmed in 11/26 (42.3%) with median time-lapsed since previous episode of 21 months (IQR: 16.3-45). Underlying comorbidities were seen in 19/26 (73.1%) of the children, all HIV infected and some with malnutrition (8/26) and chronic lung disease (3/26). Two thirds of children LHIV reported poor adherence to antiretrovirals (84.2%) and low CD4 counts.

Conclusions/Learning Points:

Recurrent TB was common in this young cohort of children with PTB. Children LHIV are at significantly higher risk for recurrent TB. More data is needed to identify other risk factors for recurrent TB and long-term follow up for repeated recurrence and post TB lung disease.

Figure 1: Identification of children with recurrent TB