今日の臨床サポート

糞線虫症

著者: 椎木創一 沖縄県立中部病院 感染症内科

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2022/06/08
患者向け説明資料

概要・推奨   

  1. 糞線虫の検出には寒天平板培養法が有用であり、繰り返し行うことで感度を上げる(推奨度2)
  1. 糞線虫症は世界各地で報告されている。日本では特に沖縄、奄美で検出例が多い(推奨度2)
  1. 播種性糞線虫症は敗血症、髄膜炎、肺炎、そしてイレウスを引き起こす。糞便以外に喀痰などから虫体を認めることが指標になる(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
椎木創一 : 未申告[2022年]
監修:具芳明 : 特に申告事項無し[2022年]

改訂のポイント:
  1. 定期レビューを行い、加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 糞線虫症はStrongyloides stercoralisという線虫が引き起こす感染症である。
  1. 世界中で3000万から一億人が感染していると推測される[1]
  1. 日本では沖縄、奄美などに限定されるが、世界的にみれば東南アジアを中心に流行が持続しており、渡航後の帰国者が日本各地で発症する可能性は十分にある。
 
 
  1. 土との接触で感染する(Soil-transmitted helminths)。人の便で汚染された土壌を裸足で歩くことで感染する。
  1. 自家感染(autoinfection)という特徴があり糞口感染した後、数十年感染が持続することがある。世代交代を行いながら継続的に宿主内にとどまり、免疫不全などにより過剰感染(hyperinfection)になる。
  1. 沖縄、奄美での症例は減少してきているが、高齢者、農家に散見される。
 
糞線虫の生活環

糞線虫の特徴的な生活環を示している(青線:人体内、赤線:外界)。糞線虫は人体内で消化管(主に十二指腸)にて成虫となり、雌成虫単体で排卵する。消化管を下りながらラブジチス型幼虫へと孵化するが、一部がフィラリア型幼虫となり「自家感染(autoinfection)」を起こす。糞便とともに外界に出た幼虫は、土壌内で発育して雌雄成虫となり交尾、産卵して孵化した幼虫はフィラリア型になる。これが経皮的に感染して体内へと移行し、静脈系から右心室、肺を介して一部が肺胞から気管を上行して喉頭、咽頭に達し、嚥下されて食道、そして十二指腸に至る。

出典

img1:  編集部作成
 
 
 
  1. 糞線虫症は、症状は全くないことも多いが、軟便や便秘、腹部膨満などを訴える場合もある。
  1. 過剰感染からグラム陰性桿菌(大腸菌、クレブシエラ)などによる敗血症や髄膜炎、肺炎、イレウスなどを伴う播種性糞線虫症(Disseminated strongyloidiasis)という重篤な病態を引き起こす。
  1. 免疫不全状態(ステロイド・免疫抑制薬の使用、HIV感染症、慢性肺疾患、慢性腎不全、アルコール多飲など)が重症化のリスクとなる。
  1. 治療にはイベルメクチンを使用するが、播種性糞線虫症であれば同時にグラム陰性桿菌を中心とした細菌をカバーする抗菌薬も必要になる。
 
  1. 糞線虫症は世界各地で報告されている。日本では特に沖縄、奄美で検出例が多い(推奨度2O)(参考文献:[2][3]
  1. 糞線虫症は主にStrongyloides stercoralisが引き起こす(アフリカではS. fuelleborniの報告もある)。世界各地から報告があり、感染者の推計は300万~1億人と幅がある。主に東南アジア、ラテンアメリカ、サハラ以南アフリカ、米国の東南部の一部に流行がある。日本では主に沖縄、奄美からの報告が多いが、南九州地方からも報告がある。
 
  1. 播種性糞線虫症は敗血症、髄膜炎、肺炎、そしてイレウスを引き起こす。糞便以外に喀痰などから虫体を認めることが指標になる(推奨度1O)(参考文献:[4][5][6][7][8][9][10]
  1. 糞線虫は腸管内に存在するだけであれば無症候のことが多い。しかし宿主に免疫不全があると通常のライフサイクルが加速され、自家感染する虫体量が増加して過剰感染(hyperinfection)の状態になる。そのため腸管からグラム陰性桿菌などの誘導を招き、敗血症や肺炎、髄膜炎を引き起こし、イレウス像を呈することもある。これが播種性糞線虫症の病態であり、適切な治療を行っても致死的な状態になり得る重篤な状態である。この場合、便以外にも喀痰、尿、腹水、皮疹などから虫体を検出することができる。各病態が合併して生じるため「不明熱」の状態を呈することもあるが、流行地での居住歴や渡航歴がある場合、また免疫不全状態にある場合には積極的に本疾患を疑い、速やかに対処する必要がある。しかし注意深く症例をみていると、明らかに髄液検査所見では「細菌性髄膜炎」を疑うが、髄液培養検査で細菌は検出されず、その一方で糞便からは糞線虫を認める場合があることを喜舎場[3]は指摘している。
問診・診察のポイント  
問診のポイント:
  1. 流行地域での居住歴や渡航歴を確認する。

