An outbreak of fatal pneumonitis caused by contamination of illicit alcohol with paraquat

Abstract

Introduction. We describe a series of unsuspected paraquat poisonings presenting as an outbreak of fatal acute pneumonitis. Exposure to paraquat occurred during the widespread practice of adding substances to alter the taste or potency of illicit alcohol. The diagnosis was suspected only after autopsy findings suggestive of paraquat toxicity were seen in the first fatality. Case series. An estimated 50 persons were exposed. Of these, 5 presented with ever and progressive dyspnoea, and died 9–30 days after exposure. We were able to trace 35 potentially exposed persons who survived, and compared them to the fatalities. Fever, headache, cough, dyspnoea, abdominal pain, hepatomegaly, and lung signs were more common among those who died. Autopsy revealed widespread renal and hepatic necrosis in the early deaths, and prominent pulmonary fibrosis in those dying later. Conclusion. This case series defines an unusual syndrome of paraquat poisoning, which should be considered in the diagnosis of outbreaks of acute pneumonitis in illicit alcohol users.

Keywords:

• Paraquat
• Disease outbreaks
• Ethanol
• Fatal

Introduction

In Sri Lanka, illicit alcohol – kasippu – is prepared by fermenting and then distilling a solution of cane sugar. Kasippu accounts for a large proportion of the alcohol intake in approximately 80% of Sri Lankans who consume alcohol daily, and in about 40% of other frequent drinkers (1). Adding various substances before and after fermentation, in order to alter its taste and potency, is a common practice among brewers. Minute quantities of paraquat are sometimes used for this purpose, presumably in the belief that drinking this well known poison will increase the ‘kick’ obtained from the brew.

Paraquat (1,1′-dimethyl-4,4′-bipyridium dichloride) is a widely available herbicide and a leading cause of death in cases of intentional self-poisoning in rural Sri Lanka (2,3). If ingested in sufficiently large amounts, paraquat results in a presentation which is easily recognized. Patients often present with abdominal pain and oropharyngeal ulcerations. Some develop an early destructive phase of toxicity associated with acute renal and liver failure. Most survivors of this phase will progress to a proliferative phase characterized by pulmonary fibrosis (4,5). As the minimum lethal dose in humans is 35 mg/kg, even small amounts of the concentrated form (containing 200 g/l of paraquat) can be fatal (5).

In November 2005, an estimated 50 men from a rural area in Sri Lanka drank kasippu contaminated with paraquat while attending a funeral. Details regarding this incident were obtained by interviewing the 40 persons who were potentially exposed and are reported in this paper, and several others in the village, including family members of those involved in illicit alcohol production. Apparently, a higher than usual amount of paraquat had been added accidentally to the kasippu containers. These had not been discarded because of the cost that would incur to the brewers. Almost all those interviewed remembered that the drink had an unusual light blue colour, but no one recollected an odd taste. This is compatible with a formulation of paraquat available in Sri Lanka at that time (Gramoxone; Syngenta, Cheshire, UK) which contains a blue dye but no additive which will overcome the taste of kasippu.

Unlike typical cases of paraquat ingestion, these patients were initially diagnosed to have respiratory infections, until autopsy of the first case led to the correct diagnosis. After it became known that 5 men had died of paraquat poisoning, 35 persons, out of the estimated 50 persons who were exposed, presented to hospital out of concerns regarding their health. We were unable to trace all those who were potentially exposed as kasippu is an illegal drink, the use of which is not always acknowledged. Clinical and laboratory data of these survivors are compared to those of the fatalities to help define this unusual form of paraquat poisoning.

Non-parametric methods were used for statistical analysis, which was done using SPSS version 10.0 (SPSS Inc., Chicago, IL, USA). P < 0.05 was considered as statistically significant.

