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Clinical and epidemiological features of 33 imported Strongyloides stercoralis infections
Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 613–616
Contents lists available at ScienceDirect
Transactions of the Royal Society of Tropical Medicine and Hygiene journal homepage: http://www.elsevier.com/locate/trstmh
Clinical and epidemiological features of 33 imported Strongyloides stercoralis infections夽 ˜ a , Laura Puyol a , Ana González a,∗ , Marina Gallo b , M. Eugenia Valls c , Jose Munoz a c a M. Jesús Pinazo , Jordi Mas , Joaquim Gascon a b c
Barcelona Centre for International Health Research (CRESIB), CIBERESP, Hospital Clínic, c/Rosselló 132, 4◦ , 08036 Barcelona, Spain Internal Medicine Department, Hospital Universitario Reína Sofía, Avda. Menéndez Pidal s/n, Córdoba, Spain Parasitology Unit, Microbiology Department, Hospital Clínic, c/Villarroel 170, 08036 Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 12 November 2009 Received in revised form 4 June 2010 Accepted 4 June 2010 Available online 16 July 2010 Keywords: Strongyloidiasis Strongyloides stercoralis hyperinfection syndrome immunocompromised host immigrant traveller
a b s t r a c t Strongyloides stercoralis has a unique ability to replicate in the human host and lead to chronic infection that can persist for several decades. Thirty-three patients (10 travellers and 23 immigrants) with imported S. stercoralis infection were studied and clinical and epidemiological characteristics described. Only 16 patients (48.5%) reported symptoms, mainly of the gastrointestinal tract. Eosinophilia was present in 21 (63.6%) patients. Seven patients (21.2%) had an immunocompromising condition. Patients were classified into chronic asymptomatic infection (17/33, 51.5%), chronic symptomatic infection (11/33, 33.3%) and hyperinfection (5/33, 15.2%). Four of the latter (80%) had an immunocompromising condition. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. Diagnosis should always be sought in immunocompromised hosts. © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
1. Introduction Around 30 to 100 million people are estimated to be infected with the intestinal nematode Strongyloides stercoralis in endemic areas of Central and South America, sub-Saharan Africa, South and Southeast Asia.1–3 Some endemic foci have also been described in industrialized countries.4,5 In Spain, several cases have been reported, mainly from the 1990s in the Valencia region, but they seem to account for former exposures in farmers and rice field workers.4 Currently, S. stercoralis infections are mainly seen in travellers or immigrants from endemic regions.
夽 Presented in part: 6th Congress of the Tropical Medicine and International Health Spanish Society, 5–7 March 2008, Segovia, Spain. ∗ Corresponding author. Tel.: +34 93 2275706; fax: +34 93 3379853. E-mail address: [email protected] (A. González).
Strongyloides stercoralis is of note due to its ability to replicate in the human host (autoinfection) and lead to chronic infection that can persist for several decades.1,2,6 Acute infection is rarely diagnosed. Chronic strongyloidiasis presents with mild or absent clinical manifestations. Hyperinfection denotes a high parasite burden in the organs usually affected due to acceleration of the autoinfection cycle. Severe gastrointestinal and pulmonary symptoms are common and larvae are usually easily identified in stools. Disseminated disease refers to systemic spread of larvae outside their usual migration pattern with possible invasion of virtually every organ. Larvae can be identified in samples from any of the affected organs. Hyperinfections or disseminated infections, are more frequent in immunocompromised hosts, and may carry a high mortality rate of up to 75%. No clear cut-off between these syndromes exists and it is sometimes difficult to classify a patient in the absence of definite criteria.1,3,7,8
0035-9203/$ – see front matter © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2010.06.001
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A. González et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 613–616
