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Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of Congo
Food and Chemical Toxicology 49 (2011) 644–649
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Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of Congo J.N. Chabwine a,e,f,⇑, C. Masheka a, Z. Balol’ebwami a, B. Maheshe a,c, S. Balegamire a, B. Rutega b, M. wa Lola b, K. Mutendela c, M.-J. Bonnet d, O. Shangalume b, J.M. Balegamire e,f, B. Nemery e a
Faculty of Medicine, Université Catholique de Bukavu (UCB), PO Box 02, Cyangugu, Rwanda Faculty of Agronomy, Université Catholique de Bukavu (UCB), PO Box 02, Cyangugu, Rwanda Hôpital Provincial de Référence de Bukavu, PO Box 02, Cyangugu, Rwanda d Bureau Diocésain des Oeuvres Médicales, Bukavu (BDOM), PO Box 02, Cyangugu, Rwanda e Katholieke Universiteit Leuven, Occupational, Environmental and Insurance Medicine, Research Unit of Lung Toxicology, Laboratory of Pneumology, Herestraat 49 (O&N 706), B-3000 Leuven, Belgium f NGO Africa Tomorrow, P.O. BOX 2278, 1211 Geneva 2, Switzerland b c
a r t i c l e
i n f o
Article history: Available online 4 August 2010 Keywords: Konzo Spastic paraparesis Cassava Toxicity Cyanogens Burhinyi
a b s t r a c t Konzo is an upper motor neuron disease characterized by sudden-onset and irreversible spastic paraparesis occurring in nutritionally compromised people. It is associated with consumption of insufficiently processed cyanogenic-toxic cassava. Cassava, the main caloric source in the Democratic Republic of Congo, has been safely consumed for decades in the Eastern Province of South-Kivu. However, in the context of long-lasting war and violent conflicts, cases of spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate concentrations (median 129, range 20–688, SD 146 lg/L), and cyanogen levels (median 20 ppm, range 5–300 ppm, SD 73 ppm) in cassava roots from their household stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava roots during harvest period, but probably also insufficiently processed roots. This first report of konzo in South-Kivu concludes that occurrence of konzo was triggered by food shortages because of the longstanding state of insecurity. Contributory factors included the introduction of new varieties of (bitter) cassava, but konzo may actually be caused by a combination of factors that are yet to be understood. Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction Cassava (Manihot esculenta, Crantz) is a very popular staple food under the tropics (Cock, 1982; Spencer, 1999). Cassava roots contain variable amounts of toxic cyanogenic glucosides (mainly linamarin). Bitter varieties of cassava, which have high levels of cyanogenic glucosides (Cardoso et al., 2005; Vetter, 2000) give a high yield and resist adverse ecological conditions. They are, therefore, more available and preferred during periods of food shortage. Their bitterness also protects them against grazing animals and thieves (Cardoso et al., 2005; Rosling, 1988; Spencer, 1999). VariAbbreviations: BDOM, Bureau Diocésain des Oeuvres Médicales; BMI, body mass index; DR Congo, Democratic Republic of Congo; HIV, human immunodeficiency virus; HTLV-1, human T-lymphotropic virus 1; NGO, non-governmental organization; SD, standard deviation; SPP, spastic paraparesis; UCB, Université Catholique de Bukavu; WHO, World Health Organization. ⇑ Corresponding author. Address: Rue Des Bossons, 94, 1213 Petit-Lancy, Geneva, Switzerland. Tel.: +41 78 944 32 30; fax: +41 22 731 99 84. E-mail address: [email protected] (J.N. Chabwine). 0278-6915/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2010.07.050
ous processing methods exist to remove those toxic cyanogens from cassava roots for safe consumption (Nambisan, 1994). Insufficient removal of cyanogenic glycosides from toxic varieties of cassava has been associated with the occurrence of konzo, an upper motor neuron disease characterized by spastic paraparesis (SPP) of sudden-onset and non-progressive course (Anonymous, 1996; Cliff et al., 1997; Rosling, 1988; Spencer, 1999). Outbreaks of konzo have been described in Western Congo (Banea-Mayambu et al., 1997; Bonmarin et al., 2002; Tshala-Katumbayi et al., 2001; Tylleskär et al., 1991) and in other regions of Africa (Cliff, 1985; Cliff et al., 1997; Howlett et al., 1990; Tylleskär et al., 1994) where people use mainly the soaking method to process cassava. In these outbreaks, konzo typically affected nutritionally compromised subjects (Cliff, 1985; Spencer, 1999; Tylleskar et al., 1995). Since 1994, the Democratic Republic of Congo (DR Congo) has been the site of war and continued violent conflicts, leading to a very high death toll (>5 million deaths), especially in its Eastern Provinces, which suffered the highest level of violence
J.N. Chabwine et al. / Food and Chemical Toxicology 49 (2011) 644–649
and insecurity (Coghlan et al., 2006). In 2001, several cases of paralysis were reported from Burinhyi, in the hinterland of Bukavu, the capital of South-Kivu, in the east of the DR Congo. Clinically, the condition was reminiscent of konzo. However, the disease had never been reported from Eastern Congo (more than 1000 km removed from the former sites), even though cassava is also an important staple food there. Two field surveys were carried out, at 2003 and 2005, in Burhinyi with the aims of (1) verifying, using clinical diagnostic criteria (Anonymous, 1996), if crippled patients in Burhinyi indeed suffered from konzo, (2) documenting cyanogen exposure by measuring urinary thiocyanate in patients and assessing cyanogen levels in cassava roots brought from their households. Overall, the surveys confirmed that konzo has made its appearance in the Kivu area. This probably resulted from the introduction of new varieties of bitter cassava, from the consumption of toxic fresh (unprocessed) cassava roots and, to a lesser extent, from shortcuts in cassava processing. The occurrence of cases of konzo coincided with the state of war and resulting insecurity in the area. 2. Subjects and methods
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tained from 30 patients (including four who had been seen in S1). Moreover, in S2 each patient also gave a blood sample (for HIV serology), a urine sample (for thiocyanate assessment) and cassava roots from his/her household stock (to analyze cyanogenic glycosides). Nutritional indices based on height and weight were evaluated according to the latest WHO guidelines (Anonymous, 2006). For patients between 5 and 19 years, malnutrition was classified as definite when indices were < 2 SD of the reference value, while severe malnutrition was defined by indices < 3 SD of the reference value. Above 19 years, malnutrition was defined as mild, moderate or severe if BMI was between 17.0 and 18.45, 16.0 and 16.99, <16.0, respectively (Anonymous, 1999). The diagnosis of konzo was made according to the WHO criteria (Anonymous, 1996) listed below: a visible symmetric spastic abnormality of gait while walking or running; a history of onset of less than 1 week followed by a non-progressive course in a formerly healthy person; bilaterally exaggerated knee or ankle jerks without signs of disease of the spine.
