Nodding syndrome--we can now prevent it.

On Monday December 21, 2015, an information session was organized by the Ugandan Health minister Dr Elioda Tumwesigye in Pader district, northern Uganda, to explain the results of the investigations performed in Uganda to identify the cause of nodding syndrome (NS). NS was first reported in Uganda in the districts of Kitgum, Pader, and Lamwo in 2009. Retrospective studies would suggest cases as early as 1997. By May 2014, a total of 3320 cases of NS had been registered and treated, as well as 5185 cases of epilepsy in the affected districts. NS is a form of atonic epilepsy. Patients with NS present with episodes of uncontrollable nodding of the head (the head drops forward), mental retardation, and stunted growth, and often develop generalized convulsions. The Ugandan Health minister informed the local population that NS was caused by onchocerciasis, probably through an autoimmune response triggered by an Onchocerca volvulus infection, the nematode causing river blindness. Indeed many studies have now confirmed the association between NS, epilepsy, and onchocerciasis. An autoimmune encephalitis caused by antibodies cross-reacting with O. volvulus or Wolbachia (a bacterial symbiont of O. volvulus) could be an explanation for this association. Johnson et al. reported that 11 (58%) of 19 patients with NS presented leiomodin 1 antibodies compared to five (26%) of 19 matched controls (matched odds ratio 7, confidence interval 0.9–11.1). These antibodies were found to be neurotoxic in vitro and to cross-react with O. volvulus tropomyosin. However, because leiomodin 1 is an intracellular protein, it is possible that these antibodies are not causing the epilepsy but are rather the consequence of repeated seizures damaging the brain. In a small pilot study in Tanzania, antibodies against N-methyl-Daspartate receptor and voltage gated potassium channel complex (VGKC) (LG1 and Caspr2) were not detected in patients with NS. In contrast, in Uganda, antibodies to the VGKC proteins were more often observed in patients with NS (15/31, 48.3%) than in controls (1/11, 9.1%) (R. Idro et al., unpublished). No patient or control subject had antibodies to the intracellular glutamic acid decarboxylase, which is also associated with complex epilepsy. Despite the fact that O. volvulus DNA has not yet been detected in the cerebrospinal fluid (CSF) of patients with NS, it is still possible that microfilariae occasionally penetrate the brain, particularly in highly infected individuals. In 1976 Duke et al. noted the presence of small numbers of O. volvulus microfilariae in the CSF (<2 mf/ml) in five of eight untreated heavily infected (>100 mf/mg skin) onchocerciasis patients; furthermore, the numbers of O. volvulus microfilariae in the CSF increased to 8–31 mf/ml during diethylcarbamazine treatment in 10 of 11 heavily