Table 2.
Distribution of Possible Etiologic and Confounding Factors among Study Groups According to Recruitment Sites.*
| Variable | Both Sites | Rural Site | Rural Site | Urban Site | |||||||||
| Case Patients (N = 381) |
Community and Hospital Control Patients (N = 757) |
P Value | Case Patients (N = 176) |
Community Control Patients (N = 177) |
P Value | Hospital Control Patients (N = 176) |
P Value | Case Patients (N = 205) |
Community Control Patients (N = 203) |
P Value | Hospital Control Patients (N = 201) |
P Value | |
| no./total no. (%) | no./total no. (%) | no./total no. (%) | no./total no. (%) | no./total no. (%) | |||||||||
| History | |||||||||||||
| Mother did not attend secondary school |
323/366 (88.3) | 554/753 (73.6) | <0.001 | 162/172 (94.2) | 154/176 (87.5) | 0.03 | 143/176 (81.2) | <0.001 | 161/194 (83.0) | 142/200 (71.0) | 0.005 | 115/201 (57.2) | <0.001 |
| Death of a parent | 25/284 (8.8) | 22/554 (4.0) | 0.004 | 13/168 (7.7) | 5/163 (3.1) | 0.06 | 3/164 (1.8) | 0.01 | 12/116 (10.3) | 6/109 (5.5) | 0.18 | 8/118 (6.8) | 0.33 |
| Recent hematinic treatment | 85/376 (22.6) | 61/754 (8.1) | <0.001 | 40/176 (22.7) | 7/177 (4.0) | <0.001 | 13/176 (7.4) | <0.001 | 45/200 (22.5) | 19/202 (9.4) | <0.001 | 22/199 (11.1) | 0.002 |
| Recent antimalarial treatment | 232/375 (61.9) | 346/755 (45.8) | <0.001 | 107/176 (60.8) | 79/177 (44.6) | 0.002 | 90/176 (51.1) | 0.07 | 125/199 (62.8) | 77/203 (37.9) | <0.001 | 100/199 (50.3) | 0.01 |
| History of transfusion | 57/378 (15.1) | 38/756 (5.0) | <0.001 | 24/176 (13.6) | 9/177 (5.1) | 0.006 | 13/176 (7.4) | 0.06 | 33/202 (16.3) | 7/203 (3.4) | <0.001 | 9/200 (4.5) | <0.001 |
| Malnutrition† | |||||||||||||
| Wasting | 52/330 (15.8) | 43/695 (6.2) | <0.001 | 24/169 (14.2) | 9/174 (5.2) | 0.005 | 19/175 (10.9) | 0.35 | 28/161 (17.4) | 6/182 (3.3) | <0.001 | 9/164 (5.5) | <0.001 |
| Iron deficiency | 97/208 (46.6) | 288/415 (69.4) | <0.001 | 71/101 (70.3) | 76/95 (80.0) | 0.12 | 63/92 (68.5) | 0.78 | 26/107 (24.3) | 76/113 (67.3) | <0.001 | 73/115 (63.5) | <0.001 |
| Vitamin B12 deficiency | 95/312 (30.4) | 94/603 (15.6) | <0.001 | 46/142 (32.4) | 20/143 (14.0) | <0.001 | 30/149 (20.1) | 0.02 | 49/170 (28.8) | 24/157 (15.3) | 0.003 | 20/154 (13.0) | <0.001 |
| Vitamin A deficiency | 228/247 (92.3) | 172/262 (65.6) | <0.001 | 113/126 (89.7) | 44/83 (53.0) | <0.001 | 60/74 (81.1) | 0.09 | 115/121 (95.0) | 32/60 (53.3) | <0.001 | 36/45 (80.0) | 0.003 |
| Viral infections | |||||||||||||
| HIV | 45/357 (12.6) | 41/682 (6.0) | <0.001 | 7/176 (4.0) | 5/176 (2.8) | 0.56 | 9/172 (5.2) | 0.58 | 38/181 (21.0) | 9/171 (5.3) | <0.001 | 18/163 (11.0) | 0.01 |
| Parvovirus B19 | 5/294 (1.7) | 2/609 (0.3) | 0.03 | 2/143 (1.4) | 0/147 | 0.15 | 1/146 (0.7) | 0.55 | 3/151 (2.0) | 1/157 (0.6) | 0.30 | 0/159 | 0.07 |
| Epstein-Barr virus | 89/269 (33.1) | 102/566 (18.0) | <0.001 | 43/128 (33.6) | 34/133 (25.6) | 0.16 | 24/127 (18.9) | 0.008 | 46/141 (32.6) | 14/148 (9.5) | <0.001 | 30/158 (19.0) | 0.007 |
| Bacteremia | 54/359 (15.0) | 14/353 (4.0) | <0.001 | 20/171 (11.7) | ND | 9/166 (5.4) | 0.04 | 34/188 (18.1) | ND | 5/187 (2.7) | <0.001 | ||
| Parasitic infections | |||||||||||||
| Plasmodium falciparum | 226/380 (59.5) | 321/750 (42.8) | <0.001 | 91/176 (51.7) | 93/175 (53.1) | 0.79 | 93/176 (52.8) | 0.83 | 135/204 (66.2) | 74/199 (37.2) | <0.001 | 61/200 (30.5) | <0.001 |
