Background
Methods
Study sites and sample collection
Pvdhfr and pvdhps amplification and genotyping
In silico modelling of mutant PvDHFR
Statistical analysis
Results
Pvdhfr and pvdhps haplotypes
Pvdhfr | Pvdhps | Haplotypes | Faryab | Takhar | Nangarhar | Kunar | Nangarhar | Laghman | Total | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
I13L | P33L | N50I | F57L | S58R | T61M | S93H | S117N | I173L | A383G | A553G | pvdhfr / pvdhps | 2007 | 2007 | 2007 | 2010 | 2017 | 2017 | n = 185 |
n = 30 | n = 30 | n = 39 | n = 28 | n = 37 | n = 21 | |||||||||||||
I | P | N | F | S | T | S | S | I | A | A | WT / WT | 23 (77%) | 24 (80%) | 33 (85%) | 18 (64%) | 12 (32%) | 9 (43%) | 119 (64%) |
I | P | I | F | S | T | S | S | I | A | A | N50I / WT | 1 (3%) | 1 (3%) | 3 (2%) | ||||
I | P | NI | F | S | T | S | S | I | A | A | 1 (3%) | |||||||
I | P | N | F | R | T | S | S | I | A | A | S58R / WT | 1 (5%) | 3 (2%) | |||||
I | P | N | F | SR | T | S | S | I | A | A | 1 (3%) | 1 (3%) | ||||||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 2 (7%) | 1 (3%) | 1 (3%) | 1 (4%) | 3 (8%) | 8 (4%) | |
I | P | N | F | S | T | S | N | I | A | A | S117N / WT | 5 (17%) | 1 (3%) | 5 (18%) | 5 (14%) | 3 (14%) | 19 (10%) | |
I | P | I | F | S | T | S | N | I | A | A | N50IS117N / WT | 3 (10%) | 5 (14%) | 2 (10%) | 10 (5%) | |||
I | P | N | FL | SR | T | S | S | I | A | A | F57LS58R / WT | 1 (3%) | 1 (1%) | |||||
I | P | N | F | R | T | S | N | I | A | A | S58RS117N / WT | 1 (3%) | 3 (11%) | 8 (22%) | 4 (19%) | 16 (9%) | ||
I | P | N | F | S | T | H | N | I | A | A | S93HS117N / WT | 1 (4%) | 2 (10%) | 3 (2%) | ||||
I | P | N | F | S | T | S | N | I | G | A | S117N / A383G | 2 (5%) | 2 (1%) | |||||
I | P | N | F | R | T | S | N | I | G | A | S58RS117N / A383G | 1 (3%) | 1 (1%) |
Temporal changes in pvdhfr and pvdhps haplotypes between 2007 and 2017
In silico modelling of novel pvdhfr mutations
Discussion
Year of sampling | Countries | States/ provinces | Pvdhfr | Pvdhps | Haplotypes | Frequencies | Prevalence | References | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
I13L | P33L | N50I | F57L | S58R | T61M | S93H | S117N | I173L | A383G | A553G | pvdhfr / pvdhps | ||||||
2008 | Afghanistan | Herat | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 92% (79/85) | ||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 5% (4/85) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 1% (1/85) | [25] | ||||
I | P | – | F | R | T | – | N | I | G | A | S58RS117N / A383G | 1% (1/85) | |||||
Nangarhar | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 79% (68/86) | ||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 15% (13/86) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 6% (5/86) | |||||
2007–2008 | Afghanistan | Faryab | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 77% (23/30) | This study | |
I | P | I | F | S | T | S | S | I | A | A | N50I / WT | 3% (1/30) | |||||
I | P | N | F | R | T | S | S | I | A | A | S58R / WT | 3% (1/30) | |||||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 7% (2/30) | |||||
I | P | I | F | S | T | S | N | I | A | A | N50IS117N / WT | 10% (3/30) | |||||
Takhar | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 80% (24/30) | ||||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 3% (1/30) | |||||
I | P | I | F | S | T | S | N | I | A | A | S117N / WT | 17% (5/30) | |||||
Nangarhar | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 85% (33/39) | ||||
I | P | I | F | S | T | S | S | I | A | A | N50I / WT | 3% (1/39) | |||||
