Fever with respiratory symptoms

Fever with respiratory symptoms is a temperature of 38.0 degrees Celsius or over together with cough, sputum, dyspnoea, pleuritic pain, sore throat or nasal symptoms. Most cases are self limiting viral upper respiratory infections.

Classification by site and course

• Upper tract: common cold, pharyngitis and tonsillitis, sinusitis, otitis media, epiglottitis, peritonsillar abscess, and diphtheria.
• Lower tract: acute bronchitis, community acquired pneumonia, aspiration pneumonia, hospital acquired pneumonia and ventilator associated pneumonia, lung abscess, empyema, and exacerbation of chronic obstructive pulmonary disease.
• Chronic or subacute: pulmonary tuberculosis, nontuberculous mycobacterial disease, fungal pneumonia, and nocardiosis.
• Epidemic and imported: influenza, COVID-19, respiratory syncytial virus, measles, Middle East respiratory syndrome, avian influenza, melioidosis, Legionnaires disease, and plague.
• Opportunistic: Pneumocystis pneumonia, cytomegalovirus pneumonitis, invasive aspergillosis in neutropenic or transplant patients.
• Non infectious: pulmonary embolism with infarction, heart failure, pulmonary vasculitis, eosinophilic pneumonia, drug induced pneumonitis, hypersensitivity pneumonitis, organising pneumonia, malignancy, and sarcoidosis.
• Malaria and other systemic infections can present mainly with cough and tachypnoea.

Epidemiology. Community acquired pneumonia affects 5 to 11 in every 1000 adults each year, with in-hospital mortality of 5% to 15% and over 30% in intensive care. Streptococcus pneumoniae remains the commonest bacterial cause, followed by Haemophilus influenzae, Mycoplasma pneumoniae, Legionella and Staphylococcus aureus. Influenza and other respiratory viruses account for a quarter or more of adult pneumonia. Tuberculosis causes a large share of chronic fever with cough in settings with high prevalence, and HIV raises risk of every cause.

Mechanisms. Microaspiration or inhalation of organisms, host defence failure (smoking, alcohol, chronic lung disease, immunosuppression, viral injury to ciliated epithelium), alveolar inflammation and exudate causing impaired gas exchange, and systemic cytokine release causing fever and sepsis.

Key distinctions. Abrupt onset with rigors, pleuritic pain and focal crackles suggests pneumococcal pneumonia. Dry cough, headache and slow onset in a young adult suggests atypical pneumonia.

Myalgia, headache and abrupt fever in an epidemic season suggests influenza. Cough over 3 weeks with night sweats and weight loss suggests tuberculosis. Diarrhoea, confusion and low sodium suggest Legionella. Fever with unilateral leg swelling, pleuritic pain and risk factors suggests pulmonary embolism. Fever with cough and cyclical pattern after tropical travel suggests malaria.

History

• Symptoms: cough (dry, productive, haemoptysis), sputum colour and volume, dyspnoea, pleuritic chest pain, wheeze, sore throat, hoarseness, stridor, ear pain, sinus pain, myalgia, headache, rigors, night sweats, weight loss.
• Time course: abrupt, gradual, over 3 weeks, or recurrent.
• Exposures: sick contacts, tuberculosis contact, travel (malaria, melioidosis, Middle East respiratory syndrome, avian influenza), animals and birds (psittacosis, Q fever, avian influenza), water systems and air conditioning (Legionella), caves and soil (histoplasmosis), occupational dusts, aspiration risk.
• Vaccination: pneumococcal, influenza, COVID-19, pertussis, measles, Haemophilus influenzae type b.
• Host factors: age, smoking, alcohol, chronic lung or heart disease, diabetes, HIV, immunosuppressive drugs, cancer, chronic kidney or liver disease, sickle cell disease, recent hospital stay, recent antibiotics, stroke or dysphagia, and pregnancy.
• Drugs: amiodarone, methotrexate, nitrofurantoin, bleomycin (pneumonitis), immune checkpoint inhibitors, ACE inhibitor cough.
• Previous microbiology, especially methicillin resistant Staphylococcus aureus and resistant Gram negative organisms.

