Travel-Associated Parasitological Infections

Travel-associated parasitological infections

Cândida Abreu Infectious Diseases Depart. HSJoão Travel Medicine Clinic, HSJoão Faculty of©Medicine, by author Porto - Portugal

Technical Workshop for ESCMIDBasic Online and Clinical Lecture Parasitology Library Porto, 21 June 2013 OUTLINE

Burden of parasitic diseases in travellers - overview

Gastroentestinal diseases Dermatological diseases Sistemic diseases Prevention © by author Take home messages ESCMID Online Lecture Library PARASITICDISEASES IN TRAVELLERS

Asymetrical world: Parasitic pathogens distribution Safe water distribution Sanitation Agricultural conditions Animal health Vectors distribution© by author

TheESCMID less developed worldOnline has a higherLecture burden Libraryof parasitic diseases Globalization can make things worse BURDEN OF PARASITICDISEASE IN TRAVELLERS

The incidence and risk of parasitic disease in returned travellers is not easy to determine The published studies  are generally from samples of ill travellers only proportionated morbidity or the rate of ill travellers with a subset of diagnoses to all ill returned travellers for a given country can© be calculatedby author  sample size is often small ESCMID many variables Online: destination Lecture, duration Libraryof travel, type of traveller,… BURDEN OF PARASITICDISEASES ANDPURPOSE OF TRAVEL

Sample: ill returned patients: 2275 canadian travellers and © by1213 author new immigrants Study: from November,97 to June,03 MoreESCMID parasitic infections Online diagnosed Lecture in immigrants Library(21.1% vs 7.1%, p < 0.001), and VFR (17.9% vs 11.8%, p < 0.001) Andrea K . Boggild Prospective Analysis of Parasitic Infections in Canadian Travelers and Immigrants. Journal of Travel Medicine, 2006 Volume 13, Issue 3,, 138–144 PARASITICDISEASESAND PURPOSE OF TRAVEL IN CANADIANS

Comparing with other travellers Tourists : more likely to acquire cutaneous larva migrans (OR=10.8) Immigrants and VFR more likely to have: malaria (OR=1.5, 2.4) schistosomiasis (OR=3.4, 1.5) filariasis (OR=4.6, 2.6) strongyloidiasis (OR=2.1, 3.9) echinococcosis© by author (OR=4.3, 4.8) Immigrants more like to have: ESCMID Onlineamebiasis Lecture ( R=2.6) Library giardiasis (OR=1.9)

Andrea K . Boggild Prospective Analysis of Parasitic Infections in Canadian Travelers and Immigrants. Journal of Travel Medicine, 2006,Volume 13, Issue 3, 138–144 PARASITICDISEASES IN CANADIAN TRAVELLERSANDIMMIGRANTS

From 3528 returned Canadian (2275 travellers , 1213 new immigrants ) between November,97 -June, 03 1010 (29%) had a parasitic infection diagnosed - 209 nonhistolytica amebiasis - 143 malaria - 105 cutaneous larva migrans - 74 giardiasis © by author - 48 schistosomiasis -- 43 strongiloidiasis ESCMID- 41 amebiasis Online (E.histolytica Lecture) Library - 38 echinococcosis Andrea K . Boggild et al. Journal of Travel Medicine, 2006, Volume 13, (3) , 138–144. PARASITICDISEASE: DESTINATIONAND EXPATRIATES VERSUS NON EXPATRIATES

From 2883 expatriates compared with 11910 non -expatriates* Those returning from Africa had higher rates of malaria, filariasis and schistosomiasis Those returning from Asia-Pacific region had higher rates of strongyloidiasis Those returning from Latin America had higher rates of© giardiasis by author ESCMIDFrom all regions Online: expatriates Lecture had higher ratesLibrary of amebiasis and gastrointestinal infections *non-expatriates: business or missionary/volunteers patients Lim et al. BMC Infectious Diseases 2012, 12:386. PARASITICDISEASESAND IMMUNOCOMPROMISEDTRAVELLERS

