Background
Methods
Study sites
Study population
Sample size
Ethical considerations
Treatment and follow-up
Rescue medication
Laboratory methods
Genotyping at baseline and recurrent infections
Genotyping for SP-resistance genes
Statistical analysis
Results
Efficacy studies on AL
Drug | Site | Study years | N | Males | Age group | Temperature D0 | Parasite count (/uL), D0 | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
<5 years | 5–14 years | ≥15 years | |||||||||||||
N | (%) | N | (%) | N | (%) | N | (%) | Mean | (SD) | Geometric mean | Range | ||||
AS + SP | Kosti | 2010 | 92 | 57 | (62) | 14 | (15) | 59 | (64) | 19 | (21) | 38.1 | (1) | 26,202 | (5470–90,940) |
Sennar | 2010 | 97 | 51 | (53) | 5 | (5) | 69 | (71) | 23 | (24) | 38.4 | (0.9) | 13,973 | (1800–71,889) | |
Gedaref | 2011–12 | 100 | 53 | (53) | 17 | (17) | 52 | (52) | 31 | (31) | 39 | (1.1) | 11,725 | (1600–129,167) | |
Kassala | 2011 | 75 | 44 | (59) | 24 | (32) | 17 | (23) | 34 | (45) | 38.1 | (0.8) | 5917 | (1020–68,421) | |
Kosti | 2011 | 98 | 55 | (56) | 17 | (17) | 63 | (64) | 18 | (18) | 38.1 | (1.1) | 14,249 | (3380–88,098) | |
Sennar | 2011 | 95 | 43 | (44) | 9 | (10) | 71 | (75) | 15 | (16) | 37.9 | (1.2) | 10,592 | (1400–57,910) | |
Kosti | 2012–13 | 95 | 45 | (47) | 20 | (21) | 58 | (61) | 17 | (18) | 37.1 | (1.1) | 18,541 | (1120–97,143) | |
Damazin | 2013–14 | 100 | 61 | (61) | 19 | (19) | 67 | (67) | 14 | (14) | 37.7 | (1) | 15,657 | (1460–90,000) | |
Sennnar | 2013–14 | 88 | 57 | (65) | 9 | (10) | 76 | (86) | 3 | (3) | 37.1 | (0.9) | 8252 | (1140–35,500) | |
New Halfa | 2013–14 | 80 | 40 | (50) | 14 | (18) | 25 | (31) | 41 | (51) | 38.6 | (1.8) | 12,798 | (2123–116,666) | |
Gedaref | 2014–15 | 93 | 47 | (51) | 15 | (16) | 58 | (62) | 20 | (22) | 37.6 | (0.9) | 11,165 | (1053–52,319) | |
AL | Damazin | 2010 | 67 | 32 | (48) | 0 | (0) | 30 | (45) | 37 | (55) | 38.2 | (0.6) | 11,203 | (1675–100,000) |
Kassala | 2010 | 85 | 57 | (67) | 11 | (13) | 40 | (47) | 34 | (40) | 37.8 | (1) | 11,245 | (1500–97,142) | |
Kosti | 2012–13 | 101 | 64 | (63) | 7 | (7) | 44 | (44) | 50 | (50) | 38.2 | (0.9) | 5339 | (1000–45,756) | |
Damazin | 2013 | 98 | 54 | (55) | 11 | (11) | 64 | (65) | 23 | (24) | 38.1 | (0.9) | 12,095 | (3020–70,961) | |
Kassala | 2013–14 | 84 | 53 | (63) | 12 | (14) | 32 | (38) | 40 | (48) | 38 | (0.7) | 16,226 | (1100–90,000) | |
Sennar | 2013–14 | 42 | 22 | (52) | 5 | (12) | 26 | (62) | 11 | (26) | 38.5 | (1.2) | 18,695 | (3280–93,939) | |
Gedaref | 2013–14 | 35 | 26 | (74) | 1 | (3) | 10 | (29) | 24 | (69) | 37.6 | (0.9) | 8524 | (1060–75,000) | |
Sennar | 2014 | 41 | 22 | (54) | 8 | (20) | 25 | (61) | 8 | (20) | 37.8 | (1.1) | 10,827 | (1040-78,110) | |
Gedaref | 2014–15 | 42 | 29 | (69) | 7 | (17) | 23 | (55) | 12 | (29) | 37 | (1.1) | 4741 | (1300–14,240) |
Site | Study years | N | PD3 | PCR un-corrected | PCR corrected | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Excl/loss | ETF | LCF | LPF | ACPR | Excl/loss | ETF | LCF | LPF | ACPR | Cure rate (KM) | (95 % CI) | |||||