Examination

• Vital signs: temperature, respiratory rate, pulse, blood pressure, oxygen saturation (room air), level of consciousness, and urine output.
• Severity scoring: CURB-65 (confusion, urea over 7 mmol/L, respiratory rate 30 or over, systolic pressure under 90 mmHg or diastolic 60 mmHg or under, age 65 years or over; 0 to 1 low risk, 2 intermediate, 3 or more high risk), qSOFA, and NEWS2.
• Chest: use of accessory muscles, cyanosis, chest expansion, percussion dullness, bronchial breathing, crackles, pleural rub, wheeze, stridor.
• Throat, ears, sinuses, lymph nodes, tonsillar exudate or membrane (diphtheria), unilateral peritonsillar swelling with trismus.
• Cardiovascular: murmurs (endocarditis), heart failure signs, deep vein thrombosis.
• Skin: rash (measles, varicella), petechiae, cellulitis, and skin lesions of disseminated infection.
• Abdomen, neurological signs (meningism), and joint swelling.

Red flags

• Respiratory rate 30 or over, oxygen saturation under 92% on room air, cyanosis, or use of accessory muscles.
• Systolic blood pressure under 90 mmHg, pulse over 125 beats/min, lactate over 2 mmol/L, or mottled skin.
• New confusion or reduced consciousness.
• Stridor, drooling, muffled voice, inability to swallow (epiglottitis, airway abscess, diphtheria with pseudomembrane).
• Haemoptysis with night sweats and weight loss (tuberculosis), or massive haemoptysis.
• Suspected novel or highly pathogenic respiratory infection (travel to affected areas, contact with cases).
• Immunosuppression, neutropenia, HIV with CD4 count under 200 cells/microlitre, or transplant.
• Pleural effusion with persistent fever (empyema).
• Pregnancy with pneumonia or influenza.
• Pleuritic pain, tachycardia, unilateral leg swelling, or risk factors for thrombosis (pulmonary embolism).
• Cough and fever in an infant with grunting, chest indrawing or poor feeding.

Special groups

• Children: tachypnoea by age (over 50 breaths/min under 1 year, over 40 breaths/min from 1 to 5 years) and chest indrawing guide severity. Consider bronchiolitis, croup, foreign body, pertussis and tuberculosis.
• Older adults: may present with confusion, falls, or reduced appetite without fever or cough.
• Pregnancy: low threshold for chest radiograph with shielding, antiviral treatment, and hospital care.
• HIV and immunosuppression: widen the range to Pneumocystis, tuberculosis, fungi and cytomegalovirus.
• Region specific: tuberculosis, melioidosis, malaria, schistosomiasis (Katayama fever), and Q fever.

Upper respiratory and ENT

• Viral upper respiratory infection and pharyngitis (group A streptococcus, infectious mononucleosis, adenovirus).
• Acute sinusitis, otitis media, and peritonsillar abscess.
• Epiglottitis and retropharyngeal abscess.
• Diphtheria and pertussis.

Lower respiratory infection

• Pneumonia: pneumococcal, Haemophilus, Moraxella, Staphylococcus aureus, Klebsiella, Mycoplasma, Chlamydophila, Legionella, and anaerobic aspiration.
• Viral: influenza, COVID-19, respiratory syncytial virus, adenovirus, parainfluenza, measles.
• Tuberculosis and nontuberculous mycobacteria.
• Fungal: Pneumocystis, histoplasmosis, coccidioidomycosis, aspergillosis, cryptococcosis.
• Empyema, lung abscess, and bronchiectasis infection.
• Acute exacerbation of COPD or asthma with infection.

Systemic and imported infection with respiratory features

• Malaria, dengue, leptospirosis, typhoid, Q fever, psittacosis, brucellosis, melioidosis, plague, tularaemia, and rickettsial disease.
• Severe acute respiratory syndromes and avian influenza.
• Infective endocarditis with septic emboli.
• Katayama fever and tropical pulmonary eosinophilia.

