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.

Simple sequence repeat marker diversity in cassava landraces: genetic diversity and differentiation in an asexually propagated crop.

Cassava (Manihot esculenta) is an allogamous, vegetatively propagated, Neotropical crop that is also widely grown in tropical Africa and Southeast Asia. To elucidate genetic diversity and differentiation in the crop's primary and secondary centers of diversity, and the forces shaping them, SSR marker variation was assessed at 67 loci in 283 accessions of cassava landraces from Africa (Tanzania and Nigeria) and the Neotropics (Brazil, Colombia, Peru, Venezuela, Guatemala, Mexico and Argentina). Average gene diversity (i.e., genetic diversity) was high in all countries, with an average heterozygosity of 0.5358 +/- 0.1184. Although the highest was found in Brazilian and Colombian accessions, genetic diversity in Neotropical and African materials is comparable. Despite the low level of differentiation [F(st)(theta) = 0.091 +/- 0.005] found among country samples, sufficient genetic distance (1-proportion of shared alleles) existed between individual genotypes to separate African from Neotropical accessions and to reveal a more pronounced substructure in the African landraces. Forces shaping differences in allele frequency at SSR loci and possibly counterbalancing successive founder effects involve probably spontaneous recombination, as assessed by parent-offspring relationships, and farmer-selection for adaptation.

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.

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.

High cassava production and low dietary cyanide exposure in mid-west Nigeria.

OBJECTIVE: To investigate if high cassava production levels indicate high consumption and high dietary cyanide exposure in three villages situated within the area of Nigeria with higher cassava production than predicted by a geographic model for cassava production in Africa. DESIGN: Exploratory assessment of: cassava production and processing by qualitative research methods and quantification of residual cyanogens in products; cassava consumption by food frequency and weighed food records and dietary cyanide exposure by urinary thiocyanate and linamarin. SETTING: Rural communities of Afuze, Ebue and Ofabo in mid-west Nigeria. SUBJECTS: 110 subjects from 42 households in three villages for food frequency interviews; 118 subjects in nine Ofabo households for weighed food records. RESULTS: Cassava cultivation was reported to have increased in the preceding 20 years. It was consumed daily by 37 (88%) households, but its mean contribution to daily energy intake was only 13% The range of residual cyanogens in cassava foods was 0 to 62 mg HCN equivalent/kg dry weight (dw). Ten samples (19%) had levels above the 10 mg HCN equivalent/kg dw FAO/WHO safety limit. Mean urinary thiocyanate and linamarin were 51 and 20 micromol/L, indicating low cyanogen intake and dietary cyanide exposure. CONCLUSION: High cassava production levels did not result in high consumption and high dietary cyanide exposure levels, therefore cassava production levels cannot be used to predict consumption or cyanide exposure levels in the study area. A large part of the production is explained by intensive sales.

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.

Dietary cyanide from insufficiently processed cassava and growth retardation in children in the Democratic Republic of Congo (formerly Zaire).

Dietary cyanide exposure from cyanogenic glucosides in insufficiently processed cassava has been advanced as a contributing factor in child growth retardation. Whether cyanide exposure aggravates children's growth retardation was studied by comparing two populations of children from the northern and the southern zones of the Bandundu region, Democratic Republic of Congo (former Zaire), using dietary interviews, anthropometry and urine analyses. Both populations consumed cassava as their staple diet, but whereas in the north the cassava was well processed, in the south it was inadequately processed. The mean urinary thiocyanate was much higher in the south, whereas mean urinary sulphate excretion was equally low in the two areas. However, the mean urinary SCN/SO4 molar ratio was higher in the south (0.20), indicating that 10-20% of sulphur amino-acids were used for cyanide detoxication. No significant differences were found between the two populations in weight-for-height and weight-for-age indices but the height-for-age index was significantly lower in children from the south, indicating more severe growth retardation in children exposed to dietary cyanide. Because of the preferential use of sulphur amino-acids for cyanide detoxification in the human body, dietary cyanide exposure from cassava may be a factor aggravating growth retardation in Bandundu.

Low dietary cyanogen exposure from frequent consumption of potentially toxic cassava in Malawi.

