APPROACH TO ACUTE FEBRILE ILLNESS- DIAGNOSIS AND MANAGEMENT

APPROACH TO ACUTE FEBRILE ILLNESS- DIAGNOSIS AND MANAGEMENT

1. APPROACH TO ACUTE FEBRILE ILLNESS DR. AMMAR SABIR SIDDIQUI DEPARTMENT OF INTERNAL MEDICINE KGMU

2. Fever is an elevation of core body temperature above the daily range for an individual. The normal early morning to late afternoon daily variation is 0.5⁰ C/0.9 F. For those who are recovering from febrile illness variation of temperature (1⁰ C) or (1.8 F) is normal. DEFINITION UP TO DATE

3. Low level is at 6 AM and highest level is at 4 to 6 PM. The maximum oral temperature at 6 AM is 37.2⁰C (98.9 F) and at 4 to 6 PM is 37.7⁰ C (99.9 F). If morning temperature > 37.2⁰ C (98.9 F) and at 4 to 6 PM > 37.7⁰ C (99.9 F) should be considered as fever. UP TO DATE

4. HYPERTHERMIA An elevation in body temperature that occurs in the absence of resetting of the hypothalamic thermoregulatory center. Usually not mediated by infectious diseases. For e.g. Hyperthyroidism, Pharmacological agents (Atropine), Neuroleptic drugs, Serotonin syndrome. UP TO DATE

5. HYPERPYREXIA Hyperpyrexia is the term for an extraordinarily high fever ( >41.5⁰ C ), which can be observed in patients with severe infections but most commonly occurs in patients with central nervous system (CNS) hemorrhages. UP TO DATE

6. PYREXIA OF UNKNOWN ORIGIN (defined by Peterson and Beeson) Fever higher than 38.3⁰ C on several occasions. Duration of fever for at least three weeks. Uncertain diagnosis after one week of study in the hospital. Harrison’s 21 th ed.

7. Nowadays, patients with PUO are seldom hospitalized as diagnostic evaluation can be done on an outpatient basis. Thus in- hospital evaluation requirement has been eliminated from the definition. The definition of PUO has been further modified by exclusion of immunocompromised patients, whose workup requires an entirely different diagnostic and therapeutic approach.

8. Fever >101 ° F (38.3° C) on at least two occasions Illness duration of > 3 week No known immunocompromised state Diagnosis uncertain after a thorough history- taking, physical examination, and the following obligatory investigations. Current Definition of PUO for immunocompetent, non hospitalized patients includes -

9. DEFINITION OF ACUTE FEBRILE ILLNESS Acute febrile illnesses are characterized by fever of less than two weeks’ duration without organ-specific symptoms at the onset. These may begin with headache, chills, and myalgia. Later, specific organs may be involved. doi : 10.1136/bmj.k4766 | BMJ 2018;363:k4766 | the bmj

10. Acute Febrile Illness Acute localized infections Respiratory, Urinary tract, Gastrointestinal etc. Acute undifferentiated febrile illness (AUFI) Malaria Non-Malaria AUFI (smear or RDT negative) Viral Bacterial Parasitic Hepatic Amoebiasis Acute Schistosomiasis Acute Trypanosomiasis Arboviral Infections Dengue Chikungunya Zika Japanese Encephalitis Influenza (Occasionally if Respiratory symptoms not prominent) Bacteremia Enteric fever, Other Bacteria Such as E Coli, S aureus Zoonotic Infections Spirochetal (such as Leptospirosis, relapsing fever) Rickettsial (scrub typhus, murine typhus, spotted fevers)

11. HISTORY TAKING PATTERN OF FEVER Continuous Or Sustained – Daily Variation In Temperature Is <1 °C e.g.- Typhoid, Pneumonia, Meningitis, Urinary Tract Infections Remittent - Temperature Spikes Fall Daily With Diurnal Variation Of >2 ° C, But Doesn’t Touch Baseline. e.g.- Infective Endocarditis. Intermittent - Exaggeration Of Normal Circadian Rhythm ( Hectic - If Variation Between High And Low Is Extremely Large). e.g.- Abscesses, Deep Seated Infections. Hutchinson’s Clinical Methods

12. PATTERN OF FEVER Relapsing - Febrile Episodes Are Separated By Interval Of Normal Temp. e.g.- Malaria, Borrelia, Brucella Quotidian - Fever Occurs Daily (Plasmodium Falciparum). Double Quotidian - Double Spike Of Fever Everyday. Tertian Fever - Occurs Every 48 Hours (P. Vivax, P. Falciparum, P. Ovale). Quartan Fever - Occurs Every 72 Hours (Plasmodium Malaria). Hutchinson’s Clinical Methods

13. PATTERN OF FEVER

14. ASSOCIATED SYMPTOMS Rash – Dengue, Typhoid, CMV, EBV, Measles, Scrub typhus, Chicken pox, Meningococcal infection. Chills And Rigor – Malaria, Pyelonephritis, Bacterial Endocarditis, Liver abscess. Myalgia – Leptospirosis, Dengue, chikungunya, Influenza. Joint Pain – Dengue, Chikungunya Infection.

15. Jaundice – Malaria, Leptospirosis, Liver Abscess, Viral Hepatitis, Cholangitis Etc. Headache – Malaria, Typhoid, CNS Infections, Dengue. Convulsions - Meningitis, Brain Abscess. Nausea & Vomiting - Viral hepatitis, Cholangitis.

