Accuracy of Xpert® MTB/RIF in diagnosing extrapulmonary tuberculosis in Indian children

BACKGROUND Diagnosing extrapulmonary tuberculosis (EPTB) can be challenging because of a variety of presentations. We assessed the accuracy of the Xpert MTB/RIF assay in diagnosing EPTB in children. METHODS Of the 255 children diagnosed to have tuberculosis (TB) who underwent testing by the Xpert MTB/ RIF assay at the TB clinic from December 2014 to April 2017, 182 had EPTB and were included in the study. The diagnostic accuracy, specificity and sensitivity of the Xpert assay were calculated with Mycobacterium growth indicator tube (MGIT) as a reference standard. RESULTS Lymph node TB was present in 58 (32%) children, 37 (20%) had neurological TB, 36 (20%) had bone TB, 31 (17%) had pleural TB, 15 (8%) had abdominal TB, 2 (1%) had abscess, 2 (1%) had congenital TB and disseminated TB was seen in 1 (0.4%) child. Xpert MTB/RIF assay was positive in 84 (46.2%) patients. The sensitivity and specificity of the Xpert MTB/RIF assay were 72% and 72.04%, respectively. Compared to MGIT, a kappa coefficient of 0.44 shows moderate agreement between the Xpert assay and MGIT. The sensitivity of Xpert MTB/RIF assay in abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 50% (15%–85%), 72.7% (15.9%– 86.9%), 80.8% (62.1%–91.5%), 75% (50.5%–90%) and 25% (4.6%–70%), respectively. The specificity of abdominal TB, bone TB, lymph node TB, neurological TB and pleural TB was 83.3% (43.7%–97%), 69.2% (42.4%– 87.3%), 55.2% (37.6%–71.6%), 85% (64%–94.8%) and 82.6% (62.9%–93%), respectively. Forty-seven (26%) patients had drug-resistant TB (DR-TB), of which 15 (8%) were rifampicin-resistant (RR), 2 (1%) were polyresistant, 14 (8%) had multi-DR (MDR), 15 (8%) had pre-extremely DR (XDR) and 1 (1%) had XDR-TB. Of the 15 patients with MDR-TB, Xpert MTB/RIF assay detected only 10 (71%) as RR (p=0.06). Of the 15 pre-XDR cases, Xpert MTB/RIF detected only 8 (53%) as RR (p=0.02). CONCLUSION Xpert MTB/RIF assay is useful in the diagnosis of EPTB. It shows good concordance with MGIT. However, it may be negative in patients with DR-TB.

Tenofovir in Indian Children.

We describe our experience with tenofovir-based antiretroviral therapy in seven HIV-infected children after failure of first line antiretroviral drugs, or due to adverse effects to other antiretrovirals. For follow-up period of average 3.4 years, none had adverse effects or failure of treatment, indicating that tenofovir has good renal and gastrointestinal safety profile in HIVinfected Indian children and adolescents.

Fetal valproate syndrome.

Antenatal use of anticonvulsant valproic acid can result in a well‑recognized cluster of facial dysmorphism, congenital anomalies and neurodevelopmental retardation. In this report, we describe a case with typical features of fetal valproate syndrome (FVS). A 26‑year‑old female with epilepsy controlled on sodium valproate 800 mg/day since 3 years, gave birth to a male child with characteristic features of FVS. She also had 3 spontaneous first‑trimester abortions during those 3 years. Sodium valproate, a widely used anticonvulsant and mood regulator, is a well‑recognized teratogen that can result in facial dysmorphism, craniosynostosis, neural tube defects, and neurodevelopmental retardation. Therefore, we strongly recommend avoidance of valproic acid and supplementation of folic acid during pregnancy.

Antibiotic Prescription Patterns in Children for Upper Respiratory Tract Infections and Diarrhea.

A cross sectional study to determine the antibiotic usage trend in children with URTI and Diarrhea in 140 children under 15 years of age visiting the Pediatric OPD. Forty four (31%) patients received antibiotics of which 5 (11.3%) patients received combination antibiotics. Eighteen (24%) patients with nasopharyngitis, 2(16%) patients with pharyngitis, 7(100%) patients with tonsillitis, 7(22.5%) patients with acute diarrhea, 5(62.5%) patients with dysentery and 5(83%) patients with chronic diarrhea received antibiotics. (p=0.014). Amoxicillin (33%) and macrolides (44%) are preferred for nasopharyngitis and only macrolides are used for pharyngitis (100%), while cefixime is used predominantly for acute diarrhea (29%) and dysentery (40%). Metronidazole (60%) is the preferred antibiotic for chronic diarrhea. All five (11%) combination antibiotics prescriptions were for diarrhea and no combinations were given for URTI [p value = 0.003]. From 110 children having symptoms < 1week, only 30 (27%) were given antibiotics while out of 29 children having symptoms for > 1week, 14 (48%) were given antibiotics (p value=0.031). Antibiotic prescriptions were judicious and seen in 31% of children with URTI and diarrhea. However use of antibiotics in nasopharyngitis should be minimized. Also use of combination antibiotics especially in children with diarrhea should be discouraged.