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文献 

A A Siddiqui, S L Berk
Diagnosis of Strongyloides stercoralis infection.
Clin Infect Dis. 2001 Oct 1;33(7):1040-7. doi: 10.1086/322707. Epub 2001 Sep 5.
Abstract/Text Strongyloides stercoralis infects 30 million people in 70 countries. Infection usually results in asymptomatic chronic disease of the gut, which can remain undetected for decades. However, in patients receiving long-term corticosteroid therapy, hyperinfection can occur, resulting in high mortality rates (up to 87%). Strongyloidiasis is difficult to diagnose because the parasite load is low and the larval output is irregular. Results of a single stool examination by use of conventional techniques fail to detect larvae in up to 70% of cases. Several immunodiagnostic assays have been found ineffective in detecting disseminated infections and show extensive cross-reactivity with hookworms, filariae, and schistosomes. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. This review describes the clinical manifestations of strongyloidiasis, as well as various diagnostic tests and treatment strategies.

PMID 11528578
E B Scowden, W Schaffner, W J Stone
Overwhelming strongyloidiasis: an unappreciated opportunistic infection.
Medicine (Baltimore). 1978 Nov;57(6):527-44.
Abstract/Text Strongyloides stercoralis is an intestinal nematode which infects a large portion of the world's population. Individuals with infection confined to the intestinal tract are often asymptomatic but may have abdominal pain, weight loss, diarrhea, and other nonspecific complaints. Enhanced proliferation of the parasite in compromised hosts causes an augmentation of the normal life-cycle. Resultant massive invasion of the gastrointestinal tract and lungs is termed the hyperinfection syndrome. If the worm burden is excessive, parasitic invasion of other tissues occurs and is termed disseminated strongyloidiasis. A variety of underlying conditions appear to predispose to severe infections. These are primarily diseases characterized by immunodeficiency due to defective T-lymphocyte function (Table 1). Individuals with less severe disorders become compromised hosts because of therapeutic regimens consisting of corticosteroids or other immunosuppressive medication. The debilitation of chronic illness or malnutrition also predisposes to systemic stronglyloidiasis. The diagnosis of strongyloidiasis can be readily made by microscopic examination of concentrates of upper small bowel fluid, stool, or sputum. Important clues suggesting this infection include unexplained gram-negative bacillary bacteremia in a compromised host who may have vague abdominal complaints, an ileus pattern on X-ray, and pulmonary infiltrates. Eosinophilia is helpful, if present, but should not be relied upon to exclude the diagnosis. The treatment of systemic infection due to Strongyloides stercoralis with either thiabensazole 25 mg/kg orally twice daily is satisfactory if the diagnosis is made early. Because of several unusual features of this illness in compromised hosts, the standard recommendation for 2 days of therapy should be abandoned in such patients. Immunodeficiency, corticosteroids, and bowel ileus reduce drug efficacy. Thus a longer treatment period of at leuch as blind loops or diverticula necessitate longer treatment. Stool specimens and upper small bowel aspirates should be monitored regularly and treatment continued several days beyond the last evidence of the parasite. In particularly difficult situations where either worm eradication is impossible or reinfection is probable, short monthly courses of antihelminthic therapy seem to be effective in averting recurrent systemic illness. Finally, prevention of hyperinfection or dissemination due to Strongyloides stercoralis can be accomplished by screening immunocompromised hosts with stool and upper small bowel aspirate examinations. These would be especially important prior to initiating chemotherapy, or before giving immunosuppressive medications or corticosteroids to patients with nonneoplastic conditions such as systemic lupus erythematosus, nephrotic syndrome, or renal allografts.

