Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Design
2.2. Ethics Statement
2.3. Study Population and Data Collection
2.4. Review: Search Strategy and Selection Criteria
2.5. Definitions
- -
- Clinical: definite loss of sensation in a pale (hypopigmented) or reddish skin patch (SP) or a thickened or enlarged peripheral nerve with loss of sensation and/or weakness of the muscles supplied by that nerve.
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- Laboratory: demonstration of acid-fast bacilli (AFB) in a slit-skin smear (SSS) or in a skin biopsy (SB) of skin lesions with loss of sensation and/or nerve biopsy (NB) of thickened peripheral nerves.
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- Histopathology: evidence of granulomatous infiltrate.
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- Biomolecular analysis: positive polymerase chain reaction (PCR) for M. leprae and/or M. lepromatosis in nasal swab, skin or nerve biopsy.
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- Paucibacillary (PB) leprosy: a case of leprosy with one to five skin lesions, without a demonstrated presence of bacilli in a slit-skin smear
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- Multibacillary (MB) leprosy: a case of leprosy with more than five skin lesions, or with nerve involvement (pure neuritis, or any number of skin lesions plus neuritis), or with the demonstrated presence of bacilli in a SSS, irrespective of the number of skin lesions.
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- TT: Tuberculoid leprosy
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- BT: Borderline tuberculoid leprosy
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- BB: Mid-borderline leprosy
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- BL: Borderline lepromatous leprosy
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- LL: Lepromatous leprosy
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- I: Indeterminate leprosy
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- Multidrug Therapy (MDT): rifampicin 600 mg monthly, dapsone 100 mg daily, clofazimine 300 mg monthly, and 50 mg daily (the treatment has to be continued until a negative SSS), or
- -
- Rifampicin–Ofloxacina–Minocyclin (ROM) regimen: alternative treatment to clofazimine is based on Rifampicin 600 mg, Ofloxacin 400 mg (recently substituted by Moxifloxacin 400 mg), and Minocycline 100 mg, all once a month for 24 months.
2.6. Statistical Analysis
3. Results
3.1. Case Series
3.2. The Review
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Appendix A
Search Strategies (Electronic Searches)
- Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 7);
- MEDLINE (PubMed) (1966 to 14 August 2018);
- EMBASE (Embase.com) (1974 to 14 August 2018);
- Latin American and Caribbean Health Science Information Database (LILACS) (Bireme) (1982 to 14 August 2018);
- ClinicalTrials.gov (www.clinicaltrials.gov);
- World Health Organization (WHO) International Clinical Trials Registry Platform (apps.who.int/trialsearch); and
- Orphanet (www.orpha.net)
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Characteristics | Total n = 55 (%) | Africa n = 23 (%) | Asia n = 22 (%) | Latin America n = 10 (%) |
---|---|---|---|---|
Male | 37 (67.3) | 18 (78.3) | 17 (77.3) | 2 (20) |
Median age (IQR), Years | 33 (28–41) | 29 (23–37) | 38 (28–43) | 34 (28–41) |
Median duration of stay in Europe (IQR), Months | 36 (12–92) | 21 (10–82) | 55 (30–103) | 35 (7–92) |
Previous Diagnosis of Leprosy | 19 (34.6) | 10 (43.5) | 2 (9.1) | 7 (70) |
Median Time from Start of Symptoms and Diagnosis (IQR), Months | 12 (3–31) | 26 (3–57) | 5 (3–24) | 11 (3–25) |
Signs and Symptoms | ||||
Skin | 50 (90.9) | 20 (87) | 21 (95.5) | 9 (90) |
Neuropathy | 39 (70.9) | 19 (82.6) | 14 (63.6) | 6 (60) |
