Intestinal schistosomiasis caused by both Schistosoma intercalatum and Schistosoma mansoni

Intestinal schistosomiasis caused by both Schistosoma intercalatum and Schistosoma mansoni

Travel Medicine and Infectious Disease (2010) 8, 184e189 available at www.sciencedirect.com journal homepage: www.elsevierhealth.com/journals/tmid ...

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Travel Medicine and Infectious Disease (2010) 8, 184e189

available at www.sciencedirect.com

journal homepage: www.elsevierhealth.com/journals/tmid

COMMENTARY

Intestinal schistosomiasis caused by both Schistosoma intercalatum and Schistosoma mansoni Konstantina Tzanetou a,*, Myrto Astriti b, Vassilios Delis c, George Moustakas d, Theodosia Choreftaki e, Eugenia Papaliodi e, Katerina Sarri b, George Adamis b a

Microbiology Department, General Hospital of Athens “G. Gennimatas”, Athens, Greece First Department of Internal Medicine and Special Infections Unit, General Hospital of Athens “G. Gennimatas”, Athens, Greece c Gastroenterology Department, General Hospital of Athens “G. Gennimatas”, Athens, Greece d Nephrology Department, General Hospital of Athens “G. Gennimatas”, Athens, Greece e Pathology Department, General Hospital of Athens “G. Gennimatas”, Athens, Greece b

Received 2 January 2010; received in revised form 30 March 2010; accepted 8 April 2010 Available online 5 May 2010

KEYWORDS Intestinal schistosomiasis; Schistosoma intercalatum; Schistosoma mansoni

Summary A case is presented of intestinal schistosomiasis due to both Schistosoma intercalatum and Schistosoma mansoni in a 30-year-old man from Senegal with discussion of diagnostic approach, species identification and determination of the effect of treatment. The patient was admitted to hospital for investigation of renal failure, arterial hypertension and hypereosinophilia. Repeated stool examinations for ova and parasites were negative. Ultrasonography (US) and computed tomography (CT) of the abdomen showed no abnormalities. US of the urinary tract showed kidneys of borderline size with increased echogenicity. Cystoscopy and histopathological examination of bladder biopsy specimens were normal. Flexible colonoscopy revealed numerous nodular lesions in the rectosigmoid region and a few similar lesions in the transverse colon, the histopathological examination of which showed deposition of Schistosoma ova with granuloma formation. Examination of multiple crush biopsy specimens from the rectosigmoid region revealed numerous granulomas formed around Schistosoma eggs which had a terminal spine and were identified as S. intercalatum (longer than Schistosoma haematobium and with a slightly curved terminal spine) and a very few S. mansoni eggs. Crush biopsies from the lesions in the transverse colon showed only S. mansoni eggs. In conclusion, the examination of multiple crush biopsy specimens is a very sensitive and specific technique

* Corresponding author. Konstantina Tzanetou, 24 Kotziadon street, 185 37, Piraeus, Greece. Tel. þ30 2104534155; fax: þ30 210 7794841. E-mail address: [email protected] (K. Tzanetou). 1477-8939/$ - see front matter ª 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.tmaid.2010.04.003

Intestinal schistosomiasis

185 for species identification of Schistosoma, especially in mixed infections, and for defining the location and extent of the granulomas evoked by each species. ª 2010 Elsevier Ltd. All rights reserved.

Introduction Schistosomiasis is a parasitic disease caused by trematode blood flukes of the genus Schistosoma and is the second most prevalent tropical disease after malaria. The species that cause human infection include Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum, Schistosoma mekongi (responsible for intestinal and hepatosplenic schistosomiasis) and Schistosoma haematobium (responsible for urinary schistosomiasis). S. intercalatum has a restricted distribution in countries such as Cameroon, Equatorial Guinea, Gabon, Nigeria, Sao Tome (Lower Guinea strain) and Democratic Republic of Congo (Congo or Zaire strain). Sporadic cases of S. intercalatum infection have been reported from the Central African Republic, Chad, Burkina Faso, Mali, Senegal, Congo, Angola and Uganda.1 S. mansoni has a wide geographical distribution in Africa (it is reported in most countries), the Middle East, South America and the Caribbean. In non-endemic countries the incidence of imported schistosomiasis is steadily rising, because of increased travelling to endemic countries and immigration from these areas.2,3 The case of intestinal schistosomiasis in a 30-year-old man from Senegal, caused by both S. intercalatum and S. mansoni is presented. The diagnostic approach is described, delineating the location and extent of granuloma formation and the species identification, and the evaluation of response to treatment is discussed.

