Geno-Spatial Distribution of Mycobacterium Tuberculosis and Drug Resistance Profiles in Myanmar–Thai Border Area
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Setting
2.2. Study Design and Participants
2.3. Samples Collection, Genomic DNA Extraction, and Whole Genome Sequencing
2.4. Genome Sequencing Data and Variant Calling
2.5. Phylogenetic Analysis
2.6. Genotyping
2.7. Prediction of Drug Resistance
2.8. Statistical Analysis
2.9. Ethics
3. Results
3.1. Socio-Demographic Information
3.2. Genotype Information
3.3. Geno-Spatial Analysis
3.4. Clinical Characteristics
3.5. Drug Resistance of TB Drug Information
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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L1 n (%) | L2 n (%) | L3 n (%) | L4 n (%) | Total n (%) | p Value * | |
---|---|---|---|---|---|---|
Total | 73 | 26 | 4 | 6 | 109 | |
Township | 0.1 | |||||
Hpa-An | 35 (48) | 10 (38) | 3 (75) | 5 (83) | 53 (49) | |
Kawkareik | 24 (33) | 5 (19) | 0 (0) | 1 (17) | 30 (28) | |
Myawaddy | 14 (19) | 11 (42) | 1 (25) | 0 (0) | 26 (24) | |
Gender | 0.02 | |||||
Male | 47 (64) | 23 (88) | 1 (25) | 4 (67) | 75 (69) | |
Female | 26 (36) | 3 (12) | 3 (75) | 2 (33) | 34 (31) | |
Age | 0.07 | |||||
Mean (SD) | 46 (15) | 43 (13) | 58 (7) | 36 (13) | 45 (14) | |
Age group (years) | 0.15 | |||||
<35 | 17 (23) | 8 (31) | 0 (0) | 3 (50) | 28 (26) | |
35−57 | 35 (48) | 14 (54) | 1 (25) | 3 (50) | 53 (49) | |
≥57 | 21 (29) | 4 (15) | 3 (75) | 0 (0) | 28 (26) | |
Ethnicity | 0.43 | |||||
Bamar | 23 (32) | 11 (42) | 2 (50) | 2 (33) | 38 (35) | |
Kayin | 33 (45) | 13 (50) | 1 (25) | 4 (67) | 51 (47) | |
Others | 17 (23) | 2 (8) | 1 (25) | 0 (0) | 20 (18) |
Major Lineage | Sublineage | n | Total (109) |
---|---|---|---|
L1 (EAI) | L1.1.1 | 8 | 73 |
L1.1.1.2 | 1 | ||
L1.1.1.5 | 2 | ||
L1.1.1.7 | 1 | ||
L1.1.1.8 | 3 | ||
L1.1.2.1 | 1 | ||
L1.1.2.2 | 10 | ||
L1.1.3 | 3 | ||
L1.1.3.1 | 17 | ||
L1.2.1 | 1 | ||
L1.2.1.1 | 2 | ||
L1.2.1.2 | 6 | ||
L1.2.1.3 | 1 | ||
L1.2.2 | 17 | ||
L2 (Beijing) | L2.2.1.1_M_Pacific | 2 | 26 |
L2.2.1_Asia_Ancestral_2 | 1 | ||
L2.2.1_Asia_Ancestral_3 | 1 | ||
L2.2.1_Asia_Ancestral_4 | 3 | ||
L2.2.1_M_Asian_African_2 | 8 | ||
L2.2.1_M_Asian_African_3 | 1 | ||
L2.2.1_M_Bmyc22 | 1 | ||
L2.2.1_Modern | 8 | ||
L2.2.2 | 1 | ||
L3 (Delhi/CAS) | L3 | 2 | 4 |
L3.1.2 | 1 | ||
L3.1.2.1 | 1 | ||
L4 (Euro-American) | L4.1.2 | 1 | 6 |
L4.3 | 1 | ||
L4.4 | 1 | ||
L4.5 | 1 | ||
L4.5.3 | 1 | ||
L4.8 | 1 |
Zone1 (97.458–97.646) | Zone2 (97.646–97.854) | Zone3 (97.854–98.244) | Zone4 (98.244–98.650) | Total | p Value * | |
---|---|---|---|---|---|---|
Total | 45 | 14 | 25 | 25 | 109 | |
Ethnicity group | <0.001 | |||||
Bamar | 17 (37.8) | 2 (14.3) | 3 (12.0) | 16 (64.0) | 38 (34.9) | |
Kayin | 22 (48.9) | 4 (28.6) | 18 (72.0) | 7 (28.0) | 51 (46.8) | |
Others | 6 (13.3) | 8 (57.1) | 4 (16.0) | 2 (8.0) | 20 (18.3) | |
Major Linage | 0.047 | |||||
L1 | 27 (60.0) | 14 (100) | 18 (72.0) | 14 (56.0) | 73 (67.0) | |
L2 | 10 (22.2) | 0 (0) | 6 (24.0) | 10 (40.0) | 26 (23.9) | |
L3 | 3 (6.7) | 0 (0) | 0 (0) | 1 (4.0) | 4 (3.7) | |
