10/15/2018. Strongyloidiasis Important health problem? Important health problems in migrants? Important health problems in migrants?

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Christina Ferguson
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ICMH, Rome 2018 Symposium, 3rd October 2018 Parasites: Malaria, Chagas, Schistosomiasis,

Schistosomiasis: Global distribution of schistosomiasis >260 million infected.

000 deaths) in sub-saharian Africa Zeno Bisoffi WHO Collaborating Center on

Strongyloidiasis Some 30 100 million people are estimated to be infected worldwide

Montresor A, Requena Méndez A, et al. (2013) Strongyloides stercoralis: A Plea for Action.

org/article/info:doi/10.1371/journal.pntd.

Monteiro Geraldo, Giorli Giovanni, Napoletano Giuseppina, Bisoffi Zeno.

and Asia, Verona province, Italy, April 2014 to June 2015. Euro Surveill.

1% Schistosomiasis: pooled prevalence >20% SSA 17.4% 14.3% 11.

1 ICMH, Rome 2018 Symposium, 3rd October 2018 Parasites: Malaria, Chagas, Schistosomiasis, and Strongyloidiasis Strongyloidiasis and schistosomiasis: screen, treat or forget? Schistosomiasis: Global distribution of schistosomiasis >260 million infected. ~ 85% (over 200 million, deaths) in sub-saharian Africa Zeno Bisoffi WHO Collaborating Center on strongyloidiasis and other i t ti l iti i f ti Adapted from Colley, Lancet 2014 Strongyloidiasis Some million people are estimated to be infected worldwide (probably an underestimate) At least 370 million people infected Bisoffi Z, Buonfrate D, Montresor A, Requena Méndez A, et al. (2013) Strongyloides stercoralis: A Plea for Action. PLoS Negl Trop Dis 7(5): e2214. doi: /journal.pntd http:// Buonfrate Dora, Gobbi Federico, Marchese Valentina, Postiglione Chiara, Badona Monteiro Geraldo, Giorli Giovanni, Napoletano Giuseppina, Bisoffi Zeno. Extended screening for infectious diseases among newly arrived asylum seekers from Africa and Asia, Verona province, Italy, April 2014 to June Euro Surveill. 2018;23(16):pii= % Schistosomiasis: pooled prevalence >20% SSA 17.4% 14.3% 11.4% Strongyloidiasis: pooled prevalence >10% EAP, SSA and LAC C. Greenaway et al Prevalence of strongyloidiasis and schistosomiasis among migrants (Lancet GH, under review) Accepted! Great job Chris!!! C. Greenaway et al Prevalence of strongyloidiasis and schistosomiasis among migrants (Lancet GH, accepted) 1

unpublished data: Strongyloidiasis prevalence

Schistosomiasis prevalence (ICT): SSA 66/400

, September 2018 Buonfrate D, Perandin F,

Clin Microbiol Infect. 2015 Jun;21(6):543-552.

uncomplicated strongyloidiasis URTICARIA

strongyloidiasis DIARRHEA ITCHING Anemia?

, TMIH 2018, under review F. Tamarozzi et al.

strongyloidiasis: 67% patients under steroids

dissemination (accelerated autoinfection) (to

BMC Infectious Diseases 2013 13(1):78 Other

2 Cicle of S. stercoralis Rome 2018, preliminary, unpublished data: Strongyloidiasis prevalence (IFAT): SSA 81/398 (20%) LAC 37/248 (15%) Schistosomiasis prevalence (ICT): SSA 66/400 (16.5%) L. Marrone et al., September 2018 Buonfrate D, Perandin F, Formenti F, Bisoffi Z. Novel approaches to the diagnosis of Strongyloides stercoralis infection. Clin Microbiol Infect Jun;21(6): ABDOMINAL PAIN Symptoms of chronic, uncomplicated strongyloidiasis URTICARIA Symptoms of chronic, uncomplicated strongyloidiasis DIARRHEA ITCHING Anemia? Stunting? Other? F. Tamarozzi et al., TMIH 2018, under review F. Tamarozzi et al., TMIH 2018, under review Severe strongyloidiasis: 67% patients under steroids Immune depression hyperinfection dissemination (accelerated autoinfection) (to ) Fatality rate: 50 86% X Buonfrate D et al. BMC Infectious Diseases (1):78 Other conditions HTLV 1 HIV Alcoholism Malnutrition Pregnancy? Transplant Cancer How to quantify the risk of hyperinfection/dissemination? We need a stroke of genius! Buonfrate D et al. BMC Infectious Diseases (1):78 2

Diagnosis: is a satisfactory test available for screening?

Ok ivermectin But how many doses? BORDIER ELISA 10,0% 85.4% 98.

8% Bisoffi Z, Buonfrate D, Sequi M, Mejia R, Cimino RO, Krolewiecki

(2014) Diagnostic Accuracy of Five Serologic Tests for Strongyloides

! WHO Collaborating Center on strongyloidiasis and other intestinal

in the mesenteric veins Schistosomiasis S.

for years; Liver fibrosis, portal hypertension, death if untreated S.