2.1. Study area 2.3. Laboratory analyses Burhinyi, a mountainous area located 100 km to the south of Bukavu, has a humid climate with a short dry season (June–August) and a long rainy season (Ntamwira, 1995). This area has been deeply affected by war and violence with mass killings, systematic rapes, etc. (Coghlan et al., 2006) (see also http://www.monuc.org/ news.aspx?newsID=15065 and Human Rights Watch reports in 2002, 2007 and 2008 at http://www.hrw.org). As elsewhere in the DR Congo, locally grown cassava (of sweet or bitter taste) is predominant in the diet of the population of Burinhyi. With approximately 65,000 inhabitants on an area of approximately 320 km2, the district of Burinhyi has a population density of about 200 inhabitants/km2, almost 10 times the national density. Because the cultivation of cassava was greatly affected by African mosaic virus diseases, international NGOs recently introduced mosaic-resistant varieties with a bitter taste and, hence, more potential toxicity (Spencer, 1999; Thresh and Cooter, 2005). 2.2. Surveys and clinical examination A first, preliminary, survey (S1) took place at November 2003 and a second one (S2) at September 2005. In both surveys, patients whom local health workers considered to suffer from spastic paraparesis were brought to the local health center for further examination by the research teams. The latter were composed of voluntary medical doctors, agronomists and trained medical students of the Université Catholique de Bukavu (UCB). The ethical committee of the UCB approved the protocol of the whole study. All subjects (or their parents) gave oral informed consent before entering the study. In total, 61 patients >5 years were recruited by the local health workers. In S1, dietary data and preliminary clinical information were obtained from 35 patients using a structured questionnaire, administered face-to-face to the patient (or a parent). The questionnaire enquired about demographic characteristics of the patient and his/her family, medical history and symptoms, dietary habits, including specific information regarding the consumption of cassava, its processing prior to consumption and any changes in the processing of sweet and bitter cassava varieties. Physical examination consisted of measuring height and weight, a general clinical examination and a specific clinical, neurological assessment (including muscle strength, tonus, motor reflexes and gait characteristics). In S2, clinical and dietary data were similarly ob-
HIV serologic tests were performed in S2 patients (n = 28) using ELISA (Biorad) and Determine (Abott) kits. Selected patients in S2 brought processed root samples (n = 21) from their household stock. We could not determine the number of plants (or fields) or varieties from which those roots were collected. Cyanogenic compounds levels were measured using kit A according to the method of Dr. Howard Bradbury (School of Botany and Zoology, Australian National University) (Cardoso et al., 1998). Thiocyanate concentrations in the urine of 27 patients were measured using kit D1, also following Dr. Bradbury’s protocol. A concentration of 100 lmol/L was taken as a cut-off of normality, as this corresponds to the cut-off value of 6 mg/g creatinine for non-smokers used in the Unit of Industrial Toxicology and Occupational Medicine of the Catholic University of Louvain (http:// www.toxi.ucl.ac.be/thiocyanate_u.htm). The effect of cassava processing was experimentally evaluated in the Laboratory of Phytopathology at the Faculty of Agronomy of the UCB in November–December 2005 on a well-known bitter variety (‘‘Mbailo”) consumed in Burhinyi. In total, 14 samples of peeled roots were subjected to 6 days of heap fermentation, as described by patients, and this was followed by incubation at 120 °C for 24 h (in order to reduce water content to the level obtained after sun-drying). Cyanide content of treated samples was measured every day. One control sample, which did not undergo treatment, was also included. Data were analyzed using Excel 2003 and Origin 7.0 softwares. 3. Results 3.1. Clinical data In total, 30 out of the 35 patients seen in S1 were considered to suffer from spastic paraparesis by the enquiry team. Among them, 17 (57%) fulfilled all WHO criteria for konzo. Of the 13 subjects who did not fulfill the criteria, four were not considered to suffer from konzo because they had complaints evoking spinal cord disease at the onset of paresis; for the remaining 9 cases, there was uncertainty about the abrupt onset of the paralysis (due to an imperfect wording of the questionnaire). In S2, 29 out of the 30 examined subjects completely met the WHO criteria for konzo,
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Table 1 Neurological signs of konzo and resulting disability. N subjects assessed
N subjects positive
% subjects positive
Loss of muscle strength (symmetrical) Exaggerated patellar reflex Spastic gait Babinski reflex
41
41
100
41 41 31
37 33 19
90.2 80.5 46.3
Affected limbs Upper limbs Upper and lower limbs Disability
25 23 2 1
61 56.1 4.9 56.1
17 5 1
41.5 12.2 2.4
Mild Moderate Severe
23
Main neurological signs found in konzo patients and disability resulting from spastic paresis due to konzo. All % are calculated out of the total of 41 patients. neurological signs (loss of strength, exaggerated patellar reflex and Babinski) were all symmetrical. In most of patients where it was evaluated (17/23), disability was mild.
5 4 3
n
including the sudden-onset of symptoms, but one of them proved to be HIV-positive and, hence, was excluded from the further analysis of data. As a result, out of the 61 subjects selected by local health workers as having spastic paraparesis, at least 41 subjects (17 from S1 and 28 from S2, including 4 cases seen in both S1 and S2) could be safely diagnosed as having konzo on clinical grounds. The mean age of these 41 patients with a definite diagnosis of konzo was 16 years (SD 6 years). All subjects were non-smokers. The age at onset of the paresis (recorded in 24 subjects from S2), averaged 12 years (SD 6 years), with three quarters of these subjects (n = 18) being younger than 15 years when the symptoms started. Patients older than 15 years at onset (n = 6) were all females. As per the diagnostic criteria, all 41 konzo patients presented evident clinical signs of a pyramidal syndrome, the hallmark of konzo (Table 1). Loss of muscle strength in arms and legs was symmetrical in all patients. An exaggerated patellar reflex was found in almost all patients (n = 37, 90%), and the typical spastic gait in a majority of subjects (n = 33, 80%). Babinski’s reflex was present in 19 (61%) of the 31 subjects in whom it was elicited. No patient was found to have somatic sensitive or sensory loss. Based on the WHO criteria, gait problems resulted in mild disability for most subjects. However, more disabling presentations with tetraparesis (2 subjects, 5%) and dysarthria (7 subjects, 17%) were also found. Based on patients’ responses to the questionnaire, the disease started appearing around 1996 with 2–4 cases appearing each subsequent year until 2005 (Fig. 1). In most patients (60%), the paralysis reportedly began during the dry season (harvest period) with a clear peak in June and July (Fig. 2). The treatment of cassava roots started, as usual, during the harvest period (July–August). This consisted of peeling, followed by 2–3 days of heap fermentation, and then 1–2 days of sun-drying and sometimes no drying at all. Respondents explained that the shorter duration of heap fermentation (normally at least 4 days) and the absence of sun-drying were due to lack of food. No differences were reported between processing sweet and bitter cassava varieties. All patients admitted having increasingly consumed bitter cassava in the current context of war. They also reported having consumed cassava as unprocessed fresh roots (raw, boiled or steamed), or as flour after some processing and pounding. The patients attributed such practices to the context of war and insecurity. About 60% of all patients (n = 23) reported a history of malnutrition (based on the medical information and treatments provided to patients by health workers) prior to the start of their neurologic
2 1 0 92 93 94 95 96 97 98 99 00 01 02 03 04 05
Year of onset Fig. 1. Year of onset of konzo. The year of onset of konzo in Burhinyi until 2005. The number of new cases remains low and does not peak over years.