AS + SP | Kosti | 2010 | 92 | 0 | 6 | 0 | 4 | 0 | 82 | 6 | 0 | 4 | 0 | 82 | 95.3 | (88.1–98.2) |
Sennar | 2010 | 97 | 0 | 5 | 0 | 4 | 1 | 87 | 6 | 0 | 3 | 1 | 87 | 95.7 | (89.0–98.4) | |
Gedaref | 2011-12 | 100 | 0 | 0 | 0 | 3 | 10 | 87 | 4 | 0 | 3 | 6 | 87 | 91 | (83.4–95.2) | |
Kassala | 2011 | 75 | 0 | 1 | 0 | 2 | 1 | 71 | 3 | 0 | 1 | 0 | 71 | 98.6 | (90.7–99.8) | |
Kosti | 2011 | 98 | 0 | 8 | 0 | 5 | 0 | 85 | 13 | 0 | 0 | 0 | 85 | 100 | (95.8–100) | |
Sennara
| 2011 | 95 | 0 | 1 | 0 | 6 | 7 | 81 | 12 | 0 | 0 | 1 | 81 | 98.9 | (92.5–99.8) | |
Kostia
| 2012-13 | 95 | 0 | 7 | 0 | 1 | 4 | 83 | 11 | 0 | 0 | 0 | 83 | 100 | (95.7–100) | |
Damazina
| 2013-14 | 100 | 0 | 26 | 0 | 3 | 5 | 66 | 30 | 0 | 1 | 2 | 66 | 95.9 | (87.9–98.7) | |
Sennnar | 2013-14 | 88 | 0 | 0 | 0 | 2 | 6 | 80 | 5 | 0 | 1 | 2 | 80 | 96.4 | (89.2–98.8) | |
New Halfa | 2013-14 | 80 | 0 | 0 | 1 | 0 | 0 | 79 | 0 | 1 | 0 | 0 | 79 | 98.7 | (91.4–99.8) | |
Gedarefa
| 2014-15 | 93 | 1 | 0 | 0 | 7 | 15 | 70 | 10 | 0 | 2 | 10 | 70 | 86.5 | (77.5–92.1) | |
AL | Damazin | 2010 | 67 | 0 | 0 | 1 | 0 | 0 | 66 | 0 | 1 | 0 | 0 | 66 | 98.5 | (89.9–99.8) |
Kassala | 2010 | 85 | 0 | 1 | 0 | 0 | 0 | 84 | 1 | 0 | 0 | 0 | 84 | 100 | (95.7–100) | |
Kosti | 2012-13 | 101 | 0 | 10 | 0 | 1 | 1 | 89 | 12 | 0 | 0 | 0 | 89 | 100 | (95.9–100) | |
Damazin | 2013 | 98 | 0 | 12 | 0 | 1 | 6 | 79 | 18 | 0 | 0 | 1 | 79 | 98.9 | (92.1–99.8) | |
Kassalaa
| 2013-14 | 84 | 0 | 1 | 0 | 1 | 0 | 82 | 1 | 0 | 0 | 0 | 82 | 100 | (95.6–100) | |
Sennar-Almazad | 2013-14 | 42 | 0 | 11 | 0 | 0 | 2 | 29 | 12 | 0 | 0 | 1 | 29 | 96.8 | (79.2–99.5) | |
Gedaref-Rawashda | 2013-14 | 35 | 0 | 0 | 0 | 0 | 0 | 35 | 0 | 0 | 0 | 0 | 35 | 100 | n/a | |
Sennar-Abei | 2014 | 41 | 0 | 0 | 0 | 1 | 1 | 39 | 1 | 0 | 1 | 0 | 39 | 97.5 | (83.5–99.6) | |
Gedaref-Karari | 2014-15 | 42 | 1 | 0 | 0 | 0 | 1 | 41 | 0 | 0 | 0 | 1 | 41 | 97.7 | (84.3–99.7) |
Efficacy studies on AS + SP
Gametocytaemia after treatment
Comparison of molecular markers of SP resistance among four sites in 2011
Number of mutations | Mutation haplotype | KASSALA N = 79 | GEDAREF N = 96 | SENNAR N = 98 | KOSTI N = 92 | p value* |
---|---|---|---|---|---|---|
None |
dhfr wild type | 2 (2.5 %) | 2 (2.1 %) | 4 (4.1 %) | 7 (7.6 %) | 0.27 |
Double | N51I, S108 N | 73 (92.4 %) | 67 (69.8 %) | 87 (88.8 %) | 78 (84.9 %) | <0.001 |
N51I, C59R | 0 | 1 (1.0 %) | 0 | 1 (1.0 %) | ||
Triple | N51I, C59R, S108 N | 4 (5.1 %) | 26** (27.1 %) | 7 (7.1) | 6 (6.5 %) | <0.001 |
Number of mutations |
Dhps haplotype | Kassala | Gedaref | Sennar | KostiI | Pearson’s Chi square | p value |
---|---|---|---|---|---|---|---|
None | wild dhps type | 14 (17.3 %) | 22 (22.9 %) | 30 (30.0 %) | 57(64.0 %)a
| 52.127 | <0.001 |
Single | S436A | 0 | 2 | 1 | 2 | ||
A437G | 0 | 4 | 0 | 4 | |||
K540E | 0 | 3 | 1 | 0 | |||