Case presentation A 30-year-old man from Senegal was admitted to hospital for investigation of renal failure, arterial hypertension, and hypereosinophilia. The patient reported intermittent abdominal pain and pruritus with no skin rash. He had experienced a brief episode of bloody diarrhoea a few years earlier. The range of his systolic/diastolic blood pressure was 180e170/90e110 mm Hg but otherwise the physical, neurological, and ophthalmological examination disclosed no abnormalities. The haematological and biochemical laboratory findings on admission were: haematocrit 35.9%; haemoglobin 12.1 g/dl; white blood cell count (WBC) 12,500/ml with 38% eosinophils (absolute count 4840/ml); platelet count 234,000/ml; erythrocyte sedimentation rate 20 mm; serum iron, ferritin, vitamin B12 and folate levels within normal limits; serum creatinine 2.3 mg/dl (reference range, 0.7e1.3 mg/dl); and cholesterol, triglyceride, sodium, potassium, phosphorus, calcium, and parathyroid hormone levels were normal. The serum total protein level was 7.8 g/dl and the albumin level 4.8 g/dl. The glomerular filtration rate was 30 ml/min. Tuberculus skin test and hemoccult stool tests were negative.

The results of liver function tests were normal. Tests for HIV, HAV, and HCV were negative. All the markers for HBV were negative except for anti-HBc (IgM anti-HBc was negative). The liver biopsy specimens revealed no abnormalities except for a few eosinophils within the sinusoids. The IgE serum level was 1050 IU/ml (normal range, 0e100 IU/ml); IgA 6.43 g/l (reference range, 0.85e4.5 g/l); IgG 16.7 g/l (reference range, 7e16 g/l); C-reactive protein (CRP) 47 mg/l (normal range 0e5 mg/l); serum C3 and C4 complement levels were within normal range; and serum ANCA and anti-dsDNA were negative. Thick and thin blood smears were negative for Plasmodium and Trypanosoma spp. The antibody titer against malaria was high 1/320 (titers  1/80 are indicative of acute or previous infection). Peripheral blood obtained at noon and midnight and examined on thin and thick blood smears and after Knott’s concentration technique revealed no microfilariae. Serologic tests for Toxoplasma, Trichinella, Toxocara, Leishmania, Echinococcus and Cysticercus were negative. A serological test for Schistosoma antibodies was not available. Repeated stool examinations on direct wet preparation and after formol-ether concentration for ova and parasites were negative. Stool culture by the HaradaeMori test-tube filter paper technique for Strongyloides and hookworm filariform larvae were negative. Urine sediment examination demonstrated a few dysmorphic erythrocytes (8e10 per dry high power field) and scarce oval fat bodies (both elements indicate glomerular disease). Measurement of 24-h urine protein excretion was 0.5 g/day. Examination of 24-h urine collection samples after sedimentation and centrifugation for S. haematobium ova was negative. Bloodless skin snip specimens for living microfilariae of Onchocerca volvulus were negative. Ultrasonography (US) and computed tomography (CT) of the abdomen showed no abnormalities and the liver and spleen size were normal. US of the urinary tract showed kidneys of borderline size (9 cm) with increased echogenicity (marker of chronic renal disease) and no abnormalities of the ureters or bladder. CT scan of the urinary tract showed no calcification of the bladder and ureters. Cystoscopy and histopathological examination of bladder biopsy specimens were normal. Renal biopsy was not performed because of absence of the patient’s compliance. Triplex of the renal arteries was normal. Flexible colonoscopy revealed numerous nodular lesions in the rectum and sigmoid colon and a few lesions in the transverse colon (Fig. 1A). The ascending and descending colon, caecum and terminal part of the ileum showed no abnormalities. The mucosa of the affected part of the rectum and sigmoid colon appeared oedematous with a few superficial ulcers. Histopathological examination of biopsy specimens obtained from the various nodular lesions showed deposition of Schistosoma ova with granuloma formation. The majority of the granulomas were early and active with intense inflammatory infiltration consisting of

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Figure 1 Flexible colonoscopy showing the rectosigmoid region of the colon: (A) on admission; numerous nodular lesions (arrow) and (B) 4 months later, after treatment; normal appearance after 3 courses of treatment with praziquantel.

