Intestinal malabsorption in acute infection with Strongyloides stercoralis

69 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE. Vol. 69. No. 1. 1975.

INTESTINAL

MALABSORPTION

IN ACUTE INFECTION STERCORALIS

WITH

STRONGYLOIDES

W. O’BRIEN

Royal Army Medical College, London Introduction Strongyluides stercoralis is a minute round worm. The female lives within the duodenal and jejunal intestinal mucosa where it lays its eggs. These eggs develop into rhabditiform larvae which enter the lumen of the intestine and are passed in the faeces. Infection is acquired in a similar way to ankylostomiasis with penetration of the skin by filariform larvae, which on their way to the intestine pass through the lungs. It seems likely that infection is maintained in many individuals by the development of filariform larvae either within the intestine or on the skin of the perianal area with subsequent autoinfection (FAUST and DE GROAT, 1940). Under certain conditions, often associated with immunological deficiency, this autoinfection may become massive. Following infection pulmonary symptoms and/or rashes with a high eosinophilia may occur followed by abdominal pain and diarrhoea. Chronic infection on the other hand is often symptomless and is not associated with a high eosinophil count. Massive autoinfection may result in a severe and indeed often fatal intestinal malabsorption syndrome with steatorrhoea, protein losing enteropathy and hypokalaemia (NALASCOand AFRICA, 1936; STEMMERMANNand NAKAZONE, 1960; DE PAOLO, 1963; WILLIS and NIVOKOLO, 1966; TOH and CHOW, 1969). Soldiers engaged in active operations in the tropics may be exposed to heavy infection with both ankylostomes (ROGERSand DAMMIN, 1946) and Strongyloides stercuralis (HAZEL and GRANT, 1969). In this paper an acute malabsorption syndrome in 7 young soldiers on active service in Borneo is described and reasons are given for ascribing it to early infection with Strongyloides stercoralis. The syndrome was characterized by diarrhoea, steatorrhoea, normal absorption of D-xylose and a high eosinophilia. Patients

and methods of investigation

The 7 patients were infantry soldiers aged 18 to 26 years who had been engaged in active operations in Borneo during 1962-1963. FaecaZfat excretion was measured by the method of VAN DE KAMER et al., (1949), D-xylose absorption by the D-xylose excretion test using an oral dose of 5 g. (SANTINI et al., 1961). Vitamin B 12 absorption was measured by means of 58 Co-labelled vitamin B 12 and the modified faecal excretion technique described by MOLLIN et al., (1957). The normal range by this method is 38-87% absorption. Jejunal biopsies were taken with a Crosby capsule (CROSBYand KUGLER, 1957). Haetnatological methods were those described by DACIE, (1956). Serum folate was measured by means of L. casei as described by WATERS and MOLLIN, (1961). The normal range by this method is 5.9 to 21 ng. per ml. However these soldiers were living on combat rations and were taking proguanil daily. Serum folate levels measured in 40 apparently healthy soldiers living under these conditions were 1.3 to 9.8 ng. per ml. (median 3.8 ng. per ml.). Serum vitamin B 12 concentrations were measured by microbiological assay using Euglena gracilis (HUTNER et al., 1956). The serum folate and vitamin B 12 assays were performed in Dr. D. Mollin’s laboratory at the Postgraduate Medical School, Hammersmith. Results Clinical features : 6 out of the 7 patients presented with diarrhoea. The other patient was admitted following the finding of a massive eosinophilia associated with respiratory symptoms. He too developed diarrhoea 4 days after admission to hospital. Initially diarrhoea was usually acute with liquid stools, but by the time these patients were admitted to hospital, most were passing 4-6 loose, pale, foul smelling, frothy stools daily. In 6 patients abdominal colic was a prominent symptom. 3 of the patients had noticed a transient irritating rash on the

70

INTESTINAL

hL4LABSORPTION

IN

ACUTE

INFECTION

WITH

STRONGYLOIDES

STERCORALIS

trunk and thighs 2 weeks before the onset of diarrhoea, whilst 2 patients (including one who had had a rash) complained of episodes of coughing, breathlessness and wheezing about the same time. Both the rash and the pulmonary symptoms had subsided spontaneously over 4-5 days. Physical examination following admission to hospital failed to reveal any abnormality. Investigation (Table I). Intestinalfunctinn: Steatorrhoea was present in all patients being severe in 3 (25-42 g. per day) and mild or moderate in 4 (7.0-13 g. per day). The D-xylose test was normal in all the patients, urinary excretion being 26-35-S%. Absorption of vitamin B 12 given with intrinsic factor was subnormal in 4 patients (8*525%) and normal in 2 patients. TABLE I.

Case No.

Fats

g.Pv 1. 2. 3. ~~ 4. 5. 6.

