Trends in burden of multidrug-resistant tuberculosis in countries, regions, and worldwide from 1990 to 2017: results from the Global Burden of Disease study.

BACKGROUND: Antituberculosis-drug resistance is an important public health issue, and its epidemiological patterns has dramatically changed in recent decades. This study aimed to estimate the trends of multidrug-resistant tuberculosis (MDR-TB), which can be used to inform health strategies. METHODS: Data were collected from the Global Burden of Disease study 2017. The estimated annual percentage changes (EAPCs) were calculated to assess the trends of MDR-TB burden at global, regional, and national level from 1990 to 2017 using the linear regression model. RESULTS: Globally, the age-standardized rate (ASR) of MDR-TB burden including incidence, prevalence, death and disability-adjusted life years (DALYs) had pronounced increasing trends from 1990 to 1999, with the EAPCs were 17.63 [95% confidence interval (CI): 10.77-24.92], 17.57 (95% CI 11.51-23.95), 21.21 (95% CI 15.96-26.69), and 21.90 (95% CI 16.55-27.50), respectively. Particularly, the largest increasing trends were seen in areas and countries with low and low-middle sociodemographic index (SDI). However, the trends in incidence, prevalence, death and DALYs of MDR-TB decreased globally from 2000 to 2017, with the respective EAPCs were - 1.37 (95% CI - 1.62 to - 1.12), - 1.32 (95% CI - 1.38 to - 1.26), - 3.30 (95% CI - 3.56 to - 3.04) and - 3.32 (95% CI - 3.59 to - 3.06). Decreasing trends of MDR-TB were observed in most regions and countries, particularly that of death and DALYs in Slovenia were - 18.96 (95% CI - 20.82 to - 17.06) and -19.35 (95% CI - 21.10 to - 17.55), respectively. Whereas the pronounced increasing trends of MDR-TB occurred in Papua New Guinea, Singapore, and Australia. CONCLUSIONS: The ASR of MDR-TB showed pronounced decreasing trends from 2000 to 2017. However, the MDR-TB burden remains a substantial challenge to the TB control globally, and requires effective control strategies and healthcare systems.

[Identification of a novel mutation of GALNS gene from a Chinese pedigree with mucopolysaccharidosis type IV A].

OBJECTIVE: To study the molecular genetic mechanism of mucopolysaccharidosis type IV A(MPS IV A), and reveal the relationship between the genotype and phenotype, and provide a basis for prenatal gene diagnosis in the future. METHODS: A preliminary diagnosis was made by qualitative detection of urinary glycosaminoglycans of the suspected MPS IV A proband. Then, mutation detection was performed on the proband and her family members with PCR and direct sequencing of the PCR products. After a novel c.1567T to G mutation was detected, Xsp I restriction enzyme digestion and amplification refractory mutation system (ARMS) fast specific identification were established to analyze the sequences of exon 14 in GALNS gene, including 110 randomly selected healthy controls, the proband and other pedigree members. At the same time, bioinformatic approaches for protein secondary, tertiary structure prediction were applied to identify the novel pathologic mutation. RESULTS: The proband's urine GAGs test was a weak positive(± ), and a c.1567T to G heterozygous termination codon mutation in exon 14 and a c.374C to T heterozygous missense mutation in exon 4 were found. The proband was compound heterozygous of the two mutations, so was her younger sister. Her mother was a carrier with only a c.1567T to G heterozygous mutation in exon 14. Her father had a heterozygous mutation of c.374C to T in exon 4. After Xsp I restriction enzyme digestion, healthy controls had three bands including 28 bp, 120 bp and 399 bp, while the proband and her mother had four bands consisting of 28 bp, 120 bp, 148 bp and 399 bp. For amplification by ARMS specific primers, it was negative for the controls, while it was positive for the proband and the carrier. The results of protein secondary and tertiary structure prediction showed that the c.1567T to G mutation located in the stop codon, resulted in stop codon (TAG) changing to glutamic acid (GAG), with the peptide chain extending 92 amino acid residues, and secondary and tertiary protein structure change, which were not found in the controls. The result of enzyme assay showed that the activity of GALNS enzyme in the affected child was 8.3 nmol/17h/mg pr, which was obviously lower than the normal value (the normal range is 41.9-92.1 nmol/17h/mg pr). CONCLUSION: These results illustrate that the c.1567 T to G is a novel pathologic mutation, which is the main cause of the disease in this family.

A new mutation (1062 del 16) of iduronate-2-sulfatase gene from a Chinese patient with Hunter syndrome.

OBJECTIVE: To identify the mutations of iduronate-2-sulfatase (IDS) gene, to reveal its mutation features, and to establish a basis for genetic counseling and prenatal gene diagnosis of Hunter syndrome. METHODS: Urine glycosaminoglycans (GAGs) assay, PCR and DNA sequencing were performed to detect mutation of IDS gene of the patient and his parents. RESULTS: The result showed that the patient was: DS(++), HS(++), KS(-), CS(-), and that both of his parents were negative. A frame-shift deletion mutation (1062 del 16) was identified in exon 7 of the patient's IDS gene. His parents' genotypes were normal. CONCLUSION: The patient's mutation was not inherited by his parents but a novel one. The mutation probably altered the primary structure and tertiary structure of IDS enzyme protein remarkably and lowered the activity of IDS enzyme greatly. Therefore it is supposed to be the direct cause of the disorder.