The aim of this study was to describe the clinical and epidemiological characteristics of imported strongyloidiasis in a non endemic area and highlight the risk factors, as well as the importance of early diagnosis and treatment in this potentially fatal infection. 2. Methods 2.1. Patients A retrospective descriptive study was conducted of adult cases diagnosed with S. stercoralis infection who attended Hospital Clinic, University of Barcelona, from July 2004 to July 2007. Patients with positive parasite samples for S. stercoralis were identified through the Microbiology Department database. The stool samples were examined by light microscopy using the merthiolate iodine formaldehyde (MIF) concentration method. The clinical charts of the patients identified were reviewed. Clinical and epidemiologic data were collected using a standardized data form and included: age, sex, country of origin, country of residence and years of residence (if immigrants), travel history (if travellers), clinical manifestations, risk factors, eosinophil count, number of stool samples, treatment and outcome. Patients were classified into groups (acute infection, chronic asymptomatic infection, chronic symptomatic infection, hyperinfection and disseminated infection) according to the clinical manifestations as described in the Introduction section. 2.2. Statistical analysis All data were introduced into a database and analyzed with SPSS software program (version 12; SPSS Inc., Chicago, IL, USA). Comparisons were made using the Fisher exact test for categorical data and the U of Mann-Whitney for continuous data, as appropriate. A P value of <0.05 was considered as statistically significant. 3. Results Thirty-three patients were diagnosed with S. stercoralis infection during the three-year study period. Patient characteristics are shown in Table 1. Most patients attended the Tropical Medicine (23/33, 69.7%) or Infectious Diseases Departments (4/33, 12.1%), but some attended different departments: Haematology (3/33, 9.1%), Digestive Diseases (2/33, 6.1%) and Cardiology (1/33, 3%). Sixteen patients reported symptoms, mainly of the gastrointestinal tract. Detailed symptoms and clinical classification are described in Table 1. Seven patients (21.2%) had one or more immunocompromised conditions. One patient with HIV infection was also diagnosed with Kaposi sarcoma. Human T-lymphotropic virus type 1 (HTLV-1) infection was tested for and negative in six patients. Five patients were considered to have a hyperinfection syndrome due to prominent clinical manifestations of the gastrointestinal tract and/or pulmonary involvement and a high number of S. stercoralis larvae found in stool samples. None presented with acute or disseminated infection. Of
Table 1 Patient characteristics (n = 33) Median age, years (IQR) Male (%) Female (%) Group and region visited/of origin, n (%) Travelers:a visited region Sub-Saharan Africab Southeast Asiac North Africad East Europee Immigrants: region of origin South Americaf Sub-Saharan Africag Indian subcontinenth Median time of residence in Spain (if immigrant), years, IQR Reason for diagnostic work-up, n (%) Eosinophiliai Gastrointestinal symptoms Asymptomatic screening Microcytic anaemiai Symptomatic patients, n (%) and type of symptoms: Gastrointestinal symptoms Epigastric pain Other abdominal pain Diarrhoea Nausea and/or vomiting Constipation Dyspepsia Abdominal bloating Pulmonary symptoms (cough and/or dyspnea) Cutaneous symptoms (pruritus) General symptomsj Eosinophilia (>500 eosinophils/mm3 ), n (%) Median eosinophil count (IQR) Median eosinophil count (IQR) if eosinophilia (n = 21) Immunocompromised, n (%) Corticosteroid treatment HIV infection (22 tested) (% of tested) Haematological malignancies Malnutrition Alcoholism Clinical group Chronic asymptomatic infection Chronic symptomatic infection Hyperinfection
35 (29.5–42) 18 (54.5) 15 (45.5) 10 (30.3) 4 (40.0) 3 (30.0) 2 (20.0) 1 (10.0) 23 (69.7) 16 (69.6) 6 (26.1) 1 (4.3) 4 (1.4–6.6)
16 (48.5) 12 (36.4) 4 (12.1) 1 (3.0) 16 (48.5) 15 (93.7) 7 (43.8) 6 (37.5) 7 (43.8) 3 (18.8) 2 (12.5) 1 (6.3) 1 (6.3) 2 (12.5) 1 (6.3) 5 (31.2) 21 (63.6) 990 (235–1865) 1630 (1005–2140) 7 (21.2) 4 (12.1) 3 (13.6) 3 (13.6) 2 (6.1) 1 (3.0) 17 (51.5) 11 (33.3) 5 (15.2)
IQR = Interquartile Range; HIV = Human Immunodeficiency Virus a Origin: Spain (9), Belgium (1) b Equatorial Guinea (1), Tanzania-Kenya (1), Angola (1), Mali (1); c Thailand (2), Thailand-Cambodia-Lao PDR-Indonesia-Malaysia (1); d Egypt (1), Algeria (1); e Kazakhstan (1); f Bolivia (5), Ecuador (4), Colombia (4), Argentina (1), Peru (1), Brazil (1); g Equatorial Guinea (3), Ghana (1), Cameroon (1), Gambia (1); h Pakistan i Three of the patients studied for eosinophilia and the patient with microcytic anaemia also referred with gastrointestinal symptoms. j Asthenia alone (3 patients), asthenia and anorexia (1), asthenia, anorexia and weight loss (1).
