15

Redda Tekle Haimanot, Yemane Kidane, Elizabeth WTb, Angelina Kassina, Yohannes Endeshaw, Tadesse Alemu, Peter S. Spencer. 1993. Ethiop Med J 31, THE EPIDEMIOLOGY OF LATHYRISM IN NORTH AND CENTRAL ETHIOPIA Redda Tekle Haimanot, MD, FRCP(C), PhD1, Yemane Kidane, MA2, Elizabeth Wuhib, BA2, Angelina Kassina, Dip. Nut2, Yohannes Endeshaw, MD3, Tadesse Alemu, MD, MSc1, Peter S. Spencer, PhD, MRC Path4. ABSTRACT: Lathyrism is a neurotoxic disorder caused by excessive, prolonged consumption of the hardy, environmentally tolerant legume, the grass-pea, Lathy rus sativus, which contains the neurotoxic amino acid beta-N-oxalylamino-L-alanine acid (BOAA). The disease develops after heavy consumption of grass-pea for over two months. It is uniformly manifested by a predominantly motor spastic paraparesis with varying degrees of disability. A door-to-door epidemiological survey for the disease using trained lay health workers was carried out in the major areas of northwest and central Ethiopia where L. sativus is grown. For security reasons, some of the other endemic areas were not accessible for the survey. The survey involved a population of 1,011,272. A total of 3,026 affected persons were identified. The disease was found to be widespread in the northwest and central highland areas of the country. The prevalence rates ranged from 1/10,000 to 7.5/1,000. The highest prevalences were in North and South Gonder, and East and West Gojam. The male.female ratio of cases was 2.6:1; the females exhibited a milder form of the disease. The cultivation ofL. sativus is increasing in Ethiopia, which makes the development of low-BOAA strains very important in order to control the high incidence of lathyrism, a crippling disease which affects the productive young members of the society.

Faculty of Medicine, P. O. Box 4147, Addis Abeba University, Addis Abeba, Ethiopia. Ethiopian Nutrition Institute, Addis Abeba, Ethiopia. Gonder College of Medical Sciences, Addis Abeba University, P.O. Box 196, Gonder, Ethiopia. Centre for Research on Occupational and Environmental Toxicology, Oregon Health Sciences Universtiy, Portland, Oregon 97201, USA.
4 3

16 INTRODUCTION Lathyrism is a neurotoxic disorder caused by excessive, prolonged consumption of grass-pea (Lathyrus sativus). Much of our knowledge about this pulse and the disabling disease it causes comes from studies in India (1-4). The neurotoxic culprit, beta-N-oxalylaminoL-alanine acid (BOAA) has been identified and characterized (5). Although in the past the disease occurred in Europe, North Africa, the Middle East and Asia (6), it is at present endemic in India (7), Bangladesh (8) and Ethiopia (9). In Ethiopia, it has been known for many years. Its leg-paralysing features have gained descriptive local names such as "sebre", "gayu" and "gwaya". Although known to be associated with L. sativus, the paralysis has given rise to false local beliefs concerning the method by which the disease is acquired. Outbreaks of lathyrism have occurred in the northern parts of the country associated with famine (10, 11), and the disorder remains endemic in several parts of the country, with the occurrence of new cases recently recorded in the northwest (12). The purpose of this study is to give a general epidemiological overview of the lathyrism problem in the endemic regions of Ethiopia with the aim of providing information essential for the prevention and possible eradication of the disabling disease. It was undertaken as part of a multidisciplinary approach to study the agricultural, medical and nutritional aspect of the disorder (13). Study areas (Figure 1): Grass-pea (L. sativus) is grown in the Ethiopian highlands at altitudes ranging from 1700 to 2220 m and a maximum temperature of 15 - 20 C. Its production is mainly in areas affected by severe natural disasters such as moisture stress, water logging and flooding. Grass-pea cultivation is concentrated predominantly in the northwest zone (58%), while the central and northeast zones produce 16.3% and 12.8% respectively. The northern and southeast regions produce the balance (14). The survey: Field investigations carried out between 1988 and 1990 were concentrated on the major grass-pea producing administrative regions of North and South Gonder, West and East Gojam and West Shewa. For security reasons, the survey was unable to cover Welo, Tigray, Eritrea, Harer, and parts of Shewa Administrative Regions. There were also inaccessible grass-pea growing districts in North and South Gonder. In each administrative region, the research team contacted the regional officers of the Ministry of Agriculture as well as the local administrative authorities responsible for crop production. Up-to-date information on grass-pea cultivation and production was obtained. A twenty-per-cent random sampling of the Peasant Associations of grass-pea cultivating districts was made. Later on in the survey, the random sampling had to be reduced to 10%, due to security considerations and the need to complete the survey before the major military escalations of late 1991 in the survey areas. The results of a