L4 | 5 (11.1) | 0 (0) | 1 (4.0) | 0 (0) | 6 (5.5) |
L1 n (%) | L2 n (%) | L3 n (%) | L4 n (%) | Total n (%) | p Value * | |
---|---|---|---|---|---|---|
Total | 73 | 26 | 4 | 6 | 109 | |
Blood in sputum | 0.9 | |||||
No | 55 (75) | 20 (77) | 4 (100) | 5 (83) | 84 (77) | |
Yes | 18 (25) | 6 (23) | 0 (0) | 1 (17) | 25 (23) | |
Fever > 2 weeks | 0.17 | |||||
No | 34 (47) | 18 (69) | 3 (75) | 4 (67) | 59 (54) | |
Yes | 39 (53) | 8 (31) | 1 (25) | 2 (33) | 50 (46) | |
Unexplained weight loss | 0.35 | |||||
No | 14 (19) | 5 (19) | 2 (50) | 2 (33) | 23 (21) | |
Yes | 59 (81) | 21 (81) | 2 (50) | 4 (67) | 86 (79) | |
Chest Pain | 0.35 | |||||
No | 26 (36) | 9 (35) | 3 (75) | 1 (17) | 39 (36) | |
Yes | 47 (64) | 17 (65) | 1 (25) | 5 (83) | 70 (64) | |
Severity of cough | 0.05 | |||||
Mild | 23 (32) | 8 (31) | 2 (50) | 3 (50) | 36 (33) | |
Moderate | 41 (56) | 10 (38) | 0 (0) | 3 (50) | 54 (50) | |
Severe | 9 (12) | 8 (31) | 2 (50) | 0 (0) | 19 (17) | |
HIV status | 0.46 | |||||
Positive | 3 (4) | 1 (4) | 0 (0) | 1 (17) | 5 (5) | |
Negative | 70 (96) | 25 (96) | 4 (100) | 5 (83) | 104 (95) | |
Type of TB Patient | 0.04 | |||||
New | 70 (96) | 20 (77) | 4 (100) | 6 (100) | 100 (92) | |
Retreated | 3 (4) | 6 (23) | 0 (0) | 0 (0) | 9 (8) | |
BCG | 0.86 | |||||
No | 23 (32) | 8 (31) | 2 (50) | 1 (17) | 34 (31) | |
Yes | 20 (27) | 10 (38) | 1 (25) | 2 (33) | 33 (30) | |
Unknown | 30 (41) | 8 (31) | 1 (25) | 3 (50) | 42 (39) | |
Sputum grading | 0.01 | |||||
Scanty | 0 (0) | 2 (8) | 0 (0) | 0 (0) | 2 (2) | |
1 + | 10 (14) | 9 (35) | 1 (25) | 2 (33) | 22 (20) | |
2 + | 16 (22) | 6 (23) | 1 (25) | 3 (50) | 26 (24) | |
3 + | 47 (64) | 9 (35) | 2 (50) | 1 (17) | 59 (54) | |
Site of TB | 0.81 | |||||
Lung | 69 (95) | 24 (92) | 4 (100) | 6 (100) | 103 (94) | |
Lung plus other | 4 (5) | 2 (8) | 0 (0) | 0 (0) | 6 (6) |
L1 n (%) | L2 n (%) | L3 n (%) | L4 n (%) | Total n (%) | p Value* | |
---|---|---|---|---|---|---|
Total | 39 | 19 | 2 | 3 | 63 | |
Isoniazid | 0.92 | |||||
Sensitive | 31 (79) | 14 (74) | 2 (100) | 3 (100) | 50 (79) | |
Resistant | 8 (21) | 5 (26) | 0 (0) | 0 (0) | 13 (21) | |
Rifampicin | 0.24 | |||||
Sensitive | 39 (100) | 17 (89) | 2 (100) | 3 (100) | 61 (97) | |
Resistant | 0 (0) | 2 (11) | 0 (0) | 0 (0) | 2 (3) | |
Pyrazinamide | 1 | |||||
Sensitive | 38 (97) | 18 (95) | 2 (100) | 3 (100) | 61 (97) | |
Resistant | 1 (3) | 1 (5) | 0 (0) | 0 (0) | 2 (3) | |
Ethambutol | 0.71 | |||||
Sensitive | 37 (95) | 17 (89) | 2 (100) | 3 (100) | 59 (94) | |
Resistant | 2 (5) | 2 (11) | 0 (0) | 0 (0) | 4 (6) | |
Streptomycin | 0.04 | |||||
Sensitive | 38 (97) | 14 (74) | 2 (100) | 3 (100) | 57 (90) | |
Resistant | 1 (3) | 5 (26) | 0 (0) | 0 (0) | 6 (10) | |
PAS | 0.38 | |||||
Sensitive | 39 (100) | 18 (95) | 2 (100) | 3 (100) | 62 (98) | |
Resistant | 0 (0) | 1 (5) | 0 (0) | 0 (0) | 1 (2) | |
Ethionamide | 0.82 | |||||
Sensitive | 35 (90) | 16 (84) | 2 (100) | 3 (100) | 56 (89) | |
Resistant | 4 (10) | 3 (16) | 0 (0) | 0 (0) | 7 (11) | |
At least one TB drug-resistant | 0.42 | |||||
Sensitive | 28 (72) | 11 (58) | 2 (100) | 3 (100) | 44 (70) | |
