Acute febrile illness

Acute febrile illness is a measured temperature of 38.0 C or over lasting under 14 days, with or without an obvious source at first assessment.

The first clinical task, within the first hour, is to separate patients who are septic or have a time critical infection from the larger group with self limiting viral illness. Time critical infections include falciparum malaria, bacterial meningitis, bacteraemia, complicated typhoid, rickettsial disease, leptospirosis and viral haemorrhagic fever. Exposure history and incubation period then narrow the cause.

Fever and hyperthermia. Fever results from interleukin 1, interleukin 6 and tumour necrosis factor alpha raising the hypothalamic set point through prostaglandin E2, and responds to antipyretics. Hyperthermia is uncontrolled heat production or failed heat loss at a normal set point (heat stroke, serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia, salicylate and anticholinergic toxicity). It does not respond to antipyretics and needs active cooling.

Thresholds. Fever is 38.0 C or over. Hyperpyrexia is over 41.0 C and is an emergency. Absence of fever does not exclude sepsis, especially in older adults, people taking corticosteroids and patients with kidney failure.

Classification by presentation

• Fever with a localising focus (respiratory, urinary, abdominal, skin, ear nose and throat, central nervous system).
• Fever without a localising focus, which is the core of this presentation.
• Fever with rash, neck stiffness, jaundice, bleeding or lymphadenopathy, each needing its own approach.
• Fever in special hosts: returning travellers, immunocompromised patients, postoperative patients, pregnancy and neonates.

Incubation periods.

• Under 3 days: influenza, bacterial gastroenteritis, meningococcal disease.
• 3 to 14 days: dengue (usually 4 to 7 days), chikungunya, Zika, rickettsioses (5 to 7 days), yellow fever (3 to 6 days).
• Also in this range: Rift Valley fever (2 to 6 days), plague (1 to 7 days), relapsing fever (4 to 18 days), typhoid (usually 8 to 14 days; range 3 to 60).
• Also in this range: viral haemorrhagic fevers (Ebola and Marburg 2 to 21 days, Lassa 3 to 21 days, Crimean-Congo haemorrhagic fever 1 to 13 days).
• 1 to 4 weeks: falciparum malaria (usually 9 to 14 days; over 90% within 3 months), leptospirosis (2 to 30 days), hepatitis A (15 to 50 days), acute schistosomiasis (14 to 84 days), Q fever (2 to 3 weeks).

Weeks to months: brucellosis, visceral leishmaniasis, amoebic liver abscess, tuberculosis, HIV seroconversion (2 to 6 weeks), and relapse of vivax or ovale malaria.

Fever patterns. Patterns are of limited value. Malaria is often irregular early and tertian or quartan later. Typhoid classically rises in a stepladder over the first week. Relapsing fever recurs after afebrile intervals, and dengue may show a saddleback curve.

History

• Onset, rigors, sweats, pattern, associated symptoms and progression over the days since onset.
• System review: headache, neck stiffness, photophobia, confusion, cough, sore throat, breathlessness, chest pain and abdominal pain. Also ask about diarrhoea, vomiting, jaundice, dysuria, flank pain, rash, joint and muscle pain, retro-orbital pain, bleeding, red eye, ear pain, genital ulcer or discharge, and seizures.
• Travel in the last 12 months with itinerary and dates. Ask about rural or forest stay, flood or freshwater contact (leptospirosis, schistosomiasis), animal and livestock contact, unpasteurised milk or raw meat (brucellosis), bushmeat, bat or rodent exposure, tick and louse exposure, mosquito bites and bed net use.
• Malaria chemoprophylaxis adherence, vaccination history (typhoid, yellow fever, meningococcal, hepatitis A and B, measles, rabies). Ask also about sexual and injecting exposures, blood or body fluid contact, funerals and healthcare contact during outbreaks, and contact with unwell people or tuberculosis.
• HIV status, CD4 count and antiretroviral therapy, sickle cell disease, splenectomy, diabetes, cirrhosis, kidney disease, malignancy and immunosuppressive drugs, including corticosteroids.
• Recent surgery, procedures, catheters, intravenous lines, prosthetic material, dental work, hospital admission, and antibiotics taken before assessment (partially treated infection).
• New drugs (beta lactams, sulphonamides, anticonvulsants, allopurinol, antimalarials), alcohol, and pregnancy.