PMID 362122
Ashley M Newberry, David N Williams, William M Stauffer, David R Boulware, Brett R Hendel-Paterson, Patricia F Walker
Strongyloides hyperinfection presenting as acute respiratory failure and gram-negative sepsis.
Chest. 2005 Nov;128(5):3681-4. doi: 10.1378/chest.128.5.3681.
Abstract/Text STUDY OBJECTIVES: Disseminated strongyloides is a rarely reported phenomenon and occurs in immunosuppressed patients with chronic Strongyloides stercoralis infection. Typically, patients present with pulmonary symptoms but subsequently acquire Gram-negative sepsis. Several cases have been noted in Minnesota, and their presentation, diagnostic evaluation, and clinical outcomes were reviewed.
DESIGN: A retrospective chart review was conducted of complicated strongyloides infections from 1993 to 2002 in Minneapolis and St. Paul, MN. Cases were identified by reviewing hospital microbiology databases.
SETTING: Metropolitan hospitals with large immigrant populations.
RESULTS: Nine patients, all of Southeast Asian heritage, were identified. Eight patients immigrated to the United States > or = 3 years prior to acute presentation. All patients were receiving antecedent corticosteroids; in five patients, therapy was for presumed asthma. Absolute eosinophil counts > 500/microL occurred in only two patients prior to steroid initiation. Eight patients presented with respiratory distress, and Gram-negative sepsis developed in four patients. Four patients had evidence of right-heart strain on ECG or echocardiography at the time of presentation. Three patients died; all had eosinophil counts of < 400/microL.
CONCLUSIONS: Serious complications, including death, may occur in patients with chronic strongyloides infection treated with corticosteroids. Strongyloides hyperinfection usually presents as acute respiratory failure and may initially mimic an asthma exacerbation or pulmonary embolism. Southeast Asian patients presenting with new-onset "asthma," acute respiratory distress, and/or Gram-negative sepsis should undergo evaluation to exclude strongyloides infection.

PMID 16304332
R A Harris, D M Musher, V Fainstein, E J Young, J Clarridge
Disseminated strongyloidiasis. Diagnosis made by sputum examination.
JAMA. 1980 Jul 4;244(1):65-6.
Abstract/Text Two immune-compromised patients had pulmonary and intestinal infection due to Strongyloides stercoralis. Diagnosis was facilitated in both cases when the parasites were found in the sputum. Treatment with thiabendazole appeared to eradicate the infection, but repeated follow-up examinations are needed because of the likelihood of relapse.

PMID 7382060
Shun Namisato, Kazuhisa Motomura, Shusaku Haranaga, Tetsuo Hirata, Masato Toyama, Takashi Shinzato, Futoshi Higa, Atsushi Saito
Pulmonary strongyloidiasis in a patient receiving prednisolone therapy.
Intern Med. 2004 Aug;43(8):731-6.
Abstract/Text Strongyloidiasis is widely distributed in tropical and subtropical areas. Disseminated strongyloidiasis may develop in patients with immunodeficiencies. In the absence of early diagnosis and treatment, the prognosis of disseminated strongyloidiasis is extremely poor. We report a case of pulmonary strongyloidiasis that was successfully treated. The patient was an 83-year-old woman who had been receiving long-term oral prednisolone therapy for uveitis. The patient visited our emergency department complaining of breathing difficulties and diarrhea. A chest X-ray revealed a diffuse enhancement of interstitial shadows. A bronchoalveolar lavage (BAL) was performed, and both Gram staining and Grocott's staining revealed the presence of multiple filariform larvae of Strongyloides stercoralis in the bronchoalveolar lavage fluid (BALF). A stool examination performed at the same time also yielded S. stercoralis. The patient was diagnosed as having pulmonary strongyloidiasis and was treated with thiabendazole and ivermectin, in addition to antimicrobial agents; her respiratory symptoms and diarrhea improved, and S. stercoralis was not detected in subsequent follow-up examinations thereafter. In endemic areas of S. stercoralis, pulmonary strongyloidiasis should be considered as part of a differential diagnosis if chest imaging findings like alveolar and interstitial shadow patterns or lobar pneumonia are seen in patients with immunodeficiencies.

