J Clin Pathol 1986;39:366-370

Strongyloides stercoralis hyperinfestation syndromewith Escherichia coli meningitis: report of two casesLESLEY A SMALLMAN,* JENNIFER A YOUNG,* WR SHORTLAND-WEBB,tMP CAREY,* J MICHAEL:

From the *Department ofPathology, The Medical School, University ofBirmingham, the tDepartment ofPathology, Dudley Road Hospital, Birmingham, and the tQueen Elizabeth Hospital, Birmingham

SUMMARY Two cases of Strongyloides stercoralis hyperinfestation syndrome accompanied by Gramnegative bacteraemia and meningitis were studied. Both occurred in non-immunosuppressed WestIndian women.

Secondary Gram negative bacteraemia and men-ingitis has previously been documented in associationwith overwhelming strongyloidiasis.' Most instances,however, have occurred in patients immuno-suppressed by disease, treatment, or both. We reporttwo cases of Escherichia coli meningitis and hyper-infestation with Strongyloides stercoralis in non-immunosuppressed West Indian women.

Case 1

A 38 year old West Indian woman was admitted toDudley Road Hospital, Birmingham, in December1978. She had a two month history of anorexia,weight loss, abdominal pain, diarrhoea, and swollenlegs. The patient had lived in England since 1960 buthad returned home to Jamaica for a month in 1976.On examination she had pitting oedema of both legsup to the knees and a distended abdomen.Investigations showed a haemoglobin of 12-2g/dl, alow serum total protein and albumin, and mildlyraised liver function tests. A barium meal x-rayshowed that the jejunum and ileum were grosslydilated; and there was slow progression of the con-trast medium through the bowel but no localisedabnormality.

In January 1979 her condition deteriorated rapidlyand she became confused, delirious, dehydrated, andshocked. Her haemoglobin had fallen to 8-5 g/dl, and,although without fever, she had leucocytosis of 24 x109/l without evidence of eosinophilia. Laparotomywas performed, but only thickening of the terminalileum and enlarged mesenteric lymph nodes werefound. Biopsy of the distal ileum, however, showedinfestation with S stercoralis (Fig. 1) and partial vil-

Accepted for publication 1 I December 1985

lous atrophy; only reactive changes were seen in themesenteric lymph nodes.

Postoperative recovery was poor, and ventilationwas necessary after two respiratory arrests. Parasiteswere isolated from the stools and nasogastric, phar-yngeal, and tracheal aspirates, and treatment withhigh dose thiobendazole was therefore started.Several days later she became feverish, and E coli wasgrown from blood cultures. Treatment with gen-tamicin was started, but there was no improvement inher condition and she died later that month.

NECROPSY FINDINGS AND HISTOLOGYAt necropsy pitting oedema of both legs up to theknees and a recent abdominal scar were found. A fewsubcutaneous nodules, which, on incision, were foundto be abscesses, were present on the left thigh. Thelungs, although firm and oedematous, showed no evi-dence of pneumonia. Small bilateral pleural effusionswere present and the peritoneal cavity contained oneand a half litres of ascitic fluid. The small intestinesappeared unremarkable apart from some serosal con-gestion in the distal portion where the biopsy hadbeen obtained, and fibrinous adhesions were presentbetween the adjacent loops of bowel. The liver(2850 g) was fatty, and small subcapsular abscesseswere identified in the right kidney. The brain (1060 g)was soft with adherent dura. Pus had collected in thesulci on the lateral aspect of the right temporal lobe,and a basal meninigitis was found. A swab from oneof the subcutaneous abscesses grew E coli and Pseu-domonas aeruginosa; the pus from the meninges grewonly E coli.

Microscopic examination showed that there wasgranulation tissue and a fibrinopurulent exudate onthe serosal aspect of the small intestine, but noresidual parasites could be identified. Ventilation

366

on June 15, 2020 by guest. Protected by copyright.

http://jcp.bmj.com

/J C

lin Pathol: first published as 10.1136/jcp.39.4.366 on 1 A

pril 1986. Dow

nloaded from

Strongyloides stercoralis hyperinfestation syndrome with Escherichia coli meningitis

4_

Vr

I*NI

_~~~~~~~0

S_

,. A..I..

p

Fig. 1 Larvae ofStrongyloides stercoralis embedded in wall ofbowel. (Haematoxylin and eosin.) x 450.

changes and a few granulomas were present in thelung but again no convincing parasites could befound. Sections of the brain showed meningitis andventriculitis. The abscesses within the subcutaneoustissues and right kidney were confirmed.