Edema | 4 (7.3) | 2 (8.7) | 2 (9.1) | 0 |
Eye Involvement | 3 (5.5) | 1 (4.3) | 2 (9.1) | 0 |
Fever | 3 (5.5) | 2 (8.7) | 0 | 0 |
Arthritis | 2 (3.6) | 0 | 1 (4.5) | 1 (10) |
Lymphadenopathy | 2 (3.6) | 1 (4.3) | 1 (4.5) | 0 |
Diagnosis | ||||
Nasal Swab AFB Positive (n = 54) * | 20 (37) | 8/23 (34.8) | 11/21 (52.4) | 1/10 (10) |
SSS AFB Positive (n = 54) * | 39 (70.9) | 13/22 (59.1) | 18/22 (81.8) | 8/10 (80) |
Granulomatous Inflammation in the Biopsy (n = 43) ^ | 21 (48.8) | 6/17 (35.3) | 13/19 (68.4) | 2/7 (28.6) |
AFB positive in the biopsy (n = 43) ^ | 13 (30.2) | 7/17 (41.2) | 5/19 (26.3) | 1/7 (14.3) |
PCR for M. leprae or M. lepromatosis DNA positive (n = 24) § | 17 (85) | 7/9 (77.8) | 8/9 (88.9) | 2/6 (33.3) |
WHO classification | ||||
PB | 19 (34.5) | 10 (43.5) | 5 (22.7) | 4 (40) |
MB | 36 (65.5) | 13 (56.5) | 17 (77.3) | 6 (60) |
Ridley–Jopling classification | ||||
TT | 3 (5.4) | 2 (8.7) | 1 (4.5) | 0 |
BT | 27 (49.1) | 12 (52.2) | 9 (40.9) | 6 (60) |
BL | 5 (9.1) | 0 | 4 (18.2) | 1 (10) |
LL | 17 (31) | 8 (34.8) | 6 (27.3) | 3 (30) |
BL/LL | 3 (5.4) | 1 (4.3) | 2 (9.1) | 0 |
Therapy | ||||
MDT | 52 (94.6) | 20 (87) | 22 (100) | 10 (100) |
ROM | 3 (5.4) | 3 (13) | 0 | 0 |
Outcome | ||||
Completed treatment | 40 (72.7) | 16 (69.6) | 16 (72.7) | 9 (90) |
Ongoing | 7 (12.7) | 5 (21.7) | 2 (9.1) | 0 |
Lost | 8 (14.6) | 2 (8.7) | 4 (18.2) | 1 (10) |
Characteristic | Portugal (Medeiros S, 2009) | Greece (Kyriakis KP, 2010) | Italy (Massone C, 2010) | Denmark (Aftab H, 2016) | Spain (Ramos JM, 2016) |
---|---|---|---|---|---|
Years Analyzed | 1968–2003 | 1988–2007 | 2002–2008 | 1980–2010 | 2003–2013 |
Number of Migrants/Total Patients (%) | 36/102 (35.3) | 6/33 (18.2) | 58/64 (90.6) | 15/15 (100) | 128/168 (76.2) |
Continent of Origin, n (%) | |||||
Africa | 20 (55.6) | 2 (33.3) | 16 (27.6) | 2 (13.3) | 27 (21.1) |
South/Central America | 11 (30.6) | 1 (16.7) | 19 (32.7) | 0 | 92 (71.9) |
Asia | 5 (13.8) | 3 (50) | 23 (39.7) | 13 (86.7) | 7 (5.5) |
Not Available | 0 | 0 | 0 | 0 | 2 (1.5) |
Reference | Country (City) | Time | Gender Age (Years) | Country of Origin | Duration of Stay in Europe (Months) | Clinical Manifestations | Methods of Diagnosis | WHO Class | R-J Class |
---|---|---|---|---|---|---|---|---|---|
[24] | France (Saint-Brieuc) | 2009 | M, 11 | Haiti | 36 | SNs (face), SPs (legs) | SB (AFB) | MB | LL |
[7,25] | Italy (Genoa) | 2006 | M, 43 | Brazil | NA | anesthetic and asymmetric SPs, erythematous SNs (abdomen, things and legs) | NB (AFB) SSS (AFB) | MB | BT |
[26] | UK (Swindon) | 2009 | F, 23 | Brazil | 48 | vascultic diffuse rash, fever, LA, SNs (face, arms and legs), polyarthritis with symmetrical synovitis (elbows, wrists, ankles, MCP joints) | SB (GI, AFB) | MB | LL, ENL |
[27] | Italy (Palermo) | 2009 | M, 15 | Senegal | 6 | anesthetic SPs, sensory loss and motor weakness (hand, forearm), claw deformity (hand), PN (ulnar, median nerves), paraesthesia (legs) | clinical | PB | TT |
[7] | Italy (Genoa) | 2010 | M, 28 | Nigeria | NA NA | SNs (face) | SB (AFB) | MB | LL |
M, 22 | Colombia | SNs (extremities) | SB (AFB) | MB | NA | ||||
M, 14 | Brazil | symmetrical SPs (entire body) | SB (AFB) | MB | NA | ||||
[28] | Italy (Milan) | 2010 | M, 14 | Brazil | 96 | erythematous SNs (face, extremities), SPs (arms), painful edema with hypoesthesia (wrists, hands), fever, LA, weight loss | SB (AFB, PCR) | MB | LL |
[36] | Italy (Verona) | 2006 | M, 20 | India | 36 | erythematous SNs and SPs (face, extremities), polyarthritis (wrists, ankles), fever, episcleritis | SB (MI, AFB) | MB | LL |
[37] | Italy (Sassari) | 2011 | M, 26 | Nigeria | 12 | SPs (trunk, extremities), symmetric edema (extremities), fever, headache, LA, PN (great auricular, ulnar nervs), | SB (GI) | MB | BB/BL |
