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Launched by the WHO on November 17, 2020, this is the first global health strategy to target the elimination of a cancer as a public health problem. It represents a coordinated global effort to reduce the burden of a disease that is almost entirely preventable and curable if detected early.

2. The "Elimination" Threshold

Cervical cancer is considered "eliminated" as a public health problem when all countries reach an annual incidence rate of $\le$ 4 cases per 100,000 women.

3. The "90-70-90" Targets (By 2030)

To reach the elimination goal within the century, every country must meet three key targets by the year 2030:

• 90% Vaccination (Primary Prevention): 90% of girls should be fully vaccinated with the HPV vaccine by the age of 15 years.
• 70% Screening (Secondary Prevention): 70% of women should be screened using a high-performance test (e.g., HPV DNA test) at least twice in their lifetime—once by age 35 and again by age 45.
• 90% Treatment (Tertiary Prevention): 90% of women identified with cervical disease should receive treatment:

• • 90% of women with pre-cancer treated.

  • 90% of women with invasive cancer managed with surgery, radiotherapy, chemotherapy, and palliative care.

     

4. The Three-Pillar Approach

The strategy is built on three interconnected pillars that must be implemented simultaneously:

1. Prevention: Expanding HPV vaccination.
2. Screening: Transitioning from cytology (Pap smear) to High-Performance HPV DNA testing, which has higher sensitivity and allows for longer screening intervals (every 5-10 years).
3. Treatment: Strengthening surgical, oncological, and palliative care services to ensure those diagnosed are not just identified but cured.

5. Significance of "High-Performance Tests"

The WHO recommends HPV DNA testing over Visual Inspection with Acetic Acid (VIA) or Cytology (Pap) because it is more objective, allows for self-sampling (increasing coverage), and is more effective at detecting high-risk HPV strains (16 and 18).

6. Expected Impact

• Short-term (By 2030): Avert an estimated 300,000 deaths.
• Long-term: Reduce the median cervical cancer incidence rate by 42% by 2045 and by 95% by 2120, preventing over 62 million deaths worldwide.

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Read at CDC

These are the changes advised by the WHO in the treatment of tuberculosis.

However these changes are not yet (until April 2026) done in NTEP program in India. So if asked according to NTEP , the already running treatment protocols are used.

1. Drug-Susceptible Pulmonary TB (DS-TB)

The traditional "6-month RIPE" regimen (2 months of HRZE / 4 months of HR) is no longer the sole standard of care for adults and adolescents.

• The Change: Introduction of a 4-month (17-week) regimen.
• The "HPMZ" regimen.
  • Intensive Phase (8 weeks): Isoniazid (H), Rifapentine (P), Moxifloxacin (M), and Pyrazinamide (Z).
  • Continuation Phase (9 weeks): Isoniazid (H), Rifapentine (P), and Moxifloxacin (M).
• Key Shift: Drug Swap: Rifapentine replaces Rifampin; Moxifloxacin replaces Ethambutol.
  • Potency: Rifapentine has a longer half-life and higher potency against M. tuberculosis than rifampin, allowing for the shorter duration.
  • Eligibility: Patients must be 12 years old, 40 kg, and have non-extrapulmonary disease (excluding lymph node TB).

2. Drug-Resistant TB (MDR/RR-TB)

Historically, multidrug-resistant TB (MDR-TB) required 18–24 months of treatment, often involving painful daily injections (aminoglycosides) and significant toxicity.

• The Change: A shift to a 6-month, all-oral, injection-free regimen.
• The Highlight: The BPaLM regimen.
  • Components: Bedaquiline, Pretomanid, Linezolid (600mg), and Moxifloxacin.
• Key Shift:
  • Elimination of Injectables: Amikacin and Kanamycin are no longer first-line.
  • Duration: Reduced by 12–18 months compared to older standards.
  • Pharmacology: Bedaquiline (inhibits mycobacterial ATP synthase) and Pretomanid (inhibits cell wall synthesis) are the "backbone" of this highly effective combination.

3. Pediatric TB (Non-Severe)

The treatment for children has been simplified based on the SHINE trial evidence, recognizing that children often have paucibacillary (low bacterial load) disease.

• The Change: Treatment shortened from 6 months to 4 months.
• The Highlight: The 2HRZ(E)/2HR regimen.
• Key Shift:
  • Duration: Children with non-severe disease (e.g., isolated hilar lymphadenopathy without cavitation) now stop treatment 2 months earlier.
  • Safety: Shorter duration significantly reduces the cumulative risk of drug-induced liver injury (DILI) in pediatric patients.

4. Treatment Delivery: From Clinic to Camera

The delivery of Directly Observed Therapy (DOT) has evolved to accommodate patient autonomy and reduce public health resource strain.

• The Change: Video DOT (vDOT) is now considered an equivalent alternative to in-person DOT.
• The Highlight: Use of synchronous (real-time) or asynchronous (recorded) video for dose verification.
• Key Shift: This removes the "stigma" of health department vehicles visiting homes and allows patients to maintain employment and education while ensuring adherence.

Summary: Then vs. Now

Rifapentine is a semisynthetic rifamycin antibiotic, that has been included in shortened tuberculosis (TB) treatment regimens, as adviced in latest WHO guidelines 2025. Its pharmacokinetic profile allows for less frequent dosing and shorter treatment durations compared to the traditional standard, Rifampin.