Cryptosporidium, Microsporidium ongoing and debilitating symptoms Strongyloides infections in patients with a cell mediated immunity defect (high dose corticosteroid use, organ transplantation, HTLV-1, HIV infection, …) can result in hyperinfection syndrome Transmission of S stercoralis through transplantation of solid organs: a single donor was© the by source author for 3 of 4 organ recipients* Reactivation of Strongyloides, Trypanosoma and Leishmania in transplantESCMID recipients Online from endemic Lecture areas; infections Library donor-derived

A Slack. Aust Fam Physician 2012;41:782-786 *Transmission of Strongyloides stercoralis Through Transplantation of Solid Organs — Pennsylvania, 2012 MMWR / April 12, 2013 / Vol. 62 / No. 14 LONG TIME CONSEQUENCES OF PARASITICDISEASES

Intestinal infections protein losing enteropathy postinfectious fatigue posinfectious irritable bowel syndrome (Cryptosporidium) posinfectious lactase deficiency (Giardia ) In children: growth/cognitive impairment (deficiencies of iron & micronutrients) Blood infections (Schistosomiasis)© by author Fibrosis and chronic diseases (hepatic, ureters , bladder) BladderESCMID cancer (squamous Online cell Lecture carcinoma) Library Cerebral malaria: retinopathy, encephalopathy Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 A. Slack. Aust Fam Physician 2012;41:782-786 COMMONPARASITICDISEASES IN TRAVELLERS

Helminth infections Gastrointestinal (strongyloidiasis, toxocariasis); Protozoarial (amebiasis; giardiasis; cryptosporidiosis)

Dermatologic Larva cutaneous © by authormigrans , myasis, tungyasis ESCMID Online Lecture Library Blood Malaria, schistosomiasis, tripanossomiasis, filariasis RISK OF ENTEROPATHOGENIC INFECTIONS* ACQUIREDDURINGTRAVEL

1996-2005 (25 867 travellers)

N=7442 (travellers with confirmed gastrointestinal disease)

From the 2902 © by author pathogens isolated 65% were parasitic ESCMID Online Lecture Library31% bacterial * Clinical symptoms appearing > 14 days after exposure Swaminathan A, et al. J Infect 2009;59:19-27. Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 PARASITIC ENTEROPATHOGENS IN RETURNEDTRAVELLERS

•Adapted from: Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 GIARDIASIS IN TRAVELLERS

Giardia lamblia (or G. intestinalis or G. duodenalis) The most likely pathogen to infect travellers by ingestion of cysts in contaminated food or water; person to person transmission also possible

Highly contagious (10-25 cysts may cause disease) © by author Rotavirus may work synergistically with GiardiaESCMID to enhance Online pathogenesis Lecture Library (attachment of trophozoites to epithelium)

A Slack. Aust Fam Physician 2012;41:782-786 Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 AMEBIASIS

E.histolytica and E moshkovski causes amebiasis: ingestion of food or water contamined with fecal cysts trophozoites invasion: days to years after initial infection: fever, abdominal pain, bloody diarrhea 90% of cases are asymptomatic and self-limiting © by author 1% of clinical cases of amebiasis envolve the liver AuranofinESCMID may be a betterOnline therapeutic Lecture option thanLibrary metronidazole* Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 * Debnath A et al. NatMed 2012;18:956-60 STRONGILOIDIASIS

Autoinfection can result in persistent infection for decades (rhabditiform larvae transform in filariform) 50% of patients with chronic infection are asymptomatic

 if eosinophilia or elevated Ig E in travellers strongyloidiasis should be considered © by author  possible symptoms: skin eruptions, pruritus, larva currens , abdominal painESCMID, diarrhea Online Lecture Library  hyperinfection syndrome (owing to reprodutive capacity of the parasite) has a mortality rate up to 90%

Ross AGP et al. N Engl J Med 2013;368:1817-25.DOI: 10.1056/NEJMra1207777 ANALITICAL/CLINICALFEATURESTHAT HELP PREDICT PARASITIC/BACTERIAL INTESTINAL INFECTION?