Examination

• Full vital signs: temperature, heart rate, respiratory rate, blood pressure, oxygen saturation, capillary refill, mental state and urine output. Calculate an early warning score and look for sepsis (respiratory rate 22 or more, altered mentation, systolic pressure 100 mmHg or less).
• General: pallor, jaundice, dehydration, lymphadenopathy, rash (blanching, petechiae, purpura, eschar, rose spots), conjunctival suffusion or haemorrhage, oral ulcers, thrush, throat exudate and Koplik spots.
• Neurological: neck stiffness, Kernig and Brudzinski signs, photophobia, focal deficit, papilloedema and fundal signs (malarial retinopathy: retinal whitening, abnormal vessel colour and white centred haemorrhages).
• Ears, sinuses, chest, heart (new murmur), and abdomen (hepatomegaly, splenomegaly, right upper quadrant tenderness, suprapubic and loin tenderness).
• Joints, muscles (calf tenderness), spine and bone tenderness, skin and soft tissue infection, injection and line sites, wounds, perineum and genitalia, and tick bites with eschars.
• Signs of plasma leakage (ascites, pleural effusion), bleeding and shock.

Red flags

• Hypotension (systolic pressure under 90 mmHg or mean arterial pressure under 65 mmHg), respiratory rate over 22, oxygen saturation under 94%, altered consciousness, prostration (unable to sit or stand), seizures, or oliguria.
• Lactate over 2 mmol/L (over 4 mmol/L indicates septic shock).
• Nonblanching rash, neck stiffness with photophobia, severe headache, or purpura.
• Jaundice with fever, or bleeding from any site.
• Severe abdominal pain or guarding.
• Haemoglobin under 7 g/dL, dark urine (haemoglobinuria), repeated vomiting or severe dehydration.
• Severe malaria features with a positive test: impaired consciousness, 2 or more seizures in 24 hours, respiratory distress, shock, acidosis (bicarbonate under 15 mmol/L), hypoglycaemia (glucose under 2.2 mmol/L). Also creatinine over 265 micromol/L, jaundice with bilirubin over 50 micromol/L, significant bleeding, pulmonary oedema, or parasitaemia over 10% of red cells.
• Fever after travel to malaria endemic areas, or contact with a suspected viral haemorrhagic fever case.
• Neutropenia (neutrophils under 0.5 x 10^9/L), asplenia, or advanced HIV (CD4 under 200 cells/microlitre).
• Pregnancy, injecting drug use, prosthetic valve or line, and age over 65 years with new confusion.

Special groups

• Pregnancy: severe malaria and anaemia, pyelonephritis, listeriosis, chorioamnionitis, hepatitis E (fulminant), influenza and typhoid. Avoid doxycycline, fluoroquinolones and primaquine.
• Older adults: blunted fever, delirium as a presentation, urinary and respiratory sources, and drug fever.
• Immunocompromised and asplenic patients: rapid deterioration with encapsulated organisms.
• Kidney and liver impairment: adjust dose of ceftriaxone, quinine, gentamicin, vancomycin and others.
• Children and neonates need age specific assessment and doses. Fever in children aged under 5 years in malaria areas is treated as malaria until excluded.
• Region specific: malaria seasonality, flood and outbreak settings (leptospirosis, cholera, Rift Valley fever), livestock exposure (brucellosis, Q fever, Rift Valley fever) and louse borne relapsing fever in crowded displacement settings.

Parasitic

• Falciparum malaria (uncomplicated and severe).
• Vivax, ovale, malariae and knowlesi malaria.
• Visceral leishmaniasis.
• East African trypanosomiasis (rhodesiense).
• Amoebic liver abscess.
• Acute schistosomiasis (Katayama syndrome).
• Toxoplasmosis.
• Trichinellosis.
• Strongyloides hyperinfection.

Bacterial

• Typhoid and paratyphoid fever.
• Invasive nontyphoidal Salmonella bacteraemia (HIV, malaria, sickle cell disease).
• Bacteraemia from pneumococcus, Staphylococcus aureus, group A streptococcus and Gram negative organisms.
• Bacterial meningitis and meningococcal disease.
• Pneumonia, including Legionella.
• Pyelonephritis.
• Cholangitis, cholecystitis, appendicitis, diverticulitis, intra-abdominal and liver abscess, and spontaneous bacterial peritonitis.
• Infective endocarditis.
• Brucellosis.
• Leptospirosis.
• Rickettsioses (African tick bite fever, spotted fever group, murine typhus, epidemic typhus, scrub typhus) and Q fever.
• Tick borne and louse borne relapsing fever.
• Plague.
• Anthrax.
• Tularaemia.
• Melioidosis.
• Tuberculosis, including miliary disease.
• Listeriosis.
• Bartonellosis.
• Toxic shock syndrome.