Non infectious

• Pulmonary embolism with infarction.
• Heart failure and pulmonary oedema.
• Granulomatosis with polyangiitis and other vasculitis; eosinophilic granulomatosis with polyangiitis.
• Drug induced pneumonitis; hypersensitivity pneumonitis; organising pneumonia; radiation pneumonitis.
• Lung cancer with obstruction, lymphoma, and sarcoidosis.
• Aspiration pneumonitis and acute respiratory distress syndrome.

Step 1. Assess severity and airway. Record vital signs, oxygen saturation, level of consciousness and perfusion. Calculate CURB-65 or NEWS2. Secure the airway for stridor or epiglottitis. Isolate patients with suspected tuberculosis, influenza, measles, COVID-19, or novel respiratory pathogens.

Step 2. First line tests

• Chest radiograph (posteroanterior, lateral in suspected effusion).
• Full blood count and differential, C-reactive protein, urea, creatinine, electrolytes, liver tests, glucose, and lactate.
• Arterial or venous blood gas when oxygen saturation is under 94% or patient is severely ill.
• Two sets of blood cultures before antibiotics.
• Sputum Gram stain and culture (good quality sample).
• Rapid antigen or polymerase chain reaction testing for influenza, COVID-19 and respiratory syncytial virus.
• Urine pneumococcal and Legionella antigen in moderate and severe pneumonia.
• Malaria rapid test or thick and thin films when there is travel or residence in an endemic area.
• HIV test with consent.
• ECG when cardiac cause is possible.

Step 3. Targeted tests

• Sputum for acid fast bacilli smear, nucleic acid amplification test (Xpert MTB/RIF) and culture for cough over 2 weeks, night sweats or weight loss, with chest radiograph.
• CT of the chest for unclear radiograph, suspected empyema, abscess, pulmonary embolism (CT pulmonary angiography), mass or interstitial disease.
• Pleural fluid analysis (pH, glucose, protein, lactate dehydrogenase, cell count, Gram stain, culture, adenosine deaminase) for effusion.
• Bronchoscopy with lavage for immunocompromised patients and nonresolving pneumonia (Pneumocystis polymerase chain reaction, fungal culture, cytology).
• Serum beta-D-glucan, galactomannan, cryptococcal antigen in immunosuppressed patients.
• Procalcitonin may help to stop antibiotics early in selected patients.
• D-dimer, Wells score, and CT pulmonary angiography for suspected pulmonary embolism.
• Throat swab and culture for Streptococcus pyogenes (centor score 3 or more) and for Corynebacterium diphtheriae where indicated.
• Antinuclear cytoplasmic antibodies and urine analysis when vasculitis is suspected.

Step 4. Interpretation. A new infiltrate with fever, cough and abnormal signs establishes pneumonia. A normal initial radiograph does not exclude pneumonia, especially early or in dehydration, so repeat or use CT when suspicion is high. Radiographic resolution lags behind clinical recovery by 6 weeks or longer. A raised C-reactive protein over 100 mg/L supports bacterial pneumonia but does not exclude viral infection. A negative sputum acid fast smear does not exclude tuberculosis, so use nucleic acid amplification and culture.

Limits. Sputum and blood cultures are positive in a minority. Urine antigens detect only some pathogens. Radiographic signs are nonspecific in older adults and in heart failure. Dual infection with a virus and bacteria is common.

Immediate. Maintain airway, give oxygen for oxygen saturation under 94% (target 94% to 98%; 88% to 92% in patients at risk of hypercapnic respiratory failure).

Treat shock with intravenous isotonic crystalloid 500 mL boluses, reassessing after each (up to 30 mL/kg in sepsis with hypotension or lactate 4 mmol/L or over). Give antibiotics within 1 hour for sepsis or septic shock and within 4 hours in other pneumonia.

Pain relief for pleuritic pain with paracetamol 1 g every 6 hours (maximum 4 g daily; 3 g if under 50 kg or hepatic risk) or ibuprofen 400 mg three times daily with food if no contraindication. Isolate and use respiratory protection for suspected airborne or droplet infection.

