Additional file 1: Table S1. of The effect of surgery on the outcome of treatment for multidrug-resistant tuberculosis: a systematic review and meta-analysis

Search terms applied. Table S2. Information sources searched to identify relevant literature. Table S3. Search limits applied in Pubmed. Table S4. PRISMA 2009 Checklist. (DOCX 24 kb

Supplementary Material from The relative fitness of drug-resistant <i>Mycobacterium tuberculosis</i>: a modelling study of household transmission in Peru

Supplementary Methods and Result

Additional file 1: Table S1. of The effect of early versus late treatment initiation after diagnosis on the outcomes of patients treated for multidrug-resistant tuberculosis: a systematic review

PRISMA checklist. Table S2: Search terms applied in PubMed. Table S3: Number of search hits by database source. Supplementary post-hoc review text. (DOCX 139 kb

A minimum spanning tree (MST) illustrating evolutionary relationships between the Peruvian spoligotypes (n = 794).

<p>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. 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, black dotted and gray dotted) denotes the number of allele/spacer changes between two patterns: solid lines, 1 or 2 changes (thicker ones indicate a single change, while the thinner ones indicate 2 changes); dotted lines, three or more changes (black dotted for 3, and grey dotted for 4 or more changes). The color of the circles is proportional to the number of clinical isolates in our study, illustrating unique isolates (sky blue) versus clustered isolates (Blue, 2–5 strains; dark blue, 6–9 strains; Bordeaux, 10–19 strains; Red, 20 and more). Note that orphan patterns are circled with the letter “o” in red. Patterns marked by an asterisk (*) indicate a strain with an unknown signature (unclassified).</p

Discrete spoligotypes relationships for all isolates (n = 794) presented through spoligoforest tree drawn as a “hierarchical layout” using the SpolTools software (available through

<p><a href="http://www.emi.unsw.edu.au/spolTools" target="_blank">http://www.emi.unsw.edu.au/spolTools</a><b>; Reyes et al. 2008 </b><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065873#pone.0065873-Zignol1" target="_blank">[<b>11</b>]</a><b>).</b> Each spoligotype pattern from the study is represented by a node with area size being proportional to the total number of isolates with that specific pattern. Changes (loss of spacers) are represented by directed edges between nodes, with the arrowheads pointing to descendant spoligotypes. In this representation, the heuristic used selects a single inbound edge with a maximum weight using a Zipf model. Solid black lines link patterns that are very similar, i.e., loss of one spacer only (maximum weight being 1.0), while dashed lines represent links of weight comprised between 0.5 and 1, and dotted lines a weight less than 0.5. Orphan isolates, indicated in cyan, are isolated strains without interconnections with the other strains. This presentation illustrates for example the parental links for PGG2/3 strains such as SIT53 and SIT42, showing how SIT53 may be considered as the precursor of all other modern PGG2/3 patterns. SIT53 leads to SIT50/H3 by the loss of spacer 31, and it leads to SIT42 by the loss of four spacers (spacers 21–24), which in turn leads to SIT1355/LAM via SIT64/LAM6 then SIT95/LAM6. Through other spacer deletions, SIT53 leads to SIT91/X3 via SIT119/X1 and SIT92/X3. Lastly, SIT222/Unknown has no parental SITs in our study.</p

Strain spoligotype (SIT) frequency by patient HIV status and strain MDR status.

1<p>12 of 794 isolates lacked either MDR or HIV status data, leaving 782 here as the denominator.</p>2<p>Percentage of SIT-specific isolates with MDR.</p

Description of 122 shared-types (SITs; n = 767 isolates) and corresponding spoligotyping defined lineages/sublineages starting from a total of 794 <i>M. tuberculosis</i> strains isolated from adults with pulmonary tuberculosis in Lima, Peru.