17
neuro-epidemiology survey from the Butajira district of South Shewa, a region which does not grow grass-pea (15), were included for control purpose. Locally recruited lay health workers (6 males and 4 females) were trained in the use of questionnaires and the recognition of motor disabilities in the legs, including the different stages of paraparesis due to lathyrism. Pilot studies were undertaken in every survey area whenever a new group of enumerators was recruited. Village elders and leaders of the different Peasant Associations were informed about the objectives of the fieid investigation, and their consent was obtained. The elders were interviewed individually and in groups on the dietary habits of the community, with particular reference to grass-pea consumption. During their door-to door interviews, the enumerators collected census data including age, sex, religion, marital status, occupation and food habits of households in each village. They also recorded information on the amount and period of grass-pea consumption in households, and the onset of walking difficulties. In the majority of cases, the age of individuals and the age of onset of symptoms were determined using local event calendars. Two physicians trained to recognize and diagnose cases of lathyrism screened all subjects with walking difficulties identified by the enumerators. The neurologist in the team saw sampled groups of cases in order to validate diagnosis. After a period of experience, the agreement between the physicians and neurologists was excellent. Inclusion criteria included leg weakness and spasticity of subacute or insidious onset and history of heavy grasspea consumption prior to and at onset of the disease. The following were considered to be exclusion criteria: sensory deficit in extremities, marked asymmetrical leg weakness, continuing bladder and/or bowel dysfunction, and presence of peripheral gangrene in the limbs (12). Resulting disability was classified according to Acton (2) with some modifications. Stage 1: mild spastic gait with no use of a stick; increased stiffness and exaggerated deep tendon reflexes (DTR) of die lower limbs; ankle clonus present, Babinski's sign present. Stage 2: spastic gait, with use of one stick; lower limbs exhibit increased stiffness; mild rigidity; exaggerated DTR; ankle clonus present, Babinski's sign present. Stage 3: spastic gait, with use of two sticks; crossed adductor gait; lower limbs exhibit exaggerated DTR; ankle clonus present; Babinski's sign present. Stage 4: crawling or bedridden state; loss of leg use, with contracture; arms strong; and pyramidal signs present. Concurrent with the medico-social field surveys, the team collected samples of grass-pea from the local market and some of the households. A total of 200 grass-pea seed and food samples collected from the surveyed areas were sent to the Addis Abeba Universtiy's Department of Chemistry for analysis of BOAA content using the