Clinical Profile of Drug Resistant Tuberculosis in Children.

This Cross-sectional observational study was conducted to determine the clinical profile of drug-resistant tuberculosis in children. Patients were classified as monoresistant TB, polyresistant TB, multidrug resistant (MDR)-TB and extensively drug resistant (XDR - TB). We coined a term called as Partial XDR-TB when isolates of Mycobacterium tuberculosis were confirmed to be resistant in vitro to be MDR along with either a fluoroquinolone or an aminoglycoside resistance (apart from streptomycin). Of 500 children analysed, 34 (6.8%) had drug resistant TB. Mean age of presentation was 6.8±3.2 years (Male: Female ratio 13:21). 18 (52.9%) children had been treated for tuberculosis in the past (1 defaulted), 7 patients had been in contact with an adult suffering from drug resistant TB and 3 patients (10.3%) were HIV co-infected. Fourteen children (41.2 %) had MDR TB, 11 (32.4 %) had Partial XDR, 1 each (2.9 %) had polyresistant TB and XDR TB. Clinical features of DR-TB are similar in all age groups. Past history of TB with treatment with antitubercular agents, and contact with adults suffering with drug-resistant TB are important risk factors in development of drug-resistant -TB in children.

Multidrug-resistant tuberculosis in an HIV-infected girl.

Multidrug-resistant tuberculosis (MDR-TB) in patients with human immunodeficiency virus (HIV) infection poses multiple challenges for treatment, and has a high mortality. MDR-TB coinfection with HIV has been reported in African children. In India, we did not come across any report of HIV and MDRTB coinfection in children, though such coinfection has been reported in adults. A 9-year-old HIV-infected girl requiring antiretroviral therapy (ART) developed MDR-TB and responded to second-line antituberculous therapy.

Clinical and biochemical factors associated with biliary atresia.

Aim: To determine the clinical and biochemical factors associated with biliary atresia. Methods: This retrospective study was carried at the Pediatric Hepatobiliary Clinic, of a tertiary care referral center, from May 2005 to April 2006. Thirty-three infants with neonatal cholestasis were enrolled. All patients were evaluated by detailed history and clinical examination. Patients diagnosed with biliary atresia on intra-operative cholangiogram and liver biopsy underwent the Kasai operation. Clinical and biochemical factors predictive of biliary atresia were determined. Results: Seventeen infants (51.5%) had neonatal hepatitis, (42.4%) biliary atresia and two (6.1%) neonatal sepsis. Clay colored stools was the only clinical feature suggestive of biliary atresia which was seen in 11 biliary atresia children (79%) and was statistically significant (p=0.05). No other biochemical markers were suggestive of biliary atresia, such as alkaline phosphatase (p=0.10) or gamma glutamyl transferase (GGTP) (p=0.64). On follow-up 6 patients (43%) with biliary atresia developed chronic liver disease and two patients (14%) died of their disease, whereas 41% patients with neonatal hepatitis made successful recovery. (p=0.02) Conclusion: Presence of clay colored stools is a predictive marker for biliary atresia and should be used as one of the markers for urgent cholangiogram, since most of the children with biliary atresia go on to develop chronic liver disease.

Smith-Lemli-Opitz-syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A severe defect in cholesterol biosynthesis has been identified leading to abnormally low plasma cholesterol levels and elevated levels of the cholesterol precursor 7-dehydrocholesterol, the result of deficiency of 7-dehydrocholesterol reductase. We describe one such child with Smith-Lemli-Opitz syndrome. This child had clinical features similar to Smith-Lemli-Opitz syndrome like facial dysmorphism and cardiac and renal anomalies with failure to thrive.

Response to Valacyclovir in an HIV-infected Girl with Epstein Barr Infection.

Response of EBV infection to valacyclovir in HIV infected children has not been reported earlier. An 8 years old HIV infected girl with undetectable viral load and normal CD4 count on regular antiretroviral therapy presented with persistent fever, lymphadenopathy and pancytopenia due to Epstein Barr virus (EBV). The child responded to valacyclovir.