7 6 5 4
n
646
3 2 1 0 J
F
M
A M
J
J
A
S
O
N
D
Month of onset Fig. 2. Seasonal distribution of konzo onset. Month of onset of SPP in Burhinyi, independent of the year. A peak of new cases is apparent from June to September (corresponding to the dry season when harvest of cassava takes place).
symptoms. Height and weight data were available for 34 patients enabling nutritional status assessment according to WHO standards. Out of them, 26 were between 5 and 19 years. Height for age index classified this group more severely than BMI for age. According to BMI for age, about 30% were classified as ‘‘wasted” (< 2 SD) and the same proportion as ‘‘severely wasted” (< 3 SD). However, height for age index showed 85% of severe stunting (< 3 SD) and 12% of stunting (< 2 SD). The BMI of patients above 19 years (mean age 26 ± 4 years, n = 8) corresponded to normal nutritional status or mild malnutrition, but the average height was only 143 cm (SD 5 cm). The median urinary thiocyanate concentration was 129 lmol/L (range 20–688 lg/l, SD 146 lmol/L) in konzo patients (n = 28) (Table 2). The majority of patients (71%) were above the cut-off concentration of 100 lmol/L. 3.2. Studies of food items Cassava roots brought from the patients’ household stocks (S2, n = 21) had already been processed, but the median cyanogen content still amounted to 20 ppm (range 5–300 ppm; SD 73 ppm). More than half of these samples were above the safety level defined by WHO (10 ppm) (Table 2).
J.N. Chabwine et al. / Food and Chemical Toxicology 49 (2011) 644–649 Table 2 HCN concentration in 21 processed cassava roots provided by patients and urinary thiocyanate concentration. n Cassava root samples HCN 610 ppm 11–50 ppm >50 ppm Urinary thiocyanate 6100 lmol/l >100 lmol/l Total
% 9 7 5
43 33 24
8 20 28
29 71 100
HCN concentration in 21 processed cassava roots provided by patients and urinary thiocyanate concentration in patients. Top part of the table. Cyanogen levels in 21 cassava roots brought by konzo-diseased patients (S2) from their household stock. The data are divided in three groups according to the threshold of safety considered by the WHO for African cassava varieties (10 ppm) and the one considered by other authors (50 ppm) (Cardoso et al., 2004). Almost half of roots contained more than 10 ppm HCN. Bottom part of the table. Urinary thiocyanate concentrations from konzo-diseased patients. In 71% of patient, the measured concentration was above cut-off value of 100 lmol/l.
Experimental heap fermentation was performed on the toxic variety ‘‘Mbailo” according to the procedure described by patients, and revealed that after 2–3 days processing, the samples still contained about 20% of the initial cyanogen concentration of 400 ppm (Fig. 3). Thus, if we apply this value to the cyanogen concentrations obtained from patients’ cassava samples, the median cyanogen level prior to processing amounted to 100 ppm (range 25– 1500 ppm). After 6 days of adequate processing in the laboratory, the cyanide concentration was lowered below the 10 ppm (corresponding to 2.5% of the initial value) threshold of safety recommended by WHO. The unprocessed control sample did not show any reduction in cyanogens (400 ppm).
4. Discussion We have documented the occurrence of 41 cases fulfilling all clinical criteria defined by the WHO for the diagnosis of konzo (Anonymous, 1996) in Southern Kivu, a geographic area where this disease had not been previously described. These sporadic cases were probably related to the introduction of new cultivars of cassava and the consumption of unprocessed fresh cassava roots
100
% HCN
80 60 40 20 0 0
1
2
3
4
5
6
Processing time (days) Fig. 3. Experimental processing of cassava roots from the variety ‘‘Mbailo” performed in the Laboratory of Phytopathology, Faculty of Agronomy, Catholic University of Bukavu. It consisted in peeling, followed by dry fermentation for six successive days. The initial HCN concentration (100%) was 400 ppm.
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and insufficiently processed cassava, probably as a result of the prevailing state of war and insecurity. In the presence of these new cases of spastic paraparesis, other etiologies than konzo must be envisaged. One subject was tested HIV-positive. Because HIV infection may occasionally lead to a similar neurologic picture (Chabwine, 2005), we excluded this patient from our cases with definite konzo, even though konzo and HIV infection may well coexist in the same patient. HTLV-1 and vitamin B12 deficiency-related myelopathies are possible causes of paraparesis (Chabwine, 2005; Healton et al., 1991; Zaninovic’, 2004), but we did not specifically test patients for these two diseases. However, the clinical presentations were not suggestive of spinal cord disease. Grass pea – incriminated in neurolathyrism, a disease somewhat similar to konzo (Getahun et al., 2002) – is not consumed in the region. Mass hysteria, as observed by Tshala et al. (1999) in Western DR Congo, could be confidently excluded. In conclusion, cases of spastic paraparesis in Burhinyi were most probably konzo. Based on these 41 subjects in a population of approximately 65,000, the estimated prevalence of the disease in Burhinyi was around 6 per 10,000 people in September 2005. However, according to the local health workers (and their unpublished written reports), the real number of cases could be at least twice as high, because many patients from more remote areas, and especially the most disabled patients, had not been able to come to the district health center during the surveys. For security reasons, it was not possible to visit these patients at their homes. This prevalence, although probably underestimated, is still lower than prevalences reported in outbreaks of konzo (Bonmarin et al., 2002; Cliff et al., 1997). Also, the distribution of cases over years did not show a clear increase or peak indicative of a real outbreak. In conclusion, these cases of konzo were most probably sporadic. Age and sex distributions found here are similar to those reported in other konzo areas (Cliff et al., 1997; Tshala-Katumbayi et al., 2001; Tylleskär et al., 1991). The typical pyramidal syndrome was retrieved in most of cases (Table 1). Konzo led to mild disability in most cases (Table 1). However, the occurrence of dysarthria and tetraparesis in some patients suggests that there might be more severe cases than those seen during the survey, especially if we take into account that severely disabled patients could not be reached. Cyanogen exposure from insufficiently processed cassava roots is the main etiological factor incriminated in konzo. Cassava roots brought by patients from their household stock contained variable cyanogen levels ranging from 5 to 300 ppm (average 20 ppm). This average concentration is above the recommended safety threshold of 10 ppm (Cardoso et al., 2004), but remains low compared to values reported in other outbreaks (Banea-Mayambu et al., 1997; Bonmarin et al., 2002). It is also low despite the reported shortcut in cassava root processing. However, based on our experimental data, we estimate that the cyanide concentration prior to processing may have been five times higher (we assumed that sun-drying in Burhinyi did not significantly affect cyanide concentration (Nambisan, 1994)). This is especially relevant in view of the reported consumption of raw cassava roots or of cassava that had only been boiled or steamed, procedures that do not efficiently reduce cyanogens (Nambisan, 1994). Many patients explicitly stated that they had resorted to these practices because of the situation of war and insecurity, disruptions that had led to food shortages and difficulties of processing cassava properly. We conclude that consumption of unprocessed cassava roots was probably one of the main sources of cyanogen exposure in Burhinyi. However, cyanogen poisoning from insufficiently processed cassava roots cannot be excluded, since the household samples we analyzed might have stayed longer in dry fermentation than the 2–3 days processing reported by patients. In fact, the
