Infectious Diseases in Immigrants and Returning Travellers

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1 Infectious Diseases in Immigrants and Returning Travellers Tom Blanchard Regional Infectious Diseases & Tropical Medicine Unit North Manchester General Hospital

2 Outline Immigrants Evidence-base GeoSentinel Specific Infections Malaria Dengue Enteric fever typhoid & paratyphoid British Infection Society Recommendations Other infections from abroad

3 Immigrants & their infections China Hepatitis B India TB Hepatitis B Pakistan Hepatitis C Hepatitis B TB

4 Immigrants & their infections Sub-Saharan Africa HIV TB Schistosomiasis Hepatitis B (esp W. Africa) North Africa Hepatitis C Schistosomiasis Middle East Brucella Hydatid

5 Immigrants and their infections Eastern Europe Hepatitis B HIV Hepatitis C TB Southern Europe Hepatitis B Hepatitis C HIV

6 Immigrants & their infections South America Hepatitis B Schistosomiasis Leishmaniasis Trypanosomiasis HIV North America HIV Hepatitis B Hepatitis C Lyme

7 Don t forget NCD s Hypertension Diabetes Ischaemic heart disease CKD COPD Vit D deficiency

8 Fever from abroad

9 Evidence-base Variable quality and utility... Usually: from single institution or region only hospitalised patients often focussed on specific diseases, age groups or types of travellers often mix immigrants and travellers Studies from several years ago may no longer be of relevance Changes in destinations/activities Shifts in disease distribution New vaccines and prophylaxis measures...

10 GeoSentinel

11 GeoSentinel 31 sites on six continents Anonymous, questionnaire-based information on all sick travellers crossed and international border within 10 years and seeking medical care for an illness presumed to be travel related Excluded those who sought medical care during travel & those travelling for immigration purposes

12 Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

13 Fever in Returned Travellers: Results from the GeoSentinel Network Fever included both reported and documented fevers 53% subjects reported from European sites Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

14 Syndromes Of all returned travellers with fever: Febrile systemic illness 35% Diarrhoeal disease 15% Respiratory illness 14% Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

15 Summary of diagnosis groups and specific diagnoses

16 Systemic febrile illness Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

17 Malaria Most common specific diagnosis in this study (14%) Generally 27-48% of hospitalised returning travellers have malaria in other studies 5 species: Plasmodium falciparum, vivax, ovale, malariae And now P. knowlsei Falciparum in 66% in this study Also contributory cause in 33% of deaths Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

18 Malaria lifecycle in man

19 Diagnostics General: Thrombocytopaenia, anaemia, leucopaenia Transaminitis Specific: Thick & thin blood films RDTs

20 Malaria blood films Thin film

21 Malaria blood film Thick film

sensitive for non-falciparum species unable to give you estimate of

22 Films vs. RDTs RDTs: almost as sensitive as good microscopists for falciparum less sensitive for non-falciparum species unable to give you estimate of parasitaemia unable to identify schizonts unable to identify mixed species Should be viewed as complementary & additive, not an alternative, to a film

23 Severity markers Parasitaemia > 2% Presence of schizonts Presence of complications ARF Cerebral ARDS Just really unwell...

24 Treatment Mild/moderate: Oral quinine (& second agent) Oral malarone Oral co-artem Severe: IV quinine (& second agent) IV artesunate (& second agent) Adjuncts: Nil work...

25 Difficulties with malaria... Can only diagnose it if you think of the diagnosis Canadian study: Diagnosis of malaria initially missed in 59% cases Average delay in falciparum from presenting to healthcare facility and treatment = 7.6 days! Kain et al. CID 1998;27:142-9

26 Don t have to have fever... Geosentinel: 10% of patients with malaria did not report fever as main reason for seeking care 1 HTD: Only 45% of patients with malaria had fever at time of presentation 2 1 Wilson et al., Clin Infect Dis. 2007;44(12): Nic Fhogartaigh et al. QJM 2008;101(8):649-56

