Fever in the returning traveller Viviana Elliott Consultant Acute Medicine

Aims To provide a practical initial approach to the diagnosis and management of febrile adult returning from abroad.

Objectives 1.To be able to understand the importance of the topic 2.To be able to take a direct related history 3.To be able to correlate incubation period with most likely diagnosis 4.To be able to identify diagnosis that you can’t miss 5.To be able to “call a friend” if you are not sure

Objectives 1.To be able to understand the importance

Why do you think it is important?

Coventry’s ethnic diversity Ethnic group% Total Population : persons100% White British78.3% White Other2.2% Indian8% Pakistani2.1% Black Caribbean1.1% Black African0.6% Black Other0.1% Chinese or other ethnic group: Chinese 0.7%

World travel Students 2 universities Coventry college Lecturers Elective students: medics, vets Visiting family and relatives Holiday

Aetiology of fever after travel to tropics DiagnosisMacLean et al (n=597)Doherty et al (n=195) Malaria3242 Hepatitis63 Respiratory infection* LRTI- Bronchitis and Pneumonia Urinary tract infection42.5 Dengue fever26 Enteric fever22 Diarrhoeal illness Epstein-Barr virus20.5 Pharyngitis12 Rickettsia10.5 Amoebic liver abscess10 Tuberculosis12 Meningitis11 Acute HIV0.31 Miscellaneous6.35 Undiagnosed ( viral and non specific infect)

Objectives 1.To be able to understand the importance 2.To be able to take a direct related history

History Brief Directed Workout timescales Then you can calculate incubation periods and group likely causes Bonus points if you find something on examination

“5 W questions” Who? What? Where? When? Why?

“5 W questions” Who? What? Where? When? Why?

Who? – risk factors Travellers Sub-Saharan –TB –HIV Homosexual –HIV –Viral Hepatitis South Asian? – TB I know this might sound prejudiced but use it is an aid memoire

“5 W questions” Who? What? Where? When? Why?

What? Occupation –Farmer recently died of listeria at UHCW –Sewerage workers and leptospirosis Activities –Ramblers and tick bites eg. Lyme disease Animal contact

“5 W questions” Who? What? Where? When? Why?

Details of travel –Malaria endemic country? – Where?

“5 W questions” Who? What? Where? When? Why?

When? When did they go? When did they return? When did the symptoms start?

Objectives 1. To be able to understand the importance 2.To be able to take a direct related history 3.To be able to correlate incubation period with most likely diagnosis

Incubation period Short (<10 days) Medium (10-21 days) Long (>21 days)

Short (<10 days) –Gastroenteritis

Medium days Malaria Enteric fever

Long (>21 days) Viral hepatitis Malaria TB HIV

“5 W questions” Who? What? Where? When? Why?

Why? (travellers) Did they go for sex? Whom did they have sex with? Package holiday? –Low risk

Objectives 1.To be able to understand the importance 2.To be able to take a direct related history 3.To be able to correlate incubation period with most likely diagnosis 4.To be able to identify diagnosis that you can’t miss

Key diagnoses not to miss Malaria Enteric fever HIV TB Because if missed they can result in… –Death –Chronic disability

Malaria Originated probably form animal Malaria in central Africa Spread around the world by human migration 500 million people infected every year Holoendemic (most people infected) Sub-saharan Africa > 75 % rate Transmission all year round 75% of the deaths are in children under 5 Adults significant immunity low parasitemia few symptoms

World-wide distribution

Malaria in the UK Imported into the UK from tropical countries cases reported each year deaths

Human Malaria – 4 species ¾ reported malaria cases in the UK are caused by Plasmodium falciparum, which can lead to life threatening multi-organ disease. Most non-falciparum malaria cases are caused by Plasmodium vivax Few cases are caused by Plasmodium ovale or Plasmodium malariae.