Case series

Clinical presentation of the acute pneumonitis cases

The 5 fatalities occurred in males aged 41–60 years. Most appeared to have been drinking heavily during that period, but reliable estimates of the amounts consumed are not available. Patients presented between 7–10 days after the exposure. All had fever, a dry cough, and progressive dyspnoea, and gave a history of abdominal pain which had begun to lessen by the time of presentation (Table 1). Examination revealed central cyanosis, bilateral basal and mid-zonal inspiratory crackles, and tender hepatomegaly at the time of admission. There was no ulceration of the tongue or pharynx.

Table 1.  Clinical features at presentation

Clinical feature	Frequency among 35 survivors (%)	Frequency among 5 fatalities (%)	P value for difference
Fever	2 (5.7)	5 (100)	<0.001
Headache	6 (17.1)	4 (80)	0.01
Cough	2 (5.7)	4 (80)	0.001
Dyspnoea	3 (8.6)	5 (100)	<0.001
Abdominal pain	11 (31.4)	5 (100)	0.007
Lung crepitations	4 (11.4)	5 (100)	<0.001
Hepatomegaly	5 (14.3)	3 (60)	0.046
Stigmata of chronic liver disease	4 (11.4)	0 (0)	0.573

P values are for a Fisher's exact test.

Chest radiographs showed bilateral fine nodular shadows with areas of confluence. Blood tests at presentation are given in Table 2. There was a trend towards peaking of the white cell count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, bilirubin, and urea levels over a few days followed by a gradual decline until death. All patients were hypoxaemic at presentation (arterial O₂ saturation 68–70% breathing ambient air). Very characteristically, this was refractory to mechanical ventilation with high inspired fractions of O₂. There was no response to broad spectrum antibiotic therapy, which in 4 cases included a macrolide. Death occurred within 9–30 days from the first exposure to paraquat.

Table 2.  Blood tests at presentation

Test (Units) (reference interval)	Survivors Median (Range)	Fatalities Median (Range)	P value for difference
Urea (mmol/l) (2.5–6.6)	3.4 (1.7–7.4)	11.8 (8.3–19.6)	0.001
ALT (U/l) (0–41)	31 (10–142)	103.5 (33–746)	0.008
AST (U/l) (0–38)	39 (26–128)	199 (50–1288)	0.003
Alkaline phosphatase (U/l) (0–270)	NA	691 (215–1096)	NA
Bilirubin (µmol/l) (1–17)	NA	11.9 (11.3–21.5)	NA
ESR (mm/1^st h)	NA	113 (105–128)	NA
White cell count (× 10^5/ml)	NA	13 (9.3–15.6)	NA

P values are for a Mann Whitney U test.NA – not available / applicable. ALT – alanine aminotransferase, AST – aspartate aminotransferase, ESR – erythrocyte sedimentation rate.

A spot urine sample from one patient tested positive using the alkali and sodium dithionite test (obtained as a test kit from Syngenta; Cheshire, UK). We were able to test only one patient as this test is not freely available in Sri Lankan hospitals.

Autopsy findings

Autopsy findings varied with the time between exposure and death, in a pattern consistent with paraquat poisoning. Ulceration of the gastro-intestinal tract was not observed.

Patients dying between 9–16 days of exposure were jaundiced, and had congestion of the liver, kidneys, and lungs. Histology revealed necrosis of renal interstitial and tubular cells, and areas of focal hepatic necrosis. Early fibrous septae formation was seen in the liver of the person who died at 16 days. Sub-pleural haemorrhages, oedema fluid in the alveoli, membrane formation, and early fibrosis were seen in the lungs. There was no evidence of lung infection.

Persons who died at 24 and 30 days were not jaundiced. Macroscopically their kidneys were normal, but histology revealed interstitial haemorrhages. In one person there was mild fatty change in the liver with preserved architecture. The most prominent findings were in the lungs, which were heavy and hard due to extensive fibrosis. One person had, in addition to extensive pulmonary fibrosis, changes of pneumonia with abscess formation. The lung infection in this patient was probably a subsequent nosocomial event, since his clinical course with early renal and hepatic involvement, and subsequent refractory hypoxaemia due to lung fibrosis, was similar to the other fatalities.