27 If in doubt of species... Sometimes labs will not commit to a species... Treat as falciparum

28 GeoSentinel Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

29 Dengue Mosquito-borne viral infection Almost certainly under-diagnosed in GeoSentinel Symptoms may be mild and non-specific Incubation period short and therefore may seek medical attention whilst still abroad Israeli traveller sero-survey % dengue seroconversion in those travelling >3 months to Tropics 1 Potasman et al., Emerg Inf Diseases 1999;5:824-7

30 Dengue map

31 Clinical presentation Incubation 3-14 days Fever, headache, retro-orbital pain, myalgias, arthralgias & rash Bleeding gums, epistaxis & GI haemorrhage

32 Diagnostics General: Thrombocytopaenia, leucopaenia Often transaminitis Specific: Acute PCR but not generally available >7 days illness IgM (not real-time) >3 weeks IgG titre rise (not real-time) Usually a clinical diagnosis

33 Treatment Supportive Watch for increasing haematocrit and dropping platelet count...

34 DHF & DSS Dengue haemorrhagic fever Triad: Bleeding Plt <100 Vascular leak (>20% increase in haematocrit, hypoproteinaemia, clinical effusions) Mortality 10-20% Dengue shock syndrome As above plus: Narrowing pulse pressure (<20mmHg) Systolic <90mmHg Mortality 40%

35 Enteric Fever Typhoid & Paratyphoid

36 % laboratory reports %llaboratory reports Typhoid: Laboratory reports of S. Typhi where there was known recent travel abroad, by region of travel, England, Wales, and Northern Ireland: In 2005, the majority of travel-associated typhoid cases had recently travelled to the Indian sub-continent (94%). 100% 80% 60% 40% 20% 0% 1996 Not stated Other South East Asia and Far East Sub-Saharan and Southern Africa Indian sub-continent Year Paratyphoid: Laboratory reports of S. Paratyphi A where there was known recent travel abroad, by region of travel, England, Wales, and Northern Ireland: In 2005, the majority of paratyphoid A cases had recently travelled to the Indian sub-continent (94%). Paratyphoid B is usually associated with travel to South America. 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1996 Other Country not stated South East Asia and Far East Indian sub-continent Year Data from the voluntary laboratory reporting system via Labbase 2 Data from the voluntary laboratory reporting system via Labbase 2

37 Clinical presentation Incubation 7-18 days Often non-specific: Fever, chills, constitutional symptoms Constipation or diarrhoea Classically: Week 1: step-wise increase in fever Week 2: fever & abdo pain Week 3: complications... Rose spots very rare...

38 Diagnostics Avoid Widal and serological assays Culture the organism Yields: Blood 80%+ (positive from 1 st week) Stool 35-65% Urine 0-58% Best of all is bone marrow

39 Typhoid treatment >70% of UK isolates of S. typhi & S. paratyphi are resistant to ciprofloxacin All remain sensitive (so far) to ceftriaxone Isolates from Africa still usually ciprofloxacin sensitive If ciprofloxacin sensitive ask if done by disk test if so need nalidixic acid sensitivities.

40 More subtleties It is not just the symptoms but also: Incubation period Areas visited Activities engaged in Prophylaxis received previously (or previous natural infection) Why did this person, from this place, develop these symptoms at this time?

41 Interval between return from travel and medical evaluation Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

42 Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

43 Other insights from GeoSentinel Mononucleosis syndrome in 1.4% EBV/CMV/Toxo but also acute HIV Leptospirosis Amoebic liver abscess 25 patients 23 patients Vaccine-preventable illnesses in 3% Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

44 Sexual contact during travel 782 travellers % reported new sexual partner on most recent trip 2/3 did not use condoms 6% acquired an STI Canadian study of international travellers 2 15% had sex with new partner or exposure to blood/body fluids Tattoos, dental work, injections etc. 1 Hawes et al., AIDS 1994;8(2): ; 2 Correia et al., J Trav Med 2001;8(5):263-6

45 VFR VFR Visiting Friends & Relatives Have different exposures Not solely tourist destinations Often stay/eat in non-tourist settings Don t often seek pre-travel advice Odds ration of seeking pre-travel advice = 0.24 (95%CI ) Odds ratio of having a vaccine-preventable illness = 1.8 (95%CI ) Wilson et al., Clin Infect Dis. 2007;44(12):1560-8