18
calorimetric ophthaldehyde (OPT) fluorescent dye method (16, 17). Statistical Methods: the two-tailed test was used to test for statistical significance. RESULTS Table 1 shows the 1988 production and yield of grass-pea cultivation in Ethiopia as depicted by the Central Statistics Office (CSO) (18). East Gojam, South Gonder, West Gojam, and South Welo are, in that descending order, the major grass-pea producing regions, followed by East Shewa, North Welo, North Gonder and Arsi. Beta-Noxalylamino-L-alanine acid (BOAA) levels in the 200 samples collected from the survey areas ranged from 0.2 to 0.96 mg/100gm of dry grass pea. High BOAA content was registered from grass-pea samples collected from Gonder and Gojam. The highest were from the sub-district of Adet (West Gojam). The grass-pea samples in Shewa are in general less toxic. The prevalence of lathyrism was highest in the subdistricts of Yilmana and Deinsa (West Gojam), Dembia (North Gonder) and Fogera (South Gonder). In all the lathyrism endemic areas, agriculture, including cattle rearing, was the main occupation, and the chief source of livelihood, for over 90% of the affected persons. Socio-economically the population was poor (i.e. below the average Ethiopian per capita GNP of 120 US dollars per year) and individuals had a hand-to-mouth existence. The age and sex distribution (Fig. 2) demonstrates that males were affected much more than females (2.6: 1). Onset of the disease took place below 10 years of age in 26.7%, between 10 and 20 years in 27.1%, between 21 and 40 years in 29.9%, and above 40 years in 16.3 per cent. Thus, 83.7% were below the age of 40 years at onset. It is noteworthy that, in females, 69.2% of cases had their disease onset before the age of 20 years as compared to 47.7% in males (p<0. 001). In over 80% of the cases, the disease developed in the months of May to August (the majority in July), after 3 to 6 months of grass-pea consumption in 65%, 2 to 3 months in 60% and one month or less in 15%. In Ethiopia, grass-pea is sown in October/November and harvested in March/April. Consumption is from May to October, with the maximum amount recorded in the months of June and July. The annual distribution of cases was found to be relatively constant except in situations of acute food shortage and famine when epidemics of lathyrism have been recorded. One such epidemic occurred in the Dembia and Fogera subdistricts in 1976/77 (11). The clinical setting of the paralysis was recalled in only 30% of the patients, who remembered the prodromal symptoms of rheumatic pain and tightness at the waist. Painful spasms of the leg muscles, the so-called myospasm, was rarely recalled. The majority experienced stiffness and heaviness of the legs at and around the time of the paralysis of the legs, which occurred in a sub-acute manner in 65%

19
of the cases and acute (occurring all of a sudden) in 25 % . The sub-acute onset refers to the presence of prodromal symptoms before the manifestation of the paralysis and gradually increasing stiffness of legs over a month or more. Concerning disabilities, 52.2% and 41.5% belonged to stage 1 and 2 respectively. Stage 3 and 4 together formed only 6.3%. Sixty-five percent of the females had the mild stage 1 disability (Table 2). The dietary interviews revealed that grass-pea was commonly consumed as snacks in the boiled "nifro" and roasted "kollo" forms. The flour form was used to prepare the Ethiopian sauce or gravy called 'shiro wot'. In a typical grasspea-producing village, this was the predominant type of sauce consumed with the injera, a pancake type of leavened bread prepared from fingermillet, sorghum or rarely, from barley, wheat and tef (Eragrostis eff), depending on the region and socio-economical standing of the household. Tef and wheat are generally expensive cereals that require good soil and a great deal of agricultural input. The bread (kitta) form of grass-pea is consumed only during acute food shortages, and in some of the villages that were repeatedly affected by flooding. When interviewed about the connection of grass-pea and lathyrism, the majority of the victims were not clear that the onset and severity of the paralysis had a direct relationship to the amount and period of grass-pea consumption. The belief that the paralysis was precipitated or accentuated by exposure to vapour or smoke from grass-pea being boiled or fried was very common. Walking in a grass-pea field, as well as drinking milk together with the pulse, was thought to be dangerous. The interviews further revealed that the afflicted peasants continued to consume grass-pea despite a clear understanding of its paralysing properties. When asked why they persisted in eating the "poisonous" pulse, they replied that there was no alternative. The clinical signs of the spastic paraparesis were uniformly similar to the classical descriptions of neurolathyism. The victims manifest varying degrees of disability which cause difficulties with mobility and hinder their occupation as farmers. The common precipitating factors identified by these surveys were heavy physical labour, febrile illness and diarrhoea. DISCUSSION Ethiopia has been undergoing serious political turmoil for the last twenty years. Because of military conflicts, many areas of the north, and later the central regions of the country, were inaccessible to civilians. Our epidemiological surveys were therefore hampered from operating in some of the administrative regions where lathyrism was known to be prevalent. Nevertheless, the results now reported represent the best obtainable data on the lathyrism problems of the major grass-pea growing regions of the country. Lathyrism is a real and serious problem which has not received the attention

