High mortality of subjects with endemic ataxic polyneuropathy in Nigeria.

BACKGROUND: Endemic ataxic polyneuropathy, a neurological syndrome that was thought to be benign, has been shown to persist in some communities in south-western Nigeria, where it was first described in the 1950s. OBJECTIVES: This study was conducted to compare mortality of cases and controls, and to determine if mortality is related to exposure to cyanide from cassava foods. MATERIAL AND METHODS: Cases of endemic ataxic polyneuropathy and two groups of controls, one group living in an endemic community and the other group living in a non-endemic community, were followed for 25 months. The outcome was death from medical causes. RESULTS: A total of 5970 subjects, 204 cases and 5766 controls - 4000 controls in the endemic community and 1766 controls in the non-endemic community, were followed. A total of 153 subjects died, 24 cases, 115 controls in the endemic community, and 14 controls in the non-endemic community. Relative risks of death (95% CI), adjusted for age and gender, were 4.5 (2.3-8.9) for cases (P < 0.0001), but 2.6 (1.5-4.6) for controls living in the endemic community (P = 0.001). CONCLUSION: This study shows that endemic ataxic polyneuropathy decreases survival. The finding of lower risk of death in the community with higher exposure to cyanide from cassava foods indicates that mortality of endemic ataxic polyneuropathy is not associated with exposure to cyanide from cassava foods.

Incidence of endemic ataxic polyneuropathy and its relation to exposure to cyanide in a Nigerian community.

BACKGROUND: The occurrence of ataxic polyneuropathy in an endemic area in south west Nigeria has been attributed to exposure to cyanide from cassava foods. However, it has been shown that the prevalence of ataxic polyneuropathy is not high in several communities in the tropics where exposure to cyanide from cassava foods is high. OBJECTIVES: To determine the incidence of ataxic polyneuropathy in an endemic community, and to compare the intake of cassava foods, exposure to cyanide, and levels of thiols in cases and controls. METHODS: A cohort of 3167 healthy subjects aged 10 years and over in Ososa, Nigeria, was followed for two years, screened, and examined neurologically. Ataxic polyneuropathy was diagnosed if sensory polyneuropathy and sensory gait ataxia were both present. Controls were selected randomly within 10 year age groups of subjects who screened negative. Intake of cassava foods, exposure to cyanide, concentrations of thiols (glutathione, cysteine, and gamma glutamylcysteine) in plasma, and visual evoked potentials were measured. RESULTS: Person-years of follow up were 6246 for 1469 male and 1698 female subjects in the cohort. The incidence of ataxic polyneuropathy was 64 per 10,000 person-years (31 for male and 93 for female subjects). Multivariate odd ratios were 0.78 (95% CI 0.23 to 2.61) for intake of the commonest cassava food, and 1.64 (0.56 to 5.09) for concentration of thiocyanate in plasma. The concentration of thiols was less than the reference limits in two controls, but in none of the cases. The latency of P100 was prolonged in 20 cases (69%) compared with 14 controls (42%) (p<0.05). CONCLUSIONS: The incidence of ataxic polyneuropathy is high in Ososa, Nigeria, but the intake of cassava foods, exposure to cyanide, and levels of thiols, are not related to the occurrence. These findings do not suggest that cyanide is the cause of endemic ataxic polyneuropathy.

Exposure to cyanide following a meal of cassava food.