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survey took place well after the harvest season, which was the period when the occurrence of konzo appeared to peak. In this hypothesis, the relatively low cyanogens levels we found may not adequately reflect the shortcut in the processing. Successful introduction of mosaic virus-resisting cassava varieties by some NGOs may also have contributed to cyanogen poisoning. These varieties produce a higher crop yield (which explains their acceptance by the population), but based on their bitter taste they probably also contain higher concentrations of cyanogenic glycosides (Cardoso et al., 2005). Urinary thiocyanate was high in the majority of patients, reflecting ongoing cyanogen exposure when the survey was carried on. Note that these urine samples were all collected at least 2 months after the onset of paresis. This means that people in Burhinyi were undergoing continuous exposure from (unprocessed) cassava roots (Banea-Mayambu et al., 1997; Cliff et al., 1997). Measuring thiocyanate during the harvest period at the peak of konzo occurrence in a larger population (e.g. in school children) would be more indicative of the real intake of cyanogens in the population of Burhinyi. The reasons why these cases of konzo appeared in an area where this disease had never been reported previously, are probably multiple and need still to be clarified. The current war situation most probably played a role (Cliff et al., 1997) as cases of spastic paraparesis appeared from 1996 onward, i.e. with the beginning of war episodes, and they have continued to appear with the persistence of the violence and insecurity. Under these conditions, bitter varieties of cassava were possibly spared, due to their resistance to difficult culture conditions and also because they were of less interest for thieves and herbivores. Food shortages probably led some people to consume bitter cassava to a larger extent and more exclusively than in peace time, without any (or with shorter) processing (Vetter, 2000). Our observations indicate that the konzo patients had suffered from starvation or were chronically malnourished. According to the WHO classification, low weight for height index and BMI are indicative of acute malnutrition, while low height for age is more typical for chronic malnutrition (Anonymous, 2006). Our konzodiseased patients were severely stunted in their great majority (5–19 years) or had very low height (>19 years), which reflected (past) chronic malnutrition regardless of age (Tylleskar et al., 1995). This observation is in accordance with the history of malnutrition reported by the majority of our patients, in a province known to have now one of the highest prevalence of malnutrition in the country (Tollens, 2003). In conclusion, our data indicate that patients with spastic paraparesis in Burinhyi indeed suffered from konzo and were chronically malnourished. Cyanogen exposure, presumably from eating unprocessed cassava roots, was documented. The violence that has prevailed in the area for a decade probably contributed to the appearance of konzo through food shortage and the resulting consumption of a diet based predominantly on unprocessed or insufficiently processed bitter cassava. The (well-intended) recent introduction of bitter varieties of cassava probably contributed to this situation. High urinary thiocyanate concentrations found in patients far from the period of onset of their disease suggest continuous cyanogenic exposure. Moreover, the Eastern Provinces of the DR Congo (including South-Kivu) are still undergoing violent episodes perpetrated by uncontrolled armed groups and organized rebel armies, as reported by numerous international bodies and NGOs (Wakabi, 2008). Consequently, the number of cases of konzo is expected to increase, as shown by later counts of spastic paraparesis in Burhinyi and observations of new cases of konzo in two other districts of South-Kivu (Uvira and Fizi) (unpublished reports). So far, there is no treatment for konzo. Prevention strategies should promote safe practices for the consumption of cassava.
The usual processing method in Burhinyi (dry fermentation) should be last up to 6 days so as to reach cyanogen levels well below the safety level, as shown by our experimental data. Finally, further investigations are needed to better understand all factors that led to the appearance of konzo in Burhinyi. Conflict of Interest The authors declare that there are no conflicts of interest. Acknowledgements Despite the lack of funding, this work was made possible thanks to the contribution of several organizations and individuals. We would like to thank in particular the Medical Service of the Archdiocese of Bukavu and Olame Center, the authorities and the Computer Service of the Catholic University of Bukavu, and the NGO Africa Tomorrow. Our gratitude goes also to Drs. Howard Bradbury and Claudine Guerrieri for having provided kits and specialized material for different tests and to Professor Fernand Lambein and Dr. Julie Cliff for their advices and comments on the manuscript. References Anonymous, 1996. Konzo – a distinct type of motoneuron disease. Wkly Epidemiol. Rec. 71, 225–228. Anonymous, 1999. Management of Severe Malnutrition: A Manual for Physicians and other Senior Health Workers. World Health Organization, Geneva. Anonymous, 2006. WHO child growth standards: length/height-for-age, weightfor-age, weight-for-length, weight-forheight and body mass index-for-age: methods and development. World Health Organization, Geneva. Banea-Mayambu, J.-P., Tylleskar, T., Gitebo, N., Matadi, N., Gebre-Medhin, M., Rosling, H., 1997. Geographical and seasonal association between linamarin and cyanide exposure from cassava and the upper motor neurone disease konzo in former Zaire. Trop. Med. Int. Health 2, 1143–1151. Bonmarin, I., Nunga, M., Perea, W., 2002. Konzo outbreak in the south west of the Democratic Republic of Congo, 1996. J. Trop. Pediatr. 