IM4.1-20 | Fever and Febrile Syndromes — Glossary

The recommended treatment for uncomplicated falciparum malaria: an artemisinin derivative (artesunate, artemether, dihydroartemisinin) combined with a partner drug (lumefantrine, amodiaquine, piperaquine); the combination prevents resistance to either component; artemether-lumefantrine (AL) is the NVBDCP-recommended first-line oral ACT for falciparum malaria in India.

An enzyme elevated in conditions associated with T-lymphocyte activation; ADA >40 U/L in a lymphocytic exudative pleural effusion has sensitivity 90–95% and specificity 85–90% for TB pleuritis in a high-TB-burden setting; particularly useful when AFB smear and culture of pleural fluid are negative (which is common in TB pleuritis).

A systemic inflammatory disorder of unknown aetiology characterised by quotidian fever ≥39°C, evanescent salmon-coloured urticarial rash, arthritis, sore throat, and markedly elevated serum ferritin (>5000–10,000 μg/L); diagnosed by Yamaguchi criteria after excluding infection, malignancy, and other autoimmune disease.

A false-negative Mantoux/TST result caused by suppression of the delayed-type hypersensitivity response; occurs in miliary/disseminated TB (high bacillary burden overwhelms T-cell response), severe malnutrition, HIV (CD4 <200), systemic corticosteroids, and other immunosuppressive states.

The crescent or banana-shaped macrogametocyte of Plasmodium falciparum, visible on peripheral blood smear at 1000× oil immersion; pathognomonic of P. falciparum infection (no other Plasmodium species produces gametocytes with this morphology); typically appears on day 7–15 of infection.

Aspiration of bone marrow (usually from posterior superior iliac spine) with smear preparation and core biopsy; indicated in FUO for suspected haematological malignancy (leukaemia, lymphoma), visceral leishmaniasis (identifies Leishman-Donovan bodies in macrophages), miliary TB (culture positive in 30–40%), and HLH (demonstrates haemophagocytosis).

Also known as Xpert MTB/RIF (GeneXpert); a real-time PCR-based diagnostic test that simultaneously detects Mycobacterium tuberculosis DNA and rifampicin resistance (a proxy for MDR-TB) in 2 hours; sensitivity 75–90% for pulmonary TB; endorsed by NTEP as the primary diagnostic test replacing sputum smear microscopy.

Pale slightly raised lesions visible on fundoscopy in the choroid layer; pathognomonic of miliary or disseminated tuberculosis when found in the context of prolonged fever, constitutional symptoms, and miliary CXR; best seen with a dilated pupil.

FUO in an immunocompetent, non-neutropenic, non-hospitalised patient; the broadest differential diagnosis across the four FUO categories.

Systematic identification and evaluation of individuals who have had close contact with a smear-positive TB case; under NTEP, all household and other close contacts are screened with Mantoux test and chest X-ray; children under 6 years old with negative Mantoux and no active TB are given isoniazid preventive therapy (IPT) for 6 months.

Pain or tenderness on firm percussion with a closed fist over the angle between the 12th rib and the vertebral column on each side; a clinical sign of pyelonephritis (upper UTI); caused by inflammation of the renal capsule and surrounding retroperitoneal tissues.

The ratio of cerebrospinal fluid glucose concentration to simultaneous serum glucose; normal ratio ≥0.6; ratio <0.5 in bacterial meningitis (bacteria and leucocytes consume glucose); ratio may be low-normal in TB meningitis (0.3–0.5); viral meningitis typically preserves the ratio; critical for distinguishing bacterial from viral meningitis.

An uncontrolled systemic inflammatory response characterised by markedly elevated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, IFN-γ); underlies the pathophysiology of sepsis, haemophagocytic lymphohistiocytosis (HLH), and severe COVID-19.

The narrowing of antimicrobial therapy from empiric broad-spectrum coverage to the narrowest effective agent once microbiological culture and sensitivity results are available; a core antimicrobial stewardship principle that reduces the emergence of antimicrobial resistance, C. difficile risk, adverse effects, and cost.

