Fever in the returning traveller Part II Dr Viviana Elliott Consultant Acute Medicine

Viral haemorrhagic Fever Lassa fever RARE!!! Only VHF reported inUK Dengue Others Ebola Marburg Yellow fever Malaria: Plasmodium falciparum 5000 x common than Lassa fever!!!!! Fever, rural area, likely contact, high fever , severe exudative sore throat, prostration out of proportion with fever

Malaria Should be thought in febrile illness in travellers returning to Europe from tropic Sub - Saharan Africa

Malaria

Early diagnosis and assessment of severity is vital to avoid deaths Symptoms are non specific Almost 50% are a febrile on presentation but all have history of fever Consider country of travel, stopovers and date of return. Incubation: at least 6 days and within 3 months more with prophylaxis Consider other infections: Typhoid fever, hepatitis, dengue fever, avian influenza, SARS, HIV, Meningitis, Encephalittis and VHF

Urgent investigations Thick (find it) and thin (typify it) and rapid antigen test ( less sensitive for non falciparum, no info about parasite count, maturity or mixed species. Use in adjunct with microscopy) FBC: Thrombocytopenia, U&Es, LFT and GLUCOSE BCM for typhoid and other bacteriemia Urine dipstick for haemoglobinuria and culture. Stool culture if diarrhoea CXR to r/o CAP

La Laboratory diagnostic approach Diagnostic Approach FBC ↑WBC with neutrophils ↓ WBC with neutrophils ↓ WBC with lymphocytes Pneumonia UTI Leptospirosis Brucella Typhoid Other Salmonella Viral Rickettsial Eosinophils: helminth, drugs. Unlikely bacterial LFTs Very High High bili + Mod trans + Renal disfunction Viral hepatitis Yellow fever Toxin Leptospirosis

Falciparum Malaria or mixed infection

Admit all cases and assess severity

Complicated Malaria

Treatment

Enteric Fever (Typhoid and Paratyphoid)) Commonest serious tropical disease from Asia Distribution: worldwide in developing countries Asia and south east Asia >100 cases per 100.000 person per year 77% in person visiting friends and family Most cases occur 7 – 18 days after exposure range 3-60 days

Clinical Presentation of Enteric Fever Fever is almost invariable Relative bradycardia only first week

Clinical presentation of Enteric Fever Constipation more common than diarrhoea initial loose stools fairly common Maybe evanescent rash: “Rose spots”

Investigations First Week: Bloods: low WBC, platelets and mildly raised LFTs BCM positive 40-80% Second week Urine culture 0-58% Stool culture 35-65% Bone marrow higher sensitivity than BCM Newer rapid serology IgM against specific S Typhi Widal test lacks sensitivity and specificity Not recommended

Complications Incidence: 10-15% illness >2 weeks GI Bleed Intestinal perforation Typhoid encephalopathy Vaccination provides incomplete protection

Treatment Unstable treat empirically pending BCM First choice: Ceftriaxone 2g iv 70% of isolated S typhi and paratyphi imported into Uk are resistant to Cipro In patients returning from Africa resistance 4% If resistance to Cipro, Azitromycin NOTE: fever take some time to respond regardless of antibiotic use failure to defervesce is not a reason to change antibiotics if sensitive

Rickettsia: Common infection in travellers to games parks in southern Africa

Ricketssias Rickettsia Africae Conorii Typhi Orientia Tsusugamuyi African tick bite fever Mediterranean spotted fever fever Murine typhus Scrub typhus from Asia Transission Catle ticks Dog tick Rat fleas Mites Distribution Sub-saharan African and safari park in southern Africa Eastern Caribean Mediterranean and Caspian Litoral, Middle East , Indian subcontinent and Africa Tropical and subtropical areas in port cities where the rodent population is dense Rural South Asia (Laos) South East Asia Western pacific Infrequently report by travellers Complications Fatal 32% Fatal 2% If untreated: Pneumonitis, CID,ARF and Meningoencephalitis

