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Antiphospholipid antibodies (aPL), particularly lupus anticoagulant or anticardiolipin antibodies (aCL), are diagnostic markers for the antiphospholipid syndrome, which is characterised by venous or arterial thrombosis or obstetric complications, or both.1 aPL may also occur in association with a multitude of infectious agents. Asherson and Cervera, while reviewing infection related aPL, mentioned malaria as one of the parasitic infections that has been associated with the presence of aPL.2 Indeed, two independent papers have described the high prevalence of aPL in patients with malaria. Jakobsen et al described the induction of IgM, but not IgG aPL during acute Plasmodium falciparum infection of Sudanese adults.3 The aPL were reactive with cardiolipin, phosphatidylinositol, and phosphatidylcholine. Facer and Agiostratidou examined adult patients of diverse ethnicity with uncomplicated non-severe malaria.4 They showed that P falciparum and P vivax infections are associated with the appearance of raised plasma levels of IgM and IgG aPL, and aCL were raised in over 75% of the patients with malaria. Patients with P falciparum had high aPL IgG levels, exceeding the levels seen in positive controls.4 Because the observed association may lack a causal relation, we recently evaluated the induction of aPL in 10 healthy white volunteers upon infection with P falciparum.
Anopheles stephensi mosquitoes were infected with the chloroquine sensitive NF54 isolate of P falciparum at the insectary, as previously described.5 Sets of female mosquitoes were allowed to feed on the forearms for 10 minutes. Subsequent dissection was performed to confirm the presence of sporozoites in the mosquito salivary glands. If not present, the feed was repeated until successful. Volunteers were carefully monitored by assessing blood films twice daily. Upon microscopic detection of parasites, volunteers were immediately treated with a standard curative regimen of chloroquine.
Blood was sampled one day before infection and 1, 7, 10, 12, and 20 days after infection. IgM and IgG aCL were analysed by commercial enzyme linked immunosorbent assay (ELISA; Pharmacia Diagnostics, Freiburg, Germany) in a serum dilution of 1:100. Results showed that all volunteers were negative for both IgM and IgG aCL before infection and remained negative for these antibodies during follow up. Thus, acute P falciparum infection does not result in the induction of aCL.
Nevertheless, although there seems to be no causal relation between malaria and aCL, the coexistence of aPL may further complicate malarial infection. For instance, thrombocytopenia is often (∼60%) seen in patients with malaria, and immune-mediated mechanisms have been suggested.6,7 Furthermore, in Gambian children with malaria the titres of aPL are significantly higher in severe than in mild malaria.3 However, a protective role of aPL has also been suggested. East African children with cerebral malaria had significantly lower titres of IgM anti-phosphatidylinositol antibodies than those with non-severe malaria.4 This is possibly explained by the neutralisation of the pathogenic properties of parasite derived phospholipid.8
Whatever the pathogenic role of aPL, our present results indicate that acute P falciparum infection does not induce these antibodies in a white population. Whether aPL develop during chronic infections remains to be determined. Because genetic factors have been demonstrated to be associated with the prevalence of aPL,9 it can be expected that people originating from malaria endemic areas are more prone to the induction of aPL. Therefore, analysis of aPL upon experimental infection with P falciparum in healthy volunteers from malaria endemic areas may further unravel the causal relation between malaria and aPL.
Competing interest statement: None of the authors have any competing interest.
Ethics approval: This study was approved by the medical ethics committee of the University Medical Centre Nijmegen.
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