I | P | N | F | R | T | S | S | I | A | A | S58R / WT | 3% (1/39) | |||||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 3% (1/39) | |||||
I | P | N | F | S | T | S | N | I | A | A | S117N / WT | 3% (1/39) | |||||
I | P | N | L | R | T | S | S | I | A | A | F57LS58R / WT | 3% (1/39) | |||||
I | P | N | F | R | T | S | N | I | A | A | S58RS117N / WT | 3% (1/39) | |||||
2009–2010 | Afghanistan | Kunar | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 64% (18/28) | ||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 4% (1/28) | |||||
I | P | N | F | S | T | S | N | I | A | A | S117N / WT | 18% (5/28) | |||||
I | P | N | F | R | T | S | N | I | A | A | S58RS117N / WT | 11% (3/28) | |||||
I | P | N | F | S | T | H | N | I | A | A | S93HS117N / WT | 4% (1/28) | |||||
2017 | Afghanistan | Nangarhar | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 32% (12/37) | ||
I | P | I | F | S | T | S | S | I | A | A | N50I / WT | 3% (1/37) | |||||
I | P | N | F | S | T | H | S | I | A | A | S93H / WT | 8% (3/37) | |||||
I | P | N | F | S | T | S | N | I | A | A | S117N / WT | 14% (5/37) | |||||
I | P | I | F | S | T | S | N | I | A | A | N50IS117N / WT | 14% (5/37) | |||||
I | P | N | F | R | T | S | N | I | A | A | S58RS117N / WT | 22% (8/37) | |||||
I | P | N | F | S | T | S | N | I | G | A | S117N / A383G | 5% (2/37) | |||||
I | P | N | F | R | T | S | N | I | G | A | S58RS117N / A383G | 3% (1/37) | |||||
Lagman | I | P | N | F | S | T | S | S | I | A | A | WT / WT | 43% (9/21) | ||||
I | P | N | F | R | T | S | S | I | A | A | S58R / WT | 5% (1/21) | |||||
I | P | N | F | S | T | S | N | I | A | A | S117N / WT | 14% (3/21) | |||||
I | P | I | F | S | T | S | N | I | A | A | N50IS117N / WT | 10% (2/21) | |||||
I | P | N | F | R | T | S | N | I | A | A | S58RS117N / WT | 19% (4/21) | |||||
I | P | N | F | S | T | H | N | I | A | A | S93HS117N / WT | 10% (2/21) | |||||
2007 | Pakistan | Bannu | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 7% | [28] | |
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 75% | |||||
I | P | – | L | R | T | – | S | I | A | A | F57LS58R / WT | 2% | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 16% | |||||
2008 | Pakistan | FATA | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 44% (72/164) | [30] | |
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 1% (3/164) | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 40% (65/164) | |||||
I | P | – | F | S | T | – | S | I | G | A | WT / A383G | 1% (1/164) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 13% (22/164) | |||||
I | P | – | F | S | T | – | N | I | G | A | S117N / A383G | 1% (1/164) | |||||
2011 | Pakistan | Baluchistan, Islamabad, Khyber Pakhtunkhwa, Punjab, Sindh, | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 44% (143/322) | ||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 1% (3/322) | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 30% (95/322) | |||||
I | P | – | F | S | T | – | S | I | G | A | WT / A383G | 0.3% (1/322) | |||||
I | P | – | F | S | T | – | S | I | A | G | WT / A553G | 0.3% (1/322) | |||||
I | P | – | L | R | T | – | S | I | A | A | F57LS58R / WT | 1.6% (5/322) | [31] | ||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 21% (69/322) | |||||
I | P | – | F | S | T | – | N | I | G | A | S117N / A383G | 0.6% (2/322) | |||||
I | P | – | F | R | T | – | N | I | G | A | S58RS117N / A383G | 0.6% (2/322) | |||||
I | P | – | F | R | T | – | N | I | G | G | S58RS117N / A383GA553G | 0.3% (1/322) | |||||
2008–2009 | Pakistan | Karachi, Sindh, Baluchistan, | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 40% (51/131) | ||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 2% (2/131) | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 18% (24/131) | |||||