3 Diagnosis: is a satisfactory test available for screening? Test Prevalence PPV NPV Is an effective available? Ok ivermectin But how many doses? BORDIER ELISA 10,0% 85.4% 98.8% 20,0% 92.9% 97.4% IVD ELISA 10,0% 91.8% 99.0% 20,0% 96.2% 97.8% Bisoffi Z, Buonfrate D, Sequi M, Mejia R, Cimino RO, Krolewiecki AJ, et al. (2014) Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection. PLoS Negl Trop Dis 8(1): e Preliminary results Schistosomiasis Lifecycle No difference!! WHO Collaborating Center on strongyloidiasis and other intestinal parasitic infections Adapted from Colley, Lancet, Schistosoma in the mesenteric veins Schistosomiasis S. mansoni (japonicum): mild to moderate (if any) intestinal symptoms for years; Liver fibrosis, portal hypertension, death if untreated S. haematobium: mild to moderate (if any) urogenital symptoms for years; Hydronephrosis, renal failure, class A carcinogen for bladder cancer Source o cambiare This bladder tumor virtually disappeared in one month after pzq Source: F. Tamarozzi, CTD Negrar 3

Patient 6 New insights: schistosomiasis and the lungs 90 days after Patient 7

Lancet Inf Dis 2017 Diagnosis: is a satisfactory test available for screening?

antigens (CCA/CAA) Symptoms and eosinophilia PCR? Urines? Stools? Table 3.

97%) and a positive (PPV) or a negative (NPV) second test, according to Latent

human schistosomiasis in immigrants and refugees from African countries: An

PLOS Neglected Tropical Diseases 11(6): e0005593 Diagnosis: is a satisfactory

guidelines/recommendations on management of (acute) and chronic schistosomiasis

4 Patient 6 New insights: schistosomiasis and the lungs 90 days after Patient 7 Gobbi F et al. Lancet Inf Dis 2017 Gobbi F et al. Lancet Inf Dis 2017 Diagnosis: is a satisfactory test available for screening? Presence of eggs in stools or in urine Serology (type and cute off) Circulating antigens (CCA/CAA) Symptoms and eosinophilia PCR? Urines? Stools? Table 3. Predictive values of a combination of positive ICT (Se 96% Sp 79%, PPV 72%, NPV 97%) and a positive (PPV) or a negative (NPV) second test, according to Latent Class Analysis (prev=35%) Beltrame A, Guerriero M, Angheben A, Gobbi F, Requena-Mendez A, et al. (2017) Accuracy of parasitological and immunological tests for the screening of human schistosomiasis in immigrants and refugees from African countries: An approach with Latent Class Analysis. PLOS Neglected Tropical Diseases 11(6): e Diagnosis: is a satisfactory test available for screening? Is an effective available? Ok praziquantel But how many doses? 40 mg/kg single dose,but In non endemic countries no existing guidelines/recommendations on management of (acute) and chronic schistosomiasis SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON ENDEMIC COUNTRIES 148 records included 56 (37.8%) different 92 (62.2%) standard 25 different 12 more than one day 13 repeated dose 1 more than one day and repeated dose 2 repeated dose and different 3 more than one day and different Cucchetto G et al., 2018 (to be submitted) 4

Natural history well understood 3. Detectable early stage 4. Early more beneficial 5. Suitable test for early stage 6. Acceptable test 7. Adequate intervals determined 8. Adequate health services 9.

5 SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON ENDEMIC COUNTRIES We have a dream Cucchetto G et al., 2018 (to be submitted) A multi center RCT in non endemic countries to assess the efficacy of praziquantel One dose vs multiple doses To screen or not to screen? 1. Important health problem 2. Natural history well understood 3. Detectable early stage 4. Early more beneficial 5. Suitable test for early stage 6. Acceptable test 7. Adequate intervals determined 8. Adequate health services 9. Risks less than benefits 10. Balance cost/benefits Wilson & Junger criteria WHO 1968 To screen or not to screen? Balance cost/benefits?? Is presumptive an option? PLoS Negl Trop Dis Aug 10;10(8):e doi: /journal.pntd ecollection 2016 Aug. Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia. Maskery B 1, Coleman MS 1, Weinberg M 1, Zhou W 1, Rotz L 1, Klosovsky A 2, Cantey PT 3, Fox LM 3, Cetron MS 1, Stauffer WM 1,4. Ivermectin: A Drug Worthy of a Nobel Prize, but Inaccessible for Those Who Need It 22 October 2015 Conclusions and an unanswered last question Relevant health problems Screening recommended (e.g. new Italian MOH guidelines) Is screening feasible considering the current political mainstream in many countries? 5

Canadian Society of Internal Medicine Annual Meeting 2018 Banff, AB

Canadian Society of Internal Medicine Annual Meeting 2018 Banff, AB Prevalence of strongyloidiasis and schistosomiasis among migrants: A systematic review and meta-analysis Xing Jian Liu Division of General