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Nipah Virus Disease (NiV)

Classification & Discovery

• Jawetz Melnick & Adelberg's Medical Microbiology, 28e
• Bradley and Daroff's Neurology in Clinical Practice

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Reservoir & Transmission

1. Contact with infected animals - pigs were the amplifying host in the original Malaysia/Singapore outbreak (1998-1999)
2. Contaminated food - particularly raw date palm sap consumed in Bangladesh/India outbreaks, when bats contaminate the sap during collection
3. Human-to-human transmission - via respiratory droplets, seen especially in Bangladesh and India (West Bengal); this mode distinguishes the Bangladesh/India strain from the Malaysian strain
4. Nosocomial (healthcare-associated) spread - has been documented, especially in West Bengal outbreaks

• Bradley and Daroff's Neurology in Clinical Practice, p. 1684

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Epidemiology

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Clinical Features

• Incubation period: 4-14 days (up to 45 days reported)
• Prodrome: Fever, headache, myalgia, sore throat, vomiting
• Neurological (encephalitic form): Drowsiness, altered consciousness, stupor, coma, seizures, focal neurological signs, stroke
• Respiratory form: Prominent in Bangladesh/India strains - atypical pneumonia, respiratory distress
• Late-onset/relapsed encephalitis: Can occur months to years after initial illness (longest interval: 11 years); presents with fever, headache, seizures, and confluent cortical MRI lesions rather than the discrete hyperintense spots of acute disease

• Malaysia strain: ~40%
• Bangladesh/India strains: 75-94%
• Late-onset/relapsed encephalitis: ~18% (lower than acute disease)

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Pathophysiology

• Focal ischemia and microinfarcts
• Possible CNS hemorrhage
• MRI: Small disseminated discrete hyperintense lesions in subcortical and deep white matter (acute disease)
• CSF: Normal or mild pleocytosis
• 21% of Malaysian survivors had persistent neurological or neuropsychiatric sequelae
• Bradley and Daroff's Neurology in Clinical Practice, p. 1684

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Diagnosis

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Treatment

• Intensive supportive care
• Seizure management
• Respiratory support as needed
• Strict infection control to prevent nosocomial spread

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Prevention & Control

• Avoid contact with sick animals (pigs, bats) and consumption of raw date palm sap
• Strict barrier nursing and personal protective equipment for healthcare workers
• Contact tracing and surveillance around confirmed cases
• India has established NiV surveillance, Rapid Response Teams (RRTs), and rapid testing capacity
• No licensed human vaccine (several candidates in trials, including subunit and mRNA platforms)

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Why It Matters Globally

• High case-fatality rate
• Limited human-to-human transmission (currently) - but with pandemic potential
• No approved treatments or vaccines
• Broad geographic range of the bat reservoir
• Recurrent spillover events in South Asia

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• Case definitions (Suspect / Probable / Confirmed)
• Lab investigations with priority tiers
• Differential diagnosis table
• Full supportive care protocol (priority-colour-coded)
• Investigational agents + dosing quick-reference
• PPE / contact tracing / IHR notification
• Prognosis, follow-up schedule, and quick-reference card

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Hantavirus

Classification & Virology

• Sherris & Ryan's Medical Microbiology, 8th ed.

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Two Major Disease Syndromes

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Viruses, Reservoirs & Geography

• Hantaan - Apodemus field mice - Eastern Asia (China, Korea, Russia) - causes severe HFRS
• Dobrava - Apodemus mice - Balkans - severe HFRS
• Seoul - Brown/Norway rats (Rattus norvegicus) - worldwide (including US ratteries, 2017 outbreak in 31 states)
• Puumala - Bank voles - Scandinavia/Western Europe - causes nephropathia epidemica (mild)
• Saaremaa - Apodemus agrarius - Central/Northern Europe - moderate HFRS