Comparison with survivors

Fever, headache, cough, dyspnoea, abdominal pain, lung signs, and hepatomegaly were significantly more common among the fatal cases (Table 1). Stigmata of chronic liver disease was seen in 4 survivors, and in no fatalities, although this difference did not reach statistical significance (p = 0.573 using a Fisher's exact test).

Survivors had normal chest radiographs except for 1 patient with hyperinflated lung fields suggestive of chronic obstructive pulmonary disease. Blood tests at time of presentation are summarized in Table 2 which shows significantly higher levels of ALT, AST, and urea levels at presentation among those who died.

All 24 men who presented for follow up at 4 weeks were well. Their chest radiographs showed no new changes. Aminotransferase levels had declined in some, but this may have been due to reduced alcohol consumption. At 6 months there were no new fatalities or serious ill-health among the survivors.

Discussion

We report a series of unsuspected paraquat poisonings mimicking an outbreak of acute respiratory tract infection. We were able to confirm paraquat toxicity by ante mortem urine testing in only one patient, since this investigation is not routinely available in Sri Lankan hospitals. Moreover, we could not obtain samples of the contaminated kasippu for analysis as they were destroyed by the brewers following news of the fatalities. However, we were able to obtain multiple, corroborating accounts from persons closely connected to the incident regarding the addition of paraquat to the illicit alcohol. All patients reported in our paper admitted to drinking this kasippu in varying amounts. This history, and the characteristic clinical and autopsy findings, strongly suggests that each of the fatalities were due to paraquat.

Fever, headache, cough, dyspnoea, abdominal pain, lung signs, and tender hepatomegaly were significantly more common among the fatalities. They also had arterial hypoxaemia, widespread fine mottling on the chest radiographs, and elevated levels of ALT, AST, alkaline phosphatase, urea, and ESR. Differential diagnoses entertained by the attending physicians included severe atypical pneumonia, leptospirosis with pulmonary involvement, hantaviral infection, and disseminated tuberculosis. The correct diagnosis would be very elusive unless a history of illicit alcohol consumption was obtained. Retrospectively, features which may have suggested paraquat poisoning included the occurrence of abdominal symptoms prior to respiratory ones, the lack of response to broad spectrum antibiotics (including macrolides), and progressive refractory hypoxaemia.

Our case series highlights the importance of autopsies in reaching the correct diagnosis in unusual disease outbreaks. An autopsy was also needed to confirm the diagnosis in a case reported by Conradi and colleagues (6) of a death caused by unsuspected ingestion of paraquat mixed with moonshine alcohol. In that report, the diagnosis was suspected prior to the patient's demise on the basis of typical clinical features. All our patients were initially thought to have severe respiratory tract infections.

The case fatality rate in this series was at most 10%. Although the kasippu containers were contaminated with paraquat, the amount ingested by an individual probably varied widely, and the total dose would have been small. Moreover, some paraquat may have been inactivated by organic compounds in kasippu. This would explain the lack of oral ulceration, the fact that initial symptoms were not severe enough to bring the patient to hospital or to suspect poisoning, and the low case fatality rate.

Conclusion

The unusual practice of adding small quantities of paraquat to kasippu should be more widely recognised since it may occasionally lead to the unsuspected ingestion of toxic doses. Typical early features of paraquat poisoning may not be present in such cases which could closely mimic severe respiratory infections complicated by multi-organ dysfunction. Hence, paraquat toxicity will need to be considered in the differential diagnosis of outbreaks of acute pneumonitis in illicit alcohol users.

Acknowledgments

We gratefully acknowledge Dr. Harith Wimalaratne for providing us with details of the patient who was managed at Teaching Hospital, Kandy, and Dr. Chamara Walathara for his help with data collection. We also thank the anonymous reviewers of this article for their helpful comments.