509 cases included; parasitic aetiology in 51/428 (11.9%) bacterial© byin 55/440 author (12.5%). Symptoms ≤ 14 days: bacterial more likely than parasitic dis. (p<0.001) Travellers to South and Southeast Asia: more ESCMIDlikely to have parasitic Online infection Lecture(p=0.041) Library

A.C. McGregor et al. Transactions of the Royal Society of Tropical Medicine and Hygiene 106 (2012) 549– 553 TRAVELRELATEDHELMINTICINFECTIONS ANDEOSINOPHILIA

A prospectively study for the occurrence of clinical or subclinical schistosomiasis, strongyloidiasis, filariasis and toxocariasis and the screening value of eosinophilia 1207 travellers included ; serology for parasites + eosinophil counts Samples were tested before and after travel (median travel duration: 21d) Previous infection: 112 travellers; recent: largely contracted in Asia

Schistos. Strongil. filariasis toxocariasis Previous infection ©2.7% by 2.4%author3.4% 1.8% Recent infection 0.51% 0.25% 0.09% 0.08% PositiveESCMID preditive value Onlineof eosinophilia Lecture for diagnosis: Library 15% for previous infection; 0% for recent infection (short-term journey)

Baaten et al. BMC Infectious Diseases 2011, 11:84 DIAGNOSIS OF INTESTINAL PARASITOSIS IN TRAVELLERS

Stool examination – gold standard Detection of trophozoites, cysts, eggs and larvae by microscopic stool examination

Enzyme immunoassays and direct fluorescent-antibodie assays (Giardia and Cryptosporidium in stools) © by author PCR (E. histolytica, G lamblia, C hominis/C parvum; S stercoralisESCMID) in faeces; Online PCR multiplex Lecture Library

R. Hove. Eur J Clin Microbiol Infect Dis (2009) 28:1045–1053 DOI 10.1007/s10096-009-0745-1 DIAGNOSIS OF INTESTINAL PARASITOSIS IN TRAVELLERS

2591 stool samples from 2591 returned travellers with and without symptoms

Multiplex real-time PCR on Entamoeba histolytica, Giardia, Cryptosporidium and Strongyloides stercoralis © by author ESCMID Online Lecture Library

R. Hove. Eur J Clin Microbiol Infect Dis (2009) 28:1045–1053 DOI 10.1007/s10096-009-0745-1 DIAGNOSIS OF INTESTINAL PARASITOSIS IN TRAVELLERS

Comparing stool examination, real-time PCR and antigen detection

Real-time PCR was more sensitive for the detection of E histolytica, G lamblia, C hominis/C parvum and S stercoralis  in non endemic countries E. histolytica PCR proven higher sensitivity compared with stool antigen assays *  real-time PCR for Schistosoma© by author, for Isospora belli and Cyclospora cayetanensis would probably be important for patientsESCMID returning fromOnline high-risk Lecture areas Library

R. Hove. Eur J Clin Microbiol Infect Dis (2009) 28:1045–1053; DOI 10.1007/s10096-009-0745-1 *Stark D et al. J Clin Microbiol 2008;46:1678-1681 MALARIA IN TRAVELLERS: THE GEO NUMBERS (FROM 2008 TO 2010)

From 7410 returned travellers (Euro TravNet sites) malaria cases increased from all main endemic countries Morbidity was much higher in VFRs P. vivax increase from 0.5% (2008) to 1% (2010) p=0.04 –short term travellers, VFR P. falciparum : the most© commonly by author reported; proportionate morbidity increased from 4% (2008) to 6% (2010) – p<0.001 SevereESCMIDP falciparum Onlinemalaria: 31 Lecture /426 in 2010, Library one died 13 cases in 2009 12 cases in 2008 (p<0.002) http//www.eurosurveillance.org/ViewArticle.aspx?Articleid=20205 SCHISTOSOMIASIS