Xylose Vit B 12 H6 y0 Excretion y0 Absorption g./lOO ml.

42.6 (3,6)

$2)

25.7 (3.0)

35.5 (41)

f675)

13.9

Serum folate ng./ml. 3.1

Serum B 12

Eosinophils Per c.mm.

P./ml.

400

6084

(800)

10-o (6.0)

29.5

-

39-o (3.0)

30.5 (37-O)

8.5

13-o (4-O)

26 (30)

$0)

g0,

30.1

50

14.5

3.2

265

23,200

14-4

5.3

265

1730 (480)

11.8

1.6

165

ww 6100 wo

13.9

2.0

145

6020

15.4

5.9

310

26,000

w-w 7.

7.0 (4.0)

31.1 -

TfO)

12.4

3.3

120

2900

Figures in brackets refer to results after treatment. Intestinal structure : Barium meal examination was normal in 5 patients and showed thickened transverse mucosal folds in 2 patients. When jejunal biopsy specimens were viewed under a dissecting microscope, the pattern was of “fingers” and/or “leaves” in 6 patients and “leaves” and ridges in I patient. The villi appeared swollen and the vascular pattern was indistinct (Figs. 1 and 6). On histological exam&+ tion the intestinal mucosa appeared normal in the 3 patients but appeared oedematous in the other 4. The epithelial cells were normal. In 2 patients there was heavy infiltration with eosinophils. The biopsy which had appeared ridged under the dissecting microscope showed partial villous atrophy. HaematoZogy: The haemoglobin concentration was normal in 5 patients and 2 patients were mildly anaemic. The bone marrow was normoblastic in 6 patients. In the patient whose jejunal biopsy had shown ridges and partial villous atrophy, the haemoglobin concentration was 11.8 g. per 100 ml. the marrow was megaloblastic and the serum folate was 1.6 ng. per ml. The serum folate concentrations were 2-5-9 ng. per ml. in the other patients (mean 3.8 ng. per ml.). Serum vitamin B 12 concentrations were normal in 4 patients and were in the equivocal range 12&165 p.g. per ml. in 3 patients. All patients showed a considerable eosinophilia which exceeded 20,000 per cmm. in 2 patients and exceeded 6000 per cmm. in another 3. Parasitology : Bhabditiform larvae of S. stercoralis were found in the stools of one patient and in the duodenal aspirate from another patient. A few hookworm ova were found in the stools of 5 patients including the 2 patients in whom S. stercoralis had been found. In 2 patients no parasites were found.

W.

O’BRIEN

71

Treatment : 3 patients were treated with bephenium hydroxynaphthoate without improvement and in addition one of these patients received tetrachlorethylene again without effect. One patient who was originally diagnosed as having tropical sprue was treated with oral broad spectrum antimicrobial drugs. On this treatment there was rapid deterioration with severe diarrhoea and vomiting so that treatment had to be stopped. All the patients received dithiazanine and responded with rapid symptomatic improvement. Steatorrhoea cleared in 6 patients and absorption of vitamin B 12 returned to normal in 3 out of the 4 patients retested. In one patient malabsorption of vitamin B 12 persisted and because of this an ileal biopsy was carried out and was normal. This patient was then given aureomycin orally and after a week, absorption of vitamin B 12 had returned to normal. Illustrative

case reports :

