key: cord-0954925-8o4kte9i authors: Beeching, Nick title: Fever in the returning traveller date: 2005-07-01 journal: Medicine DOI: 10.1383/medc.2005.33.7.3 sha: ff8b57e1d85ad83a71c0a4b74b9802e45911b0b1 doc_id: 954925 cord_uid: 8o4kte9i Abstract Fever is a common reason for acute hospital admission for tropical illness in UK referral units. A sensible working diagnosis can usually be formulated from a careful history and examination and initial simple investigations. The history should include details of exactly where the patient has been, what conditions he or she was living in, and the exact dates of arrival and departure. The quality of pre-travel advice and vaccinations, adherence to chemoprophylaxis against malaria, avoidance of insect bites and general behaviour abroad (including sexual history) are also important. Localizing features of the illness should be sought on examination. Maintain a high index of suspicion for underlying HIV. The most important illness to consider and exclude is malaria (about 40% of cases), and most of the remainder have cosmopolitan viral infections or imported infections such as an arbovirus (dengue), enteric fever or viral hepatitis. Rarer causes are usually evident from the history and examination, which presupposes a good knowledge of geographical medicine. Initial investigations should include adequate malaria films (supplemented by quick antigen detection tests in many laboratories) and blood count, repeated as necessary, blood, urine and faecal cultures, serum biochemistry, chest radiography and other imaging (e.g. liver ultrasonography) as indicated. In patients in whom malaria is suspected despite negative films, the combination of thrombocytopenia and splenomegaly is supportive but not diagnostic of malaria. Febrile illnesses account for about 40% of hospital admissions for tropical illness in UK referral units. The initial assessment of travellers is aimed primarily at early detection and treatment of malaria (see MEDICINE 33:8, 39), which can be rapidly fatal. Malaria is the most common diagnosis, followed by nonspecific, self-limiting infections, and respiratory and gastrointestinal infections. [1] [2] [3] [4] [5] Start with the question: "Have you ever been overseas?" Every possibly relevant trip should be recorded in detail. Where? -the precise area of travel should be identified, not just the continent or country. Why? -the reason for travel and the patient's activities there may suggest or exclude specific diseases. When? -precise dates of departure and return are required. Viral haemorrhagic fevers can be excluded when more than 21 days have elapsed since the traveller left an endemic area in Africa. Malaria does not develop until at least 8 days after arrival in an endemic area, and most cases of falciparum malaria present within 2 months of exposure. Malaria developing more than 9 months after leaving the Indian subcontinent is almost always caused by Plasmodium vivax, symptoms of which may develop up to 2 years after exposure. What? -a risk assessment of behaviour and activities while overseas should include a detailed sexual history. Swimming in fresh water carries a risk of schistosomiasis (Africa) or leptospirosis (particularly Asia, and Central and South America). A history of tsetse fly bite (usually vividly remembered) in a game park in Africa, or of tick bites (often unnoticed) is helpful. Who? -details of pre-travel immunization and malaria prophylaxis should be recorded, and adherence to antimalarial regimens and antimosquito measures should be assessed, though full compliance does not exclude malaria. Pre-travel health is also important, particularly in patients who are immunocompromised. Fever -the presence of fever should be confirmed; it is usually futile to pursue detailed diagnosis of a minor febrile illness that has already resolved. Patterns of fever are seldom as useful as textbooks suggest. Falciparum malaria usually causes continuous rather than periodic fever, though up to 10% of patients with malaria may be afebrile at presentation. The general condition of the patient should be assessed, looking for localizing signs and for complications of severe malaria, including confusion or drowsiness, shock and jaundice. Insect bites commonly become infected with streptococci or staphylococci. Careful examination is needed to find the eschar (scab) of tick bites (Figure 1 ), which may be hidden in the hairline or under constricting garments (e.g. bra straps, underwear elastic). Diarrhoea may be a presenting feature of falciparum malaria, pneumonia, atypical respiratory infections including severe acute respiratory syndrome, or enteric infection. Jaundice suggests malaria, hepatitis or leptospirosis. Hepatosplenomegaly is found in many infections. Less than 50% of patients with malaria have a palpable spleen, so this sign has little negative predictive value. Lymphadenopathy should always raise suspicion of HIV seroconversion illness, but is also seen in dengue, brucellosis, rickettsial infections and the 'glandular fever' group of infections. Blood tests -investigations should include full blood count, differential WBC count, renal function, liver function tests and at least two sets of blood cultures. It is always worth storing an acute serum or plasma sample on admission for paired serological tests or for polymerase chain reaction-based diagnosis later. Blood films for malaria are essential. Most laboratories are accustomed to interpreting thin blood films, which are most useful for diagnosing the type of malaria and determining the degree of parasitaemia. However, thin films are less sensitive than thick films, which are preferred where local expertise allows. Chemoprophylaxis makes blood films more difficult to interpret because the parasitaemia is more scanty. 