© 2005 Blackwell Publishing Ltd 115 Parasite Immunology , 2005, 27, 115 –120 Blackwell Publishing, Ltd. REVIEW ARTICLE Inverse age resistance in bovine babesiosis Review Article Possible mechanisms underlying age-related resistance to bovine babesiosis ANNETTA ZINTL, 1 JEREMY S. GRAY, 2 HELEN E. SKERRETT 1 & GRACE MULCAHY 1 1 Department of Veterinary Microbiology & Parasitology and Conway Institute of Biomedical & Biomolecular Research, University College Dublin, Ireland, 2 Department of Environmental Resource Management, University College Dublin, Ireland SUMMARY Calves infected with the tick-borne parasites Babesia spp. do not develop severe clinical babesiosis. Instead they display persistent low parasitaemias without any apparent ill-effects. This age-related resistance not only benefits the host, but also furthers parasite transmission. Both calves and adult animals respond with a Th I immune response to primary infection. Here we hypothesize that the difference in the outcome of infection may at least partly be explained by the localization and timing of the inflammatory response: in calves NO produc- tion occurs early and appears to be concentrated in the spleen. On the other hand, there is evidence that a delayed and systemic inflammatory response occurs in adult animals that is ineffectual and probably contributes to the pathogenesis. An improved understanding of the possible mechanisms that underlie this phenomenon may lead to new approaches for the treatment and immune prophylaxis of the disease. Keywords Babesia, bovine, enzootic stability, immune modu- lation, inflammatory response, inverse age resistance INTRODUCTION Bovine babesiosis is an important disease with an estimated 400 million cattle being at risk worldwide (1). The most important species are Babesia bovis and Babesia bigemina in the tropics and subtropics and Babesia divergens in North- ern Europe. All three are tick-borne and intraerythrocytic. Infections are generally characterized by fever, listlessness, anorexia, dehydration, and progressive haemolysis. Haemo- globinuria and haemoglobinaemia may be followed by jaun- dice. In B. bigemina and B. divergens clinical signs occur on a continuum ranging from subclinical to acute disease, the severity of the disease being determined by the degree of parasitaemia. In acutely infected animals more than 40% of erythrocytes may be infected, causing anaemic anoxia. However, only a relatively small proportion of cases are fatal (2,3). In contrast, B. bovis kills more than half the suscepti- ble cattle that it infects (4). Infections with this parasite are characterized by low levels of peripheral parasitaemia (0·2– 0·04%), as infected erythrocytes undergo sequestration by attachment to capillary endothelium, resulting in allergic reactions, organ damage, cerebral dysfunction and pulmo- nary oedema. An initial fall in haematocrit is largely due to haemodilution associated with circulatory stasis rather than erythrocyte destruction, and acute cases rapidly fulminate showing severe hypotensive shock (5,6). These disease signs occur in mature animals when they become exposed to bovine babesiosis for the first time. In contrast calves of less than about 9 months of age possess an innate resistance to disease. The levels of parasitaemia and anaemia are reduced compared with adult cattle, and peak earlier. Fever is mild and haematocrit recovers rapidly. Low level parasitaemias persist for long periods without any apparent ill-effects (7–11). In neonates this protection may be partially due to maternal antibody acquired from colo- strum. However, young animals remain resistant longer than Correspondence: Annetta Zintl, Department of Veterinary Microbiology & Parasitology and Conway Institute of Biomedical & Biomolecular Research, University College Dublin, Ireland (e-mail: annetta.zintl@ucd.ie). Received: 24 January 2005 Accepted for publication: 8 March 2005