Common presentation Incubation: 5-7 days (up to 10 days) Non specific fever, head ache , mialgia, inoculation echar/rash and lymphadenitis Consider other causes of fever and skin lesions wich resembles echar: Antrax African Trypanosomiasis (chancre at site of tsetse fly bite)

R Conorii: single R Africae: multiple R Typhi

Investigations Treatment should be started on suspicion : - illness onset within 10 days - exposure to tick in game park - fever and headache with or without rash Doxycyxline 100 mg bd for 7 days or 48 hs after fever defervescence Confimation IFA paired initial and convalescence –phase serum sample If wider differential is considered: Cipro or Azithromycin

Arbovirus infection Commonest arboviral infection in returning travellers to the UK are Dengue and Chikungunya Incubation: 4 – 8 days (range 3-14) Distribution: Asia and south America Repoted >100 countries and annual global incidence 50-100 million per year Transmission: Aedes aegypty

Clinical presentation Mild febrile illness Headache- retro-orbital pain Myalgia - arthralgia (> back pain) Rash 1st erythrodermic 2nd petechial Bleeding gums, epistaxis and GI bleed Rarely hepatitis, myocarditis, encephalities and neuropathies Convalescence desquamation and post viral fatigue

Dengue 2 days later

Dengue Haemorrhaic Fever (DHF) Plasma leak Haemorrhagic Manifestations Platelets < 100 Dengue Haemorrhaic Fever (DHF) 10-20% Mortality Plasma leak > 20% in pack cells volumen ↓Protein Clinical effusions

Dengue Shock Syndrome Mortality rate up to 40% Narrowing pulse pressure <20 mmHg or BP < systolic of < 90 mmHg

Dengue diagnosis and treatment Positive PCR or if symptoms> 5-7 days +IgM ELISA Retrospective > 4 fold ↑ Ig G by haemoaglutination inhibition test UK reference laboratory services: HPA Special Pathogens reference Unit, Poton Down Treatment identify those patients at high risk of shock with daily FBC and platelets.

Acute Schistosomiasis Katayama fever Incubation: 4-6 weeks ( range 3-10 weeks) Distribution: Africa (Asia- South America) Transmission: Swimming in lakes or rivers Cercariae release from snails penetrates intact skin

Clinical presentation Non specific signs and symptoms (? immune complex phenomenon) fever myalgia arthralgia lethargy cough/wheeze headache rash ↑Liver/spleen diarrhoea Investigations: eosinophilia egg urine-stools minority serology + seroconversion 0-6 months)

Treatment Diagnosis: Fresh water exposure 4-8 weeks previously Fever-Urticarial rash-Eosinophilia Treatment empiric!!!! Praziquantel 2 doses 20 mg/kg, 4-6 hs apart (Mature Schistosomes) Repeat after 3 months ( Immature schistosomes) Short course of Steroids may alleviate acute symptoms

Leptospirosis Distribution: Worldwide including UK (> tropical and subtropical regions) Risk: exposure to fresh surface water, rodents (infected urine) sports events river rafting rescue efforts after flooding

Leptospirosis clinical presentation Incubation : 7 – 12 days (range 2-30 days) Initial phase: “flu like symptoms” lasting 4-7 days Immune phase: “Weil’s disease” 1-3 days later fever, myalgia (calves) haepatorrenal syndrome haemorrhages Conjunctiva suffusions suggestive

Other manifestations GI: V-D, loss appetite, jaundice and hepatomegaly, liver failure, pancreatitis and GI bleed Respiratory: Cough + SOB Meningitis ARF Myocarditis Haemorrages – may confuse DHF

Investigations Urinalysis proteinuria/haematuria FBC PMN leucocytosis Thrombocytopenia Anaemia Clotting normal (capillary fragility) LFT high bili + mildly raised ALT U&Es ARF Serology IgM titre > 1:320 (early infection) > 10 days after symptoms send for IgM ELISA+ Microscopic agglutination MAT to confirm diagnosis