Schistosoma hematobium, S.mansoni and S japonicum are the more common species in Humans, also in travellers a discrete rash may arise a few hours after the percutaneous penetration by the Cercariae; a rash may appear as much as a week later © by author  acute infection may be symptomatic or asymptomaticESCMID, followed Onlineby chronic Lecture forms (genital, Library urinary, or gastrointestinal); acute schisto is the predominant form in travellers*  diagnosis may not be easily done (serologic testing+microscopy) *E, et al. Emerg Infect Dis 2006; 12: 1696–1700 SCHISTOSOMIASISSPECIESAND DISTRIBUTION

S japonicum S mansoni S haematobium snail Oncomelania Biomphalaria Bulinus Causes Intestinal and Intestinal and urinary hepatosplenic hepato Risk China, Africa, Arabian Africa areas Philipines, peninsula, Arabian peninsula Indonesia © bySouth authorAmerica ESCMID Online Lecture Library S. mekongi and S. intercalatum: are only of local importance

Jan Clerinx et al. Travel Medicine and Infectious Disease (2011) 9, 6-24 doi:10.1016/j.tmaid.2010.11.002 SCHISTO IN TRAVELLERS: REGIONS OF EXPOSURE

> 80% of infections acquired in Africa Nile and Omo river - Ethiopia Tanzania (hotel swimming pond) Mali - Dogon Country (18 israeli travellers*) Malawi - Lake Tanganyika S japonicum - Southeast©Asia by author S. mekongi - Mekong river (rare) Jan Clerinx et al. Travel Medicine and Infectious Disease (2011) 9, 6-24 ESCMID Online Lecture Library Deborah J. Nicolls et al.Am. J. Trop. Med. Hyg., 2008 79(5), pp. 729–734 Meltzer E, et al. Emerg Infect Dis 2006; 12: 1696–1700 *L Grandiere-Perez et al. Am. J. Trop. Med. Hyg., 2006,; 4(5), 814–818 SCHISTO: REGIONS OF TRAVELEXPOSURE

401 travellers/410 schisto cases

Deborah J. Nicolls et al.Am. J. Trop. Med. Hyg., 79(5), 2008, pp. 729–734 SCHISTOANDREASON OF TRAVEL

Expatriates , missionaries, volunteers, researchers, and aid workers were more than twice as likely to be diagnosed with schistosomiasis compared with other travellers.

More than half had trips that lasted ≥ 30 days; 27% presented to a clinic more than six months after the completion of travel © by author ESCMID Online Lecture Library

Deborah J. Nicolls et al.Am. J. Trop. Med. Hyg., 79(5), 2008, pp. 729–734 E, et al. Emerg Infect Dis 2006; 12: 1696–1700 SCHISTO SPECIES IN TRAVELLERS

Geo serie (n=410)* Israeli serie (n=137)** S mansoni S. mansoni 42% (102) 29.9% (40)

S haematobium 36% (88) 39.4% (54)

S. japonicum 29% (7) ------S japonicum Unknown species 87% (213) 14.7% (20)

Mixed infection 12%©(9) by author16% (22)

S. mekongi 1 S mekongi ESCMID Online Lecture Library

*Deborah J. Nicolls et al.Am. J. Trop. Med. Hyg., 79(5), 2008, pp. 729–734 **E, et al. Emerg Infect Dis 2006; 12: 1696–1700 S haematobium ACUTESCHISTO: KATAYAMASYNDROME IN TRAVELLERS

Fever or hypersensitivity symptoms- urticarial rash, angioedema, dry cough or wheeze – after exposure to infected water sources with subsequent serologic or parasitologic testing  in nonimmune travellers can be seen after infection with any Schistosoma species*  from a report of 113 cases** , 42 (37.2%) had acute schisto: Symptoms : median 3© weeks by (SD: author 3.1 ± 2.7 weeks) from exposure Fever - the prevalent symptom, followed by respiratory symptoms and rash. ESCMIDOnly 4 (9.5%) patients Online had the Lecture complete complex Library of acute schistosomiasis: fever, urticaria, and respiratory symptoms.

