Epidemiology of plasmodium-helminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control

Abstract

Human co-infection with Plasmodium falciparum and helminths is ubiquitous throughout Africa, although its public health significance remains a topic for which there are many unknowns. In this review, we adopted an empirical approach to studying the geography and epidemiology of co-infection and associations between patterns of co-infection and hemoglobin in different age groups. Analysis highlights the extensive geographic overlap between P. falciparum and the major human helminth infections in Africa, with the population at coincident risk of infection greatest for hookworm. Age infection profiles indicate that school-age children are at the highest risk of co-infection, and re-analysis of existing data suggests that co-infection with P. falciparum and hookworm has an additive impact on hemoglobin, exacerbating anemia-related malarial disease burden. We suggest that both school-age children and pregnant women--groups which have the highest risk of anemia--would benefit from an integrated approach to malaria and helminth control.

FIGURE 1

Typical age profiles of prevalence P. falciparum infection, hookworm and S. mansoni. Data taken from Ashford et al. and Kabatereine et al.

FIGURE 2

Plasmodium-helminth co-infection: hypothesised mechanisms through which helminths may alter the risk of malarial infection and disease, and the mechanisms through which anemia arises. Chronic helminth infection induces a T-helper 2 (Th2) cytokine response, which may impose cross-regulatory effects on the development of an appropriate pro-inflammatory response to initial malaria infection,- and skew anti-plasmodium antibody responses towards the production of non-cytophilic immunoglobulins ineffective against malaria (IgG4 and IgGM), instead of cytophilic ones necessary for immunity (IgG1 and IgG3)., However, induction of an anti-inflammatory immunosuppressive network may in fact prevent severe pathology in the later stages of malaria infection, with high levels of helminth-induced interleukin(IL)-10 - acting to down-module the effects of interferon (IFN)-γ and tumor necrosis factor (TNF)-α, thus reducing malaria pathology. Alternatively sequestration of infected red blood cells may be prevented through IgE-mediated activation of the CD23/NO pathway. Adapted and expanded from Hartgers and Yazdanbakhsh.

FIGURE 3

The relationship between plasmodia-hookworm co-infection and mean hemoglobin concentration in Kenya based on re-analysis of published data. (a) Pre-school children: 460 children among whom 61.5% were uninfected; 30.9% infected with P. falciparum alone; 4.1% with heavy hookworm (eggs/gram feces (epg)>2000); and 3.5% with both, based on Brooker et al. (b) School-age children: 392 children among whom 19.1% were uninfected; 27.8% infected with P. falciparum alone; 17.9% with heavy hookworm (eggs/gram feces (epg)>2000); and 35.2% with both, based on Stephenson et al. (1985). (c) Pregnant women: 251 women among whom 68.5% were uninfected; 21.1% infected with P. falciparum alone; 6.0% with heavy hookworm (eggs/gram feces (epg)>2000); and 4.4% with both, based on Shulman et al. . Mean hemoglobin based on regression modelling adjusting for age and sex, and nutrition and socio-economic status (pre-school children) and gestation (pregnant women). Error bars indicates 95% confidence intervals.

FIGURE 3

The relationship between plasmodia-hookworm co-infection and mean hemoglobin concentration in Kenya based on re-analysis of published data. (a) Pre-school children: 460 children among whom 61.5% were uninfected; 30.9% infected with P. falciparum alone; 4.1% with heavy hookworm (eggs/gram feces (epg)>2000); and 3.5% with both, based on Brooker et al. (b) School-age children: 392 children among whom 19.1% were uninfected; 27.8% infected with P. falciparum alone; 17.9% with heavy hookworm (eggs/gram feces (epg)>2000); and 35.2% with both, based on Stephenson et al. (1985). (c) Pregnant women: 251 women among whom 68.5% were uninfected; 21.1% infected with P. falciparum alone; 6.0% with heavy hookworm (eggs/gram feces (epg)>2000); and 4.4% with both, based on Shulman et al. . Mean hemoglobin based on regression modelling adjusting for age and sex, and nutrition and socio-economic status (pre-school children) and gestation (pregnant women). Error bars indicates 95% confidence intervals.