the five patients with hyperinfection, only two presented with eosinophilia (1340 and 5140 eosinophils/mm3 ). The clinical characteristics were compared between immigrants and travellers. There were no significant differences in age, sex, symptoms, or eosinophilia. All five patients in the hyperinfection group were immi-
A. González et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 613–616
grants, although this difference did not achieve statistical significance (P = 0.291). In addition, although all seven immunocompromised patients were immigrants, this difference only bordered statistical significance (P = 0.073). Differences between patients with hyperinfection and patients with chronic infection were also assessed. All five hyperinfection patients (100%) were symptomatic compared with only 11/28 (39.3%) of the chronic infection group (P = 0.018). Both immunocompromised status in general and corticosteroid treatment were significantly more frequent in the hyperinfection group. Four out of five patients (80.0%) in the hyperinfection group were immunocompromised compared with 3/28 (10.7%) in the chronic infection group (P = 0.004), and 3/5 (60%) versus 1/28 (3.6%), respectively were receiving corticosteroid treatment (P = 0.007). No differences were found in median age, sex or presence of eosinophilia. All 33 patients had S. stercoralis larvae detected in stool samples by the MIF method. Each patient had delivered a diverse number of stool samples to the Microbiology Department with a median of 3 samples per patient (range 1–6). Strongyloides stercoralis larvae were detected in 49 of the 81 (60.5%) stool samples provided by patients; each patient had at least one positive sample. Additionally, in one patient, S. stercoralis was isolated from a gut biopsy made in the context of pyloric stenosis secondary to the nematode infection. At the time of the study serologic diagnosis was not readily available at our centre, therefore an ELISA test (Microwell ELISA kit, DRG International Inc., USA) was additionally available in only two patients. One tested negative and the other was low positive. Other intestinal parasites were found in four patients: Trichuris trichiura, Hymenolepis nana, Entamoeba histolytica-dispar, A. duodenale/Necator americanus (1 each). Two patients were lost to follow-up before treatment could be prescribed. Twenty-five (75.7%) patients were treated with 200 mcg of ivermectin per kg of body weight: three patients received a single oral dose, 20 (60.6%) patients received two doses on different days and two (6.1%) patients with hyperinfection received ivermectin for 4 and 14 days respectively. Four (12.1%) patients were treated with 400 mg of albendazol bid for 3 days. Two (6.1%) patients with hyperinfection were treated with both albendazol (400 mg bid for 3 days) and ivermectin (200 mcg per kg of body weight) on days 4 and 12. Twentythree (69.7%) patients were considered cured based on the disappearance of symptoms (12 patients) or eosinophilia (11 patients); of these 14 patients had one stool sample tested and found to be negative after treatment. Cured patients were homogeneously distributed between immigrants (16/23 patients, 69.6%) and travellers (7/10 patients, 70%). Two patients died but their death was not related to S. stercoralis infection. The outcome could not be assessed in the remaining patients who were lost to follow-up. 4. Discussion Immigrants account for most patients in studies of imported strongyloidiasis, consistent with our results.5,9 Most of the immigrants had been living in Spain for many years, reflecting the potential of S. stercoralis for causing
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persistent infection. As in our study, chronic infections with S. stercoralis can be silent in more than 50% of infected patients. As expected, gastrointestinal complaints were the most common in symptomatic patients.1,5 On the contrary, none of the patients studied presented with the pathognomonic larva currens eruption and pulmonary symptoms were uncommon. We did not find differences in symptoms between travellers and immigrants as reported in other studies.5,10 Eosinophilia is an inconstant finding in S. stercoralis infection and may fluctuate with different degrees, and it is often absent in immunocompromised hosts and/or those with severe disease, consistent with our results.6,11 Impaired cellular immunity is a known risk factor for severe strongyloidiasis and 80% of hyperinfection patients in our series were immunocompromised. As in our study, corticosteroid therapy appeared to be the most strongly associated with severe