IM4.1-20 | Fever and Febrile Syndromes — Practice Quiz

Correct. The WHO 2009 dengue classification describes three phases: febrile (days 1-3, high fever, positive NS1), critical (approximately days 4-6, defervescence, plasma leakage, thrombocytopenia), and recovery. This patient is defervescing with thrombocytopenia and haemoconcentration (haematocrit 52%) — hallmarks of the critical phase. Warning signs (abdominal pain, persistent vomiting, rapid breathing, bleeding, liver enlargement >2 cm, rising haematocrit with rapid platelet drop) must be actively monitored at this phase to prevent progression to severe dengue.

The NS1 antigen is positive in the febrile phase (days 1-3). By day 5, with defervescence, thrombocytopenia to 48,000/µL, and haematocrit rise to 52% indicating plasma leakage, this patient has entered the critical phase of dengue. Warning signs such as hepatomegaly and petechiae should prompt close monitoring for severe dengue.

Correct. Blood culture is the most practical high-yield investigation for enteric fever in the first two weeks of illness, with sensitivity of 60-80% in the first week declining thereafter. Although bone marrow culture has sensitivity approaching 90% (and remains positive even after antibiotics), it is invasive and reserved for cases where blood cultures are negative or the patient has received prior antibiotics. Widal test has poor specificity in endemic areas and a single result is unreliable. Stool cultures become positive later (weeks 3-4).

In the first 1-2 weeks of enteric fever, blood culture is the investigation of first choice with 60-80% sensitivity. Bone marrow culture is more sensitive (~90%) but invasive; reserve it for cases with prior antibiotics or negative blood culture. Widal serology has poor specificity in endemic India and a single titre is insufficient for diagnosis.

Correct. This presentation — fever, severe myalgia, conjunctival suffusion (not conjunctivitis), jaundice, and AKI with occupational water exposure — is classic Weil's disease (severe leptospirosis). The Microscopic Agglutination Test (MAT) is the gold-standard confirmatory test; it uses live serovar antigens and detects serovar-specific antibodies. IgM ELISA (e.g., Leptocheck) is a useful rapid screening test but lacks serovar specificity. MAT requires ≥4-fold titre rise between acute and convalescent samples or a single titre ≥1:400 in an endemic area.

The clinical triad of fever, severe myalgia, conjunctival suffusion, jaundice, and AKI after occupational water exposure is highly characteristic of leptospirosis (Weil's disease). The Microscopic Agglutination Test (MAT) is the reference standard for confirmatory diagnosis. IgM ELISA is a rapid screening test but not confirmatory.

Correct. This is scrub typhus caused by Orientia tsutsugamushi, transmitted by chigger mites. The pathognomonic eschar (painless black scab with surrounding erythema) is present in 50-70% of Indian cases. Doxycycline 100 mg twice daily for 7-14 days is the drug of choice and produces rapid defervescence (usually within 24-48 hours). Azithromycin is an alternative in pregnancy or doxycycline intolerance. Fluoroquinolones and beta-lactams are ineffective against rickettsial organisms.

The eschar — a painless black scab with surrounding erythema — is pathognomonic of scrub typhus (Orientia tsutsugamushi) when seen in a febrile patient from a forested/scrub region. Doxycycline 100 mg twice daily for 7-14 days is the drug of choice. Defervescence typically occurs within 24-48 hours — failure to defervesce should prompt reconsideration of the diagnosis.

Correct. This is severe falciparum malaria (cerebral malaria + AKI). WHO and NVBDCP guidelines recommend IV artesunate as first-line treatment for severe malaria: 2.4 mg/kg at 0, 12, and 24 hours, then once daily until the patient can take oral therapy. Artesunate has superior efficacy to IV quinine (shown in the SEAQUAMAT and AQUAMAT trials) with lower mortality. IV quinine was the former standard but is now second-line. Oral ACT is not appropriate for severe disease.

The peripheral smear showing multiple rings per RBC, Maurer's clefts, and banana-shaped gametocytes confirms Plasmodium falciparum. Cerebral malaria (confusion) and AKI together satisfy WHO criteria for severe malaria. IV artesunate 2.4 mg/kg at 0, 12, and 24 hours then daily is the WHO/NVBDCP first-line treatment, replacing quinine, which is now second-line.