polymorphonuclear cells, mainly eosinophils (Fig. 2). Histopathological examination of biopsy specimens taken from normal-appearing mucosa revealed no abnormalities. Staining of rectal biopsy sections for amyloid deposits was negative. Because the Schistosoma egg morphology was impossible to determine on the histological sections, the patient underwent colonoscopy at which multiple biopsy specimens were taken and examined as squash preparations (crushing of the biopsy specimens between two slides and examination under the microscope of the entire sample for schistosoma eggs). Crush preparations of the rectal and sigmoid nodular lesions demonstrated numerous Schistosoma eggs with a terminal spine and very few with a large lateral spine (Fig. 3). Crush biopsies from the lesions in the transverse colon revealed only granulomas surrounding a few or single S. mansoni eggs with a large lateral spine (Fig. 4) but none with a terminal spine. The Schistosoma eggs with the terminal spine found only in the rectosigmoid region were identified as S. intercalatum ova. The identification was

based on: (a) egg morphology (longer than S. haematobium with a slightly curved terminal spine) and (b) exclusion of ectopic S. haematobium lesions (examination of the urinary tract showed no S. haematobium lesions in the bladder or ureters). The patient was treated with an angiotensin receptor blocker (irbesartan; 150 mg  2) in combination with a calcium channel blocker (amlodipine besylate; 5 mg  2) to control the blood pressure, and three courses (at two and tree week intervals) of praziquantel 40 mg/kg of body weight in a single oral dose (biltricide; 600 mg  4) for the schistosomal infection. Endoscopic examination 4 months later showed normal appearance of the large intestinal mucosa and histopathological examination of biopsy specimens taken blindly from the affected parts of the bowel disclosed no granulomas (Fig. 1B). The WBC had fallen to 5400/ml with 16% eosinophils (absolute count, 864/ml), and the CRP was normal (2.5 mg/l). The high creatinine level was not modified after the antihelminthic treatment.

Discussion

Figure 2 Histopathological examination (haematoxylineeosin stain 400) of lesions of the sigmoid colon, demonstrating early active granuloma surrounding S. intercalatum eggs with intense inflammatory infiltration consisting mainly of eosinophils. The curved terminal spine (arrow) was evaluated after the species identification by crush biopsy method.

The adult worms of S. mansoni and S. intercalatum inhabit the inferior mesenteric veins (draining the colon) and release eggs into the portal blood flow. The eggs are trapped in the intestinal submucosa or carried to the liver. The signs and symptoms of schistosomiasis are due to the host’s immune response to schistosome eggs trapped in the tissues. The eggs secrete antigens that provoke eosinophilic inflammatory and granulomatous reactions, which in the latter stages of the disease are replaced by fibrosis.4 Patients with mild intestinal disease due to S. mansoni constitute >90% of the infected population. They may be asymptomatic or have abdominal pain, transient diarrhoea and bloody stools. Less that 10% of infected persons develop hepatosplenic disease, which is manifested by hepatosplenomegaly, ascites, portal hypertension, and oesophageal varices.5 S. intercalatum is an uncommon schistosome species with low pathogenicity in humans. It causes intestinal schistosomiasis characterized by a low location of the lesions at the level of the rectum and sigmoid colon and relatively minor liver pathology. Granulomas may be seen in

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Figure 3 Crush biopsy specimens from rectosigmoid region of the colon. (A) An old fibrotic granuloma with many partially calcified S. intercalatum eggs (100). (B) Elongated S. intercalatum egg with terminal slightly curved spine (400). (C) Numerous partially calcified S. intercalatum eggs (100). (D) Higher magnification showing the terminal slightly curved spine (400) (the eggs are similar to those of S. haematobium, but are longer, with a terminal spine, which may appear bent).

liver biopsy but are smaller in size than those seen in S. mansoni infection and no evidence of portal hypertension has been reported.6 The infection is asymptomatic or presents as dysenteric syndrome with bloody stools. The endoscopic appearance of the lesions is variable, ranging from granulomas or ulceration to polyps.7

In this patient numerous granulomas formed around many S. intercalatum eggs were restricted to the rectum and sigmoid colon, resulting in recto-sigmoidal schistosomiasis. The endoscopic lesions were similar to those induced by S. mansoni and the main manifestations were abdominal pain, pruritus and hypereosinophilia. Despite repeated stool

Figure 4 Crush biopsy specimen from a nodule in the transverse colon. (A) A central single S. mansoni egg surrounded by granuloma formation (100). (B) Higher magnification (400), showing the prominent lateral spine and the partially calcified egg.

