Immune responses following experimental human hookworm infection

Abstract

To characterize the immune response following primary human hookworm infection, an adult volunteer was infected with 50 L3 larvae of Necator americanus, reinfected 27 months later and followed for a further 6 months. Clinical signs, blood picture, ex-vivo peripheral blood cytokine production (IFN-gamma, IL-5, IL-13, IL-10 to mitogen and hookworm antigen), acute phase proteins (APP) (C-reactive protein, CRP and alpha1-antitrypsin, alpha1-AT) and antibody levels were determined. Dermatitis, oedema, mild nausea and abdominal discomfort followed the primary infection. Eosinophil counts peaked early during both infections but remained elevated ( approximately 18%) throughout. Transient production of IL-5, IL-13 and APP also followed infection but there were negligible levels of IFN-gamma or IL-10. The onset of nausea, oedema and the initial rise in CRP, alpha1-AT, eosinophilia and IL-5 coincided (days 13-27) with the late larval migration and early establishment of the preadult worms in the intestine. Apart from the eosinophilia these responses declined to baseline levels within 4 months and were less pronounced on re-infection.

Fig. 1

(a) Faecal egg excretion during the course of infection. Dotted vertical line = second infection. Solid arrow indicates time of patency during the first infection and the dashed arrow indicates the same interval following the second infection. The short horizontal bars indicate the periods within which skin rash (thick bar) or peripheral oedema, nausea and abdominal discomfort occurred (thin bar). (b) Cytokine responses to somatic hookworm antigen in relation to blood eosinophilia during the course of infection. Left axis: cytokine concentration; right axis: eosinophil count. IL-5 (•), IL-13 (▴), IFN-γ (▵), eosinophil count (□), dotted vertical line = second infection; dotted horizontal line = limit of cytokine detection.(c) Cytokine responses to PHA during the course of infection. IL-5 (•), IL-13 (▴), IFN-γ (▵), IL-10 (○), dotted vertical line = second infection; dotted horizontal line = limit of cytokine detection.