Treatment Upon suspicion Penicillin and tetracycline antibiotics during bacteraemia phase Un well patients and Weil’s disease need renal and liver support Severe diseases is probably immunologically mediated ( ? Benefit from antibiotics)

Amoebic Liver Abscess Incubation: 8-20 weeks ( up to a year) Distribution : Worldwide > developing countries Presentation: 67-98% Fever 72-95% Abdominal pain 43-93% Haepatomegaly 20% PMH dysentery 10% diarrhoea on diagnosis

Investigations FBC neutrophil leucocytosis > 10 X 10 6 L LFT dearranged ↑↑ Alk Pho CRP/ESR raised Indirect haemagglutination >90% sensitivity Stools negative CxR Raised hemi-diaphragm USS DD piogenic abscess (percutanous aspiration) R/O Hydatidic disease first!

Amoebic Liver abscess

Treatment Start empiric treatment in patients with suggestive history, epidemiology and imaging Metronidazole 500 mg tds orally for 7-10 days ( Cure in 90%) Tinidazole 2 g daily for 3 days (less nauseas) Follow treatment with 10 days luminal amoebicide to reduce relapse. Furoate 500 mg tds or Paromomycin 30 mg/kg per day in 3 divided doses

Brucellocis Incubation: 2-4 weeks (up to 6 months) Distribution: world-wide ( Middle East, URRS, Balkan Peninsula and Mediterranean basin) Transmission: infected unpasteurised milk products. Farmers, vets with contact infected parts.

Clinical presentation Fever Commonest presentation acute with rigors or chronic low grade relapsing Lymphadenopathy Hepatosplenomegaly Complications: Osteoarticular disease OA: knees, hips, ankles and wrists Sacroillitis lumbar spine

Other complications Epididymo-orchitis Septic abortions Neurological: meningitis encephalitis brain abcess Endocarditis: Aortic valve and requires early surgery

Investigations and treatment LFT: mild transaminitis FBC: pancytopenia Bone marrow: gold standard BCM: sensitivity 15-70% (prolong cultures up to 4 weeks) Note: Q Fever, rarer, similar from same area Serology is key diagnosis!! Treatment: Doxycycline and Rifampicin 6-8 weeks + amynoglucosides 2 weeks Relapse 10 %

HIV Prevalence in tropical countries is high 1/3 sexually active population and not restricted to high-risk groups 5-51% travellers take part in casual sex while abroad HIV seroconversion and syphilis can present as febrile illness

Hepatitis Incubation: A 15-50 days B 60-110 days E 14-70 days Transmission A-E faecal-oral (water, food:shellfish and direct contact) B sex-blood Diagnosis IgM Traetment Supportive

Fever an respiratory symptoms Upper respiratory tract infection: viral, St.Pneumonia, H Influenza, Grup A steptoccoi Diphteria in traveller returning from URRS, India, South East Asia and South America Lower respiratory tract infections: HIV related PCP Bird flu TB (prolonged visits to families and friends) Histoplasmosis/ Coccidioidomycosis risk activities with dust and bats in caves in America

Initial treatment for “bird flu” Isolate Respiratory isolation ideally negative pressure Samples NPA & nasal swab PCR Inform Local: ICT/Virology/ID Regional: HPA/CCDC Treat: Oseltamivir/Zanamavir

Fever and Neurological Symptoms 15 per 1000 ill returned travellers Most common: Malaria and meningitis Encephalopathy: P falciparum,typhoid and HIV seroconversion Encephalitis with or without fever Common causes in UK + Arboviruses Brucellosis Rabies Rickettsias African trypanosomiasis Discussion with virologist or reference laboratory

Key points Think of the 5 Ws Risk factors for disease Don’t miss… HIV (risk group) TB (risk group) Malaria (knowledge of travel) Enteric fever (knowledge of travel)