Recurrence of konzo in southern Tanzania: rehabilitation and prevention using the wetting method.

There have been four konzo outbreaks in Tanzania from 1985 to 2002/2003 with a total of 363 cases of konzo. Every outbreak of konzo resulted from large cyanogen intakes from bitter cassava during drought, which caused food shortages and led to people using short-cut methods of cassava processing. Rehabilitation of the 214 konzo subjects from the two most recent outbreaks of konzo in southern Tanzania was carried out by screening konzo subjects and included provision of crutches and wheel chairs. The wetting method was taught to 216 women activists from the konzo-prone villages, in the first large scale community based intervention to reduce cyanogen intake. Using cassava cyanide kits, the average total cyanide content was reduced by the wetting method about 4-fold, in agreement with previous studies. This model to help prevent konzo requires the widespread education of women activists to use the wetting method.

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.

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.

A specific and sensitive method for the determination of linamarin in Urine.

A method is described for the quantitative determination of the cyanogenic glycoside linamarin. A preseparation procedure for urine samples was necessary to remove interfering substances. This was done by solid-phase extraction on a silica column containing cyclohexyl functional groups, which retained linamarin but allowed thiocyanate to pass unrestricted through the column. After elution of linamarin from the column by 35% (v/v) aqueous methanol, the glycoside was quantified following enzymatic hydrolysis, using the specified enzyme linamarase, and the free cyanide thus liberated was estimated spectrophotometrically. This method allowed quantification of linamarin in urine down to 10 mumol/l, with an estimated recovery of 91%. In 75 Tanzanian subjects consuming insufficiently processed cassava, the mean (+/- SD) urinary linamarin concentration was 104 (+/- 104) mumol/l (range 0 - 644 mumol/L), while that for thiocyanate was 486 (+/- 451) mumol/l (range 10-2,940 mumol/l), giving an approximate 1:5 molar concentration ratio between urinary linamarin and thiocyanate.

Diabetes is not caused by cassava toxicity. A study in a Tanzanian community.

OBJECTIVE: To test the hypothesis that consumption of cassava with liberation of cyanide causes diabetes in malnourished individuals. RESEARCH DESIGN AND METHODS: Glucose tolerance was assessed in two rural communities in Tanzania; in one (Nyambori), the main source of calories was cassava; and in the other (Uswaa), cassava was rarely eaten. Undernutrition was prevalent in both communities. The people of Nyambori were known to have high dietary cyanide exposure for many years from consumption of insufficiently processed cassava. Of the 1435 people in Nyambori greater than or equal to 15 yr old, 1067 (74%) were surveyed, and 1429 of 1472 (97%) eligible subjects in Uswaa were surveyed. All had 75-g oral glucose tolerance tests and measurement of BMI. Plasma and urine thiocyanate and blood cyanide also were measured in some subjects. RESULTS: Mean +/- SD plasma and urine thiocyanate levels in Nyambori were 296 +/- 190 and 497 +/- 457 microM (n = 204), respectively, compared with 30 +/- 37 and 9 +/- 13 microM, respectively, in Uswaa (n = 92) (P less than 0.001 for all differences). The mean blood cyanide level in Nyambori was elevated (1.4 [range 0.1-30.2] microM; n = 91). The prevalence of diabetes in the cassava village (Nyambori) was 0.5% compared with 0.9% in Uswaa (NS). The prevalence of IGT was similar in the two villages in the 15- to 34- and the 34- to 54-yr-old age-groups; but in those greater than or equal to 55 yr old, IGT was higher in Nyambori (17.4 vs 7.2%, P = 0.029). Mean fasting and 2-h blood glucose levels were slightly higher in Nyambori village after adjusting for age, sex, and BMI (4.5 vs. 4.2 and 5.0 vs. 4.4 mM, respectively). CONCLUSIONS: High dietary cyanide exposure was not found to have had a significant effect on the prevalence of diabetes in an undernourished population in Tanzania. Cassava consumption is thus highly unlikely to be a major etiological factor in so-called MRDM, at least in East Africa.

Konzo, an epidemic upper motor neuron disease studied in Tanzania.

An epidemic of spastic paraparesis was studied in a drought-affected rural area of Tarime district in northern Tanzania. The uniform clinical findings in 39 cases, aged 4-46 yrs, indicated abrupt symmetric isolated and permanent but not progressive damage to the upper motor neurons. Due to the failure of other food crops, the diet at onset consisted almost exclusively of bitter cassava roots, a drought-tolerant starchy root crop widely cultivated in Africa. The drought increased the natural occurrence of cyanogenic glucosides in the cassava roots, and the processing procedure normally applied in order to remove cyanide before consumption was shortened because of food shortage. The resulting high dietary cyanide exposure was confirmed by very high serum levels of thiocyanate, the detoxification product of cyanide. Tests for HTLV-1 antibodies were negative and no other findings supported an infectious aetiology. The clinical findings and the associations with cassava toxicity are almost identical to those reported from outbreaks of spastic paraparesis in Mozambique and in Zaire, where this disease was first reported under the name 'konzo'. We thus conclude that konzo constitutes a distinct upper motor neuron disease entity, probably caused by a toxic effect from insufficiently processed cassava under adverse dietary circumstances.