Community acquired pneumonia in adults

• Low severity (CURB-65 of 0 to 1) treated at home: amoxicillin 500 mg to 1 g orally three times daily for 5 days. If penicillin allergic: doxycycline 200 mg orally on day 1, then 100 mg daily for 4 more days, or clarithromycin 500 mg orally twice daily for 5 days.
• Moderate severity (CURB-65 of 2): amoxicillin 500 mg to 1 g orally three times daily plus clarithromycin 500 mg orally twice daily for 5 to 7 days; intravenous amoxicillin 1 g three times daily if oral route is not possible.
• High severity (CURB-65 of 3 or more) or intensive care: amoxicillin with clavulanic acid 1.2 g intravenously three times daily (maximum 3.6 g daily) plus clarithromycin 500 mg intravenously or orally twice daily for 7 to 10 days; alternative ceftriaxone 2 g intravenously once daily plus clarithromycin.
• For penicillin allergy, use levofloxacin 500 mg intravenously or orally twice daily (specialist advice).
• Oral step down once afebrile 24 hours and improving: amoxicillin with clavulanic acid 625 mg (500 mg amoxicillin with 125 mg clavulanic acid) orally three times daily.
• Suspected Legionella: add clarithromycin 500 mg twice daily or levofloxacin 500 mg twice daily for 7 to 14 days (21 days in severe disease).
• Staphylococcus aureus with influenza or necrotising pneumonia: flucloxacillin 2 g intravenously every 6 hours, or vancomycin 15 to 20 mg/kg intravenously every 8 to 12 hours with level monitoring if MRSA is suspected.
• Add linezolid 600 mg twice daily as a toxin suppressing option; specialist advice.
• Aspiration pneumonia: amoxicillin with clavulanic acid 1.2 g intravenously every 8 hours, or ceftriaxone 2 g daily plus metronidazole 500 mg every 8 hours.
• Total duration 5 days for most patients, extended to 7 to 10 days for severe or complicated disease, and 14 to 21 days for Staphylococcus aureus bacteraemia, Legionella or empyema.

Hospital acquired and ventilator associated pneumonia

• Piperacillin with tazobactam 4.5 g intravenously every 6 hours (extended infusion over 4 hours may be used), or meropenem 1 g intravenously every 8 hours when resistant Gram negative bacteria are likely.
• Add vancomycin 15 to 20 mg/kg every 8 to 12 hours or linezolid 600 mg every 12 hours when MRSA risk exists.
• Review at 48 to 72 hours with cultures and narrow therapy. Duration 7 days in most patients.
• Adjust doses for renal function (for piperacillin with tazobactam: creatinine clearance 20 to 40 mL/min, 4.5 g every 8 hours; under 20 mL/min, 4.5 g every 12 hours).

Viral infections

• Influenza (within 48 hours of onset, or at any time in severe disease or high risk patients): oseltamivir 75 mg orally twice daily for 5 days (10 days in severe or immunocompromised patients).
• Oseltamivir renal dose: creatinine clearance 31 to 60 mL/min, 30 mg twice daily; 11 to 30 mL/min, 30 mg once daily; 10 mL/min or under, 30 mg as a single dose.
• COVID-19 antivirals and anticoagulation for high risk patients are given by local specialist direction.
• Add antibiotics when bacterial coinfection is suspected.

Tuberculosis (confirmed or strongly suspected)

• Intensive phase for 2 months: isoniazid 5 mg/kg orally daily (maximum 300 mg), rifampicin 10 mg/kg daily (maximum 600 mg), pyrazinamide 25 mg/kg daily (maximum 2 g), and ethambutol 15 mg/kg daily (maximum 1.2 g), with pyridoxine 10 mg daily.
• Continuation phase for 4 months: isoniazid and rifampicin at the same doses. Fixed dose combinations are dosed by weight band in practice.
• Baseline liver tests, renal function, HIV test and visual acuity. Monitor liver tests at 2 and 4 weeks and when symptomatic. Stop and reassess if alanine aminotransferase exceeds 5 times the upper limit of normal (3 times with symptoms).
• Notify and arrange contact tracing and directly observed therapy.

