Control of the Crippling Neurological Disease, Konzo
Vale Howard Bradbury
Howard passed away on Monday 28 November 2016.
In memoriam - Emeritus Professor Howard Bradbury.
It was in 1974 that I first saw the poverty and deprivation of life in a developing country. This caused me to change my research orientation from mainly basic research on the chemistry of macromolecules (see previous work, below) to a new interest in the chemistry of food. Food is of course important to all people, everywhere. So I developed research work on rice and sweet potatoes and then we analysed for their nutrients the tropical root crops of the South Pacific countries. This was published as an Australian Centre for International Agricultural Research (ACIAR) monograph in 1988. In December 1988 I took early retirement from teaching and research in the Department of Chemistry at ANU and moved to the Department of Botany, which has subsequently undergone amalgamation and a name change to Ecology and Evolution within the Research School of Biology.
Realising that the most important tropical root crop cassava contained cyanide compounds, which in Africa caused cyanide poisoning sometimes leading to death, as well as neurological diseases such as konzo and tropical ataxic neuropathy, I decided to focus my attention on this field.
Kits to determine cyanide in cassava and thiocyanate in urine
In 1995 we developed a simple method that could be used by a high school student to determine the total cyanide content of cassava roots and cassava products such as flour. We use yellow picrate papers which are turned brown by hydrogen cyanide (HCN) gas, liberated from a small sample of cassava by the enzyme linamarase, that is immobilised in a small filter paper. The colour of the picrate paper is compared with a chart with 10 shades of colour covering the range 0-800 ppm total cyanide, and this is used for field work. For accurate laboratory work the coloured compound is eluted from the paper with water and the absorbance of the solution measured in a spectrometer.
Ingested cyanide is detoxified in the body to thiocyanate which is removed in the urine, hence a urinary thiocyanate measurement shows the total cyanide intake over the preceding days. We developed a urinary thiocyanate kit based on oxidation of thiocyanate by acidified potassium permanganate with quantitative liberation of HCN, which is measured with a picrate paper. As suggested by ACIAR who funded this work, kits allowing 100 analyses for total cyanide or urinary thiocyanate are given away for free to health and agricultural workers in developing countries, and are sold in first world countries. Since 1996 nearly 600 kits have been given away for free and more than 500 sold, see http://biology-assets.anu.edu.au/hosted_sites/CCDN/.
Wetting method to remove cyanogens from cassava flour
In 2004-5, I discovered the “wetting method,” to remove cyanide compounds from cassava flour. Cassava flour is placed in a bowl and the level of the flour marked on the inside of the bowl. Water is added with mixing, the volume of the flour initially decreases and then increases until the flour reaches the mark on the bowl. The wet flour is spread out in a thin layer on a mat for two hours in the sun or five hours in the shade to allow HCN gas to escape from the wet flour. This removes nearly all the residual cyanide. The method is a gift from God. The method was checked out in Mozambique, it requires little extra work or equipment and the traditional thick porridge made from treated flour is free of the bitter taste due to linamarin present in the untreated flour. Recently the World Bank, WHO and FAO recognised the wetting method as a sensitive intervention to remove cyanogens from cassava flour. I recommend that the wetting method be used as an additional method to traditional methods to remove cyanogens from cassava flour in tropical Africa.
Control of konzo
Konzo is an upper motor neuron disease of sudden onset that causes irreversible paralysis of the legs mainly in children and in young women paericularly after childbirth, due to intake of large amounts of cyanide from bitter cassava roots and flour. Konzo occurs amongst very poor families living in remote villages whose diet is predominantly bitter cassava and also konzo epidemics occur during droughts and as a result of war. Konzo occurs in the Democratic Republic of Congo (DRC), Mozambique, Tanzania, Cameroon, Central African Republic and Angola.
In 2010 we started a new collaborative project with Dr J.P. Banea, Director of the National Institute of Nutrition, Kinshasa and coworkers, to prevent konzo in Kay Kalenge village, Bandundu Province, DRC. Kay Kalenge has a population of about 1000 with 34 konzo cases. The women of the village were taught that konzo is due to a poison (cyanide) present in the cassava flour and shown how to use the wetting method. The women accepted the method willingly and found that the thick porridge (fufu) made from treated flour was tastier and stored better than that made from untreated flour. Over the 18 month intervention there were no new cases of konzo and the mean urinary thiocyanate content of school children was reduced to a safe level. This is the first time ever that konzo has been prevented. Kay Kalenge village is located in Popokabaka Health Zone, which is where konzo was first discovered by Dr Trolli in 1938. After more than a years absence from Kay Kalenge village we returned and found no new cases of konzo, the women were still using the wetting method, the school children had low urinary thiocyanate levels and the wetting method had spread by word of mouth to three nearby villages.