I | P | – | F | S | T | – | S | I | G | A | WT / A383G | 7% (9/131) | |||||
I | P | – | L | R | T | – | S | I | A | A | F57LS58R / WT | 2% (3/131) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 25% (33/131) | [29] | ||||
I | P | – | F | R | T | – | S | I | G | A | S58R / A383G | 1% (1/131) | |||||
I | P | – | F | S | T | – | N | I | G | A | S117N / A383G | 2% (3/131) | |||||
I | P | – | F | R | T | – | N | I | G | A | S58RS117N / A383G | 3% (4/131) | |||||
I | P | – | F | R | T | – | N | I | G | G | S58RS117N / A383GA553G | 1% (1/131) | |||||
2001–2006 | Iran | Sistan and Baluchistan | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 59% (85/143) | ||
I | P | – | L | S | T | – | S | I | A | A | F57L / WT | 1% (1/143) | |||||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 9% (13/143) | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 18% (26/143) | |||||
I | P | – | L | R | T | – | S | I | A | A | F57LS58R / WT | 1% (1/143) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 12% (17/141) | [27] | ||||
Ardebil | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 85% (39/46) | ||||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 2% (1/46) | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 11% (5/46) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 2% (1/46) | |||||
2010–2015 | Iran | Hormozgan | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 73% (58/80) | ||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 11% (9/80) | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 8% (6/80) | [26] | ||||
I | P | – | F | R | T | – | S | I | G | A | S58R / A383G | 6% (5/80) | |||||
I | P | – | L | R | T | – | N | I | A | A | F57LS58RS117N / WT | 3% (2/80) | |||||
2003–2004 | India | India | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 51% | ||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 1% | [38] | ||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 48% | |||||
2011–2012 | India | Aligarh | I | P | – | F | S | T | S | S | I | A | A | WT / WT | 61% (28/46) | ||
I | P | – | F | S | T | H | S | I | A | A | S93H / WT | 7% (3/46) | [39] | ||||
I | P | – | F | S | T | S | N | I | A | A | S117N / WT | 7% (3/46) | |||||
I | P | – | F | R | T | S | N | I | A | A | S58RS117N / WT | 26% (12/46) | |||||
Kolkata | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 35% | ||||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 3% | |||||
I | P | – | F | S | T | – | S | I | G | A | WT / A383G | 24% | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 6% | [37] | ||||
I | P | – | F | S | T | – | S | I | G | G | WT / A383GA553G | 1% | |||||
I | P | – | F | R | T | – | N | I | G | A | S58RS117N / A383G | 30% | |||||
I | P | – | F | R | T | – | N | I | G | G | S58RS117N / A383GA553G | 1% | |||||
2013–2014 | India | KMC | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 37% | ||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 6% | [36] | ||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 54% | |||||
I | P | – | L | R | T | – | N | I | A | A | F57LS58RS117N / WT | 4% | |||||
Purulia | I | P | – | F | S | T | – | S | I | A | A | WT / WT | 4% | ||||
I | P | – | F | R | T | – | S | I | A | A | S58R / WT | 15% | |||||
I | P | – | F | S | T | – | N | I | A | A | S117N / WT | 9% | |||||
I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 8% | |||||
2014–2015 | India | Mangaluru | I | P | – | F | R | T | – | N | I | A | A | S58RS117N / WT | 100% (25/25) | [21] |