20 it deserves, either from the Ethiopian people or from its health authorities. The disease continues to claim more and more victims in direct proportion to the increasing cultivation and consumption of grass-pea. Those that have succumbed to the disease remain permanently disabled and are without opportunities for social and physical rehabilitation. Since young men are relatively commonly affected there is a major loss of critical manpower for peasant families. The high prevalence rates of lathyrism in the Lake Tana basin (Table 1) are very strongly influenced by several factors. First, the area is repeatedly flooded during the rainy seasons (June to October), when cereals fail because of waterlogging. Second, the area is populated by very poor peasants who live on subsistence farming, using primitive agricultural practices such as oxen ploughing. Their diet is cereal based, with legumes being used for preparation of snacks and sauces. There was hardly any intake of milk, protein or vegetables (19). In the 1988/89 re-survey of the districts of Dembia and Fogera of north-west Ethiopia, a region that had been affected by an epidemic in 1977 (11), we found that the prevalence of lathyrism in some villages was as high as 3%. This was most alarming when we consider that the mean annual incidence of the disease in the same region was 0.6% (12). Although the prevalence of the disease in other regions may be lower, the disease was nevertheless found to be widespread, with its maximal concentrations in northwest Ethiopia, particularly in the administrative regions of West and East Gojam and South Gonder. The high prevalence figures correspond to the cultivation and production of grass-pea. The high BOAA levels of grass-pea from these regions may also have promoted disease outbreaks (Table 1). Unfortunately, for reasons mentioned earlier, we have been unable to survey the administrative regions of North and South Welo and North Shewa, where grass-pea production is recorded to be high. The characteristics of the affected populations, their consumption of grasspea, the onset and the clinical manifestations of the disease are very similar to those in the classical reports from India (2-4, 19-20) and Bangladesh (21). As shown in Fig. 2, the prevalence of the disease in females is low and their degree of infirmity is less severe. This is similar to the results of epidemiological studies in India (2,4). It is not because women consume less, as Acton suggested (2); our dietary enquiry confirms that their consumption is not less than that of men. The reason for the relative protection of females, particularly of child-bearing age, may be hormonal (oestrogen), as proposed by Dwivedi and Prasad (4). In India, legislation to ban the production and sale of grass-pea has proved to be difficult to implement (22). Whereas in India serious attempts have been made to tackle the problem of lathyrism, in Ethiopia very little attention has been given to the preven-

21 tion of this crippling disease. With natural and man-made calamities so commonly encountered in Ethiopia, the production of the hardy pulse is increasing, and is bound to increase further particularly in drought-prone and floodprone areas. For instance, in 1988/89 the annual production of grass-pea in the country, from 37,800 hectares of cultivated land, was estimated to be 410,000 quintals (18). Lathyrism is a very serious social problem because it cripples the young and productive age groups. Disease prevention is an important public health response. Acton, in his meticulously executed investigation of lathyrism in North Rewah, India (2) proposed measures that are both appropriate and feasible in the Ethiopian situation: 1. The public should be educated about the toxicity of grass-pea, and instructed in ways of processing it to help reduce the toxicity. It is now well documented that soaking or boiling and discarding the excess water reduces the toxic BOAA in the seed (23). 2. During poor harvest and famine situations, communities in lathyrus growing areas should get external relief supplies free, or cereals should be made available to them at affordable prices. Recently, interest and hopes have been raised by a more effective and farreaching approach to solving the lathyrism problem. This will involve the development of low BOAA varieties of grass-pea. It is interesting to observe that Acton, even in 1922, had alluded to this, suggesting that "the smallgrained kesari is less toxic than the large grained Bhagalpur dal, so that every effort should be made to grow sufficient quantity of indigenous grain to meet local requirements" (2). There are now very active breeding programmes in a number of countries, including Ethiopia (14), to develop and disseminate low-BOAA varieties of grass-pea. This is part of an international multidisciplinary collaborative effort to improve L. sativus and eradicate lathyrism (13). ACKNOWLEDGEMENTS These studies were made possible by the Third World Medical Research Foundation (TWMRF) with a grant from Band-Aid. Dr. Aregay Waktola, Principal Investigator of the Lathyrism Project in Ethiopia, Valeria Palmer of TWMRF and Penny Jenden of BandAid are thanked for their interest and support. We are grateful to Ato Noad Kebede and Dr. Birhanu Abegaz Molla of the Chemistry Department, Addis Abeba University for the BOAA assay of grass-pea samples. We would also like to thank Ato Getachew Gebre Mariam who was instrumental in the supervision of the field surveys.