We have now taught the wetting method to the women in thirteen konzo villages in DRC with nearly 10000 people, supported finanacially by AusAID. In our most recent intervention in six villages we carried out a food consumption survey from which we calculated the percentage malnutrition (% M) and also determined the percentage of children with high urinary thiocyanate levels (%T). Using the data for six villages we found a relation between the percentage konzo prevalence (%K) as follows:
%K = 0.06 %T + 0.035 %M.
This simple mathematical relation, which needs to be confirmed by further work, shows that konzo is related to malnutrition and high cyanide intake, measured by the percentage of children with high urinary thiocyanate levels.
Future work to control konzo
The incidence of konzo in DRC is increasing and the geographical spread of konzo in the other affected countries is increasing, due to the increased spread and consumption of cassava, needed to feed the rapidly increasing population of tropical Africa. The above equation shows that konzo may be prevented not only by reduction of cyanide intake from cassava but also by reduction of malnutrition. Our interventions to prevent konzo are based on reduction of cyanide intake, by village women who use the wetting method every day. We have reduced the time of intervention from 18 months in our first intervention to 9 months and reduced the cost to $16 per person. This is a much less expensive option than a broad-based approach to reduce malnutrition, which is also needed to improve the general health of village people. Our methodology using the wetting method works very well in practice and further reductions in cost would occur if it were scaled up.
We appeal to funding agencies for financial support to prevent konzo amongst the poorest of the poor children and young women of DRC.
Previous Work and Awards
I studied chemistry at Melbourne Technical College and Melbourne University followed by a PhD in polymer chemistry at Birmingham University. After a postdoctoral fellowship at Harvard University, I worked at CSIRO Wool Research Laboratories and then moved to the Chemistry Department at the Australian National University (ANU) in 1961. I had sabbatical appointments at Cornell University and on three occasions at Oxford University. My major research interests during this period were the chemistry of wool and keratin fibres and subsequently NMR studies of proteins, enzymes and carbohydrates. I was awarded a DSc and the David Syme Research Prize by Melbourne University, the Rennie Memorial Medal and H G Smith Memorial Medal by the Royal Australian Chemical Institute and a DSc by ANU.
I took early retirement in December 1988 from teaching and research in chemistry, and since then have continued to work on konzo and other health problems due to cyanogens present in cassava. In 2007 I was awarded the inaugural "$2 a day award" by the Institution of Chemical Engineers for the discovery of the wetting method. In 2007 I was appointed a Member of the Order of Australia.
Control of the Crippling Neurological Disease, Konzo
- Read more on the Konzo Prevention Unit website.
1. Cassava cyanide diseases and neurolathyrism network (CCDNN)
In 2001 we established a free information network called the Cassava Cyanide Diseases Network for those concerned about cyanide poisoning, konzo, tropical ataxic neuropathy and other diseases due to consumption of cassava. In 2009, after an International Workshop on konzo and neurolathyrism organised by Professor Fernand Lambein at the University of Ghent, Belgium, at which the close medical similarities between these diseases were highlighted, it was decided to expand the network to include neurolathyrism. The CCDNN has about 350 members from 60 countries, and we produce a six monthly newsletter called Cassava Cyanide Diseases and Neurolathyrism News (CCDN News). I was the first coordinator of CCDNN and in December 2011, I gratefully handed this on to Professor Fernand Lambein (1).
2. Mild processing of cassava leaves to retain key nutrients
Cassava leaves are used extensively in Africa as a good source of protein and vitamins which complements nutritionally starchy cassava roots. The traditional method of removing the large amount of cyanogens present in the leaves consists of pounding the leaves followed by boiling for 15-60 minutes, that destroys vitamins and S-containing amino acids, which are necessary to convert ingested cyanide to thiocyanate (1). We have developed a simple method which involves pounding of leaves followed by standing and washing in water at ambient temperature, to remove cyanogens whilst conserving key nutrients (23).
3. Wetting method to remove cyanide from gari
Whereas cassava flour is preferred and used in eastern, southern and central Africa, gari is the processed cassava product of choice in West Africa. Gari is produced by grating cassava roots followed by a fermentation process, squeezing off liquid and roasting. The residual total cyanide content is about 20 ppm, compared with about 45 ppm for cassava flour. Lactic fermentation lowers the pH of gari to about 4.1 and under these conditions the residual cyanide, present as acetone cyanohydrin, is stable. We have found that if the pH is raised to 5, by adding excess pH 5 buffer or an equal amount of cassava flour, and heating at 50 degrees C for 4 hours, the total cyanide content can be reduced by 50%. The final wetting method involves mixing gari with flour (1:1), wetting with water and standing for 4 hours in the sun. We hope that this method may prove useful to reduce the amount of tropical ataxic neuropathy (TAN) in Nigeria (19).