In a cassava-growing area in Malawi, where roots are processed by soaking and water is available throughout the year, we interviewed 176 women farmers regarding their preferences for cassava cultivars and frequency of cassava consumption. Dietary cyanogen exposure was estimated from urinary levels of linamarin, the cyanogenic glycoside in cassava, and urinary thiocyanate, the main cyanide metabolite. Protection against unplanned harvest by family members, theft and animal spoilage were stated to be very important reasons for growing bitter cassava cultivars by 91%, 90% and 74% of the women, respectively. The mean (+/- SD) number of cultivars grown by each woman was 4.6 (+/- 2.4). The correlation between mean taste and mean danger scores for the 25 most grown cultivars was strong (r > 0.98). The scoring indicated that cultivars belonged to two distinct groups, eight to a group referred to as 'cool' and 17 to a group termed 'bitter'. The dumpling-like porridge (kondowole) made from cassava flour from bitter roots was eaten twice daily by 51% and at least weekly by 81%. The mean (+/- SEM) urinary linamarin was 14 (+/- 1) mumol/L and thiocyanate was 50 (+/- 4) mumol/L, less than a tenth of levels reported from populations eating insufficiently processed bitter cassava roots, and in the same range as in a non-smoking Swedish reference population. We conclude that cyanogenesis is a preferred characteristic of cassava by the studied farmers because it enhances food security. The availability of water and their knowledge about toxicity and processing enables these women farmers to provide a safe staple food from bitter cassava roots.

Classification of thyroid size by palpation and ultrasonography in field surveys.

BACKGROUND: Goitre surveys are used to assess the degree of iodine deficiency in a population. The change of goitre classification made by WHO in 1994 implied that a smaller thyroid size should be regarded as goitre. Furthermore, the acceptable goitre prevalence was lowered from 10% to 5%, and ultrasonography was recommended as a more precise method for diagnosis of goitre. We studied the effects of the change of palpation system, and compared the precision of the old and new systems with that of ultrasonographic examination. METHODS: We studied 225 schoolchildren (aged 7-14 years) in a highland village in Tanzania. The size of the thyroid was assessed in duplicate by ultrasonography and by WHO's 1960 and 1994 palpation systems. The latter were done by three examiners. Variations within and between examination methods and examiners were assessed, and measurement errors by ultrasonography were assessed from duplicate examinations. The sensitivity and specificity of the two palpation systems were calculated, with diagnosis by ultrasonography as the gold standard. Apparent palpation prevalences were calculated at a "true" 5% prevalence. FINDINGS: The lowered criterion for goitre resulted in an extra 20-33% of children being diagnosed as having goitre by palpation. The variation between repeat examinations was only slightly smaller by ultrasonography (kappa=0.63) than by experienced examiners (kappa=0.57-0.58). The variation between thyroid volume estimation by ultrasonography and the true volume was about 50% due to both measurement error and variation in the shape of thyroid lobes. The new goitre criterion decreased specificity from 76% to 29%, whereas sensitivity rose from 56% to 80%. In contrast, a suggested sharpening of the old criterion increased specificity to 90%. INTERPRETATION: A return to the old (1960) palpation criterion for goitre: "lobes larger than the terminal phalanxes of thumbs" and to an accepted palpation goitre prevalence of 10% can allow affordable monitoring of thyroid size through palpation in field surveys.

Metabolic fates in humans of linamarin in cassava flour ingested as stiff porridge.

Insufficiently processed products from cassava roots may contain residual amounts of cyanogenic glucosides, mainly linamarin. The fate of orally ingested linamarin was studied following a meal of cassava porridge prepared from cassava flour from southern Tanzania with 82 mg cyanide equivalents (3035 micromol) of linamarin per kg dry weight. Following ingestion of amounts of porridge containing 243-571 micromol linamarin by 15 healthy adults a mean (range) of 21% (1-47%) of the linamarin ingested was excreted in the urine within 24 hours and a mean of 1% in the next 24 hours. Serum thiocyanate, the main cyanide metabolite, increased in all subjects from a mean (+/-SD) of 34+/-26 to 78+/-28 micromol/litre (P < 0.001). In a second group of seven subjects we found that the ingestion of porridge with a mean (range) of 431 micromol (203-669%) of linamarin resulted in a mean linamarin excretion of 127 micromol/litre and an excess thiocyanate excretion of 118 micromol/litre and that 216 micromol was unaccounted for. We conclude that less than one-half of orally ingested linamarin is converted to cyanide and hence thiocyanate, about one-quarter is excreted unchanged and another quarter is metabolized into an as yet unknown compound.

Coverage and cost of iodized oil capsule distribution in Tanzania.