Case No. 1. A young soldier had been serving in Borneo for 4 months. Immediately following his return to Singapore he became constipated. This was followed by acute watery diarrhoea which in turn gave place to loose copious, pale,foul smelling diarrhoea stools. Hewas admitted to hospital 30 days after the onset of symptoms. There were no abnormal physical signs. Faecal fats were 42.6 g. daily, D-xylose excretion was 32% and vitamin B 12 absorption was 17%. Thickened transverse mucosal folds were seen in the barium meal film. Jejtmal biopsy showed swollen fingers and leaf shaped villi and on histological examination some oedema and mild deformity (Figs. 1 and 2). Haemoglobin concentration was 13.9 g. per 100 ml. serum folate 3.1 ng. per ml., serum vitamin B 12 was 400 pg. per ml., absolute eosinophil count was 6,084 per cmm. At first he was thought to have tropical sprue and a course of oral broad-spectrum antimicrobial drugs was started (Fig. 3). He deteriorated with severe diarrhoea and vomiting and this treatment had to be stopped. At this time a few hookworm eggs were found in the stools. He was given dithiazanine (in error instead of bephenium) and symptoms rapidly improved. After 4 weeks faecal fats were 3.6 g. daily, D-xylose excretion was 42%, vitamin B 12 absorption 65%, jejunal biopsy normal (Figs. 4 and 5) and absolute eosinophil count was 800 per cmm. Case No. 2. A young soldier in the field developed upper abdominal pain, slight fever with difficulty in breathing and wheezing at night, as well as an irritating rash on the trunk. He reported sick and a high eosinophilia was found. He was referred to hospital. On arrival at the B.M.H. Singapore he was symptomless but had an absolute esoinophil count of 27,000 per cmm. 4 days after admission, and 2 weeks after the onset of his original symptoms, he developed diarrhoea passing P5 loose light coloured stools daily. Diarrhoea was preceded by severe abdominal colic. There was no abdominal physical signs. Faecal fats were 25.7 g. daily, D-xylose excretion 35.5%, absorption of vitamin B 12 25%, barium meal was normal. Jejunal biopsy showed swollen finger-shaped villi and histological section swollen villi with heavy eosinophilic infiltration (Figs. 6 and 7). Haemoglobin concentration was 14.5 g. per 100 ml., serum folate 3.2 ng. per ml. serum vitamin B 12 was 265 pg. per ml., absolute eosinophil count 23,200 per cmm. A few hookworm eggs were found in the stools and the larvae of S. stercoralis in the duodenal aspirate. He was treated with dithiazanine (Fig. 8). Symptoms quickly subsided,faecal fat excretion fell to 3 g. daily,D-xylose excretion was 41% and vitamin B 12 absorption 52%. A repeat jejunal biopsy was normal (Figs. 9 and 10) and the absolute eosiniphil count dropped to 1,000 per cmrn. Case No. 4. A young soldier had been serving in Borneo for 3 months. He developed flatulence, heartburn and short attacks of watery diarrhoea. 6 weeks later diarrhoea became continuous, he lost his appetite and by the time he was admitted to hospital he had lost 2 stones. On physical examination there were no abnormal signs. Faecal fats were 39 g. daily, D-xylose excretion was 30*5% and absorption of vitamin B 12 was 8.5%. A barium meal revealed no abnormality. A jejunal biopsy showed swollen “leaves” and ridges and partial villous atrophy. Haemoglobin concentration was 11.8 g. per 100 ml. serum folate was lb6 ng, per ml. and serum vitamin B 12 was 165 pg. per ml. The absolute eosinophil count was 6,100 per c.~llfn, A few hookworm eggs were found in the stools. He was treated with bephenium hydroxynaphthoate without improvement (Fig. 11) and a week later was given tetrachlorethylene but again there was no response. He was then given dithiazanine. Following this his symptoms improved though rather slowly and faecal fats fell to 6.4 g. per day. He still remained anaemic however (H6 11.6 g., serum folate 1.8 ng. per n-d.). He was then given folic acid and there was complete symptomatic remission. Faecal fats were 3 g. daily, D-xylose was 37 y. and the absolute eosinophil count 900 per cmm.

72

INTESTINAL

h4ALABSORPTION

IN ACUTE

INFECTION

WITH

STRONGYLOIDES

STERCORALIS

FIG. 1. Jejunal biopsy under dissecting microscope. Case No. 1.

FIG. 2. Jejunal biopsy, histological

section. Case No. 1.

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FIG. 3. Faecal fat excretion and eosinophilia.

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2s4&4

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Case No. 1.

FIG. 4. Jejunal biopsy under dissecting microscope after treatment. Case No. 1.

74

INTESTINAL

FIG. 5. Jejunal biopsy, treatment. Case No. 1.

-SORPTION

histological

IN ACUTE

section

INFECTION

WITH

STRONOYLOIDES

~TERCO~IS

after

FIG. 6. Jejunal biopsy dissecting microscope. No. 2.

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Jejunal biopsy, histological

75

O’BRIEN

section. Case No. 2.

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8. Faecal fat excretion and eosinophilia.

Case No. 2.

76

INTESTINAL

hbiLABSORPTION

IN ACUTE

INFECTION

WITH

STRONGYLOIDES

STERCORALIS

FIG. 9. Jejunal biopsy under dissecting microscope after treatment. Case No. 2.

FIG. 10. Jejunal biopsy, histoloaical section after treatmint. Case No. 2.

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FIG. 11. Faecal fat excretion and eosinophilia.

Case No. 4.

