Important Health Problems in Migrants? Important Health Problem?

10/15/2018

Schistosomiasis:Important health problem? ICMH, Rome 2018 Global distribution of schistosomiasis Symposium, 3rd October 2018 Parasites: Malaria, Chagas, Schistosomiasis, and Strongyloidiasis >260 million infected. ~ 85% (over 200 million, 280.000 deaths) in sub-Saharian Africa Strongyloidiasis and schistosomiasis: screen, treat or forget?

Zeno Bisoffi

WHO Collaborating Center on strongyloidiasis and other

it til itiif ti Adapted from Colley, Lancet 2014

Strongyloidiasis Important health problems in migrants? Important health problem?

At least 370 million people Some 30–100 million people infected are estimated to be infected worldwide

(probably an underestimate) Buonfrate Dora, Gobbi Federico, Marchese Valentina, Postiglione Chiara, Badona Monteiro Geraldo, Giorli Giovanni, Napoletano Giuseppina, Bisoffi Z, Buonfrate D, Montresor A, Requena‐Méndez A, et al. (2013) Strongyloides stercoralis: A Plea for Action. PLoS Negl Trop Dis 7(5): Bisoffi Zeno. Extended screening for infectious diseases among newly arrived asylum seekers from Africa and Asia, Verona province, Italy, e2214. doi:10.1371/journal.pntd.0002214http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.0002214 April 2014 to June 2015. Euro Surveill. 2018;23(16):pii=17-00527. https://doi.org/10.2807/1560-7917.ES.2018.23.16.17-00527

Important health problems in migrants? Important health problems in migrants?

24.1% 17.4% 14.3% 11.4% Strongyloidiasis: pooled Schistosomiasis: pooled prevalence >10% EAP, prevalence >20% SSA SSA and LAC

C. Greenaway et al. 2018. Prevalence of strongyloidiasis and Accepted! Great job schistosomiasis among migrants (Lancet GH, under review) Chris!!! C. Greenaway et al. 2018. Prevalence of strongyloidiasis and schistosomiasis among migrants (Lancet GH, accepted)

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Important health problems in migrants? 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Rome 2018, preliminary, unpublished data: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. 2015 Jun;21(6):543-552.

ABDOMINAL PAIN Symptoms of chronic, uncomplicated strongyloidiasis Symptoms of chronic, uncomplicated strongyloidiasis URTICARIA

Anemia? Stunting? Other? DIARRHEA ITCHING

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

Severe strongyloidiasis: 67% patients under steroids

Immune depression X Other conditions How to quantify the risk of HTLV 1 hyperinfection/dissemination? We HIV need a stroke of genius! Alcoholism hyperinfection ‐ dissemination Malnutrition (accelerated autoinfection) (to ) Fatality rate: 50‐86% Pregnancy? Transplant Cancer Buonfrate D et al. BMC Infectious Diseases 2013 13(1):78

Buonfrate D et al. BMC Infectious Diseases 2013 13(1):78

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Diagnosis: is a satisfactory test available for screening? Is an effective treatment available? Ok ivermectin…But how many doses? Test Prevalence PPV NPV

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): e2640. https://doi.org/10.1371/journal.pntd.0002640

Preliminary results… Schistosomiasis ‐ Lifecycle

No difference!!

WHO Collaborating Center on strongyloidiasis and other intestinal Adapted from Colley, Lancet, 2014 16 parasitic infections

Important health problem? Important health problem? Schistosomiasis

• S. mansoni (japonicum): This bladder “tumor” virtually disappeared in mild to moderate (if any) one month after pzq intestinal symptoms for years; treatment • Liver fibrosis, portal hypertension, death if untreated • S. haematobium: mild to moderate (if any) urogenital symptoms for years; Schistosoma in the mesenteric veins • Hydronephrosis, renal failure, class A carcinogen for bladder cancer Source o cambiare Source: F. Tamarozzi, CTD Negrar

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Patient 6

New insights: schistosomiasis and the lungs 90 days after treatment

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? 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, • Presence of eggs in stools or in urine according to Latent Class Analysis (prev=35%) • Serology (type and cute‐off) • Circulating antigens (CCA/CAA) • Symptoms and eosinophilia • PCR? Urines? Stools? 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): e0005593

Diagnosis: is a satisfactory test available for screening?

Is an effective treatment available? Ok praziquantel…But how many SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON‐ENDEMIC COUNTRIES doses? 40 mg/kg single dose,but…

• In non‐endemic countries  no existing 148 records included guidelines/recommendations on 92 (62.2%) standard management of (acute) and chronic treatment 56 (37.8%) schistosomiasis different treatment

25 3 2 different 12 1 more than one 13 repeated dose dosage more more than day and different repeated and different than one one day and dosage dose dosage day repeated dose

Cucchetto G et al., 2018 (to be submitted)

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SYSTEMATIC REVIEW ON SCHISTOSOMIASIS TREATMENT IN NON‐ENDEMIC COUNTRIES We have a dream…

…A multi center RCT in non endemic countries to assess the efficacy of praziquantel

Cucchetto G et al., 2018 (to be submitted) One dose vs multiple doses

To screen or not to screen? To screen or not to screen? Balance cost/benefits?? Is presumptive treatment an option? 1. Important health problem 2. Natural history well understood 3. Detectable early stage PLoS Negl Trop Dis. 2016 Aug 10;10(8):e0004910. doi: 10.1371/journal.pntd.0004910. 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. 4. Early treatment more beneficial Maskery B1, Coleman MS1, Weinberg M1, Zhou W1, Rotz L1, Klosovsky A2, Cantey PT3, Fox LM3, Cetron MS1, 5. Suitable test for early stage Stauffer WM1,4.

6. Acceptable test Ivermectin: A Drug Worthy of a 7. Adequate intervals determined Nobel Prize, but Inaccessible for Those Who Need It 8. Adequate health services 22 October 2015 9. Risks less than benefits

10. Balance cost/benefits Wilson & Junger criteria WHO 1968

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?