Strongyloidiasis: who should be screened, when to suspect, how to treat?

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Sherman Mitchell
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1 Strongyloidiasis: who should be screened, when to suspect, how to treat? Zeno Bisoffi, Centro Malattie Tropicali, Ospedale S.Cuore - Negrar NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

2 Immigrant from Ghana, 38 years Diagnosis of non Hodgkin lymphoma Starts chemotherapy Sudden onset of septic fever, septic shock Paralytic ileus, ARDS Exitus The cause: disseminated strongyloidiasis, invading the whole body NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

3 Larvae in the gastric juice

4 Eggs and larvae in bronchial fluid

6 Adult female of Strongyloides stercoralis collected in bronchial fluid. Scale bar = 400 μm.

7 Italian from Verona, 80 y Progressively wasting Weight loss (10 Kg) Losing strength Doctor, I think my wife is poisoning me NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

8 Reemergence of Strongyloidiasis, Northern Italy (age >= 65, eosinophil count >=500 cells/μl) we found that 37 (28%) of 132 patients were positive, with titers ranging between 20 and >320 (and >80 in most cases) Abrescia FF, Falda A, Caramaschi G, Scalzini A, Gobbi F, Angheben A, et al. Reemergence of strongyloidiasis, northern Italy [letter]. Emerg Infect Dis [serial on the Internet] 2009 Sep [date cited]. Available from NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

9 A smart host A self-maintaining infection, lifelong. Partenogenic female (no sex we are British ) Scaglia M., Gatti S., Rondanelli EG. PARASSITI E PARASSITOSI UMANE dalla clinica al laboratorio. Selecta Medica Ed. 2005

10 Acute Strongyloidiasis: A Rarity. Chronic Strongyloidiasis: A Time Bomb! Eric Caumes MD 1,2,*, Jay S. Keystone MD 3,4 Volume 18, Issue 2, pages 71 72, March/April ) We must find out people unawares carrying the time bomb 2) Treatment cannot but aim at completely removing the time bomb NB. > 63% of patients reported with severe strongylodiasis died! (Buonfrate et al. for COHEMI, 2012, submitted)

11 Severe strongyloidiasis: 67% patients under steroids Condition N (%) COPD/Asthma/lung fibrosis 30 (18.3) Organ/BM transplant 25 (15.2) Leukemia/lymphoma 13 (7.9) Systemic lupus erythematosus 9 (5.5) Cancer 8 (4.8) IBD 6 (3.6) Glomerulonephritis/CRI 6 (3.6) Multiple myeloma/myelodisplasia reasons for prescription 6 (3.6) (Buonfrate et al. for COHEMI, 2012, submitted)

12 RESULTS One patient diagnosed with idiopathic hypereosinophilic syndrome died after BM transplant Other conditions (no steroids): HTLV 1 HIV Alcoholism Malnutrition

13 Poor clinical clues Asymptomatic eosinophilia should always raise suspicion! But probably, in most cases normal eosinophil count So, what to do?? Mascarello M et al. Annals of Tropical Medicine & Parasitology, Vol. 105, No. 8, (2011) NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

14 Screening (obligatorily with serology) 1. Transplant candidates 2. Oncology patients 3. HIV patients 4. Any subject with eosinophilia 5. Immigrants (with or without eosinophilia) 6. Any candidate for any reason to corticosteroids and/or immune suppressants (what about biologicals??) Is it justified, in these groups, to treat negatives, too?? NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

15 How to treat?? Albendazole? No, please!! Thiabendazole: effective, no longer easy to procure, unpleasant side effects Ivermectin: drug of choice, but what regimen? NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

Table 4 - Outcome at follow-up (month 3 rd- 6 th ) in the two arms (92 patients whith IFAT titer >=80) Measures of efficacy Ivermectin Thiabendazole p All criteria fulfilled 32/47 (68.1%) 31/45 (68.

16 Table 4 - Outcome at follow-up (month 3 rd- 6 th ) in the two arms (92 patients whith IFAT titer >=80) Measures of efficacy Ivermectin Thiabendazole p All criteria fulfilled 32/47 (68.1%) 31/45 (68.9%) 0.93 Patients with partial response 1 included Efficacy based on negativization of direct tests 41/47 (87.2%) 40/45 (88.9%) /24 (91.7%) 27/27 (100%) 0.22^ NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

17 Toxicity Table 5 Side effects (analysis on all 223 patients included in trial) Side effects Ivermectin Thiabendazo le Grade 1 19/115 (16.5%) Grade 2 5/115 (4.3%) All 24/115 (20.9%) 36/108 (33.3%) 43/108 (39.8%) 79/108 (73.1%) p Bisoffi Z et Al. Plos Neglect Trop Dis 2011 NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY 1 JUNE 2012, VENICE, ITALY

Screening phase: identification of patients with positive serology or stool Informed consent signing and inclusion of patient Group A: 200 mcg/kg of ivermectin on

18 Screening phase: identification of patients with positive serology or stool Informed consent signing and inclusion of patient Group A: 200 mcg/kg of ivermectin on day 1 Group B: 200 mcg/kg ivermectin on days 1,2,15 and 16 Follow up visits at 6 and 12 months COHEMI RCT : single versus multiple dose, 400 patients planned to enrol

19 Drugs used in cases of severe strongyloidiasis Drug Albendazole Ivermectin Thiabendazole Other drugs Used as single treatment In combination Total of patients treated (Buonfrate et al. for COHEMI, 2012, submitted)

20 Life cycle of S. stercoralis Where is the male? Scaglia M., Gatti S., Rondanelli EG. PARASSITI E PARASSITOSI UMANE dalla clinica al laboratorio. Selecta Medica Ed. 2005

21 Thank you!

Supplementary webappendix

Supplementary webappendix This webappendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Moser W, Coulibaly JT, Ali SM, et al.