Clinical presentation In non-immune individuals(children in any area, adults in hypoendemica area (0-10 % rate) and visitors to non- malarious region Incubation days (longer) Symptoms: Malaise Fever (up to 41˚ C) Rigors Drenching sweats Vomiting or diarrhoea

P. vivax or P. ovale infection Mild illness Gradual anaemia May be tender hepatomegaly Recovery 2-4 weeks Hypnozoites in liver can cause relapses for many years after infection Chronic ill health due to anaemia and hyperactive splenomegaly

P. malariae infection Mild illness but tends to run a more chronic course In children can cause Glonerulonephritis and nephrotic syndrome

P. falciparium Vast majority of malaria death are due to P. Falciparum Patients deteriorate rapidly Higher risk of bacterial infections “Blackwater fever” is due to widespread intravascular haemolysis affecting parasitized and unparasitized red cell giving rise to dark urine

Specific and urgent investigation “Malaria parasites” Thick (find it) Thin (typify it) Rapid antigen test Less sensitive for non falciparum No info about parasite count, maturity or mixed species Use in adjunct with microscopy

Major features of severe or complicated falciparum malaria in adults Parasite count 2% or more Impaired consciousness or seizures (cerebral malaria) Renal impairment (oliguria 265mmol/l) Acidosis (pH < 7.3) Hypoglycaemia (<2.2 mmol/l) Pulmonary oedema or acute respiratory distress syndrome (ARDS) Haemoglobin 8 g/dL Spontaneous bleeding/disseminated intravascular coagulation Shock (algid malaria e BP < 90/60 mmHg) Haemoglobinuria (without G6PD deficiency )

Why high risk of hypoglycaemia in P falciparum malaria ?

Why high risk of hypoglycaemia? Plasmodium use of glucose 75% greater than normal red cell Quinine and Quinidine stimulates secretion of insuline Associated to cerebral malaria > children and pregnant woman

Review Malaria algorithm

Key features Malaria Malaria is a medical emergency and patients withsuspected malaria should be evaluated immediately Return travellers with fever and any other symptoms Geographical distribution ( beware of package holidays to the Gambia) Think of relapse in the absence of recent travel

Enteric Fever 16 million new cases worldwide mainly India and Africa death per year Typhoid is caused by Salmonella typhi Typical form of Enteric Fever Paratyphoid is caused by Salmonella paratyphy A,B or C Less severe illness

Acute systemic illness: Incubation period: days Food/water- borne Symptoms: –Headache –Fever –Abdominal discomfort

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 marrowhigher 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 Ciprofloxacin In patients returning from Africa resistance 4% If resistance to Ciprofloxacin: Azitromycin NOTE: fever take some time to respond regardless of antibiotic use failure to defervesce is not a reason to change antibiotics if sensitive

Key features Enteric fever Salmonella typhi Food/water- borne Especially South Asia travel Any traveller with fever and headache returning in the last 21 days Diarrhoea often absent or late in illness Blood culture diagnosis Septicaemia and death

Human Immunodeficiency Virus (HIV) 40 million people are HIV + and half of them are in Africa (WHO 2004) HIV 1 (retrovirus) is responsible for most cases world wilde HIV 2 related virus produces similar illness with longer latent period 3 million have acquired immunodeficiency syndrome (AIDS)

Transmission Sexual contact 75% Infected blood products IV drug abuse Perinatal

Stages of infection Acute infection: asymptomatic Sero-conversion: transient illness 2-6 weeks after HIV infection: fever, malaise, myalgia, pharyngitis, maculopapular rash or meningngoencephalitis (rare) Persistent generalised lymphadenopathy (PGL) nodes ˃ 1 cm and ≥ 2 extra-inguinal sites for ˃ 3 months+ Opportunistic infections: Candida, herpes zoster, tenia infections (AIDS related complex)

Key features HIV –Risk group –Recurrent infections Herpes zoster –Oral candida –Persistent lymphadenopathy –Anaemia, leucopaenia, thrombocytopaenia

Key features TB Risk group Chronic systemic and respiratory symptoms Unresolving symptoms, raised inflammatory markers and belonging to a risk group Beware of protean manifestions

Objectives 1.To be able to understand the importance 2.To be able to take a direct related history 3.To be able to correlate incubation period with most likely diagnosis 4.To be able to identify diagnosis that you can’t miss 5.To be able to “call a friend” if you are not sure

“Call a friend” at UHCW The Infection & Tropical Medicine Service Dr Ravi Gowda in patients ward 31 GUM Consultant service 24/7 through switchboard HIV clinics at the Coventry & Warwickshire hospitals General Infectious Diseases outpatient once a week (Tuesday am) Joint TB clinic with Dr Dhillon (Tuesday pm)

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

Useful websites Further reading : “Fever in the returning traveller part II in website”