16. SYSTEMATICALLY LOCALIZING SYMPTOMS Respiratory – Cough, Chest Pain, Sputum, Breathlessness. Gastrointestinal – Abdominal Pain, Nausea, Vomiting, Diarrhea, Jaundice. Urinary Tract – Dysuria, Urinary Frequency, Lower Abdominal Pain. CNS – Altered Consciousness, Headache, Neck Stiff-ness .

17. Red flag signs in patients with acute undifferentiated febrile illnesses indicating need for hospitalization and urgent treatment • Prostration—unable to stand, sit, or walk without support • Temperature—hyperpyrexia (temperature >41.5°C) or hypothermia (Temperature <36°C) or rigors • Respiration—shortness of breath, respiratory rate >22 breaths/minute, Cyanosis, arterial oxygen saturation <92% on room air

18. • Circulation—Blood pressure <100 mm Hg systolic, cold clammy extremities, capillary refill >3 seconds Neurological—Altered mental status (Glasgow coma scale <13), convulsions, positive meningeal signs (such as neck stiffness and Kernig’s sign) • Abdominal pain—Severe or persistent vomiting • Severe conjunctival or palmar pallor • Jaundice on examination of sclera • Petechial or purpuric rash • Bleeding—From nose, gums, or venipuncture sites, hematemesis, malena .

19. CLINICAL EXAMINATION PULSE RATE Bradycardia Relative To Temperature Typhoid , Leptospira CNS Infections

20. Skin Examination Inspect The Entire Body For Rashes, If Rash Present Characterize The Lesions. Macular/Maculopapular Measles, Rubella, Epstein–Barr Virus, Cytomegalovirus, Human Parvovirus B19, Dengue, Typhoid. HEAD TO TOE EXAMINATION

21. Vesicular Chickenpox (Varicella Virus), Herpes Simplex Virus. Erythematous Toxic Shock Syndrome, Lyme Disease (Erythema Chronica Migrans), Human Parvovirus B19. Petechial/Haemorrhage Meningococcal Septicaemia, Rickettsia, Dengue.

22. MENINGOCOCCAL RASH ESCHAR IN SCRUB VESICULAR RASH IN HERPES ZOSTER VIRUS

23. HANDS EXAMINATION Splinter Hemorrhages

24. Face- Suppurative Sinusitis, Parotitis, Mastoiditis. Eye- Conjunctival Hemorrhage (Leptospirosis, Infective Endocarditis). Fundus Examination- Roth’s Spot, Papilledema. Conjunctival hemorrhage Roth’s Spot

25. Mouth And Throat - Coated Tongue (Typhoid), Tonsilitis, Pharyngitis . Chest - Crepts/ Bronchial Breath Sound (Lung Abscess), Rub- Pleuritis, Pericarditis. CVS - New murmur/worsing of murmur (Infective Endocarditis). Coated tongue

26. Per Abdomen – Tenderness- Typhoid, Intraabdominal Abscesses Palpable Lump - Hepatomegaly- Malaria, Leptospirosis, Liver Abscess Splenomegaly-Malaria, Bacterial Endocarditis, Typhoid.

27. CNS- Altered Patient (CNS Infection, Cerebral Malaria, Typhoid), Neck Rigidity (Meningitis). Back- Renal Angle Tenderness (Pyelonephritis), Tenderness Over Spine (Spinal Epidural Abscess) Scrotum- Epididymo - Orchitis (Mumps)

28. Diagnostic and management approach for acute febrile illness Step 1 Collect epidemiological information Local disease prevalence, seasonality (malaria, arboviral infections, scrub typhus, leptospirosis), potential exposures to animals, vectors (mosquitos, mites). Step 2 Evaluate clinically with history and examination doi : 10.1136/bmj.k4766 | BMJ 2018;363:k4766 | the bmj

29. Step 3 Perform first-line and, if possible, confirmatory diagnostic tests Rule out malaria by smear microscopy and rapid diagnostic test. Evaluate non-malarial AUFI with full blood count, urine analysis, biochemical tests, and imaging if clinically indicated. Definitive tests, if available: isolation (enteric fever), isolation (enteric fever), antigen detection (dengue), serology (rickettsia, leptospirosis).

30. Step 4 Integrate information from steps 1,2,3 to formulate confirmed or probable diagnosis Initiate empirical therapy based on setting and severity of illness For severely ill patients with non-malarial, non-arboviral AUFI use a combination (3rd generation cephalosporin + doxycycline)as empirical therapy to cover to cover rickettsioses, leptospirosis, and enteric fever.

31. Step 5 Monitor patient for therapeutic response, follow up test results Monitor response to therapy. Modify therapy according to results of definitive tests Review diagnosis and evaluate for other infections if fever persistent

32. TAKE HOME MESSAGE •Malaria, arboviral infections (such as dengue), enteric fever, and bacterial zoonotic diseases (such as scrub typhus and leptospirosis) are common causes to consider in patients presenting with acute fever and no localizing symptoms in tropical regions. •A step-wise approach—with a careful interpretation of local disease patterns, possible exposures and risk factors, clinical features, and basic laboratory data—can help clinicians recognize specific diseases.

33. •Request testing for malaria and a full blood count in all patients with acute undifferentiated fever. •Early presumptive antibiotic therapy may be started for suspected bacterial zoonoses if diagnostic confirmatory tests are awaited or not available, as these infections may progress rapidly into a life threatening illness with multi-system involvement.