22

TABLE 1. The prevalence of lathyrism in the surveyed areas compared with the Lathyrus sativus production and content of beta-N-oxalylamino-L-alanine acid (BOAA) of dry grass-pea samples. Administrative region Cases/pop. surveyed Prevalence per 1,000 L. sativus prod* area '000 ha North Gonder Dembia South Gonder Fogera Simada Kemkem Dera Este West Gojam Yilmana Deinsa Bahr Dar Zuria Mecha Dega Damot Jabir Quarit Achefer East Gojam Mota Bichena Enesie Dejen Enarj-Enawga West Shewa Becho South Shewa Butajira 1.4 999/160,000 767/123,500 175/46,028 113/62,927 169/174,904 61/75,295 401/53,389 148/44,433 33/33,739 15/20,919 17/42,376 1/14,162 29/14,546 29/17,715 9/16,549 14/30,910 1/8,440 45/19,620 0/60,820 6.2 11.4 6.2 3.8 1.8 1.0 0.8 8.1 7.5 3.3 1.0 0,7 0.4 0.1 13.1 2.0 1.6 0.5 0.5 0.1 3.5 2.3 0.28 (0.5) 1.8 (4.9) 31.6 0.2-0.50 102.1 0.38-0.78 77.8 0.45-0.85 69.1 0.5-0.96 prod. '000 qt. 10.3 BOAA in grass-pea samples (mg/100gm) 0.44.85

* Production figure in hectares (ha.) and quintals (qt.) arefromAgricultural Sample Survey 1988/89; Central Statistics Office (CSO), 1990.