Exposure to cyanide from gari, a popular cassava food in West Africa, is implicated in the causation of ataxic polyneuropathy and amblyopia, but this has been questioned because cyanide was not detected in gari in a study. This study was carried out to determine if gari is a source of exposure to cyanide. Gari (150 g) containing cyanohydrin, from which 128 micromol of cyanide ions could be released, was dissolved in 500 ml of cold water for each of the 12 healthy subjects to drink. Concentrations of cyanide in plasma and erythrocytes were determined at baseline and following the meal at 30 min, 1 h, hourly for 4 h and two hourly for 12 h. The mean concentrations of cyanide in the plasma were 6 micromol/l (95% CI 2-10) at baseline, 12 micromol/l (95% CI 6-17) at peak and 6 micromol/l (95% CI 2-10) on return to baseline. The mean amount of cyanide absorbed into the plasma was 13 micromol (S.D. 12), while the transit time of absorbed cyanide was 7.3 h (S.D. 2.1). This study shows that exposure to cyanide follows consumption of gari, but the amount of cyanide absorbed into the plasma from a single meal is small and unlikely to cause acute intoxication. The long transit time of absorbed cyanide in the plasma suggests that frequent intake of gari could cause cyanide to accumulate in the plasma.

Low prevalence of ataxic polyneuropathy in a community with high exposure to cyanide from cassava foods.

INTRODUCTION: Ataxic polyneuropathy, which occurs in endemic form in an area in southwest Nigeria, is attributed to exposure to cyanide from cassava foods. Exposure to cyanide from cassava is, however, not exclusive to this endemic area. In this study, the occurrence of ataxic polyneuropathy was compared in two communities in Nigeria, one located in the endemic area and the other located outside the endemic area. Both communities have been shown to have high exposure to cyanide from cassava foods. METHOD: The prevalence of ataxic polyneuropathy in Jobele, Nigeria, a community located outside the endemic area, was compared with the prevalence of ataxic polyneuropathy in Ososa, Nigeria, a reference community located in the endemic area. Subjects aged 10 years and above in both communities were screened for ataxic polyneuropathy. Ataxic polyneuropathy was diagnosed if sensory gait ataxia and sensory polyneuropathy were present. The intake of cassava foods, biomarkers of exposure to cyanide, and intake of protein and sulphur were measured. RESULTS: Prevalence of ataxic polyneuropathy were 490 per 10,000 in Ososa, and 17 per 10,000 in Jobele. The age-adjusted prevalence ratio is 4 (95% CI 0-9). The mean intake of all cassava foods in Jobele was 7 meals/person/week (95% CI 6-8), while the mean intake of all cassava foods in Ososa was 10 meals/person/week (95 % CI 9-11). The concentration of thiocyanate in the plasma was above the reference limit in 65% (95% CI 57-73) in Jobele, and 40 % (95% CI 27-52) in Ososa. The intake of protein was significantly lower in Ososa than in Jobele, but the concentrations of glutathione, cysteine and gamma-glutamylcysteine in the plasma were within the same range in Jobele and Ososa. CONCLUSION: This study shows that the occurrence of ataxic polyneuropathy is low in a community where exposure to cyanide is high. This suggests that exposure to cyanide is not a direct cause of ataxic polyneuropathy.

Loss of residual cyanogens in a cassava food during short-term storage.

Residual cyanogens in gari, the most popular cassava food in West Africa, is implicated in the causation of tropical ataxic neuropathy. Gari is eaten by soaking its granules in cold water or by adding boiling water to make a food called eba. This study was conducted to determine whether loss of the residual cyanogens in gari during short-term storage and when gari is made into eba will reduce dietary cyanide load in consumers. Fifteen samples of gari, nine roasted from cassava mash fermented for at least 4 days (type A) and six roasted from cassava mash fermented for only 1 day (type B), were stored for 4 weeks. Free cyanide, linamarin, and cyanohydrin in gari and in eba made from the gari were determined at weekly intervals for 4 weeks. Free cyanide was absent in all samples of gari. Mean cyanohydrin dropped from 8.4 mg HCN Eq/kg dry weight to 4.6 mg HCN Eq/kg dry weight in type A gari, while it dropped from 3.0 mg HCN Eq/kg dry weight to 1.3 mg HCN Eq/kg dry weight in type B gari. Mean linamarin dropped from 6.6 mg HCN Eq/kg dry weight to 2.8 mg HCN Eq/kg dry weight in type A gari, while it dropped from 1.7 mg HCN Eq/kg dry weight to 0.4 mg HCN Eq/kg dry weight in type B gari. Loss of linamarin and cyanohydrin was significant at P < 0.001 for type A gari and at P < 0.002 for type B gari when the weekly levels were compared with initial values. When gari was made into eba, 36% of cyanohydrin and 47% of linamarin were lost from type A gari, while 38% of cyanohydrin and 5% of linamarin were lost from type B gari. Loss of linamarin and cyanohydrin when gari was made into eba was significant for both types of gari at P < 0.001. This study shows that the loss of cyanohydrin and linamarin in gari during short-term storage and when gari is made to eba will reduce dietary cyanide load in consumers.

