Recombinant human parathyroid hormone (1-84) replacement therapy in a child with hypoparathyroidism.

First line conventional therapy of hypoparathyroidism comprises oral calcium and active vitamin D analogues. This approach may fail to correct hypocalcemia and hyperphosphatemia caused by the absence of parathyroid hormone and carries the risk of long-term complications including ectopic calcifications and renal damage. Full-length recombinant human parathyroid hormone (rhPTH[1-84]) is approved for the treatment of hypoparathyroidism in adults refractory to conventional therapy. To date, there is no data in children. Here, we report the successful use of rhPTH(1-84) in a 5-year old girl with hypoparathyroidism and concomitant chronic diarrhea manifesting as part of the autoimmune polyglandular syndrome type 1. Prior to starting rhPTH(1-84), the patient had been on conventional and later on rhPTH(1-34) continuous pump therapy. Conventional therapy failed to meet serum and urinary calcium target levels, whilst the pump therapy wasn't well tolerated and posed handling difficulties. Dose optimization for rhPTH(1-84) was informed by serum ionized calcium, spot urinary calcium-to-creatinine ratio and 24-hour urinary calcium excretion. Twice-daily subcutaneous injections of rhPTH(1-84) with a total dose of 3.35 µg/kg/d was well-tolerated, raised serum ionized calcium to target range (1.05-1.15 mmol/L) and normalized serum phosphate levels. Urinary calcium excretion was slightly above the recommended limit of 4 mg/kg/24 h, but improved compared to conventional therapy, with no evidence of nephrocalcinosis. Twice-daily administration stabilized serum calcium and phosphate levels compared to once-daily injections. rhPTH(1-84) treatment was well tolerated and the girl did not manifest any acute clinical complications of hypoparathyroidism throughout the entire observation period. Our experience with this case indicates that rhPTH(1-84) may be a physiological hormone replacement for managing hypoparathyroidism in children.

A Novel Sample Processing Method for Rapid Detection of Tuberculosis in the Stool of Pediatric Patients Using the Xpert MTB/RIF Assay.

BACKGROUND: Tuberculosis (TB) is difficult to diagnose in children using molecular tests, because children have difficulty providing respiratory samples. Stool could replace sputum for diagnostic TB testing if adequate sample processing techniques were available. METHODS: We developed a rapid method to process large volumes of stool for downstream testing by the Xpert MTB/RIF (Xpert) TB-detection assay. The method was tested and optimized on stool samples spiked with known numbers of M. tuberculosis colony forming units (CFU), and stools from M. tuberculosis-infected cynomolgus macaques (Macaca fascicularis). Performance was scored on number of positive Xpert tests, the cycle thresholds (Cts) of the Xpert sample-processing control (SPC), and the Cts of the M. tuberculosis-specific rpoB probes. The method was then validated on 20 confirmed TB cases and 20 controls in Durban, South Africa. RESULTS: The assay's analytical limit of detection was 1,000 CFU/g of stool. As much as one gram of spiked stool could be tested without showing increased PCR inhibition. In analytical spiking experiments using human stool, 1g samples provided the best sensitivity compared to smaller amounts of sample. However, in Macaques with TB, 0.6g stool samples performed better than either 0.2g or 1.2g samples. Testing the stool of pediatric TB suspects and controls suggested an assay sensitivity of 85% (95% CI 0.6-0.9) and 84% (95% CI 0.6-0.96) for 0.6g and 1.2g stool samples, respectively, and a specificity of 100% (95% CI 0.77-1) and 94% (95% CI 0.7-0.99), respectively. CONCLUSION: This novel approach may permit simple and rapid detection of TB using pediatric stool samples.