• Sin Nombre - Deer mouse (Peromyscus maniculatus) - Western/Central US (>800 cases total, reported in 32 states)
• Andes - Oligoryzomys longicaudatus - Argentina, Chile - the only hantavirus with documented human-to-human transmission
• Choclo - Panama; Bayou - Louisiana/Texas; Black Creek Canal - Florida
• Jawetz Melnick & Adelberg's Medical Microbiology, 28e | Red Book 2021

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Transmission

• Primary route: Inhalation of aerosolized rodent urine, droppings, or saliva - the most important route
• Rodents are asymptomatically infected with lifelong chronic viruria - they continuously shed virus
• Direct contact with infected rodent or its excreta; rodent bites (less common)
• Contamination of broken skin
• Andes virus exception: person-to-person transmission documented during outbreaks in South America - and now confirmed in the 2026 MV Hondius cruise ship outbreak (see below)

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Clinical Features

HPS / HCPS (Americas)

HFRS (Old World)

• Febrile phase: Headache, back/abdominal pain, fever, chills, flushing of face, redness of eyes, blurred vision, petechiae
• Hypotensive phase: Low blood pressure, acute shock, vascular leakage
• Oliguric phase: Acute renal failure - the hallmark; may require dialysis
• Diuretic/Convalescent: Recovery takes weeks to months
• Severity depends on virus strain (Hantaan/Dobrava most severe; Puumala mildest)

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Pathophysiology

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Diagnosis

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Treatment

• ICU admission - mandatory for any cardiopulmonary phase
• Oxygen supplementation - escalate to mechanical ventilation early (threshold: GCS decline or worsening hypoxaemia)
• Lung-protective ventilation for ARDS (low tidal volume 6 mL/kg IBW)
• Fluid management - careful balance; both hypovolaemia (shock) and overload (worsens pulmonary oedema) are dangerous
• Vasopressors - noradrenaline for haemodynamic support
• ECMO - used in severe cases with refractory shock; some survival benefit reported at specialist centres
• Ribavirin - IV ribavirin has shown benefit in HFRS if given early; evidence in HPS is weaker and inconsistent. Not standard of care for HPS.
• Dialysis - required in severe HFRS with acute renal failure/fluid overload
• Avoid platelet transfusions unless active bleeding (thrombocytopenia is immune-mediated, not consumptive)

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Prevention

• Rodent control - the primary preventive measure
• Ventilate closed spaces before entering; wet-mop rather than sweep or vacuum rodent droppings (to avoid aerosolization)
• Wear N95 mask and gloves when cleaning rodent-infested areas
• Seal home entry points; store food in rodent-proof containers
• No licensed human vaccine in most countries (China has a bivalent vaccine for Hantaan/Seoul)
• Campers: avoid sleeping on bare ground; use tents with sealed floors

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2026 MV Hondius Outbreak - Current Event

• Andes virus is the only hantavirus known to spread person-to-person (in addition to rodent-to-human transmission)
• Multiple passengers and crew were infected; at least one confirmed case in a Swiss passenger who disembarked before the outbreak was recognized
• The ship was evacuated in Tenerife, Spain on May 10, 2026
• US passengers were transported to a military base in Nebraska for quarantine and monitoring
• Authorities raced to locate ~40 passengers who had already disembarked
• WHO and CDC issued guidance; multiple Asian countries heightened airport screening

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Bronchial Asthma: Diagnostic & Management Algorithm Protocol

Definition

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PART 1: DIAGNOSTIC ALGORITHM

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Step 1 — Recognise Characteristic Symptoms

┌─────────────────────────────────────────────────────────────┐
│  4 RESPIRATORY SYMPTOMS OF ASTHMA (GINA 2025)              │
│                                                             │
│  1. Wheeze (expiratory, high-pitched)                      │
│  2. Shortness of breath / dyspnea                          │
│  3. Chest tightness                                        │
│  4. Cough (particularly nocturnal or post-exercise)        │
│                                                             │
│  ► Pattern: variable, episodic, worse at night/morning     │
│  ► Triggered by: allergens, exercise, cold air, infections,│
│    NSAIDs, beta-blockers, emotional stress, irritants      │
└─────────────────────────────────────────────────────────────┘

