- Email: [email protected]
Comment on “Control of konzo in DRC using the wetting method on cassava flour” by Banea et al. (2012)
Food and Chemical Toxicology 50 (2012) 4232–4233
Contents lists available at SciVerse ScienceDirect
Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox
Letter to the Editor Comment on ‘‘Control of konzo in DRC using the wetting method on cassava flour’’ by Banea et al. (2012)
Dear Sir I wish to refer to the article: Control of konzo in DRC using the wetting method on cassava flour by Banea et al., 2012. The authors’ rationale for the intervention in this paper appears to be their stated opinion that konzo is caused by high cyanide intake from consumption of a monotonous diet of bitter cassava. The authors did not however provide any proof for such a causal relationship. They cited a paper (Ministry of Health, Mozambique 1984) showing a good correlation between peak consumption of cassava and incidence of konzo as their evidence linking the incidence of konzo with cyanide overload. However, that same paper stated clearly that it had not been possible to show that chronic cyanide intoxication was the cause of konzo because both the patients with konzo and their controls had high thiocyanate levels and there was no correlation between disease severity and thiocyanate levels. Patients with konzo and their family members who did not succumb to the disease have been shown to be exposed to similar levels of cassava consumption, (Tylleskar et al., 1992) with both groups having similarly high thiocyanate levels. In one recent study, the mean serum concentration of thiocyanate in apparently asymptomatic school children in Mozambique was found to be as high as 512 lmol/l (Cliff et al., 2011). Spastic paraparesis, the clinical hall mark of konzo is not a known clinical manifestation of cyanide toxicity in humans or animals; and has not been associated with cyanide exposure from any other source. It is quite instructive that in their authoritative book on the history of tropical neurology, Bryun and Poser (2003) reviewed the evidence for the ‘‘cyanide hypothesis’’ for the etiology of konzo; and concluded that it was a ‘‘poorly formulated concept supported by inadequate methodologies, and unconvincing haphazard epidemiological research’’. The data presented in the paper by Banea et al. (2012) does not justify the claim that the wetting method has prevented konzo. Fig. 2 in the paper showed no new cases of konzo in the study villages between 1993 and 1995 (3 years) and between 1997 and 2004 (8 years) without any intervention at all. Yet, the authors concluded that they have prevented konzo in the study area because there has been no new cases for a period of 1.5 years after their intervention, when the natural history of the disease indicated that periods of disease freedom for up to 8 years can occur without any intervention at all. The authors then selectively compared the 1.5 years of disease freedom following their intervention with the situation in the
q
DOI of original article: http://dx.doi.org/10.1016/j.fct.2012.02.001
0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2012.06.040
villages in 2009, when there were several cases of konzo. However, such an assessment is invalid without a comparison of data on annual rainfall (konzo is more likely during periods of drought), nutritional indices, socio-economic trends and animal protein consumption (konzo is less likely with a balanced diet) during the two time periods. No such comparison was done in their study. The decline in urinary thiocyanate levels from a pre-intervention mean of 332 lmol/l in March 2010 to a post-intervention mean of 130 lmol/l is statistically impressive, and no doubt demonstrates the efficacy of the wetting method in reducing the cyanogenic load in cassava. However, this cannot be inferred to imply control or prevention of konzo. The authors did not give any indication as to why they considered a urinary thiocynate level of 130 lmol/l to be a ‘‘safe level’’ (See line 3 of their conclusion). Chabwine et al. (2011) conducted two field surveys that identified patients with konzo in the Democratic Republic of Congo (DRC). The mean urinary thiocyanate level in their patients was 129 lmol/l (range 20–688 lmol/l). They suggested a cut-off concentration of 100 lmol, below which patients will be less likely to have konzo. Similarly, Cliff et al. (2011) considered