2 Ultrasound scan showing amoebic liver abscess in a merchant seaman with fever, neutrophilia and dullness at the right lung base. Liver abscess may mimic pneumonia. Dipsticks for plasmodium species-specific lactate dehydrogenase can detect P. falciparum and P. vivax with almost the same sensitivity as a thick film examined by an expert. In a district general hospital setting, out of hours, these tests should supplement thin film examination. If the first film is negative and malaria is possible, films should be repeated after 12 hours, and possibly repeated again 24 hours later. Thrombocytopenia is present in more than 75% of patients with malaria, but is also caused by dengue and other infections. Malaria or leptospirosis is more likely in those with both raised serum bilirubin and thrombocytopenia, 2 and the combination of spenomegaly and thrombocytopenia is strongly suggestive of malaria. 4 Neutrophilia suggests bacterial sepsis, including meningococcal disease, or amoebic liver abscess (serology is positive in the latter). Eosinophilia suggests nematodes or cestodes, typically acute schistosomiasis (serology and parasitology are often negative at this stage) or filariasis. Antibiotic sensitivities should be reported. Pneumococci from many parts of the tropics are penicillin resistant, and Salmonella typhi and S. paratyphi A isolates from Asia are usually multi-drug resistant. Tropics, bite of anopheline Undifferentiated fever, later stupor, Thrombocytopenia, hypoglycaemia, mosquito anaemia, shock, renal failure blood films (thick and thin), (Plasmodium falciparum); antigen tests regular rigors (P. vivax or P. ovale) Tropics, bite of Aedes Fever for about 5 days, severe Leucopenia, polymerase chain reaction (Stegomyia) mosquito, headache, retro-orbital pain, myalgia, analysis (early), serology (after first sometimes epidemic, lymphadenopathy, blanching skin week of illness) incubation 5-6 days rash on third day, rarely haemorrhages and shock Rural West or Central Africa Persistent fever with severe malaise, Leucopenia, virus isolation, polymerase or hospital workers exposed pharyngeal exudate, swollen face, chain reaction analysis or serology to rodent urine or blood of stupor and hypotension patients, incubation 6-21 days Isolation required (maximum) Mediterranean, southern and Black eschar (scab) at site of tick Leucopenia, serology East Africa, bite of hard tick bite, generalized maculopapular erythematous rash from fourth day, headache, cough Typhoid fever Worldwide Headache, persistent fever, Leucopenia, blood culture abdominal discomfort, splenomegaly, rose spots (rare) Worldwide, but mainly tropics Persistent fever, right upper Neutrophil leucocytosis, abdominal pain and tenderness, ultrasonography of liver, serology signs at right lung base African trypanosomiasis Visitors to African game parks, Chancre at bite site, tachycardia, Hypoglycaemia, thrombocytopenia, tsetse fly lymphadenopathy, splenomegaly, thick blood films, serology, consider transient oedema, variable rashes CSF examination only after obtaining expert advice Mediterranean, Middle East, Persistent fever and wasting in Leucopenia, bone marrow, microscopy, India, East Africa and relatively well individuals, polymerase chain reaction analysis, South America, sandflies progressive splenomegaly, culture (NNN medium); skin biopsy or anaemia and lymphadenopathy, buffy coat examination in HIV-positive infants affected in Mediterranean patients countries, pyrexia of unknown origin and skin rash in HIV-positive patients Bathing in infected fresh water Persistent fever, urticaria, diarrhoea, Eosinophilia at presentation, ova in (Katayama fever) in Africa, Asia, Middle East, liver and splenic enlargement, stool, urine or semen (later only), South America cough serology (later) Imaging -chest radiography is useful in patients with respiratory symptoms, bearing in mind Legionella infection, tuberculosis (TB) and atypical chest infections. Ultrasonography of the liver is required in patients who may have amoebic liver abscess ( Figure 2 ). Unless the patient clearly has a minor upper respiratory infection, hospital admission for investigation may be necessary for 24-48 hours. Falciparum malaria must be excluded, and is the diagnosis in 65-75% of patients hospitalized after visiting Sub-Saharan Africa, compared with 15-25% of those returning from Asia, who are more likely to have dengue fever. 2,5 A combination of geographical and exposure history, presenting syndrome and simple laboratory tests should lead to a sensible working diagnosis ( Figure 3 ). More detailed, evidence-based diagnostic algorithms have recently become available and could be adapted for local use. 6 If malaria cannot be excluded in a patient who is severely ill, empirical treatment for sepsis should include quinine. Management of malaria is discussed in MEDICINE 33:8, 39 . Further investigations and management should be determined by the most likely diagnosis. Early therapy is often appropriate before investigations confirm a clear diagnosis; this usually comprises doxycycline for leptospirosis or tick typhus, or a fluoroquinolone when there is a strong suspicion of enteric fever (with or without a third-generation cephalosporin or azithromycin). When viral haemorrhagic fever or multi-drug-resistant TB is suspected, public health authorities must be involved immediately and the patient should be managed in appropriate isolation facilities. Rare exotic infections should be discussed with an expert in tropical diseases at the earliest opportunity.  Fever from the tropics Fever as the presenting complaint of travellers returning from the tropics Fever in returned travelers: review of hospital admissions for a 3 year period Clinical and laboratory predictors of imported malaria in an outpatient setting: an aid to medical decision making in returning travelers with fever Burden and cost of imported infections admitted to infectious disease units in England and Wales in 1998 and 1999 Practice guidelines for evaluation of fever in returning travelers and migrants FURTHER READING Fever in children returning from abroad Comprehensive tables and references for all imported diseases; a good starting point.) www.nathnac.org (National Travel Health Network and Centre; risks of travel worldwide and preventive measures to reduce risk.) www.promedmail.org/ (ProMED; an excellent website