W. O’BRIEN

77

Discussion Steatorrhoea with normal absorption of D-xylose is seen in biliary and pancreatic deficiency, but these patients were not jaundiced and though pancreatic function was not tested, it seemed improbable that the steatorrhoea was due to pancreatic disease. This pattern of malabsorption may also occur in the stagnant loop syndrome but no anatomical abnormality of the intestine was demonstrated. It is also seen in a number of uncommon conditions including Whipple’s disease, intestinal lymphangiectasia a-beta-lipoproteinaemia and food allergy. The premonitary symptoms in 3 of our patients, the eosinophilia, and the confirmed presence of intestinal worms in 5 patients suggested that the steatorrhoea was likely to be due to intestinal worm infection. Infection with hookworm and S. stercoralis occurs under the same conditions and are often co-incident. Further in early infection it is often difficult to demonstrate the parasites (BIAGI 1965). The height of the eosinophilia, the response to treatment with dithiazanine and the lack of response to anti-hookworm drugs, suggested that the infection causing steatorrhoea was S. stercoralis. Nippostrongylus brasiliense infection in rats closely resembles S. stercoralis in man and it has been shown that an important element of the immune response to this worm is a hypersensitivity-rein-like reaction with liberation of histamine from mast cells in the intestinal mucosa (OGILVIE, 1964; MULLIGAN, 1868; JARRETTand URQUHART, 1971). There is increased capillary permeability accompanied by oedema of the lamina propria. It seems likely that a similar reaction may occur during early S. stercoralis infection in man. Liberation of excess histamine in the jejunal mucosa also occurs in mastocytosis and JARNIJM and ZACHARIAE (1967) have shown that this condition can be associated with steatorrhoea and normal xylose absorption. Steatorrhoea with normal xylose absorption is also found in intestinal lymphangiectasia and in this condition it has been suggested that steatorrhoea is due to loss of fat into the lumen of the intestine rather than simple malabsorption of fat. (JEFFERIESet al., 1964; MISTILIS et al., 1965). It is possible that a similar mechanism is responsible for the steatorrhoea seen in early S. stercorulis infection. The malabsorption of vitamin B 12 given with intrinsic factor in 4 of these patients was of interest. S. strongyloides infests the duodenum and jejunum, not the ileum. The situation appears to be similar to that of early tropical sprue in which there is intestinal malabsorption of this vitamin but a morphologically normal ileal mucosa. (O’BRIEN and ENGLAND, 1971). In sprue there is rapid reversion of this abnormality on oral antibiotics and the same thing occurred in one of the patients described in this paper. Summary A syndrome of intestinal malabsorption associated with a high eosinophilia occurring in 7 young soldiers from Borneo is described. It seemed likely that the cause of the malabsorption was early infection with Strongykn’des stercoralis perhaps mediated through a Type 1 hypersensitivity reaction. REFERENCES BIAGI, F. & WOODRUFF, A. W. (1965). Trans. R. Sot. trop. Med. Hyg., 59, 585. CROSBY, W. H. & KUGLER, H. W. (1957). Am. J. dig. Dis., 2, 236. DACIE, J. V. (1956). Practical Haematology, 2nd Ed. London: Churchill. FAUST, E. C. & DE GROAT, A. (1940). Am. J. trop. Med., 20, 359. HAZEL J. R. & GRANT, K. A. (1969). Med. J. Aust., 2, 1159. HUTNER, S. H., BACH, M. K. & Ross, G. I. M. (1956). J. Protozool., 3, 101. JARNIJM, S. & ZACHARIAE, H. (1967), Gut., 8, 64. JARRETT, E. E. E. & URQUHART, G. M. (1971). Int. Rev. trop. Med., 4, 53. JEFFERIES, G. H., CHAPMAN, A. & SLEISENGER, M. H. (1964). New. Engl. J. Med., 270, 761. MISTILIS, S., SKYRING, A. P. & STEPHEN, D. D. (1965). Lancet., 1, 77. MOLLIN, D. L., BOOTH, C. C. & BAKER, S. J. (1957). Br. J. Haemat., 3, 412. MULLIGAN, W. (1968). 6th Symposium of British Society for Parasitology, 51. NOLASCO, J. 0. & AFRICA, C. M. (1936). J. Philipp. IsZ. med. Ass., 16, 275. O’BRIEN, W. & ENGLAND, M. W. J. (1971). Tropical Sprue and Megaloblastic Anaemia. Wellcome

Trust Collaborative Study, p. 25. Edinburgh and London: Churchill, Livingstone.

OGILVIE, B. M. (1964). Nature (London), 204, 91. DE PAOLO, D. (1963). Trop. dis Bull., 60, 348. ROGERS, A. M. & DAMMIN, G. J. (1964). Am. J. med. Sci., 211, 531. SANTINI, R., SHEEHY, T. W. & MARTINEZ-DE-JESUS, J. (1961). Gastroenterology, 40, 772. STEMMERMANN, G. N. & NAKAZONB, N. (1960). Ann. trop. Med. Parasit., 63, 493. TOH, C. C. S. & CHOW, K. W. (1969). Ibid., 63, 493. VAN DE KAMER, J. H., HUINICK, H. TEN B. & WE~ERS, H. A. (1949). J. biol. Chem., 177, 347. WATERS, A. H. & MOLLIN, D. L. (1961). 3. clin. Path., 14, 335. WILLIS, A. J. P. & NIVOKOLO, C. (1966). Lancer, 1, 1396.