1. Mechanism of Action and Antimicrobial Spectrum

• Mechanism: Rifapentine inhibits mycobacterial DNA-dependent RNA polymerase. By binding to the β-subunit of the enzyme, it blocks RNA synthesis, leading to cell death.
• Spectrum: Potently bactericidal against Mycobacterium tuberculosis. It also has activity against Mycobacterium avium complex (MAC).
• Cross-Resistance: M. tuberculosis strains resistant to Rifampin are almost always cross-resistant to Rifapentine.

2. Pharmacokinetic Advantages (vs. Rifampin)

Rifapentine’s clinical utility stems directly from its superior pharmacokinetics:

• Half-Life: longer half-life (~15 hours) compared to Rifampin (~2–3 hours). This long duration of action allows for intermittent (weekly) or high-dose daily dosing.
• Potency: more active in vitro against M. tuberculosis than Rifampin.
• Absorption: Absorption is increased by food, particularly a high-fat meal. Patients are usually advised to take it with food to maximize bioavailability.

3. Adverse effects

Hepatotoxicity (DILI) - Baseline and monthly Liver Function Tests (LFTs). Risks increase with INH co-administration or daily high-dose RPT.

Gastrointestinal Effects - Nausea, vomiting, abdominal pain. Often mitigated by taking with food.

Hypersensitivity Reactions - Including "flu-like syndrome" (more common with intermittent dosing).

Body Fluid Discoloration: (not a side effect but should be communicated to patients) Turns urine, sweat, tears, and saliva an orange-red color. Can permanently stain contact lenses.

4. Interactions

Rifapentine is a potent inducer of the Cytochrome P450 system (especially CYP3A4), though generally less potent than Rifampin. It significantly reduces the plasma concentrations of many co-administered drugs. Key affected classes include:

• Antiretroviral Therapy (ART): Protease inhibitors, NNRTIs, and integrase inhibitors. Requires specialized consultation in HIV-positive patients.
• Oral Contraceptives: Patients must use barrier methods of birth control while on therapy.
• Warfarin
• Anticonvulsants

• Laughing epilepsy refers to gelastic seizures (from Greek gelos = laughter), a rare type of focal seizure characterized by inappropriate, unprovoked bouts of laughter.

Etiology

• Most commonly associated with hypothalamic hamartoma
• Other causes:
  • Temporal or frontal lobe lesions
  • Cortical dysplasia
  • Tumors or structural brain abnormalities

👉 Hypothalamic hamartomas are classically associated with gelastic (laughing) seizures

Clinical Features

• Sudden episodes of inappropriate laughter
• Laughter is -Stereotyped , Not associated with emotion (no happiness)
• May be accompanied by:
  • Facial flushing, autonomic features
  • Altered awareness (sometimes preserved)
• Often brief (seconds) but frequent
• Can evolve into other seizure types over time
• Associated features (especially with hypothalamic hamartoma):
  • Precocious puberty
  • Behavioral problems
  • Developmental delay

EEG Findings

• May be normal or show focal epileptiform discharges (often temporal/frontal)

Diagnosis

• Clinical suspicion based on characteristic laughter spells
• MRI brain → essential to detect hypothalamic hamartoma

Management

• Often drug-resistant epilepsy
• Treatment options:
  • Antiepileptic drugs (limited efficacy)
  • Surgical options:
    • Resection/disconnection of hamartoma
    • Stereotactic radiosurgery
    • Laser ablation

1. Screening and Recognition:

• Systematic Screening: The guidelines recommend implementing automated or manual screening tools in emergency departments and wards to identify patients earlier.
• Lactate: While helpful, lactate levels should not be used as the sole marker for septic shock; clinical assessment (capillary refill, pulses, mental status) remains paramount.

2. Resuscitation (The "First Hour") ⏱️

The guidelines introduced a nuanced approach to fluids based on the availability of intensive care resources.

• Fluid Boluses:

  • Settings WITH Intensive Care: For patients with septic shock, administer 10–20 mL/kg of balanced crystalloids (like Lactated Ringer's) over the first hour.
  • Settings WITHOUT Intensive Care: If the patient is not hypotensive, do not give a fluid bolus initially (maintenance fluids only). If they are hypotensive, give 10–20 mL/kg.
  • Why? This prevents fluid overload in settings where mechanical ventilation and advanced inotropic support aren't readily available to manage complications.

• Access: Intraosseous (IO) access is recommended if IV access is difficult to obtain quickly.

3. Antimicrobial Therapy 💊

• Septic Shock: Start broad-spectrum antibiotics within 1 hour of recognition.
• Sepsis (without shock): If shock is absent, the guidelines allow up to 3 hours to assess and start antibiotics, prioritizing diagnostic evaluation to confirm infection first.

4. Vasoactive Support 

• First Line: Epinephrine or Norepinephrine are now recommended as the first-line vasoactive medications.
• Dopamine: The guidelines explicitly suggest against using Dopamine if Epinephrine or Norepinephrine are available (a major shift from older PALS protocols).

Clinical definitions of nephrotic syndrome