Objective: We report an outbreak of epidemic dropsy following ingestion of cooking groundnut-oil adulterated with Argemone oil.
Methods: We describe 40 patients (18 families) from three towns in Gujarat in 1998, affected with epidemic dropsy during an outbreak and its control measures. They were successfully treated with supportive measures and antioxidants. The outbreak control measures used were- active and passive surveillance, media campaigns, and action against traders.
Results: Oedema, erythema, cutaneous flush, fatigue, and tachycardia were present. ESR was high. Hydroxybutyrate dehydrogenase levels (165 U/l in 33 patients), reported for the first time, showed significant rise and persisted at 1-month (128 U/l) indicating long-term cardiac toxicity. We detected in serum and urine of 25 patients, sanguinarine (2.5 and 1.4 mg/dl respectively) which at 1-month had returned to trace levels, thus confirming the consumption of oil contaminated with Argemone oil. Fatigue persisted at one month in 80%, and at six months in 38%. Groundnut oil contamination with Argemone mexicana oil was detected.
Conclusion: Groundnut oil (used in cooking) contaminated with Argemone mexicana oil was the cause of epidemic dropsy. The health department controlled the outbreak with surveillance, stopping the mixing of argemone oil, and action against culprits. There were no deaths.
Epidemic dropsy due to ingestion of mustard oil adulterated with Argemone oil (AO) has been known since 1877 and reported in 1951 from north Indian states of Bihar and Madhya Pradesh. The seeds of Argemone Mexicana (Mexican poppy/ prickly yellow poppy) resemble mustard seeds [Illustration 1 fig.]. An outbreak of epidemic dropsy detected from small focal areas of Modasa & Dhansura towns of Sabarkantha, and Godhara city of Panchmahal districts from Gujarat, India after a span of 43 years in 1998 was surprising, since in Gujarat groundnut oil is consumed and not mustard oil. We describe clinical features of dropsy along with blood & urine levels of toxic ingredient Sanguinarine, serum hydroxybutyrate dehydrogenase (HBDH) levels for the first time, and epidemic control measures implemented successfully.
We studied forty cases from 18 families, detected during 6-17 September 1998 and recorded the type, brand and duration of oil consumption. Fasting blood and urine samples from patients and others (non-dropsy patients), and follow-up samples after one month from patients, were collected for estimation of hydroxybutyrate dehydrogenase (HBDH) and other biochemical and hematological investigations. Serum sanguinarine levels were estimated by thin-layer chromatography, initially and after one month in patients.
The patients were managed symptomatically with protein rich diet, antioxidants, diuretics, antihistaminic, vitamin supplements and timolol eye drops as indicated. They were followed up at one and six months.
The epidemic was controlled by active (home visits) and passive surveillance (wide publicity, leaflet distribution, awareness creation), identification of source of contamination, destroying of contaminated groundnut oil and strict action in the form of filing of court cases against traders indulging in contamination and their arrests. Three more cases were detected after one month in October from two geographically unconnected districts (Mehsana, Junagadh) and were managed similarly. Since then no case has been reported from Gujarat state.
There were 40 patients- 17 male, 23 female (no one was pregnant), and seven children.
Clinical features: The mean pulse rate was 95 ±12. Blood pressure was normal. Burning sensation in legs was present in eight (20%). All had oedema feet or legs with erythema and cutaneous flush. Ophthalmic findings were- bilateral raised (>20 mm Hg) intra-ocular pressure in six (15%), disc hyperemia, papillitis and conjunctivitis in one (2.5%). All patients complained of fatigue that persisted at one month in 80%, and at six months in 37.5%. No patient developed renal failure. There were no deaths.
Investigations: Mean hemoglobin was 10.5 ±1.49 g/dl and mean ESR was 32.3 ±15.4 mm/hr. Serum total protein (g/dl) was 6.18 ±0.82, albumin 3.4 ±0.49 and globulin 2.81 ±0.49 (g/dl). Urine protein showed trace proteinuria in 67.5% of patients. Blood urea and serum creatinine were normal. Echocardiography showed a mean ejection fraction of 60.02 ± 5.28. Sanguinarine and HBDH values are in Illustration 2 Table.
Epidemic dropsy results from contamination of edible oil with AO that contains, the toxic alkaloid sanguinarine, and dihydrosanguinarine. Usually 2-10% adulteration with this oil causes dropsy. AO is detected from oil by nitric acid, ferric chloride, cupric acetate, and hydrochloric acid tests.
Toxic levels- From animal studies on rats, Babu has extrapolated, that safety levels of AO for human consumption should be as low as 0.00001% (100 ppb or 100 ng AO per g oil) equivalent to 0.55% or 0.6 ng sanguinarine per g oil. Current method of testing with high-pressure liquid chromatography has a minimum detectable limit of AO at 5 ppm (5µg sanguinarine per g oil); therefore, AO should be undetectable from any oil fit for human consumption .