disease.1,7 Although, a limited number of cases of HIV infection and S. stercoralis infection have been reported, it seems that strongyloidiasis is not an important opportunistic infection.7 In contrast, it appears to be a relevant opportunistic infection in patients with HTLV-1 infection.1,7,12 Strongyloidiasis diagnosis is often difficult since no gold standard procedure has been established. Definitive diagnosis is usually made by detection of larvae in stools. However, a single stool examination fails to detect larvae in up to 70% of cases. Repeated examinations of stool samples improve the sensitivity up to 50% and 90% with three and seven serial stool samples respectively.3,13 In our study, all patients had S. stercoralis detected in stool samples. The broad range of samples processed for each patient prevents from drawing further conclusions. Several serodiagnostic tests have been developed with a different sensitivity and specificity. They show crossreactivity with other helminth infections, are only available at specialized centres, and may remain positive a long time after infection cure; their role remains to be defined.3,8 Most patients in the study were treated with ivermectin. Compared with albendazole, ivermectin has shown better response rates and it is the current preferred treatment.5,7 As the immigrant population and international travel continue to increase imported tropical diseases will become more frequent in developed countries. Early diagnosis and treatment of S. stercoralis infection can prevent fatal outcomes. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. This diagnosis should be considered even in the absence of symptoms and/or eosinophilia in immunocompromised hosts or patients likely to receive corticosteroids or other immunosuppressive therapy. Authors’ contributions: AG, MG, MEV and JG designed the study protocol; MEV, LP and JMa carried out the microbiological studies and the identification of cases; AG, MG and MJP carried out the collection of clinical and epidemiological data; MEV, LP and JMa carried out the collection of microbiological data; AG, JMu, LP, MJP and JMa carried out the analysis and interpretation of data; AG, MG, MEV, LP and MJP drafted the manuscript. AG, JMu, JMa and JG
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revised the manuscript for intellectual content. All authors read and approved the final manuscript. AG and JG are guarantors of the paper Acknowledgements: The authors thank Donna Pringle for suggestions and English language review of the manuscript. Funding: None. Conflicts of interest: None declared. Ethical approval: Not required. References [1]. Concha R, Harrington Jr W, Rogers AI. Intestinal strongyloidiasis: recognition, management, and determinants of outcome. J Clin Gastroenterol 2005;39:203–11. [2]. Grove DI. Strongyloidiasis: a conundrum for gastroenterologists. Gut 1994;35:437–40. [3]. Siddiqui AA, Berk SL. Diagnosis of Strongyloides stercoralis infection. Clin Infect Dis 2001;33:1040–7. [4]. Sanchez PR, Guzman AP, Guillen SM, Adell RI, Estruch AM, Gonzalo IN, et al. Endemic strongyloidiasis on the Spanish Mediterranean coast. QJM 2001;94:357–63.
[5]. Nuesch R, Zimmerli L, Stockli R, Gyr N, Christoph Hatz FR. Imported strongyloidosis: a longitudinal analysis of 31 cases. J Travel Med 2005;12:80–4. [6]. Gill GV, Welch E, Bailey JW, Bell DR, Beeching NJ. Chronic Strongyloides stercoralis infection in former British Far East prisoners of war. QJM 2004;97:789–95. [7]. Keiser PB, Nutman TB. Strongyloides stercoralis in the Immunocompromised Population. Clin Microbiol Rev 2004;17:208–17. [8]. Olsen A, van LL, Marti H, Polderman T, Polman K, Steinmann P, et al. Strongyloidiasis–the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 2009;103:967–72. [9]. Loutfy MR, Wilson M, Keystone JS, Kain KC. Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a nonendemic area. Am J Trop Med Hyg 2002;66:749–52. [10]. Sudarshi S, Stumpfle R, Armstrong M, Ellman T, Parton S, Krishnan P, et al. Clinical presentation and diagnostic sensitivity of laboratory tests for Strongyloides stercoralis in travellers compared with immigrants in a non-endemic country. Trop Med Int Health 2003;8: 728–32. [11]. Agrawal V, Agarwal T, Ghoshal UC. Intestinal strongyloidiasis: a diagnosis frequently missed in the tropics. Trans R Soc Trop Med Hyg 2009;103:242–6. [12]. Carvalho EM, Da Fonseca PA. Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis. Parasite Immunol 2004;26:487–97. [13]. Sato Y, Kobayashi J, Toma H, Shiroma Y. Efficacy of stool examination for detection of Strongyloides infection. Am J Trop Med Hyg 1995;53:248–50.