*Clerinx et al. Journal of Travel Medicine 2013. DOI: 10.1111/jtm.12040 **E, et al. Emerg Infect Dis 2006; 12: 1696–1700 SCHISTOSOMIASIS (N=113) IN ISRAELI TRAVELLERS

Meltzer E, et al. Emerg Infect Dis 2006; 12: 1696–1700 SCHISTOSOMIASISTREATMENT

Praziquantel (PZQ) Has weak schistosomicidal efficacy before schistosome maturation is ineffective; higher doses better Praziquantel during incubation period may not prevent acute schistosomiasis neither chronic schisto; after 28th day of exposure: may prevent acute schistosomiasis Early treatment does not© prevent by author chronic schistosomiais Praziquantel during acute phase should probably not be given: toxicity and lack of efficacy. ShouldESCMIDbe defered afterOnline acute symptoms Lecture have Library subsided (steroids or spontaneously); repeat treatment after 3 months*?

L Grandiere-Perez et al. Am. J. Trop. Med. Hyg., 2006,; 4(5), 814–818 *Meltzer E, et al. Emerg Infect Dis 2006; 12: 1696–1700 ARTEMISININDERIVATES(ARTS) IN SCHISTOSOMIASIS

Is partially effective against Schistosoma (not adult forms) and schistosomules.* Eradication has been achieved in 25% of chronic infections and >95% reduction in ova production.** PZQ and artemisinin in combination are more effective than single drug PZQ therapy; may be especially suitable for the treatment of patients, who© byare repeatedlyauthor exposed to infected water*** PZQ:ESCMID multiple doses Online would improve Lecture efficacy ***Library

*Sabah AA, et al.. Exp Parasitol 1986; 61:294–303 **Boulanger D,, et al.. Trans R Soc Trop Med Hyg 2007; 101:113–116 ***Liu et al. Parasites & Vectors 2011, 4:201.. HUMANAFRICANTRYPANOSOMIASIS (HAT)

Karin Urech. PLoS Negl Trop Dis. 2011; 5; 11: e1358 ESCMID Online Lecture Library

TRIPANOSOMIASISAND TRAVELLERS HAT IN TRAVELLERSANDIMMIGRANTS

 HAT must be included in the diagnosis of any febrile patient, suspicious skin manifestations, gastrointestinal manifestations.  HAT generally presents as an acute febrile illness  a trypanosomal chancre or rash and itching are common  diarrhea, hepatomegaly, or icterus are frequent  lymphadenopathy (Winterbottom sign) or sleep disorders are only occasionally found.© by author  HAT in immigrants is similar to the patients in endemic regions: low grade fever ,neurological and psychiatric featuresESCMID Online Lecture Library  HAT has to be considered even if the patient has left endemic regions years ago. Karin Urech. PLoS Negl Trop Dis. 2011; 5; 11: e1358 ERADICATION OF SLEEPINGSICKNESS – S TOMÉ E PRINCIPE 2008

18% of all the patients seen in GeoSentinel clinics after travel 18% had a skin-related diagnosis

Most common were - cutaneous larva migrans (CLM) - insect bites - skin abscess -alergic reactions © by author -In Caribbean:ESCMID 31% skinOnline diseases Lecture Library

Lderman ER et al. International Journal of Infectious Diseases (2008) 12, 593—602 CUTANEOUS LARVA MIGRANS

Caused by the larvae of animal hookworms Ancylostoma braziliense is the species most frequently found  Humans are infected in tropical / subtropical areas of endemicity by contact with contaminated soil The hookworm larva burrows through intact skin but remains confined to© the by upper author dermis Larval migration is marked by an intensely pruritic,ESCMID linear or serpiginous Online track Lecture (creeping Library eruption). Usually heals spontaneously Eric Caumes Clinical Infectious Diseases 2000;30:811–14 TUNGIASISANDMYIASIS