46 Malaria: Malaria cases in the UK, with stated reasons for travel: 2005 In 2005, 55% of malaria cases reported had information about reason for travel. 12% 9% 5% 10% 52% Of those just over half were contracted by those, usually from minority ethnic groups, visiting friends and relations in malarious countries. The four other main risk groups are those travelling for holiday or on business, new entrants to the UK, and foreign visitors falling ill while visiting the UK. New entrant 4% 9% Visiting family in country of origin UK citizen living abroad Business/professional travel Holiday travel Foreign visitor ill while in the UK Other* *Other includes: civilian sea/air crew, British armed services, foreign student studying in the UK, and children visiting parents living abroad. Data from HPA Malaria Reference Laboratory

47 Undifferentiated fever S S A S E A S C A ME/ NA S A Diagnostics Comments / empiric Rx Amoebic Liver abscess Serology (>92% sensitive at presentation) U/S abdomen Empiric tinidazole / metronidazole if suggestive clinical and travel history with abscess on U/S. Serology is positive in 25% individuals in endemic areas Brucellosis Extended B/C, serology Suspect if contact with livestock / unpasteurised milk. Discuss treatment with ID unit Chikungunya PCR (1-4 d?) or IgM (>5 days) Manage symptomatically as an outpt Dengue IgG (secondary infection) & IgM ELISA (4-5 days) Dengue PCR (1-4 days?) Manage symptomatically as outpt with daily FBC unless high risk of shock (high haematocrit, falling platelets). Supportive management. Enteric fever (typhoid / paratyphoi d) Blood cultures (up to 80% in 1st wk) If clinically unstable Rx empirically with ceftriaxone. If travelled from SSA ciprofloxacin remains an alternative. If confirmed sensitive switch to ciprofloxacin. Azithromycin alternative. Rx 2 wks. HIV HIV (antigen and antibody) Rapid test does not pick up seroconversion illness Leptospirosis CSF + B/C < 5days EIA IgM > 5 days Rx on suspicion doxycycline / penicillin (may not be helpful after jaundice developed). Transfer B/C at room temp to reference lab Rickettsia Acute phase wk serum Consider empiric Rx doxycycline if exposure to ticks in game park, headache, fever +/- rash/eschar Schistosomiasis, acute Not helpful Empiric Rx praziquantel if appropriate presentation and exposure 4-8 wks previous. Consider steroids.

48 Fever with rash S S A S E A S C A ME /NA S A Diagnostics Comments / empiric Rx Dengue HIV Rickettsia IgG (secondary Ifn) & IgM ELISA (4-5 days) Dengue PCR (1-4 days) HIV (antigen and antibody) Acute phase wk serum Manage symptomatically as outpt with daily FBC unless high risk of shock (high haematocrit, falling platelets). Supportive management. Rapid test does not pick up seroconversion illness Consider empiric Rx doxycycline if exposure to ticks in game park, headache, fever +/- rash/eschar Schistosomiasis, acute Not helpful Empiric Rx praziquantel if appropriate presentation and exposure 4-8 wks previous. Consider steroids VHF PCR to ref lab Always contact regional centre

49 Fever with jaundice S S A S E A S C A ME/ NA S A Diagnostics Comments / empiric Rx Leptospirosis CSF + B/C < 5days EIA IgM > 5 days Rx on suspicion Doxycycline / penicillin (may not be helpful after jaundice developed). Transfer B/C at room temp to reference lab Viral Hepatitis HepA IgM, Hep B Sag, Hep E IgM Acute hepatitis C should be considered in homosexual men VHF PCR to ref lab Always contact regional centre Yellow fever