Contents lists available at ScienceDirect
Transactions of the Royal Society of Tropical Medicine and Hygiene journal homepage: http://www.elsevier.com/locate/trstmh
Clinical and epidemiological features of 33 imported Strongyloides stercoralis infections夽 ˜ a , Laura Puyol a , Ana González a,∗ , Marina Gallo b , M. Eugenia Valls c , Jose Munoz a c a M. Jesús Pinazo , Jordi Mas , Joaquim Gascon a b c
Barcelona Centre for International Health Research (CRESIB), CIBERESP, Hospital Clínic, c/Rosselló 132, 4◦ , 08036 Barcelona, Spain Internal Medicine Department, Hospital Universitario Reína Sofía, Avda. Menéndez Pidal s/n, Córdoba, Spain Parasitology Unit, Microbiology Department, Hospital Clínic, c/Villarroel 170, 08036 Barcelona, Spain
a r t i c l e
i n f o
Article history: Received 12 November 2009 Received in revised form 4 June 2010 Accepted 4 June 2010 Available online 16 July 2010 Keywords: Strongyloidiasis Strongyloides stercoralis hyperinfection syndrome immunocompromised host immigrant traveller
a b s t r a c t Strongyloides stercoralis has a unique ability to replicate in the human host and lead to chronic infection that can persist for several decades. Thirty-three patients (10 travellers and 23 immigrants) with imported S. stercoralis infection were studied and clinical and epidemiological characteristics described. Only 16 patients (48.5%) reported symptoms, mainly of the gastrointestinal tract. Eosinophilia was present in 21 (63.6%) patients. Seven patients (21.2%) had an immunocompromising condition. Patients were classified into chronic asymptomatic infection (17/33, 51.5%), chronic symptomatic infection (11/33, 33.3%) and hyperinfection (5/33, 15.2%). Four of the latter (80%) had an immunocompromising condition. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. Diagnosis should always be sought in immunocompromised hosts. © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
1. Introduction Around 30 to 100 million people are estimated to be infected with the intestinal nematode Strongyloides stercoralis in endemic areas of Central and South America, sub-Saharan Africa, South and Southeast Asia.1–3 Some endemic foci have also been described in industrialized countries.4,5 In Spain, several cases have been reported, mainly from the 1990s in the Valencia region, but they seem to account for former exposures in farmers and rice field workers.4 Currently, S. stercoralis infections are mainly seen in travellers or immigrants from endemic regions.
夽 Presented in part: 6th Congress of the Tropical Medicine and International Health Spanish Society, 5–7 March 2008, Segovia, Spain. ∗ Corresponding author. Tel.: +34 93 2275706; fax: +34 93 3379853. E-mail address: [email protected] (A. González).
Strongyloides stercoralis is of note due to its ability to replicate in the human host (autoinfection) and lead to chronic infection that can persist for several decades.1,2,6 Acute infection is rarely diagnosed. Chronic strongyloidiasis presents with mild or absent clinical manifestations. Hyperinfection denotes a high parasite burden in the organs usually affected due to acceleration of the autoinfection cycle. Severe gastrointestinal and pulmonary symptoms are common and larvae are usually easily identified in stools. Disseminated disease refers to systemic spread of larvae outside their usual migration pattern with possible invasion of virtually every organ. Larvae can be identified in samples from any of the affected organs. Hyperinfections or disseminated infections, are more frequent in immunocompromised hosts, and may carry a high mortality rate of up to 75%. No clear cut-off between these syndromes exists and it is sometimes difficult to classify a patient in the absence of definite criteria.1,3,7,8
0035-9203/$ – see front matter © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.trstmh.2010.06.001
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A. González et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 613–616
