Background
Methods
Study subjects and sample collection
Identify Plasmodium spp.
Measurement of G6PD activity
Identification of G6PD, PKLRR41Q, and thalassaemia mutations
Statistical analysis
Results
Demographic data and prevalence of G6PD and PKLRR41Q mutations in malaria patients
Number of Enrolled | Myanmarese (%) | Cambodian (%) | Karen (%) | Laotians (%) | Mons (%) | Thais (%) | Unknown (%) | Total (%) | |
---|---|---|---|---|---|---|---|---|---|
Ethnicity | Malaria patients | 189 (74.1) | 8 (3.1) | 16 (6.3) | 2 (0.8) | 4 (1.6) | 35 (13.7) | 1 (0.4) | 255 |
Age | Median ± IQR (years) | 25.0 ± 15.0 | 24.5 ± 6.0 | 20.0 ± 7.0 | 28.0 | 21.5 ± 6.0 | 29.5 ± 15.0 | 16.0 | 25.0 ± 14.0 |
Range (years) | 14–057 | 19–30 | 14–40 | 24–32 | 19–26 | 16–60 | 16 | 14–60 | |
Sex | Male (%) | 182 (96.3) | 8 (100) | 16 (100) | 2 (100.0) | 4 (100.0) | 31 (88.6) | 1 (100.0) | 244 (95.7) |
Female (%) | 7 (3.7) | – | – | – | – | 4 (11.4) | – | 11 (4.3) | |
Plasmodium spp. | P. falciparum (%) | 81 (42.9) | 1 (12.5) | 7 (43.8) | 2 (100.0) | 1 (25.0) | 14 (40.0) | – | 106 (41.6) |
P. vivax (%) | 105 (55.6) | 6 (75.0) | 9 (56.3) | – | 3 (75.0) | 21 (60.0) | 1(100.0) | 145 (56.9) | |
Co-infection (Pf + Pv) (%) | 2 (1.1) | 1 (12.5) | – | – | – | – | – | 3 (1.2) | |
P. malariae (%) | 1 (0.5) | – | – | – | – | – | – | 1 (0.4) | |
G6PD (n = 45) | G6PD deficiency (%) | 19 (10.1) M:18, F:1 | 1 (12.5) M:1 | 3 (18.8) M:3 | – | – | 5 (14.3) M: 5 | – | 28 (11.0) M: 27 (11.1), F: 1 (9.1) |
G6PD intermediate (%) | 11 (5.8) M: 10, F: 1 | – | 1 (6.3) M: 1 | – | – | 5 (14.3) M: 3, F: 2 | – | 17 (6.7) M: 14 (5.7), F: 3 (27.3) | |
MahidolG487A mutation (%) | 14 (7.4) (Hemi: 13) (Homo: 1) | – | 2 (12.5) (Hemi: 2) | – | – | 2 (5.7) (Hemi: 2) | – | 18 (7.1) (Hemi: 17, Homo: 1) | |
MAF | |||||||||
Overall | |||||||||
G allele (%) | 181 (92.3) | 8 (100.0) | 14 (87.5) | 2 (100.0) | 4 (100.0) | 37 (94.9) | 1 (100.0) | 242 (92.9) | |
A allele (%) | 15 (7.7) | – | 2 (12.5) | – | – | 2 (5.1) | – | 19 (7.1) | |
Male only | |||||||||
G allele (%) | 169 (92.9) | 8 (100.0) | 14 (87.5) | 2 (100.0) | 4 (100.0) | 29 (93.6) | 1 (100.0) | 227 (93.0) | |
A allele (%) | 13 (7.1) | – | 2 (12.5) | – | – | 2 (6.4) | – | 17 (7.0) | |
ViangchanG871A mutation (%) | – | 1 (100.0) (Hemi:1) | – | – | – | 2 (5.7) (Hemi: 2) | – | 3 (1.2) (Hemi: 3) | |