Mixing- As the seeds of mustard and argemone look alike, accidental or intentional mixing before crushing is possible or easier. However, this outbreak occurred after consumption of groundnut oil so intentional mixing with argemone oil was more likely. Familial clustering of cases and seasonal (August to October) prevalence due to fresh milling of seeds in May has been reported. Our findings were similar.
Pathology- The toxicity is dose related. Liver, kidney, skin, heart, lung and eyes are the target organs. Cytotoxic sanguinarine inhibits the Na+K+ ATPase & hepatic cytochrome p-450, and decreases the active transport of glucose. Decrease in plasma total antioxidant capacity, alpha-tocopherol, retinol and retinyl esters, superoxide desmutase, catalase, glutathione reductase and glutathione-s-transferase with a concomitant increase (69%) in glutathione peroxidase activity is observed in dropsy patients. This suggests that there is a mismatch between free radicals formation and enzymatic and non-enzymatic antioxidant scavengers, which causes oxidative damage to proteins and lipids in dropsy patients[5-7]. Prostaglandin, and histamine release due to suppression of histaminase, plays a role in the pathogenesis of skin manifestations & oedema.
Clinical- Oedema is a symptom in all studies. Burning sensation in feet and tingling were present but no neurological lesion could be detected. Due to early case-detection, none of our patients developed severe congestive heart failure that is an important prognostic factor for mortality. Sachdev have reported hypersecretory open angle glaucoma due to prostaglandin and histamine release. Hypoalbuminemia due to effect on liver, and dilatation of capillaries, and anemia presumably due to increased circulatory volume or toxic effect of alkaloid on erythrocytes have been observed.
Biochemistry- Sanguinarine was found in serum and urine; and Tandon, Shenolikar observed similar values. In follow-up samples after 1-month it was extremely low (serum) or not detectable (urine) due to stoppage of consumption of contaminated oil. The initial serum HBDH value (mean 165 U/l) in 33 dropsy patients was high as compared to 35 non-dropsy patients (mean 97, p< 0.1). At 1-month follow-up in 17 patients, decrease in the levels was not statistically significant (mean 135 vs 128 U/l). This reflected the persisting of degenerative changes in cardiac muscles, even after stopping the consumption of adulterated oil, due to interaction of sanguinarine with cardiac glycoside receptor sites. This probably was the cause of fatigue observed, and its persistence at six months.
Therapy- Extensive public campaign to inform population from the day of first case and identification of source of contamination and control of adulteration resulted in rapid resolution of epidemic, no deaths and fewer cases, as compared to 1998 dropsy in Delhi where there were 3000 victims and 60 deaths. Since then others have validated as part of therapy, antioxidants that we had used. Three more cases were observed from two other parts of Gujarat within two months. No other cases have been seen since then in Gujarat.
Patients with epidemic dropsy presented with varied manifestations involving heart, eyes & skin and, fatigue. Absence of other diseases, high index of suspicion, history of consumption of loose oil and involvement of more than one family member played an important role in suspecting epidemic dropsy. Estimation of serum and urine sanguinarine led to a definite diagnosis. Serum hydroxybutyrate dehydrogenase was elevated and persisted at follow-up. The patients were treated with supportive measures and anti-oxidant vitamins. The outbreak was controlled in a short time with concerted effort by the state food and health departments.
1. Dropsy leads to cardiac toxicity as shown by increased levels of HBDH, which remain high for weeks. Sanguinarine in blood and urine is eliminated after stopping consumption of contaminated oil. It takes months for complete recovery to occur.
2. It is possible to control the outbreak of dropsy in a short time, with extensive public campaign and by identification of source of contamination, leading to fewer cases and no deaths.
3. Contamination of groundnut oil with argemone oil can also cause dropsy.
4. Antioxidants may be useful to treat epidemic dropsy.
5. Fatigue as a complaint was present in all, and in more than one third, it persisted at six months. Role of sanguinarine in fatigue syndrome should be explored.
1. Sale of loose-unpacked cooking oil should be monitored for contamination with argemone oil. Cooking oil should be used in moderation. Facility to test edible oil by competent authority should be available in each region.
2. Strict enforcement of the Indian Food Adulteration Act and exemplary punishment to unscrupulous traders is the measure to prevent future occurrences.
3. Zero tolerance policy for sanguinarine presence in food for man as well as animals.
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We thank the Industrial Toxicology Research Centre, Lucknow- 226001, Uttar Pradesh, India, and the Commissioner Health, Government of Gujarat, Gandhinagar for the liaison and encouragement. We thank Dr AB Karnik, Director Dr Saiyyad and the statistician Vijay Shivgotra of National Inst. Occupational Health, Ahmedabad for the help. Figure: Agmark Laboratories, Nagpur http://agmarknet.nic.in/adulterants.htm
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