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Step 2 — Confirm Variable Expiratory Airflow Limitation

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Step 3 — Type 2 Biomarkers (GINA 2025 New Addition)

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Step 4 — Classify Asthma Severity at Initial Presentation

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Step 5 — Differential Diagnosis: Rule Out Alternatives

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PART 2: ASTHMA CONTROL ASSESSMENT (ONGOING)

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Asthma Control Tool (ACT / ACQ)

• Washington Manual of Medical Therapeutics | GINA 2025

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PART 3: LONG-TERM MANAGEMENT — STEPWISE PROTOCOL

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Two Treatment Tracks

• Reduces exacerbation risk vs SABA reliever
• Simpler regimen; better adherence

• For patients unlikely to adhere to daily controller
• ICS-LABA limited to 3-6 months at high doses to minimise side effects

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Stepwise Treatment (Adults/Adolescents ≥12 yrs)

═══════════════════════════════════════════════════════════════════
STEP 1  ─────────────────────────────────────────────────────────
Track 1: As-needed low-dose ICS-formoterol (AIR therapy only)
Track 2: As-needed low-dose ICS taken whenever SABA taken (or
         SABA alone - if ICS-formoterol not available)
───────────────────────────────────────────────────────────────────
STEP 2  ─────────────────────────────────────────────────────────
Track 1: As-needed low-dose ICS-formoterol (same as Step 1)
Track 2: Daily low-dose ICS + as-needed SABA
         Alt: leukotriene receptor antagonist (LTRA)
───────────────────────────────────────────────────────────────────
STEP 3  ─────────────────────────────────────────────────────────
Track 1: Low-dose ICS-formoterol maintenance + as-needed ICS-
         formoterol (MART)
Track 2: Low-dose ICS-LABA + as-needed SABA
         Alt: medium-dose ICS; or low-dose ICS + LTRA
───────────────────────────────────────────────────────────────────
STEP 4  ─────────────────────────────────────────────────────────
Track 1: Medium-dose ICS-formoterol MART
Track 2: Medium-dose ICS-LABA + as-needed SABA
         Alt: Add tiotropium (LAMA) or LTRA to ICS-LABA
         ► GINA 2025 change: medium-dose ICS-LABA preferred
           over high-dose (minimises steroid side effects)
───────────────────────────────────────────────────────────────────
STEP 5  ─────────────────────────────────────────────────────────
Refer to specialist / severe asthma service
Phenotype-guided add-on biologic therapy:
  ┌─────────────────────────────────────────────────────────────┐
  │ Blood eos ≥300 + FeNO ≥25 → Anti-IL-5 (mepolizumab,       │
  │   reslizumab, benralizumab) OR dupilumab (anti-IL-4/13)    │
  │ Allergic asthma + total IgE ↑ + sensitised → Omalizumab   │
  │   (anti-IgE)                                               │
  │ Blood eos ≥150 OR FeNO ≥25 → Dupilumab (anti-IL-4Rα)      │
  │ Tezepelumab (anti-TSLP) for all phenotypes incl. non-T2    │
  │ LAMA (tiotropium) add-on if not already used               │
  │ Maintenance OCS: LAST RESORT only; assess adrenal risk     │
  └─────────────────────────────────────────────────────────────┘
═══════════════════════════════════════════════════════════════════

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ICS Dose Reference (Beclomethasone Equivalent)

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PART 4: ACUTE EXACERBATION MANAGEMENT

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Classification of Exacerbation Severity

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Acute Exacerbation Treatment Protocol