The aim of this study was to describe the clinical and epidemiological characteristics of imported strongyloidiasis in a non endemic area and highlight the risk factors, as well as the importance of early diagnosis and treatment in this potentially fatal infection. 2. Methods 2.1. Patients A retrospective descriptive study was conducted of adult cases diagnosed with S. stercoralis infection who attended Hospital Clinic, University of Barcelona, from July 2004 to July 2007. Patients with positive parasite samples for S. stercoralis were identified through the Microbiology Department database. The stool samples were examined by light microscopy using the merthiolate iodine formaldehyde (MIF) concentration method. The clinical charts of the patients identified were reviewed. Clinical and epidemiologic data were collected using a standardized data form and included: age, sex, country of origin, country of residence and years of residence (if immigrants), travel history (if travellers), clinical manifestations, risk factors, eosinophil count, number of stool samples, treatment and outcome. Patients were classified into groups (acute infection, chronic asymptomatic infection, chronic symptomatic infection, hyperinfection and disseminated infection) according to the clinical manifestations as described in the Introduction section. 2.2. Statistical analysis All data were introduced into a database and analyzed with SPSS software program (version 12; SPSS Inc., Chicago, IL, USA). Comparisons were made using the Fisher exact test for categorical data and the U of Mann-Whitney for continuous data, as appropriate. A P value of <0.05 was considered as statistically significant. 3. Results Thirty-three patients were diagnosed with S. stercoralis infection during the three-year study period. Patient characteristics are shown in Table 1. Most patients attended the Tropical Medicine (23/33, 69.7%) or Infectious Diseases Departments (4/33, 12.1%), but some attended different departments: Haematology (3/33, 9.1%), Digestive Diseases (2/33, 6.1%) and Cardiology (1/33, 3%). Sixteen patients reported symptoms, mainly of the gastrointestinal tract. Detailed symptoms and clinical classification are described in Table 1. Seven patients (21.2%) had one or more immunocompromised conditions. One patient with HIV infection was also diagnosed with Kaposi sarcoma. Human T-lymphotropic virus type 1 (HTLV-1) infection was tested for and negative in six patients. Five patients were considered to have a hyperinfection syndrome due to prominent clinical manifestations of the gastrointestinal tract and/or pulmonary involvement and a high number of S. stercoralis larvae found in stool samples. None presented with acute or disseminated infection. Of
Table 1 Patient characteristics (n = 33) Median age, years (IQR) Male (%) Female (%) Group and region visited/of origin, n (%) Travelers:a visited region Sub-Saharan Africab Southeast Asiac North Africad East Europee Immigrants: region of origin South Americaf Sub-Saharan Africag Indian subcontinenth Median time of residence in Spain (if immigrant), years, IQR Reason for diagnostic work-up, n (%) Eosinophiliai Gastrointestinal symptoms Asymptomatic screening Microcytic anaemiai Symptomatic patients, n (%) and type of symptoms: Gastrointestinal symptoms Epigastric pain Other abdominal pain Diarrhoea Nausea and/or vomiting Constipation Dyspepsia Abdominal bloating Pulmonary symptoms (cough and/or dyspnea) Cutaneous symptoms (pruritus) General symptomsj Eosinophilia (>500 eosinophils/mm3 ), n (%) Median eosinophil count (IQR) Median eosinophil count (IQR) if eosinophilia (n = 21) Immunocompromised, n (%) Corticosteroid treatment HIV infection (22 tested) (% of tested) Haematological malignancies Malnutrition Alcoholism Clinical group Chronic asymptomatic infection Chronic symptomatic infection Hyperinfection
35 (29.5–42) 18 (54.5) 15 (45.5) 10 (30.3) 4 (40.0) 3 (30.0) 2 (20.0) 1 (10.0) 23 (69.7) 16 (69.6) 6 (26.1) 1 (4.3) 4 (1.4–6.6)
16 (48.5) 12 (36.4) 4 (12.1) 1 (3.0) 16 (48.5) 15 (93.7) 7 (43.8) 6 (37.5) 7 (43.8) 3 (18.8) 2 (12.5) 1 (6.3) 1 (6.3) 2 (12.5) 1 (6.3) 5 (31.2) 21 (63.6) 990 (235–1865) 1630 (1005–2140) 7 (21.2) 4 (12.1) 3 (13.6) 3 (13.6) 2 (6.1) 1 (3.0) 17 (51.5) 11 (33.3) 5 (15.2)
IQR = Interquartile Range; HIV = Human Immunodeficiency Virus a Origin: Spain (9), Belgium (1) b Equatorial Guinea (1), Tanzania-Kenya (1), Angola (1), Mali (1); c Thailand (2), Thailand-Cambodia-Lao PDR-Indonesia-Malaysia (1); d Egypt (1), Algeria (1); e Kazakhstan (1); f Bolivia (5), Ecuador (4), Colombia (4), Argentina (1), Peru (1), Brazil (1); g Equatorial Guinea (3), Ghana (1), Cameroon (1), Gambia (1); h Pakistan i Three of the patients studied for eosinophilia and the patient with microcytic anaemia also referred with gastrointestinal symptoms. j Asthenia alone (3 patients), asthenia and anorexia (1), asthenia, anorexia and weight loss (1).
