Seroepidemiology of helminths and the association with severe malaria among infants and young children in Tanzania

Abstract

The disease burden of Wuchereria bancrofti and Plasmodium falciparum malaria is high, particularly in Africa, and co-infection is common. However, the effects of filarial infection on the risk of severe malaria are unknown. We used the remaining serum samples from a large cohort study in Muheza, Tanzania to describe vector-borne filarial sero-reactivity among young children and to identify associations between exposure to filarial parasites and subsequent severe malaria infections. We identified positive filarial antibody responses (as well as positive antibody responses to Strongyloides stercoralis) among infants as young as six months. In addition, we found a significant association between filarial seropositivity at six months of age and subsequent severe malaria. Specifically, infants who developed severe malaria by one year of age were 3.9 times more likely (OR = 3.9, 95% CI: 1.2, 13.0) to have been seropositive for filarial antigen at six months of age compared with infants who did not develop severe malaria.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1

Receiver operating curves for filaria (a), Strongyloides (b) using sera from US naïve donors as negative controls and from parasitologically proven infected donors as positive controls. The analysis suggested good performance characteristics for both assays, with optimal cutoff values for seropositivity of 107 for filaria and 170 for Strongyloides.

Fig 2. Flowchart of children and samples included in the study.

A total of 471 children were assessed for eligibility in the study. Children were excluded from the study due to HIV or sickle cell anemia, if it was a multiple birth, or if they moved from the study area. Children with blood samples at 6 months (n = 261 samples) and 1 year (n = 196 samples) were used for the risk factor analysis, of which 180 children had serum for the assays and a positive blood smear between 6 months and one year of age, and 125 children had serum and a positive blood smear between one year and 18 months of age.

Fig 3. Proportions of children seropositive for filaria and for Strongyloides by age.

The proportion of children with filarial antibodies increased with age: 16.8% at 6 months, 18.9% at one year, 32.9% at 1.5 years, 39.2% at 2 years to 60.0% at 2.5 years. In contrast, the proportion of children with antibodies to Strongyloides stayed fairly constant: 8.1% at 6 months, 3.1% at 1 year, 4.5% at 1.5 years, 5.4% at 2 years and 8.0% at 2.5 years.

Fig 4. Proportions of children who subsequently developed severe malaria by filaria serostatus and age.

The proportion of children with filarial antibodies who developed severe malaria over the subsequent 6 months was 12.2% at 6 months of age and 5.7% at one year. The proportions of children without filarial antibodies who developed severe malaria over the ensuing 6 months was lower: 2.83% at 6 months and 0.04% at one year. No subsequent severe malaria events were observed at time points past 18 months of age in these subjects.

Fig 5. Cytokine profiles of children in the study at 6 months by filarial serostatus, stratified by whether they experienced (“Severe Malaria”) or did not experience (“No Severe Malaria”) severe malaria between 6 and 12 months of age.

No significant differences in cytokine levels were detected for children who did versus did not develop severe malaria.

Fig 6. Cytokine profiles of children in the study at 12 months by filarial serostatus, stratified by whether they experienced (“Severe Malaria”) or did not experience (“No Severe Malaria”) severe malaria between 12 and 18 months of age.