A coagulation disorder characterised by widespread activation of the coagulation cascade (driven by tissue factor release from monocytes and endothelial injury), resulting in microvascular thrombi and simultaneous consumption of clotting factors leading to bleeding; complicates severe sepsis, obstetric catastrophes, and malignancy.

Rifampicin induces hepatic UGT1A1 and CYP3A4 enzymes, reducing dolutegravir plasma levels by approximately 75%; to maintain therapeutic dolutegravir concentrations, the dose is increased from 50 mg once daily to 50 mg twice daily (100 mg/day) during rifampicin co-administration; this is a mandatory dose adjustment in TB-HIV co-treated patients.

The WHO-endorsed TB treatment strategy requiring direct observation of medication ingestion by a trained health worker; now integrated into NTEP as nikshay posanposhen yojana (nutritional support) and nikshay mitra (patient support) components; ensures adherence and provides a safety net for adverse drug reactions.

A febrile reaction caused by drug hypersensitivity (Type IV delayed hypersensitivity), typically appearing 7–10 days after initiating the causative drug; no rash in 50% of cases; resolves within 48–72 hours of stopping the drug.

Diagnostic criteria for infective endocarditis requiring: major criteria (positive blood cultures from typical organisms on ≥2 occasions, or evidence of endocardial involvement on echocardiography) and minor criteria (predisposing condition, fever, embolic phenomena, immunological phenomena, microbiological evidence); 2 major, or 1 major + 3 minor, or 5 minor = definite infective endocarditis.

Standardised diagnostic criteria: major criteria — positive blood cultures for typical organisms ≥2 occasions, or echocardiographic evidence (vegetation, abscess, new valve regurgitation); minor criteria — predisposing condition, fever, embolic phenomena (Janeway, arterial emboli), immunological phenomena (Osler, Roth, glomerulonephritis); definite IE = 2 major, or 1 major + 3 minor, or 5 minor.

Initiation of therapy for a probable diagnosis before microbiological or definitive diagnostic confirmation; indicated when the probability of a dangerous diagnosis is high and the cost of waiting for confirmation exceeds the risk of starting treatment without certainty.

Host-derived cytokines — principally IL-1β, IL-6, TNF-α, and interferons — produced by activated monocytes and macrophages in response to pathogens or tissue injury, that act on the hypothalamic preoptic area via PGE2 to raise the thermoregulatory set-point.

A painless black necrotic skin lesion (0.5–2 cm) at the site of a mite bite, pathognomonic of scrub typhus (Orientia tsutsugamushi); found in concealed sites — axillae, inguinal folds, scalp, behind ears, between toes; present in 50–70% of Indian scrub typhus cases.

A single oral temperature reading of ≥38.3°C (or two readings ≥38°C one hour apart) in a patient with an absolute neutrophil count <500 cells/mm³ (or expected to fall to <500); a medical emergency requiring immediate broad-spectrum intravenous antibiotics within one hour.

A controlled elevation of core body temperature above 38.3°C in which the hypothalamic thermoregulatory set-point has been raised by endogenous pyrogens (IL-1β, IL-6, TNF-α) acting via prostaglandin E2; responds to antipyretics.

A temperature >38.3°C on multiple occasions persisting for ≥3 weeks, undiagnosed after at least 3 outpatient visits or 3 days of hospitalisation with appropriate investigation (Petersdorf-Beeson, updated by Durack and Street).

A granulomatous vasculitis affecting the aorta and its branches, predominantly in patients >50 years; presents with temporal headache, scalp tenderness, jaw claudication, and polymyalgia rheumatica; most feared complication is ischaemic optic neuropathy leading to sudden blindness; confirmed by temporal artery biopsy; treated with high-dose corticosteroids immediately.

Percussion technique for detecting splenic enlargement before the spleen is palpable: percuss from resonant tympany in the left upper quadrant to dullness; a dull area >6 cm in the long axis in the left flank suggests splenomegaly and warrants bimanual palpation beginning from the right iliac fossa.