the five patients with hyperinfection, only two presented with eosinophilia (1340 and 5140 eosinophils/mm3 ). The clinical characteristics were compared between immigrants and travellers. There were no significant differences in age, sex, symptoms, or eosinophilia. All five patients in the hyperinfection group were immi-
A. González et al. / Transactions of the Royal Society of Tropical Medicine and Hygiene 104 (2010) 613–616
grants, although this difference did not achieve statistical significance (P = 0.291). In addition, although all seven immunocompromised patients were immigrants, this difference only bordered statistical significance (P = 0.073). Differences between patients with hyperinfection and patients with chronic infection were also assessed. All five hyperinfection patients (100%) were symptomatic compared with only 11/28 (39.3%) of the chronic infection group (P = 0.018). Both immunocompromised status in general and corticosteroid treatment were significantly more frequent in the hyperinfection group. Four out of five patients (80.0%) in the hyperinfection group were immunocompromised compared with 3/28 (10.7%) in the chronic infection group (P = 0.004), and 3/5 (60%) versus 1/28 (3.6%), respectively were receiving corticosteroid treatment (P = 0.007). No differences were found in median age, sex or presence of eosinophilia. All 33 patients had S. stercoralis larvae detected in stool samples by the MIF method. Each patient had delivered a diverse number of stool samples to the Microbiology Department with a median of 3 samples per patient (range 1–6). Strongyloides stercoralis larvae were detected in 49 of the 81 (60.5%) stool samples provided by patients; each patient had at least one positive sample. Additionally, in one patient, S. stercoralis was isolated from a gut biopsy made in the context of pyloric stenosis secondary to the nematode infection. At the time of the study serologic diagnosis was not readily available at our centre, therefore an ELISA test (Microwell ELISA kit, DRG International Inc., USA) was additionally available in only two patients. One tested negative and the other was low positive. Other intestinal parasites were found in four patients: Trichuris trichiura, Hymenolepis nana, Entamoeba histolytica-dispar, A. duodenale/Necator americanus (1 each). Two patients were lost to follow-up before treatment could be prescribed. Twenty-five (75.7%) patients were treated with 200 mcg of ivermectin per kg of body weight: three patients received a single oral dose, 20 (60.6%) patients received two doses on different days and two (6.1%) patients with hyperinfection received ivermectin for 4 and 14 days respectively. Four (12.1%) patients were treated with 400 mg of albendazol bid for 3 days. Two (6.1%) patients with hyperinfection were treated with both albendazol (400 mg bid for 3 days) and ivermectin (200 mcg per kg of body weight) on days 4 and 12. Twentythree (69.7%) patients were considered cured based on the disappearance of symptoms (12 patients) or eosinophilia (11 patients); of these 14 patients had one stool sample tested and found to be negative after treatment. Cured patients were homogeneously distributed between immigrants (16/23 patients, 69.6%) and travellers (7/10 patients, 70%). Two patients died but their death was not related to S. stercoralis infection. The outcome could not be assessed in the remaining patients who were lost to follow-up. 4. Discussion Immigrants account for most patients in studies of imported strongyloidiasis, consistent with our results.5,9 Most of the immigrants had been living in Spain for many years, reflecting the potential of S. stercoralis for causing
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persistent infection. As in our study, chronic infections with S. stercoralis can be silent in more than 50% of infected patients. As expected, gastrointestinal complaints were the most common in symptomatic patients.1,5 On the contrary, none of the patients studied presented with the pathognomonic larva currens eruption and pulmonary symptoms were uncommon. We did not find differences in symptoms between travellers and immigrants as reported in other studies.5,10 Eosinophilia is an inconstant finding in S. stercoralis infection and may fluctuate with different degrees, and it is often absent in immunocompromised hosts and/or those with severe disease, consistent with our results.6,11 Impaired cellular immunity is a known risk factor for severe strongyloidiasis and 80% of hyperinfection patients in our series were immunocompromised. As in our study, corticosteroid therapy appeared to be the most strongly associated with severe disease.1,7 Although, a limited number of cases of HIV