KaipingG1388A mutation (%) | – | – | 1 (6.3) (Hemi: 1) | – | – | – | – | 1 (0.4) (Hemi: 1) | |
AuresT143C mutation (%) | 1 (0.5) (Hemi: 1) | – | – | – | – | – | 1 (0.4) (Hemi: 1) | ||
Unknown mutation (%) | 4 (2.1) | – | – | – | – | 1 (2.9) | – | 5 (2.0) | |
PKLR (n = 12) | PKLRR41Q mutation (%) | 9 (4.8) | 1 (12.5) | – | – | – | 2 (5.7) | – | 12 (4.7) |
Genotype G A (%) | 8 (88.9) | 1 (100.0) | – | – | – | 2 (100.0) | – | 11 (4.3) | |
Genotype A A (%) | 1 (11.1) | – | – | – | – | – | – | 1 (0.4) | |
MAF | |||||||||
G allele (%) | 368 (97.4) | 15 (93.7) | 32 (100.0) | 4 (100.0) | 8 (100.0) | 68 (97.1) | 2 (100.0) | 497 (97.5) | |
A allele (%) | 10 (2.6) | 1 (6.3) | – | – | – | 2 (2.9) | – | 13 (2.6) |
Haematological profiles of malaria patients with G6PD and PKLR mutations
Clinical parameters | G6PD Phenotypic status (n = 255, missing 1) | G6PD and PKLR mutations (n = 255, missing 1) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(n = 255) | G6PD normal | G6PD intermediate | p | G6PD deficiency | p | Wild-type | Mahidol | p | Other G6PD mutations | p | PKLRR41Q | p | Mahidol + PKLRR41Q |
(n = 209) | (n = 17) | (n = 28) | (n = 215) | (n = 17) | (n = 10) | (n = 11) | (n = 1) | ||||||
Hb | 12.7 ± 2.0 | 13.2 ± 1.1 | 0.084 | 11.0 ± 2.5 | 0.003 | 12.7 ± 1.9 | 11.2 ± 2.7 | 0.041 | 10.6 ± 2.4 | 0.001 | 13.2 ± 1.8 | 0.353 | 13.1 |
(g/dl) | (6.4–17.0) | (11.6–15.3) | (6.5–15.3) | (6.4–17.0) | (6.5–15.2) | (7.8–15.3) | (8.2–15.3) | ||||||
RBCs | 4.9 ± 0.8 | 5.0 ± 0.5 | 0.542 | 4.3 ± 1.0 | 0.005 | 4.8 ± 0.8 | 4.0 ± 0.9 | <0.001 | 4.6 ± 1.0 | 0.417 | 5.2 ± 0.5 | 0.100 | 4.95 |
(× 106/ul) | (1.3–7.1) | (4.3–5.8) | (2.2–6.0) | (1.3–7.1) | (2.2–5.3) | (2.7–6.0) | (4.5–6.3) | ||||||
Hct | 38.4 ± 5.7 | 40.2 ± 4.9 | 0.060 | 34.17 ± 7.1 | 0.006 | 38.4 ± 5.5 | 34.0 ± 7.2 | 0.029 | 33.9 ± 7.4 | 0.014 | 41.2 ± 5.3 | 0.094 | 39.9 |
(%) | (19.4–52.8) | (35.3–48.4) | (20.7–44.7) | (19.4–52.8) | (20.7–44.7) | (22.0–44.4) | (29.7–47.4) | ||||||
MCV | 79.3 ± 8.6 | 81.4 ± 6.7 | 0.327 | 81.2 ± 8.9 | 0.281 | 79.5 ± 8.4 | 85.8 ± 7.3 | 0.004 | 74.1 ± 6.9 | 0.046 | 79.3 ± 9.7 | 0.938 | 80.6 |
(fl) | (47.8–96.5) | (66.0–88.8) | (62.5–95.9) | (47.8–96.5) | (71.4–95.9) | (62.5–82.2) | (58.9–90.0) | ||||||