50 Fever with hepato +/- splenomegaly S S A S E A S C A ME /NA S A Diagnostics Comments / empiric Rx Amoebic LA Serology (>92% sensitive at presentation) U/S abdomen Empiric tinidazole / metronidazole if suggestive clinical and travel history with abscess on U/S. Serology is positive in 25% individuals in endemic areas Brucellosis Extended B/C, serology Suspect if contact with livestock / unpasteurised milk Leptospirosis CSF + B/C < 5days EIA IgM > 5 days Rx on suspicion doxycycline / penicillin (may not be helpful after jaundice developed). Transfer B/C at room temp to reference lab Trypanosomiasis Blood film Travel to game parks in SSA; discuss with tropical centre Visceral leishmaniasis Leishmaniasis serology, bone marrow Travel to Mediterranean, Horn of Africa, Bihar, Nepal, Bangladesh, Brazil

51 Incubation periods Incubation period Short ( <10 days) Medium (10-21 days) Long ( >21 days) Infection Acute gastroenteritis (bacterial, viral) Respiratory tract infection (bacterial, viral including avian influenza) Meningitis (bacterial, viral) Arboviral infections e.g. dengue, Chikungunya Rickettsial infection e.g. tick typhus, scrub typhus Relapsing fever (borrelia) Protozoal Malaria (Plasmodium falciparum) Trypanosomiasis rhodesiensae Acute Chagas disease Viral HIV, CMV, EBV, viral haemorrhagic fevers Bacterial Enteric fever (typhoid and paratyphoid fever) Brucellosis Q fever Leptospirosis Protozoal Malaria (including Plasmodium falciparum) Amoebic liver abscess Visceral leishmaniasis Viral Viral hepatitis HIV

52 Geographical exposure Risk factor Common Occasional Rare but important Geographical area Sub-Saharan Africa Malaria, P. falciparum Malaria, non-falciparum Rickettsial infection HIV-associated infections (inc seroconversion) Acute Schistosomiasis (Katayama) Dengue Enteric fever Meningococcus Brucellosis Viral haemorrhagic fever Trypanosomiasis Other Arbovirus e.g. Rift Valley, West Nile fever, Yellow fever Histoplasmosis Visceral leishmaniasis Visceral leishmaniasis North Africa, Middle East and Brucellosis Mediterranean Eastern Europe and Scandanavia Lyme Disease Tick Borne encephalitis South and Central Asia Enteric fever Dengue Malaria, non-falciparum Malaria, P. falciparum Chikungunya Visceral leishmaniasis South East Asia Enteric fever Leptospirosis Scrub typhus Dengue Meliodosis Chikungunya Penicilliosis Malaria, non-falciparum Malaria, P. falciparum North Australia Ross River Fever Meliodosis Latin America and Caribbean Dengue Enteric fever Malaria, non-falciparum Malaria, P. falciparum Histoplasmosis Coccidiomycosis North America Lyme Disease Ehrlichiosis Histoplasmosis West Nile fever Coccidiomycosis Rocky Mounted Spotted fever Congo-Crimean haemorrhagic fever Yellow fever Hanta virus Acute Trypanosomiasis (Chagas)

53 Initial Ix in undifferentiated fever Investigation Interpretation Malaria film +/- dipstick antigen test (RDT) Perform in all patients who have visited a tropical country within 1 year of presentation The sensitivity of a thick film read by an expert is equivalent to that of an RDT, however blood films are necessary for speciation and parasite count Three thick films / RDTs over 72 hours (as an outpatient if appropriate) should be performed to exclude malaria with confidence Blood films (thick and thin) should be sent to the reference lab for confirmation FBC Lymphopaenia: common in viral infection (dengue, HIV) and typhoid Eosinophilia (>0.5 x 10 3 ul): incidental or indicative of infectious (e.g parasitic, fungal) or non-infectious cause table 7 Thromobocytopaenia: malaria, dengue, acute HIV, typhoid, also seen in severe sepsis Blood cultures Two sets should be taken prior to antibiotics Sensitivity of up to 80% in typhoid U&E, LFTs See table 5 Serum save HIV should be offered to all patients with pneumonia, lymphocytic meningitis, diarrhoea, unexplained fever Other e.g. arboviral, brucella serology if indicated EDTA for PCR Consider if other features suggestive of arboviral infection, VHF Urinalysis Proteinuria and haematuria in leptospirosis Haemoglobinuria in malaria (rare) CXR