infection and S. stercoralis infection have been reported, it seems that strongyloidiasis is not an important opportunistic infection.7 In contrast, it appears to be a relevant opportunistic infection in patients with HTLV-1 infection.1,7,12 Strongyloidiasis diagnosis is often difficult since no gold standard procedure has been established. Definitive diagnosis is usually made by detection of larvae in stools. However, a single stool examination fails to detect larvae in up to 70% of cases. Repeated examinations of stool samples improve the sensitivity up to 50% and 90% with three and seven serial stool samples respectively.3,13 In our study, all patients had S. stercoralis detected in stool samples. The broad range of samples processed for each patient prevents from drawing further conclusions. Several serodiagnostic tests have been developed with a different sensitivity and specificity. They show crossreactivity with other helminth infections, are only available at specialized centres, and may remain positive a long time after infection cure; their role remains to be defined.3,8 Most patients in the study were treated with ivermectin. Compared with albendazole, ivermectin has shown better response rates and it is the current preferred treatment.5,7 As the immigrant population and international travel continue to increase imported tropical diseases will become more frequent in developed countries. Early diagnosis and treatment of S. stercoralis infection can prevent fatal outcomes. Strongyloides stercoralis infection should be considered in immigrants and travellers with eosinophilia or compatible symptoms coming from endemic areas. This diagnosis should be considered even in the absence of symptoms and/or eosinophilia in immunocompromised hosts or patients likely to receive corticosteroids or other immunosuppressive therapy. Authors’ contributions: AG, MG, MEV and JG designed the study protocol; MEV, LP and JMa carried out the microbiological studies and the identification of cases; AG, MG and MJP carried out the collection of clinical and epidemiological data; MEV, LP and JMa carried out the collection of microbiological data; AG, JMu, LP, MJP and JMa carried out the analysis and interpretation of data; AG, MG, MEV, LP and MJP drafted the manuscript. AG, JMu, JMa and JG
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revised the manuscript for intellectual content. All authors read and approved the final manuscript. AG and JG are guarantors of the paper Acknowledgements: The authors thank Donna Pringle for suggestions and English language review of the manuscript. Funding: None. Conflicts of interest: None declared. Ethical approval: Not required. References [1]. Concha R, Harrington Jr W, Rogers AI. Intestinal strongyloidiasis: recognition, management, and determinants of outcome. J Clin Gastroenterol 2005;39:203–11. [2]. Grove DI. Strongyloidiasis: a conundrum for gastroenterologists. Gut 1994;35:437–40. [3]. Siddiqui AA, Berk SL. Diagnosis of Strongyloides stercoralis infection. Clin Infect Dis 2001;33:1040–7. [4]. Sanchez PR, Guzman AP, Guillen SM, Adell RI, Estruch AM, Gonzalo IN, et al. Endemic strongyloidiasis on the Spanish Mediterranean coast. QJM 2001;94:357–63.
[5]. Nuesch R, Zimmerli L, Stockli R, Gyr N, Christoph Hatz FR. Imported strongyloidosis: a longitudinal analysis of 31 cases. J Travel Med 2005;12:80–4. [6]. Gill GV, Welch E, Bailey JW, Bell DR, Beeching NJ. Chronic Strongyloides stercoralis infection in former British Far East prisoners of war. QJM 2004;97:789–95. [7]. Keiser PB, Nutman TB. Strongyloides stercoralis in the Immunocompromised Population. Clin Microbiol Rev 2004;17:208–17. [8]. Olsen A, van LL, Marti H, Polderman T, Polman K, Steinmann P, et al. Strongyloidiasis–the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 2009;103:967–72. [9]. Loutfy MR, Wilson M, Keystone JS, Kain KC. Serology and eosinophil count in the diagnosis and management of strongyloidiasis in a nonendemic area. Am J Trop Med Hyg 2002;66:749–52. [10]. Sudarshi S, Stumpfle R, Armstrong M, Ellman T, Parton S, Krishnan P, et al. Clinical presentation and diagnostic sensitivity of laboratory tests for Strongyloides stercoralis in travellers compared with immigrants in a non-endemic country. Trop Med Int Health 2003;8: 728–32. [11]. Agrawal V, Agarwal T, Ghoshal UC. Intestinal strongyloidiasis: a diagnosis frequently missed in the tropics. Trans R Soc Trop Med Hyg 2009;103:242–6. [12]. Carvalho EM, Da Fonseca PA. Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis. Parasite Immunol 2004;26:487–97. [13]. Sato Y, Kobayashi J, Toma H, Shiroma Y. Efficacy of stool examination for detection of Strongyloides infection. Am J Trop Med Hyg 1995;53:248–50.