PMID 15468976
J H Woodring, H Halfhill, J C Reed
Pulmonary strongyloidiasis: clinical and imaging features.
AJR Am J Roentgenol. 1994 Mar;162(3):537-42. doi: 10.2214/ajr.162.3.8109492.
Abstract/Text Strongyloides stercoralis is an important cause of severe pulmonary infection and death in many areas of the world [1, 2]. The nematode is endemic in the tropical and subtropical regions of the world, including the southeastern United States and Puerto Rico, where infection rates may exceed 6% of the population [1, 3-7]. Although pulmonary symptoms from strongyloidiasis can be mild, consisting only of cough and bronchospasm, the potential for severe pulmonary disease and adult respiratory distress syndrome is great in certain persons at high risk for strongyloidiasis [1, 2]. Unfortunately, pulmonary strongyloidiasis is seldom diagnosed until late in the course of the disease, which contributes to a high death rate [1, 2, 5, 8]. We review the clinical and imaging features of pulmonary strongyloidiasis and emphasize clues that can lead to earlier diagnosis, recognition of complications, and prompt treatment.

PMID 8109492
Y Igra-Siegman, R Kapila, P Sen, Z C Kaminski, D B Louria
Syndrome of hyperinfection with Strongyloides stercoralis.
Rev Infect Dis. 1981 May-Jun;3(3):397-407.
Abstract/Text Two patients hyperinfected with Strongyloides stercoralis (an intestinal nematode) are described. Both were both in Puerto Rico and had left the island six to 15 years previously; both were receiving adrenal steroids (one for Hodgkin's disease and the other for Goodpasture's syndrome). One died shortly after diagnosis, but the other survived the hyperinfection syndrome and complicating bacterial sepsis and meningitis. In addition to our case reports, 103 previously described cases of presumed strongyloides hyperinfection are reviewed. Among 89 patients immunocompromised by therapy or disease, the mortality rate was 86%; bacterial sepsis often contributed to the fatal outcome. In most cases, infection was acquired in an endemic area, sometimes long before the hyperinfection syndrome occurred. The few patients who had never been to an endemic area had a history of prolonged contact with highly soiled material, an observation suggesting cross infection from a contaminated person. When administered in time, thiabendazole, the drug of choice for strongyloidiasis, was effective in 70% of cases. If intestinal infection with S. stercoralis is detected and treated before immunosuppressive therapy is initiated and if a high index of suspicion for the hyperinfection syndrome is maintained while immunosuppressive therapy is given, the mortality from this disease should decrease.

PMID 7025145
A Belani, D Leptrone, J W Shands
Strongyloides meningitis.
South Med J. 1987 Jul;80(7):916-8.
Abstract/Text Acute pyogenic meningitis occurred in a 46-year-old woman receiving long-term steroid therapy. Cultures for bacteria and fungi were negative, and the meningitis failed to respond to broad spectrum antibiotics. Abundant Strongyloides stercoralis larvae were found in the patient's feces a sputum, and a filariform larva was found in a hanging drop preparation from centrifuged cerebrospinal fluid. Therapy with thiabendazole eradicated the Strongyloides from feces and sputum. The abnormal CSF values returned toward normal, and the patient has had no recurrence of illness.

PMID 3603116
O Patey, A Gessain, J Breuil, A Courillon-Mallet, M T Daniel, J M Miclea, A M Roucayrol, F Sigaux, C Lafaix
Seven years of recurrent severe strongyloidiasis in an HTLV-I-infected man who developed adult T-cell leukaemia.
AIDS. 1992 Jun;6(6):575-9.
Abstract/Text OBJECTIVE: Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is endemic in Japan, the Caribbean basin and Africa, where it has been aetiologically linked to certain chronic myelopathies and adult T-cell leukamia (ATL). We sought to investigate whether strongyloidiasis, a parasitic disease common in these areas, might be a cofactor in the pathogenesis of ATL, as some reports have suggested.
PATIENTS, PARTICIPANTS: One 35-year-old HTLV-I-seropositive French West Indian man with a 7-year history of recurrent strongyloidiasis associated with episodic hyperinfestation presenting at the Centre Hospitalier Intercommunal, Villeneuve St Georges, France.
INTERVENTIONS: Treatment with various chemotherapeutic agents and symptomatic therapy for hypercalcaemia and antiviral therapy (zidovudine and interferon).
RESULTS: The patient developed ATL and died shortly after, despite chemotherapy. Immunological and virological studies performed during the last 15 months of his life showed an increase of the percentage of peripheral ATL cells, and progression from a polyclonal to a monoclonal integration of HTLV-I proviral DNA in the peripheral blood mononuclear and lymph-node cells.
CONCLUSIONS: Recurrent strongyloidiasis appears to have been a possible cofactor associated with progression from healthy carrier state to ATL in our patient.

