335 Am. J. Trop. Med. Hyg., 65(4), 2001, pp. 335–337 Copyright  2001 by The American Society of Tropical Medicine and Hygiene ASSOCIATION OF HELMINTH INFECTION WITH DECREASED RETICULOCYTE COUNTS AND HEMOGLOBIN CONCENTRATION IN THAI FALCIPARUM MALARIA MATHIEU NACHER, PRATAP SINGHASIVANON, FRE ´ DE ´ RICK GAY, WEERAPONG PHUMRATANAPRAPIN, UDOMSAK SILACHAMROON, AND SORNCHAI LOOAREESUWAN Unite ´ INSERM 511: Immunobiologie Cellulaire et Mole ´culaire des Infections Parasitaires, Faculte ´ de me ´decine Pitie ´-Salpe ´trie `re, Paris, France; Faculty of Tropical Medicine, Mahidol University, Hospital for Tropical Diseases, Bangkok, Thailand Abstract. Following a study showing an association between Ascaris and protection from cerebral malaria, we conducted a cross-sectional study comparing admission hemoglobin concentrations in relation to exposure to helminth infection in 2 separate groups of patients: 111 cerebral malaria cases and 180 mild Plasmodium falciparum malaria cases. Hookworm infections were excluded. Mean hemoglobin concentrations were significantly lower in helminth- infected patients compared to those without helminths, both in the cerebral malaria group (10.1  3 [n = 47] versus 11.2  2.4 g/dl [n = 64], P = 0.04) and the mild malaria group (11  2.5 [n = 89] vs 12.2  2.7 g/dl [n = 91], P = 0.004). Median reticulocyte counts, only available in the cerebral malaria group, were lower in helminth-infected patients compared to those without helminths (15,340/23,760 per l, P = 0.03). Adjustments for confounders such as body mass index did not alter these associations. These data are consistent with a mechanism causing anemia linked to differences in the immune response of helminth-infected patients during malaria. INTRODUCTION Malarial anemia is an important cause of morbidity and mortality. 1 The pathophysiology of malarial anemia is still unclear but likely involves destruction of parasitized eryth- rocytes at schizont rupture, suppression of erythropoiesis by nitric oxide 2 and cytokines such as TNF- and IFN-, 3 and destruction of non-parasitized red blood cells because of re- duced red cell deformability. 4 We have recently proposed to explain an association between Ascaris infection and protec- tion from cerebral malaria by hypothesizing that endothelial and leukocyte CD23 ligation by IgE-anti IgE immune com- plexes induce nitric oxide, preventing cytoadherence of par- asitized red blood cells. 5 Although severe malarial anemia is rare in Thailand, our objective was to see if the magnitude of malarial anemia was influenced by helminth infection. PATIENTS, MATERIALS, AND METHODS We performed a retrospective study of 2 separate groups of malaria patients hospitalized between 1991 and 1997 at the Hospital for Tropical Diseases, Bangkok. First, we com- pared hemoglobin concentrations and reticulocyte counts on admission between helminth-infected and non-infected pa- tients in a group of 111 cerebral malaria cases (reticulocyte counts on admission were only available for 61 cerebral ma- laria cases because they were part of routine clinical testing from 1991 to 1993). Second, we compared hemoglobin con- centrations in relation to the presence or absence of hel- minths in a group of 180 mild P. falciparum malaria cases. The body mass index (BMI: weight/height 2 ) and details of peripheral blood smears were available for 93 mild P. fal- ciparum malaria patients. We did not compare mild malaria and cerebral malaria assuming they were different diseases. Statistical methods. Quantitative values were compared using the ranksum test when distributions were non-Gauss- ian and the unpaired t-test for unequal variances was used for normally distributed variables. Adjustments for potential confounding variables were performed using multiple linear regression (STATA 6.0). Since helminths are related to so- cioeconomic factors that can potentially influence hemoglo- bin concentrations, we analyzed the relationship between helminth infection and hemoglobin in the Mon ethnic group alone. The Mon are political and economic refugees residing in the mountains of the western Thai border. Analyzing the relation between helminths and hemoglobin in this homo- geneous group was assumed to avoid socioeconomic con- founding. All patients had a stool examination by direct examination of a wet preparation of 1.5 mg of stool. Since hookworm is known to be associated with iron deficiency we excluded patients with hookworm infection (135 patients). Since heavy Trichuris trichiura infections have been described as associated with blood loss, 6 9 patients with infections of more than 5,000 eggs per gram of stool were excluded. For the subgroup where erythrocyte abnormalities were record- ed, a logistic regression model was generated using the pres- ence or absence of anisocytosis as the dependent variable. RESULTS There was no significant difference in the median duration of symptoms between helminth-infected and non-infected patients (respectively: median 4/4 days, quartiles 3/3 days and 6/7days). Types of helminths. There were 47 Ascaris lumbricoides infections, 61 moderate Trichuris trichiura infections, and 23 Strongyloides stercoralis infections. Forty-seven patients had single helminth infections, 30 had dual helminth infec- tions, and 10 had 3 triple helminth infections. Hemoglobin and helminths. In both study groups the mean hemoglobin concentration was significantly lower in helminth-infected patients when compared to patients with- out helminths (Table 1). Adjustments for age, sex, ethnicity, mean corpuscular vol- ume, P. falciparum parasitemia, and symptom duration did not alter the result (Table 1). There was a negative linear trend (P = 0.01) between the proportion of helminth-infect- ed patients and the level of hemoglobin (Table 2). Similarly, there was a linear trend (P = 0.03) between the number of