48, 234–238. Cardoso, A.P., Ernesto, M., Cliff, J., Egan, S.V., Bradbury, J.H., 1998. Cyanogenic potential of cassava: field trial in Mozambique of a simple kit. Int. J. Food Sci. Nutr. 49, 93–99. Cardoso, A.P., Ernesto, M., Nicala, D., Mirione, E., Chavane, L., N’zwalo, H., Chikumba, S., Cliff, J., Mabota, A.P., Haque, R.M., Bradbury, J.H., 2004. Combination of casava flour cyanide and urinary thiocyanate measurements of school children in Mozambique. Int. J. Food Sci. Nutr. 55, 183–190. Cardoso, A.P., Mirione, E., Ernesto, M., Massaza, F., Cliff, J., Haque, R.M., Bradbury, J.H., 2005. Processing of cassava roots to remove cyanogens. J. Food Compost. Anal. 18, 451–460. Chabwine, J.N., 2005. Differential diagnosis of spastic paraparesis relative to Konzo. CCDN, 3–4. Cliff, J., 1985. Association of high cyanide intake and low sulphur intake in cassavainduced spastic paraparesis. Lancet 2, 1211–1213. Cliff, J., Nicala, D., Saute, F., Givragy, R., Azambuja, G., Taela, A., Chavane, L., Howarth, J., 1997. Konzo associated with war in Mozambique. Trop. Med. Int. Health 2, 1068–1074. Cock, J.H., 1982. Cassava: a basic energy source in the tropics. Science 218, 755–762. Coghlan, B., Brennan, R.J., Ngoy, P., Dofara, D., Otto, B., Clements, M., Stewart, T., 2006. Mortality in the Democratic Republic of Congo: a nationwide survey. Lancet 367, 44–51. Getahun, H., Lambein, F., Vanhoorne, M., Van der Stuyft, P., 2002. Pattern and associated factors of the neurolathyrism epidemic in Ethiopia. Trop. Med. Int. Health 7, 118–124. Healton, E.B., Savage, D.G., Brust, J.C., Garret, T.J., Lindenbaum, J., 1991. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 70, 229–245. Howlett, W.P., Brubaker, G.R., Mlingi, N., Rosling, H., 1990. Konzo, an epidemic upper motor neuron disease studied in Tanzania. Brain 113, 223–235. Nambisan, B., 1994. Evaluation of effect of various processing techniques on cyanogen content reduction in cassava. Acta Hortic. 375, 193–201. Ntamwira, A., 1995. De la recherche des causes de la malnutrition protéinoénergetique chez les enfants de 0–5 ans en collectivité-chefferie de Burhinyi. Bukavu: Institut Supérieur des Techniques Médicales. Inédit. Rosling, H., 1988. Cassava toxicity and food security. Unicef, Uppsala. Spencer, P.S., 1999. Food toxins, AMPA receptors, and motor neuron diseases. Drug Metab. Rev. 31, 561–587. Thresh, J.M., Cooter, R.J., 2005. Strategies for controlling cassava mosaic virus disease in Africa. Plant Pathol. 54, 587–614. Tollens, E., 2003. Current situation of food security in the D.R.Congo: Diagnostic and perspectives. Leuven: Katholieke Universiteit Leuven, Department of Agricultural and Environmental Economics, 80.
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Appearance of konzo in South-Kivu, a wartorn area in the Democratic Republic of Congo J.N. Chabwine a,e,f,⇑, C. Masheka a, Z. Balol’ebwami a, B. Maheshe a,c, S. Balegamire a, B. Rutega b, M. wa Lola b, K. Mutendela c, M.-J. Bonnet d, O. Shangalume b, J.M. Balegamire e,f, B. Nemery e a
Faculty of Medicine, Université Catholique de Bukavu (UCB), PO Box 02, Cyangugu, Rwanda Faculty of Agronomy, Université Catholique de Bukavu (UCB), PO Box 02, Cyangugu, Rwanda Hôpital Provincial de Référence de Bukavu, PO Box 02, Cyangugu, Rwanda d Bureau Diocésain des Oeuvres Médicales, Bukavu (BDOM), PO Box 02, Cyangugu, Rwanda e Katholieke Universiteit Leuven, Occupational, Environmental and Insurance Medicine, Research Unit of Lung Toxicology, Laboratory of Pneumology, Herestraat 49 (O&N 706), B-3000 Leuven, Belgium f NGO Africa Tomorrow, P.O. BOX 2278, 1211 Geneva 2, Switzerland b c
a r t i c l e
i n f o
Article history: Available online 4 August 2010 Keywords: Konzo Spastic paraparesis Cassava Toxicity Cyanogens Burhinyi
a b s t r a c t Konzo is an upper motor neuron disease characterized by sudden-onset and irreversible spastic paraparesis occurring in nutritionally compromised people. It is associated with consumption of insufficiently processed cyanogenic-toxic cassava. Cassava, the main caloric source in the Democratic Republic of Congo, has been safely consumed for decades in the Eastern Province of South-Kivu. However, in the context of long-lasting war and violent conflicts, cases of spastic paraparesis resembling konzo appeared in a populous area (Burhinyi). Two field surveys (2003 and 2005) identified 41 subjects meeting clinical criteria of konzo and suffering from (chronic) malnutrition. Their urinary thiocyanate concentrations (median 129, range 20–688, SD 146 lg/L), and cyanogen levels (median 20 ppm, range 5–300 ppm, SD 73 ppm) in cassava roots from their household stocks were high. The source of cyanogenic-toxicity was unprocessed fresh cassava roots during harvest period, but probably also insufficiently processed roots. This first report of konzo in South-Kivu concludes that occurrence of konzo was triggered by food shortages because of the longstanding state of insecurity. Contributory factors included the introduction of new varieties of (bitter) cassava, but konzo may actually be caused by a combination of factors that are yet to be understood. Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction Cassava (Manihot esculenta, Crantz) is a very popular staple food under the tropics (Cock, 1982; Spencer, 1999). Cassava roots contain variable amounts of toxic cyanogenic glucosides (mainly linamarin). Bitter varieties of cassava, which have high levels of cyanogenic glucosides (Cardoso et al., 2005; Vetter, 2000) give a high yield and resist adverse ecological conditions. They are, therefore, more available and preferred during periods of food shortage. Their bitterness also protects them against grazing animals and thieves (Cardoso et al., 2005; Rosling, 1988; Spencer, 1999). VariAbbreviations: BDOM, Bureau Diocésain des Oeuvres Médicales; BMI, body mass index; DR Congo, Democratic Republic of Congo; HIV, human immunodeficiency virus; HTLV-1, human T-lymphotropic virus 1; NGO, non-governmental organization; SD, standard deviation; SPP, spastic paraparesis; UCB, Université Catholique de Bukavu; WHO, World Health Organization. ⇑ Corresponding author. Address: Rue Des Bossons, 94, 1213 Petit-Lancy, Geneva, Switzerland. Tel.: +41 78 944 32 30; fax: +41 22 731 99 84. E-mail address: [email protected] (J.N. Chabwine). 0278-6915/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.fct.2010.07.050
ous processing methods exist to remove those toxic cyanogens from cassava roots for safe consumption (Nambisan, 1994). Insufficient removal of cyanogenic glycosides from toxic varieties of cassava has been associated with the occurrence of konzo, an upper motor neuron disease characterized by spastic paraparesis (SPP) of sudden-onset and non-progressive course (Anonymous, 1996; Cliff et al., 1997; Rosling, 1988; Spencer, 1999). Outbreaks of konzo have been described in Western Congo (Banea-Mayambu et al., 1997; Bonmarin et al., 2002; Tshala-Katumbayi et al., 2001; Tylleskär et al., 1991) and in other regions of Africa (Cliff, 1985; Cliff et al., 1997; Howlett et al., 1990; Tylleskär et al., 1994) where people use mainly the soaking method to process cassava. In these outbreaks, konzo typically affected nutritionally compromised subjects (Cliff, 1985; Spencer, 1999; Tylleskar et al., 1995). Since 1994, the Democratic Republic of Congo (DR Congo) has been the site of war and continued violent conflicts, leading to a very high death toll (>5 million deaths), especially in its Eastern Provinces, which suffered the highest level of violence
J.N. Chabwine et al. / Food and Chemical Toxicology 49 (2011) 644–649
