Distribution of reported single nucleotide polymorphisms (SNPs) throughout the <i>pncA</i> gene.

<p>Dashed lines indicate the open reading frame for the <i>pncA</i> gene.</p

Forest plot for the summary estimates of pyrazinamide prevalence by WHO region and presence or risk of MDR-TB.

<p>Abbreviations: CI, confidence interval; DST, drug susceptibility test; MDR-TB, multi-drug resistant tuberculosis; N/A, not applicable; WHO, world health organization. MDR-TB was defined as an isolate being resistant to RIF and INH. High risk of MDR-TB was defined as an isolate being resistant to at least one anti-TB drug. *Any TB was defined as the inclusion of patients independent of drug resistance profile.</p

Flow diagram describing article selection.

<p>Flow diagram describing article selection.</p

Global distribution of included studies.

<p>Countries are shaded if a study was included in this review.</p

Estimated annual burden of new PZA resistant tuberculosis cases, overall and among MDR-TB patients, globally and by WHO region.

<p>Abbreviations: MDR-TB, multi-drug resistant tuberculosis; PZA, pyrazinamide; TB, tuberculosis; WHO, World Health Organization.</p><p>* Incidence of TB cases from the World Health Organization Global Tuberculosis Report 2014.</p><p>Estimated annual burden of new PZA resistant tuberculosis cases, overall and among MDR-TB patients, globally and by WHO region.</p

Frequency of strain genotype combinations cultured on MGIT or LJ media.

<p>Frequency of strain genotype combinations cultured on MGIT or LJ media.</p

Strain genotypes present in single and mixed infections.

<p>Strain genotypes present in single and mixed infections.</p

A minimum spanning tree (MST) illustrating evolutionary relationships between <i>M</i>. <i>tuberculosis</i> spoligotypes.

<p>MST constructed on all isolates including the orphan patterns (n = 293) in function of various characteristics. (<b>A</b>)MST based on phylogenetical lineages; (<b>B</b>) MST based on cities of isolation; and (<b>C</b>) MST based on HIV serology. The phylogenetic tree connects each genotype based on degree of changes required to go from one allele to another. The structure of the tree is represented by branches (continuous vs. dashed and dotted lines) and circles representing each individual pattern. Note that the length of the branches represents the distance between patterns while the complexity of the lines (continuous, gray dashed and gray dotted) denotes the number of allele/spacer changes between two patterns: solid lines, 1 or 2 or more changes (thicker ones indicate a single change, while the thinner one indicate 2 changes); gray dashed lines represent 3 changes; and gray dotted lines represent 4 or more changes. The size of the circle is proportional to the total number of isolates in our study, illustrating unique isolates (smaller nodes) versus clustered isolates (bigger nodes). The color of the circles indicates the phylogenetic lineage to which the specific pattern belongs.</p

Distribution of Spoligotype International Types (SIT) in this study.

<p>Distribution of Spoligotype International Types (SIT) in this study.</p

Strain genotypes cultured on MGIT and LJ media classified according to PCR amplification.

a<p>strain genotypes other than the strains tested with the 5 primer sets.</p>b<p>isolates did not amplify or amplified with an unknown product.</p>c<p>more than 1 strain genotype was present in the primary culture.</p>d<p>in combination, mixed infection was observed in 15% of cases.</p