Ecological variation of intake of cassava food and dietary cyanide load in Nigerian communities.

AIM: To study the ecological variation of intake of cassava foods and dietary cyanide load. DESIGN: Ecological study design. SETTING: Five communities in south-western Nigeria where tropical ataxic neuropathy (TAN) was described as endemic (area A), 11 communities in south-western Nigeria where TAN was described as absent (area B), and five communities in northern Nigeria (area C). SUBJECTS: Subjects were randomly sampled from selected communities. Intake of cassava foods was estimated from dietary history and dietary cyanide load was estimated from urine thiocyanate concentrations. Residual cyanogens in cassava food samples from the community markets were determined. RESULTS: In total, 1272 subjects from 21 communities - 238 from area A, 659 from area B and 375 from area C - were selected. Intake of cassava food per person per week was 17 meals in area A, 10 meals in area B, and one meal in area C. Geometrical mean urine thiocyanate concentrations were 73 micromol l(-1), 51 micromol l(-1) and 17 micromol l(-1) in areas A, B and C, respectively. Mean residual cyanogen content in cassava food samples was 16 mg HCN eq kg(-1) (confidence interval (CI) 13-18) in area A, and 13 mg HCN eq kg(-1) in area B (CI 11-14). CONCLUSION: This study shows that the intake of cassava foods and dietary cyanide load is high in several communities in south-western Nigeria, predominantly in communities where TAN has been reported. Dietary cyanide load in these communities appears to be determined by the combination of frequency of intake and cyanogen content of cassava foods. Measures to improve the effectiveness of removal of cyanogen from cassava roots during processing are needed in the affected communities.

Persistence of tropical ataxic neuropathy in a Nigerian community.

OBJECTIVES: The term tropical ataxic neuropathy (TAN) is currently used to describe several neurological syndromes attributed to toxiconutritional causes. However, TAN was initially proposed to describe a specific neurological syndrome seen predominantly among the Ijebu speaking Yorubas in south western Nigeria. In this study, the prevalence of TAN was determined in Ososa, a semiurban community in south western Nigeria described as endemic for TAN in 1969, and its neurological features were compared with Strachan's syndrome, prisoners of war neuropathy, the epidemic neuropathy in Cuba, and konzo. METHODS: A census of Ososa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjects who screened positive had a neurological examination, and the diagnosis of TAN was made if any two or more of bilateral optic atrophy, bilateral neurosensory deafness, sensory gait ataxia, or distal symmetric sensory polyneuropathy were present. RESULTS: A total of 4583 inhabitants were registered in the census. Of these, 3428 subjects aged 10 years and above were screened. The diagnosis of TAN was made in 206 of 323 subjects who screened positive for TAN. The prevalence of TAN was 6. 0%, 3.9% in males and 7.7% in females. The highest age specific prevalence was 24% in the 60-69 years age group in women. CONCLUSION: The occurrence of TAN in Ososa continues at a higher prevalence than was reported 30 years ago. Its neurological features and natural history do not resemble those described for Strachan syndrome, epidemic neuropathy in Cuba, or konzo. The increasing consumption of cassava foods linked to its causation makes TAN of public health importance in Nigeria, the most populous African country.