| Hyperparasitemic P. falciparum‡ | 45/380 (11.8) | 24/750 (3.2) | <0.001 | 17/176 (9.7) | 3/175 (1.7) | 0.001 | 11/176 (6.2) | 0.24 | 28/204 (13.7) | 3/199 (1.5) | <0.001 | 7/200 (3.5) | <0.001 |
| Recent or current P. falciparum | 243/334 (72.8) | 336/696 (48.3) | <0.001 | 113/169 (66.9) | 98/171 (57.3) | 0.07 | 98/175 (56.0) | 0.04 | 130/165 (78.8) | 83/180 (46.1) | <0.001 | 57/170 (33.5) | <0.001 |
| Hookworm | 29/296 (9.8) | 12/642 (1.9) | <0.001 | 27/154 (17.5) | 4/160 (2.5) | <0.001 | 8/156 (5.1) | <0.001 | 2/142 (1.4) | 0/164 | 0.13 | 0/162 | 0.13 |
| Schistosoma mansoni | 2/296 (0.7) | 8/643 (1.2) | 0.43 | 2/154 (1.3) | 4/160 (2.5) | 0.44 | 4/156 (2.6) | 0.42 | 0/142 | 0/164 | 0/163 | ||
| S. haematobium | 4/307 (1.3) | 8/669 (1.2) | 0.89 | 4/159 (2.5) | 6/168 (3.6) | 0.58 | 1/162 (0.6) | 0.17 | 0/148 | 0/171 | 1/168 (0.6) | 0.35 | |
| Genetic disorders§ | |||||||||||||
| G6PD−202/−376 | 44/318 (13.8) | 54/601 (9.0) | 0.02 | 21/152 (13.8) | 11/141 (7.8) | 0.10 | 9/145 (6.2) | 0.03 | 23/166 (13.9) | 20/161 (12.4) | 0.70 | 14/154 (9.1) | 0.18 |
| Sickle cell disease | 4/238 (1.7) | 4/404 (1.0) | 0.45 | 2/118 (1.7) | 2/101 (2.0) | 0.88 | 0/86 | 0.23 | 2/120 (1.7) | 0/106 | 0.18 | 2/111 (1.8) | 0.94 |
| IL10 −1117 (C/C+C/T vs. T/T) | 196/324 (60.5) | 332/607 (54.7) | 0.09 | 98/155 (63.2) | 75/141 (53.2) | 0.08 | 83/147 (56.5) | 0.23 | 98/169 (58.0) | 92/162 (56.8) | 0.83 | 82/157 (52.2) | 0.30 |
| IL10 −3585 (A/A vs. A/T+T/T) | 22/308 (7.1) | 25/575 (4.3) | 0.08 | 8/148 (5.4) | 6/134 (4.5) | 0.72 | 5/140 (3.6) | 0.45 | 14/160 (8.8) | 4/153 (2.6) | 0.02 | 10/148 (6.8) | 0.51 |
| IL10 +4949 (G/G vs. G/A+A/A) | 97/322 (30.1) | 134/606 (22.1) | 0.007 | 48/155 (31.0) | 31/140 (22.1) | 0.09 | 34/147 (23.1) | 0.13 | 49/167 (29.3) | 34/162 (21.0) | 0.08 | 35/157 (22.3) | 0.15 |
| Abnormal ratio of interleukin-10 to TNF-α |
4/276 (1.4) | NA | 1/122 (0.8) | NA | NA | 3/154 (1.9) | NA | NA | |||||
All P values are for the comparisons between case patients and community control patients, hospital control patients, or both. Among variables not included in the table (because they did not meet the preset cutoff for significance) are parental unemployment, household assets, folate deficiency, trichuriasis, ascariasis, cytomegalovirus infection, hemoglobin C, and tumor necrosis factor α (TNF-α) alleles or genotypes (−238, −308, and −1031). Recent is defined as within 8 weeks before recruitment. HIV denotes human immunodeficiency virus, IL10 the gene encoding interleukin-10, NA not available, and ND not done. G6PD−202/−376 denotes boys who are hemizygous and girls who are homozygous for both the G6PD202A and the G6PD376G alleles.
Wasting is defined as a weight-for-height z score of less than −2. Iron deficiency is defined as a ratio of soluble transferrin receptor to log ferritin (TfR-F index)10 that is greater than 5.6 (unpublished data). Folate concentrations of less than 0.3 µg per deciliter (6.8 nmol per liter), vitamin B12 concentrations of less than 20 ng per deciliter (148 pmol per liter), and vitamin A concentrations of less than 20 µg per deciliter (0.7 µmol per liter) are considered to indicate deficiencies.
Hyperparasitemia is defined as more than 100,000 parasites per microliter of blood.
The rs classifications for the genetic markers are as follows: IL10 −1117, rs1800896; IL10 −3585, rs1800890; IL10 +4949, rs3024500; TNF −238, rs361525; TNF −308, rs1800629; and TNF −1031, rs1799964. A ratio of interleukin-10 to TNF-α that is less than 1 is considered abnormal.22