Viral

• Influenza, SARS-CoV-2, respiratory syncytial virus and adenovirus.
• Dengue.
• Chikungunya, o'nyong nyong and Zika.
• Rift Valley fever.
• Yellow fever.
• West Nile virus.
• Crimean-Congo haemorrhagic fever, Ebola, Marburg and Lassa fever.
• Acute HIV infection.
• Epstein-Barr virus and cytomegalovirus infection.
• Hepatitis A, B and E.
• Measles.
• Enterovirus infection.
• Herpes simplex and varicella.
• Mpox.
• Rabies, early.

Fungal

• Histoplasmosis.
• Cryptococcosis.
• Penicilliosis.
• Candidaemia.

Noninfective

• Drug fever.
• Sickle cell crisis.
• Venous thromboembolism and pulmonary embolism.
• Acute pancreatitis.
• Myocardial infarction and pericarditis.
• Thyroid storm.
• Adrenal crisis.
• Transfusion reaction.
• Gout and pseudogout.
• Vasculitis and Kawasaki disease.
• Adult onset Still disease and systemic lupus erythematosus.
• Haemophagocytic lymphohistiocytosis.
• Lymphoma, leukaemia and tumour fever (renal cell carcinoma).
• Subarachnoid haemorrhage.
• Alcohol withdrawal.
• Inflammatory bowel disease.
• Hyperthermia syndromes: heat stroke, serotonin syndrome, neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic and salicylate toxicity.

Step 1. Severity. Check vital signs and mental state. If sepsis is present, start treatment before diagnosis is complete. Isolate patients with suspected viral haemorrhagic fever, measles, varicella, tuberculosis, meningococcal disease or other transmissible infection before any further testing.

Step 2. Localising features and exposure. Check each system, then match incubation period and exposure to the likely list.

Step 3. Tests for every patient

• Capillary glucose, urine dipstick, pulse oximetry and bedside malaria rapid antigen test.
• Thick and thin blood films for malaria with parasite density. If negative and suspicion remains, repeat every 12 to 24 hours for 3 sets. A negative rapid test does not exclude malaria when parasitaemia is low or the infecting strain lacks HRP2 (microscopy remains necessary, and HRP2 can stay positive for 2 to 4 weeks after cure).
• Blood cultures, 2 sets before antibiotics (20 mL for each set in adults).
• Full blood count with differential. Thrombocytopenia is frequent in malaria, dengue, rickettsial disease, leptospirosis and sepsis. Leucopenia suggests typhoid, dengue, rickettsial disease, brucellosis or HIV. Neutrophilia suggests bacterial infection. Eosinophilia suggests helminth infection or drug reaction.
• CRP (procalcitonin where available has limited specificity), urea, creatinine, electrolytes, liver tests, glucose, creatine kinase and lactate.
• Urinalysis and urine culture. Chest radiograph. HIV test. Pregnancy test. Coagulation screen and fibrinogen when bleeding, jaundice or shock.
• Blood gas if unwell or breathless.

