The recent review by Zaccone et al.[1] on the prevention of autoimmune disease by helminths demonstrated how much knowledge of this topic has advanced in recent years. However, for those unfamiliar with this field, evidence for malaria acting similarly was published 40 years ago, although it was not mentioned by these authors. In 1968 Greenwood reported that the number of admissions for systemic lupus erythematosis (SLE) in a Nigerian hospital was almost negligible in comparison with admissions for SLE in European hospitals. Because people of African descent in the US and Europe have a higher rate of lupus than do Caucasians, there should have been relatively more lupus patients in Nigeria than in Europe (summarised in Ref.[2]). Greenwood suggested that parasites might be responsible for these results and later demonstrated that Plasmodium berghei would prevent the spontaneous development of lupus in a mouse model [2]. Similarly, Plasmodium infection prevented the onset of Freunds’s-adjuvant-induced arthritis in rats [2]. Regrettably, these observations, made before the current understanding of such things as immune-cell types and cytokines, were not effectively followed up. There is a delicate balance between pro-and antiinflammatory responses in helminth infections and in malaria [3], in which the initial acute phase of the blood infection is characterised by proinflammatory mediators, particularly tumour necrosis factor (TNF) and related cytokines; these subsequently give way to anti-inflammatory mediators, including transforming growth factor (TGF), IL-10 and antibody-mediated immunity. Parasite replication is initially controlled by activated macrophages releasing various cytotoxic mediators, including oxygen free radicals and high molecular weight proteins [4]. Recently, it was reported that the plasma level of chitotriosidase, an enzyme expressed by macrophages, is increased in malaria [5]. CHIT1, a chitotriosidase gene mutant that conveys increased protection from P. falciparum, has been found in the inhabitants of Sardinia. Malaria was eradicated from the island 40 years ago, however, and since then there has been a significant rise in multiple sclerosis (MS) cases; the rise is thought to be related to CHIT1 [5]. This is said to be uncommon in Asia and Africa, but the children of Asian and African immigrants in the UK have a similar prevalence to the general population [6], suggesting that a protective environmental factor, such as parasites, might be missing in the immigrants.

New information on genotype selection by malaria includes a report of a protective variant of the inhibitory receptor FcgRIIb that enhances phagocytosis of P. falciparum-infected erythrocytes [7]. The variant is present with an increased frequency in Asians and Africans, but in carriers in malaria-free areas FcgRIIb is associated with an increased predisposition to SLE [7]. The increased incidence of MS in Sardinia has led Sotgui et al.[5] to propose that in populations from endemic areas malaria has selected for macrophages that overrespond to environmental triggers. However, selection could, arguably, be in the other direction. Because of the over-reaction to Plasmodium infection that generates very high levels of proinflammatory mediators, selection for macrophages innately less responsive to this infection would be more logical. Thus, in experiments on volunteers, naive Afro-Americans exposed to P. falciparum experienced less fever than naive Caucasians at equivalent parasitaemias [2]. Furthermore, people of African descent in the US and Europe are over ten times more at risk from sarcoidosis (now suggested to be caused by infection [8]) than …