PMID 1388880
Mark E Viney, Michael Brown, Nicholas E Omoding, J Wendi Bailey, Michael P Gardner, Emily Roberts, Dilys Morgan, Alison M Elliott, James A G Whitworth
Why does HIV infection not lead to disseminated strongyloidiasis?
J Infect Dis. 2004 Dec 15;190(12):2175-80. doi: 10.1086/425935. Epub 2004 Nov 16.
Abstract/Text We investigated the hypothesis that host immunosuppression due to advancing human immunodeficiency virus (HIV) disease favors the direct development of infective larvae of Strongyloides stercoralis, which may facilitate hyperinfection and, hence, disseminated strongyloidiasis. To do this, we sought correlations between the immune status of the subjects and the development of S. stercoralis infections. Among 35 adults, there were significant negative rank correlations between CD4+ cell counts and the proportions of free-living male and female worms. Thus, in individuals with preserved immune function, direct development of S. stercoralis is favored, whereas, in individuals with lesser immune function, indirect development is relatively more common. These results may explain the notable absence of disseminated strongyloidiasis in advanced HIV disease. Because disseminated infection requires the direct development of infective larvae in the gut, the observed favoring of indirect development in individuals immunosuppressed by advancing HIV disease is not consistent with the promotion of disseminated infection.

PMID 15551217
M R Kramer, P A Gregg, M Goldstein, R Llamas, B P Krieger
Disseminated strongyloidiasis in AIDS and non-AIDS immunocompromised hosts: diagnosis by sputum and bronchoalveolar lavage.
South Med J. 1990 Oct;83(10):1226-9.
Abstract/Text In conclusion, disseminated strongyloidiasis is a fatal disease that commonly affects the lungs. The disease should be suspected in an immunocompromised host who came from an area endemic for S stercoralis even years before the onset of symptoms or in patients with unexplained gram-negative bacteremia or meningitis. Treatment should be started promptly and should be maintained for a long time.

PMID 2218668
Abstract/Text We describe a North American human immunodeficiency virus (HIV)-positive patient with Strongyloides stercoralis infection of the gastrointestinal tract, who required repeated "standard" courses of thiabendazole. Pulmonary infection with numerous roundworms developed, as suspected by bronchoalveolar lavage, and while he was receiving therapy, dissemination occurred. On autopsy, S stercoralis was recovered in the gastrointestinal tract, liver, lung, and heart. After a literature review, we conclude that HIV-positive patients have a higher risk of dissemination and "standard" treatment failure. This may occur without elevation of IgE or eosinophilia. Those patients may require prolonged courses of thiabendazole or alternatively ivermectin therapy.

PMID 8325052
Iliana Neumann, Rhianna Ritter, Anne Mounsey
Strongyloides as a cause of fever of unknown origin.
J Am Board Fam Med. 2012 May-Jun;25(3):390-3. doi: 10.3122/jabfm.2012.03.110101.
Abstract/Text Strongyloides is endemic in parts of the United States. Most often it is asymptomatic but it has a wide range of clinical presentations. Because of the unusual capacity of strongyloides for autoinfection, it can cause hyperinfection, when it effects the pulmonary and gastrointestinal systems, or disseminated infection, when other organs are involved. Both hyperinfection and disseminated strongyloides usually occur in immunosuppressed patients. We report a case of hyperinfection with strongyloides in a man presenting with fever of unknown origin who was not immunosuppressed.

PMID 22570402
Ramnik J Xavier, Manish K Gala, Brian K Bronzo, Paul J Kelly
Case records of the Massachusetts General Hospital. Case 23-2012. A 59-year-old man with abdominal pain and weight loss.
N Engl J Med. 2012 Jul 26;367(4):363-73. doi: 10.1056/NEJMcpc1109275.
Abstract/Text
PMID 22830467
Silvia A Repetto, Pablo A Durán, María B Lasala, Stella M González-Cappa
High rate of strongyloidosis infection, out of endemic area, in patients with eosinophilia and without risk of exogenous reinfections.
Am J Trop Med Hyg. 2010 Jun;82(6):1088-93. doi: 10.4269/ajtmh.2010.09-0332.
Abstract/Text Strongyloides stercoralis chronic infections are usually asymptomatic and underestimated. We used direct fresh stool examination, Ritchie's method, and agar plate culture for diagnosis in patients with eosinophilia and previous residence in endemic areas. The frequency of strongyloidosis detected among these patients was high: 21 of 42 were positive. Among them, 10 were positive only by agar plate culture. After ivermectin treatment, patients resulted negative for parasitological tests and reduced their eosinophil counts. Half of the submitted patients that were followed 4-12 months after treatment remained negative without eosinophilia, except one who showed an eosinophil ascending curve before reappearance of larvae in stools. The high frequency of strongyloidosis found in this group emphasizes the relevance of including this parasitosis among differential diagnosis in patients with eosinophilia and past risk of S. stercoralis infection to prevent disseminated infections secondary to corticoid therapy.

