Filariasis attenuates anemia and proinflammatory responses associated with clinical malaria: a matched prospective study in children and young adults

Abstract

Background: Wuchereria bancrofti (Wb) and Mansonella perstans (Mp) are blood-borne filarial parasites that are endemic in many countries of Africa, including Mali. The geographic distribution of Wb and Mp overlaps considerably with that of malaria, and coinfection is common. Although chronic filarial infection has been shown to alter immune responses to malaria parasites, its effect on clinical and immunologic responses in acute malaria is unknown.

Methodology/principal findings: To address this question, 31 filaria-positive (FIL+) and 31 filaria-negative (FIL-) children and young adults, matched for age, gender and hemoglobin type, were followed prospectively through a malaria transmission season. Filarial infection was defined by the presence of Wb or Mp microfilariae on calibrated thick smears performed between 10 pm and 2 am and/or by the presence of circulating filarial antigen in serum. Clinical malaria was defined as axillary temperature ≥37.5°C or another symptom or sign compatible with malaria infection plus the presence of asexual malaria parasites on a thick blood smear. Although the incidence of clinical malaria, time to first episode, clinical signs and symptoms, and malaria parasitemia were comparable between the two groups, geometric mean hemoglobin levels were significantly decreased in FIL- subjects at the height of the transmission season compared to FIL+ subjects (11.4 g/dL vs. 12.5 g/dL, p<0.01). Plasma levels of IL-1ra, IP-10 and IL-8 were significantly decreased in FIL+ subjects at the time of presentation with clinical malaria (99, 2145 and 49 pg/ml, respectively as compared to 474, 5522 and 247 pg/ml in FIL- subjects).

Conclusions/significance: These data suggest that pre-existent filarial infection attenuates immune responses associated with severe malaria and protects against anemia, but has little effect on susceptibility to or severity of acute malaria infection. The apparent protective effect of filarial infection against anemia is intriguing and warrants further study in a larger cohort.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Study flowchart.

Figure 2. Incidence of clinical malaria.

The bars represent the number of FIL+ (black bars) and FIL− (gray bars) subjects who experienced 0, 1, 2 or 3 episodes of clinical malaria during the first transmission season.

Figure 3. Time to first episode of clinical malaria.

The cumulative % of FIL+ (black line) and FIL− (gray line) subjects who had experienced at least one episode of malaria is shown for each week of the first transmission season (estimated by Kaplan-Meier method to account for subjects who withdrew from the study).

Figure 4. Parasitemia at the time of the first episode of clinical malaria.

The symbols represent individual values for FIL+ (black circles) and FIL− (gray circles) subjects. The horizontal lines represent the GM values for the groups.

Figure 5. Hgb levels during monthly asymptomatic visits.

GM Hgb with 95% confidence intervals are show for FIL+ (black) and FIL− (gray) subjects over time. *p

Figure 6. Plasma cytokine and chemokine levels at the time of acute malaria.

The symbols represent individual values for FIL+ (black circles) and FIL− (gray circles) subjects. The horizontal lines represent the GM values for the groups.

Figure 7. Negative correlation between serum levels of IP-10 during acute malaria and Hgb levels at the peak of malaria transmission.

The symbols represent the values for individual study subjects.