Think central nervous system tuberculosis, also in low-risk children: a Danish nationwide survey

BACKGROUND: Paediatric central nervous system (CNS) tuberculosis (TB) imposes a high risk of death and neurologic sequelae, particularly if the diagnosis is delayed. Children from non-TB endemic countries are particularly at risk of delayed or missed diagnosis. We aimed to investigate CNS TB in Denmark, a TB low-endemic country and where Bacillus Calmette-Guerin (BCG) vaccination is not a part of the vaccination schedule.

METHODS: A nationwide retrospective case survey of all children with CNS TB in 2000-2015 identified through the National Danish TB Notification Register. We assessed epidemiology, clinical and paraclinical features, diagnostic criteria, treatment and outcome.

RESULTS: Nine ethnic Danes and 12 children from TB-endemic countries with CNS TB were identified. Clinical features, C-reactive protein, chest X-ray and indirect TB screening assays all had low sensitivity (19-75%). All (18/18) patients had elevated cerebrospinal fluid (CSF) white blood cells and 15 of 17 (88%) had a combination of at least two characteristic CSF findings (lymphocyte predominance, elevated protein and/or hypoglycorrhachia). Cerebral computed tomography and magnetic resonance imaging were abnormal in 10 of 16 (63%) and 12 of 14 (86%), respectively. Treatment was initiated after a median of 3 days in children from TB-endemic countries, and after 10 days in ethnic Danish children. One patient died (5%): A native Danish girl who died before the diagnosis was established.

CONCLUSIONS: Children from non-TB endemic countries may be at risk of delayed diagnosis and poorer prognosis compared to high-risk children. Cerebral magnetic resonance imaging and characteristic CSF findings had high diagnostic sensitivity.