A581G | 1 | 0 | 1 | 1 | |||
S436C | 0 | 0 | 9 | 0 | |||
Double | A437G, K540E | 26 (32.1 %) | 44 (45.8 %) | 34 (34.0 %) | 24 (27.0 %)b
| 7.824 | 0.050 |
S436C, A581G | 0 | 0 | 2 | 0 | |||
S436C, K540E | 0 | 0 | 1 | 0 | |||
A437G, A581G | 0 | 0 | 1 | 0 | |||
Triple | S436A, A437G, K540E | 6 (7.4 %) | 6 (6.2 %) | 0 | 0 | ||
A437G, K540E, A581G | 33 (40.7 %) | 15 (15.6 %) | 20 (20 %) | 1 (1 %)c
| <0.001d
| ||
Quadruple | S436A, A437G, K540E, A581G | 1 | 0 | 0 | 0 | ||
Total | 81 | 96 | 100 | 89 |
Haplotypes | Kassala, n = 79 | Gedaref, n = 96 | Sennar, n = 98 | Kosti, n = 88 | Total | p value* |
---|---|---|---|---|---|---|
N (%) | N (%) | N (%) | N (%) | N | ||
dhfr wild type + dhps wild type | 1 (1.3) | 1 (1) | 4 (4.1) | 6 (6.8) | 12 | 0.133 |
All double mutants | 9 (11.4) | 17 (17.7) | 23 (23.5) | 48 (54.5) | 97 | <0.001 |
dhfr N51I, S108 N + dhps wild type | 9 (11.4) | 17 (17.7) | 23 (23.5) | 47 (53.4) | 96 | <0.001 |
dhfr wild type + dhps A437G + K540E | 0 (0) | 0 (0) | 0 (0) | 1 (1.1) | 1 | |
All triple mutants | 6 (7.6) | 13 (13.5) | 15 (15.3) | 11 (12.5) | 45 | 0.467 |
dhfr N51I, C59R, S108 N + dhps wild type | 4 (5.1) | 4 (4.2) | 3 (3.1) | 4 (4.5) | 15 | 0.911 |
dhfr N51I, S108 N + dhps S436A | 0 (0) | 0 (0) | 1 (1.0) | 2 (2.3) | 3 | |
dhfr C59R, S108 N + dhps S436A | 0 (0) | 1 (1) | 0 (0) | 0 (0) | 1 | |
dhfr N51I, S108 N + dhps A437G | 0 (0) | 4 (4.2) | 0 (0) | 4 (4.5) | 8 | |
dhfr N51I, S108 N + dhps K540E | 0 (0) | 3 (3.1) | 1 (1.0) | 0 (0) | 4 | |
dhfr N51I, S108 N + dhps A581G | 1 (1.3) | 0 (0) | 1 (1.0) | 1 (1.1) | 3 | |
dhps A437G, K540E, A581G | 1 (1.3) | 1 (1) | 0 (0) | 0 (0) | 2 | |
dhfr N51I, S108 N + dhps S436C | 0 (0) | 0 (0) | 9 (9.2) | 0 (0) | 9 | |
All quadruple mutants | 25 (31.6) | 28 (29.2) | 38 (38.8) | 20 (22.7) | 111 | 0.125 |
dhfr N51I, C59R, S108 N + dhps S436A | 0 (0) | 1 (1) | 0 (0) | 0 (0) | 1 | |
dhfr N51I, S108 N + dhps A437G, K540E | 25 (31.6) | 27 (28.1) | 34 (34.7) | 20 (22.7) | 106 | 0.325 |
dhfr N51I, S108 N + dhps A437G, A581G | 0 (0) | 0 (0) | 1 (1.0) | 0 (0) | 1 | |
dhfr N51I, S108 N + dhps A436C, K540E | 0 (0) | 0 (0) | 1 (1.0) | 0 (0) | 1 | |
dhfr N51I, S108 N + dhps A436C, A581G | 0 (0) | 0 (0) | 2 (2.0) | 0 (0) | 2 | |
All quintuple mutants | 37 (46.8) | 33 (34.4) | 14 (14.3) | 3 (3.4) | 87 | <0.001 |
dhfr N51I, C59R, S108 N + dhps A437G, K540E | 0 (0) | 17 (17.7) | 0 (0) | 2 (2.3) | 19 | <0.001 |
dhfr N51I, S108 N + dhps S436A, A437G, K540E | 5 (6.3) | 5 (5.2) | 0 (0) | 0 (0) | 10 | 0.004 |
dhfr N51I, S108 N + dhps A437G, K540E, A581G | 32 (40.5) | 11 (11.5) | 14 (14.3) | 1 (1.1) | 58 | <0.001 |
All sextuple mutants | 1 (1.3) | 4 (4.2) | 4 (4.1) | 0 (0) | 9 | |
dhfr N51I, C59R, S108 N + dhps S436A, A437G, K540E | 0 (0) | 1 (1) | 0 (0) | 0 (0) | 1 | |
dhfr N51I, C59R, S108 N + dhps A437G, K540E, A581G | 0 (0) | 3 (3.1) | 4 (4.1) | 0 (0) | 7 | |
dhfr N51I, S108 N + dhps S436A, A437G, K540E, A581G | 1 (1.3) | 0 (0) | 0 (0) | 0 (0) | 1 |