Case 2

A 68 year old West Indian woman was admitted tothe Queen Elizabeth Hospital, Birmingham, in Sep-tember 1984 with a history of anorexia, weight loss,

'A. v V _U

abdominal pain, drowsiness, and restlessness. Onexamination she was dehydrated and had abdominaltenderness. Investigations showed poor renal func-tion, a metabolic acidosis and a haemoglobin of7-6 g/dl (hypochromic, normocytic). The cause of theanaemia was not discovered; there was no evidence ofsickle haemoglobin or faecal occult blood, and a bar-ium enema x-ray showed normal results. Renal func-tion and the metabolic acidosis improved with intra-venous fluids and bicarbonate, and she wasdischarged from hospital having been prescribed iron

Fig. 2 Purulent exudate within the meninges over temporoparietal lobes ofbrain.

367

on June 15, 2020 by guest. Protected by copyright.

http://jcp.bmj.com

/J C

lin Pathol: first published as 10.1136/jcp.39.4.366 on 1 A

pril 1986. Dow

nloaded from

Smallman, Young, Shortland- Webb, Carey, Michael

4::A 4X--

Fig. 3 Cross section ofStrongyloides stercoralis seen in wallofbowel. (Haematoxylin and eosin.) x 620.

supplements.In December 1984 she had to be readmitted. She

was now delirious, unresponsive, and feverish with atachycardia. There was stiffness of the neck, and Ker-nig's sign was positive. Laboratory findings includedperipheral blood leucocytosis of 9-3 x 109/l (noeosinophilia), a raised white cell count (neutrophils,polymorphs), a low glucose concentration, and occa-sional Gram negative bacilli in the cerebrospinalfluid. A heavy growth of E coli was cultured. Despitetreatment with chloramphenicol and cefataxime hercondition deteriorated and she died three days afteradmission.

.A,W,^

Fig. 5 Higher magnification ofone ofnumerousrhabditiform larvae present in scrapingsfrom bowel.(Papanicolaou.) x 480.

NECROPSY FINDINGS AND HISTOLOGYThe lungs were heavy, congested, and oedematousbut without evidence of pneumonia. There were smallbilateral effusions. The stomach, and small and largeintestines appeared macroscopically unremarkable.The liver (1265 g) was fatty, and there was mild acutepancreatitis. On dissecting the thyroid and para-thyroids, abscesses were found within the strap mus-cles of the neck. The brain (1245 g) showed atrophicchanges and pus in the subarachnoid space, particu-larly overlying the superior aspects of the left pre-central and postcentral gyri (Fig. 2). The pus in themeninges contained moderate numbers of Gram

Fig. 4 Scrapingfrom bowel wall containing two adult worms and many small larvae. (Papanicolaou.)x 120.

368.11. ,.

l. i. .'Z.!,:-,.:%.. ......0.,

..f.W.:....

on June 15, 2020 by guest. Protected by copyright.

http://jcp.bmj.com

/J C

lin Pathol: first published as 10.1136/jcp.39.4.366 on 1 A

pril 1986. Dow

nloaded from

Strongyloides stercoralis hyperinfestation syndrome with Escherichia coli meningitisnegative bacilli, and a heavy growth of E coli wascultured.

Histological examination showed that the duo-denum, jejunum, and ileum were honeycombed withadult worms, larvae, and eggs of S stercoralis (Fig. 3).Larvae were present in the crypts of Lieberkuhn, thebowel wall, and the veins of the submucosa andserosa. Material was scraped off the mucosal surfaceof the fixed bowel, mixed with saline, and centrifuged.Smears were made from the deposit and stained bythe Papanicolaou method. Complete adult worms(Fig. 4) and intact larvae (Fig. 5) were clearlyidentifiable. Sections of the brain showed a meningitisand ventriculitis, and Gram negative bacilli wereshown within the purulent exudate. The abscesseswithin the strap muscles of the neck were confirmed.No parasites were seen in tissues outside the bowel.