The proportion of blood volume occupied by erythrocytes; rising haematocrit (≥20% increase from baseline) in dengue indicates plasma leakage (capillary permeability from endothelial injury by the dengue virus); a rising haematocrit concurrent with falling platelets is a WHO 2009 warning sign for dengue; the haematocrit peaks at the critical phase (day 3–6) when the risk of severe plasma leakage is highest.

The microscopic finding on bone marrow (or other tissue) of macrophages engulfing erythrocytes, leucocytes, and platelets; a diagnostic criterion for haemophagocytic lymphohistiocytosis (HLH); can also be seen as a reactive finding in sepsis and other inflammatory states without fulfilling criteria for HLH.

Painful involuntary muscle contractions during or after exertion in heat, caused by selective sodium depletion from sweat replaced with hypotonic fluid; normal or mildly elevated temperature; normal sensorium; treated with electrolyte-containing oral rehydration.

A heat-related illness with core temperature <40°C, profuse sweating (thermoregulatory mechanism intact but overwhelmed), volume depletion, and intact sensorium; treated with removal from heat and IV isotonic fluid rehydration.

A medical emergency defined by core temperature >40°C plus CNS dysfunction (confusion, delirium, seizures, or coma); classic form: passive individuals in heat waves, absent sweating; exertional form: young individuals in intense physical work, sweating may be present; treated with immediate physical cooling.

FUO in an HIV-positive patient; differential stratified by CD4 count — below 200 cells/mm³ dominated by MAC, PJP, cryptococcosis, CMV, and disseminated TB.

A life-threatening hyperinflammatory syndrome driven by uncontrolled macrophage and CD8+ T-cell activation; characterised by fever, cytopenias, splenomegaly, elevated ferritin (>10,000 ng/mL is suggestive), and haemophagocytosis on bone marrow biopsy.

A set of time-critical actions to be completed within one hour of sepsis recognition: (1) measure serum lactate; (2) obtain blood cultures before antibiotics; (3) administer broad-spectrum IV antibiotics; (4) administer 30 mL/kg IV crystalloid for hypotension or lactate ≥4 mmol/L; (5) start vasopressors for persistent hypotension (MAP <65 mmHg); compliance with the bundle is associated with improved mortality in sepsis.

The standard four-drug intensive phase regimen for drug-sensitive TB under India's NTEP: H = isoniazid, R = rifampicin, Z = pyrazinamide, E = ethambutol; given as daily fixed-dose combination tablets, weight-band dosed, for 2 months (intensive phase); followed by HRE (3 drugs, without Z) for 4 months (continuation phase) = total 6 months.

Core temperature exceeding 41°C; at this level direct cellular (particularly neuronal) injury begins to occur regardless of the mechanism; warrants urgent management.

An uncontrolled rise in core body temperature due to failure or overwhelming of heat-dissipation mechanisms, without any resetting of the hypothalamic set-point; does NOT respond to antipyretics; requires physical cooling.

An in vitro blood test (QuantiFERON-TB Gold, T-SPOT.TB) measuring interferon-gamma release from sensitised T-cells in response to M. tuberculosis-specific antigens (ESAT-6, CFP-10); more specific than Mantoux in BCG-vaccinated individuals; does not distinguish active from latent TB.

A paradoxical worsening of an existing or previously occult opportunistic infection after initiation of ART, caused by the recovering immune system mounting an inflammatory response against pathogen antigens; most common in TB-HIV co-infection (TB-IRIS) occurring 2–8 weeks after ART initiation; managed with NSAIDs; severe IRIS may require corticosteroids.

A negative staining technique in which India ink particles are excluded by the Cryptococcus neoformans capsule, creating a clear halo around the encapsulated yeast against a dark background on CSF microscopy; positive in 50–80% of cryptococcal meningitis cases; the cryptococcal antigen (CrAg) test is more sensitive (>95%).