[38] | Spain (Malaga) | 2004–2009 | F, 28 | Brazil | 8 | SP (harm) | SB (MI) | PB | I |
M, 33 | Mali | 8 | SPs (extremities) | SB (MI) | PB | I | |||
F, 32 | Nigeria | 48 | SP (trunk) | SB (MI) | PB | I | |||
F, 31 | Paraguay | 36 | SPs (extremities) | SB (GI) | PB | TT | |||
F, 26 | Brazil | 12 | SP (leg) | SB (GI) | PB | TT | |||
M, 40 | Colombia | 12 | SPs (extremities, trunk) | SB (GI) | PB | BT | |||
[29] | Spain (Alicante) | 2011 | M, 41 | Colombia | 108 | painful edema (extremities), synovitis (wrists, MCP joints), tenosynovitis, SNs (legs), LA, mild skin rash on trunk | SB and LB (GI, AFB) | MB | LL, ENL |
[30] | Spain (Valladolid) | 2012 | M, 19 | Mauritania | 48 | SPs, sensory loss and motor weakness (extremities), claw deformity (hand) | SB (AFB) | MB | I |
[31] | Italy (Ferrara) | 2015 | M, 22 | Ghana | 24 | infiltration facial skin, pain, sensory loss and motor weakness (hand), ulnar palsy, erythematous SNs (face), arthralgia, arthritis (hands, ankles, knees), hair loss and madarosis | SB (AFB, GI) | MB | BT |
[32] | UK (London) | 2016 | M, 60 | Nigeria | 36 | facial weakness and numbness (extremities, face), thickened peripheral nerves, ulnar palsy, difficulty walking | NB (MI) | MB | PNL BT |
[39] | Spain (Madrid) | 1989 | F, 40 | Eq. Guinea | 2 w | SP (face) | SB (GI) | PB | TT |
1990 | M, 30 | Philippines | 48 | SPs (face, extremities) | SSS (AFB) | MB | LL | ||
1994 | M, 28 | Eq. Guinea | 96 | erythematous SNs, PN | SSS (AFB) | MB | LL | ||
1996 | M, 48 | Colombia | 12 | hypoesthetic SPs | SSS/SB (AFB, MI) | MB | BB | ||
2002 | F, 65 | Colombia | 12 | infiltration facial skin, symmetrical PN | SSS/NB (AFB) | MB | LL | ||
2005 | M, 59 | DR | 96 | erythematous SNs | SSS (AFB) | MB | BB-BL | ||
2004 | F, 62 | DR | 3 | claw deformity (hands), PN legs, plantar ulcer | clinical | MB | LL | ||
2006 | M, 24 | Mali | 12 | SPs, asymmetric PN (left ulnar) | SB (GI) | MB | BB | ||
2006 | F, 28 | Brazil | 24 | infiltration facial skin, hypoesthesia legs | SSS (AFB) | MB | BL | ||
2007 | M, 22 | Brazil | 12 | SPs, thickening ear lobes/cheeks, fever, PN | SSS (AFB) | MB | LL | ||
2008 | F, 32 | Paraguay | 84 | asymmetric hypoesthetic SPs | SSS (AFB) | PB | BT | ||
2011 | F, 27 | Paraguay | 12 | painful SNs, fever, PN | SSS/SB (AFB, PCR) | MB | LL | ||
2013 | M, 40 | Venezuela | 96 | SPs, madarosis, PN | SSS (AFB) | MB | BL-LL | ||
2015 | F, 38 | Paraguay | 60 | SPs, PN (right ulnar) | SSS/SB (AFB, PCR) | MB | LL | ||
[33] | UK (Birmingham) | 2017 | F, 15 | Afghanistan | 60 | left ulnar palsy | clinical | MB | PNL |
[34] | Germany (Homburg/Saar) | 2016 | M, 28 | Afghanistan | NA | erythematous SNs and SPs (face, extremities) | SB (AFB, PCR, GI) | MB | NA |
[35] | Italy (Rimini) | 2017 | M, 29 | Nigeria | 36 | SNs (face, hands) | SB (AFB, PCR, GI) | MB | LL |
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Beltrame, A.; Barabino, G.; Wei, Y.; Clapasson, A.; Orza, P.; Perandin, F.; Piubelli, C.; Monteiro, G.B.; Longoni, S.S.; Rodari, P.; et al. Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018. Microorganisms 2020, 8, 1113. https://doi.org/10.3390/microorganisms8081113
Beltrame A, Barabino G, Wei Y, Clapasson A, Orza P, Perandin F, Piubelli C, Monteiro GB, Longoni SS, Rodari P, et al. Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018. Microorganisms. 2020; 8(8):1113. https://doi.org/10.3390/microorganisms8081113
Chicago/Turabian StyleBeltrame, Anna, Gianfranco Barabino, Yiran Wei, Andrea Clapasson, Pierantonio Orza, Francesca Perandin, Chiara Piubelli, Geraldo Badona Monteiro, Silvia Stefania Longoni, Paola Rodari, and et al. 2020. "Leprosy in Refugees and Migrants in Italy and a Literature Review of Cases Reported in Europe between 2009 and 2018" Microorganisms 8, no. 8: 1113. https://doi.org/10.3390/microorganisms8081113