23 TABLE 2. Degree of disability by sex Males Stage 1. 2. 3. 4. No stick One stick Two sticks Crawler Females Total

No.
621 607 54 36 1,318

%
47.1 46.1 4.1 2.7 100.0

No.
339 157 15 10

%
65.1 30.1 2.9 1.9 100.0

No.
960 764 69 46 1,839

%
52.2 41.5 3.8 2.5 100.0

Total

521

REFERENCES 1. Sleeman WH. Rambles and Recollections of an Indian Official. Vol 1. London: Hatchard and Sons, 1844. 2. Acton HW. An investigation into the causation of lathyrism in man. Ind Med Gaz 1922;57:241-7. 3. Ganpathy KT, Dwivedi MP. Studies on clinical epidemiology of lathyrism. Lathyrism Enquiry Field Unit. Indian Council of Medical Research, Ghandi Memorial Hospital, Rewa, Madhya Pradesh, 1961. 4. Dwivedi MP, Prasad VG. An epidemiological study of lathyrism in the district of Rewa, Madhya Pradesh. Ind J Med Res 1964;52:81-114. 5. Rao SLN, Malathi K, Sharma PS. Lathyrism. World Rev Nutr Diet 1964; 10: 214-38. 6. Spencer PS, Schaumburg HH. Lathyrism: a neurotoxic disease. Neurobehavioral toxicology and teratology 1983;5:625-9. 7. Dwivedi MP. Epidemiological aspects of lathyrism in India - a changing scenario. In? Spencer PS (ed). Grass-pea: Threat and Promise. New York: Third World Medical Research Foundation, 1989:1-26. 8. Hague A, Mannan MA. The problems of lathyrism in Bangladesh. In: Spencer PS (ed). Grass-pea: Threat and Promise. New York: Third World Medical Research Foundation, 1989:27-35. 9. Tekle Haimanot R. Lathyrism in Ethiopia. In: Spencer PS (ed). Grass-pea: Threat and Promise. New York: Third World Medical Research Foundation, 1989:36-40. 10. Effo-Luzzi G. Malatia da "sebere" e lathyrismo in Eritrea. Bulletino della societa Italiana di medicina e igiene tropicale 1947;7:483-93. 11. Gebre-Ab T, Wolde-Gabriel Z, Maffi M, Ahmed Z, Ayele TM, Fanta H.

24 Neurolathyrism - a review and a report of an epidemic. Ethiop Med J 12. Tekle-Haimanot R, Kidane Y, Wuhib E, Kalissa A, Alemu T, Zein AZ, Spencer PS. Lathyrism in rural northwestern Ethiopia: a highly prevalent neurotoxic disorder. Int J Epidemiol 1990; 19:664-72. 13. Palmer VS, Kaul AK, Spencer PS. International network for the improvement of Lathyrus sativus and the eradication of lathyrism (INILSEL): a TWMRF initiative, In: Spencer PS (ed). Grass-pea: Threat and Promise. New York: Third World Medical Research Foundation, 1989;218-33. 14. Araya W, Dibabe A, Hundie B, Ensermu R, Haile W, Ashagrie Y. Grass-pea (Lathyrus sativus) research and its production potential in Ethiopia. (A paper presented at the 3rd Triennial Colloquium of INILSEL, Dhaka, Bangladesh, 30 November - 3 December 1991). 15. Tekle-Haimanto R, Abebe M, Gebre-Mariam A, Forsgren L, Holmgren G, Heijbel J, Ekstedt J. Community-based study of neurological disorders in rural central Ethiopia. Neurepidemiology 1990;9:263-77. 16. Rao SLN. A sensitive and specific calorimetric method for the determination of L.B. diaminoproprionic acid and the Lathyrus sativus neurotoxin. Anal Biochem 1978;864:386-95. 17. Abegaz B, Kebede N, Asmelash S. HPLC analysis of B-N-Oxalylamino-Lalanine, the neurotoxin in the legume Lathyrus sativus. In: Spencer PS (ed). Grass-pea: Threat and Promise. New York: Third World Medical Research Foundation, 1989; 128-32. 18. Ethiopia. Central Statistics Office. 1990. Agricuture sample survey 1988/1989. Result on area, production and yield of major crops by sector and season. Statistical Bulletin no. 79 ONCCP, Addis Abeba. 19. Kulkarni SW, Attal HC, Choubey BS. An epidemiologic study of lathyrism in Amgaon Block, Bahandra district. Ind Med J Res 1977;66:602-10. 20. Attal HC, Kulkarni SW, Choubey BS, Palkar ND, Deotale PG. A field study of lathyrism - some clinical aspects. Ind J Med Res 1978;67:608-15. 21. Ludolph AC, Hugon J, Dwivedi MP, Schaumburg HH, Spencer PS. Studies on the aetiology and pathogenesis of motor neuron diseases. 1. Lathyrism: clinical findings in established cases. Brain 1987; 110:149-65. 22. Dwivedi MP, Singh SP. The lathyrism problem: Current status and new dimension. In: Scientific Report, Nutrition Foundation of India. 1984; 19-33. 23. Mohan VS, Nagarajan V, Gopalan C. Simple practical procedures for the removal of toxic factors in Laythyrus sativus (Khesari dal). Ind J Med Res 1966;54:410-9. (Accepted 2 November 1992)