The parenteral artemisinin derivative of choice for severe falciparum malaria; administered at 2.4 mg/kg at 0, 12, and 24 hours then daily; superior to IV quinine in head-to-head trials (AQUAMAT, SEAQUAMAT) for mortality reduction; after clinical improvement, transition to a full course of oral ACT (artemether-lumefantrine or equivalent).

Painless flat erythematous or haemorrhagic macules on the palms and soles caused by septic microemboli from cardiac vegetations; a minor Duke criterion for infective endocarditis.

A clinical sign of meningeal irritation: with the hip flexed to 90°, attempted extension of the knee beyond 135° produces resistance and pain due to meningeal and radicular traction; positive in bacterial meningitis, tuberculous meningitis, subarachnoid haemorrhage, and carcinomatous meningitis.

The amastigote stage of Leishmania donovani — 2–4 μm ovoid intracellular forms within macrophages; identified on bone marrow aspirate by the presence of a round nucleus and a rod-shaped kinetoplast (appearing as two dark dots); pathognomonic of visceral leishmaniasis when found in the appropriate clinical context.

Criteria for distinguishing pleural exudate from transudate: pleural fluid protein >3 g/dL OR pleural:serum protein ratio >0.5 OR pleural:serum LDH ratio >0.6 = exudate; sensitivity >99% for exudates; relevant in febrile patients where lymphocytic exudative effusion with elevated ADA (>40 U/L) suggests TB pleuritis.

A pharmacogenetic disorder caused by a mutation in the ryanodine receptor (RYR1) that causes uncontrolled calcium release from the sarcoplasmic reticulum when triggered by volatile anaesthetic agents or succinylcholine; manifests as life-threatening hyperthermia, rigidity, and rhabdomyolysis; treated with dantrolene.

An intradermal injection of 0.1 mL (5 TU) purified protein derivative (PPD) of Mycobacterium tuberculosis into the volar forearm; the induration (not erythema) is measured at 48–72 hours; threshold for positivity: ≥10 mm in the general (BCG-vaccinated) population, ≥5 mm in immunosuppressed patients; a positive test indicates sensitisation, NOT active TB.

The gold-standard serological test for leptospirosis; detects agglutinating antibodies against Leptospira serovars; requires live cultures of Leptospira and specialist laboratory facilities; a four-fold rise in paired titres (≥1:100 or ≥1:400 in endemic areas) is diagnostic.

Disseminated haematogenous spread of Mycobacterium tuberculosis producing bilateral fine nodular (miliary) shadowing on chest X-ray; involves bone marrow, liver, spleen, and meninges; Mantoux may be falsely negative due to anergy; treated with standard anti-TB therapy (NTEP: 2HRZE + 4HRE).

FUO with ANC <500 cells/mm³, usually post-chemotherapy; mandates immediate empiric broad-spectrum antibiotics; after day 7 of neutropenia, consider invasive fungal infection (Aspergillus).

FUO developing in a hospitalised patient who was not febrile at admission; differential dominated by catheter-related infections, C. difficile colitis, drug fever, acalculous cholecystitis, and DVT/PE.

India's national TB programme (formerly RNTCP); prescribes daily fixed-dose combination regimens for drug-sensitive TB: 2HRZE (intensive phase, 2 months) + 4HRE (continuation phase, 4 months), weight-band dosed.

Raised tender painful erythematous nodules on the pulps of fingers and toes caused by immune-complex deposition; a minor Duke criterion for infective endocarditis; distinguishable from Janeway lesions by being painful, raised, and on finger and toe pulps.

A classical fever pattern historically described in Hodgkin's lymphoma, comprising alternating weeks of high fever and afebrile periods; rare in practice but of historical and examination significance.

An imaging technique using fluorodeoxyglucose (FDG) as a tracer; metabolically active tissues (malignant cells, inflammatory foci, active infection) take up more glucose and appear as 'hot spots'; in FUO workup, PET-CT identifies occult malignancy, infected prostheses, sarcoidosis, and vasculitis that are missed by conventional CT; highest diagnostic yield among imaging modalities for classic FUO at tertiary centres.