Step 4. Targeted tests

• Typhoid: blood cultures (sensitivity 40 to 80%, lower after antibiotics), bone marrow culture (80 to 95% even after antibiotics) when needed. Stool and urine cultures become positive later. The Widal test is unreliable.
• Dengue: NS1 antigen or RT PCR in days 1 to 5, IgM from day 5. Chikungunya RT PCR in the first 5 to 7 days, then IgM. Cross reactivity between flaviviruses limits serology.
• Brucellosis: prolonged incubation of blood cultures (inform the laboratory), Rose Bengal screening and serum agglutination titre of 1:160 or more.
• Leptospirosis: PCR of blood in the first 10 days and urine later, with IgM or microscopic agglutination test on paired samples.
• Rickettsial disease: PCR of eschar swab or blood. Serology is positive only after 7 to 14 days, so treat before confirmation.
• Relapsing fever and trypanosomiasis: thick and thin blood films taken during fever.
• Lumbar puncture when meningitis is possible: opening pressure, cell count, protein, glucose with paired blood glucose, Gram stain, culture, PCR, cryptococcal antigen and India ink.
• Image first only for focal deficit, papilloedema, new seizure, immunocompromise or Glasgow Coma Scale of 12 or less, and never delay antibiotics.
• Bacterial meningitis typically shows neutrophils, protein over 1 g/L and CSF to blood glucose ratio under 0.4.
• Tuberculosis: sputum nucleic acid amplification test, chest radiograph, and urine lipoarabinomannan in HIV with CD4 under 200 cells/microlitre or critical illness.
• HIV: fourth generation antigen and antibody test with HIV RNA when acute infection is suspected.
• Hepatitis A, B and E serology, EBV and CMV serology (heterophile tests miss early infection), syphilis serology, and ASO titre.
• Viral haemorrhagic fever: contact public health and the reference laboratory before taking samples. Take malaria tests first and use full precautions.
• Imaging: ultrasound of abdomen for liver abscess, cholecystitis, obstruction and collections. CT for deep abscess. Echocardiography for bacteraemia with Staphylococcus aureus or viridans streptococci, new murmur, or prosthetic valve.
• Ferritin over 10,000 micrograms/L with cytopenias and raised triglycerides supports haemophagocytic lymphohistiocytosis (and adult onset Still disease).
• Cryptococcal antigen and urine histoplasma antigen in advanced HIV.

Interpretation. Clinical features overlap widely, and many patients have more than one infection (malaria with bacteraemia, typhoid with malaria). Do not stop looking after finding one cause when the patient is severely ill. In many patients no pathogen is identified and the illness resolves, so reassess if fever persists beyond 72 to 96 hours of appropriate treatment.

Immediate: sepsis or severe illness

• Oxygen to saturation 94 to 98% (88 to 92% in patients at risk of hypercapnia), intravenous access, blood cultures, glucose, lactate and urine output monitoring.
• Fluids: for hypotension or lactate over 4 mmol/L give crystalloid boluses of 250 to 500 mL with reassessment after each (up to 30 mL/kg within 3 hours when clearly hypovolaemic).
• In severe malaria, dengue and settings without critical care support, give smaller boluses with close reassessment, because aggressive fluid loading causes pulmonary oedema.
• Start noradrenaline to keep mean arterial pressure at 65 mmHg or over if hypotension persists.
• Antibiotics within 1 hour of recognising septic shock, and within 3 hours when sepsis is possible: ceftriaxone 2 g intravenously once daily (reduce only when severe combined kidney and liver impairment).
• Add doxycycline 100 mg orally or intravenously twice daily when rickettsial disease or leptospirosis is possible.
• Hospital acquired or line related sepsis: piperacillin with tazobactam 4.5 g intravenously every 6 hours (3.375 g every 6 hours at creatinine clearance 20 to 40 mL/min; 2.25 g every 6 hours under 20 mL/min).
• Alternative: meropenem 1 g intravenously every 8 hours (1 g every 12 hours at 26 to 50 mL/min; 500 mg every 12 hours at 10 to 25 mL/min; 500 mg every 24 hours under 10 mL/min).
• Add vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours when MRSA is likely.
• Control the source early (drainage, catheter removal, surgery).
• Suspected bacterial meningitis: ceftriaxone 2 g intravenously every 12 hours with dexamethasone 10 mg intravenously every 6 hours for 4 days, started before or with the first antibiotic dose. Add amoxicillin 2 g intravenously every 4 hours when over 50 years or immunocompromised. Do not delay for imaging or lumbar puncture.
• Suspected viral haemorrhagic fever: isolate in a single room, restrict staff to those with full protective equipment, notify public health at once, and give supportive care. Give antimalarial and antibiotic treatment because malaria and sepsis are more likely.
• Hyperthermia: for heat stroke cool rapidly (ice water immersion or evaporative cooling) to a core temperature under 39 C, without antipyretics. Serotonin syndrome and neuroleptic malignant syndrome: stop the causative drug and give benzodiazepines, with specialist advice.