Distribution of oral iodized oil capsules (IOC) is an important intervention in areas with iodine deficiency disorders (IDD) and low coverage of iodized salt. The mean reported coverage of 57 IOC distribution campaigns from 1986-1994 of people aged 1-45 years in 27 districts of Tanzania was 64% (range 20-96%). This declined over subsequent distribution rounds. However, due to delayed repeat distribution, only 43% of person-time was covered, based on the programme objective of giving two IOC (total 400 mg iodine) at 2-year intervals. Three different capsule distribution strategies used in 20 distribution rounds in 1992-1993 were analyzed in depth. Withdrawal of financial support for district distribution expenses under the 'district team' strategy, and the subsequent change to integrated 'primary health care' distribution, increased delays and capsule wastage. The third, more vertical strategy, 'national and district teams', accomplished rapid distribution of IOC about to expire and subsequently a return to the initial 'district team' allowance strategy was made. Annual cost of 'district team' distribution was 26 cents per person (400 mg iodine/2 years). Cost analysis revealed that the IOC itself accounts for more than 90% of total costs at the levels of coverage achieved. IOC will be important in the elimination of IDD in target areas of severe iodine deficiency and insufficient use of iodized salt, provided that high coverage can be achieved. Campaign distribution of medication with high item cost and long distribution intervals may be more cost-effectively performed if separated from regular PHC services at their present resource level. However, motivating health workers and community leaders to do adequate social mobilization remains crucial even if logistics are vertically organized. Insufficient support of distribution expenses and health education may lead to overall wastage of resources.

PIP: This paper analyzes the experience of using iodized oil capsules (IOCs) in Tanzania as a stopgap measure to control iodine deficiency disorder (IDD) in a target population of 7 million during a 9-year period (1986-94). The article also evaluates the costs and coverages of three different mass distribution strategies used in 1992-93. The assessment revealed that the distribution of oral IOCs was an important intervention in areas with IDD and low coverage of iodized salt. The mean reported coverage of 57 IOC distribution campaigns during 1986-94 of people aged 1-45 years in 27 districts of Tanzania was 64% (range, 20-96%). This declined over subsequent distribution rounds. However, due to delayed repeat distribution, only 43% of person-time was covered, based on the program objective of giving 2 IOCs (total of 400 mg iodine) at 2-year intervals. Further analysis of the 1992-93 data on the three different capsule distribution strategies used in 20 distribution rounds indicates the withdrawal of financial support for district distribution expenses under the "district team" strategy, and the subsequent change to integrated "primary health care" distribution, increased delays and capsule wastage. The third, more vertical strategy "national and district teams", accomplished a rapid distribution of IOCs and subsequently made a return to the initial "district team" allowance strategy. Annual cost of "district team" distribution was 26 cents per person (400 mg iodine per 2 years). Cost analysis revealed that the IOCs themselves account for more than 90% of total costs at the levels of coverage achieved.

Low cyanide exposure from consumption of cassava in Dar es Salaam, Tanzania.

The extent of cyanide exposure from cassava consumption was studied in low income suburbs of Dar es Salaam, Tanzania. Mean cyanogen levels in sun-dried root pieces called makopa was 9.4 (range 0-79) mg HCN equivalents kg(-1) dry weight. The mean glucoside and hydrogen cyanide levels were 6.4 and 3.2 mg HCN equivalents kg(-1) dry weight, respectively, while cyanohydrins were lower with a mean of 2.0 (range 0-27) equivalents kg(-1) dry weight. Food frequency interviews with 193 schoolchildren revealed that 13% of the children consumed cassava stiff porridge in the previous week. Fried cassava pieces were consumed by 82% and boiled cassava pieces by 49% of the children. The urinary thiocyanate in these children was 36 +/- 3 (mean +/- SEM) micromol l(-1) and mean urinary linamarin level was 18 +/- 1 micromol l(-1), indicating low cyanide exposure. Multiple regression analysis revealed a positive correlation between urinary thiocyanate and consumption of boiled cassava pieces as well as between urinary linamarin levels and daily intake of fried cassava pieces.

Geographical and seasonal association between linamarin and cyanide exposure from cassava and the upper motor neurone disease konzo in former Zaire.