PMID 20519604
P Uparanukraw, S Phongsri, N Morakote
Fluctuations of larval excretion in Strongyloides stercoralis infection.
Am J Trop Med Hyg. 1999 Jun;60(6):967-73.
Abstract/Text Follow-up stool examinations were carried out on two groups of the subjects who were screened negative (group 1) or positive (group 2) for Strongyloides stercoralis by the agar plate culture. This technique could detect S. stercoralis larvae in 87.5-96.4% of the subjects in group 2 and 0-5.9% of the subjects in group 1 on various days of the eight-week and four-week follow-up periods, respectively. The detection rate on each day of examination was not statistically different from that on the first day in both groups. Quantitative measurement of S. stercoralis larvae excreted in the feces of the subjects in group 2 by the standard direct smear method of Beaver and others revealed slight to marked fluctuations of the larval output in individual subjects. From the results of both stool examination methods, it could be implied that 52% of S. stercoralis-infected individuals had low-level infection.

PMID 10403329
K Koga, S Kasuya, C Khamboonruang, K Sukhavat, M Ieda, N Takatsuka, K Kita, H Ohtomo
A modified agar plate method for detection of Strongyloides stercoralis.
Am J Trop Med Hyg. 1991 Oct;45(4):518-21.
Abstract/Text The agar plate method is a new technique with high detection rates for coprological diagnosis of human strongyloidiasis. This report details modifications of the technique and establishes a standardized procedure. We recommend that all plates should be carefully observed using a microscope because macroscopic observation can lead to false negative results. It is also advisable to pour formalin solution directly into microscopically positive dishes to collect worms by sedimentation. This procedure enables one to observe worms otherwise hidden. Sealing dishes with adhesive tape prevents larvae from crawling out of the dishes, eliminating any possibility in the reduction of detection rates, and greatly improves the safety conditions for the technician performing the procedure. We consider the agar plate method to be superior to the filter paper method in detecting Strongyloides, and we believe that it will eventually become the technique of choice.

PMID 1951861
Tetsuo Hirata, Hiroshi Nakamura, Nagisa Kinjo, Akira Hokama, Fukunori Kinjo, Nobuhisa Yamane, Jiro Fujita
Increased detection rate of Strongyloides stercoralis by repeated stool examinations using the agar plate culture method.
Am J Trop Med Hyg. 2007 Oct;77(4):683-4.
Abstract/Text To clarify the efficacy of repeated stool examinations by the agar plate culture method for the detection of Strongyloides stercoralis infection, 4,071 stool samples collected from 2,406 patients > 50 years of age in Ryukyu University Hospital were examined. The cumulative detection rate of S. stercoralis infection was 4.7% (112/2,406). At the first, second, third, and beyond fourth examinations, the detection rates were 3.6% (86/2,406), 1.5% (12/786), 2.6% (10/392), and 2.0% (4/198), respectively. From these results, the cumulative detection rate was estimated to be 7.4% when three stool samples were examined for all patients. Our study showed that repeated stool examinations increase the sensitivity of detection of S. stercoralis infection.

PMID 17978071
Yupin Suputtamongkol, Nalinee Premasathian, Kid Bhumimuang, Duangdao Waywa, Surasak Nilganuwong, Ekkapun Karuphong, Thanomsak Anekthananon, Darawan Wanachiwanawin, Saowaluk Silpasakorn
Efficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis.
PLoS Negl Trop Dis. 2011 May 10;5(5):e1044. doi: 10.1371/journal.pntd.0001044. Epub 2011 May 10.
Abstract/Text BACKGROUND: Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined.
METHODS: A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up.
RESULTS: Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2-76) weeks in albendazole group, 39 (2-74) weeks in single dose ivermectin group, and 26 (2-74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups.
CONCLUSION/SIGNIFICANCE: This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00765024.