Antipyretics and fluids. Paracetamol 1 g orally every 4 to 6 hours (maximum 4 g daily; 3 g daily in hepatic impairment, chronic alcohol use or weight under 50 kg; 15 mg/kg each dose under 50 kg, maximum 60 mg/kg daily). Avoid aspirin and NSAIDs in suspected dengue, viral haemorrhagic fever, kidney impairment and volume depletion. Encourage oral fluids and use oral rehydration solution for diarrhoea.

Malaria

• Uncomplicated falciparum malaria: artemether with lumefantrine (20 mg/120 mg tablets) orally with fatty food or milk. For 35 kg or over: 4 tablets at 0, 8, 24, 36, 48 and 60 hours.
• Weight bands: 5 to under 15 kg 1 tablet; 15 to under 25 kg 2 tablets; 25 to under 35 kg 3 tablets.
• Observe the first dose and repeat it if vomiting occurs within 30 minutes. Avoid with other QT prolonging drugs. Strong CYP3A4 inducers (rifampicin, carbamazepine, phenytoin) lower levels.
• Alternatives: dihydroartemisinin with piperaquine once daily for 3 days (36 to under 60 kg 3 tablets of 40/320 mg; 60 to under 80 kg 4 tablets; 80 kg or over 5 tablets), or artesunate with amodiaquine once daily for 3 days. Avoid combinations that prolong the QT interval.
• Severe malaria: artesunate 2.4 mg/kg intravenously (or intramuscularly) at 0, 12 and 24 hours, then once daily until oral therapy is possible (children under 20 kg 3 mg/kg for each dose).
• After at least 24 hours of parenteral therapy and 3 doses, give a full 3 day course of oral artemether with lumefantrine.
• If artesunate is unavailable: artemether 3.2 mg/kg intramuscularly then 1.6 mg/kg daily.
• Alternatively, quinine 20 mg salt/kg intravenously over 4 hours then 10 mg/kg every 8 hours (omit the loading dose if quinine was taken in the previous 24 hours), with clindamycin 10 mg/kg twice daily for 7 days.
• Monitor glucose every 4 to 6 hours, give dextrose 25 g intravenously (50 mL of 50%) for hypoglycaemia, lorazepam 4 mg intravenously for seizures (repeat once after 10 minutes), and transfuse for haemoglobin under 7 g/dL in adults.
• Give ceftriaxone 2 g daily for suspected bacteraemia. Avoid corticosteroids. Check haemoglobin at 1, 2 and 4 weeks for delayed haemolysis after artesunate.
• Vivax and ovale malaria: treat the blood stage with an artemisinin combination, then give primaquine 0.25 to 0.5 mg/kg base orally daily for 14 days (dose depends on regional relapse patterns) after G6PD testing. Avoid in pregnancy and breastfeeding unless the infant is G6PD normal.
• Pregnancy: severe malaria needs artesunate in all trimesters. For uncomplicated disease in the first trimester use quinine 10 mg salt/kg three times daily with clindamycin 7 to 10 mg/kg twice daily for 7 days, or an artemisinin combination when these are unavailable. From the second trimester use an artemisinin combination.