High cyanide intake from consumption of insufficiently processed cassava has been advanced as a possible aetiology of the upper motor neurone disease konzo. However, similar neurodamage has not been associated with cyanide exposure from any other source. With an ecological study design, we compared 22 cases of konzo, 57 unaffected household members and 116 members from unaffected households, a total of 195 subjects, in konzo-affected savanna villages with 103 subjects in adjacent non-affected forest villages in the Paykongila area in the Bandundu Region, Zaire. In the dry season, the mean value (+/- SEM) of urinary thiocyanate, the main cyanide metabolite, was higher in the three groups in konzo-affected villages (563 +/- 105, 587 +/- 44 and 629 +/- 47 micromol/l) than in unaffected villages (241 +/- 17 micromol/l). In affected villages in the dry season when konzo incidence was high, mean urinary thiocyanate was also higher than the levels found in the wet season when incidence was low. The wet season values (mean +/- SEM) were 344 +/- 60, 381 +/- 35 and 351 +/- 27 micromol/l. Urinary levels of inorganic sulphate were low in all groups, indicating low intake of the sulphur amino-acids which provide a substrate for cyanide detoxification. These findings support an aetiological role for cyanide in konzo. However, urinary linamarin, the cyanogenic glucoside and source of cyanide in cassava, was more closely associated with the occurrence of konzo. The mean value (+/- SEM) of urinary linamarin in the konzo cases was 632 +/- 105 micromol/l and in their household members 657 +/- 52 micromol/l, which was significantly higher than in members of control households in the same village (351 +/- 28 micromol/l) and in unaffected villages (147 +/- 18 micromol/l). This suggests that a specific neurotoxic effect of linamarin, rather than the associated general cyanide exposure resulting from glucoside breakdown in the gut, may be the cause of konzo.

Milling reduces the goitrogenic potential of cassava.

Cyanide exposure from consumption of insufficiently processed cassava has been implicated in aggravating iodine deficiency disorders (IDD). The cyanide metabolite, thiocyanate (SCN) may interfere with iodine (I) uptake of the thyroid gland. A study on 217 women in an IDD endemic area in western Tanzania showed that 98% consumed cassava daily. Total and visible goitre rates were 72.8% and 13.3%, respectively. Median urinary iodine was 3.6 micrograms/dl indicating moderate iodine deficiency. Processing methods which remove cyanogens from cassava roots have changed with time. Urinary thiocyanate (mean; 128 mumol/l) was moderately increased, but women who frequently milled cassava had significantly lower urinary thiocyanate levels. This indicates that mechanical milling could reduce the goitrogenic potential of cassava and we conclude that IDD in the studied area is mainly due to iodine deficiency and sustainable iodine supplementation should be given highest priority.

Cyanide detoxification in rats exposed to acetonitrile and fed a low protein diet.

Different neurological syndromes have been associated with exposure to cyanide. Dietary cyanide exposure from cassava roots combined with a low intake of the sulfur amino acids necessary for cyanide detoxification has been implicated in the causation of konzo, an upper motoneuron disease identified in Africa. We have investigated the effect of a low protein diet on the capacity for cyanide detoxification. Rats were fed normal chow containing 18% protein or a low protein diet with 5% protein. To expose rats to cyanide the drinking water was supplemented with 40 or 80 mM acetonitrile (CH3CN) for up to 4 weeks. Weight gain was monitored and 24-hr urines were collected for analyses of total sulfur, inorganic sulfate, thiocyanate, and 2-aminothiolazine-4-carboxylic acid (ATC). Blood was collected for analyses of cyanide and cyanate. Rats on a normal diet grew throughout the experiment, while those on a low protein diet initially lost weight and then stabilized at a constant weight. Rats exposed to acetonitrile all progressively lost weight, those on a low protein diet at the highest rate. Signs of neurological damage were not observed. Rats not exposed to acetonitrile excreted < 0.2% of sulfur as thiocyanate and those on a low protein diet reduced their total sulfur excretion to one-third that of rats of the normal diet. Rats on the normal diet did not change total sulfur excretion during exposure to acetonitrile, although thiocyanate now contributed more than two-thirds of excreted sulfur. Rats on a low protein diet exposed to acetonitrile increased both total sulfur and thiocyanate excretion to the levels of rats on a normal diet. Rats exposed to acetonitrile had manyfold increases of circulating concentrations of cyanide and cyanate and of urinary excretion of ATC. There was a positive correlation between blood cyanide concentrations and the plasma concentration of cyanate. It is concluded that the rat has a high capacity for detoxification of cyanide. During adaptation to a low protein intake, sulfur is conserved but cyanide detoxification is still possible at the cost of extensive protein catabolism. It is thus possible that subclinical cyanide exposure could interfere with normal growth and development. The observation of a relationship between circulating cyanide on the one hand and circulating cyanate and urinary excretion of ATC on the other highlights the possibility that cyanide metabolites may mediate neurotoxic effects of cyanide.