54 Other issues Diagnoses established abroad......best not to believe them!

55 Other thoughts Always think: Why did this person, from this place, develop these symptoms at this time? Always think: Malaria Always: Phone us up at any time if at all unsure Regional Infectious Diseases Unit, North Manchester General Hospital, Pennine Acute NHS Trust

56 No of visits (thousands) Travel trends: Number of visits abroad by UK residents to tropical regions of the world: Since 2003, visits to tropical destinations increased by 28% compared to a decrease of 0.2% for visits to EU15. All other regions saw an overall increase except Sub-Saharan and Southern Africa Indian sub-continent (ISC) South and Central America Caribbean Sub-Saharan and Southern Africa Other Asia (not ISC) Year Data from the International Passenger Survey, Office for National Statistics

57 Risk to traveller - 1 month in tropics Any health problem 55% Travellers diarrhoea 35% Malaria (W Africa, no prophylaxis) 2% Giardiasis 0.6% Hepatitis 0.45% Steffen R 1988

58 Exposure and infection Raw foods enterococci, trichinosis Untreated water, milk hepatitis, brucellosis, shigella Fresh water contact schistosomiasis, leptospirosis Sex HIV, syphilis, GC Insect bites malaria, arbovirus, trypanosomes Animals rabies, Q fever, brucellosis, plague People VHF, hepatitis, meningococcal

59 Fever and localizing signs Rash Jaundice Lymphadenopathy Hepatomegaly Splenomegaly Eschar Haemorrhage - dengue, typhoid, HIV, syphilis - malaria, hepatitis, leptospirosis - HIV, rickettsial infections - amoebic liver abscess, leptospirosis - malaria, typhoid, brucella - rickettsial - VHF, rickettsial infection

60 Investigations FBC, U & E s, LFT s Thick and thin films (antigen detection) Blood cultures Save serum for serology Urine analysis and culture Stool microscopy and culture CXR

61 Tuberculosis

62 More tuberculosis

63 CXR November 07

64 CXR January 08

65 Echo Global semi-solid looking pericardial collection. Degree of pericardial thickening. LV normal size, severely reduced performance (25-35%). Estimated RV pressure 26 mmhg.

66 Echo

67 Eosinophilia means worms

68 Schistosoma haematobium

69 Acute schistosomiasis (Katayama syndrome) Headache Cough, wheeze Fever Fatigue Urticaria Eosinophilia Hepatosplenomegaly

70 Blood in urine, semen, faeces Look for eggs in urine, semen, faeces Serological tests stay positive after Rx Treat praziquantel

73 Cutaneous larva migrans Cat or dog hookworm larvae

74 Cutaneous larva migrans

75 Myiaisis Tumbu fly

76 Dermatobium hominis

77 Cutaneous leishmaniasis

78 Other rashes? leishmaniasis Herpes virus phagadenic ulcer Severely immunocompromised patient Travel related HIV

79 Indian sea captain

80 Clinical and radiological signs Right lung base

81 Amoebic liver abscess Abscess in right lobe of liver on US Positive amoebic serology

82 Tick typhus - His South African game reserve Fever, headache, dry cough Wife also affected Eschar on inspection

83 Hers Eschar under bra strap Rash on legs

85 Thai imports - rash & fever HIV seroconversion Secondary syphilis

86 Top tips for screening Blood-borne viruses HIV Hep C Hep B Think of tuberculosis Don t forget malaria in the febrile patient Don t forget non-communicable diseases

Post Travel Fever. Dr. Eyal Leshem. Center for Geographic Medicine Sheba Medical Center Tel Hashomer, Israel

Post Travel Fever. Dr. Eyal Leshem. Center for Geographic Medicine Sheba Medical Center Tel Hashomer, Israel Post Travel Fever Dr. Eyal Leshem Center for Geographic Medicine Sheba Medical Center Tel Hashomer, Israel Introduction Fever in returned traveler: Trivial vs. life threatening infections Tropical and