*<p>A total of 100/122 SITs (n = 718) matched a preexisting shared-type in the database, whereas 22/122 SITs (n = 49 isolates) were newly created either within the present study or after a match with an orphan in the database. A total of 66 SITs containing 711 isolates were clustered within this study (2 to 130 isolates per cluster), while 56 SITs contained a unique strain within this study.</p><p>Note that SITs followed by an asterisk indicates “newly created shared-type” (n = 22 containing 49 isolates) due to 2 or more strains belonging to an identical new pattern within this study or after a match with an orphan in the database. SIT designations followed by number of strains: 2961* this study (n = 2); 3000* this study (n = 3); 3001* this study (n = 8) and USA (n = 1); 3004* this study (n = 2); 3005* this study (n = 2); 3006* this study (n = 2) and South Africa (n = 1); 3007* this study (n = 1) and USA (n = 1); 3008* this study (n = 1) and USA (n = 1); 3009* this study (n = 2); 3010* this study (n = 1) and USA (n = 1); 3011* this study (n = 4); 3012* this study (n = 2); 3013* this study (n = 3) and USA (n = 1); 3014* this study (n = 1) and Argentina (n = 1); 3015* this study (n = 2); 3016* this study (n = 1) and Panama (n = 1); 3017* this study (n = 3); 3089* this study (n = 2) and Mexico (n = 1); 3168* this study n = 1, Sweden (n = 1); 3431* this study (n = 2); 3432* this study (n = 2); 3433* this study (n = 2), BRA (n = 1).</p>**<p>Lineage designations according to SITVIT2 using revised SpolDB4 rules; “Unknown” designates patterns with signatures that do not belong to any of the major clades described in the database.</p>***<p>Clustered strains correspond to a similar spoligotype pattern shared by 2 or more strains “within this study”; as opposed to unique strains harboring a spoligotype pattern that does not match with another strain from this study. Unique strains matching a preexisting pattern in the SITVIT2 database are classified as SITs, whereas in case of no match, they are designated as “orphan” (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065873#pone-0065873-t001" target="_blank">Table 1</a>).</p

Associations with drug resistance.

<p>OR = odds ratio; 95% CI = 95% confidence interval; clustered SIT = in 9 most common SITs (accounting for 63% of all strains); bold type indicates statistically significant associations.</p>1<p>all adjusted ORs incorporate SIT42 and SIT53 and clustered SIT variable and into model.</p

Description of spoligotypes with corresponding spoligotyping defined lineages/sublineages and demographic information for 27 orphan strains identified from amongst 794 strains of <i>M. tuberculosis</i> isolated from adults with pulmonary tuberculosis in Lima, Peru.

*<p>Lineage designations for orphan patterns were done manually as Expert-based interpretations using revised SpolDB4 rules.</p>**<p>Drug-R code: 1, pansusceptible; 2, MDR (combined resistance to INH-RIF); 3, any other resistance; 4, XDR-TB (combined resistance to INH, RIF, fluoroquinolones, and 1 of 3 injectable drugs, i.e., capreomycin, kanamycin, or amikacin).</p

Description of clusters composed of predominant shared types (defined as SITs representing >2% strains, n = 16) in our study and their worldwide distribution in the SITVIT2 database.

*<p>Worldwide distribution is reported for regions with more than 3% of a given SITs as compared to their total number in the SITVIT2 database. The definition of macro-geographical regions and sub-regions (<a href="http://unstats.un.org/unsd/methods/m49/m49regin.htm" target="_blank">http://unstats.un.org/unsd/methods/m49/m49regin.htm</a>) is according to the United Nations; Regions: AFRI (Africa), AMER (Americas), ASIA (Asia), EURO (Europe), and OCE (Oceania), subdivided in: E (Eastern), M (Middle), C (Central), N (Northern), S (Southern), SE (South-Eastern), and W (Western). Furthermore, CARIB (Caribbean) belongs to Americas, while Oceania is subdivided in 4 sub-regions, AUST (Australasia), MEL (Melanesia), MIC (Micronesia), and POLY (Polynesia). Note that in our classification scheme, Russia has been attributed a new sub-region by itself (Northern Asia) instead of including it among rest of the Eastern Europe. It reflects its geographical localization as well as due to the similarity of specific TB genotypes circulating in Russia (a majority of Beijing genotypes) with those prevalent in Central, Eastern and South-Eastern Asia.</p>**<p>The 3 letter country codes are according to <a href="http://en.wikipedia.org/wiki/ISO_3166-1_alpha-3" target="_blank">http://en.wikipedia.org/wiki/ISO_3166-1_alpha-3</a>; countrywide distribution is only shown for SITs with ≥3% of a given SITs as compared to their total number in the SITVIT2 database.</p