a urinary thiocyanate level of 113 lmol to be indicative of cyanide intoxication. From the above, it appears that a urinary thiocyanate level of 130 lmol/l cannot be considered safe, and does not portend protection from, or prevention of konzo, as Banea et al. (2012) appear to suggest. In conclusion, while consumption of high levels of cyanide in bitter cassava may somehow facilitate the occurrence of konzo in susceptible populations, there is no evidence of a causal association. Facilitation does not equal causation. The etiologic mechanisms of konzo still remain unknown. The study design and data presented by Banea et al. (2012) have not justified their study conclusion that the wetting method prevents konzo. References Banea, J.P., Nahimana, G., Mandombi, C., Bradbury, J.H., Denton, I.C., Kuwa, N., 2012. Control of konzo in DRC using the wetting method on cassava flour. Food Chem. Toxicol. 50, 1517–1523. Bruyn, G.W., Poser, C.M., 2003. Konzo and Tropical ataxic Neuropathy. In: The history of Tropical Neurology: Nutritional Disorders. Science History Publications, Canton, USA, pp. 75–88. Chabwine, J.N., Masheka, C., Balol’ebwami, Z., Maheshe, B., Balegamire, S., Rutega, B., waLola, M., Mutendela, K., Bonnet, M.J., Shangalume, O., Balegamire, J.M., Nemery, B., 2011. Appearance of konzo in South-Kivu, a war-torn area in the Democratic Republic of Congo. Food Chem Toxicol. 49, 644–649. Cliff, J., Muquigue, H., Nhassico, D., Nzwalo, H., Bradbury, J.H., 2011. Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem. Toxicol. 49, 631–635. Ministry of Health, Mozambique, 1984. Mantakassa: an epidemic of spastic paraparesis associated with chronic cyanide intoxication in a cassava staple area of Mozambique. 1. Epidemiology and clinical laboratory findings in patients. Bull World Health Organ 62 (3), 477–484. Tylleskar, T., Banea, M., Bikangi, N., Cooke, R.D., Poulter, N.H., Rosling, H., 1992. Cassava cyanogens and Konzo, an upper motor neurone disease found in Africa. Lancet 339 (8787), 208–211.
Letter to the Editor / Food and Chemical Toxicology 50 (2012) 4232–4233
4233
Bola Adamolekun MD, FWACP Department of Neurology, University of Tennessee Health Science Center, Memphis TN 38163, USA E-mail address: [email protected] Available online 29 June 2012
Contents lists available at SciVerse ScienceDirect
Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox
Letter to the Editor Comment on ‘‘Control of konzo in DRC using the wetting method on cassava flour’’ by Banea et al. (2012)
Dear Sir I wish to refer to the article: Control of konzo in DRC using the wetting method on cassava flour by Banea et al., 2012. The authors’ rationale for the intervention in this paper appears to be their stated opinion that konzo is caused by high cyanide intake from consumption of a monotonous diet of bitter cassava. The authors did not however provide any proof for such a causal relationship. They cited a paper (Ministry of Health, Mozambique 1984) showing a good correlation between peak consumption of cassava and incidence of konzo as their evidence linking the incidence of konzo with cyanide overload. However, that same paper stated clearly that it had not been possible to show that chronic cyanide intoxication was the cause of konzo because both the patients with konzo and their controls had high thiocyanate levels and there was no correlation between disease severity and thiocyanate levels. Patients with konzo and their family members who did not succumb to the disease have been shown to be exposed to similar levels of cassava consumption, (Tylleskar et al., 1992) with both groups having similarly high thiocyanate levels. In one recent study, the mean serum concentration of thiocyanate in apparently asymptomatic school children in Mozambique was found to be as high as 512 lmol/l (Cliff et al., 2011). Spastic paraparesis, the clinical hall mark of konzo is not a known clinical manifestation of cyanide toxicity in humans or animals; and has not been associated with cyanide exposure from any other source. It is quite instructive that in their authoritative book on the history of tropical neurology, Bryun and Poser (2003) reviewed the evidence for the ‘‘cyanide hypothesis’’ for the etiology of konzo; and concluded that it was a ‘‘poorly formulated concept supported by inadequate methodologies, and unconvincing haphazard epidemiological research’’. The data presented in the