Other time critical infections

• Typhoid fever, uncomplicated: azithromycin 500 mg orally once daily for 7 days, or ceftriaxone 2 g intravenously once daily for 7 to 14 days.
• Complicated disease: ceftriaxone 2 g intravenously once daily for 10 to 14 days. Fluoroquinolone resistance is common. Fever typically takes 4 to 5 days to settle. Watch for intestinal perforation and bleeding in the second and third weeks.
• Rickettsial disease: doxycycline 100 mg orally or intravenously twice daily for 5 to 7 days (and for at least 3 days after fever settles), started on clinical suspicion. Children under 45 kg: 2.2 mg/kg twice daily, maximum 100 mg each dose.
• Leptospirosis: doxycycline 100 mg orally twice daily for 7 days for mild disease. Severe disease: benzylpenicillin 1.5 million units intravenously every 6 hours, or ceftriaxone 1 g intravenously once daily, for 7 days.
• Brucellosis: doxycycline 100 mg orally twice daily for 6 weeks plus gentamicin 5 mg/kg intravenously or intramuscularly once daily for 7 days, or rifampicin 600 to 900 mg daily for 6 weeks (specialist). Avoid doxycycline in pregnancy.
• Relapsing fever: tick borne, doxycycline 100 mg orally twice daily for 7 to 10 days. Louse borne, doxycycline 100 mg orally as a single dose or erythromycin 500 mg once. Observe for 4 hours for the Jarisch-Herxheimer reaction (rigors, hypotension), and give supportive care. Pregnancy: erythromycin 500 mg orally four times daily for 7 days.
• Plague (suspected): isolation, gentamicin 5 mg/kg intravenously once daily with doxycycline 100 mg twice daily, notification, and prophylaxis for contacts.
• Influenza: oseltamivir 75 mg orally twice daily for 5 days, started within 48 hours (later when severe or high risk). Reduce to 30 mg twice daily at creatinine clearance 30 to 60 mL/min, and 30 mg once daily at 10 to 30 mL/min.
• Dengue: oral fluids and paracetamol. Admit for warning signs (abdominal pain, persistent vomiting, mucosal bleeding, lethargy, liver enlargement over 2 cm, rising haematocrit with falling platelets).
• Give isotonic crystalloid 5 to 7 mL/kg/h for 1 to 2 hours, then 3 to 5 mL/kg/h, adjusted to haematocrit and clinical response. For shock give 10 to 20 mL/kg over 15 to 30 minutes.
• Amoebic liver abscess: metronidazole 500 to 800 mg orally (or 500 mg intravenously) three times daily for 7 to 10 days, then diloxanide furoate 500 mg orally three times daily for 10 days. Aspirate abscesses over 5 cm, in the left lobe, or not responding after 72 hours. Avoid alcohol and monitor for neuropathy.
• Acute schistosomiasis (Katayama syndrome): prednisolone 20 to 40 mg orally daily for 5 days for severe symptoms, with praziquantel 40 mg/kg orally as 2 divided doses given 6 to 8 weeks after exposure.
• Acute HIV infection: start antiretroviral therapy in line with the local regimen, and test partners.
• Suspected infective endocarditis: three sets of blood cultures before antibiotics. Then give flucloxacillin 2 g intravenously every 4 to 6 hours plus gentamicin 1 mg/kg intravenously every 12 hours (vancomycin 15 to 20 mg/kg every 8 to 12 hours with levels for MRSA risk, penicillin allergy or prosthetic valves).
• Drug fever: stop the suspected drug. Fever usually settles within 72 hours.
• Do not give empirical antibiotics for self limiting viral illness without sepsis features, and do not use broad cover without cultures.

Public health. Notify malaria (where required), typhoid, dengue, viral haemorrhagic fever, plague, anthrax, meningococcal disease, measles and yellow fever. Chemoprophylaxis for meningococcal contacts: ciprofloxacin 500 mg orally as a single dose, or rifampicin 600 mg twice daily for 2 days.

Monitoring. Vital signs every 15 minutes in shock and every 1 to 4 hours in sepsis. Urine output hourly in shock. Repeat lactate within 2 hours.

Glucose every 4 to 6 hours in severe malaria. Repeat malaria films at 24 and 48 hours (parasite count should fall by at least 75% at 48 hours). Daily creatinine, liver tests and blood count. Persisting fever after 72 to 96 hours on appropriate treatment needs review for abscess, resistant organism, a second infection, drug fever and noninfective causes.

Referral and escalation. Intensive care for shock, respiratory failure, severe malaria with organ dysfunction and refractory acidosis. Infectious diseases for returned travellers, suspected viral haemorrhagic fever, and unexplained fever. Surgery for intra-abdominal sepsis, abscess and necrotising infection. Public health for notifiable disease and outbreaks.

Admission criteria. Sepsis or any red flag, severe malaria features, falciparum malaria diagnosed outside an endemic setting, inability to take oral fluids or drugs, persistent vomiting, hypoxia, jaundice, bleeding, dengue warning signs, pregnancy, immunocompromise, asplenia, extremes of age, uncontrolled comorbidity and unreliable follow up.

Discharge and follow up. Discharge only when haemodynamically stable, tolerating oral intake and with confirmed access to follow up within 24 to 48 hours and a plan for pending results.

Give malaria prevention advice (bed nets, repellents, chemoprophylaxis for travel), and vaccination advice (yellow fever, typhoid, meningococcal, hepatitis A and B).

Safety net advice: return for

• fever over 48 to 72 hours
• confusion
• severe headache
• neck stiffness
• rash
• bleeding
• breathing difficulty
• jaundice
• persistent vomiting
• severe abdominal pain
• reduced urine
• fainting