PMID 21572981
K Shikiya, N Kinjo, T Uehara, H Uechi, J Ohshiro, T Arakaki, F Kinjo, A Saito, M Iju, K Kobari
Efficacy of ivermectin against Strongyloides stercoralis in humans.
Intern Med. 1992 Mar;31(3):310-2.
Abstract/Text Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.

PMID 1611180
Rafael Igual-Adell, Carlos Oltra-Alcaraz, Enrique Soler-Company, Pilar Sánchez-Sánchez, Josefa Matogo-Oyana, David Rodríguez-Calabuig
Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis.
Expert Opin Pharmacother. 2004 Dec;5(12):2615-9. doi: 10.1517/14656566.5.12.2615.
Abstract/Text Treatment of strongyloidiasis has been traditionally based on thiabendazole, despite its frequent gastrointestinal side effects and failure to achieve eradication of the parasite from faeces in approximately 30% of cases. Ivermectin has been shown to be more effective for treating chronic uncomplicated strongyloidiasis. The efficacy and tolerability of these drugs in a series of patients treated from 1999 to 2002 at the Oliva Health Centre, Valencia, Spain, are reported. A total of 88 patients diagnosed of strongyloidiasis were treated using the following regimens: thiabendazole 25 mg/kg/12 h for 3 consecutive days in 31 patients; ivermectin 200 mug/kg as a single dose in 22 patients; and ivermectin 200 mug/kg for 2 consecutive days in 35 patients. The efficacy and side effects were recorded. A total of 65 patients were male, and 23 female. The mean age was 64 +/- 12 years. Of the patients, 44 had worked barefoot in rice fields. Among the 31 patients treated with thiabendazole, 25 (78%) met the criteria for cure (the absence of parasite in faeces after examination of three samples collected on alternate days), and 5 (16%) experienced side effects (asthenia, epigastralgia and disorientation). Of the 22 patients treated with ivermectin on a single day, 17 (77%) met the criteria for cure, and 2 (9%) reported side effects (dizziness, dyspepsia). Among the 35 patients treated with ivermectin on 2 consecutive days, 100% met the criteria for cure, and 0% experienced side effects. In chronic uncomplicated strongyloidiasis, a treatment regimen consisting of ivermectin 200 mug/kg for 2 consecutive days provided the best results with regard to efficacy and tolerability. When the eosinophilia continued after treatment, we observed a high percentage of not-cure rate (7 of 9 patients, 77%).

PMID 15571478
Prapaporn Pornsuriyasak, Kannika Niticharoenpong, Atipoom Sakapibunnan
Disseminated strongyloidiasis successfully treated with extended duration ivermectin combined with albendazole: a case report of intractable strongyloidiasis.
Southeast Asian J Trop Med Public Health. 2004 Sep;35(3):531-4.
Abstract/Text We describe a patient with an overlapping syndrome disseminated strongyloidiasis and gram-negative sepsis. She was previously treated with albendazole 400 mg/day 14 days before admission without success. This admission, she was treated with a combination of oral ivermectin (injectable solution form), with a dosage of 200-400 microg/kg/day, and albendazole for 14 days. Strongyloides larvae disappeared from the stool by day 4 and from the sputum by day 10. No side effects were encountered during hospitalization or at the 1-month follow-up visit.

PMID 15689061
J R Torres, R Isturiz, J Murillo, M Guzman, R Contreras
Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.
Clin Infect Dis. 1993 Nov;17(5):900-2.
Abstract/Text Nine adult male homosexuals who were infected with the human immunodeficiency virus (five with AIDS-defining conditions) and harbored Strongyloides stercoralis received ivermectin on a compassionate basis for persistent intestinal infection. Hyperinfection was present in all cases. Ivermectin was given either as a single oral dose (200 micrograms/kg) or on a multidose schedule (200 micrograms/kg.d) on days 1, 2, 15, and 16. All seven patients who received multiple doses showed sustained clinical and parasitological cure, whereas one of two patients who received single-dose therapy relapsed promptly and fatally. Remissions have been maintained for at least 7 months and up to 3 years of follow-up. Ivermectin appears promising in the treatment of strongyloidiasis in patients with AIDS. Because of the risk of hyperinfection and/or disseminated disease, multidose courses are warranted. We are not aware of other reports describing the efficacy of antiparasitic drugs for strongyloidiasis in patients with AIDS.