Resistant | 11 (28) | 8 (42) | 0 (0) | 0 (0) | 19 (30) |
Sub lineage | Rif | INH | PZA | ETB | STM | FQ | AM | ETO | PAS | CS |
---|---|---|---|---|---|---|---|---|---|---|
2_2_1_M_ Asian_ African_2 | rpoB_p.Ser450Leu | katG_p.Ser315Thr | pncA_p.Gly97Asp | embB_p.Met306Val | rpsL_p.Lys43Arg | - | - | - | - | - |
2_2_2 | rpoB_p.His445Asp | katG_p.Ser315Thr | - | embB_p.Met306Ile | rpsL_p.Lys43Arg | - | - | - | - | - |
1_1_2_2 | - | katG_p.Ser315Thr | - | embB_p.Asp328Gly | rrs_r.514a > c | - | - | - | - | - |
2_2_1_Modern | - | katG_p.Ser315Thr | - | - | rrs_r.517c > t | - | - | - | - | - |
1_2_1 | - | katG_p.Ser315Thr | - | - | - | - | - | fabG1_c.-15C > T | - | - |
2_2_1_M_ Asian_ African_2 | - | fabG1_c.-15C > T | - | - | - | - | - | fabG1_c.-15C > T | - | - |
1_1_3_1 | - | fabG1_c.-15C > T | - | - | - | - | - | fabG1_c.-15C > T | - | - |
2_2_1_Modern | - | katG_p.Ser315Thr | - | - | rpsL_p.Lys43Arg | - | - | - | - | - |
1_1_2_2 | - | - | panD_p.Ile49Val | - | - | - | - | ethA_c.1054_1054del | - | - |
2_2_1_Modern | - | - | - | - | rpsL_p.Lys43Arg | - | - | ethR_p.Ala95Thr | - | - |
1_1_1_8 | - | katG_p.Ser315Thr | - | - | - | - | - | - | - | - |
1_1_3 | - | katG_p.Ser315Thr | - | - | - | - | - | - | - | - |
1_1_3_1 | - | katG_p.Ser315Thr | - | - | - | - | - | - | - | - |
1_2_1_2 | - | katG_p.Ser315Thr | - | - | - | - | - | - | - | - |
1_2_2 | - | - | - | - | - | - | - | ethA_c.341_341del | - | - |
1_1_1 | - | ahpC_c.-52C > T | - | - | - | - | - | - | - | - |
2_2_1_Asia_ Ancestral_3 | - | - | - | - | - | - | - | - | folC_p.Thr20Pro | - |
2_2_1_M_ Asian_ African_2 | - | - | - | - | - | - | - | ethA_c.24_25insC | - | - |
1_2_2 | - | - | - | embB_p.Phe285Leu | - | - | - | - | - | - |
Our Study n (%) | Yangon n (%) | Thailand n (%) | Philippines n (%) | Nepal n (%) | |
---|---|---|---|---|---|
Lineage | 109 | 72 | 1170 | 178 | 498 |
L1 | 73 (67%) | 9 (13%) | 480 (41%) | 143 (80%) | 32 (6%) |
L2 | 26 (23%) | 55 (76%) | 521 (45%) | 2 (1%) | 241 (48%) |
L3 | 4 (4%) | 4 (5%) | 11 (1%) | 0 | 153 (32%) |
L4 | 6 (6%) | 4 (5%) | 158 (13%) | 33 (19%) | 72 (14%) |
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Maung, H.M.W.; Palittapongarnpim, P.; Aung, H.L.; Surachat, K.; Nyunt, W.W.; Chongsuvivatwong, V. Geno-Spatial Distribution of Mycobacterium Tuberculosis and Drug Resistance Profiles in Myanmar–Thai Border Area. Trop. Med. Infect. Dis. 2020, 5, 153. https://doi.org/10.3390/tropicalmed5040153
Maung HMW, Palittapongarnpim P, Aung HL, Surachat K, Nyunt WW, Chongsuvivatwong V. Geno-Spatial Distribution of Mycobacterium Tuberculosis and Drug Resistance Profiles in Myanmar–Thai Border Area. Tropical Medicine and Infectious Disease. 2020; 5(4):153. https://doi.org/10.3390/tropicalmed5040153
Chicago/Turabian StyleMaung, Htet Myat Win, Prasit Palittapongarnpim, Htin Lin Aung, Komwit Surachat, Wint Wint Nyunt, and Virasakdi Chongsuvivatwong. 2020. "Geno-Spatial Distribution of Mycobacterium Tuberculosis and Drug Resistance Profiles in Myanmar–Thai Border Area" Tropical Medicine and Infectious Disease 5, no. 4: 153. https://doi.org/10.3390/tropicalmed5040153