The causation of konzo studies on a paralytic disease in Africa

Sammanfattning: Epidemics of a permanent, non-progressive spastic paraparesis with sudden onset hasbeen reported from several rural areas of sub-Saharan Africa. Studies in East Africasuggested an association with dietary cyanide intake from unprocessed cassava. InZaire the disease was attributed to an infectious cause as the cyanogenic glucosides inthe cassava consumed were known to be removed by traditional soaking. The aims ofthe thesis were to define the disease entity and elucidate its etiology. A communitybasedsurvey in rural Zaire identified 110 live and 24 dead cases among 6764inhabitants (16/1000). The clinical findings were identical to earlier studies and it wasdecided to name the disease konzo as in the first known report. Annual and monthlyincidence of konzo was associated with almost exclusive consumption of shortsoakedbitter cassava roots. The appearence of konzo coincided with the completionof a tarmac road from the capital, which turned cassava into the main cash crop, andinduced short-cuts in the processing. A processing experiment showed that flour fromshort-soaked roots was high in cyanogens. A higher cyanide intake in affectedcompared to un-affected populations was confirmed by much higher urinarythiocyanate levels, the main metabolite. A low urinary sulphate indicated lowavailability of sulphur, the substrate for detoxification. All three konzo patientsexamined at onset had blood cyanide levels above 4 Ilmolll, versus only 2 out of 23controls (p<O.Ol). This supports an etiological role for cyanide. An odds ratio of 11was found for short-soaking of cassava, in a multivariate logistic regression analysis ofa case referent study in Zaire, with a dose-response curve indicating higher risk ofkonzo with frequent consumption of short-soaked cassava. Serological investigationsof 33 cases in Zaire excluded retrovirus etiology for konzo. Konzo was also identifiedin low prevalence in the Central African Republic, again associated with consumptionof insufficiently processed cassava. Investigation in Sweden of two severely disabledTanzanian patients revealed normal magnetic resonance imaging but neurophysiologyshowed isolated upper motor neuron dysfunction. This is consistent with clinicalfindings and identifies konzo as a distinct disease entity. The evidence for anetiological role of high cyanide and low sulphur intake in konzo is now strongenough to urge for prevention by promotion of efficient processing of cassava roots.