4. Asia Pacific Food Analysis Network (APFAN)
In 1989 I started APFAN and was its Coordinator until I stepped down in 1999. APFAN promoted food safety and good nutrition by serving the needs of food analysts, particularly in developing countries.
- Bradbury, j.H., Cliff, J., Banea, J.P. 2015. Making cassava safe using the wetting method. South Sudan Medical J., 8, 4-7. (PDF)
- Banea, J.P., Bradbury, J.H., Nahimana, D., Denton, I.C., Mashukano, N., and Kuwa, N. 2015. Survey of the konzo prevalence of village people and their nutrition in Kwilu District, Bandundu Province, DRC. African J. Food Sci. 9, 43-50. (PDF)
- Banea, J.P., Bradbury, J.H., Mandombi, C., Nahimana, D., Denton, I.C., Foster, M.P., Kuwa, N., Katumbay, D.T. 2014. Prevention of konzo in the Democratic Republic of Congo (DRC) using the wetting method and correlation between konzo incidence and percentage of children with high urinary thiocyanate level. African Journal of Food Science 8(6): 297-304. (PDF, 270KB)
- Banea, J.P., Bradbury, J.H., Mandombi, C., Nahimana, D., Denton, I.C., Kuwa, N., and Tshala Katumbay, D. (2014) Effectiveness of wetting method for control of konzo and reduction of cyanide poisoning by removal of cyanogens from cassava flour. Food Nutrition Bulletin, 35, 28-32. (PDF)
- Bradbury, J.H. and Denton, I.C. (2014) Mild method for removal of cyanogens from cassava leaves with retention of vitamins and protein. Food Chem. 158, 417-420. (PDF)
- Banea, J.P., Bradbury, J.H., Mandombi, C., Nahimana, D., Denton, I.C., Kuwa, N. and Tshala Katumbay, D. (2013) Control of konzo by detoxification of cassava flour in three villages in the Democratic Republic of Congo. Food Chem. Toxicol. 60, 506-513. (PDF)
- Banea, J.P., Nahimana, G., Mandombi, C., Bradbury, J.H., Denton, I.C. and Kuwa, N. (2012) Control of konzo in DRC using the wetting method on cassava flour. Food Chem. Toxicol. 50, 1517-1523. (PDF, 483KB)
- Bradbury, J.H. and Denton, I.C. (2011) Mild methods of processing cassava leaves to remove cyanogens and conserve key nutrients. Food Chem. 127, 1755-1759.[(PDF, 358KB)
- Bradbury, J.H., Cliff, J. and Denton, I.C. (2011) Uptake of wetting method in Africa to reduce cyanide poisoning and konzo from cassava. Food Chem Toxicol. 49, 539-542. (PDF, 762KB)
- Cliff, J., Muquingue, H., Nhassico,D., Nzwalo, H, and Bradbury, J.H. (2011) Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem Toxicol. 49, 631-635. (PDF, 309KB)
- Bradbury, J.H. and Denton, I.C (2010) Rapid wetting method to reduce cyanogen content of cassava flour. Food Chem. 121, 591-594. (PDF, 338KB)
- Bradbury, J.H. and Denton, I.C. (2010) Simple method to reduce the cyanogen content of gari made from cassava. Food Chemistry, 123, 840-845. (PDF, 372KB)
- Mlingi, N.L.V., Nkya, S., Tatala, S.R., Rashid, S. and Bradbury, J.H. (2011) Recurrence of konzo in southern Tanzania: rehabilitation and prevention using the wetting method. Food Chem Toxicol 49, 673-677. (PDF, 479KB)
- Bradbury, J.H. (2009) Development of a sensitive picrate method to determine total cyanide and acetone cyanohydrin contents of gari from cassava. Food Chem. 113, 1329-1333.