MCH | 26.3 ± 3.3 | 26.7 ± 1.7 | 0.404 | 26.2 ± 3.7 | 0.879 | 26.3 ± 3.2 | 28.0 ± 2.8 | 0.046 | 23.2 ± 3.3 | 0.002 | 25.5 ± 3.68 | 0.371 | 26.6 |
(pg/cell) | (16.2–38.5) | (23.2–29.3) | (17.3–30.7) | (16.3–38.5) | (23.1–30.7) | (17.3–29.1) | (16.2–29.3) | ||||||
MCHC | 32.8 ± 2.4 | 32.8 ± 1.4 | 0.975 | 31.0 ± 6.0 | 0.137 | 32.9 ± 2.4 | 30.7 ± 7.6 | 0.269 | 31.4 ± 2.5 | 0.055 | 32.0 ± 2.8 | 0.239 | 33.0 |
(g/dl) | (9.0–36.6) | (30.9–35.8) | (3.0–36.6) | (9.00–36.6) | (3.0–36.6) | (26.9–35.4) | (27.5–35.0) | ||||||
RDW | 15.2 ± 1.6 | 14.7 ± 0.7 | 0.015 | 14.9 ± 2.2 | 0.387 | 15.1 ± 1.5 | 14.4 ± 1.4 | 0.054 | 15.7 ± 3.1 | 0.558 | 15.8 ± 2.2 | 0.319 | 15.3 |
(%) | (12.7–23.8) | (13.4–16.2) | (12.3–23.8) | (12.7–23.8) | (12.3–17.5) | (12.8–23.8) | (13.1–19.1) | ||||||
Reticulocyte | 1.5 ± 1.1 | 1.1 ± 0.4 | 0.120 | 2.8 ± 2.1 | 0.005 | 1.5 ± 1.1 | 3.6 ± 2.4 | 0.008 | 1.9 ± 0.9 | 0.225 | 1.5 ± 1.0 | 0.812 | 1.5 |
(%) | (0.3–7.8) | (0.5–2.0) | (0.5–9.6) | (0.3–7.8) | (1.6–9.6) | (0.5–3.0) | (0.7–3.8) | ||||||
Platelet | 107.2 ± 82.3 | 73.71 ± 56.1 | 0.102 | 111.26 ± 57.8 | 0.803 | 105.6 ± 83.0 | 131.8 ± 60.0 | 0.215 | 83.0 ± 41.2 | 0.392 | 84.0 ± 31.2 | 0.390 | 65 |
(× 103/mm3) | (14.0–790.0) | (7.0–217.0) | (11.0–275.0) | (7.0–790.0) | (52.0–275.0) | (11.0–150.0) | (44.0–146.0) | ||||||
MPV | 13.3 ± 52.1 | 9.6 ± 3.1 | 0.770 | 9.3 ± 1.4 | 0.693 | 13.2 ± 51.3 | 9.5 ± 1.5 | 0.773 | 9.0 ± 1.9 | 0.795 | 8.4 ± 0.9 | 0.754 | 9.1 |
(fl) | (0.0–738.0) | (0.0–13.6) | (7.2–13.5) | (0.0–738.0) | (7.2–13.5) | (7.4–10.9) | (7.5–10.5) | ||||||
TB | 1.3 ± 2.0 | 3.3 ± 9.0 | 0.357 | 1.4 ± 0.8 | 0.668 | 1.4 ± 3.2 | 1.6 ± 0.9 | 0.875 | 1.3 ± 0.7 | 0.862 | 0.9 ± 0.5 | 0.548 | 0.55 |
(mg/dl) | (0.2–21.3) | (0.4–38.0) | (0.3–3.3) | (0.2–37.98) | (0.3–3.3) | (0.5–2.4) | (0.3–2.0) | ||||||
DB | 0.6 ± 1.6 | 2.3 ± 7.9 | 0.377 | 0.6 ± 0.5 | 0.915 | 0.8 ± 2.8 | 0.6 ± 0.6 | 0.863 | 0.5 ± 0.3 | 0.753 | 0.4 ± 0.2 | 0.591 | 0.29 |
(mg/dl) | (0.0–17.7) | (0.2–33.0) | (0.0–2.4) | (0.0–33.0) | (0.1–2.4) | (0.04–1.06) | (0.1–0.7) | ||||||
IDB | 0.6 ± 0.5 | 0.9 ± 1.3 | 0.305 | 0.8 ± 0.5 | 0.055 | 0.6 ± 0.6 | 0.9 ± 0.6 | 0.120 | 0.7 ± 0.4 | 0.617 | 0.5 ± 0.3 | 0.461 | 0.26 |
(mg/dl) | (0.1–3.6) | (0.2–5.0) | (0.1–2.5) | (0.0–5.0) | (0.1–2.5) | (0.3–1.67) | (0.2–1.3) | ||||||
