P-1375. Clinical Profiles and Treatment Outcomes of Indian Children with Drug-resistant Central Nervous System Tuberculosis

TL;DR

This study examines the clinical features, treatment regimens, and outcomes of Indian children with drug-resistant central nervous system tuberculosis, highlighting the challenges and adverse effects of treatment.

Contribution

The study provides one of the first detailed clinical analyses of pediatric drug-resistant central nervous system tuberculosis in India.

Findings

Most children presented with both TB meningitis and tuberculomas, and many experienced neurological deficits during treatment.

Adverse drug reactions were common, occurring in over 80% of patients, with long treatment durations averaging 22.57 months.

Unfavorable neurological outcomes, including residual deficits and hearing loss, were observed in a significant proportion of patients.

Abstract

Pediatric central nervous system tuberculosis (CNS-TB) accounts for 10% of all pediatric TB cases in India and carries the highest morbidity and mortality. However, data on pediatric drug resistant (DR) CNS-TB remains scarce. Regional data from Mumbai suggests that pediatric DR CNS-TB accounts for about 12% of all pediatric DR-TB cases. This dearth of epidemiological data translates to a lack of clinical studies on pediatric DR CNS-TB. This study aims to address this knowledge gap by analyzing the clinico-demographic profiles, laboratory findings, treatment regimens and outcomes, and adverse drug reactions (ADR) in a cohort of Indian children diagnosed with DR CNS-TB.Table 1:Clinical characteristics of the patients at presentationNote: SD- Standard deviation, IQR- interquartile range, TB- Tuberculosis, PTB- Pulmonary tuberculosis, EPTB- Extrapulmonary tuberculosis, LN- Lymph node, DR-TB- Drug-resistant tuberculosis, RR- Rifampicin resistant, MDR- Multidrug resistant, XDR- Extensively drug resistant.Table 2:CSF, microbiological, and blood investigations of the patients at presentationNote: CSF- Cerebrospinal fluid, SD- Standard deviation, TLC- Total leukocyte count, RR- Rifampicin resistant, RI- Rifampicin indeterminate, RS- Rifampicin sensitive, MGIT- Mycobacterial Growth Indicator Tube, ATT- Antitubercular therapy, LPA- Line probe assay, pDST- Phenotypic drug sensitivity testing, Hb- Hemoglobin, ALC- Absolute lymphocyte count, ESR- Erythrocyte sedimentation rate.

Clinical characteristics of the patients at presentation

Note: SD- Standard deviation, IQR- interquartile range, TB- Tuberculosis, PTB- Pulmonary tuberculosis, EPTB- Extrapulmonary tuberculosis, LN- Lymph node, DR-TB- Drug-resistant tuberculosis, RR- Rifampicin resistant, MDR- Multidrug resistant, XDR- Extensively drug resistant.

CSF, microbiological, and blood investigations of the patients at presentation

Note: CSF- Cerebrospinal fluid, SD- Standard deviation, TLC- Total leukocyte count, RR- Rifampicin resistant, RI- Rifampicin indeterminate, RS- Rifampicin sensitive, MGIT- Mycobacterial Growth Indicator Tube, ATT- Antitubercular therapy, LPA- Line probe assay, pDST- Phenotypic drug sensitivity testing, Hb- Hemoglobin, ALC- Absolute lymphocyte count, ESR- Erythrocyte sedimentation rate.

A retrospective study was conducted from May 2020 to April 2024 and included 44 children less than 18 years of age, diagnosed with DR CNS-TB, treated with second-line antitubercular therapy (ATT) regimens, and followed-up on an outpatient basis. Demographic, clinical, laboratory, treatment, ADR, and outcome data was collected and analysed.Table 3:Treatment details of the patientsNote: SD- Standard deviation, SLI- Second-line injectable, DLM- Delamanid, BDQ- Bedaquiline, IQR- Interquartile range, ATT- Antitubercular therapy.Table 4:ADRs of antitubercular therapy, thalidomide and steroidsNote: ADRs- adverse drug reactions, QTcF- QT interval corrected for heart rate by Fridericia's formula, BDQ- Bedaquiline, DLM- Delamanid, Cfz- Clofazimine, Mfx- Moxifloxacin, DILI- Drug-induced liver injury, Eto- Ethionamide, Cys- Cycloserine, PAS- Para-aminosalicylic acid, PZA- Pyrazinamide, Lzd- Linezolid.

Treatment details of the patients

Note: SD- Standard deviation, SLI- Second-line injectable, DLM- Delamanid, BDQ- Bedaquiline, IQR- Interquartile range, ATT- Antitubercular therapy.

ADRs of antitubercular therapy, thalidomide and steroids

Note: ADRs- adverse drug reactions, QTcF- QT interval corrected for heart rate by Fridericia's formula, BDQ- Bedaquiline, DLM- Delamanid, Cfz- Clofazimine, Mfx- Moxifloxacin, DILI- Drug-induced liver injury, Eto- Ethionamide, Cys- Cycloserine, PAS- Para-aminosalicylic acid, PZA- Pyrazinamide, Lzd- Linezolid.

Mean age at presentation was 9.67±4.41 years.Sixteen (36.36%) patients presented with TB meningitis alone, 7 (15.91%) patients presented with tuberculomas alone, and 21 (47.73%) presented with both. Past exposure to ATT was seen in 1 (2.27%) patient. Neurological deficits were observed in 16 (36.36%) patients during therapy, of which 4 (25%) had hemiparesis ± cranial nerve palsies, 1 (6.25%) had paraparesis with facial palsy, 1 (6.25%) had monoplegia with motor aphasia, and 10 (62.5%) patients had isolated cranial nerve palsies. Visual abnormalities during treatment were seen in 7 (15.91%) patients and sensorineural hearing loss (SNHL) was seen in 11 (25%) patients during treatment. New tuberculomas while on treatment were seen in 26 (59.09%) patients. ADR were seen in 36 (81.82%) patients. Mean duration of ATT given was 22.57±13.13 months. Of the 16 patients who developed motor deficits, 6 (37.5%) had residual motor deficits (1 had blindness, 6 had SNHL, 1 had residual hemiparesis and facial palsy, 3 had cranial nerve palsies), 3 (18.75%) recovered, 5 (31.25%) were still ongoing treatment, and 2 (12.5%) were lost to follow-up.

Pediatric DR CNS-TB is difficult to treat with high rates of ADR, long treatment durations, and unfavourable neurological outcomes.

All Authors: No reported disclosures

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