Malaria (fever with cough in endemic area or recent travel)

• Severe malaria: artesunate 2.4 mg/kg intravenously at 0, 12 and 24 hours, then once daily until oral therapy is possible (minimum 3 doses), followed by a full oral course of artemether with lumefantrine. Uncomplicated falciparum malaria: artemether 20 mg with lumefantrine 120 mg, four tablets orally at 0, 8, 24, 36, 48 and 60 hours with fatty food.

Pneumocystis pneumonia (HIV or immunosuppression)

• Co-trimoxazole 120 mg/kg daily in 3 to 4 divided doses (intravenous or oral) for 21 days, then prophylaxis.
• Add prednisolone 40 mg twice daily for 5 days, then 40 mg daily for 5 days, then 20 mg daily for 11 days when arterial oxygen pressure is under 9.3 kPa (70 mmHg) on room air.
• Monitor potassium, creatinine and blood count. Start antiretroviral therapy within 2 weeks.

Other conditions

• Empyema or complicated parapneumonic effusion: drainage with chest tube and antibiotic therapy for 2 to 6 weeks; surgery or intrapleural fibrinolysis for loculated disease.
• Lung abscess: amoxicillin with clavulanic acid 1.2 g intravenously every 8 hours for 4 to 6 weeks, or until radiograph clears.
• Epiglottitis: secure the airway by a senior anaesthetist, ceftriaxone 2 g intravenously daily, avoid examination of the throat.
• Diphtheria: diphtheria antitoxin and benzylpenicillin or erythromycin 500 mg every 6 hours for 14 days under isolation.
• Pertussis: azithromycin 500 mg on day 1 then 250 mg daily for 4 days to limit spread.
• Streptococcal pharyngitis (centor score 3 or more): phenoxymethylpenicillin 500 mg orally four times daily (or 1 g twice daily) for 5 to 10 days. Peritonsillar abscess: drainage and antibiotics.
• Pulmonary embolism: anticoagulation by risk.
• Bronchitis and viral upper respiratory infection: symptomatic treatment only, without antibiotics.

Special populations

• Pregnancy: treat influenza and pneumonia promptly. Amoxicillin, cefalexin, and macrolides (erythromycin, azithromycin) are used. Avoid doxycycline, fluoroquinolones and co-trimoxazole in the first trimester where alternatives exist.
• Children: amoxicillin 40 to 50 mg/kg orally twice daily or 30 mg/kg three times daily (maximum 1 g for each dose) for 5 days, with oxygen and fluids; hospital care for chest indrawing or oxygen saturation under 92%.
• Older adults: lower threshold for admission and caution with fluids in heart failure.
• Kidney and liver impairment: adjust antibiotic doses, avoid nephrotoxins, and monitor drug levels.
• Smokers: advise cessation and offer nicotine replacement.

Monitoring.

• Temperature, respiratory rate, pulse, blood pressure, oxygen saturation and consciousness every 4 hours (hourly in severe disease).
• Fluid balance, C-reactive protein at 48 to 72 hours, culture results.
• Clinical stability criteria for oral switch and discharge (afebrile 24 hours, respiratory rate under 24, pulse under 100, systolic pressure 90 mmHg or over, oxygen saturation 92% or over, normal mentation, able to eat).

Referral and escalation. Intensive care for refractory hypoxaemia, shock, or need for ventilation. Respiratory medicine for effusion, abscess, bronchiectasis and nonresolving pneumonia. Infectious disease for resistant organisms, immunocompromise, tuberculosis, and imported infection. Public health notification for tuberculosis, diphtheria, pertussis, measles, legionellosis, influenza clusters and novel pathogens.

Admission criteria. CURB-65 of 2 or more, oxygen saturation under 92%, haemodynamic instability, confusion, immunosuppression, empyema, inability to take oral therapy, failure of outpatient treatment, pregnancy with pneumonia, or social inability to manage at home.

Discharge and follow up. Written advice on rest, fluids, completing antibiotics and smoking cessation. Review at 48 to 72 hours if treated at home, and chest radiograph at 6 weeks for patients over 50 years, smokers or with persisting symptoms. Vaccinate against pneumococcus and influenza. Safety net advice: return for breathlessness, chest pain, confusion, haemoptysis, persistent fever beyond 3 days of treatment, inability to drink, or lip swelling.