PMID 8286637
Francisco M Marty, Colleen M Lowry, Martin Rodriguez, Danny A Milner, Walter S Pieciak, Anushua Sinha, Lawrence Fleckenstein, Lindsey R Baden
Treatment of human disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin.
Clin Infect Dis. 2005 Jul 1;41(1):e5-8. doi: 10.1086/430827. Epub 2005 May 11.
Abstract/Text There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

PMID 15937753
Nobuyoshi Takashima, Shogo Yazawa, Akira Ishihara, Sei-ichiro Sugimoto, Kazutaka Shiomi, Kenji Hiromatsu, Masamitsu Nakazato
[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case].
Rinsho Shinkeigaku. 2008 Jan;48(1):30-5.
Abstract/Text We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.

PMID 18386629
K Shikiya, O Zaha, S Niimura, T Uehara, J Ohshiro, F Kinjo, A Saito, R Asato
[Clinical study on ivermectin against 125 strongyloidiasis patients].
Kansenshogaku Zasshi. 1994 Jan;68(1):13-20.
Abstract/Text We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral doses of ivermectin (6 mg) at 2-week interval, and obtained the following results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients), responsively. Out of the total 17 patients were resistant (non-responsive) to treatment, 8 patients received a further course of ivermectin and all Strongyloides stercoralis in their feces were eradicated. 2. Side effects were observed in 7.2% of the patients after the first dose treatment and in 3.2% after the second dose. But all symptoms were mild and self-limited. Although liver disfunction developed in 13.6% of the patients, no symptoms occurred and no special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the resistant group was significantly higher (80.0%) than in the eradicated group (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before treatment in the eradicated group was significantly higher than that of controls, there was no significant difference between the resistant group and controls. IgE levels in the resistant group was significantly lower than in the eradicated group. We would like to conclude that IVM is the best drug for treatment of the patient with Strongyloides stercoralis not only from this results but also our previous reports which had investigated the clinical efficacy on thiabendazole, mebendazole and albendazole.

PMID 8138669
Stephen A Turner, J Dick Maclean, Lawrence Fleckenstein, Christina Greenaway
Parenteral administration of ivermectin in a patient with disseminated strongyloidiasis.
Am J Trop Med Hyg. 2005 Nov;73(5):911-4.
Abstract/Text We report the case of a 23-year-old Caribbean man with disseminated strongyloidiasis (co-infected with human T cell lymphotropic virus I/II)), severe hypoalbuminemia, and a paralytic ileus. Subcutaneous ivermectin (200 microg/kg) was administered daily for 14 days because of the inability to effectively administer oral albendazole and oral ivermectin. Three hours after the third daily dose of oral ivermectin, the serum ivermectin concentration was only 0.8 ng/mL, but it increased several fold to 5.8 ng/mL 16 hours after the first dose of subcutaneous ivermectin. During the course of subcutaneous treatment, ivermectin clearance was higher than expected (46.0 L/hour, normal = 31.8 L/hour). This is likely the result of severe hypoalbuminemia since ivermectin is highly protein bound. The ability to achieve adequate levels of ivermectin after oral administration in patients with disseminated strongyloidiasis may be impaired, highlighting the need for alternative routes of administration of ivermectin in these patients.

PMID 16282302
Edmilson Bastos de Moura, Marcelo de Oliveira Maia, Monalisa Ghazi, Fábio Ferreira Amorim, Henrique Marconi Pinhati
Salvage treatment of disseminated strongyloidiasis in an immunocompromised patient: therapy success with subcutaneous ivermectin.
Braz J Infect Dis. 2012 Sep-Oct;16(5):479-81. doi: 10.1016/j.bjid.2012.08.008. Epub 2012 Sep 10.
Abstract/Text Disseminated strongyloidiasis is a disease with high mortality rate, especially in immunocompromised individuals. Paralytic ileus and intestinal malabsorption are frequent symptoms caused by this severe disease. As there are no licensed parenteral anthelmintic drugs for human use, off-label formulations are often used in the treatment of this disease. In this case report, the use of subcutaneous ivermectin is described as a successful therapy for this life-threatening infection.

Copyright © 2012 Elsevier Editora Ltda. All rights reserved.
PMID 22975175

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