┌──────────────────────────────────────────────────────────────┐
│  IMMEDIATE ASSESSMENT (ALL PATIENTS)                        │
│  • SpO2, RR, HR, use of accessory muscles, ability to speak │
│  • Peak flow / FEV1 if possible                             │
│  • IV access, ECG if severe                                 │
└──────────────────────────────────────┬───────────────────────┘
                                       │
          ┌────────────────────────────┼────────────────────────┐
          ▼                            ▼                        ▼
     MODERATE                      SEVERE              IMPENDING ARREST
    (PEF 40-69%)                 (PEF <40%)             (PEF <25%)
          │                            │                        │
          ▼                            ▼                        ▼
  SABA 4-8 puffs MDI         SABA via nebuliser         Intubate +
  + ipratropium               + ipratropium              mechanical
  q20min × 3                  q20min × 3                 ventilation
          │                    + IV/PO steroids
          ▼                    + O2 to SpO2 93-95%
  Reassess 1hr                          │
          │                             ▼
  Improving? ──YES──→          Reassess 1 hour
          │                             │
          NO                  Improving? ──YES──→ Continue;
          │                             │           admit ward
          ▼                             NO
   Treat as                             │
   SEVERE                               ▼
                                  ICU ESCALATION
                                  + MgSO4 IV
                                  + IV aminophylline
                                  (consider NIV)

Pharmacological Treatment — Acute Phase

Discharge Criteria

• PEF ≥70% predicted / personal best sustained ≥60 minutes
• SpO2 ≥94% on room air
• Able to walk without dyspnoea
• Prednisolone prescription × 5-7 days
• Written asthma action plan
• Review appointment within 2-7 days
• Inhaler technique checked

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PART 5: WRITTEN ASTHMA ACTION PLAN (Traffic Light System)

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PART 6: SPECIAL POPULATIONS

Asthma in Children <5 Years (GINA 2025 — New Guidance)

1. Recurrent acute wheezing episodes (with or without interval symptoms)
2. Alternative diagnosis unlikely
3. Response to asthma treatment (symptom improvement within minutes of SABA)

Asthma in Pregnancy

• Approximately 4% of pregnant women have asthma; 1/3 experience exacerbations
• FEV1 and PEF remain unchanged in pregnancy (progesterone increases tidal volume but not FVC)
• Poorly controlled asthma increases risk of: preterm labour, low birth weight, preeclampsia, perinatal death
• Management: Continue all controller therapy - risk of uncontrolled asthma >> risk of ICS
• Avoid oral steroids in first trimester if possible; use lowest effective dose if needed
• Montelukast: continue if needed for control; data reassuring
• Biologics: limited safety data; individualise decision

Occupational Asthma

• Remove from offending exposure early (may result in complete resolution)
• Document sensitisation (skin test or specific IgE)
• Same pharmacological management as other asthma

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Summary Algorithm Flowchart

Patient presents with respiratory symptoms
             │
             ▼
  ┌─────────────────────────────────┐
  │ ≥2 of: wheeze, SOB, chest      │
  │ tightness, cough (recurrent,   │
  │ variable, nocturnal)           │
  └─────────────┬───────────────────┘
                │
                ▼
   Perform spirometry + BDR test
                │
       ┌────────┴────────┐
       ▼                 ▼
  FEV1/FVC <0.7      FEV1/FVC normal
  BDR positive       (consider BPT,
  → ASTHMA           PEF variability,
   CONFIRMED         exercise test)
       │                  │
       └────────┬──────────┘
                ▼
   Classify severity + check T2 biomarkers
   (blood eos, FeNO, IgE)
                │
                ▼
   Rule out differentials (COPD, VCD,
   cardiac failure, etc.)
                │
                ▼
   ┌──────────────────────────────────┐
   │ INITIATE STEPWISE TREATMENT     │
   │ Steps 1→5 (GINA 2025 tracks)   │
   │ + Non-pharmacological measures  │
   │ + Written action plan           │
   │ + Inhaler technique education   │
   └──────────────────────────────────┘
                │
                ▼
   Review control every 1-6 months
   ┌────────────┬─────────────────────┐
   ▼            ▼                     ▼
Well         Not well              Very poorly
controlled   controlled            controlled
   │            │                     │
Step down    Step up 1              Step up 1-2
if stable    + review               + OCS course
≥3 months    adherence/             + urgent review
             technique

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