- Bradbury, J.H. (2008) Simple solution fights konzo. tce – The Chemical Engineer, February 2008, 24-25. (PDF, 5059KB)
- Nhassico, D., Muquingue, H., Cliff, J., Cumbana, A. and Bradbury, J.H. (2008) Rising African cassava production, diseases due to high cyanide intake and control measures. J. Sci. Food Agric. 88, 2043-2049. (PDF, 115KB)
- Cumbana, A., Mirione, E., Cliff, J. and Bradbury, J.H. (2007) Reduction of cyanide content of cassava flour in Mozambique by the wetting method. Food Chem., 101, 894-897. (PDF, 168KB)
- Bradbury, J.H. (2006) Simple wetting method to reduce cyanogen content of cassava flour. J Food Comp. Anal., 19, 388-393. (PDF, 168KB)
- Cardoso, A.P., Mirione, E., Ernesto, M., Massaza, F., Cliff, J., Haque, M. and Bradbury, J.H. (2005) Processing of cassava roots to remove cyanogens. J. Food Comp. Anal. 18, 451-460. (PDF, 226KB)
- Muquingue, H., Nhassico, D., Cliff, J., Sitoe, L., Tonela, A, and Bradbury, J.H. (2005) Field trial in Mozambique of a new method for detoxifying cassava in cassava products. CCDN News, No 6, 3-4. (PDF, 258KB)
- Cardoso, A.P., Ernesto, M., Nicala, D., Mirione, E., Chavane, L., N’zwalo, H., Chikumba, S., Cliff, J., Mabota, A.P., Haque, M. and Bradbury, J.H. (2004) Combination of cassava flour cyanide and urinary thiocyanate measurements of school children in Mozambique. Int. J. Food Sci. Nutr. 55, 183-190. (PDF, 116KB)
- Haque, M., and Bradbury, J.H. (2002). Total cyanide determination of plants and foods using the picrate and acid hydrolysis methods. Food Chem 77, 107-114. (PDF, 136KB)
- Ernesto, M., Cardoso, A.P., Nicala, D., Mirione, E., Massaza, F., Cliff, J., Haque, M. and Bradbury, J.H. (2002) Persistent konzo and cyanogens toxicity from cassava in northern Mozambique, Acta Tropica, 82, 357-362. (PDF, 98KB)
- Bradbury, M G, Egan, S V and Bradbury, J H (1999) Picrate paper kits for determination of total cyanogens in cassava roots and all forms of cyanogens in cassava products. J. Sci. Food Agric., 79, 593-601. (PDF, 419KB)
- Bradbury, M G, Egan, S V and Bradbury, J H (1999) Picrate paper kits for determination of total cyanogens in cassava roots and all forms of cyanogens in cassava products. J. Sci. Food Agric., 79, 593-601. (PDF, 419KB)Haque, M.R. and Bradbury, J.H.(1999) Simple method for determination of thiocyanate in urine. Clinical Chemistry, 45, 1459-1464. (PDF, 280KB)
- Haque, M.R. and Bradbury, J.H.(1999) Simple method for determination of thiocyanate in urine. Clinical Chemistry, 45, 1459-1464. [PDF]
- Egan, S.V., Yeoh, H.H. and Bradbury, J.H. (1998) Simple picrate paper kit for determination of the cyanogenic potential of cassava flour. J. Sci. Food Agric.76, 39-48. (PDF, 417KB)
- Cardoso, A. P., Ernesto, M., Cliff, J., Egan, S. V. and Bradbury, J. H. (1998) Cyanogenic potential of cassava flour: Field trial in Mozambique of a simple kit. Intern J Food Sci Nutr, 49, 93-99. (PDF,273KB)
- King, N.L.R. and Bradbury, J.H. (1995) Bitterness of cassava: identification of a new apiosyl glycoside and other compounds that affect its bitter taste. J. Sci.Food Agric. 68, 223-230.[(PDF, 4099KB)
- Bradbury, J.H. and Holloway, W. D. 1988. Chemistry of tropical root crops : significance for nutrition and agriculture in the Pacific, Australian Centre for International Agricultural Research (ACIAR). Monograph No 6, 201 pp.
- Carver J.A. and Bradbury, J.H. (1984) Assignment of 1H NMR Resonances of Histidine and Other Aromatic Residues in Met, Cyano, Oxy and Carbon Monoxy Myoglobins, Biochemistry, 23, 4890-4905.
- Bradbury, J.H. (1973) The structure and chemistry of keratin fibres. Advances in Protein Chemistry, 27, 111- 211.
- King, N.L.R. and Bradbury, J.H. (1971) Simplification of the proton magnetic resonance spectroscopy of ribonuclease by difference spectroscopy. Nature 229, 404-406.
- Bradbury, J.H. and Scheraga, H.A. (1966) Structural studies of ribonuclease. XXIV Application of NMR spectroscopy to distinguish between the histidine residues of ribonuclease. J. Amer. Chem. Soc. 88, 4240-46.
- Doty, P., Bradbury, J.H. and Holtzer, A.M. (1956) Polypeptides IV: The molecular weight, configuration and association of poly-gamma-benzyl glutamate in various solvents. J. Amer. Chem. Soc. 78, 947-954.
- Bradbury, J.H. and Melville, H.W (1954) The Copolymerization of Styrene and Butyl Acrylate in Benzene Solution, Proc.Roy.Soc., 222A, 456-470.