Discussion

S stercoralis was first isolated from the faeces ofFrench colonial troops suffering from diarrhoea inCochin-China (Vietnam) in 1876.2 It is an intestinalnematode that infests a large proportion of theworld's population but is particularly common inwarm moist climates.

Filariform larvae within the soil penetrate the skin,enter lymphatics and veins, and are thus carried to thelungs. After migrating up the trachea to the glottisthey are swallowed and reach the duodenum and jeju-num. Here the larvae burrow into the gut mucosa andbecome hermaphrodite adult females, able to lay upto 40 eggs a day. The ova develop into rhabditiformlarvae, which enter the bowel, and are expelled in thefaeces. As they traverse the intestinal tract some meta-morphose into infective filariform larvae. Theseinvade the gut wall or perianal skin gaining access tothe bloodstream, thus establishing an endogenouscycle. This recycling process, known as "auto-infestation" is unique to S stercoralis and mayaccount for the persistence of the parasite even 40years after the host has left the area where theinfestation was acquired.34 Unfortunately, no infor-mation concerning residence was available for case 2,but case I had lived in England since 1960 returningto Jamaica for one month only in 1976. The parasitewas presumably acquired in the West Indies in bothcases and had persisted due to autoinfestation.The normal host parasite equilibrium with the

nematode seems to be predominantly maintained bycell mediated immunity.5 6 Breakdown of thesedefences due to disease or immunosuppression mayresult in hyperinfestation (augmentation of the nor-mal life cycle), or disseminated infestation (spread toorgans not normally part of the life cycle).' Over-whelming infestation can, however, develop in nor-

mal hosts.' The mechanisms of pathogenesis are notwell understood; general debility and protein-caloriemalnutrition have been implicated,5 but mal-absorption, protein losing enteropathy, and hypo-proteinaemia may be produced by S stercoralis itself.7Both our patients had hyperinfestation with S ster-coralis. In case 2 parasites were found only in sectionsof the small intestine at necropsy. In case 1, however,larvae were seen in a surgical biopsy and were alsoisolated from stools and nasogastric, pharyngeal, andtracheal aspirates. This patient had two respiratoryarrests, and larvae were also most probably presentwithin the lungs. Treatment with thiobendazoleseemed to be successful as no parasites were seen inthe sections of bowel or lungs at necropsy, althoughthere were granulomata in the lungs. No cause ofimmunosuppression was found in either case.

Hyperinfestation and disseminated infestation maybe accompanied by persistent or recurrent bacte-raemia due to organisms of enteric origin.' It hasbeen suggested that these bacteria gain access to thecirculation by one or all of three mechanisms. Firstly,disruption of the bowel wall could provide entranceto the circulation for faecal flora.8 - " Secondly, it isalso thought more likely that bacteria adhere to theexternal surface of larvae and are transported fromthe gut in piggy back fashion.12 Finally, bacteria maybe excreted into the circulation from the intestinaltract of migrating larvae.12Only a few cases of S stercoralis hyperinfestation

syndrome had been documented before 1964. In 1981Igra-Siegman et al described two cases, one of whichwas accompanied by Klebsiella pneumoniae bacte-raemia and meningitis. The same authors reviewed103 other cases published since 1964. Eighty nine ofthe patients were immunosuppressed by disease,treatment, or both; the 14 others had no apparentimmune deficiency. Thirty two of the immuno-suppressed patients were included in a report that wasbased on necropsy material; sepsis due to Gram nega-tive bacteria was mentioned in three of these cases,but, unfortunately, no further details were given.5Thirty of the residual 71 cases reviewed had a second-ary bacterial infection, 25 of whom died- 1I withmeningitis.