188 examination after the formol ether concentration method Schistosoma eggs were not detected. The biopsy specimens taken from the nodular lesions of the colon were more sensitive than stool specimens for diagnosing Schistosoma infection by histopathological examination, but multiple crush biopsy specimens were more specific for identification of the species, even in mixed infections and were used to define the location and extent of the granulomas evoked by each of the species identified. It has been documented that S. mansoni and S. haematobium are competitively dominant over S. intercalatum in terms of pairing ability making difficult for S. intercalatum to become established in areas where S. mansoni and S. haematobium are present. The occurrence in man of competitive mating interactions between S. mansoni and S. intercalatum could reduce the reproductive ability of S. intercalatum in the case of co-infection.8 Despite these epidemiological observations, in the present case the eggs and granulomas produced by S. intercalatum were observed in significantly higher numbers than those of S. mansoni. Huyse et al9 provide evidence for natural hybridization between the cattle parasite Schistosoma bovis and the human parasite S. haematobium (based on molecular studies), with hybrid infecting children in northern Senegal, but they do not describe, on clinical level, the pathology or the features of intestinal schistosomiasis caused by the hybrid parasite. The same authors support inter-specific mating between S. mansoni and S. haematobium in children with mixed infection and terminal spined eggs in the stools. In our case after extensive work-up there was no evidence of co-infection with S. haematobium. Glomerulonephritis often complicates parasitic infections. In the majority of cases the disease is subclinical, transient or mild.10 Schistosomiasis is one of the few exceptions, and it has often been reported in association with nephrotic syndrome, hypertension and chronic renal disease. The clinicopathological spectrum of schistosomal glomerulopathy is the widest among the parasitic nephropathies, with 5 classes of glomerular lesions associated with schistosomal infection: class I is histologically defined as mesangial proliferative glomerulonephritis (encountered in S. haematobium, S. mansoni and sporadically in S. japonicum infections),11 class II is defined as an exudative glomerulonephritis, class III (membranoproliferative) and class IV (focal and segmental glomerulosclerosis) cover the majority of patients with progressive disease, and are often associated with abnormalities in serum IgA components,12 and class V is systemic amyloidosis, which occurs in prolonged active infection with either S. haematobium or S. mansoni.13 The classes III and IV are associated with nephrotic syndrome, hypertension (observed in onehalf of the cases) and progression to end stage chronic renal disease. Both of these forms of glomerulopathy are associated with hepatosplenic schistosomiasis and encountered mostly in S. mansoni infection. The type of glomerulonephritis in this patient was not defined because renal biopsy was not performed. The glomerular disease leading to advanced renal insufficiency could be idiopathic (black African people tend to develop focal and segmental glomerulosclerosis) or secondary to hepatitis B or to schistosomiasis. The latter hypothesis, however, is not compatible with the mild intestinal

K. Tzanetou et al. schistosomiasis of the patient and the absence of hepatosplenic disease. The IgG anti-HBc antibodies of the patient may be a marker of resolved past infection. Hepatitis B is one of the most common causes of membranous nephropathy in black African people. The renal failure was not affected by antihelminthic treatment. Control of hypertension is important in the progression of renal disease. The eosinophil count was decreased dramatically during the 4 months of follow-up but was not completely normalized following treatment, despite there being no evidence of another helminthic infection. The histopathological examination of biopsy material obtained after treatment with praziquantel did not reveal any old granulomas but this may be because the biopsy was performed blindly, due to the absence of macroscopic intestinal lesions at follow-up. An earlier study showed that early active granulomas with intense inflammatory infiltration respond completely to the specific therapy, while the old fibrotic and calcified granulomas reveal reduction of inflammatory infiltration only (fibrotic deposits and calcified eggs are not affected).14 The present report illustrates the problems concerning the diagnosis of intestinal schistosomiasis in the case of light infection. We suggest that every patient from an endemic area with unexplained eosinophilia and repeated stool examination testing negative for ova and parasites should be examined by colonoscopy and rectal biopsy. The histopathological examination of biopsy specimens of mucosal lesions is more sensitive than stool examination for diagnosing Schistosoma infection. The examination of multiple crush biopsy specimens is more specific for species identification, especially in mixed infections, and for defining the location and extent of granulomas induced by each species. One approach for the determination of the effect of treatment for intestinal schistosomiasis is endoscopy and the histopathological examination of biopsy material, since specific antibodies continue to be present long after successful treatment, eosinophil counts may remain elevated for long periods, and the detection of parasite antigens (such as circulating anodic and cathodic antigens) is performed only in certain research laboratories.15,16

Conflict of interest declaration The author has no conflicts of interests.

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