Per WHO dengue guidelines: prophylactic platelet transfusion is NOT recommended based on platelet count alone; transfusion is indicated only for active significant bleeding with severe thrombocytopaenia; the platelet count nadir is expected during the critical phase (days 3–6) and spontaneous recovery occurs in the recovery phase (days 6–7 onwards).

The preferred site for bone marrow aspiration and biopsy in adults; located at the posterolateral sacral dimple; provides access to the iliac bone marrow with the lowest risk of injury to major vessels or nerves; the patient is positioned in lateral decubitus with knees drawn up.

A biomarker of bacterial infection; induced specifically by bacterial LPS; rises above 0.5 ng/mL in bacterial infections; not elevated in viral infections or most autoimmune conditions; useful for distinguishing bacterial from non-bacterial causes of fever.

A lipid mediator synthesised from arachidonic acid by cyclooxygenase-2 (COX-2) in hypothalamic endothelial cells; binds EP3 receptors in the preoptic area to raise the thermoregulatory set-point and produce fever; the molecular target of NSAIDs and paracetamol.

A bedside sepsis screening tool scoring 1 point each for: altered mentation, respiratory rate ≥22 breaths/min, systolic BP ≤100 mmHg; a score ≥2 suggests high risk of sepsis.

A technique for malaria diagnosis using centrifugation of blood in a capillary tube, followed by acridine-orange staining and UV fluorescence microscopy of the buffy coat; more sensitive than thin smear but less useful for species identification and parasite density counting; the fluorescent parasites appear as bright dots in the RBC layer.

A heart rate lower than expected for the height of fever; in enteric fever, Salmonella typhi endotoxin directly depresses cardiac conduction, producing a pulse that is inappropriately low for the temperature (e.g., pulse 78 bpm with temperature 39.5°C); also seen in leptospirosis, legionellosis, and yellow fever.

Breakdown of skeletal muscle releasing myoglobin into the circulation; myoglobin is nephrotoxic and can precipitate in renal tubules causing acute tubular necrosis; complicates heat stroke, severe exertion, and severe infections; managed with aggressive IV fluid hydration to flush myoglobin.

Rifampicin is a potent inducer of hepatic CYP450 enzymes (CYP3A4, CYP2C9) and UGT1A1; it reduces plasma levels of: warfarin (increase INR monitoring, adjust dose), oral contraceptives (alternative contraception needed), methadone (increase dose or switch methadone to buprenorphine), many antiretrovirals (adjust dolutegravir, avoid efavirenz dose issues, replace certain PIs with DTG); drug interaction review is mandatory before starting rifampicin.

Uncontrollable whole-body shivering with teeth chattering caused by a rapid cytokine-driven thermostat rise; characteristic of malaria (synchronous merozoite release every 48 hours) and bacteraemia; distinguishable from simple chills by the whole-body shaking quality and the sequence: cold-and-shaking → temperature rises → hot-and-sweating.

A recombinant antigen-based rapid immunochromatographic test for visceral leishmaniasis; sensitivity >90% in the Indian subcontinent; a positive result in a patient from an endemic area with the compatible clinical picture is sufficient for diagnosis and treatment.

Salmon-pink 2–4 mm blanching macules on the trunk, caused by bacterial emboli in dermal capillaries; appearing in crops on days 7–10 of enteric fever; present in only 10–30% of typhoid cases; pathognomonic when found in the clinical context of step-ladder fever and splenomegaly.

Pale-centred oval retinal haemorrhages visible on fundoscopy; caused by immune-complex or embolic deposition in retinal vessels; a minor Duke criterion for infective endocarditis.

Small pink stippling dots visible within the enlarged erythrocytes infected with Plasmodium vivax (or P. ovale) on Giemsa-stained peripheral blood smear; represent the remains of parasitophorous vacuole membrane proteins; their presence confirms P. vivax or P. ovale infection; NOT present in P. falciparum or P. malariae infections.