and insecurity (Coghlan et al., 2006). In 2001, several cases of paralysis were reported from Burinhyi, in the hinterland of Bukavu, the capital of South-Kivu, in the east of the DR Congo. Clinically, the condition was reminiscent of konzo. However, the disease had never been reported from Eastern Congo (more than 1000 km removed from the former sites), even though cassava is also an important staple food there. Two field surveys were carried out, at 2003 and 2005, in Burhinyi with the aims of (1) verifying, using clinical diagnostic criteria (Anonymous, 1996), if crippled patients in Burhinyi indeed suffered from konzo, (2) documenting cyanogen exposure by measuring urinary thiocyanate in patients and assessing cyanogen levels in cassava roots brought from their households. Overall, the surveys confirmed that konzo has made its appearance in the Kivu area. This probably resulted from the introduction of new varieties of bitter cassava, from the consumption of toxic fresh (unprocessed) cassava roots and, to a lesser extent, from shortcuts in cassava processing. The occurrence of cases of konzo coincided with the state of war and resulting insecurity in the area. 2. Subjects and methods
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tained from 30 patients (including four who had been seen in S1). Moreover, in S2 each patient also gave a blood sample (for HIV serology), a urine sample (for thiocyanate assessment) and cassava roots from his/her household stock (to analyze cyanogenic glycosides). Nutritional indices based on height and weight were evaluated according to the latest WHO guidelines (Anonymous, 2006). For patients between 5 and 19 years, malnutrition was classified as definite when indices were < 2 SD of the reference value, while severe malnutrition was defined by indices < 3 SD of the reference value. Above 19 years, malnutrition was defined as mild, moderate or severe if BMI was between 17.0 and 18.45, 16.0 and 16.99, <16.0, respectively (Anonymous, 1999). The diagnosis of konzo was made according to the WHO criteria (Anonymous, 1996) listed below: a visible symmetric spastic abnormality of gait while walking or running; a history of onset of less than 1 week followed by a non-progressive course in a formerly healthy person; bilaterally exaggerated knee or ankle jerks without signs of disease of the spine.
2.1. Study area 2.3. Laboratory analyses Burhinyi, a mountainous area located 100 km to the south of Bukavu, has a humid climate with a short dry season (June–August) and a long rainy season (Ntamwira, 1995). This area has been deeply affected by war and violence with mass killings, systematic rapes, etc. (Coghlan et al., 2006) (see also http://www.monuc.org/ news.aspx?newsID=15065 and Human Rights Watch reports in 2002, 2007 and 2008 at http://www.hrw.org). As elsewhere in the DR Congo, locally grown cassava (of sweet or bitter taste) is predominant in the diet of the population of Burinhyi. With approximately 65,000 inhabitants on an area of approximately 320 km2, the district of Burinhyi has a population density of about 200 inhabitants/km2, almost 10 times the national density. Because the cultivation of cassava was greatly affected by African mosaic virus diseases, international NGOs recently introduced mosaic-resistant varieties with a bitter taste and, hence, more potential toxicity (Spencer, 1999; Thresh and Cooter, 2005). 2.2. Surveys and clinical examination A first, preliminary, survey (S1) took place at November 2003 and a second one (S2) at September 2005. In both surveys, patients whom local health workers considered to suffer from spastic paraparesis were brought to the local health center for further examination by the research teams. The latter were composed of voluntary medical doctors, agronomists and trained medical students of the Université Catholique de Bukavu (UCB). The ethical committee of the UCB approved the protocol of the whole study. All subjects (or their parents) gave oral informed consent before entering the study. In total, 61 patients >5 years were recruited by the local health workers. In S1, dietary data and preliminary clinical information were obtained from 35 patients using a structured questionnaire, administered face-to-face to the patient (or a parent). The questionnaire enquired about demographic characteristics of the patient and his/her family, medical history and symptoms, dietary habits, including specific information regarding the consumption of cassava, its processing prior to consumption and any changes in the processing of sweet and bitter cassava varieties. Physical examination consisted of measuring height and weight, a general clinical examination and a specific clinical, neurological assessment (including muscle strength, tonus, motor reflexes and gait characteristics). In S2, clinical and dietary data were similarly ob-
HIV serologic tests were performed in S2 patients (n = 28) using ELISA (Biorad) and Determine (Abott) kits. Selected patients in S2 brought processed root samples (n = 21) from their household stock. We could not determine the number of plants (or fields) or varieties from which those roots were collected. Cyanogenic compounds levels were measured using kit A according to the method of Dr. Howard Bradbury (School of Botany and Zoology, Australian National University) (Cardoso et al., 1998). Thiocyanate concentrations in the urine of 27 patients were measured using kit D1, also following Dr. Bradbury’s protocol. A concentration of 100 lmol/L was taken as a cut-off of normality, as this corresponds to the cut-off value of 6 mg/g creatinine for non-smokers used in the Unit of Industrial Toxicology and Occupational Medicine of the Catholic University of Louvain (http:// www.toxi.ucl.ac.be/thiocyanate_u.htm). The effect of cassava processing was experimentally evaluated in the Laboratory of Phytopathology at the Faculty of Agronomy of the UCB in November–December 2005 on a well-known bitter variety (‘‘Mbailo”) consumed in Burhinyi. In total, 14 samples of peeled roots were subjected to 6 days of heap fermentation, as described by patients, and this was followed by incubation at 120 °C for 24 h (in order to reduce water content to the level obtained after sun-drying). Cyanide content of treated samples was measured every day. One control sample, which did not undergo treatment, was also included. Data were analyzed using Excel 2003 and Origin 7.0 softwares. 3. Results 3.1. Clinical data In total, 30 out of the 35 patients seen in S1 were considered to suffer from spastic paraparesis by the enquiry team. Among them, 17 (57%) fulfilled all WHO criteria for konzo. Of the 13 subjects who did not fulfill the criteria, four were not considered to suffer from konzo because they had complaints evoking spinal cord disease at the onset of paresis; for the remaining 9 cases, there was uncertainty about the abrupt onset of the paralysis (due to an imperfect wording of the questionnaire). In S2, 29 out of the 30 examined subjects completely met the WHO criteria for konzo,
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Table 1 Neurological signs of konzo and resulting disability. N subjects assessed
N subjects positive
% subjects positive
Loss of muscle strength (symmetrical) Exaggerated patellar reflex Spastic gait Babinski reflex
41
41
100
41 41 31
37 33 19
90.2 80.5 46.3
Affected limbs Upper limbs Upper and lower limbs Disability
25 23 2 1
61 56.1 4.9 56.1
17 5 1
41.5 12.2 2.4
Mild Moderate Severe
23
Main neurological signs found in konzo patients and disability resulting from spastic paresis due to konzo. All % are calculated out of the total of 41 patients. neurological signs (loss of strength, exaggerated patellar reflex and Babinski) were all symmetrical. In most of patients where it was evaluated (17/23), disability was mild.