paper by Banea et al. (2012) does not justify the claim that the wetting method has prevented konzo. Fig. 2 in the paper showed no new cases of konzo in the study villages between 1993 and 1995 (3 years) and between 1997 and 2004 (8 years) without any intervention at all. Yet, the authors concluded that they have prevented konzo in the study area because there has been no new cases for a period of 1.5 years after their intervention, when the natural history of the disease indicated that periods of disease freedom for up to 8 years can occur without any intervention at all. The authors then selectively compared the 1.5 years of disease freedom following their intervention with the situation in the
q
DOI of original article: http://dx.doi.org/10.1016/j.fct.2012.02.001
0278-6915/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2012.06.040
villages in 2009, when there were several cases of konzo. However, such an assessment is invalid without a comparison of data on annual rainfall (konzo is more likely during periods of drought), nutritional indices, socio-economic trends and animal protein consumption (konzo is less likely with a balanced diet) during the two time periods. No such comparison was done in their study. The decline in urinary thiocyanate levels from a pre-intervention mean of 332 lmol/l in March 2010 to a post-intervention mean of 130 lmol/l is statistically impressive, and no doubt demonstrates the efficacy of the wetting method in reducing the cyanogenic load in cassava. However, this cannot be inferred to imply control or prevention of konzo. The authors did not give any indication as to why they considered a urinary thiocynate level of 130 lmol/l to be a ‘‘safe level’’ (See line 3 of their conclusion). Chabwine et al. (2011) conducted two field surveys that identified patients with konzo in the Democratic Republic of Congo (DRC). The mean urinary thiocyanate level in their patients was 129 lmol/l (range 20–688 lmol/l). They suggested a cut-off concentration of 100 lmol, below which patients will be less likely to have konzo. Similarly, Cliff et al. (2011) considered a urinary thiocyanate level of 113 lmol to be indicative of cyanide intoxication. From the above, it appears that a urinary thiocyanate level of 130 lmol/l cannot be considered safe, and does not portend protection from, or prevention of konzo, as Banea et al. (2012) appear to suggest. In conclusion, while consumption of high levels of cyanide in bitter cassava may somehow facilitate the occurrence of konzo in susceptible populations, there is no evidence of a causal association. Facilitation does not equal causation. The etiologic mechanisms of konzo still remain unknown. The study design and data presented by Banea et al. (2012) have not justified their study conclusion that the wetting method prevents konzo. References Banea, J.P., Nahimana, G., Mandombi, C., Bradbury, J.H., Denton, I.C., Kuwa, N., 2012. Control of konzo in DRC using the wetting method on cassava flour. Food Chem. Toxicol. 50, 1517–1523. Bruyn, G.W., Poser, C.M., 2003. Konzo and Tropical ataxic Neuropathy. In: The history of Tropical Neurology: Nutritional Disorders. Science History Publications, Canton, USA, pp. 75–88. Chabwine, J.N., Masheka, C., Balol’ebwami, Z., Maheshe, B., Balegamire, S., Rutega, B., waLola, M., Mutendela, K., Bonnet, M.J., Shangalume, O., Balegamire, J.M., Nemery, B., 2011. Appearance of konzo in South-Kivu, a war-torn area in the Democratic Republic of Congo. Food Chem Toxicol. 49, 644–649. Cliff, J., Muquigue, H., Nhassico, D., Nzwalo, H., Bradbury, J.H., 2011. Konzo and continuing cyanide intoxication from cassava in Mozambique. Food Chem. Toxicol. 49, 631–635. Ministry of Health, Mozambique, 1984. Mantakassa: an epidemic of spastic paraparesis associated with chronic cyanide intoxication in a cassava staple area of Mozambique. 1. Epidemiology and clinical laboratory findings in patients. Bull World Health Organ 62 (3), 477–484. Tylleskar, T., Banea, M., Bikangi, N., Cooke, R.D., Poulter, N.H., Rosling, H., 1992. Cassava cyanogens and Konzo, an upper motor neurone disease found in Africa. Lancet 339 (8787), 208–211.
Letter to the Editor / Food and Chemical Toxicology 50 (2012) 4232–4233
4233
Bola Adamolekun MD, FWACP Department of Neurology, University of Tennessee Health Science Center, Memphis TN 38163, USA E-mail address: [email protected] Available online 29 June 2012