Spread to the brain is extremely rare, even in dis-seminated strongyloides, but published examplesinclude one case each of meningitis, 3 brainabscess,14 and cerebral infarction.15Both of our patients had a Gram negative (E coli)

meningitis. In addition, there were subcutaneous andrenal abscesses in case 1, and abscesses in the strapmuscles of the neck in case 2. The first patient's condi-tion deteriorated shortly before laparotomy.Although E coli was only isolated from the blood cul-ture several days after the operation, and disruption

369

on June 15, 2020 by guest. Protected by copyright.

http://jcp.bmj.com

/J C

lin Pathol: first published as 10.1136/jcp.39.4.366 on 1 A

pril 1986. Dow

nloaded from

370

of the bowel wall during biopsy may have resulted inthe Gram negative bacteraemia, the onset of thesymptoms and signs does not suggest this. It seemsmore likely that the infection occurred either as aresult of bacteria adhering to the external surface oflarvae or to bacteria being excreted into the circu-lation from the intestinal tract of migrating larvae.One or both of these mechanisms are also the likelyexplanation for the Gram negative bacteraemia incase 2. No larvae were found in the meninges or brainparenchyma in either case.

Secondary Gram negative bacteraemia and men-ingitis developing in association with strongyloidiasisis considered to be rare and occurs almost exclusivelyin immunocompromised subjects. Our two casesshow that the hyperinfestation syndrome should beconsidered even in non-immunosuppressed immi-grant patients with Gram negative bacteraemia, men-ingitis, and unexplained anaemia.

We thank Dr A Paton for permission to report case 1.Our thanks are also due to Miss M Trumper fortechnical help, Mr A Cooper for help in preparing thephotomicrographs, and Miss A Wright for typing themanuscript.

References1 Igra-Siegman Y, Kapila R, Sen P, Kaminski ZC, Louria BD. Syn-

drome of hyperinfection with Strongyloides stercoralis. RevInfect Dis 1981;3:397-407.

Smallman, Young, Shortland- Webb, Carey, Michael

2Normnand A. Sur la maladie dite diarrhee de Cochin-chine. C RSeaonces Acad Sci (111) 1876;83:316-8.

3Grove DI. Strongyloidiasis. In: Warren KS, Mohamoud AAF, eds.Tropical and geographical medicine. New York: McGraw-Hill1984:373-9.

'Grove DI. Strongyloidiasis in allied ex-prisonei of war in south-east Asia. Br Med J 1980;280:598-601.

sPurtilo DR, Meyers WM, Connor DH. Fatal strongyloidiasis inimmunosuppressed patients. Am J Med 1974;56:488-93.

6Dwork KG, Jaffe JR, Lieberman HD. Strongyloidiasis with mas-sive hyperinfection. NY State J Med 1975;75:1230-4.

Liepman M. Strongyloides stercoralis, a complication of immuno-suppression. JAMA 1975;231:387-8.

8De Paola D, Dias LB, Da Silva JR. Enteritis due to Strongyloidesstercoralis. A report of five fatal cases. Am J Dig Dis1962;7:1086-98.

'Faust EC, DeGroat A. Internal autoinfection in human strongy-loidiasis. Am J Trop Med 1940;20:359-71.

"Meyers AM, Shapiro DJ, Milne FJ, Myburgh JA, Robkin R.Strongloides stercoralis hyperinfection in a renal allograft recip-ient. S Afr Med J 1976;50:1301-2.

" Rivera E, Maldonado N, Velez-Garcia E, Grillo AJ. Malaret G.Hyperinfection syndrome with Strongyloides stercoralis. AnnIntern Med 1970;72:199-204.

12 Brown HW, Perna VP. An overwhelming strongyloides infection.JAMA 1958;168:648-51.

"Owar R, Wamukota WM. A fatal case of strongyloidiasis withstrongyloides larvae in the meninges. Trans R Soc Trop MedHyg 1970;70:497-9.

14Neefe LI, Pinilla I, Garagusi VF, Bauer H. Disseminated strongy-loidiasis with cerebral involvement. A complication of cortico-steroid therapy. Am J Med 1973;55:832-8.

'5Masdeu JC, Trantulavanich S, Gorelick PP, et al. Brain abscesscaused by Stronglyoides stercoralis. Arch Neurol 1982;39:62-3.

Requests for reprints to: Dr Lesley A Smallman,Department of Pathology, The Medical School, Universityof Birmingham, Birmingham B15 2TJ, England.

on June 15, 2020 by guest. Protected by copyright.

http://jcp.bmj.com

/J C

lin Pathol: first published as 10.1136/jcp.39.4.366 on 1 A

pril 1986. Dow

nloaded from