Tungiais Caused by a sand flea (Tunga penetrans) Nodular subcutaneous lesion with a central dark spot The flea is extracted surgically Myasis Caused by the larva stage of the tumbu (Cordylobia antropophaga© ) byor bot author fly (Dermatobia hominis) AfricaESCMID and Latin America Online Lecture Library Oclusion of the punctum with petroleum jelly James H . Diaz. J Travel Med 2006; 13: 100–111 TUNGIASISDISTRIBUTION

Onchocerciasis caused by the filarial Onchocerca volvulus. generalized pruritus, often associated with a papular rash. filariae are transmitted by the bites of day-biting black flies. the main risk: long-stay travellers living in rural sub-Saharan Africa; rarely in Latin America. Loa loa filariasis transmitted by day-biting deer flies. transient, migratory, subcutaneous,© by author painful, or pruritic swellings produced by the adult nematode migration. Rarely, the worm can be seen in the conjunctiva of the eye Diagnose:ESCMID larval stages Online (microfilaria) Lecture in blood collected Library (day) rarely occur in long-term travelers (rural sub-Saharan Africa) GNATHOSTOMIASIS nematode infection found in Southeast Asia less commonly in Africa and Latin America. Infection results from eating undercooked or raw freshwater fish. Symptoms: transient, migratory, subcutaneous, pruritic, or painful swellings ; may occur weeks or years after exposure. worm larva(e) migrates© throughout by author the body, including the central nervous system. Eosinophilia is common, diagnosisESCMID can be made Online by serology Lecture Library PHOTOQUIZ

23-year-old woman returned from beach vacation in Thailand, severe widespread pruritic rash erythematous, infiltrative papules and papulopustules over her entire body, specially on her buttocks and back Skin biopsy: intraepidermal pustule rich in eosinophils and necrotic keratinocytes ; ©epidermal by author and upper dermal chronic infiltrate with many eosinophils. No parasites ESCMID Online Lecture Library A. Bacterial folliculitis. D. Scabies B. Gnathostomiasis E. Hookworm folliculitis C. Larva currens (S. stercoralis). . PREVENTION-1

Pre-travel advise is essential, focus on preventing parasites transmitted via  mosquitoes (filariasis, malaria), ingestion (amebiasis, cryptosporidiasis, giardiasis, microsporidiosis ),  environmental contact (schistosomiasis, strongyloidiasis) © by author pre-travel interventions focus on these issues, target type of travellers ESCMID Onlinedestinations Lecture Library health risks to consider PREVENTION-2

keep dogs and cats and cattle off the beach (CLM, tungyasis)

freshwater avoidance (shistosomiasis) only 26% of Peace Corps Volunteers did not swim in freshwater for their entire tour of 27 months*  mass chemotherapy for both human and livestock shistosomiasis whenever© applied by author Public Health and animals health should beESCMID take in consideration Online Lecture Library TRAVEL SAFE. TRAVEL SMART

*Outwater A, et al., J Travel Med 2005; 12: 265–269 TAKE HOME MESSAGES -1

Parasites affect the traveller frequently; Asia and Africa are most common destinations Immigrants, VFR and expatriates seems more prone to get parasite infection Although for CLM tourists (and children) are more commonly afected

Special care should be taken© by in immunocompromisedauthor travellers GoodsESCMID, animals and Online even organs Lecture for transplant Library also travel Long term consequences of parasitic infections should be considered TAKE HOME MESSAGES -2

Enteric infections, malaria and cutaneous larva migrans are frequently diagnosed Rare diagnosis must be consider in special situations

Prevention is essential and pre travel appointments should be implemented

Public Health , safe water© distributionby author, sanitation agricultural conditions and animal health are important in the controlESCMIDof parasitic diseasesOnline Lecture Library