Correct. The Petersdorf-Beeson definition of classic FUO requires: (1) temperature greater than 38.3°C on multiple occasions, (2) duration of at least 3 weeks, and (3) failure to diagnose after appropriate investigation (conventionally, one week of inpatient evaluation or its outpatient equivalent). This patient meets all three criteria. Nosocomial FUO applies to hospital-acquired fever (>38.3°C after >48 hours of hospitalisation). Neutropenic FUO applies to patients with ANC <500/µL. HIV-associated FUO applies to HIV-positive patients with CD4 <200.

Classic FUO is defined as fever >38.3°C on multiple occasions over at least 3 weeks, undiagnosed after appropriate initial investigation, in an immunocompetent ambulatory patient. The four subtypes are: classic (immunocompetent, community), nosocomial (hospital-acquired, not present on admission), neutropenic (ANC <500), and HIV-associated (HIV-positive, CD4 usually <200).

Correct. This is classic (exertional or non-exertional) heat stroke — hyperthermia (not fever), confusion, and anhydrosis distinguish it from heat exhaustion. The hypothalamic set-point is NOT raised in heat stroke; antipyretics (paracetamol, aspirin) have no role because there is no PGE2-mediated set-point elevation. Rapid external cooling (ice water immersion, cool water spray with fanning, ice packs to axillae and groin) to reduce core temperature to below 38.9°C within 30 minutes is the life-saving intervention. Delay causes irreversible neurological damage, rhabdomyolysis, DIC, and multi-organ failure.

Heat stroke is hyperthermia — not fever — caused by failure of thermoregulatory mechanisms. The hypothalamic set-point is not elevated, so antipyretics (paracetamol, aspirin, NSAIDs) are ineffective. Immediate rapid external cooling to below 38.9°C is the life-saving intervention. Antibiotics are not indicated at this stage.

Correct. For suspected inflammatory/rheumatological fever, the first-line panel includes markers of systemic inflammation (ESR, CRP), ANA for systemic lupus erythematosus screening, anti-dsDNA and complement (C3, C4) if ANA is positive, and ferritin (markedly elevated ferritin >5000 ng/mL is a hallmark of adult-onset Still's disease, haemophagocytic lymphohistiocytosis, and severe sepsis). Bone marrow biopsy is reserved for refractory FUO or when haematological malignancy or HLH is suspected. Empiric corticosteroids must NEVER be started before excluding TB and kala-azar.

When rheumatological fever is suspected, ANA, anti-dsDNA, complement levels, ESR, CRP, and ferritin form the appropriate first-line panel. Markedly elevated ferritin is a key diagnostic pointer for adult-onset Still's disease and HLH. Bone marrow biopsy and PET-CT are reserved for subsequent steps. Never start empiric corticosteroids without excluding TB and visceral leishmaniasis.

Correct. Sepsis-3 (Singer et al., JAMA 2016) defines septic shock as sepsis (organ dysfunction from dysregulated host response to infection) PLUS circulatory and cellular/metabolic abnormalities sufficient to substantially increase mortality — specifically, persisting hypotension requiring vasopressors to maintain MAP ≥65 mmHg AND serum lactate >2 mmol/L despite adequate fluid resuscitation. The term 'severe sepsis' is obsolete under Sepsis-3. SIRS criteria (fever/hypothermia, tachycardia, tachypnoea, WBC abnormality) are neither sensitive nor specific for infection-related organ dysfunction.

Sepsis-3 (JAMA 2016) uses three tiers: sepsis = life-threatening organ dysfunction from dysregulated host response (SOFA score ≥2); septic shock = sepsis + vasopressor requirement to maintain MAP ≥65 mmHg + lactate >2 mmol/L despite resuscitation. 'Severe sepsis' is an obsolete Sepsis-2 term. SIRS is not part of Sepsis-3 definitions.

Correct. Mantoux (PPD) test interpretation uses induration (palpable firmness), NOT erythema — this is the single most common reading error. The cutoffs are: ≥5 mm positive in HIV-positive, close TB contact, immunosuppressed patients, or chest X-ray suggestive of TB; ≥10 mm positive in BCG-vaccinated individuals, recent immigrants from endemic countries, healthcare workers, residents of congregate settings, persons with medical risk factors; ≥15 mm positive in low-risk individuals with no special circumstances. In this BCG-vaccinated immunocompetent woman with FUO in an endemic area, 12 mm is positive and warrants further evaluation for TB.

Mantoux interpretation measures INDURATION (not erythema) at 72 hours. In BCG-vaccinated immunocompetent individuals, ≥10 mm is considered positive. While BCG vaccination can contribute to false positives, an induration of ≥10 mm in an Indian adult with FUO should be considered as evidence of TB infection and triggers further workup (CXR, sputum, CT thorax/abdomen).