5 4 3
n
including the sudden-onset of symptoms, but one of them proved to be HIV-positive and, hence, was excluded from the further analysis of data. As a result, out of the 61 subjects selected by local health workers as having spastic paraparesis, at least 41 subjects (17 from S1 and 28 from S2, including 4 cases seen in both S1 and S2) could be safely diagnosed as having konzo on clinical grounds. The mean age of these 41 patients with a definite diagnosis of konzo was 16 years (SD 6 years). All subjects were non-smokers. The age at onset of the paresis (recorded in 24 subjects from S2), averaged 12 years (SD 6 years), with three quarters of these subjects (n = 18) being younger than 15 years when the symptoms started. Patients older than 15 years at onset (n = 6) were all females. As per the diagnostic criteria, all 41 konzo patients presented evident clinical signs of a pyramidal syndrome, the hallmark of konzo (Table 1). Loss of muscle strength in arms and legs was symmetrical in all patients. An exaggerated patellar reflex was found in almost all patients (n = 37, 90%), and the typical spastic gait in a majority of subjects (n = 33, 80%). Babinski’s reflex was present in 19 (61%) of the 31 subjects in whom it was elicited. No patient was found to have somatic sensitive or sensory loss. Based on the WHO criteria, gait problems resulted in mild disability for most subjects. However, more disabling presentations with tetraparesis (2 subjects, 5%) and dysarthria (7 subjects, 17%) were also found. Based on patients’ responses to the questionnaire, the disease started appearing around 1996 with 2–4 cases appearing each subsequent year until 2005 (Fig. 1). In most patients (60%), the paralysis reportedly began during the dry season (harvest period) with a clear peak in June and July (Fig. 2). The treatment of cassava roots started, as usual, during the harvest period (July–August). This consisted of peeling, followed by 2–3 days of heap fermentation, and then 1–2 days of sun-drying and sometimes no drying at all. Respondents explained that the shorter duration of heap fermentation (normally at least 4 days) and the absence of sun-drying were due to lack of food. No differences were reported between processing sweet and bitter cassava varieties. All patients admitted having increasingly consumed bitter cassava in the current context of war. They also reported having consumed cassava as unprocessed fresh roots (raw, boiled or steamed), or as flour after some processing and pounding. The patients attributed such practices to the context of war and insecurity. About 60% of all patients (n = 23) reported a history of malnutrition (based on the medical information and treatments provided to patients by health workers) prior to the start of their neurologic
2 1 0 92 93 94 95 96 97 98 99 00 01 02 03 04 05
Year of onset Fig. 1. Year of onset of konzo. The year of onset of konzo in Burhinyi until 2005. The number of new cases remains low and does not peak over years.
7 6 5 4
n
646
3 2 1 0 J
F
M
A M
J
J
A
S
O
N
D
Month of onset Fig. 2. Seasonal distribution of konzo onset. Month of onset of SPP in Burhinyi, independent of the year. A peak of new cases is apparent from June to September (corresponding to the dry season when harvest of cassava takes place).
symptoms. Height and weight data were available for 34 patients enabling nutritional status assessment according to WHO standards. Out of them, 26 were between 5 and 19 years. Height for age index classified this group more severely than BMI for age. According to BMI for age, about 30% were classified as ‘‘wasted” (< 2 SD) and the same proportion as ‘‘severely wasted” (< 3 SD). However, height for age index showed 85% of severe stunting (< 3 SD) and 12% of stunting (< 2 SD). The BMI of patients above 19 years (mean age 26 ± 4 years, n = 8) corresponded to normal nutritional status or mild malnutrition, but the average height was only 143 cm (SD 5 cm). The median urinary thiocyanate concentration was 129 lmol/L (range 20–688 lg/l, SD 146 lmol/L) in konzo patients (n = 28) (Table 2). The majority of patients (71%) were above the cut-off concentration of 100 lmol/L. 3.2. Studies of food items Cassava roots brought from the patients’ household stocks (S2, n = 21) had already been processed, but the median cyanogen content still amounted to 20 ppm (range 5–300 ppm; SD 73 ppm). More than half of these samples were above the safety level defined by WHO (10 ppm) (Table 2).
J.N. Chabwine et al. / Food and Chemical Toxicology 49 (2011) 644–649 Table 2 HCN concentration in 21 processed cassava roots provided by patients and urinary thiocyanate concentration. n Cassava root samples HCN 610 ppm 11–50 ppm >50 ppm Urinary thiocyanate 6100 lmol/l >100 lmol/l Total
% 9 7 5
43 33 24
8 20 28
29 71 100
HCN concentration in 21 processed cassava roots provided by patients and urinary thiocyanate concentration in patients. Top part of the table. Cyanogen levels in 21 cassava roots brought by konzo-diseased patients (S2) from their household stock. The data are divided in three groups according to the threshold of safety considered by the WHO for African cassava varieties (10 ppm) and the one considered by other authors (50 ppm) (Cardoso et al., 2004). Almost half of roots contained more than 10 ppm HCN. Bottom part of the table. Urinary thiocyanate concentrations from konzo-diseased patients. In 71% of patient, the measured concentration was above cut-off value of 100 lmol/l.
Experimental heap fermentation was performed on the toxic variety ‘‘Mbailo” according to the procedure described by patients, and revealed that after 2–3 days processing, the samples still contained about 20% of the initial cyanogen concentration of 400 ppm (Fig. 3). Thus, if we apply this value to the cyanogen concentrations obtained from patients’ cassava samples, the median cyanogen level prior to processing amounted to 100 ppm (range 25– 1500 ppm). After 6 days of adequate processing in the laboratory, the cyanide concentration was lowered below the 10 ppm (corresponding to 2.5% of the initial value) threshold of safety recommended by WHO. The unprocessed control sample did not show any reduction in cyanogens (400 ppm).
4. Discussion We have documented the occurrence of 41 cases fulfilling all clinical criteria defined by the WHO for the diagnosis of konzo (Anonymous, 1996) in Southern Kivu, a geographic area where this disease had not been previously described. These sporadic cases were probably related to the introduction of new cultivars of cassava and the consumption of unprocessed fresh cassava roots
100
% HCN
80 60 40 20 0 0
1
2
3
4
5
6
Processing time (days) Fig. 3. Experimental processing of cassava roots from the variety ‘‘Mbailo” performed in the Laboratory of Phytopathology, Faculty of Agronomy, Catholic University of Bukavu. It consisted in peeling, followed by dry fermentation for six successive days. The initial HCN concentration (100%) was 400 ppm.