Life-threatening organ dysfunction caused by a dysregulated host response to infection, identified by an acute increase in the SOFA score of ≥2 points in the context of a suspected or confirmed infection (Singer et al., JAMA 2016).

A subset of sepsis with circulatory and cellular/metabolic failure, identified clinically as MAP <65 mmHg requiring vasopressors despite adequate fluid resuscitation, with serum lactate >2 mmol/L.

An acute-phase reactant that is markedly elevated in adult-onset Still's disease (>5000–10,000 μg/L), haemophagocytic lymphohistiocytosis (>10,000 ng/mL), and some infections; a ferritin >500 μg/L in the context of prolonged fever warrants consideration of AOSD and HLH.

Clinical or laboratory features of severe Plasmodium falciparum malaria requiring IV artesunate: impaired consciousness (Blantyre coma score ≤2 in children, GCS <15 in adults), prostration, multiple convulsions (>2 per 24 hours), respiratory distress, pulmonary oedema, abnormal bleeding, severe anaemia (Hb <5 g/dL in adults), haemoglobinuria, jaundice + parasitaemia >5%, hyperparasitaemia (>5% RBCs infected), circulatory collapse, acute kidney injury (creatinine >265 μmol/L).

A clinical sign for free peritoneal fluid (ascites): dullness on percussion shifts to the dependent side when the patient rolls, because ascitic fluid redistributes by gravity; detectable when ascites exceeds approximately 1–1.5 litres.

Sequential Organ Failure Assessment score; a 24-point aggregate of organ dysfunction across six systems (respiration, coagulation, liver, cardiovascular, CNS, renal); an increase of ≥2 from baseline defines sepsis per Sepsis-3.

Enlargement of the spleen measured by palpation below the left costal margin in the midclavicular line: mild <4 cm; moderate 4–8 cm; massive (Hackett Grade 4–5) >8 cm, crossing the midline or reaching the right iliac fossa; massive splenomegaly in the context of fever in India suggests kala-azar, malaria (chronic), or myeloid leukaemia.

The standard serological test for brucellosis; a single titre ≥1:160 is considered significant; paired sera showing a four-fold rise in titre is diagnostic; positive result in the appropriate clinical context (unpasteurised dairy/animal contact) with fever and hepatosplenomegaly warrants doxycycline + rifampicin treatment.

The NACO first-line ART regimen: tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + dolutegravir 50 mg; taken as a single daily fixed-dose combination tablet; dolutegravir dose must be doubled to 50 mg twice daily when co-administered with rifampicin (a potent CYP3A4/UGT1A1 inducer) due to drug-drug interaction.

A communication strategy to verify patient and family understanding: after explaining a concept (diagnosis, danger signs, treatment instructions), the clinician asks the patient to explain it back in their own words; if the explanation is incorrect or incomplete, the clinician re-explains and repeats; studies show teach-back reduces non-adherence and improves health outcomes.

Systemic infection with Leishmania donovani transmitted by the sandfly Phlebotomus argentipes; endemic in Bihar, Jharkhand, West Bengal, Uttar Pradesh; presents with prolonged fever, progressive massive splenomegaly, pancytopaenia, and polyclonal hypergammaglobulinaemia; diagnosed by rK39 rapid test or bone marrow aspirate; treated with liposomal amphotericin B in India.

An agglutination test based on cross-reactivity between rickettsial antigens and Proteus OX strains; OXK positivity suggests scrub typhus; low specificity but widely used in India; being superseded by immunofluorescence assay (IFA) serology at tertiary centres.

Diagnostic criteria for adult-onset Still's disease requiring ≥5 features (at least 2 major) after exclusion of infection, malignancy, and other rheumatic disease. Major criteria: fever ≥39°C ≥1 week, arthralgia ≥2 weeks, typical rash, leucocytosis ≥10,000/mm³ with ≥80% granulocytes. Minor criteria: sore throat, lymphadenopathy, hepatosplenomegaly, abnormal LFTs, negative ANA and RF.