Parasitemia | 27,419.2 ± 38,747.8 | 33,379.0 ± 59,709.0 | 0.691 | 24,841.9 ± 26,411.5 | 0.738 | 27,988.3 ± 41,225.2 | 25,633.9 ± 24,868.7 | 0.822 | 25,982.3 ± 30,289.8 | 0.879 | 24,681.4 ± 25,455.0 | 0.793 | 765 |
(parasite/ul) | (35–278,250) | (1–185,820) | (133–81,900) | (1–278,250) | (133–72,750) | (800–81,900) | (1018–69,940) |
Analysis type | Variable | Haemoglobin | Variable | Haemoglobin | ||||||
---|---|---|---|---|---|---|---|---|---|---|
B* | SE | Beta | p-value | B* | SE | Beta | p-value | |||
Univariate | ||||||||||
G6PD deficiency/G6PD normal | − 1.619 | 0.417 | − 0.248 | < 0.001 | G6PD Mahidol/G6PD wildtype | − 1.415 | 0.495 | − 0.182 | 0.005 | |
Gender | − 0.773 | 0.66 | − 0.074 | 0.243 | Gender | − 0.773 | 0.66 | − 0.074 | 0.243 | |
Age | 0.002 | 0.014 | 0.008 | 0.905 | Age | 0.002 | 0.014 | 0.008 | 0.905 | |
Parasite count | 5.492 × 106 | 0.000 | 0.106 | 0.095 | Parasite count | 5.462 × 106 | 0.000 | 0.106 | 0.095 | |
Parasite species (P. falciparum/P. vivax) | − 0.485 | 0.264 | − 0.117 | 0.067 | Parasite species (P. falciparum/P. vivax) | − 0.485 | 0.264 | − 0.117 | 0.067 | |
PKLRR14Q | 0.723 | 0.605 | 0.076 | 0.233 | PKLRR14Q | 0.723 | 0.605 | 0.076 | 0.233 | |
Thalassaemia, haemoglobinopathies | − 0.467 | 0.258 | − 0.114 | 0.072 | Thalassaemia, haemoglobinopathies | − 0.467 | 0.258 | − 0.114 | 0.072 | |
Multivariate | ||||||||||
G6PD deficiency/G6PD normal | − 1.895 | 0.447 | − 0.270 | < 0.001 | G6PD Mahidol/G6PD wildtype | − 2.01 | 0.555 | − 0.232 | < 0.001 | |
Gender | − 1.292 | 0.780 | − 0.108 | 0.099 | Gender | − 0.865 | 0.643 | − 0.088 | 0.18 | |
Age | 0.002 | 0.014 | 0.011 | 0.871 | Age | 0.009 | 0.013 | 0.042 | 0.525 | |
Parasite count | 1.011 × 105 | 0.000 | 0.183 | 0.008 | Parasite count | 9.231 × 106 | 0.000 | 0.179 | 0.009 | |
Parasite species (P. falciparum/P. vivax) | − 0.753 | 0.292 | − 0.176 | 0.011 | Parasite species (P. falciparum/P. vivax) | − 0.594 | 0.277 | − 0.145 | 0.033 | |
PKLRR14Q | 0.862 | 0.616 | 0.089 | 0.164 | PKLRR14Q | 0.766 | 0.574 | 0.085 | 0.184 | |
Thalassaemia, haemoglobinopathies | − 0.496 | 0.271 | − 0.117 | 0.069 | Thalassaemia, haemoglobinopathies | − 0.491 | 0.259 | − 0.122 | 0.060 | |
Constant | 14.567 | 1.196 | < 0.001 | Constant | 13.883 | 1.064 | < 0.001 |