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and insufficiently processed cassava, probably as a result of the prevailing state of war and insecurity. In the presence of these new cases of spastic paraparesis, other etiologies than konzo must be envisaged. One subject was tested HIV-positive. Because HIV infection may occasionally lead to a similar neurologic picture (Chabwine, 2005), we excluded this patient from our cases with definite konzo, even though konzo and HIV infection may well coexist in the same patient. HTLV-1 and vitamin B12 deficiency-related myelopathies are possible causes of paraparesis (Chabwine, 2005; Healton et al., 1991; Zaninovic’, 2004), but we did not specifically test patients for these two diseases. However, the clinical presentations were not suggestive of spinal cord disease. Grass pea – incriminated in neurolathyrism, a disease somewhat similar to konzo (Getahun et al., 2002) – is not consumed in the region. Mass hysteria, as observed by Tshala et al. (1999) in Western DR Congo, could be confidently excluded. In conclusion, cases of spastic paraparesis in Burhinyi were most probably konzo. Based on these 41 subjects in a population of approximately 65,000, the estimated prevalence of the disease in Burhinyi was around 6 per 10,000 people in September 2005. However, according to the local health workers (and their unpublished written reports), the real number of cases could be at least twice as high, because many patients from more remote areas, and especially the most disabled patients, had not been able to come to the district health center during the surveys. For security reasons, it was not possible to visit these patients at their homes. This prevalence, although probably underestimated, is still lower than prevalences reported in outbreaks of konzo (Bonmarin et al., 2002; Cliff et al., 1997). Also, the distribution of cases over years did not show a clear increase or peak indicative of a real outbreak. In conclusion, these cases of konzo were most probably sporadic. Age and sex distributions found here are similar to those reported in other konzo areas (Cliff et al., 1997; Tshala-Katumbayi et al., 2001; Tylleskär et al., 1991). The typical pyramidal syndrome was retrieved in most of cases (Table 1). Konzo led to mild disability in most cases (Table 1). However, the occurrence of dysarthria and tetraparesis in some patients suggests that there might be more severe cases than those seen during the survey, especially if we take into account that severely disabled patients could not be reached. Cyanogen exposure from insufficiently processed cassava roots is the main etiological factor incriminated in konzo. Cassava roots brought by patients from their household stock contained variable cyanogen levels ranging from 5 to 300 ppm (average 20 ppm). This average concentration is above the recommended safety threshold of 10 ppm (Cardoso et al., 2004), but remains low compared to values reported in other outbreaks (Banea-Mayambu et al., 1997; Bonmarin et al., 2002). It is also low despite the reported shortcut in cassava root processing. However, based on our experimental data, we estimate that the cyanide concentration prior to processing may have been five times higher (we assumed that sun-drying in Burhinyi did not significantly affect cyanide concentration (Nambisan, 1994)). This is especially relevant in view of the reported consumption of raw cassava roots or of cassava that had only been boiled or steamed, procedures that do not efficiently reduce cyanogens (Nambisan, 1994). Many patients explicitly stated that they had resorted to these practices because of the situation of war and insecurity, disruptions that had led to food shortages and difficulties of processing cassava properly. We conclude that consumption of unprocessed cassava roots was probably one of the main sources of cyanogen exposure in Burhinyi. However, cyanogen poisoning from insufficiently processed cassava roots cannot be excluded, since the household samples we analyzed might have stayed longer in dry fermentation than the 2–3 days processing reported by patients. In fact, the
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survey took place well after the harvest season, which was the period when the occurrence of konzo appeared to peak. In this hypothesis, the relatively low cyanogens levels we found may not adequately reflect the shortcut in the processing. Successful introduction of mosaic virus-resisting cassava varieties by some NGOs may also have contributed to cyanogen poisoning. These varieties produce a higher crop yield (which explains their acceptance by the population), but based on their bitter taste they probably also contain higher concentrations of cyanogenic glycosides (Cardoso et al., 2005). Urinary thiocyanate was high in the majority of patients, reflecting ongoing cyanogen exposure when the survey was carried on. Note that these urine samples were all collected at least 2 months after the onset of paresis. This means that people in Burhinyi were undergoing continuous exposure from (unprocessed) cassava roots (Banea-Mayambu et al., 1997; Cliff et al., 1997). Measuring thiocyanate during the harvest period at the peak of konzo occurrence in a larger population (e.g. in school children) would be more indicative of the real intake of cyanogens in the population of Burhinyi. The reasons why these cases of konzo appeared in an area where this disease had never been reported previously, are probably multiple and need still to be clarified. The current war situation most probably played a role (Cliff et al., 1997) as cases of spastic paraparesis appeared from 1996 onward, i.e. with the beginning of war episodes, and they have continued to appear with the persistence of the violence and insecurity. Under these conditions, bitter varieties of cassava were possibly spared, due to their resistance to difficult culture conditions and also because they were of less interest for thieves and herbivores. Food shortages probably led some people to consume bitter cassava to a larger extent and more exclusively than in peace time, without any (or with shorter) processing (Vetter, 2000). Our observations indicate that the konzo patients had suffered from starvation or were chronically malnourished. According to the WHO classification, low weight for height index and BMI are indicative of acute malnutrition, while low height for age is more typical for chronic malnutrition (Anonymous, 2006). Our konzodiseased patients were severely stunted in their great majority (5–19 years) or had very low height (>19 years), which reflected (past) chronic malnutrition regardless of age (Tylleskar et al., 1995). This observation is in accordance with the history of malnutrition reported by the majority of our patients, in a province known to have now one of the highest prevalence of malnutrition in the country (Tollens, 2003). In conclusion, our data indicate that patients with spastic paraparesis in Burinhyi indeed suffered from konzo and were chronically malnourished. Cyanogen exposure, presumably from eating unprocessed cassava roots, was documented. The violence that has prevailed in the area for a decade probably contributed to the appearance of konzo through food shortage and the resulting consumption of a diet based predominantly on unprocessed or insufficiently processed bitter cassava. The (well-intended) recent introduction of bitter varieties of cassava probably contributed to this situation. High urinary thiocyanate concentrations found in patients far from the period of onset of their disease suggest continuous cyanogenic exposure. Moreover, the Eastern Provinces of the DR Congo (including South-Kivu) are still undergoing violent episodes perpetrated by uncontrolled armed groups and organized rebel armies, as reported by numerous international bodies and NGOs (Wakabi, 2008). Consequently, the number of cases of konzo is expected to increase, as shown by later counts of spastic paraparesis in Burhinyi and observations of new cases of konzo in two other districts of South-Kivu (Uvira and Fizi) (unpublished reports). So far, there is no treatment for konzo. Prevention strategies should promote safe practices for the consumption of cassava.
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